A compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, pharmaceutical composition, methods of modulating follicle-stimulating hormone receptor activity in a subject and of treating a disease or disorder in a subject requiring the same, and use of a compound, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof.

Description

A compound, or a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, pharmaceutical composition, methods of modulating follicle-stimulating hormone receptor activity in a subject and of treating a disease or disorder in a subject requiring the same, and use of a pharmaceutically acceptable compound, stereoisomer, tautomer, or salt thereof. SAME FIELD

[001] The present disclosure is in the field of pharmaceutical compounds and compositions and therapeutic methods of their use. In particular, the present disclosure is in the field of follicle-stimulating hormone (FSH) receptor modulators and their use. BACKGROUND

[002] Gonadotropins serve important functions in several physiological processes, including metabolism, temperature regulation, and reproduction. Gonadotropins act on specific types of gonadal cells to initiate ovarian and testicular cell differentiation and steroidogenesis. The gonadotropin FSH (follicle-stimulating hormone) is released from the anterior pituitary gland under the influence of gonadotropin-releasing hormone and estrogens. FSH is a heterodimeric glycoprotein hormone that shares structural similarities with luteinizing hormone (LH), human chorionic gonadotropin (hCG), and thyroid-stimulating hormone (TSH), all of which are proteins (28-38 kDa) composed of a common α subunit non-covalently linked to a distinct β subunit that confers receptor-binding specificity. See, for example, Ulloa-Aguirre, A., et al., Front Endocrinol (Lausanne), 2018, 9:707. FSH, LH, and TSH are produced in the gland. Petition 870260076443, dated 07 / 31 / 2026, page 11 / 508 / 448 pituitary gland, while hCG is produced mainly by the placenta. The cellular receptor for FSH (FSHR) is expressed in testicular Sertoli cells and ovarian granulosa cells. See, for example, Anderson, RC, et al., Endocr Rev, 2018, 39(6):911-937.

[003] In females, FSH plays a fundamental role in stimulating the development and maturation of follicles. The binding of FSH to FSHR initiates an increase in the level of the second intracellular messenger adenosine 3' 5'-monophosphate (cAMP), which stimulates the induction of aromatase that catalyzes the conversion of androstenedione to estradiol within the ovary, allowing follicle growth. See, for example, Donadeu, FX and M. Ascoli, Endocrinologia, 2005, 146 (9):3907-16.

[004] Activation of FSH also stimulates the expression of LH receptors in granulosa cells, allowing them to respond to the pre-ovulatory LH surge. In males, FSH is expressed in Sertoli cells of the testes and plays a key role in stimulating spermatogenesis. Pre-pubertally, FSH is responsible for Sertoli cell proliferation and, in adulthood, FSH stimulates spermatogonial proliferation and can support spermatogenesis to the round sperm stage.

[005] The FSH receptor is a Class A member of the G-coupled protein (GPCR) receptor class, belonging to the glycoprotein hormone receptor subfamily, which also includes luteinizing hormone / chorionic gonadotropin receptor (LHCGR) and thyroid-stimulating hormone receptor (TSHR). See, for example, Ulloa-Aguirre, supra. Hydropathic plots of the amino acid sequences of these receptors reveal three general domains: a hydrophilic amino-terminal region, considered the extracellular amino-terminal domain; seven hydrophobic membrane-spanning segments, considered the transmembrane domain; and a carboxy-terminal region that Petition 870260076443, dated 07 / 31 / 2026, page 12 / 508 / 448 contains potential phosphorylation sites (serine, threonine, and tyrosine residues), considered to be the intracellular or cytoplasmic carboxy-terminal domain. The family of glycoprotein hormone receptors is distinguished from other G protein-coupled receptors, such as β-2-adrenergic, rhodopsin, and substance K receptors, by the large size of the hydrophilic amino-terminal domain, which is involved in hormone binding.

[006] Every year in the U.S., there are 2.4 million couples experiencing infertility who are potential candidates for treatment. FSH, extracted from urine or produced by recombinant DNA technology, is a parenterally administered protein product used by specialists for ovulation induction and controlled ovarian stimulation. While ovulation induction is aimed at targeting a single follicle to ovulate, controlled ovarian stimulation is aimed at retrieving multiple oocytes for use in various in vitro assisted reproductive technologies, for example, in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). See, for example, ESHRE guideline: Ovarian Stimulation for IVF / ICSI, (October 2019). FSH is also used clinically to treat male hypogonadism and male infertility, for example, some types of spermatogenesis failure. See, for example, Behre, HM, Front Endocrinol (Lausanne), 2019, 10:322.

[007] FSH is a highly specific target in the ovarian follicle growth process in females and is almost exclusively expressed in the ovary. However, the use of FSH is limited by its high cost, lack of oral dosage, and the need for extensive monitoring by specialist physicians. Therefore, the identification of a small non-peptidic molecule substitute for FSH that could potentially be developed for oral administration is desirable.

[008] FSH and small molecule FSH receptor modulators Petition 870260076443, dated 07 / 31 / 2026, p. 13 / 508 / 448, can be used to treat diseases, disorders, and conditions such as female infertility, male infertility, hypogonadism, and spermatogenesis failure. Small molecule FSH agonists have been disclosed, for example, in documents no. WO 2002 / 09706, WO 2009 / 098283, WO 2010 / 136438, US Patent no. 6,653,338, US Patent no. 8,431,564, WO 2011 / 012600, WO 2014 / 209978, and WO 2015 / 196759. A small molecule FSH receptor modulator, MK-8389, was evaluated in clinical trials but did not achieve approval. See, for example, Gerrits, MGF et al., Fertility and Sterility volume 105, no. 4, April 2016. There remains a need for small molecule FSH receptor modulators that selectively activate FSHR. SUMMARY

[009] In one aspect, a compound of Formula (A) is provided in this document. or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein R1e -NRfRg, wherein (i) RfRg together with the nitrogen to which they are attached form a 4- to 8-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 13 substituents (e.g., 1 to 6 or 1 to 5 substituents) independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally Petition 870260076443, dated 07 / 31 / 2026, page 14 / 508 / 448 wherein 2 R4 groups, together with the atoms to which they are attached, form a 4- to 6-membered ring; and each R4a and R4b independently selected from C1-C3 alkyl; or (ii) Rf C1-C6 alkyl; and Rg C1-C6 alkyl substituted by 1 to 4 R4c groups, wherein each R4c group independently selected from halogen, hydroxyl and nitrile; R2 is selected from C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 hydroxyalkyl; -(C1-C3 alkyl)-SO2CH3; -(C1-C6 alkyl)-O-(C1-C6 alkyl) optionally substituted with 1 to 13 halogens; -(C1-C6 alkyl)-NR5aR5b; phenyl; C4-C6 cycloalkyl; and a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the phenyl, C4-C6 cycloalkyl, and the 5- to 6-membered heteroaryl ring may be optionally substituted with 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b independently selected from H and C1-C3 alkyl; X is CR20 or N; R20 is selected from H, halogen, nitrile, C1-C6 alkyl and C1-C6 haloalkyl; R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl, 5- to 6-membered heterocycloalkyl ring and 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring contain 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2; Petition 870260076443, dated 07 / 31 / 2026, page 15 / 508 / 448 R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted with nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted with 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently; Petition 870260076443, dated 07 / 31 / 2026, p. 16 / 508 / 448 selected from H, C1-C6 alkyl and C1-C6 haloalkyl; or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; or R11 and R12 together form a double bond, and R10 and R13 are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[0010] In some modalities, R1é -NRfRg, where: (i) RfRgm together with the nitrogen to which they are attached form a 4- to 8-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, -SR4a, -S(O)2R4ae C1-Có alkyl optionally substituted with 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4ae R4bé independently selected from C1-C3 alkyl; or (ii) Rfé C1-Có alkyl; and Rgé C1-Có alkyl substituted with 1 to 4 R4c groups, wherein each R4c group independently selected from halogen, hydroxyl and nitrile.

[0011] In some embodiments, R1 is -NRfRg, wherein RfRg together with the nitrogen to which they are attached form a 4-membered heterocycloalkyl ring that optionally contains 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, wherein the ring is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, SR4a, -S(O)2R4a and C1-C alkyl optionally substituted by 1 to 4 Petition 870260076443, dated 07 / 31 / 2026, page 17 / 508 / 448 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b independently selected from C1-C3 alkyl.

[0012] In some embodiments, R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 5-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, wherein the ring is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4- to 6-membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl.

[0013] In some embodiments, R1 is C-ζ wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl.

[0014] In some embodiments, R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 6-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, wherein the ring is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, Petition 870260076443, dated 07 / 31 / 2026, page 18 / 508 / 448 SR4a, -S(O)2R4ae C1-C6 alkyl optionally substituted with 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4ae R4bé independently selected from C1-C3 alkyl.

[0015] In some embodiments, R1e -NRfRg, wherein Rfé is C1-C6 alkyl; and Rgé is C1-C6 alkyl substituted by 1 to 4 R4c groups, wherein each R4c group is independently selected from halogen, hydroxyl and nitrile.

[0016] In some embodiments, R2 is C1-C6 alkyl or C1-C6 alkenyl. In some embodiments, R2 is C1-C6 haloalkyl. In some embodiments, R2 is C1-C6 hydroxyalkyl. In some embodiments, R2 is phenyl optionally substituted by 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl. In some embodiments, R2 is 4-fluorophenyl. In some embodiments, R2 is a C4-C6 cycloalkyl optionally substituted by 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl.In some embodiments, R2 is a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the ring may optionally be substituted by 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl. In some embodiments, R2 is 3,3-difluorocyclobutyl, 5-fluoropyridin-2-yl, 2-thiophenyl, 5-thiazolyl, or 1,3,4-thiadiazolyl. Petition 870260076443, dated 07 / 31 / 2026, p. 19 / 508 / 448

[0017] In some modalities, X is CR20. In some modalities, X is N.

[0018] In another aspect, a compound of Formula (B) is provided in this document. or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein R1 is ^---^, wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C3 alkyl optionally substituted by 1 to 4 substituents independently selected from C3C3 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl; Het is a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, optionally substituted by 1 to 4 R5 groups independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b are independently selected from H and C1-C3 alkyl; R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl, 5- to 6-membered heterocycloalkyl ring and 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring contain 1 to 4 heteroatoms of Petition 870260076443, dated 07 / 31 / 2026, page 20 / 508 / 448 rings independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxy, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted with nitrile or a 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the ring may be optionally substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, and hydroxyl; and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or a 5- to 6-membered heteroaryl ring, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxygen, sulfur, and nitrogen. Petition 870260076443, dated 07 / 31 / 2026, page 21 / 508 / 448 selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 independently selected halogens, and C1-C3 alkoxy optionally substituted by 1 to 7 independently selected halogens; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[0019] In some embodiments, Het is a 5-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, optionally substituted by 1 to 4 R5 groups independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b are independently selected from H and C1-C3 alkyl. In some embodiments, Het is a 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, optionally substituted by 1 to 4 R5 groups independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b are independently selected from H and C1-C3 alkyl groups.

[0020] In another aspect, a compound of Formula (C) is provided in this document. Formula (C) or a stereoisomer, a tautomer, or a salt Petition 870260076443, dated 07 / 31 / 2026, page 22 / 508 / 448, pharmaceutically acceptable of the same, in which R1 is C·-!, wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C3 alkyl optionally substituted by 1 to 4 substituents independently selected from C3C3 cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl; R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl, 5- to 6-membered heterocycloalkyl ring and 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring contain 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; Petition 870260076443, dated 07 / 31 / 2026, page 23 / 508 / 448 (ii) C1-C6 alkyl optionally substituted by nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[0021] In another aspect, a compound of Formula (D) is provided in this document. Petition 870260076443, dated 07 / 31 / 2026, p. 24 / 508 / 448 Formula F (D) or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, wherein R1e5X--J, wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3C6cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl; R3 is selected from -C(O)NHR6, -SO2-(C1-C3alkyl), SO2-(C3-C6cycloalkyl), phenyl, 5- to 6-membered heterocycloalkyl ring and 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring contain 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2; m is 0, 1, 2, 3 or 4; each R5 is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy; and each R5ae R5bé is independently selected from H and C1-C3 alkyl; R6 is selected from: Petition 870260076443, dated 07 / 31 / 2026, page 25 / 508 / 448 (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted with nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted with 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; or any two of; Petition 870260076443, dated 07 / 31 / 2026, p. 26 / 508 / 448 R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[0022] In another aspect, a compound of Formula (E) is provided in this document. or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein R1 is C·-!, wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C3 alkyl optionally substituted by 1 to 4 substituents independently selected from C3C3 cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl; R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl, a 5- to 6-membered heterocycloalkyl ring and a 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring contain 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 Petition 870260076443, dated 07 / 31 / 2026, page 27 / 508 / 448 alkyl, C1-C3 haloalkyl and -C(O)NH2; Alk is C1-C6 alkyl or C1-C6 alkenyl; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted by nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the ring may be optionally substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens; Petition 870260076443, dated 07 / 31 / 2026, p. 28 / 508 / 448 independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[0023] In another aspect, a compound of Formula (F) is provided in this document. or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein R1e -NRfRg, wherein (i) RfRg together with the nitrogen to which they are attached form a 4- to 8-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4- to 6-membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl; or (i) RfC1-C6 alkyl; and Rgé C1-Có alkyl substituted by 1 to 4 R4c groups, wherein each R4c group is independently selected from Petition 870260076443, dated 07 / 31 / 2026, page 29 / 508 / 448 halogen, hydroxyl and nitrile; R2 is selected from C1-C0 alkyl; C1-C0 alkenyl; C1-C0 haloalkyl; C1-C0 hydroxyalkyl; -(C1-C3 alkyl)-SO2CH3; -(C1-C0 alkyl)-O(Ci-C0 alkyl) optionally substituted by 1 to 13 halogens; -(Ci-Có alkyl)-NR5aR5b; phenyl; C4-C6 cycloalkyl; and a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the phenyl, C4-C6 cycloalkyl, and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl; R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl, 5- to 6-membered heterocycloalkyl ring and 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring contain 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxy, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; Petition 870260076443, dated 07 / 31 / 2026, page 30 / 508 / 448 each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted with nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted with 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the two remaining members are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; or R11 and R12 together form a double bond, and R10 and R13 are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s). Petition 870260076443, dated 07 / 31 / 2026, p. 31 / 508 / 448

[0024] In some embodiments, R1 is 5%4, wherein each R4 is independently selected from nitrile and C1-C0 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C0 cycloalkyl, hydroxyl and halogen. In some embodiments, R1 is *, wherein R4a is C1-C0 alkyl and R4b is selected from nitrile and C1-C0 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C0 cycloalkyl, hydroxyl and halogen. In some embodiments, R1 is , wherein R4b is C1-C0 alkyl and R4a is selected from nitrile and C1-C0 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C0 cycloalkyl, hydroxyl and halogen.

[0025] In some embodiments, R3 is a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the 5- to 6-membered heteroaryl ring may be optionally substituted with 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl, and -C(O)NH2. In some embodiments, R3 is a 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heteroaryl ring contains 1 to 4 ring nitrogens, and wherein the 5- to 6-membered heteroaryl ring may be optionally substituted with 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl, and C(O)NH2. In some embodiments, R3 is a tetrazole, pyrazole, imidazole, oxazole, or pyridine, wherein R3 may be optionally replaced by 1 to 3 independently selected substituents of hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl, and -C(O)NH2.In some modalities, R3 is C(O)NHR6.

[0026] In some forms, R6e -(CR7R8)nC(O)NRdRe. In Petition 870260076443, dated 07 / 31 / 2026, page 32 / 508 / 448 In some embodiments, each of R7 and R8 is independently selected from H and C1-C3 alkyl. In some embodiments, R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur and nitrogen.

[0027] In some embodiments, R6 is a C1-C6 alkyl optionally substituted with nitrile or a 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the ring may be optionally substituted with 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, and hydroxyl. In some embodiments, R6 is a C1-C6 alkyl optionally substituted with nitrile or tetrazole.In some embodiments, R6 is a phenyl, saturated or partially unsaturated ring of 3 to 6 members or a heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected. In some embodiments, R6 is cyclopropane optionally substituted by nitrile or is cyclobutene optionally substituted by nitrile.

[0028] In some embodiments, each of R10, R11, R12 and R13 are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl. In some embodiments, any two of R10, R11, R12 and Petition 870260076443, dated 07 / 31 / 2026, p. 33 / 508 / 448 R13, together with the carbon atom(s) to which they are attached, form a 3- to 6-membered ring, and the two remaining members are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl.

[0029] In another aspect, a compound of Formula (I') is provided in this document. or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein R1e -NRfRg, wherein RfRg together with the nitrogen to which they are attached form a 4- to 8-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, NR4aR4b, -SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4- to 6-membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl; R2 is selected from C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 hydroxyalkyl; -(C1-C3 alkyl)-SO2CH3; -(C1-C6 alkyl)-O-(C1-C6 alkyl) optionally substituted with 1 to 13 halogens; -(C1-C6 alkyl)-NR5aR5b; phenyl; C4-C6 cycloalkyl; and a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the phenyl, C4-C6 cycloalkyl, and the 5- to 6-membered heteroaryl ring may optionally be substituted with 1 to 4 R5 groups, wherein each R5 group is Petition 870260076443, dated 07 / 31 / 2026, page 34 / 508 / 448 independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy; and each R5a and R5b independently selected from H and C1-C3 alkyl; R20 is selected from H, halogen, nitrile, C1-C1 alkyl and C1-C1 haloalkyl; R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl and a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the phenyl and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and C(O)NH2; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted with nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted with 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl; and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 Petition 870260076443, dated 07 / 31 / 2026, page 35 / 508 / 448 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl ring, saturated or partially unsaturated, and the heteroaryl ring may optionally be substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the two remaining members are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; or R11 and R12 together form a double bond, and R10 and R13 are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[0030] In another aspect, a compound of Formula (I) is provided in this document. or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein R1e -NRfRg, where RfRg together with nitrogen to Petition 870260076443, dated 07 / 31 / 2026, page 36 / 508 / 448 which are linked to form a 4- to 6-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and substituted by 1 to 3 R4 groups, wherein each R4 group is independently selected from nitrile and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from hydroxyl and halogen; R2 is selected from C1-C6 alkyl; C1-C6 haloalkyl; phenyl; and a 5- to 6-membered heteroaryl ring containing 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the phenyl and the 5- to 6-membered heteroaryl ring may optionally be replaced by 1 or 2 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; R3 is selected from -C(O)NHR6 and a 5- to 6-membered heteroaryl ring containing 1 to 3 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, and C1-C3 alkyl; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted by nitrile or ring Petition 870260076443, dated 07 / 31 / 2026, page 37 / 508 / 448 5- or 6-membered heteroaryl containing 1 to 4 ring heteroatoms independently selected from oxygen and nitrogen, wherein the ring may optionally be substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from halogen, hydroxyl, nitrile and C1-C3 alkyl optionally substituted by one or more halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring and the two remaining members are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl, wherein 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[0031] In another aspect, a compound selected from Table 1, or a pharmaceutically acceptable stereoisomer, tautomer or salt thereof, is provided herein. In another aspect, a compound selected from Table 2, or a pharmaceutically acceptable stereoisomer, tautomer or salt thereof, is provided herein.

[0032] In another aspect, salts, hydrates, solvates, analogues, conjugates, isomers, polymorphs, esters, prodrugs, metabolites, complexes, cocrystals, intermediates, modifications and are provided in this document. Petition 870260076443, dated 07 / 31 / 2026, page 38 / 508 / 448 derived from the compounds, stereoisomers and tautomers described in this document.

[0033] In another aspect, a pharmaceutical composition is provided herein comprising the compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof, as described herein, and a pharmaceutically acceptable carrier.

[0034] In another aspect, a method for modulating follicle-stimulating hormone receptor (FSHR) activity in a subject is provided herein, comprising administering to a subject in need thereof the compound disclosed herein, or a pharmaceutically acceptable stereoisomer, tautomer or salt thereof, or the composition disclosed herein.

[0035] In another aspect, a method for modulating follicle-stimulating hormone receptor (FSHR) activity in a biological sample is provided herein, comprising contacting the biological sample with the compound disclosed herein, or a pharmaceutically acceptable stereoisomer, tautomer or salt thereof, or the composition disclosed herein.

[0036] In another aspect, a method is provided herein for treating a disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound disclosed herein, or a pharmaceutically acceptable stereoisomer, tautomer or salt thereof, or the composition disclosed herein. In some embodiments, the disease or disorder is selected from hypogonadotropic hypogonadism, isolated idiopathic hypogonadotropic hypogonadism, Kallmann syndrome, idiopathic hypogonadotropic hypogonadism, craniopharyngiomas, combined pituitary hormone deficiency, fertile eunuch syndrome, abnormal beta subunit of LH, abnormal beta subunit of FSH, mass lesions, Petition 870260076443, dated 07 / 31 / 2026, page 39 / 508 / 448 pituitary adenomas, cysts, metastatic cancer in the sella (breasts in women, lung and prostate in men), infiltrative lesions, hemochromatosis, sarcoidosis, histiocytosis, lymphoma, lymphocytic hypophysitis, meningitis, pituitary apoplexy, hyperprolactinemia, hypothyroidism, intentional (iatrogenic) secondary hypogonadism, empty sella, pituitary infarction, Sheehan's syndrome, anorexia nervosa, congenital adrenal hyperplasia and disorders related to GnRH deficiency.

[0037] In another aspect, a method is provided herein for treating a fertility disorder in a female or male subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound as disclosed herein, or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, or a composition as disclosed herein. The method may be a method for stimulating follicular development, a method for ovulation induction, a method of controlled ovarian hyperstimulation, a method of controlled ovarian stimulation, a method of assisted reproductive technology (ART) (including in vitro fertilization), a method for treating male hypogonadism or a method for treating male infertility, including failure of spermatogenesis.

[0038] In another aspect, a compound as disclosed herein or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, or a composition disclosed herein, is provided herein for use in modulating follicle-stimulating hormone receptor (FSHR) activity in a subject, or for use in treating a disease or disorder in a subject requiring such treatment, such as a disease or disorder selected from hypogonadotropic hypogonadism, isolated idiopathic hypogonadotropic hypogonadism, Kallmann syndrome, hypogonadotropic hypogonadism Petition 870260076443, dated 07 / 31 / 2026, page. 40 / 508 / 448 idiopathic, craniopharyngiomas, combined pituitary hormone deficiency, fertile eunuch syndrome, abnormal beta subunit of LH, abnormal beta subunit of FSH, mass lesions, pituitary adenomas, cysts, metastatic cancer of the sella (breasts in women, lung and prostate in men), infiltrative lesions, hemochromatosis, sarcoidosis, histiocytosis, lymphoma, lymphocytic hypophysitis, meningitis, pituitary apoplexy, hyperprolactinemia, hypothyroidism, intentional (iatrogenic) secondary hypogonadism, empty sella, pituitary infarction, Sheehan's syndrome, anorexia nervosa, congenital adrenal hyperplasia, and disorders related to GnRH deficiency, or for use in the treatment of a fertility disorder in a subject who needs it, such as to stimulate follicular development, ovulation induction, controlled ovarian hyperstimulation, controlled ovarian stimulation,Assisted reproductive technology (including in vitro fertilization), treatment of male hypogonadism or treatment of male infertility, including failure of spermatogenesis.

[0039] In another aspect, the use of a compound as disclosed herein or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, or a composition disclosed herein, is provided for in the preparation of a medicament to modulate follicle-stimulating hormone receptor (FSHR) activity in a subject, or in the treatment of a disease or disorder in a subject requiring the same, such as a disease or disorder selected from hypogonadotropic hypogonadism, isolated idiopathic hypogonadotropic hypogonadism, Kallmann syndrome, idiopathic hypogonadotropic hypogonadism, craniopharyngiomas, combined pituitary hormone deficiency, fertile eunuch syndrome, abnormal beta subunit of LH, abnormal beta subunit of FSH, mass lesions, pituitary adenomas, cysts, metastatic cancer in the sella (breasts in women, lung and prostate in men), infiltrative lesions, hemochromatosis, sarcoidosis, histiocytosis, Petition 870260076443, dated 07 / 31 / 2026, page 41 / 508 / 448 lymphoma, lymphocytic hypophysitis, meningitis, pituitary apoplexy, hyperprolactinemia, hypothyroidism, intentional (iatrogenic) secondary hypogonadism, empty sella, pituitary infarction, Sheehan's syndrome, anorexia nervosa, congenital adrenal hyperplasia, and disorders related to GnRH deficiency, or for the treatment of a fertility disorder in a subject who needs it, such as to stimulate follicular development, ovulation induction, controlled ovarian hyperstimulation, controlled ovarian stimulation, assisted reproductive technology (including in vitro fertilization), treatment of male hypogonadism or treatment of male infertility, including failure of spermatogenesis. DETAILED DESCRIPTION DEFINITIONS

[0040] The technical and scientific terms used in this document have the meanings commonly understood by a person of ordinary skill in the technique to which the present disclosure pertains, unless otherwise defined.

[0041] As used herein, the singular forms “um”, “uma”, and “o”, “a” and the like designate both the singular and the plural, unless expressly stated as designating only the singular.

[0042] As used herein, the term “about” means that the stated parameter is not limited to the exact number indicated. As used in this document, “about” will be understood by persons of ordinary skill in the art and will vary to some extent in the context in which it is used. If there are uses of the term that are not clear to persons of ordinary skill in the art given the context in which it is used, “about” will mean up to plus or minus 10% of the particular term. As used in this document, ranges are to be interpreted as shorthand for each and every value that is within the range, and each separate value is to be understood as expressly disclosed in this document. Petition 870260076443, dated 07 / 31 / 2026, page 42 / 508 / 448

[0043] The expression “consisting essentially of” shall be understood as including those elements specifically cited and those additional elements that do not materially affect the basic and novel characteristics of the claimed technology. When “consisting essentially of” is used to refer to compositions with only one active agent disclosed herein, the compositions may not include any additional active agents not otherwise cited. When “consisting essentially of” is used to refer to combinations of active agents disclosed herein, the combinations may not include any additional active agents not otherwise cited.

[0044] As used in this document, “pharmaceutically acceptable salt” refers to a salt of a compound that does not cause significant irritation to a patient to whom it is administered and does not negate the biological activity and properties of the compound. Pharmaceutical salts can be obtained by reacting a compound disclosed in this document with an acid or base. Typically, but not necessarily unless otherwise indicated, the salts of the present invention are pharmaceutically acceptable salts. The salts encompassed within the term “pharmaceutically acceptable salts” refer to non-toxic salts of the compounds of this invention. The salts of the compounds of the present disclosure may comprise acid addition salts.Representative salts include acetate, benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, borate, bromide, calcium edetate, camsylate, carbonate, chloride, clavulanate, citrate, dihydrochloride, edetate, edisylate, estolate, esilate, fumarate, gluceptate, gluconate, glutamate, glycolillarsanilate, hexylresorcinate, hydrazamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, laurate, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulfate, monopotassium maleate, mucate, napsylate, nitrate, N-methylglucamine, oxalate, pamoate (embonate), palmitate, pantothenate. Petition 870260076443, dated 07 / 31 / 2026, page 43 / 508 / 448 phosphate / diphosphate, polygalacturonate, potassium, salicylate, sodium, stearate, subacetate, succinate, sulfate, tannate, tartrate, theoaclate, tosylate, trietiodide, trimethylammonium and valerate salts. Other salts, which are not pharmaceutically acceptable, may be useful in the preparation of compounds of this disclosure and these should be considered to form an additional aspect of the present technology.

[0045] Where compounds disclosed herein have one or more chiral centers, they may exist as, be supplied or formulated as, or be used as, a racemate or as individual enantiomers. It should be noted that all such stereoisomers and mixtures thereof are included within the scope of this disclosure. Thus, the illustration of a chiral center without an R or S designation means that the scope of the disclosure includes the R isomer, the S isomer, racemic mixtures of the isomers, and mixtures in which one isomer is present in greater abundance than the other.

[0046] Where the processes for the preparation of compounds disclosed in this document give rise to mixtures of stereoisomers, such isomers can be separated by conventional techniques, such as preparative chiral chromatography. The compounds can be prepared in racemic form or individual enantiomers can be prepared by stereoselective synthesis or by resolution. The compounds can be resolved into their component enantiomers by standard techniques, such as the formation of diastereomeric pairs by salt formation with an optically active acid, such as (-)-di-p-toluoyl-d-tartaric acid and / or (-)-di-p-toluoyl-l-tartaric acid, followed by fractional crystallization and regeneration of the free base. The compounds can also be resolved by the formation of diastereomeric esters or amides followed by chromatographic separation and removal of the chiral auxiliary.

[0047] As used in this document, “arila” refers to a Petition 870260076443, dated 07 / 31 / 2026, page 44 / 508 / 448 A carbocyclic ring (all carbon) that is fully aromatized. An “aryl” group can be composed of two or more fused rings (rings that share two adjacent carbon atoms). When an aryl group is a fused ring system, then the ring that is connected to the rest of the molecule is fully aromatized. The other ring (or rings) in the fused ring system may or may not be fully aromatized. Examples of aryl groups include, without limitation, the benzene, naphthalene, and azulene radicals. Additional non-limiting examples include:

[0048] As used in this document, “heteroaryl” refers to a ring that is fully aromatized and contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur in the ring. In some examples, a heteroaryl ring may comprise an oxo group directly attached to a ring carbon, the oxo group forming part of the aromatized system. A “heteroaryl” group may be composed of two or more fused rings (rings that share two adjacent carbon atoms). When a heteroaryl group is a fused ring system, then the ring that is connected to the rest of the molecule is fully aromatized. The other ring (or rings) in the fused ring system may or may not be fully aromatized. Examples of heteroaryl rings include, but are not limited to, furan, thiophene, phthalazione, pyrrole, oxazole, thiazole, imidazole, pyrazole, isoxazole, isothiazole, triazole, thiadiazole, pyridine, 2-pyridonyl, pyridazine, pyrimidine, pyrazine, and triazine.As described in this document, in some examples, the heteroaryl group can be substituted. In other words, the heteroaryl group can comprise one or more substituents on the heteroaromatic ring. When a heteroaryl group is substituted, any hydrogen atom(s) can be replaced by the substituent(s) as long as the valences are satisfied. In some cases, the heteroaryl group can be... Petition 870260076443, dated 07 / 31 / 2026, p. 45 / 508 / 448 substituted in the heteroatom, for example, a heteroaryl group containing N can be an N-substituted heteroaryl group (such as an N-substituted 2-pyridonyl group).

[0049] As used in this document, “alkyl” refers to a fully saturated (without double or triple bonds) linear or branched chain hydrocarbon group. An alkyl group of the compounds disclosed herein may comprise from 1 to 20 carbon atoms. An alkyl group in this document may have from 1 to 4 carbon atoms, 1 to 5 carbon atoms, 1 to 6 carbon atoms, 1 to 7 carbon atoms, 1 to 8 carbon atoms, 1 to 9 carbon atoms, 1 to 10 carbon atoms, 1 to 11 carbon atoms, 1 to 12 carbon atoms, 1 to 13 carbon atoms, 1 to 14 carbon atoms, or 1 to 15 carbon atoms. As used herein, a C1-C6 alkyl represents an alkyl group having 1 to 6 carbon atoms, a C1-C4 alkyl represents an alkyl group having 1 to 4 carbon atoms, and a C1-C4 alkyl represents an alkyl group having 1 to 3 carbon atoms, etc.Examples of alkyl groups include, without limitation, methyl, ethyl, n-propyl, isopropyl, n-butyl, i-butyl, sec-butyl, t-butyl, amyl, t-amyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, and dodecyl.

[0050] As used herein, “cycloalkyl” refers to a fully saturated hydrocarbon ring (without double bonds). The cycloalkyl groups of the compounds disclosed herein may range from C3 to C5, C3 to C6, C3 to C7, or C3 to C8. As used herein, a C3-C5 cycloalkyl represents a cycloalkyl group containing 3 to 5 carbon atoms and a C3-C6 cycloalkyl represents a cycloalkyl group containing 3 to 6 carbon atoms.

[0051] As used in this document, “heterocycloalkyl” refers to a ring having in the ring system one or more heteroatoms independently selected from nitrogen, oxygen, and sulfur. The ring Petition 870260076443, dated 07 / 31 / 2026, p. 46 / 508 / 448 may also contain one or more double bonds provided the ring is not fully aromatized. A “heterocycloalkyl” ring, as defined in this document, may be a stable 3- to 18-membered ring (which includes a 3- to 5-membered or 3- to 6-membered ring) consisting of carbon atoms and one to five ring heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur.

[0052] As used in this document, “alkoxy” refers to an alkyl group, as defined above, attached to the parent molecular chemical moiety via an oxy group, -O-. As used in this document, a C1-C2 alkoxy represents an alkoxy group containing 1 to 6 carbon atoms and a C1-C3 alkoxy represents an alkoxy group containing 1 to 3 carbon atoms. Representative examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, 2-propoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy, etc.

[0053] As used herein, “haloalkyl” refers to an alkyl group, as defined above, in which one or more of the hydrogen atoms therein have been replaced by a halogen atom (e.g., F, Cl, Br, or I). As used herein, “Ci-Co haloalkyl” represents an alkyl group containing 1 to 6 carbon atoms, in which one or more hydrogens therein have been replaced by a halogen atom.

[0054] As used herein, “haloalkoxy” refers to an alkoxy group, as defined herein, in which one or more of the hydrogen atoms therein have been replaced by a halogen atom (e.g., F, Cl, Br, or I). As used herein, “C1-C3 haloalkoxy” represents a haloalkoxy group containing 1 to 3 carbon atoms.

[0055] As used in this document, unless otherwise indicated, “regardless selected” indicates that each Petition 870260076443, dated 07 / 31 / 2026, page 47 / 508 / 448 one from a designated group is selected independently of a subsequent list of species.

[0056] As used in this document, and unless otherwise indicated, where a group is described as being optionally substituted, one or more hydrogen atoms in the group may each independently be substituted by a substituent, provided the valences are satisfied.

[0057] It should be understood that, in any compound of the presently disclosed compounds having one or more chiral centers, unless an absolute stereochemistry is expressly indicated, then each center may independently be R or S. Furthermore, it should be understood that, in any compound of the presently disclosed compounds having one or more double bonds generating geometric isomers that may be defined as E or Z, each double bond may independently be E or Z.

[0058] It should be understood that the disclosure of a compound in this document inherently includes the disclosure of a tautomer thereof, if applicable. For example, the disclosure of: (where Rxé H) also includes the revelation of: and vice versa, even if only one of the two structures is revealed.

[0059] Throughout the present disclosure, when a compound is illustrated or named, it should be understood that isotopically enriched analogues of the compound are also contemplated and encompassed by the disclosure. For example, a compound may have an incorporated deuterium instead of a hydrogen, or a carbon-13 instead of carbon with a natural isotopic distribution. The isotopic enrichment may be in a location Petition 870260076443, dated 07 / 31 / 2026, page 48 / 508 / 448 in the compound, that is, only one hydrogen is replaced by a deuterium, or in more than one location, that is, two or more or all or a plurality less than all hydrogens are replaced by deuterium. For example, in some embodiments, 1 to 10 hydrogens are replaced by deuterium. The present disclosure also covers compounds in which all like atoms are replaced by a less common isotope, for example, a pertherio compound in which all hydrogen atoms are replaced by deuterium. Isotopically enriched compounds can be useful, for example, in obtaining NMR spectra or in making use of an isotopic effect in managing the kinetics of the reaction in which the compound is undergoing.

[0060] Throughout this disclosure, when a compound is illustrated or named, it should be understood that salts, hydrates, solvates, analogues, conjugates, isomers, polymorphs, esters, prodrugs, metabolites, complexes, cocrystals, intermediates, modifications and derivatives thereof are contemplated and encompassed by the disclosure.

[0061] The term “pharmaceutical composition” refers to a mixture of one or more compounds disclosed herein with another pharmaceutically acceptable excipient, such as one or more pharmaceutically acceptable diluents or carriers or one or more other pharmaceutically acceptable excipients known in the art. The formulation of a compound into a pharmaceutical composition may facilitate the administration of the compound to an organism, for example, the subject to be treated. The specific components of a pharmaceutical composition may depend on and vary with the intended route of administration.

[0062] As used herein, the terms “patient” and “subject” refer to a vertebrate, such as, but not limited to, a mammal (including a human), bird, fish, or reptile, that has been or will be the object of treatment, observation, or experimentation. “Subject” and “patient” may be used Petition 870260076443, dated 07 / 31 / 2026, page 49 / 508 / 448 indiscriminately. Mammals include, but are not limited to, humans, mice, rodents, rats, apes, farm animals, dogs, cats, sporting animals, and pets. The methods described in this document may be useful in human therapy and / or veterinary / animal breeding applications. Without limitation, the following discussion is written with reference to adult human patients.

[0063] As used in this document, the terms “therapeutically effective amount” and “effective amount” are used interchangeably and refer to an amount that provides the specific intended pharmacological effect in a patient in need of treatment. It is emphasized that a therapeutically effective amount will not always be effective in treating the conditions described in this document in a given patient, even if such an amount is considered a therapeutically effective amount by those skilled in the art. Exemplary therapeutically effective amounts are provided below with reference to adult human patients. The therapeutically effective amount may vary depending on the characteristics of the patient being treated, the condition being treated, and the severity of the condition, for example. COMPOUNDS

[0064] In one aspect, a compound of Formula (A) is disclosed in the present document. Formula (A) or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, wherein R1 is -NRfRg, where Petition 870260076443, dated 07 / 31 / 2026, page 50 / 508 / 448 (i) Rfe Rgem together with the nitrogen to which they are attached form a 4- to 8-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, -SR4a, -S(O)2R4ae C1-C6 alkyl optionally substituted with 1 to 13 substituents (e.g., 1 to 6 or 1 to 5 substituents) independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4ae R4bé independently selected from C1-C3 alkyl; or (ii) Rfé C1-C6 alkyl; and Rgé C1-C6 alkyl substituted with 1 to 4 R4c groups, wherein each R4c group independently selected from halogen, hydroxyl and nitrile; R2 is selected from C1-C6 alkyl; C1-C6 alkenyl; C1-C6 haloalkyl; C1-C6 hydroxyalkyl; -(C1-C3 alkyl)-SO2CHs; -(C1-C6 alkyl)-O(C1-C6 alkyl) optionally substituted by 1 to 13 halogens; -(C1-C6 alkyl)-NR5aR5b; phenyl; C4-C6 cycloalkyl; and a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the phenyl, C4-C6 cycloalkyl, and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl; X is CR20 or N; R20 is selected from H, halogen, nitrile, C1-C6 alkyl and C1-C6 haloalkyl; R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), Petition 870260076443, dated 07 / 31 / 2026, page 51 / 508 / 448 SO2-(C3-C6 cycloalkyl), phenyl, 5- to 6-membered heterocycloalkyl ring and 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring contain 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted with nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the ring may be optionally substituted with 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, and hydroxyl; and (iii) phenyl, saturated or partially unsaturated 3- to 6-membered ring or 5- to 6-membered heteroaryl ring, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently Petition 870260076443, dated 07 / 31 / 2026, page 52 / 508 / 448 selected from oxygen, sulfur and nitrogen, and wherein the phenyl ring, saturated or partially unsaturated, and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C0 alkyl and C1-C0 haloalkyl; or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the two remaining members are independently selected from H, C1-C0 alkyl and C1-C0 haloalkyl; or R11 and R12 together form a double bond, and R10 and R13 are independently selected from H, C1-C0 alkyl and C1-C0 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[0065] In another aspect, a compound of Formula (A) is disclosed in the present document. or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein R1e -NRfRg, wherein (i) RfRg together with the nitrogen to which they are attached form a 4- to 8-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and substituted by 1 to 4 R4 groups, wherein each R4 group Petition 870260076443, dated 07 / 31 / 2026, page 53 / 508 / 448 is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, -SR4a, -S(O)2R4ae C1-C0 alkyl optionally substituted with 1 to 4 substituents independently selected from C3-C0 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4ae R4bé independently selected from C1-C3 alkyl; or (ii) Rfé C1-C0 alkyl; and Rgé C1-C0 alkyl substituted with 1 to 4 R4c groups, wherein each R4c group independently selected from halogen, hydroxyl and nitrile; R2 is selected from Ci-Có alkyl; Ci-Có alkenyl; Ci-Có haloalkyl; Ci-Có hydroxyalkyl; -(C1-C3 alkyl)-SO2CH3; -(Ci-Có alkyl)-O(Ci-Có alkyl) optionally substituted by 1 to 13 halogens; -(Ci-Có alkyl)-NR5aR5b; phenyl; C4-C6 cycloalkyl; and a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the phenyl, C4-C6 cycloalkyl, and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl; X is CR20 or N; R20 is selected from H, halogen, nitrile, C1-C0 alkyl and C1-C0 haloalkyl; R3 is selected from -C(O)NHRó, -SO2-(C1-C3 alkyl), SO2-(C3-Có cycloalkyl), phenyl, a 5- to 6-membered heterocycloalkyl ring and a 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring contain 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the ring Petition 870260076443, dated 07 / 31 / 2026, page 54 / 508 / 448 5- to 6-membered heteroaryl groups may optionally be replaced by 1 to 3 substituents independently selected from among hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted with nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted with 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently; Petition 870260076443, dated 07 / 31 / 2026, p. 55 / 508 / 448 selected, and C1-C3 alkoxy optionally substituted by 1 to 7 independently selected halogens; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; or R11 and R12 together form a double bond, and R10 and R13 are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[0066] In some modalities, X is CR20. In some modalities, X is N.

[0067] In another aspect, a compound of Formula (I') is disclosed in the present document. or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein R1e -NRfRg, Rf and Rgem together with the nitrogen to which they are attached form a 4- to 8-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, -SR4a, -S(O)2R4ae C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the Petition 870260076443, dated 07 / 31 / 2026, page 56 / 508 / 448 atoms to which they are attached, form a ring of 4 to 6 members; and each R4ae R4bé independently selected from C1-C3 alkyl; R2 is selected from C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 hydroxyalkyl; -(C1-C3 alkyl)-SO2CH3; -(C1-C6 alkyl)-O-(C1-C6 alkyl) optionally substituted with 1 to 13 halogens; -(C1-C6 alkyl)-NR5aR5b; phenyl; C4-C6 cycloalkyl; and a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the phenyl, C4-C6 cycloalkyl, and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl; R20 is selected from H, halogen, nitrile, C1-C6 alkyl and C1-C6 haloalkyl; R3 is selected from -C(O)NHR6, -SÜ2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl and a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the phenyl and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxy, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and C(O)NH2; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; Petition 870260076443, dated 07 / 31 / 2026, page 57 / 508 / 448 each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted with nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted with 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the two remaining members are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; or R11 and R12 together form a double bond, and R10 and R13 are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s). Petition 870260076443, dated 07 / 31 / 2026, p. 58 / 508 / 448

[0068] In another aspect, a compound of Formula (I) is disclosed in this document. or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 4- to 6-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and substituted by 1 to 3 R4 groups, wherein each R4 group is independently selected from nitrile and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from hydroxyl and halogen; R2 is selected from C1-C6 alkyl; C1-C6 haloalkyl; phenyl; and a 5- to 6-membered heteroaryl ring containing 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the phenyl and the 5- to 6-membered heteroaryl ring may optionally be replaced by 1 or 2 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; R3 is selected from -C(O)NHR6 and a 5- to 6-membered heteroaryl ring containing 1 to 3 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, and C1-C3 alkyl; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where Petition 870260076443, dated 07 / 31 / 2026, page 59 / 508 / 448 n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted with nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen and nitrogen, wherein the ring may be optionally substituted with 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from halogen, hydroxyl, nitrile and C1-C3 alkyl optionally substituted by one or more halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; where 0 to 10 hydrogen atoms are bonded to one or more Petition 870260076443, dated 07 / 31 / 2026, p. 60 / 508 / 448 carbon atoms are replaced by deuterium atom(s).

[0069] In some embodiments, R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 4-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, wherein the ring is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 13 substituents (e.g., 1 to 6 or 1 to 5 substituents) independently selected from C3-C6 cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4- to 6-membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl.

[0070] In some embodiments, R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 4-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, wherein the ring is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4- to 6-membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl.

[0071] In some embodiments, R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 4-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and wherein the ring is substituted by 1 to 3 R4 groups, wherein each R4 group is Petition 870260076443, dated 07 / 31 / 2026, page 61 / 508 / 448 independently selected nitrile and C1-C alkyl optionally substituted by 1 to 4 substituents independently selected from among hydroxyl and halogen.

[0072] In some embodiments, R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 5-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, wherein the ring is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 13 substituents (e.g., 1 to 6 or 1 to 5 substituents) independently selected from C3-C6 cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4- to 6-membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl.In some embodiments, R1 is -NRfRg, wherein RfRg together with the nitrogen to which they are attached form a 5-membered heterocycloalkyl ring that optionally contains 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, wherein the ring is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4- to 6-membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl.In some embodiments, R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 5-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and wherein the ring is substituted by 1 to 4 R4 groups. Petition 870260076443, dated 07 / 31 / 2026, page 62 / 508 / 448 that each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, -SR4a, -S(O)2R4ae C1-C0 alkyl optionally substituted by 1 to 4 substituents independently selected from C3C0 cycloalkyl, hydroxy and halogen.

[0073] In some embodiments, R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 5-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and wherein the ring is substituted by 1 to 3 R4 groups, wherein each R4 group is independently selected from nitrile and C1-C1 alkyl optionally substituted by 1 to 4 substituents independently selected from hydroxyl and halogen.

[0074] In some embodiments, R1 is C·^, wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 13 substituents (for example, 1 to 6 or 1 to 5 substituents) independently selected from C3-C-cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4 is independently selected from C1-C3 alkyl.In some embodiments, R1 is C^, wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C0 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C0 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4- to 6-membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl. In some embodiments, R1 is O, in. Petition 870260076443, dated 07 / 31 / 2026, page 63 / 508 / 448, stating that R1 is replaced by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, SR4a, -S(O)2R4a and C1-C6 alkyl optionally replaced by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; and each R4a and R4b independently selected from C1-C3 alkyl. In some embodiments, R1 is 0, wherein R1 is replaced by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile and C1-C6 alkyl optionally replaced by 1 to 4 substituents independently selected from C3C6 cycloalkyl, hydroxyl and halogen.In some embodiments, R1 is ^----^, wherein R1 is replaced by 2 to 4 R4 groups, wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring and each remaining R4 group, if present, is independently selected from halogen, hydroxyl, nitrile and C1-C6 alkyl optionally substituted by 1 to 4 substituents, independently selected from C3-C6 cycloalkyl, hydroxyl and halogen.

[0075] In some embodiments, R1 is C·^, wherein R1 is substituted by 1 to 3 R4 groups, wherein each R4 group is independently selected from nitrile and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from hydroxyl and halogen.

[0076] In some embodiments, R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 6-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, wherein the ring is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 13 substituents (e.g., 1 to 6 or 1 to 5 substituents) independently Petition 870260076443, dated 07 / 31 / 2026, page 64 / 508 / 448 selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b independently selected from C1-C3 alkyl.In some embodiments, R1 is -NRfRg, wherein RfRg together with the nitrogen to which they are attached form a 6-membered heterocycloalkyl ring that optionally contains 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, wherein the ring is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, SR4a, -S(O)iR4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4- to 6-membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl.In some embodiments, R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 6-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and wherein the ring is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, -SR4a, -S(O)iR4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3C6 cycloalkyl, hydroxy and halogen; and each R4a and R4b are independently selected from C1-C3 alkyl.In some embodiments, R1 is -NRfRg, wherein RfRg together with the nitrogen to which they are attached form a 6-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, wherein the ring is substituted by 2 to 4 R4 groups, wherein 2 R4 groups together with the atoms to which they are attached form a 4 to 6-membered ring and each remaining R4 group, if present, is independently selected from. Petition 870260076443, dated 07 / 31 / 2026, page 65 / 508 / 448 halogen, hydroxy, nitrile and a hydroxy ring, and 1-C6 alkyl optionally substituted with 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxy and halogen. In some embodiments, R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 6-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and wherein the ring is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxy and halogen.

[0077] In some embodiments, R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 6-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and wherein the ring is substituted by 1 to 3 R4 groups, wherein each R4 group is independently selected from nitrile and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from hydroxyl and halogen.

[0078] In some embodiments, R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 7-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, wherein the ring is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 13 substituents (e.g., 1 to 6 or 1 to 5 substituents) independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4- to 6-membered ring; and each R4a and R4b independently Petition 870260076443, dated 07 / 31 / 2026, page 66 / 508 / 448 selected from C1-C3 alkyl. In some embodiments, R1 is -NRfRg, wherein RfRg together with the nitrogen to which they are attached form a 7-membered heterocycloalkyl ring that optionally contains 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, wherein the ring is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4- to 6-membered ring; and each R4ae R4bé independently selected from C1-C3 alkyl.

[0079] In some embodiments, R1 is -NRfRg, wherein RfRg together with the nitrogen to which they are attached form an 8-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, wherein the ring is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 13 substituents (e.g., 1 to 6 or 1 to 5 substituents) independently selected from C3-C6 cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6-membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl.In some embodiments, R1 is -NRfRg, wherein RfRg together with the nitrogen to which they are attached form an 8-membered heterocycloalkyl ring that optionally contains 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, wherein the ring is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4. Petition 870260076443, dated 07 / 31 / 2026, page 67 / 508 / 448 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b independently selected from C1-C3 alkyl.

[0080] In some embodiments, R1e -NRfRg, where Rfé is C1-C6 alkyl; and Rgé is C1-C6 alkyl substituted by 1 to 4 R4c groups, wherein each R4c group is independently selected from halogen, hydroxyl and nitrile. In some sports, R1 is

[0081] In some modes, R1 Petition 870260076443, dated 07 / 31 / 2026, p. 68 / 508 / 448 or In some modes, R1 is

[0082] In some embodiments, R2 is C1-C0 alkyl. In some embodiments, R2 is C1-C4 alkyl. In some embodiments, R2 is C1-C3 alkyl. In some embodiments, R2 is C1-C0 alkenyl. In some embodiments, R2 is C1-C0 alkyl or C1-C0 alkenyl. In some or

[0083] In some embodiments, R2 is C1-C0 haloalkyl. In some embodiments, R2 is C1-C4 haloalkyl. In some embodiments, R2 is C1-C3 haloalkyl.

[0084] In some embodiments, R2 is C1-C0 hydroxyalkyl. In some embodiments, R2 is C1-C4 hydroxyalkyl. In some embodiments, R2 is C1-C3 hydroxyalkyl.

[0085] In some embodiments, R2 is phenyl optionally substituted by 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl. In some embodiments, R2 is phenyl optionally substituted by 1 or 2 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy. [008ó] In some embodiments, R2 is optionally replaced by 1 or 2 R5 groups, where each R5 group is independently Petition 870260076443, dated 07 / 31 / 2026, page 69 / 508 / 448 selected from halogen, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy. In some embodiments, R2 is 4-fluorophenyl.

[0087] In some embodiments, R2 is C4-C6 cycloalkyl optionally substituted by 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl. In some embodiments, R2 is C4-C6 alkyl optionally substituted by 1 or 2 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy.

[0088] In some embodiments, R2 is a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the ring may optionally be substituted by 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl. In some embodiments, R2 is a 5- to 6-membered heteroaryl ring containing 1 to 4 heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the ring may optionally be substituted by 1 or 2 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy.

[0089] In some modes, R2 is In some modes, R2 is or In

[0090] In some embodiments, R2 is a 5 to 6 heteroaryl ring Petition 870260076443, dated 07 / 31 / 2026, page 70 / 508 / 448 members containing 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may optionally be substituted by 1 or 2 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy. In some embodiments, R2 is a 5-membered heteroaryl ring containing 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may optionally be substituted by 1 or 2 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy.In some embodiments, R2 is a 6-membered heteroaryl ring containing 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the ring may optionally be substituted by 1 or 2 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy. In some embodiments, R2 is 2-thiophene.

[0091]

[0092] In some modes, R2 is or In some modes, R2 is or In some modes, R2 is or In another aspect, a compound of Formula (B) is disclosed in this document. Petition 870260076443, dated 07 / 31 / 2026, p. 71 / 508 / 448 Formula (B) or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, wherein R1e5, wherein R1e is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl; Het is a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, optionally substituted by 1 to 4 R5 groups independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b are independently selected from H and C1-C3 alkyl; R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl, 5- to 6-membered heterocycloalkyl ring and 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring contain 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2; Petition 870260076443, dated 07 / 31 / 2026, page 72 / 508 / 448 R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted with nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted with 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently; Petition 870260076443, dated 07 / 31 / 2026, p. 73 / 508 / 448 selected from H, C1-C6 alkyl and C1-C6 haloalkyl; or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[0093] In another aspect, a compound of Formula (II') is disclosed in the present document. or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein R1 is C^, wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl; Het is a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, optionally substituted by 1 to 4 R5 groups independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b are independently selected from H and C1-C3 alkyl; R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl and 5- to 6-membered heteroaryl rings containing Petition 870260076443, dated 07 / 31 / 2026, page 74 / 508 / 448 to 4 independently selected ring heteroatoms from oxygen, sulfur and nitrogen, wherein the phenyl and 5 to 6 membered heteroaryl ring may optionally be substituted by 1 to 3 independently selected substituents from hydroxy, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and C(O)NH2; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted with nitrile or a 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the ring may be optionally substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, and hydroxyl; and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or a 5- to 6-membered heteroaryl ring, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxygen, sulfur, and nitrogen. Petition 870260076443, dated 07 / 31 / 2026, page 75 / 508 / 448 selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 independently selected halogens, and C1-C3 alkoxy optionally substituted by 1 to 7 independently selected halogens; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[0094] In another aspect, a compound of Formula (II) is disclosed in the present document or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein R1 is C^, wherein R1 is substituted by 1 to 3 R4 groups, wherein each R4 group is independently selected from nitrile and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from hydroxyl and halogen; Het is a 5- to 6-membered heteroaryl ring containing 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, optionally substituted by 1 or 2 R5 groups, independently selected from halogen, nitrile, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; R3 is selected from -C(O)NHR6 and is a 5- to 6-membered heteroaryl ring containing 1 to 3 independently ring heteroatoms. Petition 870260076443, dated 07 / 31 / 2026, page 76 / 508 / 448 selected from oxygen, sulfur and nitrogen, wherein the 5 to 6 membered heteroaryl ring may be optionally substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile and C1-C3 alkyl; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted with nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen and nitrogen, wherein the ring may be optionally substituted with 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from halogen, hydroxyl, nitrile and C1-C3 alkyl optionally substituted by one or more halogens independently selected; and each of R10, R11, R12 and R13 is independently; Petition 870260076443, dated 07 / 31 / 2026, p. 77 / 508 / 448 selected from H, C1-C6 alkyl and C1-C6 haloalkyl; or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[0095] In some embodiments, Het is a 5-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, optionally substituted by 1 to 4 R5 groups independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b are independently selected from H and C1-C3 alkyl. In some embodiments, Het is a 5-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, optionally substituted by 1 to 4 R5 groups independently selected from halogen, nitrile, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy.

[0096] In some embodiments, Het is a 5-membered heteroaryl ring containing 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, optionally substituted by 1 or 2 R5 groups, independently selected from halogen, nitrile, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; In some embodiments, Het H, or_. In some embodiments, Het is 2-thiophene \ —1 / . In some forms, Het is . In some forms, Het is_. In some forms, Het is

[0097] In some embodiments, Het is a 6-membered heteroaryl ring. Petition 870260076443, dated 07 / 31 / 2026, page 78 / 508 / 448 members containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, optionally substituted by 1 to 4 R5 groups independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b are independently selected from H and C1-C3 alkyl. In some embodiments, Het is a 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, optionally substituted by 1 to 4 R5 groups independently selected from halogen, nitrile, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy.

[0098] In some embodiments, Het is a 6-membered heteroaryl ring containing 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, optionally substituted by 1 or 2 R5 groups, independently selected from halogen, nitrile, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; In some JT' embodiments, Het is .

[0099] In another aspect, a compound of Formula (C) is disclosed in the present document. or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein R1 is O, wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and optionally C1-C6 alkyl Petition 870260076443, dated 07 / 31 / 2026, page 79 / 508 / 448 replaced by 1 to 4 substituents independently selected from C3C cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b independently selected from C1-C3 alkyl; R3 is selected from -C(O)NHR6, -SÜ2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl, 5- to 6-membered heterocycloalkyl ring and 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring contain 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C3 alkyl optionally substituted with a nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted with 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 Petition 870260076443, dated 07 / 31 / 2026, page 80 / 508 / 448 haloalkyl and hydroxy; and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[00100] In another aspect, a compound of Formula (IIa') is disclosed in the present document. or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein Petition 870260076443, dated 07 / 31 / 2026, p. 81 / 508 / 448 R1e?v-^, wherein R1e is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3C6 cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl; R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl and a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the phenyl and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and C(O)NH2; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted with nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted by 1 to 4 substituents Petition 870260076443, dated 07 / 31 / 2026, page 82 / 508 / 448 independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl; and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected;and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[00101] In another aspect, a compound of Formula (IIa) is disclosed in the present document. or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, Petition 870260076443, dated 07 / 31 / 2026, p. 83 / 508 / 448 in which R1 is 0, wherein R1 is substituted by 1 to 3 R4 groups, wherein each R4 group is independently selected from nitrile and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from hydroxyl and halogen; R3 is selected from -C(O)NHR6 and a 5- to 6-membered heteroaryl ring containing 1 to 3 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, and C1-C3 alkyl; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur and nitrogen; each of Rde Reé is independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted with nitrile or a 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen and nitrogen, wherein the ring may be optionally substituted with 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl; and (iii) phenyl, a saturated or partially unsaturated 3- to 6-membered ring or a 5- to 6-membered heteroaryl ring, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the Petition 870260076443, dated 07 / 31 / 2026, page 84 / 508 / 448 heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl ring, saturated or partially unsaturated, and the heteroaryl ring may optionally be substituted by 1 or 2 substituents independently selected from halogen, hydroxyl, nitrile and C1-C3 alkyl optionally substituted by one or more halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C0 alkyl and C1-C0 haloalkyl; or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C0 alkyl and C1-C0 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[00102] In another aspect, a compound of Formula (D) is disclosed in the present document. or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein R1 is O, wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3C cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 Petition 870260076443, dated 07 / 31 / 2026, p. 85 / 508 / 448 alquila; R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SU2-(C3-C6 cycloalkyl), phenyl, 5- to 6-membered heterocycloalkyl ring and 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring contain 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2; m is 0, 1, 2, 3 or 4; each R5 is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy; and each R5ae R5bé is independently selected from H and C1-C3 alkyl; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted by nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 Petition 870260076443, dated 07 / 31 / 2026, page 86 / 508 / 448 haloalkyl and hydroxy; and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[00103] In another aspect, a compound of Formula (III') is disclosed in the present document. or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein Petition 870260076443, dated 07 / 31 / 2026, p. 87 / 508 / 448 R1e?^, wherein R1e is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3C6 cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl; R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl and a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the phenyl and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and C(O)NH2; m is 0, 1, 2, 3 or 4; each R5 is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy; and each R5ae R5bé is independently selected from H and C1-C3 alkyl; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; Petition 870260076443, dated 07 / 31 / 2026, page 88 / 508 / 448 (ii) C1-C6 alkyl optionally substituted by nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[00104] In another aspect, a compound of Formula (III) is disclosed in the present document. Petition 870260076443, dated 07 / 31 / 2026, p. 89 / 508 / 448 or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein R1 is C^, wherein R1 is substituted by 1 to 3 R4 groups, wherein each R4 group is independently selected from nitrile and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from hydroxyl and halogen; R3 is selected from -C(O)NHR6 and a 5- to 6-membered heteroaryl ring containing 1 to 3 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, and C1-C3 alkyl; m is 0, 1, or 2; Each R5 is independently selected from among halogens; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C alkyl optionally substituted by nitrile or ring Petition 870260076443, dated 07 / 31 / 2026, page 90 / 508 / 448 5- or 6-membered heteroaryl containing 1 to 4 ring heteroatoms independently selected from oxygen and nitrogen, wherein the ring may optionally be substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from halogen, hydroxyl, nitrile and C1-C3 alkyl optionally substituted by one or more halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[00105] In another aspect, a compound of Formula (E) is disclosed in the present document. Formula (E) or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, wherein Petition 870260076443, dated 07 / 31 / 2026, p. 91 / 508 / 448 R1e5^, wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C3 alkyl optionally substituted by 1 to 4 substituents independently selected from C3C cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl; R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl, 5- to 6-membered heterocycloalkyl ring and 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring contain 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2; Alk is C1-Có alkyl or C1-Có alkenyl; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C alkyl optionally substituted by nitrile or ring Petition 870260076443, dated 07 / 31 / 2026, page 92 / 508 / 448 5- or 6-membered heteroaryl containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the ring may optionally be substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[00106] In some embodiments, Alk is C1-C6 alkyl. In some embodiments, Alk is C1-C6 alkenyl. In some embodiments, Alk is , , I ,-z\ or \ .

[00107] In another aspect, it is revealed in the present document a Petition 870260076443, dated 07 / 31 / 2026, p. 93 / 508 / 448 composed of Formula (IV') or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein R1 is 0, wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C3 alkyl optionally substituted by 1 to 4 substituents independently selected from C3C cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl; R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl and a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the phenyl and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and C(O)NH2; Alk is C1-C6 alkyl; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members. Petition 870260076443, dated 07 / 31 / 2026, page 94 / 508 / 448, optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted by nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the ring may be optionally substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s). Petition 870260076443, dated 07 / 31 / 2026, p. 95 / 508 / 448

[00108] In another aspect, a compound of Formula (IV) is disclosed in the present document. or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein R1 is 0, wherein R1 is substituted by 1 to 3 R4 groups, wherein each R4 group is independently selected from nitrile and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from hydroxyl and halogen; R3 is selected from -C(O)NHR6 and a 5- to 6-membered heteroaryl ring containing 1 to 3 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, and C1-C3 alkyl; Alk is C1-C6 alkyl; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted by nitrile or ring Petition 870260076443, dated 07 / 31 / 2026, page 96 / 508 / 448 5- or 6-membered heteroaryl containing 1 to 4 ring heteroatoms independently selected from oxygen and nitrogen, and wherein the ring may optionally be substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from halogen, hydroxyl, nitrile and C1-C3 alkyl optionally substituted by one or more halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[00109] In another aspect, a compound of Formula (F) is disclosed in the present document. Formula (F) or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, Petition 870260076443, dated 07 / 31 / 2026, p. 97 / 508 / 448 in which R1e -NRfRg, wherein (i) RfRg together with the nitrogen to which they are attached form a 4- to 8-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, -SR4a, -S(O)2R4ae C1-C6 alkyl optionally substituted with 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4ae R4bé independently selected from C1-C3 alkyl; or (i) Rfé C1-C6 alkyl; and Rgé C1-C6 alkyl substituted with 1 to 4 R4c groups, wherein each R4c group independently selected from halogen, hydroxyl and nitrile; R2 is selected from C1-C alkyl; C1-Có alkenyl; C1-Có haloalkyl; C1-C hydroxyalkyl; -(C1-C3 alkyl)-SO2CH3; -(C1-Có alkyl)-O(C1-Có alkyl) optionally substituted by 1 to 13 halogens; -(C1-C6 alkyl)-NR5aR5b; phenyl; C4-C6 cycloalkyl; and a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the phenyl, C4-C6 cycloalkyl, and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl; R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl, 5- to 6-membered heterocycloalkyl ring and 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring Petition 870260076443, dated 07 / 31 / 2026, page 98 / 508 / 448 members and the 5- to 6-membered heteroaryl ring contains 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxy, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen; each of Rde Reé independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted with nitrile or a 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the ring may be optionally substituted with 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, and hydroxyl; and (iii) phenyl, saturated or partially unsaturated 3- to 6-membered ring or a 5- to 6-membered heteroaryl ring, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be Petition 870260076443, dated 07 / 31 / 2026, page 99 / 508 / 448 optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C0 alkyl and C1-C0 haloalkyl; or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C0 alkyl and C1-C0 haloalkyl; or R11 and R12 together form a double bond, and R10 and R13 are independently selected from H, C1-C0 alkyl and C1-C0 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[00110] In another aspect, a compound of Formula (A) is disclosed in the present document. or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein R1e -NRfRg, wherein (i) RfRg together with the nitrogen to which they are attached form a 4- to 8-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, -SR4a, -S(O)2R4ae C1-C0 alkyl optionally substituted by Petition 870260076443, dated 07 / 31 / 2026, page 100 / 508 / 448 to 13 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4- to 6-membered ring; and each R4a and R4b independently selected from C1-C3 alkyl; or (ii) Rf C1-C6 alkyl; and Rg C1-C6 alkyl substituted by 1 to 4 R4c groups, wherein each R4c group independently selected from halogen, hydroxyl and nitrile; R2 is selected from C1-C6 alkyl; C1-C6 alkenyl; C1-C6 haloalkyl; C1-C6 hydroxyalkyl; -(C1-C3 alkyl)-SO2CH3; -(C1-C6 alkyl)-O(C1-C6 alkyl) optionally substituted by 1 to 13 halogens; -(C1-C6 alkyl)-NR5aR5b; phenyl; C4-C6 cycloalkyl; and a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the phenyl, C4-C6 cycloalkyl, and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl; X is CR20 or N; R20 is selected from H, halogen, nitrile, C1-C6 alkyl and C1-C6 haloalkyl; and R3 is a 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heteroaryl ring contains 1 to 4 ring nitrogens, and wherein the 5- to 6-membered heteroaryl ring may be optionally substituted with 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NHg; Each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; or any two of Petition 870260076443, dated 07 / 31 / 2026, p. 101 / 508 / 448 R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the two remaining members are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; or R11 and R12 together form a double bond, and R10 and R13 are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; in which 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

[00111] As indicated above, for each of Formulas (A), (B), (C), (D), (E) and (F), R1 is or may be represented as 0, wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C-cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl.

[00112] As stated above, for each of Formulas (I'), (II'), (IIa'), (III') and (IV'), R1 is or may be represented as C--I, wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl.

[00113] As indicated above, for each of Formulas (I), (II), (IIa), (III) and (IV), R1 is or can be represented as C·^, where R1 is replaced by 1 to 3 groups R4, where each group R4 is independently Petition 870260076443, dated 07 / 31 / 2026, page 102 / 508 / 448 selected from nitrile and C1-C alkyl optionally substituted by 1 to 4 substituents independently selected from hydroxyl and halogen.

[00114] In some embodiments, R1 may be a pyrrolidinyl ring (as shown above) that may be substituted by two R4 groups. By way of example, the pyrrolidinyl ring may be substituted by at least two R4 groups on an atom adjacent to the nitrogen atom. For example, the pyrrolidinyl group may comprise two R4 groups in a geminal substitution pattern (i.e., each R4 group may be attached to the same atom in the pyrrolidinyl ring).

[00115] As such, in some modalities of any of the In Formulas (A), (B), (C), (D), (E), and (F), R1 can be represented as , wherein two R4 groups are attached to a carbon atom adjacent to the nitrogen atom. In some embodiments of any of Formulas (I'), (II'), (IIa'), (III'), and (IV'), R1 can be represented as , wherein two R4 groups are attached to a carbon atom adjacent to the nitrogen atom. In some embodiments of any of Formulas (I), (II), (IIa), (III), and (IV), R1 can be represented as , wherein two R4 groups are attached to a carbon atom adjacent to the nitrogen atom. At least one of the R4 groups can be C1-C₂ alkyl. At least one of the R4 groups can be selected from nitrile and C1-C₂ alkyl optionally substituted by 1 to 4 substituents independently selected from hydroxyl and halogen. [0011ó] Just as an example, R1 can be represented as , where R4a is C1-C6 alkyl (like methyl); and R4b is selected Petition 870260076443, dated 07 / 31 / 2026, page 103 / 508 / 448, including nitrile and C1-C1 alkyl groups optionally substituted with 1 to 4 substituents independently selected from among hydroxyl and halogen groups. Representative examples of suitable R4b groups include, but are not limited to, nitrile, methyl, ethyl, CH2OH, CH(OH)CHs and CH(OH)CFs.

[00117] Just as an example, R1 can be represented as Λ, wherein R4 is a C1-C6 alkyl group (such as methyl); and R4a is selected from nitrile and C1-C6 alkyl groups optionally substituted by 1 to 4 substituents independently selected from hydroxyl and halogen groups. Representative examples of suitable R4a groups include, but are not limited to, nitrile, methyl, ethyl, CH2OH, CH(OH)CHs and CH(OH)CFs.

[00118] In some embodiments, R1 can be represented as , where R4 and R4b are as defined above.

[00119] In some embodiments of any one or more of Formulas (A), (B), (C), (D), (E), (F), (I'), (II'), (IIa'), (III'), (IV'), (I), (II), (lia), (III) and (IV), R3 is a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the 5- to 6-membered heteroaryl ring may be optionally substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and C(O)NH2. In some embodiments, R3 is a tetrazole, pyrazole, imidazole, oxazole, or pyridine, wherein R3 may be optionally replaced by 1 to 3 independently selected substituents of hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl, and -C(O)NH2.

[00120] In some modalities of any one or more of Formulas (I), (II), (IIa), (III) and (IV), R3 is a 5- to 6-membered heteroaryl ring containing 1 to 3 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the heteroaryl ring Petition 870260076443, dated 07 / 31 / 2026, p. 104 / 508 / 448, of 5 to 6 members may be optionally replaced by 1 to 3 substituents independently selected from hydroxy, nitrile and C1-C3 alkyl. In some embodiments, R3 is pyrazole, imidazole, oxazole, pyridonyl (e.g., 2-pyridonyl), or pyridine, wherein R3 may be optionally replaced by 1 to 3 substituents independently selected from hydroxy, nitrile and C1-C3 alkyl. When the heteroaryl ring comprises a ring nitrogen atom, the substituent may be directly attached to the nitrogen atom. By way of example only, R3 may be an N-(C1-C5 alkyl)pyridonyl group.

[00121] In some embodiments of any one or more of the Formulas (A), (B), (C), (D), (E), (F), (I'), (II'), (IIa'), (III'), (IV'), (I), (II), (IIa), (III) and (IV), R3 is a 5- to 6-membered heteroaryl ring containing 1 to 4 ring nitrogens, wherein the 5- to 6-membered heteroaryl ring may be optionally substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and C(O)NH2. In some embodiments, R3 is a tetrazolyl, optionally substituted by C1-C3 alkyl, for example, a methyl-substituted tetrazolyl ring.

[00122] As indicated above, in some embodiments of Formulas (A), (B), (C), (D), (E) and (F), R3 is -C(O)NHR6. In some embodiments of any one or more of Formulas (I'), (II'), (IIa'), (III') and (IV'), R3 is -C(O)NHR6. In some embodiments of any one or more of Formulas (I), (II), (IIa), (III) and (IV), R3 is -C(O)NHR6.

[00123] In some forms, R6e -(CR7R8)nC(O)NRdRe.

[00124] In some modes, n is 1. In some modes, n is 2.

[00125] In some embodiments, each of R7 and R8 is independently selected from H and C1-C3 alkyl. In some embodiments, R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members containing Petition 870260076443, dated 07 / 31 / 2026, p. 105 / 508 / 448 optionally a ring heteroatom selected from oxygen, sulfur and nitrogen.

[00126] In some embodiments, Rde Resão are both C1-C3 alkyl. In some embodiments, Rde Resão are both methyl.

[00127] In some modalities, R3é / or R3 is / or . In some modalities, In some modes, R3 Petition 870260076443, dated 07 / 31 / 2026, p. 106 / 508 / 448 or .

[00128] In some embodiments, R6 is a C1-C6 alkyl optionally substituted with nitrile or a 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the ring may be optionally substituted with 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, and hydroxyl. In some embodiments, R6 is a C1-C6 alkyl optionally substituted with nitrile or a 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen and nitrogen, wherein the ring may be optionally substituted with 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, and hydroxyl. In some embodiments, R6 is a C1-C6 alkyl optionally substituted with nitrile.In some embodiments, R6 is a 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen and nitrogen, wherein the ring may be optionally substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl, and hydroxyl. In some embodiments, R6 is pyrazolyl, oxazolyl, imidazolyl, pyridinyl, or 2-pyridonyl, each of which may be optionally substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, and C1-C3 haloalkyl. When the heteroaryl ring comprises a ring nitrogen atom, the substituent may be directly attached to the nitrogen atom.

[00129] In some embodiments, R6 is a C1-C5 alkyl optionally substituted with a nitrile or tetrazole. By way of example only, R6 may be a C1-C3 alkyl (such as a C3 alkyl) optionally substituted with a nitrile. Petition 870260076443, dated 07 / 31 / 2026, p. 107 / 508 / 448 or tetrazole.

[00130] In some embodiments, R6 is phenyl, a saturated or partially unsaturated ring of 3 to 6 members, or a heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from halogen, hydroxyl, nitrile, C1-C3 alkyl optionally substituted by one or more halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected.In some embodiments, R6 is phenyl, a saturated or partially unsaturated ring of 3 to 6 members, or a heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from halogen, hydroxyl, nitrile, and C1-C3 alkyl optionally substituted by one or more halogens independently selected. In some embodiments, R6 is phenyl optionally substituted by 1 or 2 substituents independently selected from halogen, hydroxyl, nitrile, and C1-C3 alkyl optionally substituted by one or more halogens independently selected.In some embodiments, R6 is a saturated or partially unsaturated ring with 3 to 6 members optionally containing 1 or 2 independently selected ring heteroatoms. Petition 870260076443, dated 07 / 31 / 2026, page 108 / 508 / 448, among oxygen, sulfur, and nitrogen, and the ring may be optionally substituted by 1 or 2 substituents independently selected from halogen, hydroxyl, nitrile, and C1-C3 alkyl optionally substituted by one or more halogens independently selected. In some embodiments, R6 is cyclopropane optionally substituted by nitrile or is cyclobutene optionally substituted by nitrile. In some embodiments, R6 is a 5- to 6-membered heteroaryl ring, wherein the ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, and the ring may be optionally substituted by 1 or 2 substituents independently selected from halogen, hydroxyl, nitrile, and C1-C3 alkyl optionally substituted by one or more halogens independently selected.Representative examples include, but are not limited to, pyridonyl (e.g., 2-pyridonyl) which may be optionally substituted with one or two substituents independently selected from halogen, hydroxyl, nitrile, and C1-C3 alkyl optionally substituted by one or more halogens independently selected. In some examples, R6 may be 2-pyridonyl optionally substituted by a C1-C3 alkyl (e.g., methyl), further optionally wherein the 2-pyridonyl is substituted at the nitrogen atom by a C1-C3 alkyl (e.g., methyl).

[00131] In some forms of any one or more of Formulas (A), (B), (C), (D), (E), and (F), each of R10, R11, R12, and R13 are independently selected from H, C1-C6 alkyl, and C1-C6 haloalkyl. In some embodiments, each of R10, R11, R12, and R13 is hydrogen. In some embodiments, two of R10, R11, R12, and R13, together with the carbon atom(s) to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl, and C1-C6 haloalkyl. In some embodiments, two of R10, R11, R12, and R13, together with the carbon atom(s) to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl, and C1-C6 haloalkyl. Petition 870260076443, dated 07 / 31 / 2026, p. 109 / 508 100 / 448 linked, form a cyclopropyl ring, and the two remaining are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl.

[00132] In some embodiments of any one or more of Formulas (I'), (II'), (IIa'), (III') and (IV'), each of R10, R11, R12 and R13 are independently selected from H, C1-C6 alkyl, and C1-C6 haloalkyl. In some embodiments, each of R10, R11, R12 and R13 is hydrogen. In some embodiments, two of R10, R11, R12 and R13, together with the carbon atom(s) to which they are attached, form a 3- to 6-membered ring, and the two remaining are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl. In some embodiments, two of R10, R11, R12 and R13, together with the carbon atom(s) to which they are attached, form a cyclopropyl ring, and the remaining two are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl.

[00133] In some embodiments of any one or more of the Formulas (I), (II), (IIa), (III) and (IV), each of R10, R11, R12 and R13 are independently selected from H, C1-C6 alkyl, and C1-C6 haloalkyl. In some embodiments, each of R10, R11, R12 and R13 is hydrogen. In some embodiments, two of R10, R11, R12 and R13, together with the carbon atom(s) to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl.

[00134] In some embodiments of Formula (A), R11 and R12 together form a double bond, and R10 and R13 are independently selected from H, C1-C6 alkyl, and C1-C6 haloalkyl. In some embodiments of Formula (I'), R11 and R12 together form a double bond, and R10 and R13 are independently selected from H, C1-C6 alkyl, and C1-C6 haloalkyl.

[00135] The compounds presently disclosed were and can be synthesized using the general synthetic procedures presented in the reaction schemes below. The execution of each illustrated step individually Petition 870260076443, dated 07 / 31 / 2026, page 110 / 508 101 / 448 is within the ability of an average expert guided by this disclosure, who also knows how to modify the synthetic procedures of the schemes below to synthesize the full scope of compounds disclosed in this document. The synthetic procedure for individual compounds is provided in the Examples section below.

[00136] In another aspect, a compound selected from Table 1, or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, is disclosed in the present document. bee 1 Comp. No. Name 4-1 [8-methoxy-9-(1-methylpyrazol-3-yl)-1-thiazol-5-yl-5,6-di-hidropyrrolo[2,1- a ]isoquinolin-3-yl]-[(2 S)2-methyl-2-[(1 R )-2,2,2-trifluoro-1-hidroxyethyl]pyrrolidin-1-yl]methane 4-2 (1-(5-fluoropyridin-2-yl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hidropyrrolo[2,1a]isoquinoline-3-yl)((S)-2-methyl-2-((R)-2,2,2-trifluoro-1-hidroxyethyl)pyrrolidin-1-yl)methanone 4-3 (R )-8-methoxy-5-methyl-3-((R )-2-methyl-2-((.S')-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidine-1-carbonyl)N-(1-methyl-2-oxo-1,2-di-hydropyridin-3-yl)-1-(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1- a]isoquinoline-9-carboxamide 6-1 (3 S)-4-[8-methoxy-9-(1-methylpyrazol-3-yl)-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-3carbonyl]-3-methyl-morpholine-3-carbonitrila 6-2 (2R )-1-[8-methoxy-9-(1-methylpyrazol-3 -yl)-1-thiazol-5-yl-5,6-di-hidropyrrolo[2,1- a ]isoquinoline-3carbonyl]-2-methyl-pyrrolidine-2-carbonitrila 6-3 (R )-1-(1-(1-hidroxy-2-methylpropan-2-yl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-dihydropyrrolo[2,1-a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila 6-4 (R )-1-(1-(2,2-difluoropropyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hydropyrrolo[2,1a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila 6-5 (R )-1-(1-(2,2-difluoropropyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hydropyrrolo[2,1a]isoquinolina-3-carbonyl)-2-methylazetidine-2-carbonitrila 6-6 (R )-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-propyl-5,6-di-hydropyrrolo[2,1-a]isoquinolina-3-carbonyl)-2-methylazetidin-2-carbonitrila 6-7 (R )-1-(1-(5-fluoropyridin-2-yl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hydropyrrolo[2,1a]isoquinolina-3-carbonyl)-2-methylazetidin-2-carbonitrila 6-8 (R )-1-(1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hydropyrrolo[2,1a]isoquinoline-3-carbonyl)-2-methylazetidine-2-carbonitrila 7-1 (2R )-1-[8-methoxy-9-oxazol-2-yl-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-3-carbonyl]2-methyl-pyrrolidine-2-carbonitrila 7-2 4-[3-[(2R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-1-(2-thienyl)-5,6-dihydropyrrolo[2,1- a ]isoquinolin-9-yl]-6-methyl-1 H-pyridin-2-one 7-3 (2R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidin-1-yl]-[8-methoxy-9-oxazol-2-yl-1-(2-thienyl)-5,6-dihydropyrrolo[2,1 - a ]isoquinolin-3 -yl]methanone 7-4 3-[3-[(2R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-1-(4-fluorophenyl)-8-methoxy-5,6-dihydropyrrolo[2,1- a ]isoquinolin-9-yl]pyridine-2-carbonitrila, Petition 870260076443, 07 / 31 / 2026, pág. 111 / 508 102 / 448 Comp. No. Name 7-5 3-[3-[(2R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-1-propyl-5,6-dihydropyrrolo[2,1- a ]isoquinolin-9-yl]pyridine-2-carbonitrila 7-6 [8-methoxy-9-(2-methyltetrazol-5-yl)-1-(2-thienyl)-5,6-dihydropyrrolo[2,1- a ]isoquinolin-3-yl]-[(2R )2-methyl-2-[(1 S)-2,2,2-trifluoro-1 -hydroxy-ethyl]pyrrolidin-1 -yl]methanone 7-7 (2R )-1-[9-(1 H-imidazol-2-yl)-8-methoxy-1-(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1a ]isoquinolina-3-carbonyl]-2-methyl-pyrrolidine-2-carbonitrila 7-8 (2R )-1-[8-methoxy-9-(2-methyltetrazol-5-yl)-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinolina-3carbonyl]-2-methyl-pyrrolidine-2-carbonitrila 7-9 (2R )-1-[8-methoxy-9-(2-methyltetrazol-5-yl)-1-propyl-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-3carbonyl]-2-methyl-pyrrolidine-2-carbonitrila 7-10 [(2R )-2-[(1 R )-1-hidroxyethyl]-2-methyl-pyrrolidin-1-yl]-[8-methoxy-9-(2-methyltetrazol-5-yl)-1-(2thienyl)-5,6-di-hidropyrrole[2,1 - a ]isoquinolin-3 -yl]metanona 7-11 (2R )-1-[8-methoxy-9-(2-methyltetrazol-5-yl)-1-(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1a ]isoquinolina-3-carbonyl]-2-methyl-pyrrolidine-2-carbonitrila 7-12 [(5 R )-8-methoxy-5-methyl-9-(2-methyltetrazol-5-yl)-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinolin-3-yl]-[(2 S)-2-methyl-2-[(1 R )-2,2,2-trifluoro-1-hydroxy-ethyl]pyrrolidin-1-yl]metanona 7-13 [(5 R )-8-methoxy-5-methyl-9-(2-methyltetrazol-5-yl)-1-thiazol-5-yl-5,6-di-hydropyrrolo[2,1- a ]isoquinolin-3 -yl]-[(2 R )-2-methyl-2-[(1 S)-2,2,2-trifluoro-1 -hydroxy-ethyl]pyrrolidin-1 -yl]methanone 7-14 (2R )-1-[8-methoxy-9-(2-methyltetrazol-5-yl)-1-thiazol-5-yl-5,6-di-hydropyrrolo[2,1- a ]isoquinolina-3carbonyl]-2-methyl-pyrrolidine-2-carbonitrila 7-15 (R )-3-(3 -(2-cyano-2-methylpyrrolidine-1-carbonyl)-8-methoxy-1 -(2,2,2-trifluoroethyl)-5,6-dihydropyrrolo[2,1-a]isoquinolin-9-yl)-5-(trifluoromethyl)picolinonitrila 7-16 (R )-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(2,2,2-trifluoroethyl)-5,6-dihydropyrrolo[2,1a]isoquinolin-3-carbonyl)-2-methylazetidine-2-carbonitrila 7-17 (8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(1,3,4-thiadiazol-2-yl)-5,6-di-hydropyrrolo [2,1a]isoquinolin-3-yl)(( S)-2-methyl-2-((R )-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)methanone 7-18 (R )-1-(1 -(3,3-difluorocyclobutyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hydropyrrolo[2,1a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila 7-19 (R )-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(thiophen-2-yl)-5,6-di-hydropyrrolo[2,1a]isoquinolina-3-carbonyl)-2-methylazetidine-2-carbonitrila 7-20 (R )-1-(1-(5-fluoropyridin-2-yl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hydropyrrolo[2,1a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila 7-21 (R )-1-(1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hydropyrrolo[2,1a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila 7-22 ((R )-8-methoxy-5-methyl-9-(2-methyl-2H-tetrazol-5-yl)-1-(thiophen-2-yl)-5,6-di-hydropyrrolo[2,1a]isoquinolin-3-yl)((R)-2-methyl-2-(( S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidm-1-yl)methanone 7-23 5-((R )-8-methoxy-5-methyl-3-((R )-2-methyl-2-((S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidine-1carbonyl)-1-(2,2,2-trifluoroethyl)-5,6-di-hydropyrrole[2,1-a]isoquinolin-9-yl)(24R4amide 3-7- )-8-methoxy-5-methyl-3-((R )-2-methyl-2-((S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1carbonyl)-1-(2,2,2-trifluoroethyl)-5,6-di-hi dropyrrolo-95[triquilapicolin-a ((R )-8-methoxy-5-methyl-9-(2-methyl-2H-tetrazol-5-yl)-1-(2,2,2-trifluoroethyl)-5,6-di- hydropyrrole[2,1-a]isoquinoline-3-yl)((R )-2-methyl-2-((S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1yl)methanone 7-26 ((1aR ,9bR )-8-methoxy-7-(2-methyl-2H-tetrazol-5-yl)-5-(thiophene-2-yl)-1a,9b-di-hydro-1Hcyclopropa[c]pyrrole[2,1-a]isoquinoline-3-yl)((R )-2-methyl-2-((S)-2,2,2-trifluoro-1hydroxyethyl)pyrrolidin-1 -yl)methanone, Petition 870260076443, dated 07 / 31 / 2026, p. 112 / 508 103 / 448 Comp. No. Name 7-27 [(2R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidin-1-yl]-[8-methoxy-9-(2-methyltetrazol-5-yl)-1-thiazol5-yl-5,6-di-hydropyrrolo[2,1- a ]isoquinolin-3-yl]methanone 7-28 [8-methoxy-9-(2-methyltetrazol-5-yl)-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinolin-3-yl]-[(2 S)2-methyl-2-[(1 R )-2,2,2-trifluoro-1-hydroxy-ethyl]pyrrolidin-1-yl]methanone 8-1 (2R )-1-[8-methoxy-9-(1-methylpyrazol-3 -yl)-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinolina-3carbonyl]-2-methyl-pyrrolidine-2-carbonitrila 8-2 (2R )-1-[8-methoxy-9-(1 H-pyrazol-3-yl)-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinolina-3carbonyl]-2-methyl-pyrrolidine-2-carbonitrila 8-3 (2R )-1-[1-(4-fluorophenyl)-8-methoxy-9-(1-methylpyrazol-3-yl)-5,6-di-hydropyrrolo[2,1a ]isoquinolina-3-carbonyl]-2-methyl-pyrrolidine-2-carbonitrila 8-4 (2R )-1-[8-methoxy-9-(1-methylpyrazol-3 -yl)-1-propyl-5,6-dihydropyrrolo[2,1- α ]isoquinolin-9-yl]-1-methyl-pyridin-2-ona 8-6 [(2R )-2-[(1 R )-1-hidroxyethyl]-2-methyl-pyrrolidin-1-yl]-[8-methoxy-9-(1 H-pyrazol-3-yl)-1-(2-thienyl)5,6-di-hidropyrrole[2,1- a ]isoquinolin-3-yl]methanone 8-7 6-[8-methoxy-3-[(2R )-2-methyl-2-[(1 S)-2,2,2-trifluoro-1-hydroxy-ethyl]pyrrolidine-1-carbonyl]-1-(2thienyl)-5,6-dihydropyrrolo[2,1- a ]isoquinolin-9-yl]-1 H-pyridin-2-one 8-8 4-[3-[(2R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-1-(2-thienyl)-5,6-dihydropyrrolo[2,1- a ]isoquinolin-9-yl]-1-methyl-pyridin-2-one 8-9 3-[3-[(2R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-1-(2,2,2-trifluoroethyl)-5,6-dihydropyrrolo[2,1- a ]isoquinolin-9-yl]pyridine-2-carbonitrila 8-10 [(5 R )-8-methoxy-5-methyl-9-(1-methylpyrazol-3-yl)-1-thiazol-5-yl-5,6-dihydropyrrolo [2,1- to ]isoquinolin-3 -yl]-[(2 R )-2-methyl-2-[(1 S)-2,2,2-trifluoro-1 -hydroxy-ethyl]pyrrolidin-1 -yl]methanone 8-11 (R )-1-(8-methoxy-9-(1-methyl-1H-pyrazol-3-yl)-1-(thiophene-2-yl)-5,6-di-hydropyrrole[2,1a]isoquinoline-3-carbonyl)-2-methylazetidine-2-carbonitrile 8-12( ((S )-1-1 *)-(-8-methoxy-6-methyl-9-(1-methyl-1H-pyrazol-3-yl)-1-(thiophene-2-yl)-5,6-dihydropyrrole[2,1-a]isoquinoline-3-carbonyl)-2-methylpyrrolidin-2-carbonitrile( R 8 )-8-methoxy-5-methyl-9-(1-methyl-1H-pyrazol-3-yl)-1-(thiophen-2-yl)-5,6-di-hydropyrrole[2,1a]i soquinolin-3-yl)((R)-2-methyl-2-((S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)methanone 8-14 ((R )-2-((R )-1-hydroxyethyl)-2-methylpyrrolidin-1-yl)(( S)-8-methoxy-5-methyl-9-(1-methyl-1H-pyrazol-3yl)-1 -(thiophen-2-yl)-5,6-lol-a[di]2hydropyr -yl)methanone 8-15 ((1aR ,9bR )-8-methoxy-7-(1-methyl-1H-pyrazol-3-yl)-5-(thiophen-2-yl)-1a,9b-di-hydro-1Hcyclopropa[c]pyrrole[2,1(-a-3]isoquinoline) )-2-methyl-2-((S)-2,2,2-trifluoro-1hidroxyethyl)pyrrolidin-1 -yl)methanone 8-16 (8-methoxy-9-(1-methyl-1H-pyrazol-3-yl)-1-(1,3,4-thiadiazol-2-yl)-5,6-di-hidropyrrolo[2,1a]isoquinoline-3-yl)((S)-2-methyl-2-((R)-2,2,2-trifluoro-1-hidroxyethyl)pyrrolidin-1-yl)methanone 9-1 [(2R )-2-[(1 R) -1-hidroxyethyl]-2-methyl-pyrrolidin-1-yl]-[9-(1 H-imidazol-2-yl)-8-methoxy-1-(2-thienyl)-5,6-di-hidropyrrole[2,1 - a ]isoquinolin-3 -yl]metanona 9-2 (2R )-1-[9-(1 H-imidazol-2-yl)-8-methoxy-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinolina-3carbonyl]-2-methyl-pyrrolidine-2-carbonitrila 10-1 N-(1-cyanocyclobutyl)-3-[(2R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy- 1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinolina-9-carboxamide 10-2 N-(1-cyano-1-methyl-ethyl)-3-[(2R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl] -1-(4-fluorophenyl)-8methoxy-5,6-di-hydropyrrolo[2,1-a ]isoquinoline-9-carboxamide 10-3 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-1-(4-fluorophenyl)-8-methoxy-N-(2-oxo-1 Hpyridin-3-yl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide, Petition 870260076443, dated 07 / 31 / 2026, p. 113 / 508 104 / 448 Comp. No. Name 10-4 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-1-(4-fluorophenyl)-8-methoxy-N-(1-methyl-2-oxo-3pyridyl)-5,6-di-hydropyrrolo[2,1-a ]isoquinoline-9-carboxamide 10-5 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-N-(2-oxo-1 H-pyridin-3-yl)-1-propyl- 5,6-di-hydropyrrolo[2,1-a ]isoquinoline-9-carboxamide 10-6 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-caibonyl]-8-methoxy-N-(1-methyl-2-oxo-3-pyridyl)-1-propyl- 5,6-di-hidropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-7 N-(1-cyano-1-methyl-ethyl)-3-[(2R )-2-[(1 R )-1-hidroxyethyl]-2-methyl-pyrrolidine-1-carbonyl]-8methoxy-1 -propyl-5,6-di-hidropyrrolo[2,1 - a ]isoquinoline-9-carboxamide 10-8 N-(1-cyanocyclobutyl)-3-[(2R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy1-propyl-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-9 N-(1-cyano-1-methyl-ethyl)-3-[(2R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-1-propyl-5,6di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-10 N-[2-(dimethylamino)-2-oxo-ethyl]-3-[(2R )-2-(hidroximetil)-2-metil-pirrolidina-1-carbonyl]-8methoxy-1-(2-thienyl)-5,6-dihidropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-11 3-(2,2-dimetilpirrolidina-1-carbonyl)-8-methoxy-N-(1 H-tetrazol-5-ylmetil)-1-(2-thienyl)-5,6-dihidropyrrolo[2,1 - a ]isoquinoline-9 -carboxamide 10-12 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-caibonil]-8-methoxy-N-(1-methyl-2-oxo-3-pyridyl)-1-(2thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-13 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-caibonil]-8-methoxy-N-(2-oxo-1 H-pyridin-3-yl)-1-(2thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-14 N-(1-cyano-1-methyl-ethyl)-8-methoxy-3-[(2 R )-2-methyl-2-[(1 S)-2,2,2-trifluoro-1-hidroxietil]pyrrolidine-1-carbonyl]-1-(2-thienyl)-5,6-di-hidropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-15 N-(1-cyanocyclobutyl)-3-[(2R )-2-[(1 R )-1-hidroxietil]-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy1-(2-thienyl)-5,6-di-hidropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-16 N-(1-cyano-1-methyl-ethyl)-3-[(2R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidine-1-carbonyl]-8methoxy-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-17 N-(1-cyanocyclobutyl)-1-(4-fluorophenyl)-3-[(2R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-18 N-(1-cyano-1-methyl-ethyl)-1-(4-fluorophenyl)-3-[(2 R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-19 N-(1-cyanocyclopropyl)-8-methoxy-3-[(2R )-2-methyl-2-[(1 S)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidine-1-carbonyl]-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-20 N-(1-cyanocyclopropyl)-3-[(2R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-21 8-methoxy-N-(1-methyl-2-oxo-3-pyridyl)-3-[(2R )-2-methyl-2-[(1 S)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidine-1-carbonyl]-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-22 N-(1-cyanocyclobutyl)-8-methoxy-3-[(2R )-2-methyl-2-[(1 S)-2,2,2-trifluoro-1-hydroxy- ethyl]pyrrolidine-1-carbonyl]-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-23 N-(1-cyanocyclobutyl)-3-[(2R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy1-(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-24 N-(1-cyanocyclobutyl)-3-[(2R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-1-(4-fluorophenyl)-8methoxy-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-25 N-(3-cyano-oxetan-3-yl)-8-methoxy-3-[(2 R )-2-methyl-2-[(1 S)-2,2,2-trifluoro-1-hidroxietil]pyrrolidine-1-carbonyl]-1-(2-thienyl)-5,6-di-hidropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-26 N-(3-cyano-oxetan-3-yl)-3-[(2R )-2-[(1 R )-1-hidroxietil]-2-methyl-pyrrolidine-1-carbonyl]-8methoxy-1-(2-thienyl)-5,6-di-hidropyrrolo[2,1- a ]isoquinoline-9-carboxamide, Petition 870260076443, dated 07 / 31 / 2026, p. 114 / 508 105 / 448 Comp. No. Name 10-27 N-(1-cyano-1-methyl-ethyl)-3-[(2R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-1-(2-thienyl)- 5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-28 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-N-[(3 R *)-3-cyanotetra-hydrofuran-3-yl]-8methoxy-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-29 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-N-[(3 S *)-3-cyanotetra-hydrofuran-3-yl]-8methoxy-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-30 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-N-(3-cyano-oxetan-3-yl)-8-methoxy-1-(2,2,2trifluoroethyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-31 N-(1-cyanocyclopropyl)-3-[(2R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-1-(2,2,2trifluoroethyl)-5,6-dihydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-32 N-(1-cyanocyclobutyl)-3-[(2R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy- 1-propyl-5,6-dihydropyrrole [2,1 - a ]isoquinoline-9 -carboxamide 10-33 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-N-(3-cyano-oxetan-3-yl)-8-methoxy-1-propyl-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-34 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-N-(3-cyano-oxetan-3-yl)-8-methoxy-1-(2-thienyl)- 5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 10-35 N-(1-cyanocyclobutyl)-3-[(2R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy- 1-thiazol-5-yl5,6-di-hidropyrrolo[2,1- a ]isoquinolina-9-carboxamida 10-36 (R )-3-(2-cyano-2-methylazetidine-1-carbonyl)-8-methoxy-N-(1-methyl-2-oxo-1,2-di-hidropyridin-3yl)-1-(2,2,2-trifluoroethyl)-5,6-di-hidropyrrolo[2,1-a]isoquinolina-9-carboxamida 10-37 (R )-3-(2-cyano-2-methylazetidine-1-carbonyl)-8-methoxy-N-(2-oxo-1,2-di-hydropyridin-3-yl)-1(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1-a]isoquinoline-9-carboxamide 10-38 N-(1 -cyanocyclobutyl)-8-methoxy-3-((S)-2-methyl-2-((R)-2,2,2-trifluoro-1 -hydroxyethyl)pyrrolidine1-carbonyl)-1-(1,3,4-thiadiazol-2-yl)-5,6-di-hydropyrrolo[2,1-a]isoquinoline-9-carboxamide 10-39 (R )-3-(2-cyano-2-methylazetidine-1-carbonyl)-N-(1-cyanocyclobutyl)-8-methoxy-1-(thiophen-2-yl)-5,6-di-hydropyrrolo[2,1 -a]isoquinoline-9 -carboxamide 10-40 (S* )-N-(1-cyanocyclobutyl)-3-((R )-2-((R )-1-hydroxyethyl)-2-methylpyrrolidine-1-carbonyl)-8-methoxy6-methyl-1-(thiophen-2-yl)-5,6-di-hydropyrrolo[2,1-a]isoquinoline-9-carboxamide 10-41 (S* )-3-((R )-2-cyano-2-methylpyrrolidine-1-carbonyl)-N-(1-cyanocyclobutyl)-8-methoxy-6-methyl-1-(thiophen-2-yl)-5,6-di-hydropyrrolo[2,1-a]isoquinoline-9-carboxamide 10-42 (R )-N-(1-cyanocyclobutyl)-3-((R)-2-((R )-1-hydroxyethyl)-2-methylpyrrolidine-1-carbonyl)-8-methoxy5-methyl-1-(thiophen-2-yl)-5,6-di-hydropyrrolo[2,1-a]isoquinoline-9-carboxamide 10-43 (R )-N-(1-cyanocyclobutyl)-8-methoxy-5-methyl-3-((R )-2-methyl-2-((S)-2,2,2-trifluoro-1hydroxyethyl)pyrrolidine-1-carbonyl)-1-(thiophen-2-yl)-5,6-di-hydropyrrolo[2,1-a]isoquinoline-9-carboxamide 10-44 (S)-N-(1-cyanocyclobutyl)-3-((R )-2-((R )-1-hydroxyethyl)-2-methylpyrrolidine-1-carbonyl)-8-methoxy-5-methyl-1-(thiophen-2-yl)-5,6-di-hydropyrrolo[2,1-a]isoquinoline-9-carboxamide 10-45 (4 S)-N-(1-cyanocyclobutyl)-7-methoxy-4-methyl-3-((R )-2-methyl-2-((S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidine-1-carbonyl)-1-(thiophen-2-yl)-3a,5-di-hydro-4H-cyclopenta[a]naphthalene-8-carboxamide 10-46 (S)-3-((R )-2-cyano-2-methylpyrrolidine-1-carbonyl)-N-(1-cyanocyclobutyl)-8-methoxy-5-methyl-1(thiophen-2-yl)-5,6-di-hydropyrrolo[2,1-a]isoquinoline-9-carboxamide 10-47 (R )-N-(1-cyanocyclobutyl)-8-methoxy-5-methyl-3-((R )-2-methyl-2-((S)-2,2,2-trifluoro-1- hydroxyethyl)pyrrolidine-1-carbonyl)-1-(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1-a]isoquinoline-9-carboxamide, Petition 870260076443, 07 / 31 / 2026, pág. 115 / 508 106 / 448 Comp. No. Name 10-48 (1aR ,9bR )-N-(1-cyanocyclobutyl)-8-methoxy-3-((R )-2-methyl-2-((S)-2,2,2-trifluoro-1- hydroxyethyl)pyrrolidine-1-carbonyl)-5 -(thiophen-2-yl)-1a,9b-di-hydro- 1H-cyclopropa[c]pyrrolo[2,1a]isoquinoline-7-carboxamide 11-1 N-[2-(dimethylamino)-2-oxo-ethyl]-3-[(2 S)-2-ethyl-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-1-(2thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 13-1 [(2R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidin-1-yl]-[8-methoxy-9-(1-methylpyrazol-3-yl)-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1 - a ]isoquinolin-3 -yl]methanone 13-2 [8-methoxy-9-(1-methylpyrazol-3-yl)-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinolin-3-yl]-[(2R )2-methyl-2-[(1 S)-2,2,2-trifluoro-1 -hydroxy-ethyl]pyrrolidin-1 -yl]methanone 13-3 [(2R )-2-[(1 S)-1-hydroxyethyl]-2-methyl-pyrrolidin-1-yl]-[8-methoxy-9-(1-methylpyrazol-3-yl)-1-propyl5,6-di-hydropyrrolo[2,1- a ]isoquinolin-3-yl]methanone 13-4 [1-(4-fluorophenyl)-8-methoxy-9-(1-methylpyrazol-3-yl)-5,6-di-hydropyrrolo[2,1- a ]isoquinolin-3-yl][(2 S)-2-methyl-2-[(1 R )-2,2,2-trifluoro-1-hydroxy-ethyl]pinOlidin-1-yl]methanone 13-5 [1-(4-fluorophenyl)-8-methoxy-9-(1-methylpyrazol-3-yl)-5,6-di-hydropyrrole[2,1- to ]isoquinoline-3-yl][(2 R )-2-[(1 S) -1 -hydroxyethyl] -2-limethyl-ano-6pyrrole [1-(4-fluorophenyl)-8-methoxy-9-(1-methylpyrazol-3-yl)-5,6-di-hydropyrrole[2,1- to ]isoquinolin-3-yl][(2 R )-2-[(1 R )-1 -hydroxyethyl] -2-methylnane-7-pyrrolyl] [1-(4-fluorophenyl)-8-methoxy-9-(1-methylpyrazol-3-yl)-5,6-di-hydropyrrole[2,1- to ]isoquinoline-3-yl][(2 S)-2-[(1 S) -1 -hydroxyethyl] -2-limethylane-1-pyrro S)-2-[(1 S)-1-hydroxyethyl]-2-methyl-pyrrolidin-1-yl]-[8-methoxy-9-(1-methylpyrazol-3-yl)-1-(2thienyl)-5,6-di-hydropyrrole[2,1 - a ]isoquinolin-9methanone-13 -yl [1-(4-fluorophenyl)-8-methoxy-9-(2-methyltetrazol-5-yl)-5,6-di-hydropyrrole[2,1- to ]isoquinolin-3-yl][(2 S)-2-methyl-2-[(1 R )-2,2,2-trifluoro-1-hydroxy-ethyl]pinOlidin-1-yl]metanona 13-10 [1-(4-fluorophenyl)-8-methoxy-9-(2-methyltetrazol-5-yl)-5,6-di-hydropyrrolo[2,1- a ]isoquinolin-3-yl][(2 S* )-2-[(1 S)-1-hydroxypropyl]-2-methyl-pyrrolidin-1-yl]metanona 13-11 [1-(4-fluorophenyl)-8-methoxy-9-(2-methyltetrazol-5-yl)-5,6-di-hydropyrrolo[2,1- a ]isoquinolin-3-yl][(2 S)-2-[(1 S)-1 -hydroxyethyl]-2-methyl-pyrrolidin-1-yl]metanona 13-12 (R* )-2-(R*)-cyclopropyl(hydroxy)methyl)-2-methylpyrrolidin-1-yl)(1-(4-fluorophenyl)-8-methoxy-9-(2methyl-2H-tetrazol-5 -yl)-5,6-di-hydropyrrolo[2,1 -a]isoquinolin-3 -yl)methanone 18-1 (R )-3-(2-cyano-2-methylpyrrolidin-1-carbonyl)-N-(2-cyanopropan-2-yl)-8-methoxy-1-(2,2,2trifluoroethyl)-5,6-di-hydropyrrolo[2,1-a]isoquinoline-9-carboxamide 18-2 N-(1-cyanocyclobutyl)-3-[(2R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-1-(2,2,2trifluoroethyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 18-3 3-[(2 R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-N-(1-methyl-2-oxo-3-pyridyl)-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 18-4 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-N-(1-methyl-2-oxo-3-pyridyl)-1-(2,2,2trifluoroethyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 18-5 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-N-(2-oxo-1 H-pyridin-3-yl)-1-(2,2,2trifluoroethyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide 18-6 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-N-[(3 R* )-3-cyanotetra-hydrofuran-3-yl]-8methoxy-1 -(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1 - a ]isoquinoline-9-carboxamide 18-7 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-N-[(3 S* )-3-cyanotetra-hydrofuran-3-yl]-8methoxy-1 -(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1 - a ]isoquinoline-9-carboxamide 20-1 [1-(4-fluorophenyl)-8-methoxy-9-(2-methyltetrazol-5-yl)-5,6-di-hydropyrrolo[2,1- a ]isoquinolin-3-yl][(2R ou S)-4,4-difluoro-2-methyl-2-[(1 R ou S)-1-hidroxietil]pyrrolidin-1-yl]methanona 24-1 N-(1-cyanocyclobutyl)-3-[(2R )-2-[(1 R )-1-hidroxietil]-2-methyl-pyrrolidin-1-carbonyl]-8-methoxy1 -thiazol-5 -yl-5,6-di-hidropyrrolo[2,1 - a ]isoquinolina-9 -carboxamide, Petition 870260076443, 07 / 31 / 2026, pág. 116 / 508 107 / 448 Comp. No. Name 24-2 N-(1-cyanocyclobutyl)-8-methoxy-3-[(2R )-2-methyl-2-[(1 S)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidine-1 -carbonyl]-1 -thiazol-5 -yl-5,6-di-hydropyrrolo[2,1 - a ]isoquinoline-9-carboxamide 25-1 (2R*-2-ethyl-1-[8-methoxy-9-(1-methylpyrazol-3-yl)-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1a ]isoquinoline-3-carbonyl]pyrrolidine-2-carbonitrila 26-1 rel -(2R, 3 S)-3-hydroxy-1-[8-methoxy-9-(2-methyltetrazol-5-yl)-1-propyl-5,6-di-hydropyrrolo[2,1a ]isoquinolina-3-carbonyl]-2-methyl-pyrrolidine-2-carbonitrila 26-2 rel -(2R ,3 S)-1-[1-(4-fluorophenyl)-8-methoxy-9-(2-methyltetrazol-5-yl)-5,6-di-hydropyrrolo[2,1a ]isoquinolina-3 -carbonyl]-3 -hydroxy-2-methyl-pyrrolidine-2-carbonitrila 32-1 (1S* ,6R* )-2-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-propyl-5,6-di-hydropyrrolo[2,1a]isoquinolina-3 -carbonyl)-2-azabicyclo[4.2.0]octano-1 -carbonitrila 32-2 (1S,5S)-2-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-propyl-5,6-di-hydropyrrolo[2,1a]isoquinolina-3-carbonyl)-5-methyl-2-azabicyclo[3.2.0]heptane-1-carbonitrile 33-1 (2R,4 S)-4-hydroxy-1-[8-methoxy-9-(2-methyltetrazol-5-yl)-1-propyl-5,6-dihydropyrro-lo[2,1a]isoquinoline-3-carbonyl]-2-methyl-pyrrolidine-2-carbonitrile 34-1 (2R,4 S)-1-[1-(4-fluorophenyl)-8-methoxy-9-(2-methyltetrazol-5-yl)-5,6-dihydropyrrolo[2,1a]isoquinoline-3-carbonyl]-4-hydroxy-2-methyl-pyrrolidine-2-carbonitrile.

[00137] In another aspect, a compound selected from Table 2, or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, is disclosed in the present document. bee 2 Example Name 1 (2R,4S)-4-hydroxy-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(thiophen-2-yl)-5,6-dihydroimidazo[5,1-a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila 2 (R)-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(thiophen-2-yl)-5,6-dihydroimidazo[5,1a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila 3 (8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(thiophen-2-yl)-5,6-di-hidroimidazo[5,1-a]isoquinolin-3yl)((S)-2-methyl-2-((R)-3,3,3-trifluoro-1-hidroxypropyl)pyrrolidin-1 -yl)methanone 4 (8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(thiophen-2-yl)-5,6-di-hidroimidazo[5,1-a]isoquinolin-3yl)((S)-2-methyl-2-((S)-3,3,3-trifluoro-1 -hidroxypropyl)pyrrolidin-1 -yl)methanone 5 (S)-N-(2-cyano-4,4,4-trifluorobutan-2-yl)-8-methoxy-N-methyl-9-(2-methyl-2H-tetrazol-5-yl)-1(thiophen-2-yl)-5,6-di-hidroimidazo[5,1-a]isoquinoline-3 -carboxamida 6 (2R,4S)-1-(1-(3,3-difluorocyclobutyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-dihidroimidazo[5,1-a]isoquinoline-3-carbonyl)-4-hydroxy-2-methylpyrrolidine-2-carbonitrila 7 (R)-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(2,2,2-trifluoroethyl)-5,6-di-hydroimidazo[5,1a]isoquinoline-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila 8 (8-methoxy-9-(1-methyl-1H-pyrazol-3-yl)-1-(thiophen-2-yl)-5,6-di-hydroimidazo[5,1-a]isoquinolin-3yl)((S)-2-methyl-2-((R)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)methanone 9 10 11 (8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(thiophen-2-yl)-5,6-di-hidroimidazo[5,1-a]isoquinoline-3yl)((R)-2-methyl-2-((S)-2,2,2-trifluoro-1-hidroxyethyl)pyrrolidin-1-yl)methanone, Petition 870260076443, 07 / 31 / 2026, pág. 117 / 508 108 / 448 Exemplo Name 12 (R)-3-(2-cyano-2-methylpyrrolidine-1-carbonyl)-8-methoxy-N-(1-methyl-2-oxo-1,2-di-hidropyridin-3yl)-1-(thiophen-2-yl)-5,6-di-hidroimidazo[5,1-a]isoquinolina-9-carboxamida 13 (R)-3-(2-cyano-2-methylpyrrolidine-1-carbonyl)-8-methoxy-N-(2-oxo-1,2-di-hidropyridin-3-yl)-1(thiophen-2-yl)-5,6-di-hidroimidazo[5,1-a]isoquinolina-9-carboxamida 14 15 ((S)-2-((R)-1,2-di-hidroxi-2-methylpropyl)-2-methylpyrrolidin-1-yl)(1-(4-fluorophenyl)-8-methoxy-9(2-methyl-2H-tetrazol-5-yl)-5,6-di-hidropyrrolo[2,1-a]isoquinoline-3-yl)methanone 16 17 (1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hidropyrrolo[2,1-a]isoquinolin3-yl)((S)-2-methyl-2-((S)-3,3,3-trifluoro-1 -hydroxypropyl)pyrrolidin-1 -yl)methanone 18 (R)-3-(2-cyano-2-methylazetidine-1-carbonyl)-8-methoxy-N-(1-methyl-2-oxo-1,2-di-hydropyridin-3 il)-1 -propyl-5,6-di-hydropyrrolo[2,1 -a]isoquinoline-9-carboxamide 19 (R)-3-(2-cyano-2-methylazetidine-1-carbonyl)-8-methoxy-N-(2-oxo-1,2-di-hydropyridin-3-yl)-1propyl-5,6-di-hydropyrrolo[2,1-a]isoquinoline-9-carboxamide 20 21 (8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-propyl-5,6-di-hidroimidazo[5,1-a]isoquinoline-3-yl) ((R)-2-methyl-2-((S)-2,2,2-trifluoro-1-hidroxiethyl)pyrrolidm-1 -yl)methanone 22 (R)-3-(2-cyano-2-methylazetidine-1-carbonyl)-1-isobutyl-8-methoxy-N-(2-oxo- 1,2-di-hidropyridin3-yl)-5,6-di-hidropyrrolo[2,1-a]isoquinoline-9-carboxamide 23 (R)-3-(2-cyano-2-methylazetidine-1-carbonyl)-1-isobutyl-8-methoxy-N-(1-methyl-2-oxo-1,2-dihidropyridin-3-yl)-5,6-di-hidropyrrolo[2,1-a]isoquinoline-9-carboxamida 24 (8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1a]isoquinolin-3-yl)((S)-2-methyl-2-((S)-3,3,3-trifluoro-1-hydroxypropyl)pyrrolidin-1-yl)methanone 25 (R)-3-(2-cyano-2-methylazetidine-1-carbonyl)-8-methoxy-N-(1-methyl-2-oxo-1,2-di-hydropyridin-3 yl)-1-(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1-a]isoquinoline-9-carboxamida 26 (1-(4-fluorophenyl)-8-methoxy-9-(1-methyl-1H-pyrazol-3-yl)-5,6-di-hidroimidazo[5,1-a]isoquinolin3-yl)((S)-2-methyl-2-((R)-2,2,2-trifluoro-1 -hidroxyethyl)pyrrolidin-1 -yl)methanone 27 (1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hidroimidazo[5,1-a]isoquinolin3-yl)((S)-2-methyl-2-((R)-2,2,2-trifluoro-1 -hidroxyethyl)pyrrolidin-1 -yl)methanone 28 (R)-3-(2-cyano-2-methylpyrrolidine-1-carbonyl)-1-(4-fluorophenyl)-8-methoxy-N-(1-methyl-2-oxo-1,2di-hidropyridin-3-yl)-5,6-di-hidroimidazo[5,1-a]isoquinoline-9-carboxamide 29 (1-(3,5-difluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hydropyrrolo[2,1a]isoquinolin-3-yl)((S)-2-methyl-2-((S)-3,3,3-trifluoro-1-hydroxypropyl)pyrrolidin-1-yl)metanona 30 {(S)-2-[(S)-3,3,3-trifluoro-1-hydroxypropyl]-2-methyl-1-pyrrolidinyl}{11-methoxy-12-(2-methyl-2Htetraazol-5-yl)-3-(2-thienyl)-6-azatricyclo[7.4.0.02,6]trideca-1(13),2,4,9,11-pentaen-5-yl}metanona 31 (R)-1-(8-methoxy-9-(1-methyl-1H-pyrazol-3-yl)-1-(thiophen-2-yl)-5,6-di-hydroimidazo[5,1a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila 32 (R)-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(2-methylprop-1 -en-1-yl)-5,6-di-hydropyrrolo[2,1a]isoquinolina-3-carbonyl)-2-methylazetidine-2-carbonitrila 33 (S)-3-(1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hydropyrrolo[2,1a]isoquinolina-3-carbonyl)-4-methyloxazolidine-4-carbonitrila 34 (S)-3 -(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-propyl-5,6-di-hydropyrrolo[2,1-a]isoquinolina-3 carbonyl)-4-methyloxazolidine-4-carbonitrila, Petition 870260076443, 07 / 31 / 2026, pág. 118 / 508 109 / 448Example Name 35 (R)-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-propyl-5,6-di-hydroimidazo[5,1-a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila 36 (R)-1-(8-methoxy-9-(1-methyl-1H-pyrazol-3-yl)-1-(2,2,2-trifluoroethyl)-5,6-di-hydroimidazo[5,1a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila 37 (R)-1-(1-(3,3-difluorocyclobutyl)-8-methoxy-9-(1-methyl-1H-pyrazol-3-yl)-5,6-di-hydroimidazo[5,1a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila 38 (S)-3-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1a]isoquinolina-3-carbonyl)-4-methyloxazolidine-4-carbonitrila 39 (R)-1-(1-(4-fluorophenyl)-8-methoxy-9-(1-methyl-1H-pyrazol-3-yl)-5,6-di-hidroimidazo[5,1a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila 40 (R)-1-(1-(4-fluorophenyl)-8-methoxy-9-(1-methyl-1H-pyrazol-3-yl)-5,6-di-hidroimidazo[5,1a]isoquinolina-3-carbonyl)-2-methylazetidine-2-carbonitrila 41 (R)-1-(1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-dihydroimidazo[5,1a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila 42 (R)-1-(1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-dihydroimidazo[5,1a]isoquinolina-3-carbonyl)-2-methylazetidine-2-carbonitrila 43 (R)-3-(3-(2-cyano-2-methylpyrrolidine-1-carbonyl)-1-(4-fluorophenyl)-8-methoxy-5,6-dihydroimidazo[5,1-a]isoquinolin-9 -yl)picolinonitrila 44 (R)-3-(3-(2-cyano-2-methylazetidine- (R)-1-(9-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)-8-methoxy-1-(thiophen-2-yl)-5,6-dihydroimidazo[5,1-a]isoquinoline-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila 46 (R)-8-methoxy-5-methyl-3-((R)-2-methyl-2-((S)-2,2,2-trifluoro-1-hidroxyethyl)pyrrolidine-1carbonyl)-N-(1-methyl-2-oxo-1,2-di-hidropyridin-3-yl)-1-(2,2,2-trifluoroethyl)-5,6-dihidropyrrole [2,1 -a]isoquinoline-9-carboxamida 47 3-((R)-3-((2R,4S)-2-cyano-4-hidroxy-2-methylpyrrolidine-1-carbonyl)-8-methoxy-5-methyl-1-(2,2,2trifluoroethyl)-5,6-di-hydropyrrolo[2,1-a]isoquinolin-9-yl)picolinonitrila 48 (8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(2-methylprop-1 -en-1-yl)-5,6-di-hydropyrrolo[2,1a]isoquinolin-3-yl)((S)-2-methyl-2-((S)-3,3,3-trifluoro-1-hydroxypropyl)pyrrolidin-1-yl)methanona 49 (2R,4S)-4-hydroxy-1-(1-isobutyl-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hydropyrrolo[2,1a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila 50 (S)-N-(2-cyano-4,4,4-trifluorobutan-2-yl)-8-methoxy-N-methyl-9-(2-methyl-2H-tetrazol-5-yl)-1-(2metilprop-1 -en-1 -yl)-5,6-di-hidropyrrolo[2,1 -a]isoquinolina-3 -carboxamide 51 (S)-N-(2-cyano-4,4,4-trifluorobutan-2-yl)-1-(2,2-diflu oropropyl)-8-methoxy-N-methyl-9-(2-metil2H-tetrazol-5-yl)-5,6-di-hidropyrrolo[2,1-a]isoquinolina-3-carboxamide 52 (S)-N-(2-cyano-4,4,4-trifluorobutan-2-yl)-8-methoxy-N-methyl-9-(2-methyl-2H-tetrazol-5-yl)-1(1,3,4-thiadiazol-2-yl)-5,6-di-hydropyrrolo[2,1 -a]isoquinoline-3 -carboxamide 53 (S)-N-(2-cyano-4,4,4-trifluorobutan-2-yl)-1-(5-fluoropyridin-2-yl)-8-methoxy-N-methyl-9-(2-methyl2H- 1,2,3-triazol-4-yl)-5,6-dihydropyrrolo[2,1-a]isoquinolina-3-carboxamide 54 ((R)-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(2-methylprop-1-en-1-yl)-5,6-dihydropyrrolo[2,1-a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila 55 (1-(tert-butyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hidroimidazo[5,1-a]isoquinolin-3yl)((S)-2-methyl-2-((S)-3,3,3-trifluoro-1 -hidroxypropyl)pyrrolidin-1 -yl)methanone 56 (R)-1-(1-isobutyl-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hidroimidazo[5,1a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila 57 (R)-1-(1-(3,3-difluorocyclobutyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-dihydroimidazo[5,1-a]isoquinoline-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila, Petition 870260076443, 07 / 31 / 2026, pág. 119 / 508 110 / 448 Example Name 58 (1-isobutyl-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hydropyrrolo[2,1-a]isoquinolin-3yl)((S)-2-methyl-2-((S)-3,3,3-trifluoro-1 -hydroxypropyl)pyrrolidin-1 -yl)methanone 59 (1-(tert-butyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hydropyrrolo[2,1-a]isoquinolin-3yl)((S)-2-methyl-2-((S)-3,3,3-trifluoro-1 -hydroxypropyl)pyrrolidin-1 -yl)methanone 60 (1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hydroimidazo[5,1-a]isoquinolin-3-yl)((S)-2-methyl-2-((S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)methanone 61 (2R,4S)-1-(1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hydroimidazo[5,1a]isoquinolina-3-carbonyl)-4-hydroxy-2-methylpinOlidin-2-carbonitrila 62 (R)-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(2-methylalyl)-5,6-di-hydropyrrolo[2,1a]isoquinoline-3-carbonyl)-2-methylazetidine-2-carbonitrila ATIVIDADE DOS COMPOSTOS

[00138] As noted above, the compounds disclosed herein have activity as FSHR modulators. This activity can be evaluated by any suitable FSHR interaction assay, such as a cAMP accumulation assay, as illustrated in the Examples, and the other assays described below and illustrated in the Examples. The compounds disclosed herein may show EC50 values ​​less than 1000 nM, less than or equal to 500 nM, less than or equal to 100 nM, less than or equal to 10 nM, or less than or equal to 1 nM, where EC50 is the effective concentration of a compound at which 50% of the maximum response that would be obtained with FSH is observed.

[00139] The glycoprotein hormone receptors FSHR, TSHR, and LHR / LHCGR predominantly activate the Gas class of intracellular G proteins, resulting in cAMP accumulation. The Homogeneous Time-Resolved Fluorescence (HTRF) assay illustrated in the Examples is based on the competition between native cell-produced cAMP and d2-dye-labeled cAMP (red acceptor) for binding to a cryptate-labeled antibody (europium donor). The specific energy transfer signal is inversely proportional to the cAMP concentration in the standard or sample. See, for example, Nataraja, SG, et al., Frontiers in Endocrinology. 2015, 6:142.

[00140] Another assay uses the steroidogenic granulosa cell line Petition 870260076443, dated 07 / 31 / 2026, page 120 / 508 111 / 448 immortalized mouse cells, GFSHR-17, which stably express the FSH receptor and are responsive to FSH stimulation with human FSH. See, for example, Keren-Tal, I., et al., Molecular and Cellular Endocrinology, 1993, 95:RL-Rl0. This engineered cell line lacks the aromatase found in primary granulosa cells necessary for the conversion of androgenic precursors to estrogens. However, it shows a robust progesterone response that can serve as a surrogate to verify the activity of FSHR agonists. It can be used in a cell-based assay to evaluate the ability of compounds to activate FSHR in GFSHR-17 cells by measuring the progesterone released into the supernatant, such as using a Cisbio progesterone HTRF kit. A ratiometric HTRF reading has been established to assess the agonist activity of compounds and is described in the examples below.

[00141] The activity of the compounds described in this document as FSHR agonists can be investigated using a modification of the classic FSH bioassay (Steelman-Pohley) that is based on the increase in ovarian weight in immature female rats. See Steelman, SL and FM Pohley, Endocrinology, 1953, 53(6):604-16. It is well documented that FSHR activation in women stimulates the granulosa cells of ovarian follicles to proliferate and induce the expression of aromatase and luteinizing hormone receptors. See, for example, Donadeu, FX and M. Ascoli, Endocrinology, 2005, 146 (9):3907-16. Proper granulosa cell expansion and gene expression are essential to induce steroid synthesis and secretion, enabling the follicle to respond to the pre-ovulatory luteinizing hormone surge, which triggers ovulation of the oocytes contained within the follicles in the oviduct where they can be fertilized.Therefore, it is reasonable to measure ovarian weight gain as a function of granulosa cell expansion, the number of ovulated oocytes as a function of follicular maturation, and uterine weight as a function of estradiol synthesis and secretion. Petition 870260076443, dated 07 / 31 / 2026, p. 121 / 508 112 / 448

[00142] In some embodiments, a compound, as disclosed in this document, selectively activates FSHR compared to, for example, TSHR. This selective activity can be assessed by any suitable FSHR / TSHR assay comparing the potency in the accumulation of cAMP specific to individual receptors, such as an assay illustrated in the Examples (assessing selectivity based on EC50 ratios).

[00143] In some embodiments, a compound, as disclosed herein, selectively activates FSHR compared to, for example, luteinizing hormone receptor. This selective activity can be assessed by any suitable FSHR / LHR assay comparing the potency on cAMP accumulation specific to individual receptors, such as an assay illustrated in the Examples (assessing selectivity based on EC50 ratios).

[00144] In some embodiments, a compound as disclosed herein exhibits at least 5 times greater selectivity for FSHR than for TSHR. This includes 5-, 6-, 7-, 8-, 9-, 10-, 11-, 12-, 13-, 14-, 15-, 16-, 17-, 18-, 19-, 20-, 21-, 22-, 23-, 24-, 25-, 26-, 27-, 28-, 29-, 30-, 31-, 32-, 33-, 34-, 35-, 36-, 37-, 38-, 39-, 40-, 41-, 42-, 43-, 44-, 45-, 46-, 47-, 48-, 49-, less or 50 times, or more, greater selectivity for the hormone receptor. It is more effective against follicle-stimulating hormone than against the thyroid-stimulating hormone receptor. A compound as disclosed herein may exhibit approximately 5-, 6-, 7-, 8-, 9-, 10-, 11-, 12-, 13-, 14-, 15-, 16-, 17-, 18-, 19-, 20-, 21-, 22-, 23-, 24-, 25-, 26-, 27-, 28-, 29-, 30-, 31-, 32-, 33-, 34-, 35-, 36-, 37-, 38-, 39-, 40-, 41-, 42-, 43-, 44-, 45-, 46-, 47-, 48-, 49-, or 50 times greater selectivity for hormone receptors. follicle-stimulating hormone rather than thyroid-stimulating hormone receptor-stimulating hormone.

[00145] In some embodiments, a compound as disclosed herein exhibits at least 5 times greater selectivity for FSHR than for luteinizing hormone receptor. This includes 5-, 6-, 7-, 8-, Petition 870260076443, dated 07 / 31 / 2026, page 122 / 508 113 / 448 9-, 10-, 11-, 12-, 13-, 14-, 15-, 16-, 17-, 18-, 19-, 20-, 21-, 22-, 23-, 24-, 25-, 26-, 27-, 28-, 29-, 30-, 31-, 32-, 33-, 34-, 35-, 36-, 37-, 38-, 39-, 40-, 41-, 42-, 43-, 44-, 45-, 46-, 47-, 48-, 49-, less or 50 times, or more, greater selectivity for the follicle-stimulating hormone receptor than for the luteinizing hormone receptor. A compound as disclosed herein may exhibit approximately 5-, 6-, 7-, 8-, 9-, 10-, 11-, 12-, 13-, 14-, 15-, 16-, 17-, 18-, 19-, 20-, 21-, 22-, 23-, 24-, 25-, 26-, 27-, 28-, 29-, 30-, 31-, 32-, 33-, 34-, 35-, 36-, 37-, 38-, 39-, 40-, 41-, 42-, 43-, 44-, 45-, 46-, 47-, 48-, 49-, or 50 times greater selectivity for hormone receptors. follicle-stimulating hormone (FSH) is more effective than luteinizing hormone receptor-stimulating hormone (LCH). Synthesis of the Compounds

[00146] In another aspect, a method of manufacturing any of the compounds disclosed herein is provided. The compounds presently disclosed have been and can be synthesized using the general synthetic procedures presented in the AD Schemes below. The performance of each individual illustrated step is within the ability of an ordinary expert guided by this disclosure, who also knows how to modify the synthetic procedures of the schemes below to synthesize the full scope of the compounds disclosed herein. Definitions for R1, R2, R3, R6, R10, R11, R12, R13, Rf and Rg are as provided in the formulas described herein. The synthetic procedure for individual compounds is disclosed in the Examples section below. Scheme A Petition 870260076443, dated 07 / 31 / 2026, p. 123 / 508 114 / 448

[00147] As shown in Scheme A, compound Al (which can be synthesized as described in Method 1 below) was converted to oxalyl amide A-2. Cyclization of intermediate compound A-2 yielded intermediate compound A-3. Subsequent saponification of intermediate compound A-4 followed by coupling with amine HNRfRg resulted in intermediate compound A-5. Metal-mediated coupling of intermediate compound A-5 led to intermediate compound A-6, which after ester hydrolysis yielded intermediate compound A-7. Coupling of compound A-7 with amine H2NR6 yielded compound A-8 (compounds as disclosed herein). Scheme B

[00148] Scheme B illustrates the metal-mediated conversion of compound B1 into a boronate ester which is then reacted with R3X (X = Cl, Br, I or OTf) to compound B-3 (a compound as disclosed in the present document) via another metal-mediated conversion. Scheme C Petition 870260076443, dated 07 / 31 / 2026, p. 124 / 508 115 / 448

[00149] Scheme C illustrates the metal-mediated conversion of compound B-1 with an R3 boronate ester to compound B-3 (a compound as disclosed herein). Scheme D

[00150] Scheme D illustrates the amine coupling of compound D1 with amine HNRfRg to arrive at compound B-3 (a compound as disclosed in this document). PHARMACEUTICAL COMPOSITIONS

[00151] In another aspect, pharmaceutical compositions are disclosed herein which comprise, consist essentially of, or consist of a compound as described herein, and one or more pharmaceutically acceptable excipients.

[00152] In another aspect, pharmaceutical compositions are disclosed herein which comprise, consist essentially of, or consist of a compound of Formulas (I), (II), (IIa), (III) or (IV) as described herein, and one or more pharmaceutically acceptable excipients.

[00153] The compounds can be formulated for administration by any suitable route of administration, such as oral, topical (including transdermal), rectal, vaginal, transmucosal or intestinal administration; parenteral distribution, including intramuscular, Petition 870260076443, dated 07 / 31 / 2026, p. 125 / 508 116 / 448 subcutaneous, or intravenous injection, as well as distribution by inhalation, intrathecal, direct intraperitoneal or intranasal injection.

[00154] The pharmaceutical compositions, as disclosed herein, may comprise, as one or more pharmaceutically acceptable excipients, a carrier, diluent, disintegrant, sweetening agent, glidant (such as magnesium stearate), flavoring agent, emulsifying agent, suspending agent, stabilizer, isotonic agent, etc. The pharmaceutical compositions, as disclosed herein, may be formulated in an oral dosage form, such as tablets, capsules, powders, granules, suspensions, emulsions or syrups; or a topical (including transdermal) or transmucosal dosage form, such as liquids, suspensions, emulsions, gels (ointments or similar), or a parenteral dosage form, such as liquids, suspensions, emulsions and lyophilized powders. Said dosage forms may be formulated in various forms, for example, a dosage form for single administration or for multiple administrations.

[00155] Exemplary excipients include, without limitation, lactose, polyethylene glycol (PEG), hydrogenated castor oil (HCO), cremofos, carbohydrates, starches (e.g., corn starch), inorganic salts, antimicrobial agents, antioxidants, binders / fillers, surfactants, lubricants (e.g., calcium or magnesium stearate), glidants such as talc, disintegrants, diluents, buffers, acids, bases, film coaters, combinations thereof and the like.

[00156] The amount of any individual excipient in the composition will vary depending on the role of the excipient, the dosage requirements of the active agent, and the particular needs of the composition. Generally, however, the excipient will be present in the composition in an amount of about 1% to about 99% by weight, such as from about 5% to about 98% by weight, including from about 15% to about 95% by weight of the composition. Petition 870260076443, dated 07 / 31 / 2026, page 126 / 508 117 / 448 In general, the amount of excipient present in a developing composition is selected from the following: approximately 1%, 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% by weight.

[00157] A pharmaceutical composition, as disclosed herein, may include a compound disclosed herein as the sole active agent, or it may be formulated with other active agents.

[00158] Techniques for formulating and administering the compounds disclosed in this document can be found in “Remington: The Science and Practice of Pharmacy,” Academic Press, London, United Kingdom, 23rd edition, 2020.

[00159] The pharmaceutical compositions, as disclosed herein, may be formulated to provide a therapeutically effective amount of a compound, as disclosed herein, in a reasonable volume or mass of the composition, which may be administered by any effective dosing regimen, such as once daily. Although the exact dosage may be determined on a drug-by-drug (compound-by-compound) basis, for most compounds, some generalizations regarding dosage may be made. For example, the daily dosing regimen for an adult human patient may be between 0.001 mg and 1000 mg, such as between 0.01 mg and 500 mg, for example, from 1 to 200 mg of the compound or pharmaceutically acceptable salt thereof, calculated as the free base or free acid. TREATMENT METHODS

[00160] In another aspect, methods for modulating follicle-stimulating hormone receptor (FSHR) activity in a subject are disclosed in this document, comprising, essentially consisting of, or consisting of administering to a subject in need thereof, a compound as disclosed in this document or a composition. Petition 870260076443, dated 07 / 31 / 2026, page 127 / 508 118 / 448 pharmaceutical as disclosed herein. In an alternative aspect, methods of modulating follicle-stimulating hormone receptor activity in a biological sample are disclosed herein, comprising contacting the biological sample with a pharmaceutical compound or composition as disclosed herein.

[00161] In another aspect, methods of treating a disease or disorder in a subject in need thereof are disclosed herein, comprising, essentially consisting of, or consisting of administering to the subject a therapeutically effective amount of a compound as disclosed herein or a pharmaceutical composition as disclosed herein.The disease or disorder may be any for which modulation of FSHR activity is desirable, such as one or more of the following: hypogonadotropic hypogonadism, isolated idiopathic hypogonadotropic hypogonadism, Kallmann syndrome, idiopathic hypogonadotropic hypogonadism, craniopharyngiomas, combined pituitary hormone deficiency, fertile eunuch syndrome, abnormal beta subunit of LH, abnormal beta subunit of FSH, mass lesions, pituitary adenomas, cysts, metastatic cancer in the sella (breasts in women, lung and prostate in men), infiltrative lesions, hemochromatosis, sarcoidosis, histiocytosis, lymphoma, lymphocytic hypophysitis, meningitis, pituitary apoplexy, hyperprolactinemia, hypothyroidism, intentional (iatrogenic) secondary hypogonadism, empty sella, pituitary infarction, Sheehan's syndrome, anorexia nervosa, congenital adrenal hyperplasia, and deficiency-related disorders. GnRH.

[00162] In another aspect, methods for treating a fertility disorder in a male or female subject who needs it are disclosed in the present document, comprising, essentially consisting of, or consisting of administering to the subject a therapeutically effective amount of a compound as disclosed in the present document or a Petition 870260076443, dated 07 / 31 / 2026, page 128 / 508 119 / 448 pharmaceutical composition as disclosed in this document. Such a method may be for stimulating follicular development, ovulation induction, controlled ovarian hyperstimulation, controlled ovarian stimulation, assisted reproductive technology (ART) (including in vitro fertilization), treatment of male hypogonadism or treatment of male infertility, including failure of spermatogenesis.

[00163] In another aspect, compounds for use in modulating follicle-stimulating hormone receptor (FSHR) activity in a subject are disclosed in this document.

[00164] In another aspect, compounds for use in the treatment of a disease or disorder in a subject who needs them are disclosed in this document.The disease or disorder may be any for which modulation of FSHR activity is desirable, such as one or more of the following: hypogonadotropic hypogonadism, isolated idiopathic hypogonadotropic hypogonadism, Kallmann syndrome, idiopathic hypogonadotropic hypogonadism, craniopharyngiomas, combined pituitary hormone deficiency, fertile eunuch syndrome, abnormal beta subunit of LH, abnormal beta subunit of FSH, mass lesions, pituitary adenomas, cysts, metastatic cancer in the sella (breasts in women, lung and prostate in men), infiltrative lesions, hemochromatosis, sarcoidosis, histiocytosis, lymphoma, lymphocytic hypophysitis, meningitis, pituitary apoplexy, hyperprolactinemia, hypothyroidism, intentional (iatrogenic) secondary hypogonadism, empty sella, pituitary infarction, Sheehan's syndrome, anorexia nervosa, congenital adrenal hyperplasia, and deficiency-related disorders. GnRH.

[00165] In another aspect, compounds for use in the treatment of a fertility disorder in a female or male subject in need thereof are disclosed in this document, such as to stimulate follicular development, ovulation induction, controlled ovarian hyperstimulation, controlled ovarian stimulation, reproductive technology. Petition 870260076443, dated 07 / 31 / 2026, page 129 / 508 120 / 448 assisted reproductive technology (ART) (including in vitro fertilization), treatment of male hypogonadism or treatment of male infertility, including failure of spermatogenesis.

[00166] In other respects, uses of the compounds disclosed herein are disclosed in the preparation of medicaments to modulate follicle-stimulating hormone receptor (FSHR) activity in a subject, to treat a disease or disorder in a subject in need thereof, such as any one or more listed above, or to treat a fertility disorder in a female or male subject in need thereof, such as to stimulate follicular development, ovulation induction, controlled ovarian hyperstimulation, controlled ovarian stimulation, assisted reproductive technology (ART) (including in vitro fertilization), treatment of male hypogonadism or treatment of male infertility, including failure of spermatogenesis.

[00167] According to any of these methods or uses, the compound or composition may be administered by any suitable route of administration as discussed above, and may be administered in a therapeutically effective amount as discussed above. As also discussed above, administration may be by any effective dosage regimen, such as once daily, 1 to 4 times daily, once weekly, 1 to 4 times weekly, once monthly, 1 to 4 times monthly, etc. Although the exact dosage may be determined on a drug-by-drug (compound-by-compound) basis, the daily dosage regimen for an adult human patient may be, for example, between 0.001 mg and 1000 mg, such as between 0.01 mg and 500 mg, for example 1 to 200 mg of the compound or pharmaceutically acceptable salt thereof, calculated as the free base or free acid.

[00168] The present technology, as generally described, can be Petition 870260076443, dated 07 / 31 / 2026, p. 130 / 508 121 / 448 additionally understood by reference to the following examples, which are provided by way of illustration and are not intended to be limiting of the present technology. EXAMPLES The analytical conditions for LCMS were as follows: Analytical method 1 (M1):

[00169] Analytical HPLC-MS was performed on a Shimadzu LCMS system using a Kinetex Core Shell C18 column (2.1 mm x 50 mm, 5 µm; temperature: 40 °C) and a gradient of B at 5-100% (A = 0.1% formic acid in water; B = 0.1% formic acid in acetonitrile) over 1.2 min, then B at 100% for 0.1 min. A second gradient of B at 100%-5% was then applied over 0.01 min and maintained for 0.39 min with an injection volume of 3 µl at a flow rate of 1.2 ml / min. UV spectra were recorded at 215 nm using an SPD-M20A PDA detector spectrum range: 200-400 nm. Mass spectra were obtained using a 2010 EV detector. The data were integrated and reported using Shimadzu LCMS-Solutions and PsiPort software. Analytical method 2 (M2)

[00170] Analytical uHPLC-MS were performed on a Waters ACQUITY uPLC system using a Waters uPLC® BEHTMC18 column (2.1 mm x 50 mm, 1.7 µm; temperature 40 °C) and a gradient of B at 5-100% (A = 0.1% formic acid in water; B = 0.1% formic acid in acetonitrile) over 1.1 min, then B at 100% for 0.25 min. A second gradient of B at 100%-5% was then applied over 0.05 min and maintained for 0.1 min with an injection volume of 1 µl at a flow rate of 0.9 ml / min. UV spectra were recorded at 215 nm on a Waters ACQUITY PDA with a spectral range of 200-400 nm. Mass spectra were obtained using a Waters SQD (MSQ1) or Waters ACQUITY QDA (MSQ2, MSQ4). The data were integrated and reported using the software. Petition 870260076443, dated 07 / 31 / 2026, page 131 / 508 122 / 448 Waters MassLynx and OpenLynx. Analytical method 3 (M3):

[00171] Analytical uHPLC-MS were performed on a Waters ACQUITY uPLC system using a Waters uPLC® BEHTMC18 column (2.1 mm x 30 mm, 1.7 µm; temperature 40 °C) and a 5-100% B gradient (A = 2 mM ammonium bicarbonate, buffered at pH 10, B: acetonitrile) over 0.75 min, then 100% B for 0.1 min. A second 100-5% B gradient was then applied over 0.05 min and maintained for 0.1 min with an injection volume of 1 µl at a flow rate of 1 ml / min. UV spectra were recorded at 215 nm on a Waters ACQUITY PDA with a spectral range of 200-400 nm. Mass spectra were obtained using a Waters Quattro Premier XE. The data were integrated and reported using Waters MassLynx and OpenLynx software. Analytical method 4 (M4):

[00172] Analytical UHPLC-MS were performed on a Waters ACQUITY uPLC system using a Phenomenex Kinetex-XB C18 column (2.1 mm x 100 mm, 1.7 µm; temperature: 40 °C) and a gradient of B at 5-100% (A = 0.1% formic acid in water; B = 0.1% formic acid in acetonitrile) over 5.3 min, then B at 100% for 0.5 min. A second gradient of B at 100%-5% was then applied over 0.02 min and maintained for 1.18 min with an injection volume of 1 µl at a flow rate of 0.6 ml / min. UV spectra were recorded at 215 nm using a Waters ACQUITY PDA detector spectrum range: 200-400 nm. ELS data were collected using a Waters ACQUITY ELS detector (when installed). Mass spectra were obtained using a Waters SQD (MSQ1) or Waters ACQUITY QDA (MSQ2, MSQ4). Data were integrated and reported using Waters MassLynx and OpenLynx software. Analytical method 5 (M5):

[00173] uPLC-MS analytical tests were performed on a Waters system. Petition 870260076443, dated 07 / 31 / 2026, page 132 / 508 123 / 448 ACQUITY uPLC was used with a Waters uPLC® BEHTMC18 column (column 2.1 mm x 100 mm, 1.7 μm; temperature: 40 °C) and a gradient of 5-100% B (A = 2 mM ammonium bicarbonate, buffered at pH 10; B = acetonitrile) over 5.3 min, then 100% B for 0.5 min. A second gradient of 100% B was then applied over 0.02 min and maintained for 1.18 min with an injection volume of 1 μl and a flow rate of 0.6 ml / min. UV spectra were recorded at 215 nm using a Waters ACQUITY PDA detector spectrum range: 200-400 nm. Mass spectra were obtained using a Waters Quattro Premier XE (MS16) or a Waters SQD2 (MSQ5) mass detector. The data were integrated and reported using Waters MassLynx and OpenLynx software. Analytical method 6 (M6):

[00174] Analytical uPLC-MS were performed on a Waters ACQUITY uPLC system using a Phenomenex Kinetex Core-Shell C8 column (50 mm x 2.1 mm, 5 μm column; temperature: 40 °C) and a gradient of B to 5100% (A = 0.1% formic acid in water; B = 0.1% formic acid in acetonitrile) over 1.83 min, then B to 100% for 0.42 min. A second gradient of B to 100-5% was then applied over 0.42 min and maintained for 0.54 min with an injection volume of 3 μl and a flow rate of 1.2 ml / min. UV spectra were recorded at 215 nm using an SPD-M20A PDA detector spectrum range: 200-400 nm. Mass spectra were obtained using a 2010 EV detector. Data were integrated and reported using Shimadzu LCMS-Solutions and PsiPort software. Analytical method 7 (M7):

[00175] Analytical HPLC-MS were performed on Waters LCMS systems using a Waters uPLC CORTEX C8 column (2.1 mm x 100 mm, 1.6 μm; temperature: 40 °C) and a gradient of B at 5-100% (A = 0.1% formic acid in water; B = 0.1% formic acid in acetonitrile) along Petition 870260076443, dated 07 / 31 / 2026, page 133 / 508 124 / 448 5.3 min, then B at 100% for 0.5 min. A second gradient of B at 100-5% was then applied over 0.02 min and maintained for 1.18 min with an injection volume of 1 μL at a flow rate of 0.6 ml / min. UV spectra were recorded at 215 nm using a Waters ACQUITY PDA detector spectrum range: 200-400 nm; ELS data were collected using a Waters ACQUITY ELS detector (when fitted). Mass spectra were obtained using a Waters SQD or Waters ACQUITY QDa. Data were integrated and reported using Waters MassLynx and OpenLynx software. Analytical method 8 (M8):

[00176] Analytical HPLC-MS were performed on Waters LCMS systems using a Waters uPLC CORTEX C8 column (2.1 mm x 50 mm, 1.6 μm; temperature: 40 °C) and a gradient of B at 5-100% (A = 0.1% formic acid in water; B = 0.01% formic acid in acetonitrile) over 1.1 min, then B at 100% for 0.3 min. A second gradient of B at 100%-5% was then applied over 0.02 min and maintained for 0.28 min with an injection volume of 1 μl at a flow rate of 0.9 ml / min. UV spectra were recorded at 215 nm using a Waters ACQUITY PDA detector spectrum range: 200-400 nm. ELS data were collected using a Waters ACQUITY ELS detector (when installed). Mass spectra were obtained using a Waters SQD or Waters ACQUITY QDa. Data were integrated and reported using Waters MassLynx and OpenLynx software. Analytical method 9 (M9):

[00177] Analytical HPLC-MS were performed on Waters LCMS systems using a Waters CSH C18 column (2.1 mm x 100 mm, 1.7 μm; temperature: 40 °C) and a gradient of B at 5-100% (A = 5 mM ammonium acetate, buffered at pH 7; B = acetonitrile) over 5.3 min, then B at 100% for 0.5 min. A second gradient of B at 100%-5% was then applied. Petition 870260076443, dated 07 / 31 / 2026, page 134 / 508 125 / 448 over 0.02 min and maintained for 1.18 min with an injection volume of 1 μl at a flow rate of 0.6 ml / min. UV spectra were recorded at 215 nm using a Waters ACQUITY PDA detector spectrum range: 200-400 nm. ELS data were collected using a Waters ACQUITY ELS detector (when fitted). Mass spectra were obtained using a Waters SQD or Waters ACQUITY QDa. Data were integrated and reported using Waters MassLynx and OpenLynx software. Analytical method 10 (M10):

[00178] Analytical uHPLC-MS (M14) were performed on a Waters ACQUITY uPLC system using a Waters uPLC® BEHTMC18 column (2.1 mm x 30 mm, 1.7 μm; temperature 40 °C) and a gradient of 1100% B (A = 2 mM ammonium bicarbonate, buffered at pH 10, B: acetonitrile) over 1.1 min, then 100% B for 0.25 min. A second gradient of 100-1% B was then applied over 0.05 min and maintained for 0.4 min with an injection volume of 1 μl at a flow rate of 1.0 ml / min. UV spectra were recorded at 215 nm on a Waters ACQUITY PDA with a spectral range of 200-400 nm. Mass spectra were obtained using a Waters Quattro Premier XE (MS16) or a Waters SQD2 (MSQ5) mass detector. The data were integrated and reported using Waters MassLynx and OpenLynx software. Analytical method 11 (M11): Instrument: Shimadzu LC-20AD&MS 2020; Column: Kinetex C18 2.6μm, 2.1*30mm; column temperature: 40oC Mobile Phase A (MPA) H2O + 0.04% (v / v) TFA Mobile Phase B (MPB) ACN at 0.02% (v / v) TFA Flow Rate: 1.0 ml / min Gradient Ratio: Time (min) 0.01 3.00 3.50 3.51 4.30 MPA (%) 95 5 5 95 95 MPB (%) 5 95 95 5 5 Petition 870260076443, dated 07 / 31 / 2026, page 135 / 508 126 / 448 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 100-1000 Analytical method 12 (M12): Instrument: Shimadzu LC-20AD&MS 2020; Column: Kinetex C18 2.6μm, 2.1*30mm; column temperature: 40oC Mobile Phase A (MPA) H2O + 0.04% (v / v) TFA Mobile Phase B (MPB) ACN at 0.02% (v / v) TFA Flow rate: 1.5 ml / min Gradient Ratio: Time (min) 0.01 0.70 1.15 1.16 1.50 MPA (%) 95 5 5 95 95 MPB (%) 5 95 95 5 5 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 100-1000 Analytical method 13 (M13): Instrument: Shimadzu LC-20AD&MS 2020; Column: HALO C18 5.0 μm, 3.0*30 mm; column temperature: 40°C Mobile Phase A (MPA) H2O + 0.04% (v / v) TFA Mobile Phase B (MPB) ACN at 0.02% (v / v) TFA Flow rate: 1.0 ml / min (0.01-3.0 min, 1.2 ml / min (3.01-3.5 min) Gradient Ratio: Time (min) 0.01 2.5 3.0 3.01 3.5 Detection: MPA (%) 95 5 5 95 95 MPB (%) 5 95 95 5 5 220 nm and 254 nm; MS Mode: Positive; MS Range: 50-2000 Analytical method 14 (M14): Instrument: Shimadzu LC-20AD&MS 2020; Column: HALO C18 2.7 μm, 3.0*30 mm; column temperature: 40°C Mobile Phase A (MPA) Mobile phase B (MPB) Flow rate: Gradient Ratio: Time (min) H2O + 0.04% (v / v) TFA ACN 0.02% (in v / v) TFA 1.5 ml / min 0.01 0.70 1.15 1.16 1.50 Petition 870260076443, dated 07 / 31 / 2026, page 136 / 508 127 / 448 MPA (%) 95 5 5 95 95 MPB (%) 5 95 95 5 5 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 100-1000 Analytical method 15 (M15): Instrument: Shimadzu LC-20AD XR&MS 2020; Column: HALO C18 5 μm, 3.0*30 mm; Column temperature: 40°C Mobile Phase A (MPA) H2O + 0.04% (v / v) TFA Mobile Phase B (MPB) ACN at 0.02% (v / v) TFA Flow rate: 2.0 ml / min (0.00-0.9 min) Gradient Ratio: Time (min) 0.00 0.50 0.90 MPA (%) 90 0 0 MPB (%) 10 100 100 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 50-2000 Analytical method 16 (M16): Instrument: Shimadzu LC-20AD&MS 2020; Column: Mobile phase A (MPA) Mobile phase B (MPB) Flow rate: Gradient Ratio: Time (min) MPA (%) MPB (%) Xbridge-C18 2.1*30 mm 5 μm; Column temperature: 40°C H2O + NH4HCO3 10 mM Acetonitrile 1.5 ml / min 0.01 0.70 1.16 1.50 95 5 5 95 5 95 95 5 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 100-1000 Analytical method 17 (M17): Instrument: Waters Arc™ Column: HALO 2.7 μm C18 90A 30x3.0 mm; Column temperature: °C Mobile Phase A (MPA) H2O + 0.04% (v / v) TFA Mobile Phase B (MPB) ACN at 0.02% (v / v) TFA Petition 870260076443, dated 07 / 31 / 2026, p. 137 / 508 128 / 448 Flow rate: 1.0 ml / min (0.01-4.00 min) Gradient Ratio: Time(min) 0.01 3.00 3.50 3.51 4 MPA (%) 95 5 5 95 95 MPB (%) 5 95 95 5 5 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 100-1200 Analytical method 18 (M18): Instrument: Shimadzu LC-30AD&MS 2020; Column: InfinityLab Poroshell 120 SB-C18 2.7 μm 3.0*30 mm; Column temperature: 40°C Mobile Phase A (MPA) H2O + 0.04% (v / v) TFA Mobile Phase B (MPB) ACN at 0.02% (v / v) TFA Flow rate: 1.5 ml / min (0.01-1.50 min) Gradient Ratio: Time(min) 0.01 0.70 1.16 1.50 MPA (%) 95 5 5 95 MPB (%) 5 95 95 5 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 50-2000 Analytical method 19 (M19): Instrument: Shimadzu LC-30AD&MS 2020; Column: InfinityLab Poroshell 120 SB-C18 2.7 μm 3.0*30 mm; Column temperature: 40°C Mobile Phase A (MPA) H2O + 0.04% (v / v) TFA Mobile Phase B (MPB) ACN at 0.02% (v / v) TFA Flow rate: 1.5 ml / min (0.01-1.50 min) Gradient Ratio: Time(min) 0.01 0.70 1.16 1.50 MPA (%) 95 5 5 95 MPB (%) 5 95 95 5 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 50-2000 Petition 870260076443, dated 07 / 31 / 2026, page 138 / 508 129 / 448 Analytical method 20 (M20): Instrument: Shimadzu LC-20AD&MS 2020; Column: Kinetex EVO C18 30*2.1 mm, 5 μm; Column temperature: °C Mobile Phase A (MPA) H2O + 0.04% (v / v) TFA Mobile Phase B (MPB) ACN at 0.02% (v / v) TFA Flow rate: 1ml / min (0.01-3.00min)-1.2ml / min (3.01-3.50min) Gradient Ratio: Time(min) 0.01 2.50 3.00 3.01 MPA (%) 95 5 5 95 MPB (%) 5 95 95 5 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 50-2000 Analytical method 21 (M21): Instrument: Shimadzu LC-20AD XR&MS 2020; Column: HALO C18 3.0*30 mm, 5 μm; Column temperature: 40°C Mobile Phase A (MPA) H2O + 0.04% (v / v) TFA Mobile Phase B (MPB) ACN at 0.02% (v / v) TFA Flow rate: 1.5 ml / min (0.00-1.30 min) Gradient Ratio: Time(min) 0.01 0.8 1.30 MPA (%) 90 0 0 MPB (%) 10 100 100 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 50-2000 Analytical method 22 (M22): Instrument: Shimadzu LC-20AD XR&MS 2020; Column: HALO C18 5 μm, 3.0*30 mm; Column temperature: 40°C Mobile Phase A (MPA) Mobile phase B (MPB) Flow rate: Gradient Ratio: Time (min) MPA (%) H2O+0.04% (in v / v) TFA ACN 0.02% (in v / v) TFA 1.50 ml / min 0.70 1.30 5 5 Petition 870260076443, dated 07 / 31 / 2026, page 139 / 508 130 / 448 MPB (%) 5 95 95 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 50-500 Analytical method 23 (M23): Instrument: Shimadzu LC-20AD XR&MS 2020; Column: HALO C18 5 μm, 3.0*30 mm; Column temperature: 40°C Mobile Phase A (MPA) H2O + 0.04% (v / v) TFA Mobile Phase B (MPB) ACN at 0.02% (v / v) TFA Flow rate: 2.0 ml / min (0.00-0.9 min) Gradient Ratio: Time (min) 0.00 0.50 0.90 MPA (%) 90 0 0 MPB (%) 10 100 100 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 50-2000 Analytical method 24 (M24): Instrument: Agilent 1260 & 6125B; Column: Xbridge C18 2.1*50 mm, 5 μm; Column temperature: 40°C Mobile phase A (MPA) Mobile phase B (MPB) Flow rate: Gradient Ratio: Time (min) MPA (%) MPB (%) H2O + NH4HCO3 10 mM Acetonitrile 0.8 ml / min 0.00 0.40 3.40 3.85 3.86 4.50 95 5 5 9595 5 95 95 55 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 100-1000 Analytical method 25 (M25): Instrument: Shimadzu 20AB&MS 2020; Column: Xbridge C18 2.1*50 mm, 5 μm; Column temperature: 40°C Mobile Phase A (MPA) Mobile Phase B (MPB) Flow rate: H2O + 10 mmol / l NH4HCO3 ACN 100% 1.0 ml / min Gradient Ratio: Petition 870260076443, dated 07 / 31 / 2026, p. 140 / 508 131 / 448 Time(min) 0.01 3.00 3.50 3.51 4.30 MPA (%) 95 5 5 95 95 MPB (%) 5 95 95 5 5 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 50-2000 Analytical method 26 (M26): Instrument: Shimadzu LC-20AB&MS 2020; Column: Xbridge-C18 2.1*50 mm 5 µm; Column temperature: 40°C Mobile phase A (MPA) H2O+NH4HCO3 10 mM Mobile phase B (MPB) Acetonitrile Flow rate: 1.0 ml / min (0.01-3.01 min, 1.2 ml / min (3.02-3.50 min) Gradient Ratio: Time(min) 0.01 2.50 3.00 3.01 3.5 MPA (%) 95 5 5 95 95 MPB (%) 5 95 95 5 5 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 50-2000 Analytical Method 27 (M27): Instrument: Shimadzu 20AB&MS 2020; Column: Mobile phase A (MPA) Mobile phase B (MPB) Flow rate: 1.0 ml / min Gradient Ratio: Time (min) MPA (%) MPB (%) Detection: 220 nm and 254 nm; MS Mode: 2000 Analytical method 28 (M28): Instrument: Agilent 1260 & 6125B; Column: Xbridge C18 2.1*50 mm, 5 μm; Column temperature: 40°C H2O + 10 mmol / L NH4HCO3 ACN 100% 0.01 3.00 5 95 3.50 3.51 4.30 4.30 95 95 95 5 5 5 Negative; MS range: 100 Luna-C18 (2) 2.0*50 mm, 5 μm; Column temperature: 40 Petition 870260076443, dated 07 / 31 / 2026, page 141 / 508 132 / 448 Mobile Phase A (MPA) H2U + 0.04% (v / v) TFA Mobile Phase B (MPB) ACN at 0.02% (v / v) TFA Flow rate: 1.0 ml / min Gradient Ratio: Time (min) 0.00 0.40 3.00 4.00 4.01 4.50 MPA (%) 95 95 5 5 95 95 MPB (%) 5 5 95 95 5 5 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 100 1000 Analytical method 29 (M29): Instrument: Shimadzu LC-20AD XR&MS 2020; Column: HALO C18 5 μm, 3.0*30 mm; Column temperature: 40°C Mobile Phase A (MPA) H2O + 0.04% (v / v) TFA Mobile Phase B (MPB) ACN at 0.02% (v / v) TFA Flow rate: 1.50 ml / min Gradient Ratio: Time (min) 0 0.70 1.30 MPA (%) 90 0 0 MPB (%) 10 100 100 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 50-1500 Analytical method 30 (M30): Instrument: Shimadzu LC-20AD XR&MS 2020; Column: HALO C18 5 μm, 3.0*30 mm; Column temperature: 40°C Mobile Phase A (MPA) H2O + 0.04% (v / v) TFA Mobile Phase B (MPB) ACN at 0.02% (v / v) TFA Flow rate: 2.0 ml / min (0.00-0.9 min) Gradient Ratio: Time(min) 0 0.5 0.90 MPA (%) 90 0 0 MPB (%) 10 100 100 Petition 870260076443, dated 07 / 31 / 2026, page 142 / 508 133 / 448 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 50-2000 Analytical method 31 (M31): Instrument: Shimadzu LC-20AD XR&MS 2020; Column: HALO C18 3.0*30 mm, 5 μm; Column temperature: 40°C Mobile Phase A (MPA) H2O + 0.04% (v / v) TFA Mobile Phase B (MPB) ACN at 0.02% (v / v) TFA Flow rate: 1.5 ml / min (0.00-1.30 min) Gradient Ratio: Time(min) 0.01 0.8 1.30 MPA (%) 90 0 0 MPB (%) 10 100 100 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 50-2000 Analytical method 32 (M32): Instrument: Shimadzu LC-20AD XR&MS 2020; Column: HALO C18 5 μm, 3.0*30 mm; Column temperature: 40°C Mobile Phase A (MPA) H2O + 0.04% (v / v) TFA Mobile Phase B (MPB) ACN at 0.02% (v / v) TFA Flow rate: 2.0 ml / min (0.00-0.9 min) Gradient Ratio: Time(min) 0 0.5 0.90 MPA (%) 90 0 0 MPB (%) 10 100 100 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 50-2000 Analytical method 33 (M33): Instrument: Shimadzu LC-20AD XR&MS 2020; Column: HALO C18 5 μm, 3.0*30 mm; Column temperature: 40°C Mobile Phase A (MPA) H2O + 0.04% (v / v) TFA Mobile Phase B (MPB) ACN at 0.02% (v / v) TFA Flow rate: 2.0 ml / min (0.00-0.9 min) Gradient Ratio: Petition 870260076443, dated 07 / 31 / 2026, p. 143 / 508 134 / 448 Time(min) 0 0.5 0.90 MPA (%) 90 0 0 MPB (%) 10 100 100 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 50-2000 Analytical method 34 (M34): Instrument: Agilent 1260 & 6125B; Column: Luna-C18 (2) 2.0*50 mm, 5 μm; Column temperature: 40oC Mobile Phase A (MPA) Mobile phase B (MPB) Flow rate: 1.0 ml / min H2O + 0.04% (v / v) TFA ACN at 0.02% (v / v) TFA Gradient Ratio: Time(min) 0.00 0.40 3.00 4.00 4,014.50 MPA (%) 95 95 5 5 9595 MPB (%) 5 5 95 95 55 Detection: 220 nm & 254 nm; MS Mode: Positive; MS Range: 100-1000 Analytical method 35 (M35): Instrument: Agilent 1200 & 6110A; Column: Luna-C18 (2) 2.0*50 mm, 5 μm; Column temperature: 40 o Mobile Phase A (MPA) Mobile phase B (MPB) Flow rate: 1.0 ml / min H2O + 0.04% (v / v) TFA ACN at 0.02% (v / v) TFA Gradient Ratio: Time(min) 0.00 0.40 3.00 4.00 4,014.50 MPA (%) 95 95 5 5 9595 MPB (%) 5 5 95 95 55 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 100-1000 Analytical method 36 (M36): Instrument: Agilent 1200 & 6130; Column: Xbridge-C18 2.1*50 mm 5 μm; Column temperature: 40°C Mobile phase A (MPA) H2O+NH4HCO3 10 mM Mobile phase B (MPB) Acetonitrile Petition 870260076443, dated 07 / 31 / 2026, p. 144 / 508 135 / 448 Flow rate: 0.8 ml / min Gradient Ratio: Time(min) 0.00 0.40 3.40 3.85 3.86 4.50 MPA (%) 95 95 5 5 95 95 MPB (%) 5 5 95 95 5 5 Positive; Detection: 220 nm and 254 nm; MS Mode: 1000 MS range: 100 Analytical method 37 (M37): Instrument: Agilent 1200 & 6110A; Column: Luna-C18 (2) 2.0*50mm,5μm; Column temperature: 40oC Mobile Phase A (MPA) Mobile Phase B (MPB) Flow Rate: 1.0 ml / min Gradient Ratio: H2O + 0.04% (v / v) TFA ACN at 0.02% (v / v) TFA Time(min) 0.00 0.40 3.00 4.00 4.01 4.50 MPA (%) 95 95 5 5 95 95 MPB (%) 5 5 95 95 5 5 Positive; Detection: 220 nm and 254 nm; MS Mode: MS range: 1001000 Analytical Method 38 (M38): Instrument: Shimadzu LC-20AD&MS 2020; Column: Gemini C18 2.0*50 mm, 5 μm; Column temperature: 40°C Mobile phase A (MPA) H2O+NH4HCO3 10 mM Mobile phase B (MPB) Acetonitrile Flow rate: 1.0 ml / min Gradient Ratio: Time(min) 0.01 2.50 3.00 3.01 3.50 MPA (%) 95 5 5 95 95 MPB (%) 5 95 95 5 5 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 50-2000 Petition 870260076443, dated 07 / 31 / 2026, page 145 / 508 136 / 448 Analytical Method 39 (M39): Instrument: Agilent 1200 HPLC MSD: 1956A single quadrupole MSD; Column: Luna C18, 2.0*50 mm, 5 μm; Column temperature: 40°C Mobile Phase A (MPA) TFA 0.04% in H2O Mobile Phase B (MPB) TFA 0.02% in ACN Flow rate: 1.0 ml / min Gradient Ratio: Time(min) 0.01 0.40 3.00 4.00 4,014.50 MPA (%) 95 95 5 5 9595 MPB (%) 5 5 95 95 55 Detection: 220 nm and 254 nm; MS Mode: Positive; MS Range: 1001000 Analytical method 40 (M40):

[00179] All analysis was performed using an Agilent G1956A LC / MSD quadrupole coupled to an Agilent 1100 series liquid chromatography (LC) system consisting of a binary pump with degasser, autosampler, thermostated column compartment, and diode array detector. The mass spectrometer (MS) was operated with an atmospheric pressure electrospray ionization (API-ES) source in positive ion mode. The capillary voltage was set to 3000 V, the fragmentation voltage to 70 V, and the quadrupole temperature was maintained at 100 °C. The drying gas flow rate and temperature were 12.0 l / min and 350 °C, respectively. Nitrogen was used as the nebulizing gas at a pressure of 0.24 MPa (35 psig). Data acquisition was performed using Agilent Chemstation software.

[00180] The analysis was performed on a YMC pack ODS-AQ C18 column (50 mm length x 4.6 mm ID; 3 μm particle size) at 35 °C, with a flow rate of 2.6 ml / min. A gradient elution was performed from 95% (Water + 0.1% Formic Acid) / acetonitrile to 5% (Water + 0.1% Formic Acid) / 95% Acetonitrile in 4.8 min; the composition Petition 870260076443, dated 07 / 31 / 2026, page 146 / 508 The resulting 137 / 448 was maintained for 1.0 min; from 5% (water + 0.1% formic acid) / acetonitrile to 95% (water + 0.1% formic acid) / 5% acetonitrile in 0.2 min. The injection volume was 2 pl. The acquisition ranges were set to 190-400 nm for the UV-PDA detector and 100-1400 m / z for the MS detector. Analytical method 41 (M41):

[00181] All analysis was performed using an Agilent G6224A TOC-LC / MS quadrupole coupled to an Agilent 1290 Infinity series liquid chromatography (LC) system consisting of a binary pump with degasser, autosampler, thermostated column compartment, and diode array detector. The TOF-mass spectrometer (TOF-MS) was operated with a dual atmospheric pressure electrospray ionization (Dual-ESI) source in positive ion mode. The capillary voltage was set to 3000 V, the fragmentation voltage to 70 V, and the quadrupole temperature was maintained at 100 °C. The drying gas flow rate and temperature were 12.0 l / min and 350 °C, respectively. Nitrogen was used as the nebulizing gas at a pressure of 0.24 MPa (35 psig). Data acquisition was performed using MassHunter software.

[00182] The analysis was performed on a YMC pack ODS-AQ C18 column (50 mm length x 4.6 mm ID; 3 µm particle size) at 35 °C, with a flow rate of 2.6 ml / min. A gradient elution was performed using an ISET 2V1.0 Emulated Agilent Pump G1312A V1.0 from 94.51% (Water + Formic Acid 0.1%) / 5.49% acetonitrile to 5% (Water + Formic Acid 0.1%) / 95% acetonitrile in 4.8 min; the resulting composition was held for 1.0 min; 5% (water + 0.1% formic acid) / Acetonitrile to 95% (water + 0.1% formic acid) / 5% Acetonitrile in 0.2 min. The injection volume was 4 pl. The acquisition ranges were set to 190-400 nm for the UV-PDA detector and 100-1000 m / z for the TOF-MS detector. Analytical method 42 (M42): Petition 870260076443, dated 07 / 31 / 2026, page 147 / 508 138 / 448

[00183] Analytical HPLC-MS assays were performed on an Agilent 1260 Infinity (Quat. Pump) DAD LC / MS G6120B system using a Thermo Scientific Accucore C18 (50 x 4.6 mm, 2.6 μm; temperature: 35 °C) and a gradient from A 90% to A 10% in 1.5 min, held for 0.9 min, to A 95% in 0.1 min (A: 0.1% HCOOH in H2O; B: CH3CN) with an injection volume of 3 μL at a flow rate of 3 ml / min. UV spectra were recorded at 254 nm using an HS spectrum range of the Infinity II 1260 Diode Array Detector: 200-400 nm. Mass spectra were obtained using an LC / MS G6120B system. The data were integrated and reported using ACD Labs software. Analytical method 43 (M43):

[00184] Analytical HPLC-MS assays were performed on an Agilent 1290 Infinity II HPLC DAD LC / MSD G6125C ISET emulating the Agilent G4220A system using a Phenomenex Kinetex C18 (50 x 2.1 mm, 1.7 μm; temperature: 60 °C) and a gradient from A 90% to A 10% in 2.4 min, held for 0.4 min, to A 90% in 0.2 min (A: 0.1% HCOOH in H2O; B: CH3CN) with an injection volume of 3 μl at a flow rate of 0.9 ml / min. 254 nm using the spectral range of the Infinity II 1290 Diode Array Detector: 200-400 nm. Mass spectra were obtained using a G6125C LC / MSD detector. The data were integrated and reported using ACD Labs software. Analytical method 44 (M44):

[00185] Analytical HPLC-MS assays were performed on an Agilent 1290 Infinity II HPLC DAD LC / MSD iQ G6160A using a Phenomenex Kinetex C18 (50 x 2.1 mm, 1.7 μm; Temperature: 60 °C) and a gradient from A 90% to A 10% in 1.6 min, held for 0.4 min, to A 90% in 0.2 min (A: 0.1% HCOOH in H2O; B: CH3CN) for 2.2 min with an injection volume of 3 μl at a flow rate of 1.2 ml / min. UV spectra were recorded at 254 nm using a spectral range of the Infinity II 1290 Diode Array Detector: 200-400 nm. Mass spectra were obtained using a detector Petition 870260076443, dated 07 / 31 / 2026, page 148 / 508 139 / 448 LC / MSD iQ G6160A. The data were integrated and reported using ACD Labs software. Analytical method a: Instrument: Column: Shimadzu LC-20AD&MS 2020 HALO C18 5.0 μm, 3.0*30 mm Column temperature: Mobile phase A (MPA) Mobile phase B (MPB) Flow rate: 40°C H2O + 0.04% (v / v) TFA ACN + TFA 0.02% (v / v) 1.0 ml / min (0.01-3.0 min) 1.2 ml / min (3.01-3.5 min) Time (min) 0.01 2.5 3.0 3.01 3.5 Gradient Ratio: MPA (%) 95 5 5 95 95 MPB (%) 5 95 95 5 5 Detection: 220 nm 254 nm MS Mode: Positive MS Range: 50-2000 Method Analytical b. Instrument: Agilent 1260 & 6125B Column: Luna-C18(2) 2.0*50 mm, 5 μm Column temperature: 40 C Mobile phase A(MPA) H2O+ TFA 0.04 % (v / v) Mobile phase B(MPB) ACN+TFA 0.02 % (v / v) Flow rate: 1.0 ml / min Time(min) 0.00 0.40 3.00 4.00 4.01 4.50 Gradient Ratio: Detection: MS Mode: MS Range: Analytical Method c. Instrument: MPA(%) 95 95 5 5 95 95 MPB(%) 5 5 95 95 5 5 220 nm Positive 100-1000 SHIMADZU LC-20AD XR&MS 2020 Petition 870260076443, dated 07 / 31 / 2026, p. 149 / 508 140 / 448 Column: Halo C18 3.0*30 mm, 5 μm Column temperature: 40°C Mobile phase A (MPA) Mobile phase B (MPB) Flow rate: H2O + TFA 0.04% (v / v) ACN + TFA 0.02% (v / v) 1.5 ml / min (0.00-1.30 min) Time (min) 0.01 0.8 1.30 Gradient Ratio: MPA (%) 90 0 0 MPB (%) 10 100 100 Detection: 220 nm 254 nm MS Mode: Positive MS Range: 50-2000 Analytical Method d. Instrument: SHIMADZU LC-20AD XR&MS 2020 Column: Halo C18 3.0*30 mm, 5 μm Column temperature: 40°C Mobile phase A (MPA) Mobile phase B (MPB) Flow rate: H2O + TFA 0.04% (v / v) ACN + TFA 0.02% (v / v) 1.5 ml / min (0.00-1.30 min) Time (min) 0.01 0.8 1.30 Gradient Ratio: MPA (%) 90 0 0 MPB (%) 10 100 100 Detection: 220 nm 254 nm MS Mode: Positive MS Range: 50-2000 Analytical Method e.Instrument: SHIMADZU LC-20AD XR&MS 2020 Column: HALO C18 5 pm, 3.0*30 mm Column temperature: 40C Mobile phase A (MPA) Mobile phase B (MPB) Flow rate: H2O + TFA 0.04% (v / v) ACN + TFA 0.02% (v / v) 2.0 ml / min (0.00-0.9 min) Gradient Ratio: Time (min) 0 0.5 0.90. Petition 870260076443, dated 07 / 31 / 2026, page 150 / 508 141 / 448 MPA (%) 90 0 0 MPB (%) 10 100 100 Detection: 220 nm 254 nm MS Mode: Positive MS Range: 50-2000 Analytical Method f. Instrument: Agilent 1260 & 6125B Column: Xbridge C18 2.1*50 mm, 5 μm Column temperature: 40°C Mobile phase A (MPA) H2O+NH4HCO3 10 mM Mobile phase B (MPB) Acetonitrile Flow rate: 0.8 ml / min Gradient Ratio: Time (min) 0.00 0.40 3.40 3.85 3.86 MPA (%) 95 95 5 5 95 Detection: MPB (%) 5 5 95 95 5 220 nm and 254 nm MS Mode: Positive MS Range: 100-1000 Analytical Method g. Instrument: SHIMADZU LC-20AD XR&MS 2020 Column: HALO C18 5 pm, 3.0*30 mm Column temperature: 40°C Mobile phase A (MPA) H2O + TFA 0.04% (v / v) Mobile phase B (MPB) ACN + TFA 0.02% (v / v) Flow rate: 2.0 ml / min (0.00-0.9 min) Gradient Ratio: Time (min) 0 0.5 0.90 MPA (%) 90 0 0 Detection: MPB (%) 10 100 100 220 nm 254 nm MS Mode: Positive MS Range: 50-2000 Analytical Method h. 4.50 Petition 870260076443, dated 07 / 31 / 2026, page 151 / 508 142 / 448 Instrument: Shimadzu LC-20AB&MS 2020 Column: Xtimate C18 2.1*50 mm, 5 μm Column temperature: 40°C Mobile phase A (MPA) H2O+NH4HCO3 10 mM Mobile phase B (MPB) Acetonitrile Flow rate: 1.0 ml / min (0.01-3.01 min), 1.2 ml / min (3.02-3.50 min) Time (min) 0.01 2.50 3.00 3.01 3.5 Gradient Ratio: MPA (%) 95 5 5 95 95 MPB (%) 5 95 95 55 Detection: 220 254 nm MS Mode: Positive MS Range: 50-2000 Analytical Method i. Instrument: SHIMADZU LC-20AD XR&MS 2020 Column: Halo C18 3.0*30 mm, 5 μm Column temperature: 40°C Mobile phase A (MPA) H2O + TFA 0.04% (v / v) Mobile phase B (MPB) ACN + TFA 0.02% (v / v) Flow rate: 1.5 ml / min (0.00-1.30 min) Time (min) 0.01 0.8 1.30 Gradient Ratio: MPA (%) 90 0 0 MPB (%) 10 100 100 Detection: 220 nm 254 nm MS Mode: Positive MS Range: 50-2000 Analytical Method j. Instrument: Agilent 1260 & 6125B Column: Luna-C18(2) 2.0*50 mm, 5 μm Column temperature: 40°C Mobile phase A (MPA) H2O + TFA 0.04% (v / v) Mobile phase B (MPB) ACN + TFA 0.02% (v / v) Petition 870260076443, dated 07 / 31 / 2026, p. 152 / 508 143 / 448 Flow rate: 1.0 ml / min 4.50 Time (min) 0.00 0.40 3.00 4.00 4.01 Gradient Ratio: MPA (%) 95 95 5 5 95 95 MPB (%) 5 5 95 95 5 5 Detection: 220 nm and 254 nm MS Mode: Positive MS Range: 100-1000 Analytical Method k. Instrument: SHIMADZU LC-20AD XR&MS 2020 Column: Tiank C18 50*2.1 mm, 5 μm Column temperature: 40°C Mobile phase A (MPA) H2O+NH4HCO3 10 mM Mobile phase B (MPB) Acetonitrile Flow rate: 1 ml / min (0.00-4.5 min) Time (min) 0.01 3.5 4.5 Gradient Ratio: MPA (%) 95 5 5 MPB (%) 5 95 95 Detection: 220 nm 254 nm MS Mode: Positive MS Range: 50-2000 Analytical Method l. Instrument: SHIMADZU LC-20AD XR&MS 2020 Column: HALO C18 5 µm, 3.0*30 mm Column temperature: 40°C Mobile phase A (MPA): H2O + TFA 0.04% (v / v) Mobile phase B (MPB): ACN + TFA 0.02% (v / v) Flow rate: 2.0 ml / min (0.00-0.9 min) Time (min): 0 0.5 0.90 Gradient Ratio: MPA (%) 90 0 0 MPB (%) 10 100 100 Detection: 220 nm 254 nm MS Mode: Positive Petition 870260076443, dated 07 / 31 / 2026, page 153 / 508 144 / 448 MS Range: Analytical Method m. Instrument: Column: 50-2000 SHIMADZU LC-20AD XR&MS 2020 Halo C18 3.0*30 mm, 5 μm Column Temperature: 40°C Mobile Phase A (MPA) H2O + TFA 0.04% (v / v) Mobile Phase B (MPB) ACN + TFA 0.02% (v / v) Flow Rate: 2.0 ml / min (0.00-0.90 min) Time (min) 0.01 0.5 0.9 Gradient Ratio: MPA (%) 90 0 0 MPB (%) 10 100 100 Detection: 220 nm 254 nm MS Mode: Positive MS Range: 50-2000 Analytical Method n. Instrument: SHIMADZU LC-20AD XR&MS 2020 Column: Titank C18, 3.0*30 mm, 5 μm Column temperature: 40°C Mobile phase A (MPA) H2O+NH4HCO3 10 mM Mobile phase B (MPB) Acetonitrile Flow rate: 1.5 ml / min (0.00-0.90 min) Time (min) 0.01 0.5 0.9 Gradient Ratio: MPA (%) 90 0 0 MPB (%) 10 100 100 Detection: 220 nm 254 nm MS Mode: Positive and negative MS Range: 50-2000 Analytical Method o. Instrument: Shimadzu LC-20ADXR&MS 2020 Column: Xtimate C18 2.1*50 mm, 5 μm Column temperature: 40°C Mobile phase A(MPA) H2O+NH4HCO3 10 mM Petition 870260076443, dated 07 / 31 / 2026, page 154 / 508 145 / 448 Mobile phase B(MPB) Acetonitrile Flow rate: 1.0 ml / min Time (min) 0.01 2.50 3.00 Gradient Ratio: MPA (%) 95 5 5 MPB (%) 5 95 95 Detection: 220 nm 254 nm MS Mode: Positive MS Range: 50-2000 Analytical Method p. Instrument: Agilent 1260 & 6125B Column: Luna-C18(2) 2.0*50 mm, 5 μm Column temperature: 40°C Mobile phase A (MPA) H2O + TFA 0.04% (v / v) Mobile phase B (MPB) ACN + TFA 0.02% (v / v) Flow rate: 1.0 ml / min Time (min) 0.00 0.40 3.00 4.00 4.01 4.50 Gradient Ratio: MPA (%) 95 95 5 5 95 95 MPB (%) 5 5 95 95 55 Detection: 220 nm MS Mode: Positive MS Range: 100-1000 Analytical Method q. Instrument: Agilent 1260 & 6125B Column: Luna-C18(2) 2.0*50 mm, 5 μm Column temperature: 40°C Mobile phase A (MPA) H2O + TFA 0.04% (v / v) Mobile phase B (MPB) ACN + TFA 0.02% (v / v) Flow rate: 1.0 ml / min Time (min) 0.00 0.40 3.00 4.00 4.01 4.50 Gradient Ratio: MPA (%) 95 95 5 5 95 95 MPB (%) 5 5 95 95 55 Detection: 220 nm and 254 nm Petition 870260076443, dated 07 / 31 / 2026, p. 155 / 508 146 / 448 MS Mode: Positive MS Range: 100-1000 Analytical Method r. Instrument: Agilent 1200 & 6120B Column: Xbridge C18 2.1*50 mm, 5 μm Column Temperature: 40°C Mobile Phase A (MPA) H2O+NH4HCO3 10 mM Mobile Phase B (MPB) Acetonitrile Flow Rate: 0.8 ml / min Time (min) 0.00 0.40 3.40 3.85 3.86 4.50 Gradient Ratio: MPA (%) 95 95 5 5 95 95 MPB (%) 5 5 95 95 5 5 Detection: 220 nm and 254 nm MS Mode: Positive MS Range: 100-1000 Analytical Method s. Instrument: Agilent 1200 & 6130 Column: Xbridge-C18 2.1*50 mm 5 μm Column temperature: 40°C Mobile phase A (MPA) H2O+NH4HCO3 10 mM Mobile phase B (MPB) Acetonitrile Flow rate: 0.8 ml / min Time (min) 0.00 0.40 3.40 3.85 3.86 4.50 Gradient Ratio: MPA (%) 95 95 5 5 95 95 MPB (%) 5 5 95 95 5 5 Detection: 220 nm 254 nm MS Mode: Positive MS Range: 100-1000 Analytical Method t. Instrument: Shimadzu LC-20AD&MS 2020 Column: Xtimate C18 2.1*50 mm, 5 μm Column temperature: 40C Petition 870260076443, dated 07 / 31 / 2026, page 156 / 508 147 / 448 Mobile Phase A (MPA) H2O + NH4HCO3 10 mM Mobile Phase B (MPB) Flow Rate: Gradient Ratio: Acetonitrile 1.0 ml / min Time (min) 0.01 2.50 MPA (%) 95 5 3.00 5 3.01 95 3.5 95 MPB (%) 5 95 95 5 5 Detection: ELSD 220 nm 254 nm MS Mode: Positive MS Range: 50-2000 Analytical Method u. Instrument: Shimadzu LC-30AD&MS 2020 Column: Halo C18 3.0*30 mm, 5 μm Column temperature: 40°C Mobile phase A (MPA) H2O + TFA 0.04% (v / v) Mobile phase B (MPB) ACN + TFA 0.02% (v / v) Flow rate: 1 ml / min (0.01-3.00 min), 1.2 ml / min (3.01-3.50 min) Gradient Ratio: Time (min) 0.01 2.50 MPA (%) 95 5 3.00 5 3.01 95 3.5 95 Detection: MS Mode: MS Range: MPB (%) 5 95 ELSD 220 nm 254 nm Positive 50-2000 95 5 5 The purification methods were as follows: Purification Method 1 (P1):

[00186] LC purifications were performed on a Gilson LC system using a Waters Sunfire C18 column (30 mm x 100 mm, 10 μM; temperature: rt) and a 10-95% B gradient (A = 0.1% formic acid in water; B = 0.1% formic acid in acetonitrile) over 14.44 min, then 95% B for 2.11 min. A second 95-10% B gradient was then applied over 0.2 min with an injection volume of 1500 μL at a flow rate of 40 ml / min. UV spectra were recorded at 215 nm. Petition 870260076443, dated 07 / 31 / 2026, p. 157 / 508 148 / 448 using a Gilson detector. Purification Method 2 (P2):

[00187] LC purifications were performed on a Gilson LC system using a Waters Sunfire C18 column (30 mm x 10 mm, 10 μM; temperature: rt) and a 30-95% B gradient (A = 0.1% formic acid in water; B = 0.1% formic acid in acetonitrile) over 11.00 min, then 95% B for 2.10 min. A second 95-30% B gradient was then applied over 0.2 min with an injection volume of 1500 μl at a flow rate of 40 ml / min. UV spectra were recorded at 215 nm using a Gilson detector. Purification Method 3 (P3):

[00188] LC purifications were performed on a Gilson LC system using a Waters X-Bridge C18 column (30 mm x 100 mm, 10 μM; temperature: rt) and a 10-95% B gradient (A = 0.2% ammonium hydroxide in water; B = 0.2% ammonium hydroxide in acetonitrile) over 14.44 min, then 95% B for 2.11 min. A second 95-10% B gradient was then applied over 0.2 min with an injection volume of 1500 μl at a flow rate of 40 ml / min. UV spectra were recorded at 215 nm using a Gilson detector. Purification Method 4 (P4):

[00189] LC purifications were performed on a Gilson LC system using a Waters X-Bridge C18 column (30 mm x 10 mm, 10 μM; temperature: rt) and a gradient of 30-95% B (A = 0.2% ammonium hydroxide in water; B = 0.2% ammonium hydroxide in acetonitrile) over 11.00 min, then 95% B for 2.10 min. A second 95-30% B gradient was then applied over 0.21 min with an injection volume of 1500 μl at a flow rate of 40 ml / min. UV spectra were recorded at 215 nm using a Gilson detector. Purification Method 5 (P5): Petition 870260076443, dated 07 / 31 / 2026, page 158 / 508 149 / 448 Instrument: Gilson 281 semi-preparative HPLC system; Mobile phase: A: H2O (HCl 0.04%); B: ACN; Column: Phenomenex Luna C18 100*30 mm*3 μm; Column temperature: Ambient, variable gradient; Flow rate: 25 ml / min; Monitor wavelength: 220 nm and 254 nm Purification Method 6 (P6): Instrument: Gilson 281 semi-preparative HPLC system; Mobile phase: A: water (NH4HCO3); B: ACN; Column: Phenomenex C18 80*40 mm*3 μm; Column temperature: Ambient, variable gradient; Flow rate: 25 ml / min; Monitor wavelength: 220 nm and 254 nm Purification Method 7 (P7): Instrument: Gilson 281 semi-preparative HPLC system; Mobile phase: A: water (NH4HCO3); B: ACN; Column: Waters Xbridge Prep OBD C18 150*40 mm*10 μm; Column temperature: Ambient, variable gradient; Flow rate: 25 ml / min; Monitor wavelength: 220 nm and 254 nm Purification Method 8 (P8): Instrument: Gilson 281 semi-preparative HPLC system; Mobile phase: A: water (NH4HCO3); B: ACN; Column: Waters Xbridge BEH C18 100*30 mm*10 μm; Column temperature: Ambient, variable gradient; Flow rate: 25 ml / min; Monitor wavelength: 220 nm and 254 nm Purification Method 9 (P9): Instrument: Gilson 281 semi-preparative HPLC system; Petition 870260076443, dated 07 / 31 / 2026, page 159 / 508 150 / 448 Mobile phase: A: water (NH4HCO3); B: ACN; Column: Waters Xbridge BEH C18 250*70 mm*10 μm; Column temperature: Ambient, variable gradient; Flow rate: 25 ml / min; Monitor wavelength: 220 nm and 254 nm Purification Method 10 (P10): Instrument: Guidance; Mobile phase: A: water + HCl; B: ACN Column: Angela C18 column weighing 4 kg; Flow rate: 500 ml / min; Purification Method 11 (P11): Instrument: Waters SFC350 preparative SFC; Mobile phase: A for CO2 and B for EtOH (NH3H2O ​​0.1%); B% = isocratic elution mode 55% Column: DAICEL CHIRALPAK AD (250 mm*50 mm,10 pm); Column temperature: Ambient, variable gradient; Flow rate: 200 g / min; Monitor wavelength: 220 nm Purification Method 12 (P12): Instrument: Waters SFC350 preparative SFC; Mobile phase: A for CO2 and B for EtOH; B% = isocratic elution mode 20% Column: DAICEL CHIRALCEL OJ (250 mm*50 mm,10 pm); Column temperature: Ambient, variable gradient; Flow rate: 200 g / min; Monitor wavelength: 220 nm Purification Method 13 (P13):

[00190] The raw material was purified using a Jasco System consisting of a CO2 preparative pump (PU-4387), a pump Petition 870260076443, dated 07 / 31 / 2026, page 160 / 508 151 / 448 preparative organic solvent autosampler (PU-4087 with six-channel selector), preparative SFC autosampler (AS-4358), column oven with four valve selectors (CO-4065), a PDA detector (MD-1201), a backpressure regulator (BP-4340), two open-bed recirculating collectors (FL-223), and a Julabo recirculating cooler (FL-4015). Data acquisition was performed using ChromNAV 2.04.00 software, equipped with a Phenomenex Lux Amylose-1 column (250 x 30 mm 5 μm, 5 μM; temperature: 35 °C), with a flow rate of 30 ml / min and BPR set at 12 MPa (120 Bar). An isocratic elution was performed with 60% B (A = CO2; B = 0.1% diethylamine in 2-propanol) over 20 min in a stacked injection mode. The acquisition frequency was set to 220 nm for the PDA detector. Purification Method 14 (P14):

[00191] The raw material was purified using a Jasco System consisting of a CO2 preparative pump (PU-4387), an organic solvent preparative pump (PU-4087 with six-channel selector), a preparative SFC autosampler (AS-4358), a column oven with four valve selectors (CO-4065), a PDA detector (MD-1201), a backpressure regulator (BP-4340), two open-bed recirculating collectors (FL-223) and a Julabo recirculating cooler (FL-4015). Data acquisition was performed using ChromNAV 2.03.05 software, equipped with a Phenomenex Lux Amylose-1 column (250 x 30 mm 5 μm, 5 μm; temperature: 35 °C), with a flow rate of 30 ml / min and BPR set at 12 MPa (120 Bar). An isocratic elution was performed with 55% B (A = CO2; B = 0.1% diethylamine in 2-propanol) in 20 min in a stacked injection mode. The acquisition frequency was set to 220 nm for the PDA detector. Purification Method 15: Instrument: Gilson 281 semi-preparative HPLC system; Petition 870260076443, dated 07 / 31 / 2026, p. 161 / 508 152 / 448 Mobile phase: A: H2O (NH4HCO3 10 mM); B: ACN; Column: Waters Xbridge Prep OBD C18 150*40 mm*10 μm; Column temperature: ambient; Gradient: B 30%-60% over 8.0 min; Flow rate: 25 ml / min; Monitor wavelength: 220 and 254 nm Purification Method 16: Instrument: Gilson 281 semi-preparative HPLC system; Mobile phase: A: H2O (NH4HCO3 10 mM); B: ACN; Column: Phenomenex Gemini-NX 150*30 mm*5 μm; Column temperature: ambient; Gradient: B 30%-70% over 20.0 min; Flow rate: 25 ml / min; Monitor wavelength: 220 and 254 nm Purification Method 17: Instrument: Gilson 281 semi-preparative HPLC system; Mobile phase: A: H2O (FA 0.2%)-ACN; B: ACN; Column: Phenomenex Luna C18 100*30 mm*3 μm; mobile phase; Column temperature: ambient; Gradient: B 25%-55% over 8.0 min; Flow rate: 25 ml / min; Monitor wavelength: 220 and 254 nm Purification Method 18: Instrument: Gilson 281 semi-preparative HPLC system; Mobile phase: A: H2O (NH4HCO3 10 mM); B: ACN; Column: Agela DuraShell C18 250*70 mm*10 μm; Column temperature: ambient; Gradient: B 80%-95% over 20.0 min; Flow rate: 25 ml / min; Petition 870260076443, dated 07 / 31 / 2026, p. 162 / 508 153 / 448 Monitor wavelength: 220 and 254 nm Purification Method 19: Instrument: Gilson 281 semi-preparative HPLC system; Mobile phase: A: H2O (NH3H2O ​​0.05% + NH4HCO3 10 mM); B: ACN; Column: Welch Xtimate C18 250*100 mm*10 μm; Column temperature: ambient; Gradient: B 40%-70% over 24.0 min; Flow rate: 25 ml / min; Monitor wavelength: 220 and 254 nm SFC A Purification Method: Instrument: Auno-600; Mobile phase: A for Heptane and B for EtOH (NH3H2O ​​0.1%); B% = 20% isocratic elution mode; Column: DAICEL CHIRALPAK IG (250 mm*50 mm,10 pm) ; Column temperature: 25 °C Flow rate: 130 ml / min Monitor wavelength: 200 nm NMR conditions

[00192] Unless otherwise indicated, 1H NMR spectra were recorded at 500 MHz or 400 MHz on a Bruker Avance III HD 500 MHz or Bruker Avance III HD 400 MHz spectrometer, respectively. Chemical shifts, δ, are quoted in parts per million (ppm) and are referenced to the residual solvent peak. The following abbreviations are used to denote multiplicities and general assignments: s (singlet), d (doublet), t (triplet), q (quartet), dd (doublet of doublets), ddd (doublet of doublets of doublets), dt (doublet of triplets), dq (doublet of quartets), hep (heptet), m (multiplet), pent (pentet), td (triplet of doublets), qd (quartet of doublets), app. (apparent) and br. (wide). The coupling constants, J, are quoted for the nearest 0.1 Hz. Petition 870260076443, dated 07 / 31 / 2026, page 163 / 508 154 / 448 Table 3. List of Abbreviations AIBN α,α'-azoisobutyronitrile Ac acyl AcN acetonitrile AC2O acetic anhydride Ar aromatic aqueous solution Bn benzyl BOC tert-butoxycarbonyl Cbz carboxybenzyl group CDI carbonyldiimidazole CuI copper iodide CV column volumes of doublets DAST diethylaminosulfur trifluoride DCM dichloromethane DCE 1,2-dichloroethane DBA dibenzylideneacetone DIAD diisopropyl azodicarboxylate DIPEA diisopropyl ethylamine DMA NN-dimethylacetamide DME dimethoxyethane DMF NN-dimethylformamide DMSO dimethyl sulfoxide DPPA diphenyl phosphoryl azide DPPE ethylenebis(diphenylphosphine) dppb 1,3-bis(diphenylphosphino)propane dppf 1,1' -bis(diphenylphosphino)ferrocene dtbpf 1,1-bis(di-tert-butylphosphino)phenOcene EDCI 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride ESI ionization by electrospray in positive ion mode Et2O diethyl ether EtOAc or EA ethyl acetate EtOH ethyl alcohol EtONa sodium ethoxide FCC flash column chromatography h hour(s) HATU (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5- b ]pyridinium 3-oxide HFIP hexafluoroisopropanol, Petition 870260076443, dated 07 / 31 / 2026, page 164 / 508 155 / 448 HOAc acetic acid HOBt 1-hydroxybenzotriazole HPLC high-performance liquid chromatography i-PrOH isopropyl alcohol KOAc potassium acetate KOH potassium hydroxide LAH lithium aluminum hydride LCMS liquid chromatography and mass spectrometry LiHMDS lithium bis(trimethylsilyl)amide M+H ion observed by mass spectrometry created by addition of a hydrogen cation mCPBA 3-chloroperbenzoic acid MeCN acetonitrile MeOH methanol Me4tBuXphos 2-di-tert-butylphosphos-3,4,5,6-tetramethyl-2',4',6'-tri-isopropyl-1,1'-biphenyl MTBE tert-butyl methyl ether m multiplet min minute(s) ml milliliter mol / M mol / molar mmol millimol N2 nitrogen NBS N-bromo succinimide NH4OAC ammonium acetate NMO N-oxide of 4-methylmorpholine NMP 1-methyl-2-pyrrolidinone NMR nuclear magnetic resonance OTf trifluoromethanesulfonate PE petroleum ether PPA polyphosphoric acid q quartet rt room temperature RT retention time s singlet Sat.Saturated SFC supercritical fluid chromatography STAB sodium triacetoxy borohydride t triplet TBAF tetrabutyl ammonium fluoride TBAT tetrabutylammonium difluorotriphenylsilicate. Petition 870260076443, dated 07 / 31 / 2026, page 165 / 508 156 / 448 TBDPS tert-butyl diphenyl silyl TBSCl tert-butylchlorodimethylsilane t-BuOH tert-butanol t-BuOK potassium tert-butoxide t-BuOLi lithium tert-butoxide TCFH N,N,N',N'-tetramethylchloroformamidin hexafluorophosphate TEA triethylamine TFA 2,2,2-trifluoroacetic acid TFAA trifluoroacetic anhydride THF tetrahydrofuran TLC thin-layer chromatography TMS trimethylsilyl TMSN3 azidotrimethylsilane TMSOK potassium trimethylsilanolate μΐ microliter XPhos Pd G2 chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) XPhos Pd G3 (2-Dicyclohexylphosphine-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'amino-1,1'-biphenyl)]palladium(II) methanesulfonate

[00193] The compounds were named using OpenEye Scientific software (Lexichem TK). Synthetic Method 1 Outline for Method 1 Step 1, Method 1

[00194] Ethyl 2-chloro-2-oxo-acetate (12.0 ml, 105.0 mmol, CAS 4755-77-5) was added to a solution of 7-bromo-6-methoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid (20.00 g, 69.9 mmol) in anhydrous THF (300 ml) and the reaction mixture was stirred at RT for 1 h. The reaction mixture was concentrated in vacuo to generate 7-bromo-2-(2-ethoxy-2-oxo-acetyl)-6-methoxy-3,4-dihydro-1H-isoquinoline-carboxylic acid as a yellow solid which was used directly in the next step assuming quantitative yield. RT (M2) = 0.75 min, [M+H]+ (ESI+) 386.1 / 388.1. Petition 870260076443, dated 07 / 31 / 2026, page 166 / 508 157 / 448 Step 2, Method 1

[00195] Pent-1-yne (8.6 ml, 87.4 mmol, CAS 627-19-0) was added to a stirred solution of 7-bromo-2-(2-ethoxy-2-oxo-acetyl)-6-methoxy-3,4-dihydro-1H-isoquinoline-1-carboxylic acid (26.99 g, 69.9 mmol) in acetic anhydride (207 ml). The reaction mixture was placed in a heating block preheated to 140 °C and stirred for 45 min. The reaction mixture was cooled and concentrated in vacuo. The resulting residue was absorbed in DCM (200 ml) and stirred with saturated aqueous NaHCO3 (100 ml). The organic layer was separated, dried over MgSO4, and concentrated in vacuo. Heptane (200 ml) and diethyl ether (50 ml) were added and the resulting mixture heated to 85 °C for 30 min. A hot filtration was performed to provide a solid. This solid was dried and ground with a mortar and pestle to yield ethyl 9-bromo-8-methoxy-1-propyl-5,6-dihydropyrrolo[2,1a]isoquinoline-3-carboxylate (13.90 g, 48% yield) as a brown solid.The filtrate was left overnight and orange crystals formed which were isolated by filtration to generate the most desirable product (3.13 g, 11% yield) as an orange solid. RT (M2) = 1.31 min, [M+H]+ (ESI+) 392.3 / 394.3; 1H NMR (500 MHz, DMSO) δ 7.68 (s, 1H), 7.16 (s, 1H), 6.78 (s, 1H), 4.48 (t, J = 6.6 Hz, 2H), 4.21 (q, J = 7.1 Hz, 2H), 3.88 (s, 3H), 2.99 (t, J = 6.5 Hz, 2H), 2.63 (t, J = 7.6 Hz, 2H), 1.66 1.57 (m, 2H), 1.27 (t, J = 7.1 Hz, 3H), 0.97 (t, J = 7.3 Hz, 3H). Table 4. The following analogues were made using the analogous method: Structure Name LCMS 9-bromo-1-(4-fluorophenyl)-8-methoxy-5,6dihydropyrrolo [2,1- a ]isoquinoline-3 ethyl carboxylate RT (M8) = 1.10 min, [M+H]+ (ESI+) 444.1 / 446.1 ' XX? ji ethyl 9-bromo-8-methoxy-1-thiazol-5-yl-5,6-dihydropyrrolo[2,1- a ]isoquinoline-3carboxylate RT (M3) = 1.10 min, [M+H]+ (ESI+) 433.1 / 435.1 Petition 870260076443, dated 07 / 31 / 2026, p. 167 / 508 158 / 448Structure Name LCMS O (5R )-9-bromo-8-methoxy-5-methyl-1-thiazol- 5-yl-5,6-di-hidropyrrolo[2,1- a ]isoquinoline-3-ethyl carboxylate RT (M2) = 1.09 min, [M+H]+ (ESI+) 447.1 / 449.0 ' XjCX o (5 R )-9-bromo-8-methoxy-5-methyl-1-(2thienyl)-5,6-di-hidropyrrole [2,1a ]isoquinoline-3-ethyl carboxylate RT (M2) = 1.32 min, [M+H]+ (ESI+) 446.1 / 448.1 / O.,, / ^ / ^ „ NJ Br^^J'V\ 9-bromo-8-methoxy-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylate ethyl RT (M11) = 2.04 min, [M+H]+ (ESI+) 350.1 / 352.1. 1-(1 -(benzyloxy)-2-methylpropan-2-yl)-9bromo-8-methoxy-5,6-dihydropyrrolo[2,1- a]isoquin-oline-3-carboxylate ethyl RT (M13) = 2.67 min, [M+H]+ (ESI+) 512.3 / 514.1. x XX? 9-bromo-8-methoxy-1-(1,3,4-thiadiazol-2yl)-5,6-di-hidropyrrolo[2,1-a]isoquinolina-3-carboxylate de ethyla RT (M14) = 1.13 min, [M+H]+ (ESI+) 434.1 / 436.0 XX? ji 9-bromo-1-(3,3-difluorociclobutil)-8methoxy-5,6-di-hidropyrrolo[2,1a]isoquinolina-3-carboxylate de ethyla RT (M22) = 0.97 min, [M+H]+ (ESI+) 440.1 / 442.1.XX?^ X 9-bromo-1-(5-fluoropyridin-2-yl)-8methoxy-5,6-di-hydropyrrole[2,1a]isoquinoline-3-ethyl carboxylate RT (M19) = 0.89 min, [M+H]+ (ESI+) 445.1.2. X (R*)-9-bromo-8-methoxy-6-methyl-1(thiophen-2-yl)-5,6-di-hydropyrrole[2,1a]isoquinoline-3-ethyl carboxylate RT (M25) = 3.13 min, [M+I]+ (ESI+) H] min = [0.89 445.2 / 447.1. Petition 870260076443, dated 07 / 31 / 2026, p. 168 / 508 159 / 448 Structure Name LCMS XX? jj (R*)-9-bromo-8-methoxy-6-methyl-1(thiophen-2-yl)-5,6-dihydropyrrolo[2,1a]isoquinoline-3-carboxylate ethyl Method SFC (11) First enantiomer RT (M25) = 0.89 min, [M+H]+ (ESI+) 446.0 / 447.9. Second enantiomer RT (M25) = 1.80 min, [M+H]+ (ESI+) 417.9 / 419.9. XX?j V (R*)-9-bromo-8-methoxy-5-methyl-1(thiophen-2-yl)-5,6-dihydropyrrolo[2,1a] ethyl isoquinoline-3-carboxylate SFC method (11) Second enantiomer RT (M15) = 1.08 min, [M+H]+ (ESI+) 444.8 / 446.1. XXX? ethyl-9-bromo-8-methoxy-5-methyl-5,6-dihydropyrrolo[2,1-a]isoquinoline-3carboxylate RT (M1) = 2.07 min, [M+H]+ (ESI+) 364.1 / 366.1. x XX? 0 (1aR,9bR)-7-bromo-8-methoxy-5-(thiophen2-yl)-1a,9b-dihydro-1H-cyclopropa [c]pyrrolo[2,1-a]isoquinoline-3carboxylate ethyl RT (M22) = 1.02 min, [M+H]+ (ESI+) 444.1 / 446.1. * Denotes unknown stereochemistry, isolated from a diastereomeric mixture using SFC chromatography. Synthetic Method 2 Outline for Method 2 Step 1, Method 2

[00196] Potassium hydroxide (7.93 g, 139.0 mmol) was added to a stirred solution of ethyl 9-bromo-8-methoxy-1-(2-thienyl)-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylate (prepared according to a method analogous to method 1 (steps 1 and 2) using 2-ethynyl-thiophene) (15.00 g, 34.7 mmol) in ethanol (300 ml) and water (100 ml) at 80 °C. After 1 h, the reaction mixture was cooled to rt and concentrated in vacuo. The aqueous residue was acidified to pH 1 using 1 M aqueous HCl, and the solid suspended in the aqueous layer was collected by filtration to yield 9-bromo-8-methoxy-1-(2 Petition 870260076443, dated 07 / 31 / 2026, page 169 / 508 160 / 448 tienil)-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylic acid (83% purity, 14.70 g, 87% yield) as a pale brown solid. RT (M2) = 1.03 min, [M+H]+ (ESI+) 402.9 / 404.9. Step 2, Method 2

[00197] DIPEA (30 ml, 173.0 mmol, CAS 7087-68-5), HATU (14.11 g, 37.1 mmol, CAS 148893-10-1) and (2R)-2-methylpyrrolidine-2-carboxamide hydrochloride (4.89 g, 29.7 mmol, CAS 1262381-66-7) were added to a stirred solution of 9-bromo-8-methoxy-1-(2-thienyl)-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylic acid (10.00 g, 24.7 mmol) in DCM (400 ml) at rt. The reaction mixture was stirred overnight and then diluted with DCM and water. The layers were separated, the organic material passed through a phase separator, and then concentrated in vacuo to yield the crude product as a brown oil. The crude product was purified by FCC (silica, eluting with 0-100% EtOAc in heptane, then 0-20% MeOH in EtOAc). The product-containing fractions were concentrated in vacuo to generate (2R)-1-[9-bromo-8-methoxy-1-(2-thienyl)-5,6-dihydropyrrolo[2,1a]isoquinoline-3-carbonyl]-2-methylpyrrolidine-2-carboxamide (10.27 g, 77% yield) as a pale brown foam.RT (M2) = 1.00 min, [M+H]+ (ESI+) 514.2 / 516.2; 1H NMR (400 MHz, DMSO) δ 8.16 (s, 1H), 7.57 (dd, J = 5.2, 1.2 Hz, 1H), 7.45 (s, 1H), 7.18 - 7.10 (m, 2H), 7.07 (dd, J = 3.4, 1.2 Hz, 1H), 6.82 (s, 1H), 6.66 (s, 1H), 4.24 - 4.20 (m, 1H), 3.96 - 3.91 (m, 1H), 3.86 (s, 3H), 3.81 - 3.74 (m, 1H), 3.69 - 3.57 (m, 1H), 3.20 - 3.09 (m, 1H), 3.05 - 2.97 (m, 1H), 2.10 - 2.02 (m, 1H), 1.89 - 1.84 (m, 3H), 1.53 (s, 3H). Table 5. The following analogues were made using the analogous method: Structure Name LCMS VJT? / 7 = [9-bromo-8-methoxy-1-(2-thienyl)-5,6dihydropyrrolo[2,1- a ]isoquinolin-3-yl]-[(25-2-ethyl-2-methyl-pyrrolidin-1-yl]methanone RT (M2) = 1.23 min, [M+H]+ (ESI+) 499.1 / 501.1. Petition 870260076443, dated 07 / 31 / 2026, page 170 / 508 161 / 448 Structure Name LCMS ?OO jj - [9-bromo-8-methoxy-1-(2-thienyl)-5,6-dihidropyrrole [2,1- a ]isoquinolin-3-yl]-[(2R )-2(hidroximethyl)-2-methyl-pyrrolidin-1-yl]methane RT (M2) = 0.95 min, [M+H]+ (ESI+) 501.2 / 503.2 XX? j V [9-bromo-8-methoxy-1-(2-thienyl)-5,6-dihidropyrrole [2,1- a ]isoquinolin-3-yl]-(2,2dimethylpyrrolidin-1-yl)methanone RT (M2) = 1.18 min, [M+H]+ (ESI+) 485.1 / 487.1 XX^ (2R )-1-(9-bromo-8-methoxy-1-propyl-5,6-dihidropyrrole [2,1- a ]isoquinoline-3-carbonyl)-2- methyl-pyrrolidine-2-carboxamida RT (M2) = 0.96 min, [M+H]+ (ESI+) 474.2 / 476.2 (2R )-1-[9-bromo-1-(4-fluorophenyl)-8-methoxy- 5,6-dihydropyrrolo[2,1- a ]isoquinoline-3carbonyl]-2-methyl-pyrrolidine-2-carboxamide RT (M2) = 0.98 min, [M+H]+ (ESI+) 526.0 / 528.0 ΧΧΧ \ [9-bromo-1-(4-fluorophenyl)-8-methoxy-5,6-dihydropyrrolo[2,1- a ]isoquinolin-3-yl]-[(2R )-2[(1R)-1-hydroxyethyl]-2-methyl-pyrrolidin-1yl]methanone RT (M3) = 0.99 min, [M+H]+ (ESI+) 527.3 / 529.3 ' X?O / , - (2R )-1-[9-bromo-8-methoxy-1-(2,2,2trifluoroethyl)-5,6-di-hydropyrrole[2,1 a ]isoquinoline-3 -carbonyl]-2 -methyl-pyrrolidine2-carboxamide RT (M3) = 0.90 min, [M+H]+ (ESI+) 514.1 / 516.1 XX? ji - [9-bromo-8-methoxy-1-(2,2,2-trifluoroethyl)-5,6di-hydropyrrole [2,1- a ]isoquinolin-3-yl]-[(2R )-2[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidin-9 min (RT,M03]methano3 [M+H]+ (ESI+) 515.3 / 517.3 1 cT [(2R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidin1-yl]-[8-methoxy-9-(4,4,5-5-tetramethyl-5-1,3-2-dioxaborolan) -dihydropyrrole [2,1- to ]isoquinolin-3-yl]methanone RT (M2) = 0.91 min, [M+H]+ (ESI+) 516.1 / 518.1, Petition 870260076443, dated 07 / 31 / 2026, p. 171 / 508 162 / 448 Structure Name LCMS 1 ΧϊΟ jj < 3γ Y (9-bromo-8-methoxy-1-thiazol-5-yl-5,6-dihydropyrrolo [2,1- a ]isoquinolin-3-yl)-[(2R )-2metil-2-[(1 .S')-2,2,2-trifluoro-1-hidroxyethyl]pyrrolidin-1-yl]methanone RT (M2) = 0.99 min, [M+H]+ (ESI+) 570.0 / 572.0 ^XX? U ' 43 M (2R )-1-(9-bromo-8-methoxy-1-thiazol-5-yl-5,6-dihidropyrrole [2,1- a ]isoquinoline-3-carbonyl)-2methyl-pyrrolidine-2-carboxamida RT (M2) = 0.97 min, [M+H]+ (ESI+) 515.1 / 517.1 ' XXO u -w γί [9-bromo-8-methoxy-1-(2-thienyl)-5,6-dihidropyrrole [2,1- a ]isoquinolin-3-yl]-[(2 S)-2methyl-2-[(1 R )-2,2,2-trifluoro-1-hidroxyethyl]pyrrolidin-1-yl]methanone RT (M2) = 1,14 min, [M+H]+ (ESI+) 569.1 / 571.1 XjO λ YY^ (R )-1-(9-bromo-8-methoxy-1-(2,2,2trifluoroethyl)-5,6-di-hydropyrrolo[2,1 a]isoquinolina-3-carbonyl)-2-methylazetidine-2-carboxamide RT (M13) = 1.74 min [M+H]+ (ESI+) 500.3 / 502.0 γθγ ji - 1 0 (R )-1-(1-(2,2-difluoropropyl)-8-methoxy-9-(2methyl-2H-tetrazol-5-yl)-5,6-di-hydropyrrolo[2,1 a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carboxamide RT (M29) = 0.62 min, [M+H]+ (ESI+) 514.1 x ΤΊΟ / / .'?YYr* / í (R )-1-(1-(2,2-difluoropropyl)-8-methoxy-9-(2methyl-2H-tetrazol-5-yl)-5,6-di-hidropyrrolo[2,1a]isoquinoline-3-carbonyl)-2-methylazetidine-2carboxamida RT (M13) = 1.38 min, [M+H]+ (ESI+) 500.3 ^Χγ^ Vy <Y Q (9-bromo-8-metoxi-1-(1,3,4-tiadiazol-2-il)-5,6di-hidropirrolo [2,1-a]isoquinolin-3 -il)((S)-2metil-2-((R )-2,2,2-trifluoro-1hidroxietil)pirrolidin-1-il)metanona RT (M11) = 1,13 min [M+H]+ (ESI+) 571,2 / 573,2 ' XX? jj ~ γ^ Y (R )-1-(9-bromo-1-(3,3-difluorociclobutil)-8metoxi-5,6-di-hidropirrolo[2,1-a]isoquinolina3-carbonil)-2-metilpirrolidina-2-carboxamida RT (M13) = 1,86 min [M-128,1]+ (ESI+) 394,2 / 396,2. Petition 870260076443, 07 / 31 / 2026, pág. 172 / 508 163 / 448 Structure Name LCMS 5.13 Hz, 2 H), 7.41 (s, 1 H), 7.21 (br s, 1 H), 7.10 - 7.16 (m, 2 H), 7.06 (br d, J = 2.75 Hz, 1 H), 6.69 (br s, 1 H), 4.46 - 4.57 (m, 1 H), 4.28 - 4.45 (m, 3 H), 3.86 (s, 3 H), 3.01 (br t, J = 6.38 Hz, 2 H), 2.36 - 2.46 (m, 1 H), 1.97 - 2.09 (m, 1 H), 1.68 (br s, 3 H) ' XX? 0? (R )-1-(9-bromo-1-(5-fluoropyridin-2-yl)-8methoxy-5,6-di-hydropyrrolo[2,1-a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carboxamide RT (M13) = 1.48 min [M+H]+ (ESI+) 528.2 / 530.2 300^7 .. A 00 0 (R )-1-(1 -(5-fluoropyridin-2-yl)-8-methoxy-9-(2metil-2H-tetrazol-5-yl)-5,6-di-hydropyrrolo[2,1a]isoquinolina-3-carbonyl)-2-metilazetidine-2-carboxamide RT (M20) = 1.34 min, [M+H]+ (ESI+) 517.2 'XX? - 0 ((5*)-9-bromo-8-methoxy-6-methyl-1-(thiophen-2yl)-5,6-di-hydropyrrole[2,1-a]isoquinoline-3yl)((R)-2-((R)-1-hydroxyethyl)-2-methylpyrrolidin1-yl)methanone RT (M11) = 2.11 min [M+H]+ (ESI+) 529.2 / 531.2 ?CO ji (50 )- 1 - ^^ *)-9-bromo-8-methoxy-6 -methyl-1- (thiophen-2-yl)-5,6-di-hydropyrrole[2,1a]isoquinoline-3-carbonyl)-2-methylpyrrolidine- 2-carboxamide RT (M11) = 3.21 / 5 min [M8,+2) ?0Cr for − − 0< 0 ((R )-9-bromo-8-methoxy-5-methyl-1-(thiophene-2-yl)5,6-di-hydropyrrole[2,1-a]isoquinoline-3-yl)((R)2-methyl-2-((S)-2,2,2-trifluoro-1hydroxyethyl)2pyrrolidine1-1-1- [M+H]+ (ESI+) 583.3 / 585.3 x XX?0 = ? ^^040 ;0 0 ((5)-9-bromo-8-methoxy-5-methyl-1-(thiophen-2-yl)5,6-di-hydropyrrole[2,1-a]isoquinoline-3-yl)((R)2-methyl-2-1-((S)-2,2,2-RThydroxyfluorodine)pyroxyfluorodine-1 (M11) = 2.28 min [M+H]+ (ESI+) 583.2 / 585.3, Petition 870260076443, dated 07 / 31 / 2026, p. 173 / 508 164 / 448 Structure LCMS Name XXX j 0 ((R )-9-bromo-8-methoxy-5-methyl-1-(thiophen-2-yl)5,6-di-hydropyrrole[2,1-a]isoquinoline-3-yl)((R)- ((R)- 2-((R)-1-hydroxyethyl-pyr)RT)-meth1-2-methyl = 2.12 min [M+H]+ (ESI+) 529.1 / 531.1 ' XX? Jj - 3 0 ((S)-9-bromo-8-methoxy-5-methyl-1-(thiophene-2-yl)5,6-di-hydropyrrole[2,1-a]isoquinolin-3-yl)((R)2-((R)-1-hydroxyethyl)-2-methylpyrromethanone-1 = 1 [M+H]+ (ESI+) 529.1 / 531.2 x XXX ji -^^00^ J / C 0 (R )-1-((S)-9-bromo-8-methoxy-5-methyl-1- (thiophen-2-yl)-5,6-li-hydropyrrole[2,methylpyro-3iso 2-carboxamide RT (M27) = 2.47 min [M+H]+ (ESI+) 528.4 / 530.0 x XXXji -004 χχ ((R )-9-bromo-8-methoxy-5-methyl-1-(2,2,2trifluoroethylhydroethyl[5-methyl)-2,2,2trifluoroethyl[5-methyl)-2 a]isoquinolin-3-yl)((R)-2-methyl-2-((S)-2,2,2trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)methanone RT (M30) = 0.62 min [M+H]+ (ESI+) 583.2 / jJ J.,1.^0L0- 00 0 ((1aR,9bR)-7-bromo-8-methoxy-5-(thiophen-2-yl)1a,9b-dihydro-1H-cyclopropa[c]pyrrolo[2,1a]isoquinolin-3-yl)((R)-2-methyl-2-((S)-2,2,2trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)methanone RT (M11) = 0.72 min [M+H]+ (ESI+) 581.2 / 583.2. * Denotes unknown stereochemistry, isolated from a diastereomeric mixture using SFC chromatography. Synthetic Method 3 Outline for Method 3 Step 1, Method 3

[00198] (1S)-2,2,2-trifluoro-1-[(2R)-2-methylpyrrolidin-2-yl]ethanol hydrochloride (447 mg, 2.0 mmol, synthesized by method 16) was added to a stirred solution of di(imidazol-1-yl)methanone (412 mg, 2.5 mmol, CAS 530-62-1) and 9-bromo-8-methoxy-1-(2-thienyl)-5,6-dihydropyrrolo[2,1a]isoquinoline-3-carboxylic acid (690 mg, 1.7 mmol) in anhydrous DMF (10 ml) and left at room temperature overnight. The reaction was then heated to 50 °C. Petition 870260076443, dated 07 / 31 / 2026, page 174 / 508165 / 448 and stirred for 8 h before being retreated with (15)-2,2,2-trifluoro-1-[(2R)-2-methylpyrrolidin-2-yl]ethanol hydrochloride (447 mg, 2.0 mmol) and stirred at rt for a further 72 h. The reaction mixture was concentrated in vacuo and split between DCM and water. The layers were separated, the organic passed through a phase separator and was concentrated in vacuo to yield the crude product as a yellow oil which was purified by FCC (silica, eluting 0-100% EtOAc in heptane). The product-containing fractions were collected, combined, and the solvent removed in vacuo to generate [9-bromo-8-methoxy-1(2-thienyl)-5,6-dihydropyrrolo[2,1-a]isoquinolin-3-yl]-[(2R)-2-methyl-2-[(1S)2,2,2-trifluoro-1-hydroxyethyl]pyrrolidin-1-yl]methanone (80% purity, 1.05 g, 87% yield) as a beige solid.RT (M2) = 1.15 min [M+H]+(ESI+) 569.1 / 571.1; 1H NMR (400 MHz, DMSO) δ 7.56 (dd, J = 5.2, 1.2 Hz, 1H), 7.43 (s, 1H), 7.16 - 7.09 (m, 2H), 7.06 (dd, J = 3.5, 1.2 Hz, 1H), 6.66 (d, J = 7.2 Hz, - 2.28 (m, 1H), 1.85 - 1.74 (m, 2H), 1.74 - 1.63 (m, 1H), 1.60 (s, 3H). Synthetic Method 4 Outline for Method 4 Step 1, Method 4 (1R)-1-[(2R)-2-methylpyrrolidin-2-yl]ethanol hydrochloride (492 mg, 3.0 mmol, synthesized by method 15) was added to a stirred solution of di(imidazol-1-yl)methanone (602 mg, 3.7 mmol, CAS 530-62-1) and 9-bromo-8-methoxy-1-(2-thienyl)-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxylic acid (1.00 g, 2.5 mmol) in DMF (14 ml) and the reaction mixture heated to 90 °C for 2.5 h. DIPEA (1.1 ml, 6.2 mmol, CAS 7087-68-5) was Petition 870260076443, dated 07 / 31 / 2026, p. 175 / 508 166 / 448 added and the mixture stirred at 90 °C overnight. The reaction mixture was concentrated in vacuo and dissolved in DCM and water. The layers were separated, the organic passed through a phase separator and was concentrated in vacuo to generate an oil that was purified by FCC (silica, eluting 0-100% EtOAc in heptane). The fractions were concentrated in vacuo to generate [9-bromo-8-methoxy-1-(2-thienyl)-5,6-dihydropyrrolo[2,1a]isoquinolin-3-yl]-[(2R)-2-[(1R)-1-hydroxyethyl]-2-methylpyrrolidin-1-yl]methanone (purity 72.0%) (594 mg, 0.8 mmol, yield 34%) as a pale brown solid. RT (M3) = 0.99 min, (ESI+) (M+H)+515.3 / 517.3.1H NMR (500 MHz, DMSO) δ 7.55 (dd, J = 5.2, 1.1 Hz, 1H), 7.43 (s, 1H), 7.14 - 7.10 (m, 2H), 7.06 (dd, J = 3.5, 1.2 Hz, 1H), 6.53 (s, 1H), 4.96 (d, J = 4.9 Hz, 1H), 4.44 (p, J = 6.3 Hz, 1H), 4.31 (dt, J = 13.0, 6.5 Hz, 1H), 4.11 - 4.05 (m, 1H), 3.85 (s, 3H), 3.81 (ddd, J = 10.0, 6.6, 3.5Hz, 1H), 3.67 - 3.59 (m, 1H), 3.01 (t, J = 6.5 Hz, 2H), 2.07 (ddd, J = 12.6, 10.2, 7.7 Hz, 1H), 1.81 - 1.71 (m, 2H), 1.57 - 1.51 (m, 1H), 1.50 (s, 3H), 1.00 (d, J = 6.3 Hz, 3H). Table 6. The following analogues were made using the analogous method: Structure LCMS Name 1 jj χχχν [(5 R )-9-bromo-8-methoxy-5-methyl-1-(2-thienyl)-5,6di-hydropyrrole [2,1- to ]isoquinoline-3-yl]-[(2 S)-2methyl-2-trif-2,(2, R hydroxyethyl]pyrrolidin-1-yl]metanone RT (M2) = 1.25 min, (ESI+) (M+H)+ 583.0 / 585.0 1 XXX« Xv [(5 R )-9-bromo-8-methoxy-5-methyl-1-thiazol-hydro1,6-lo-5-yl-methanone ]isoquinolin-3-yl]-[(2 R )-2methyl-2-[(1 S)-2,2,2-trifluoro-1hydroxyethyl]pyrrolidine-1-yl]methanone RT (M2) = 1.25 min, (ESI+) (M+H)+ 583 Xχ 1 Compt 1 d X585,0 4-1 [8-methoxy-9-(1-methylpyrazol-3-yl)-1-thiazol-5-yl-5,6di-hydropyrrole [2,1- a ]isoquinoline-3-yl]-[(2 S)-2methyl-2-[(1 R )-2,2,2-trihydroxymethyl-1pyroxymethyl-1 (M4) = 3.46 min, (ESI+) (M+H)+ 572.2 Petition 870260076443, dated 07 / 31 / 2026, p. 176 / 508 167 / 448 Structure LCMS Name 'JOO / / ==( F / Compound 4-2 (l-(5-fluoropyridin-2-yl)-8-methoxy-9-(2-methyl-2Htetrazol-5-yl)-5,6-di-hydropyrrole[2,la]isoquinoline-3-yl)((S)-2-methyl-2-((R)-2,2,2-trifluoroxyl-ethyl)1 RT (M36) = 3.99 min, (ESI+) (M+H)+ 586.3 ah f FF Compound 4-3 ( / ?)-8-mctoxy-5-mctyl-3-(( / ?)-2-mclil-2-((.S')-2.2.2trifluoroxyethyl-1 -1 -carbonyl)-N(l-methyl-2-oxo-1,2-di-hydropyridine-3-yl)-l-(2,2,2trifluoroethyl)-5,6-di-hydropyrrole[2,1 - a] isoquinoline-9-carboxamide RT (M34) = (+5,I)+3) min Synthetic Method 5 Scheme for Method 5 Stage 1, Method 5

[00199] Aqueous lithium hydroxide at 1 M (1.1 ml, 1.1 mmol) was added to a stirred suspension of ethyl 9-bromo-8-methoxy-1-propyl-5,6-dihydropyrrolo[2,1a]isoquinoline-3-carboxylate (200 mg, 0.5 mmol, synthesized by method 1) in ethanol (4.7 ml) and the mixture was heated to 80 °C for 3 h, forming a solution. After cooling to rt, the mixture was concentrated in vacuo to yield lithium 9-bromo-8-methoxy-propyl-5,6-dihydropyrrolo[2,1a]isoquinoline-3-carboxylate hydroxide (226 mg, quantitative) as a whitish powder. RT (M2) = 1.03 min, (ESI+) (M+H)+364.1 / 366.1; - 2.53 (m, 2H), 1.59 (h, J= 7.3 Hz, 2H), 0.97 (t, J= 7.3 Hz, 3H). Step 2, Method 5

[00200] DIPEA (1.4 ml, 8.0 mmol, CAS 7087-68-5) was added to a stirred suspension of lithium 9-bromo-8-methoxy-1-propyl-5,6-dihydropyrrolo[2,1a]isoquinoline-3-carboxylate hydroxide (1.04 g, 2.6 mmol) and Petition 870260076443, dated 07 / 31 / 2026, p. 177 / 508 168 / 448 (1A)-1-[(2A)-2-methylpyrrolidin-2-yl]ethanol hydrochloride (580 mg, 1.3 mmol, synthesized by method 15) in DMA (25 ml) and the mixture was stirred at 20 °C for 5 min, forming a cloudy solution. 2-chloro-1-methylpyridinium iodide (1.50 g, 5.9 mmol, CAS 14338-32-0) was added and the reaction mixture was stirred at 20 °C for 17 h. The reaction mixture was diluted with water (150 ml), sonicated, and allowed to stand for 10 min. The solids were collected by filtration and washing with water (3 x 30 ml). The solids were then dissolved in EtOAc (200 ml) and the organic mixture filtered through hydrophobic filter paper. The organic filtrate was concentrated in vacuo to provide the crude product (913 mg) as a brown powder.The raw product was purified by FCC (silica, eluting with EtOAc 10-100 % in heptane) to obtain (9bromo-8-methoxy-l-propyl-5,6-di-hidropyrrolo[2,la]isoquinolin-3-yl)-[(2A)-2[(lA)-l-hidroxyethyl]-2-methyl-pyrrolidin-l-yl]methane (507 mg, 38% yield) as a pale brown powder. RT (M2) = 1.02 min, (ESI+) (M+H)+475.2 / 477.2; Ή NMR (400 MHz, DMSO) δ 7.62 (s, 1H), 7.12 (s, 1H), 6.38 (s, 1H), 5.01 (d, J= 4.7 Hz, 1H), 4.47 - 4.35 (m, 1H), 4.25 (dt, J = 13.0, 6.5 Hz, 1H), 4.05 (dt, J= 12.6, 6.2 Hz, 1H), 3.86 (s, 3H), 3.77 (dt, J = 10.4, 5.2 Hz, 1H), 3.66 - 3.52 (m, 1H), 2.93 (t, J= 6.5 Hz, 2H), 2.66 - 2.57 (m, 2H), 2.05 (dt, J= 12.8, 8.8 Hz, 1H), 1.86 - 1.68 (m, 2H), 1.67 - 1.44 (m, 3H), 1.49 (s, 3H), 1.02 - 0.92 (m, 6H). Synthetic Method 6 Esquema para Método 6 Stage 1, Method 6

[00201] (A-(triethylamonioxulfonyl)methylcarbamate) (2.35 g, 9.9 mmol, CAS 29684-56-8) (Burgess reagent) added to a mixture Petition 870260076443, dated 07 / 31 / 2026, p. 178 / 508 169 / 448 of (2R)-1-[9-bromo-8-methoxy-1-(2-thienyl)-5,6-dihydropyrrolo[2,1a]isoquinoline-3-carbonyl]-2-methylpyrrolidine-2-carboxamide (2.54 g, 4.9 mmol, synthesized by method 2) in THF (20 ml) and DCM (20 ml) at 0 °C and the reaction mixture was heated to 20 °C and stirred for 1 h. The reaction mixture was poured into water (20 ml) and the aqueous phase extracted with DCM (3 x 20 ml). The combined organic phases were washed with brine (saturated NaCl solution in deionized water) (50 ml), dried with anhydrous Na2SO4, filtered and concentrated in vacuo. The resulting residue was purified by FCC (silica, 0-100% EtOAc elution in heptane) and the product-containing fractions concentrated in vacuo to yield (2R)-1-[9-bromo-8-methoxy-1-(2-thienyl)-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carbonyl]-2-methylpyrrolidine-2-carbonitrile (92%) (2.10 g, 79% yield) as a pale yellow solid.RT (M2) = 1.09 min, (ESI+) (M+H)+ 496.0 / 497.9; 1H NMR (500 MHz, DMSO) δ 7.58 (dd, J = 5.2, 1.2 Hz, 1H), 7.43 (s, 1H), 7.16 - 7.11 (m, 2H), 7.08 (dd, J = 3.5, 1.2 Hz, 1H), 6.72 (s, 1H), 4.46 - 4.37 (m, 1H), 4.33 4.20 (m, 1H), 3.91-3.85 (m, 4H), 3.84 - 3.77 (m, 1H), 3.05 (t, J = 6.5 Hz, 2H), 2.47 (dd, J = 9.0, 3.7 Hz, 1H), 2.12 (ddd, J = 12.8, 10.1, 6.0 Hz, 1H), 2.02 - 1.99 (m, 1H), 1.95 - 1.85 (m, 1H), 1.74 (s, 3H). Table 7. The following analogues were made using the analogous method: Structure Name LCMS (2R )-1-[9-bromo-1-(4-fluorophenyl)-8-methoxy-5,6dihydropyrrolo [2,1- a ]isoquinoline-3-carbonyl]-2methyl-pyrrolidine-2-carbonitrile RT (M2) = 1.11 min, (ESI+) (M+H)+ 508.0 / 510.0 (2R )-1-(9-bromo-8-methoxy-1-propyl-5,6-dihydropyrrole [2,1- a ]isoquinoline-3-carbonyl)-2-methyl-pyrrolidine-2-carbonitrile RT (M2) = 1.13 min, (ESI+) (M+H)+ 456.2 / 458.2 Petition 870260076443, dated 07 / 31 / 2026, p. 179 / 508 170 / 448 Structure Name LCMS 1 300x® - (2R )-1-[9-bromo-8-methoxy-1-(2,2,2-trifluoroethyl)- 5,6-di-hydropyrrolo[2,1- a ]isoquinolina-3-carbonyl]2-methyl-pyrrolidine-2-carbonitrila RT (M3) = 1.06 min, (ESI+) (M+H)+ 496.2 / 498.2 1 YYW Compound 6-1 (3 .S')-4-[8-methoxy-9-(1-methylpyrazol-3-yl)-1-(2-thienyl)- 5,6-di-hydropyrrolo[2,1- a ]isoquinolina-3-carbonyl]3-methyl-morpholine-3-carbonitrila RT (M5) = 3.78 min, (ESI+) (M+H)+ 514.3 '300 / - 1 çÇ Compound 6-2 (2R )-1-[8-methoxy-9-(1-methylpyrazol-3-yl)-1-thiazol-5yl-5,6-di-hydropyrrolo[2,1- a ]isoquinolina-3-carbonyl]-2-methyl-pyrrolidine-2-carbonitrila RT (M4) = 3.17 min, (ESI+) (M+H)+ 499.3 '300 I - (2R )-1-(9-bromo-8-methoxy-1-thiazol-5-yl-5,6-dihydropyrrolo[2,1- a ]isoquinolina-3-carbonyl)-2methyl-pyrrolidine-2-carbonitrila RT (M2) = 0.93 min, (ESI+) (M+H)+ 497.1 / 499.1 ' XX? j ^Oo^o^ (R )-1-(9-bromo-8-methoxy-1-(2,2,2-trifluoroethyl)-5,6dihydropyrrolo [2,1-a]isoquinoline-3 -carbonyl)-2methylazetidine-2-carbonitrila RT (M11) = 1.99 min, (ESI+) (M+H)+ 482.2 / 484,1 ' 300 j / OO <X (R )-1-(9-bromo-1 -(3,3-difluorociclobutil)-8-metoxi- 5,6-di-hidropirrolo[2,1-a]isoquinolina-3-carbonil)2-metilpirrolidina-2-carbonitrila RT (M27) = 2,61 min, (ESI+) (M+H)+ 504,0 / 506,0 OO u o (R )-1-(9-bromo-8-metoxi-1-(tiofen-2-il)-5,6-dihidropirrolo[2,1-a]isoquinolina-3-carbonil)-2metilazetidina-2-carbonitrila RT (M25) = 2,66 min, (ESI+) (M+H)+ 482,0 / 484,0 300 χΟΟ Õ 0 (R )-1-(9-bromo-1 -(5-fluoropiridin-2-il)-8-metoxi- 5,6-di-hidropirrolo[2,1-a]isoquinolina-3-carbonil)2-metilpirrolidina-2-carbonitrila RT (M13) = 1,88 min, (ESI+) (M+H)+ 509,2 / 511,1 ' 300 J - / ΌΟ X 0 (R *)-1-((S)-9-bromo-8-metoxi-6-metil-1-(tiofen-2il)-5,6-di-hidropirrolo[2,1-a]isoquinolina-3carbonil)-2-metilpirrolidina-2-carbonitrila RT (M11) = 2,14 min, (ESI+) (M+H)+ 510,2 / 512,2, Petition 870260076443, dated 07 / 31 / 2026, p. 180 / 508 171 / 448 Structure Name LCMS or (R )-1-((S)-9-bromo-8-methoxy-5-methyl-1-(thiophen-2yl)-5,6-di-hydropyrrolo[2,1-a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila RT (M12) = 0.733 min, (ESI+) (M+H)+ 510.2 / 512.2 1 XXX ji - 1 ~7\ Compound 6-3 (R )-1-(1 -(1-hydroxy-2-methylpropan-2-yl)-8-methoxy-9(2-methyl-2H-tetrazol-5-yl)-5,6-di-hydropyrrolo[2,1a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2carbonitrila RT (M36) = 3.08 min, (ESI+) (MOH)+ 472.1 ' XXX n Compound 6-4 (R )-1-(1-(2,2-difluoropropyl)-8-methoxy-9-(2-methyl2H-tetrazol-5-yl)-5,6-di-hidropyrrolo[2,1a]isoquinoline-3-carbonyl)-2-methylpyrrolidine-2carbonitrila RT (M36) = 2.92 min, (ESI+) (M+H)+ 496.3 ' XX? u / ( Compound 6-5 (R )-1-(1-(2,2-difluoropropyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hydropyrrolo[2,1a]isoquinoline-3-carbonyl)-2-methylazetidine-2carbonitrila RT (M24) = 2.84 min, (ESI+) (M+H)+ 482.2 ' XX? ' / ( Compound 6-6 (R )-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1propyl-5,6-di-hydropyrrolo[2,1-a]isoquinolina-3carbonyl)-2-methylazetidine-2-carbonitrila RT (M37) = 2.67 min, (ESI+) (M+H)+ 446.2 XX? - / / =4 X Compound 6-7 (R )-1-(1-(5-fluoropyridin-2-yl)-8-methoxy-9-(2-methyl2H-tetrazol-5-yl)-5,6-di-hydropyrrolo[2,1a]isoquinolina-3-carbonyl)-2-methylazetidine-2carbonitrila RT (M24) = 2.76 min, (ESI+) (M+H)+ 499.1 XX? jt Compound 6-8 (R )-1-(1 -(4-fluorophenyl)-8-methoxy-9-(2-methyl-2Htetrazol-5-yl)-5,6-di-hydropyrrolo[2,1-a]isoquinoline- 3-carbonyl)-2-methylazetidine-2-carbonitrila RT (M24) = 3.02 min, (ESI+) (M+H)+ 498.2, * Denotes foreign chemical chemistry, isolated from a diastereomeric mixture using SFC chromatography Synthetic Method 7 Esquema para Método 7 Stage 1, Method 7 Petition 870260076443, 07 / 31 / 2026, pág. 181 / 508 172 / 448

[00202] In a pressure relief flask, 4,4,5,5-tetramethyl-2(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (338 mg, 1.3 mmol, CAS 73183-34-3), (2R)-1-[9-bromo-8-methoxy-1-(2-thienyl)-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carbonyl]-2-methylpyrrolidine-2-carbonitrile (600 mg, 1.2 mmol, synthesized by method 6) and potassium acetate (300 mg, 3.0 mmol, CAS 127-08-2) were dissolved in anhydrous 1,4-dioxane (13 ml) and degassed with nitrogen. [1,1'bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (99 mg, 121 μmol, CAS 95464-05-4) was added and the reaction mixture was stirred at 90 °C overnight. The reaction mixture was concentrated and partitioned between DCM and water. The layers were separated, the organic layers passed through a phase separator cartridge and concentrated in vacuo. The crude material was then purified by FCC (silica, eluting with 0-100% EtOAc in heptane).The product-containing fractions were collected, combined, and the solvent removed in vacuo to generate (2R)-1-[8-methoxy-9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2-thienyl)-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carbonyl]-2-methylpyrrolidine-2-carbonitrile (425 mg, 57% yield) as a pale brown solid. RT (M2) = 1.1 min [M+H]+ (ESI+) 544.3; 1H NMR (500 MHz, DMSO) δ 7.67 (s, 1H), 7.50 (dd, J = 5.1, 1.2 Hz, 1H), 7.09 - 7.03 (m, 2H), 6.94 (s, 1H), 6.72 (s, 1H), 4.40 (dt, J = 13.3, 6.5 Hz, 1H), 4.26 (dt, J = 13.1, 6.2 Hz, 1H), 3.89 (td, J = 8.8, 7.3, 3.8 Hz, 1H), 3.84 - 3.78 (m, 1H), 3.76 (s, 3H), 3.06 (t, J = 6.5 Hz, 2H), 2.48 - 2.44 (m, 1H), 2.17 - 2.08 (m, 1H), 1.99 (s, 1H), 1.93 (dd, J = 15.5, 6.8 Hz, 1H), 1.74 (s, 3H), 1.17 (s, 12H). Step 2, Method 7

[00203] Uma solução de (2R)-1-[8-metoxi-9-(4,4,5,5-tetrametil-1,3,2dioxaborolan-2-il)-1-(2-tienil)-5,6-di-hidropirrolo[2,1-a]isoquinolina-3carbonyl]-2-metil-pirrolidina-2-carbonitrila (100 mg, 184 μmol), 2-bromo-1,3oxazol (34 mg, 221 μmol, CAS 125533-82-6) e carbonato de dicésio (240 mg, Petition 870260076443, 07 / 31 / 2026, pág. 182 / 508 173 / 448 A compound of 736 iimol (CAS 534-17-8) in 1,4-dioxane (2.4 ml) and water (0.6 ml) was degassed with nitrogen for 5 min. XPhos Pd G2 (29 mg, 18 iimol, CAS 1310584-14-5) was then added and the mixture degassed with nitrogen for 5 min. The reaction mixture was stirred at 80 °C overnight. The reaction was allowed to cool to rt, treated with water (5 ml) and extracted with EtOAc (3 x 5 ml). The organic phases were combined, passed through a phase separator and concentrated in vacuo. The compound was purified by acidic prep HPLC (Method P2) and then basic prep HPLC (Method P4) to yield a white solid. The white solid was further purified by chiral preparation (Chiralpak AD-H, mobile phase ethanol at 9 ml / min) and lyophilized to yield (2R)-1-[8-methoxy-9-oxazol-2-yl-1-(2-thienyl)5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carbonyl]-2-methylpyrrolidine-2carbonitrile (Compound 7-1) (24 mg, 27% yield) as a white solid.RT (M4) = 3.62 min, (ESI+) (M+H)+ 485.2; 1H NMR (400 MHz, DMSO) δ 8.09 (s, 1H), 7.96 (s, 1H), 7.51 (dd, J = 3.9, 2.5 Hz, 1H), 7.28 7.20 (m, 2Hz), 7.12 - 7.05 m, (s, 1H), (6,7H), 4.50 - 4.39 (m, 1H), 4.35 4.23 (m, 1H), 3.93 - 3.86 (m, 4H), 3.86 - 3.77 (m, 1H), 3.13 (t, J = 6.4 Hz, 2H), 2.47 - 2.12 (m, 1H), 2.08 (m, 1H), 2.05 - 1.85 (m, 2H), 1.74 (s, 3H). Table 8. The following analogs were made by the analog method: Structure Name LCMS 1 TV Compound 7-2 4-[3-[(2R )-2-[(1 R )-1-hydroxyethyl]-2-methylpyrrolidine-1-carbonyl]-8-methoxy-1-(2-thienyl)5,6-di-hydropyrrole[2,1- a ]isoquinoline-9-methyl-16] H-pyridin-2-one RT (M4) = 3.17 min, [M+H]+ (ESI+) 544.3 1 SOO yielded Compound 7-3 [(2R )-2-[(1 R )-1-hydroxyethyl]-2-methylpyrrolidin-1-yl]-[8-methoxy-9-oxazol-2-yl-1-(2thienyl)-5,6-di-hydropyrrole [2,1- a ]isoquinolin3-yl]methanone RT (M4) = 3.54 min, [M+4,+3]) Petition 870260076443, of 31 / 07 / 2026, p. 183 / 508 174 / 448 Structure LCMS Name 1 jj - Compound 7-4 3-[3-[(2R )-2-cyano-2-methyl-pyrrolidin-1carbonyl]-1-(4-fluorophenyl)-8-methoxy-5,6-dihydropyrrole[2,1- a ]-RT-RTMpyridine =-9 4.02 min, [M+H]+ (ESI+) 532.3 1 Compound 7-5 3-[3-[(2R )-2-[(1 R )-1-hydroxyethyl]-2-methyl- pyrrolidine-1-carbonyl]-8-methoxy-1-propyl-iso-quino1,6-lo ]di il]pyridine-2-carbonitrile RT (M2) = 0.99 min, [M+H]+ (ESI+) 499.7 1 300 g - : 4A< Compound 7-6 [8-methoxy-9-(2-methyltetrazol-5-yl)-1-(2,6-hydrodienyl a[M2) ]isoquinolin-3-yl][(2R )-2-methyl-2-[(1 á)-2,2,2-trifluoro-1hydroxy-ethyl]pyrrolidin-1-yl]methanone RT (M4) = 3.80 min, [M+H]+ (ESI+) 573,2 . 1 JCCA v Compound 7-7 (2R )-1-[9-(1 H-imidazol-2-yl)-8-methoxy-1- (2,2,2-trifluoroethyl)-5,6-di-hydropyrrole[2,1a ]isoquinoline-3 -carbonyl]-2-methyl-RTyrrolitridine-min [M+H]+ (ESI+) 484.3 1 3C0 j - 1 <0 Compound 7-8 (2R )-1-[8-methoxy-9-(2-methyltetrazol-5-yl)-1(2-thienyl)-5,6-di-hydropyrrole[2,1- a ]isoquinoline-3 -carbonyl]-2-methyl- pyrrolidine-2-carbonitrile RT (M4) = 3.53 min [M+H]+ (ESI+) 500.2 1 300 a - t ( Compound 7-9 (2R )-1-[8-methoxy-9-(2-methyltetrazol-5-yl)-1propyl-5,6-di-hydropyrrole [2,1- to ]isoquinoline3-carbonyl]-2-methyl-pyrrolidine-2-carbonitrile RT (M4) = 3.61] j] 4 (ESM+H Ό 1 0 Compound 7-10 [(2R )-2-[(1 R )-1-hydroxyethyl]-2-methylpyrrolidin-1-yl]-[8-methoxy-9-(2-methyltetrazol5-yl)-1-(2-thienyl)-5,6-a-di-anon3 [2,hydromethyl-RT] (M4) = 3.57 min [M+H]+ (ESI+) 519.1 1 130 ii - / \ Compound 7-11 (2R )-1-[8-methoxy-9-(2-methyltetrazol-5-yl)-1(2,2,2-trifluoroethyl-dihydroethyl[5-hydroethyl)-2 ]isoquinoline-3 -carbonyl]-2-methylpyrrolidine-2-carbonitrile RT (M4) = 3.52 min [M+H]+ (ESI+) 500.1, Petition 870260076443, dated 07 / 31 / 2026, p. 184 / 508 175 / 448 Structure LCMS Name 1 1 0 Compound 7-12 [(5 Λ )-8-methoxy-5-methyl-9-(2-methyltetrazol-5yl)-1-(2-thienyl)-5,6-di-hydropyrrole[2,1a ]isoquinolin-3-R-2]-[(2 methyl-S-2]-2 )2,2,2-trifluoro-1-hydroxy-ethyl]pyrrolidin-1yl]methanone RT (M4) = 4.04 min [M+H]+ (ESI+) 587.4 1 TJ2X - ' o Compound 7-13 [(5 R )-8-methoxy-5-methyl-9-(2-methyltetrazol-5yl)-1-thiazol-5-yl-5,6-di-hydropyrrole [2,1a ]isoquinolin-3-yl]-[(2 R )-2-methyl-2-[(1 S)2,2,2,2-dinyl-hydroxyfluoro-ethyl RT (M5) = 3.49 min [M+H]+ (ESI+) 588.3 '130 / - 1 cÇ Compound 7-14 (2R )-1-[8-methoxy-9-(2-methyltetrazol-5-yl)-1thiazol-5-yliso-quino1-hydropyl a-[2,6-di-di- -carbonyl]-2-methyl- pyrrolidine-2-carbonitrile RT (M4) = 2.93 min [M+H]+ (ESI+) 501.2 1 11 ΊΡΟ Compound 7-15 (R )-3-(3 -(2-cyano-2-methylpyrrolidine-1carbonyl)-8-methoxy-1-(2,2,2-trifluoroethyl)-5,6di-hydropyrrole [2,1-a] isoquinoline-9-yl)-5(trifluoromethyl)picolinotrile RT (RT 3,+H36) min [ESI+M36) 588,3 / ( Compound 7-16 (R )-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)1-(2,2,2-trifluoroethyl)-5,6-di-hydropyrrole[2,1a]isoquinoline-3-carbonyltrilyl)-2-carbonylene)(RT 2.89 min [M+H]+ (ESI+) 489.1 XOO 11 I 1 Q Compound 7-17 (8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1(1,3,4-thiadiazol-2-yl)-5(3-aro]diquino-hydropyr(ESI+) S)-2-methyl-2-((R )-2,2,2trifluo ro-1-hydroxyethyl)pyrro lidin-1yl)methanone RT (M36) = 2.71 min [M+H]+ (ESI+) 575.3 / p( kz Compound 7-18 (R )-(1-1- -(3,3-difluorocyclobutyl)-8-methoxy-9(2-methyl-2H-tetrazol-5-yl)-5,6-di- hydropyrrole[2,1-a]isoquinoline-3-carbonyl)-2methylpyrrolidine-2-carbonitrile RT (RTM (+M30]) min 508.3 x 1OO - 1 X Compound 7-19 (R )-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)1-(thiophen-2-yl)-5,6-di-hydropyrrole[2,1a]isoquinolinetrine-tribonyl-32-carbonyl) = 2.96 min [M+H]+ (ESI+) 486.1, Petition 870260076443, dated 07 / 31 / 2026, p. 185 / 508 176 / 448 Structure LCMS Name / / =4 C / X Compound 7-20 (R )-1-(1-(5-fluoropyridin-2-yl)-8-methoxy-9-(2methyl-2H-tetrazol-5-yl)-5,6-di- hydropyrrole[2,1-a]isoquinoline-3-carbonyl)-2methylpyrrolidine-2-carbonitrile RT (M36) = 2.82 min [M+H]+ (ESI+) 513.2 ? 4^ / / =4 4 / j4 Compound 7-21 (R )-1-(1-(4-fluorophenyl)-8-methoxy-9-(2-methyl2H-tetrazol-5 -yl)-5,6-di-hydropyrrole[2,1a]isoquinoline-3-bonytrimethylpyr2-rhonytribonyl)-2 (M24) = 3.10 min [M+H]+ (ESI+) 512.1 j - Compound 7–22 ((R )-8-methoxy-5-methyl-9-(2-methyl-2H-tetrazol5-yl)-1-(thiophen-2-yl)-5,6-di-hydropyrrole[2,1a]isoquinoline-3-yl)((R)-2-methyl-2-(( S)-2,2,2ano-nayl-1)tripylhydrohydro RT (M35) = 3.07 min [M+H]+ (ESI+) 587.2 1 -XCXX j - - Compound 7-23 5-((R )-8-methoxy-5-methyl-3-((R )-2-methyl-2((S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin1-carbonyl)-1-(2,2,2-trifluoroethyl)-5,6-dihydropyrrole[2,1-a]isoquinolin-9yl)nicotinamide] = [ESM3+9) = RT 625.0 1 III ιχι ' J,_- Compound 7-24 3-((R )-8-methoxy-5-methyl-3-((R )-2-methyl-2((S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidine1-carbonyl)-1-(2,2,2-trifluoroethyl-di[2,12-trifluoroethyl-[2,5)-- -a]isoquinoline-9yl)picolinotrile RT (M35) = 3.14 min [M+H]+ (ESI+) 607.3 1 XOCX jj 44 ' \ 4 / Compound 7-25 ((R )-8-methoxy-5-methyl-9-(2-methyl-2H-tetrazol5-yl)-1-(2,2,2-trifluoroethyl)-5,6-dihydropyrrole[2,1-a]isoquinoline-3-yl)((R )-2methyl-2-(( S)-2,2,2-trifluoro-1hydroxyethyl)pyrrolidin-1-yl)methanone RT (M25) = 2.42 min [M+H]+ (ESI+) 587.2 XO...

Claims

1. Compound of Formula (A) or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, characterized in that R1 is -NRfRg, wherein (i) Rf and Rg together with the nitrogen to which they are attached form a 4- to 8-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 13 substituents independently selected from C3-C6 cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups together with the atoms to which they are attached form a 4- to 6-membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl; or (ii) Rf is C1-C6 alkyl;and Rg is C1-C6 alkyl substituted by 1 to 4 R4c groups, wherein each R4c group is independently selected from halogen, hydroxyl and nitrile; R2 is selected from C1-C6 alkyl; C1-C6 alkenyl; C1-C6 haloalkyl; C1-C6 hydroxyalkyl; -(C1-C3 alkyl)-SO2CH3; -(C1-C6 alkyl)-O(C1-C6 alkyl) optionally substituted by 1 to 13 halogens; -(C1-C6 alkyl)-NR5aR5b; phenyl; C4-C6 cycloalkyl; and a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the phenyl, C4-C6 cycloalkyl and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl; X is CR20 or N;R20 is selected from H, halogen, nitrile, C1-C6 alkyl and C1-C6 haloalkyl; R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl, 5- to 6-membered heterocycloalkyl ring and 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring contain 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxy, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2;(i) each of R7 and R8 is independently selected from H and C1-C3 alkyl or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur and nitrogen; each of Rd and Re is independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted with nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms Petition 870260076443, 07 / 31 / 2026, p. 460 / 508 3 / 49 independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the two remaining members are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; or R11 and R12 together form a double bond, and R10 and R13 are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; wherein 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

2. A pharmaceutically acceptable compound, stereoisomer, tautomer or salt thereof according to claim 1, characterized in that X is CR20.

3. Compound, stereoisomer, tautomer or pharmaceutically acceptable salt of the same according to any of claims 1 or 2, characterized in that X is N.

4. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, characterized in that R1 is -NRfRg, wherein: (i) Rf and Rg together with the nitrogen to which they are attached form a 4- to 8-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4- to 6-membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl; or (ii) Rf is C1-C6 alkyl;and Rg is C1-C6 alkyl substituted by 1 to 4 R4c groups, wherein each R4c group is independently selected from halogen, hydroxyl, and nitrile.

5. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, characterized in that R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 4-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, wherein the ring is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with Petition 870260076443, dated 07 / 31 / 2026, p. 462 / 508 5 / 49 atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl.

6. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, characterized in that R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 5-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, wherein the ring is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4- to 6-membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl groups.

7. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, characterized in that R1 is X? wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl.

8. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, characterized in that R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 6-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, wherein the ring is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen; optionally, wherein 2 R4 groups, together with the atoms to which they are attached, form a 4- to 6-membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl.

9. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, characterized in that R1 is -NRfRg, wherein Rf is C1-C6 alkyl; and Rg is C1-C6 alkyl substituted by 1 to 4 R4c groups, wherein each R4c group is independently selected from halogen, hydroxyl and nitrile.

10. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to any one of claims 1 to 9, characterized in that R2 is C1-C6 alkyl or C1C6 alkenyl.

11. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to any one of claims 1 to 9, characterized in that R2 is a C1-C6 haloalkyl.

12. A pharmaceutically acceptable compound, stereoisomer, tautomer or salt thereof according to any one of claims 1 to 9, characterized in that R2 is C1-C6 hydroxyalkyl.

13. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to any one of claims 1 to 9, characterized in that R2 is phenyl optionally substituted by 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl.

14. A pharmaceutically acceptable compound, stereoisomer, tautomer or salt thereof according to any one of claims 1 to 9, characterized in that R2 is 4-fluorophenyl.

15. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to any one of claims 1 to 9, characterized in that R2 is C4-C6 cycloalkyl optionally substituted by 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl.

16. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to any one of claims 1 to 9, characterized in that R2 is a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may optionally be substituted by 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl.

17. A pharmaceutically acceptable compound, stereoisomer, tautomer or salt thereof according to any one of claims 1 to 9, characterized in that R2 is 3,3-difluorocyclobutyl, 5-fluoropyridin-2-yl, 2-thiophenyl, 5-thiazolyl or 1,3,4-thiadiazolyl.

18. Compound of Formula (B) Petition 870260076443, dated 07 / 31 / 2026, page 465 / 508 8 / 49 or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, characterized in that R1 is C?, wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C3 alkyl optionally substituted by 1 to 4 substituents independently selected from C3C3 cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl;Het is a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, optionally substituted by 1 to 4 R5 groups independently selected from halogen, nitrile, -C(O)NR5aR5b, C1C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b are independently selected from H and C1-C3 alkyl;R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl, 5- to 6-membered heterocycloalkyl ring and 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring contain 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 Petition 870260076443, dated 07 / 31 / 2026, page. 466 / 508 9 / 49 alkyl, C1-C3 haloalkyl and -C(O)NH2; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2;(i) each of R7 and R8 is independently selected from H and C1-C3 alkyl or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur and nitrogen; each of Rd and Re is independently selected from H and C1-C3 alkyl; (ii) optionally nitrile-substituted C1-C6 alkyl or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and Petition 870260076443, dated 07 / 31 / 2026, p. 467 / 508 10 / 49 each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12, and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring; wherein 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

19. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to claim 18, characterized in that Het is a 5-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, optionally substituted by 1 to 4 R5 groups independently selected from halogen, nitrile, -C(O)NR5aR5b, C1C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy; and each R5a and R5b are independently selected from H and C1-C3 alkyl.

20. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to claim 18, characterized in that Het is a 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, optionally substituted by 1 to 4 R5 groups independently selected from halogen, nitrile, -C(O)NR5aR5b, C1C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy; and each R5a and R5b are independently selected from H and C1-C3 alkyl.

21. Compound of Formula (C) or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, Petition 870260076443, dated 07 / 31 / 2026, page 468 / 508 11 / 49 characterized in that R1 is X^, wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C3 alkyl optionally substituted by 1 to 4 substituents independently selected from C3C3 cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl;R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl, 5- to 6-membered heterocycloalkyl ring and 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring contain 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, wherein n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen;each of Rd and Re is independently selected from H and C1-C3 alkyl; (ii) C1-C3 alkyl optionally substituted with nitrile or ring Petition 870260076443, dated 07 / 31 / 2026, page 469 / 508 12 / 49 5- or 6-membered heteroaryl containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted with 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the two remaining members are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; wherein 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

22. Compound of Formula (D) Formula (D) Petition 870260076443, dated 07 / 31 / 2026, page 470 / 508 13 / 49 or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, characterized in that R1 is +---^, wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C alkyl optionally substituted by 1 to 4 substituents independently selected from C3C cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl groups;R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl, 5- to 6-membered heterocycloalkyl ring and 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring contain 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2; m is 0, 1, 2, 3 or 4; Each R5 is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2;Each of R7 and R8 is independently selected from H and C1-C3 alkyl or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur and nitrogen; each of Rd and Re is independently selected from H and C1-C3 alkyl; (ii) optionally nitrile-substituted C1-C6 alkyl or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the two remaining members are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; wherein 0 to 10 hydrogen atoms attached to one or more carbon atoms are replaced by deuterium atom(s).

23. Compound of Formula (E) Formula (E) or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, characterized in that R1 is * +X, wherein R1 is substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxyl, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3C6 cycloalkyl, hydroxyl and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl;R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl, 5- to 6-membered heterocycloalkyl ring and 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring contain 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxy, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2; Alk is C1-C6 alkyl or C1-C6 alkenyl; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, where n is 1 or 2;Petition 870260076443, dated 07 / 31 / 2026, page 473 / 508 16 / 49 each of R7 and R8 is independently selected from H and C1-C3 alkyl or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur and nitrogen; each of Rd and Re is independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted with nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the ring may be optionally substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the two remaining members are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; wherein 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

24. Compound of Formula (F) or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, characterized in that R1 is -NRfRg, wherein (i) Rf and Rg together with the nitrogen to which they are attached form a 4 to 8 membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and substituted by 1 to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, -NR4aR4b, -SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C5-C6 cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups together with the atoms to which they are attached form a 4 to 6 membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl; or (i) Rf is C1-C3 alkyl;and Rg is C1-Có alkyl substituted by 1 to 4 R4c groups, wherein each R4c group is independently selected from halogen, hydroxyl and nitrile; R2 is selected from C1-Có alkyl; C1-Có alkenyl; C1-Có haloalkyl; C1-Có hydroxyalkyl; -(C1-C3 alkyl)-SO2CHs; -(C1-Có alkyl)-O(C1-Có alkyl) optionally substituted by 1 to 13 halogens; -(C1-Có alkyl)-NR5aR5b; phenyl; C4-C6 cycloalkyl; and a 5- to 6-membered heteroaryl ring containing 1 to 4 independently substituted ring heteroatoms. Petition 870260076443, dated 07 / 31 / 2026, page. 475 / 508 18 / 49 selected from oxygen, sulfur and nitrogen, wherein the phenyl, C4-C6 cycloalkyl and the 5- to 6-membered heteroaryl ring may be optionally substituted by 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl;R3 is selected from -C(O)NHR6, -SO2-(C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl, 5- to 6-membered heterocycloalkyl ring and 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring contain 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the phenyl, the 5- to 6-membered heterocycloalkyl ring and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, wherein n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl groups, or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur, and nitrogen;(i) each of Rd and Re is independently selected from H and C1-C3 alkyl; (ii) C1-C6 alkyl optionally substituted with nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted with 1 to 4 substituents Petition 870260076443, dated 07 / 31 / 2026, page 476 / 508 19 / 49 independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the two remaining members are independently selected from H, C1-C10 alkyl and C1-C10 haloalkyl; or R11 and R12 together form a double bond, and R10 and R13 are independently selected from H, C1-C10 alkyl and C1-C10 haloalkyl; wherein 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

25. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, 6, 7 or 10 to 24, and characterized in that R1 is , wherein each R4 is independently selected from nitrile and C1-C0 alkyl optionally substituted by 1 to 4 substituents Petition 870260076443, dated 07 / 31 / 2026, p. 477 / 508 20 / 49 independently selected from C3-C6 cycloalkyl, hydroxy and halogen.

26. A pharmaceutically acceptable compound, stereoisomer, tautomer or salt thereof according to any one of claims 1 to 4, 6, 7 or 10 to 24, characterized in that R1 is , wherein R4b is C1-C6 alkyl and R4a is selected from nitrile and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen.

27. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, 6, 7 or 10 to 24, characterized in that R1 is , wherein R4a is C1-C6 alkyl and R4b is selected from nitrile and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxyl and halogen.

28. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to any one of claims 1 to 27, characterized in that R3 is a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2.

29. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to any one of claims 1 to 27, characterized in that R3 is a 5- to 6-membered heteroaryl ring, wherein the 5- to 6-membered heteroaryl ring contains 1 to 4 ring nitrogens, and wherein the 5- to 6-membered heteroaryl ring may be optionally substituted with 1 to 3 substituents independently selected from among hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and C(O)NH2.

30. A pharmaceutically acceptable compound, stereoisomer, tautomer or salt thereof according to any one of claims 1 to 27, characterized in that R3 is a tetrazole, pyrazole, imidazole, oxazole or pyridine, wherein R3 may be optionally substituted by 1 to 3 substituents independently selected from among hydroxyl, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and -C(O)NH2; optionally wherein R3 is a tetrazole optionally substituted by C1-C3 alkyl.

31. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to any one of claims 1 to 27, characterized in that R3 is -C(O)NHR6.

32. A pharmaceutically acceptable compound, stereoisomer, tautomer or salt thereof according to claim 31, characterized in that R6 is -(CR7R8)nC(O)NRdRe 33. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to claim 32, characterized in that each of R7 and R8 is independently selected from H and C1-C3 alkyl.

34. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to claim 32, characterized in that R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur and nitrogen.

35. Compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to claim 31, characterized in that R6 is C1-C6 alkyl optionally substituted Petition 870260076443, dated 07 / 31 / 2026, page 479 / 508 22 / 49 by a nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxy.

36. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to claim 31, characterized in that R6 is a C1-C6 alkyl optionally substituted with a nitrile or tetrazole.

37. A compound, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof according to claim 31, characterized in that R6 is a phenyl, saturated or partially unsaturated ring of 3 to 6 members or a heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected. selected.

38. A pharmaceutically acceptable compound, stereoisomer, tautomer or salt thereof according to claim 31, characterized in that R6 is cyclopropane optionally substituted with nitrile or is cyclobutane optionally substituted with nitrile.

39. Compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to any of claims 1 to 38, characterized in that each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl.

40. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof according to any one of claims 1 to 38, characterized in that any two of R10, R11, R12 and R13, together with the carbon atom(s) to which they are attached, form a 3- to 6-membered ring, and the remaining two are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl.

41. Compound of Formula (I') or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, characterized in that R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 4- to 8-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and substituted by 1- to 4 R4 groups, wherein each R4 group is independently selected from halogen, hydroxy, nitrile, NR4aR4b, -SR4a, -S(O)2R4a and C1-C6 alkyl optionally substituted by 1- to 4 substituents independently selected from C3-C6 cycloalkyl, hydroxy and halogen; optionally wherein 2 R4 groups, together with the atoms to which they are attached, form a 4- to 6-membered ring; and each R4a and R4b is independently selected from C1-C3 alkyl; R2 is selected from C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 hydroxyalkyl; -(C1-C3 alkyl)-SO2CH3;-(C1-C6 alkyl)-O-(C1-C6 alkyl) optionally replaced by Petition 870260076443, dated 07 / 31 / 2026, page 481 / 508 24 / 49 1 to 13 halogens; -(C1-C6 alkyl)-NR5aR5b; phenyl; C4-C6 cycloalkyl; and a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the phenyl, C4-C6 cycloalkyl, and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 4 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, -C(O)NR5aR5b, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; and each R5a and R5b is independently selected from H and C1-C3 alkyl; R20 is selected from H, halogen, nitrile, C1-C6 alkyl, and C1-C6 haloalkyl;R3 is selected from -C(O)NHR6, -SO2 / C1-C3 alkyl), SO2-(C3-C6 cycloalkyl), phenyl and a 5- to 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, wherein the phenyl and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxy, nitrile, C1-C3 alkyl, C1-C3 haloalkyl and C(O)NH2; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, wherein n is 1 or 2; Each of R7 and R8 is independently selected from H and C1-C3 alkyl or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur and nitrogen; each of Rd and Re is independently selected from H and C1-C3 alkyl;(ii) C1-C6 alkyl optionally substituted by nitrile or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms Petition 870260076443, dated 07 / 31 / 2026, page 482 / 508 25 / 49 independently selected from oxygen, sulfur and nitrogen, wherein the ring may be optionally substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may optionally be substituted by 1 or 2 substituents independently selected from oxo, halogen, hydroxy, nitrile, C1-C3 alkyl optionally substituted by 1 to 7 halogens independently selected, and C1-C3 alkoxy optionally substituted by 1 to 7 halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring, and the two remaining members are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; or R11 and R12 together form a double bond, and R10 and R13 are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl; wherein 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

42. Compound of Formula (I) Formula (I) Petition 870260076443, dated 07 / 31 / 2026, page 483 / 508 26 / 49 or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, characterized in that R1 is -NRfRg, wherein Rf and Rg together with the nitrogen to which they are attached form a 4- to 6-membered heterocycloalkyl ring optionally containing 1 additional ring heteroatom selected from oxygen, sulfur and nitrogen, and substituted by 1 to 3 R4 groups, wherein each R4 group is independently selected from nitrile and C1-C6 alkyl optionally substituted by 1 to 4 substituents independently selected from hydroxyl and halogen; R2 is selected from C1-C6 alkyl; C1-C6 haloalkyl; phenyl;and a 5- to 6-membered heteroaryl ring containing 1 or 2 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the phenyl and the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 or 2 R5 groups, wherein each R5 group is independently selected from halogen, nitrile, C1-C3 alkyl, C1-C3 haloalkyl, and C1-C3 alkoxy; R3 is selected from -C(O)NHR6 and a 5- to 6-membered heteroaryl ring containing 1 to 3 ring heteroatoms independently selected from oxygen, sulfur, and nitrogen, wherein the 5- to 6-membered heteroaryl ring may optionally be substituted by 1 to 3 substituents independently selected from hydroxy, nitrile, and C1-C3 alkyl; R6 is selected from: (i) -(CR7R8)nC(O)NRdRe, wherein n is 1 or 2;(i) each of R7 and R8 is independently selected from H and C1-C3 alkyl or R7 and R8 together with the carbon to which they are attached form a saturated or partially unsaturated ring of 3 to 6 members optionally containing a ring heteroatom selected from oxygen, sulfur and nitrogen; each of Rd and Re is independently selected from H and C1-C3 alkyl; (ii) optionally nitrile-substituted C1-C6 alkyl or 5- or 6-membered heteroaryl ring containing 1 to 4 ring heteroatoms independently selected from oxygen and nitrogen, wherein the ring may optionally be substituted by 1 to 4 substituents independently selected from halogen, C1-C3 alkyl, C1-C3 haloalkyl and hydroxyl;and (iii) phenyl, saturated or partially unsaturated ring of 3 to 6 members or heteroaryl ring of 5 to 6 members, wherein the saturated or partially unsaturated ring optionally contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen and the heteroaryl ring contains 1 or 2 ring heteroatoms independently selected from oxygen, sulfur and nitrogen, and wherein the saturated or partially unsaturated phenyl ring and the heteroaryl ring may be optionally substituted by 1 or 2 substituents independently selected from halogen, hydroxyl, nitrile and C1-C3 alkyl optionally substituted by one or more halogens independently selected; and each of R10, R11, R12 and R13 is independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl;or any two of R10, R11, R12 and R13, together with the carbon atom to which they are attached, form a 3- to 6-membered ring and the two remaining members are independently selected from H, C1-C6 alkyl and C1-C6 haloalkyl, wherein 0 to 10 hydrogen atoms bonded to one or more carbon atoms are replaced by deuterium atom(s).

43. Compound characterized by the fact that it is selected within the group that consists of: [8-methoxy-9-(1-methylpyrazol-3-yl)-1-thiazol-5-yl-5,6-dihidropyrrolo[2,1- a ]isoquinolin-3-yl]-[(2 S)-2-methyl-2-[(1 R )-2,2,2-trifluoro-1 Petição 870260076443, dated 31 / 07 / 2026, pág. 485 / 508 28 / 49 hidroxyethyl]pyrrolidin-1-yl]methanone; (1-(5-fluoropyridin-2-yl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)5,6-di-hydropyrrolo[2,1-a]isoquinolin-3-yl)((S)-2-methyl-2-((R)-2,2,2-trifluoro1-hydroxyethyl)pyrrolidin-1-yl)methanone; (R )-8-methoxy-5-methyl-3-((R )-2-methyl-2-(( S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidine-1-carbonyl)-N-( 1-methyl-2-oxo-1,2-di-hydropyridin-3-yl)1-(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1-a]isoquinoline-9-carboxamide; (3 S)-4-[8-methoxy-9-(1-methylpyrazol-3-yl)-1-(2-thienyl)-5,6-dihydropyrrolo[2,1- a ]isoquinoline-3-carbonyl]-3-methyl-morpholine-3-carbonitrila;(2R )-1-[8-methoxy-9-(1-methylpyrazol-3-yl)-1-thiazol-5-yl-5,6-dihydropyrrolo[2,1- a ]isoquinolina-3-carbonyl]-2-methyl-pyrrolidine-2-carbonitrila; (R )-1-(1-(1-hydroxy-2-methylpropan-2-yl)-8-methoxy-9-(2-methyl2H-tetrazol-5-yl)-5,6-dihydropyrrolo[2,1- a ]isoquinolina-3-carbonyl)-2methylpyrrolidine-2-carbonitrila; (R )-1-(1-(2,2-difluoropropyl)-8-methoxy-9-(2-methyl-2H-tetrazol5-yl)-5,6-di-hydropyrrolo[2,1-a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2carbonitrila; (R )-1-(1-(2,2-difluoropropyl)-8-methoxy-9-(2-methyl-2H-tetrazol5-yl)-5,6-di-hydropyrrolo[2,1-a]isoquinolina-3-carbonyl)-2-methylazetidine-2carbonitrila; (R )-3-(2-cyano-2-methylazetidine-1-carbonyl)-N-(1-cyanocyclobutyl)-8-methoxy-1-(thiophen-2-yl)-5,6-di-hydropyrrolo[2,1a]isoquinoline-9-carboxamide; (R)-1-(1-(5-fluoropyridin-2-yl)-8-methoxy-9-(2-methyl-2Htetrazol-5-yl)-5,6-di-hydropyrrolo[2,1-a]isoquinoline-3-carbonyl)-2methylazetidine-2-carbonitrila;(R )-1-(1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)5,6-di-hydropyrrolo[2,1-a]isoquinolina-3-carbonyl)-2-methylazetidine-2-carbonitrila; Petition 870260076443, of 31 / 07 / 2026, pág. 486 / 508 29 / 49 (2R )-1-[8-methoxy-9-oxazol-2-yl-1-(2-thienyl)-5,6-dihydropyrrolo[2,1- a ]isoquinolina-3-carbonyl]-2-methyl-pyrrolidine-2-carbonitrila; 4-[3-[(2 R )-2-[(1 R )-1-hidroxyethyl]-2-methyl-pyrrolidine-1carbonyl]-8-methoxy-1-(2-thienyl)-5,6-di-hidropyrrolo[2,1-a ]isoquinoline-9-yl]-6methyl-1 H-pyridin-2-ona; (2 R )-2-[(1 R )-1-hidroxyethyl]-2-methyl-pyrrolidin- 1-yl]-[8-methoxy9-oxazol-2-yl-1-(2-thienyl)-5,6-di-hidropyrrolo[2,1- a ]isoquinolin-3-yl]methanone; 3-[3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-1-(4fluorophenyl)-8-methoxy-5,6-di-hidropyrrolo[2,1-a ]isoquinoline-9-yl]pyridine-2carbonitrila; 3-[3-[(2 R )-2-[(1 R )-1-hidroxyethyl]-2-methyl-pyrrolidine-1carbonyl]-8-methoxy-1-propyl-5,6-di-hidropyrrolo[2,1- a ]isoquinolin-9yl]pyridine-2-carbonitrila;[8-Methoxy-9-(2-methyltetrazol-5-yl)-1-(2-thienyl)-5,6-dihydropyrrolo[2,1-a ]isoquinolin-3-yl]-[(2 R )-2-methyl-2-[(1 S')-2,2,2-trifluoro-1-hydroxy-ethyl]pyrrolidin-1-yl]methanone; (2 R )-1-[9-(1 H-imidazol-2-yl)-8-methoxy-1-(2,2,2-trifluoroethyl)5,6-dihydropyrrolo[2,1- a ]isoquinoline-3-carbonyl]-2-methyl-pyrrolidine-2carbonitrila; (2 R )-1-[8-methoxy-9-(2-methyltetrazol-5-yl)-1-(2-thienyl)-5,6-dihydropyrrolo[2,1-a ]isoquinolina-3-carbonyl]-2-methyl-pyrrolidine-2-carbonitrila; (2 R )-1-[8-methoxy-9-(2-methyltetrazol-5-yl)-1-propyl-5,6-dihydropyrrolo[2,1-a ]isoquinolina-3-carbonyl]-2-methyl-pyrrolidine-2-carbonitrila; [(2 R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidin-1-yl]-[8-methoxy9-(2-methyltetrazol-5-yl)-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinolin-3yl]methanone; (2R )-1-[8-methoxy-9-(2-methyltetrazol-5-yl)-1-(2,2,2trifluoroethyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinolina-3-carbonyl]-2-methylpyrrolidine-2-carbonitrila;Petition 870260076443, 07 / 31 / 2026, pág. 487 / 508 30 / 49 [(5 R )-8-methoxy-5-methyl-9-(2-methyltetrazol-5-yl)-1-(2-thienyl)5,6-di-hidropyrrolo[2,1- a ]isoquinolin-3-yl]-[(2 S)-2-methyl-2-[(1 R )-2,2,2trifluoro-1-hidroxy-ethyl]pyrrolidin-1-yl]methanone; [(5 R )-8-methoxy-5-methyl-9-(2-methyltetrazol-5-yl)-1-thiazol-5-yl5,6-dihydropyrrolo[2,1- a ]isoquinolin-3-yl]-[(2 R )-2-methyl-2-[(15)-2,2,2trifluoro-1-hydroxy-ethyl]pyrrolidin-1-yl]methanone; (2R )-1-[8-methoxy-9-(2-methyltetrazol-5-yl)-1-thiazol-5-yl-5,6-dihydropyrrolo[2,1- a ]isoquinoline-3-carbonyl]-2-methyl-pyrrolidine-2-carbonitrila; (R )-3-(3-(2-cyano-2-methylpyrrolidine-1-carbonyl)-8-methoxy-1(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1-a]isoquinolin-9-yl)-5(trifluoromethyl)picolinonitrila; (R )-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(2,2,2trifluoroethyl)-5,6-di-hydropyrrolo[2,1-a]isoquinolina-3-carbonyl)-2methylazetidine-2-carbonitrila;(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(1,3,4-thiadiazol-2-yl)5,6-di-hydropyrrolo[2,1-a]isoquinolin-3-yl)(( 5)-2-methyl-2-((R )-2,2,2-trifluoro1-hydroxyethyl)pyrrolidin-1-yl)methanone; (R )-1-(1-(3,3-difluorocyclobutyl)-8-methoxy-9-(2-methyl-2Htetrazol-5-yl)-5,6-di-hydropyrrolo[2,1-a]isoquinolina-3-carbonyl)-2methylpyrrolidine-2-carbonitrila; (R )-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(thiophen-2-yl)5,6-di-hydropyrrolo[2,1-a]isoquinolina-3-carbonyl)-2-methylazetidine-2-carbonitrila; (R )-1-(1-(5-fluoropyridin-2-yl)-8-methoxy-9-(2-methyl-2Htetrazol-5-yl)-5,6-di-hydropyrrolo[2,1-a]isoquinolina-3-carbonyl)-2methylpyrrolidine-2-carbonitrila; (R )-1-(1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)5,6-di-hydropyrrolo[2,1-a]isoquinoline-3-carbonyl)-2-methylpyrrolidine-2carbonitrila;Petition 870260076443, dated 07 / 31 / 2026, p. 488 / 508 31 / 49 ((R )-8-methoxy-5-methyl-9-(2-methyl-2H-tetrazol-5-yl)-1-(thiophene-2yl)-5,6-di-hydropyrrole[2,1-a]isoquinoline-3-yl)(((R)-2-methyl 5)-2,2,2trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)methanone; 5-((R )-8-methoxy-5-methyl-3-((R )-2-methyl-2-(( S)-2,2,2-trifluoro1-hydroxyethyl)pyrrolidin-1-carbonyl)-1-(2,2,2-trifluoroethyl)-5,6-dihydropyrrole[2,1-a]isoquinolin-9-yl)nicotinamide; 3-((R )-8-methoxy-5-methyl-3-((R )-2-methyl-2-(( S)-2,2,2-trifluoro1-hydroxyethyl)pyrrolidin-1-carbonyl)-1-(2,2,2-trifluoroethyl)-5,6-di-hi dropyrrole[2,1-a]isoquinoline-9-yl)picolinotrile; ((R )-8-methoxy-5-methyl-9-(2-methyl-2H-tetrazol-5-yl)-1-(2,2,2trifluoroethyl)-5,6-di-hydropyrrole[2,1-a]isoquinolin-3-yl)((R )-2-methyl-lu,2-(- trif)2 1-hydroxyethyl)pyrrolidin-1-yl)methanone;((1aR ,9bR )-8-methoxy-7-(2-methyl-2H-tetrazol-5-yl)-5-(thiophen-2yl)-1a,9b-di-hidro-1H-cyclopropa[c]pyrrolo[2,1-a]isoquinoline-3-yl)((R )-2-methyl2-(( S)-2,2,2-trifluoro-1-hidroxyethyl)pyrrolidin-1-yl)methanone; [(2 R )-2-[(1 R )-1-hidroxyethyl]-2-methyl-pyrrolidin-1-yl]-[8-methoxy9-(2-methyltetrazol-5-yl)-1-thiazol-5-yl-5,6-di-hidropyrrolo[2,1- a ]isoquinolin-3yl]methanone; [8-Methoxy-9-(2-methyltetrazol-5-yl)-1-(2-thienyl)-5,6-dihydropyrrolo[2,1-a ]isoquinolin-3-yl]-[(2 S)-2-methyl-2-[(1 R )-2,2,2-trifluoro-1-hydroxy-ethyl]pyrrolidin-1-yl]methanone; (2 R )-1-[8-methoxy-9-(1-methylpyrazol-3-yl)-1-(2-thienyl)-5,6-dihydropyrrolo[2,1-a ]isoquinolina-3-carbonyl]-2-methyl-pyrrolidine-2-carbonitrila; (2 R )-1-[8-methoxy-9-(1 H-pyrazol-3-yl)-1-(2-thienyl)-5,6-dihydropyrrolo[2,1-a ]isoquinolina-3-carbonyl]-2-methyl-pyrrolidine-2-carbonitrila; (2 R )-1-[1-(4-fluorophenyl)-8-methoxy-9-( 1-methylpyrazol-3-yl)-5,6dihydropyrrolo[2,1- a ]isoquinolina-3-carbonyl]-2-methyl-pyrrolidine-2-carbonitrila;(2 R )-1-[8-methoxy-9-(1-methylpyrazol-3-yl)-1-propyl-5,6-di Petition 870260076443, dated 07 / 31 / 2026, p. 489 / 508 32 / 49 hydropyrrole[2,1- a ]isoquinolin-3-carbonyl]-2-methyl-pyrrolidine-2-carbonitrile; 4-[3-[(2 R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidin-1carbonyl]-8-methoxy-1-propyl-5,6-di-hydropyrrole[2,1- a ]isoquinolin-9-yl]-1methyl-pyridine-2-one; [(2 R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidin-1-yl]-[8-methoxy9-(1 H-pyrazol-3-yl)-1-(2-thienyl)-5,6-di-hydropyrrole[2,1- to ]isoquinoline;3yl] 6-[8-methoxy-3-[(2 R )-2-methyl-2-[(15)-2,2,2-trifluoro-1-hydroxyethyl]pyrrolidine-1-carbonyl]-1-(2-thienyl)-5,6-di-hydropyrrole[2,1- to ]ylisoquinolin-one H 4-[3-[(2 R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidin-1carbonyl]-8-methoxy-1-(2-thienyl)-5,6-di-hydropyrrole[2,1- a ]isoquinolin-9-yl]-1-methyl-one;pyridine 3-[3-[(2 R )-2-cyano-2-methyl-pyrrolidin-1-carbonyl]-8-methoxy-1(2,2,2-trifluoroethyl)-5,6-di-hydropyrrole[2,1- a ]isoquinolin-9-yl]pyridine-2carbonitrile;[(5 R )-8-methoxy-5-methyl-9-(1-methylpyrazol-3-yl)-1-thiazol-5-yl5,6-di-hydropyrrolo[2,1- a ]isoquinolin-3-yl]-[(2 R )-2-methyl-2-[(15)-2,2,2trifluoro-1-hydroxy-ethyl]pyrrolidin-1-yl]methanone; (R )-1-(8-methoxy-9-(1-methyl-1H-pyrazol-3-yl)-1-(thiophen-2-yl)-5,6di-hydropyrrolo[2,1- a]isoquinoline-3-carbonyl)-2-methylazetidine-2-carbonitrila; (R )-1-(8-methoxy-6-methyl-9-(1-methyl-1H-pyrazol-3-yl)- 1-(thiophen2-yl)-5,6-di-hidropyrrolo[2,1-a]isoquinoline-3-carbonyl)-2-methylpyrrolidine-2carbonitrila; ((R)-8-methoxy-5-methyl-9-(1-methyl-1H-pyrazol-3-yl)-1-(thiophen-2yl)-5,6-di-hidropyrrolo[2,1-a]isoquinoline-3-yl)((R)-2-methyl-2-((S)-2,2,2trifluoro-1-hidroxyethyl)pyrrolidin-1-yl)methanone;((R )-2-((R )-1-hydroxyethyl)-2-methylpyrrolidine-1-yl)(( 5)-8-methoxy5-methyl-9-(1-methyl-1H-pyrazol-3-yl)-1-(thiophen-2-yl)-5,6-di-307ohydropyrrolo4ão246[2 of 31 / 07 / 2026, pp. 490 / 508 33 / 49 a]isoquinolin-3-yl)methanone ((1aR ,9bR )-8-methoxy-7-(1-methyl-1H-pyrazol-3-yl)-5-(thiophene-2yl)-1a,9b-di-hydro-1H-cyclopropa[c]pyrrole[2,1-a]isoquinoline-3-yl)((R )-2-methyl2-((S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)methanone; (8-methoxy-9-(1-methyl-1H-pyrazol-3-yl)-1-(1,3,4-thiadiazol-2-yl)5,6-di-hydropyrrole[2,1-a]i soquinolin-3-yl)((S)-2-methyl-2-((R)-2,2,2-trifluoro1-hydroxyethyl)pyrrolidin-1-yl)methanone; [(2 R )-2-[(1 R) -1-hydroxyethyl]-2-methyl-pyrrolidin-1-yl]-[9-(1 Himidazol-2-yl)-8-methoxy-1-(2-thienyl)-5,6-di-hydropyrrole[2,1- to ]isoquinoline-3yl; (2 R )-1-[9-(1 H-imidazol-2-yl)-8-methoxy-1-(2-thienyl)-5,6-dihydropyrrole[2,1-a ]isoquinoline-3-carbonyl]-2-methyl-pyrrolidine-2-carbonitrile;N-(1-cyanocyclobutyl)-3-[(2R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1-a ]isoquinoline-9carboxamide; N-(1-cyano-1-methyl-ethyl)-3-[(2R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-1-(4-fluorophenyl)-8-methoxy-5,6-di-hydropyrrolo[2,1-a ]isoquinoline-9carboxamide; 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-1-(4fluorophenyl)-8-methoxy-N-(2-oxo-1 H-pyridin-3-yl)-5,6-di-hydropyrrolo[2,1a]isoquinoline-9-carboxamida; 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-1-(4fluorophenyl)-8-methoxy-N-(1-methyl-2-oxo-3-pyridyl)-5,6-di-hydropyrrolo[2,1a]isoquinoline-9-carboxamida; 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy- N-(2oxo-1 H-pyridin-3-yl)-1-propyl-5,6-di-hidropyrrolo[2,1- a ]isoquinolina-9carboxamida; 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy- N-(1metil-2-oxo-3-piridil)-1-propyl-5,6-di-hidropyrrolo[2,1- a ]isoquinolina-9Petição 870260076443, de 31 / 07 / 2026, pág. 491 / 508 34 / 49 carboxamida;N-(1-cyano-1-methyl-ethyl)-3-[(2R )-2-[(1 R )-1-hydroxyethyl]-2-methylpyrrolidine-1-carbonyl]-8-methoxy-1-propyl-5,6-di-hydropyrrolo[2,1a ]isoquinoline-9-carboxamide; N-(1-cyanocyclobutyl)-3-[(2 R )-2-[(1 R )-1-hydroxyethyl]-2-methylpyrrolidine-1-carbonyl]-8-methoxy-1-propyl-5,6-di-hydropyrrolo[2,1a]isoquinoline-9-carboxamide; N-(1-cyano-1-methyl-ethyl)-3-[(2R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-1-propyl-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide; N-[2-(dimethylamino)-2-oxo-ethyl]-3-[(2R )-2-(hydroxymethyl)-2methyl-pyrrolidine-1-carbonyl]-8-methoxy-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1a]isoquinoline-9-carboxamide; 3-(2,2-dimethylpyrrolidine-1-carbonyl)-8-methoxy- N-(1 H-tetrazol5-ylmethyl)-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide; 3-[(2R)-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-N-(1methyl-2-oxo-3-pyridyl)-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9-carboxamide;3-[(2R)-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-N-(2oxo-1 H-pyridin-3-yl)-1-(2-thienyl)-5,6-dihydropyrrolo[2,1-a ]isoquinoline-9-carboxamide; N-(1-cyano-1-methyl-ethyl)-8-methoxy-3-[(2 R )-2-methyl-2-[(1 S)2,2,2-trifluoro-1-hydroxy-ethyl]pyrrolidine-1-carbonyl]-1-(2-thienyl)-5,6-dihydropyrrolo[2,1-a ]isoquinoline-9-carboxamide; N-(1-cyanocyclobutyl)-3-[(2 R )-2-[(1 R )-1-hidroxietil]-2-metilpirrolidina-1-carbonyl]-8-metoxi-1-(2-tienil)-5,6-di-hidropirrolo[2,1a]isoquinolina-9-carboxamida; N-(1-cyano-1-metil-ethyl)-3-[(2R )-2-[(1 R )-1-hidroxietil]-2-metilpirrolidina-1-carbonyl]-8-metoxi-1-(2-tienil)-5,6-di-hidropirrolo[2,1Petição 870260076443, de 31 / 07 / 2026, pág. 492 / 508 35 / 49 a ]isoquinoline-9-carboxamide; N-(1-cyanocyclobutyl)-1-(4-fluorophenyl)-3-[(2 R )-2-[(1 R )-1hydroxyethyl]-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-5,6-di-hydropyrrolo[2,1a ]isoquinoline-9-carboxamide;N-(1-cyano-1-methyl-ethyl)-1-(4-fluorophenyl)-3-[(2 R )-2-[(1 R )-1hydroxyethyl]-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-5,6-dihydropyrrolo[2,1a ]isoquinoline-9-carboxamide; N-(1-cyanocyclopropyl)-8-methoxy-3-[(2 R )-2-methyl-2-[(15)-2,2,2trifluoro-1-hydroxy-ethyl]pyrrolidine-1-carbonyl]-1-(2-thienyl)-5,6-dihydropyrrolo[2,1-a ]isoquinoline-9-carboxamide; N-(1-cyanocyclopropyl)-3-[(2 R )-2-[(1 R )-1-hydroxyethyl]-2-methylpyrrolidine-1-carbonyl]-8-methoxy-1-(2-thienyl)-5,6-dihydropyrrolo[2,1a ]isoquinoline-9-carboxamide; 8-methoxy- N-(1-methyl-2-oxo-3-pyridyl)-3-[(2 R )-2-methyl-2-[(1 S)2,2,2-trifluoro-1-hydroxy-ethyl]pyrrolidine-1-carbonyl]-1-(2-thienyl)-5,6-dihydropyrrolo[2,1-a ]isoquinoline-9-carboxamide; N-(1-cyanocyclobutyl)-8-methoxy-3-[(2 R )-2-methyl-2-[(1 5)-2,2,2trifluoro-1-hidroxy-ethyl]pyrrolidine-1-carbonyl]-1-(2-thienyl)-5,6-dihydropyrrolo[2,1-a ]isoquinoline-9-carboxamide;N-(1-cyanocyclobutyl)-3-[(2 R )-2-[(1 R )-1-hydroxyethyl]-2-methylpyrrolidine-1-carbonyl]-8-methoxy-1-(2,2,2-trifluoroethyl)-5,6-dihydropyrrolo[2,1-a ]isoquinoline-9-carboxamide; N-(1-cyanocyclobutyl)-3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-1-(4-fluorophenyl)-8-methoxy-5,6-dihydropyrrolo[2,1-a ]isoquinoline-9-carboxamide; N-(3-cyano-oxetan-3-yl)-8-methoxy-3-[(2 R )-2-methyl-2-[(1 S)2,2,2-trifluoro-1-hidroxy-ethyl]pyrrolidine-1-carbonyl]-1-(2-thienyl)-5,6-dihidropyrrolo[2,1-a ]isoquinoline-9-carboxamida; N-(3-cyano-oxetan-3-yl)-3-[(2 R )-2-[(1 R )-1-hidroxietil]-2-methyl Petição 870260076443, dated 31 / 07 / 2026, pág. 493 / 508 36 / 49 pyrrolidine-1-carbonyl]-8-methoxy-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1a ]isoquinoline-9-carboxamide; N-(1-cyano-1-methyl-ethyl)-3-[(2R )-2-cyano-2-methyl-pyrrolidine-1carbonyl]-8-methoxy-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1-a ]isoquinoline-9-carboxamide;3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]- N-[(3 R )-3cyanotetra-hydrofuran-3-yl]-8-methoxy-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1a]isoquinoline-9-carboxamida; 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]- N-[(3 S)-3cyanotetra-hydrofuran-3-yl]-8-methoxy-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1a]isoquinoline-9-carboxamida; 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]- N-(3-cyanooxetan-3-yl)-8-methoxy-1-(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1a]isoquinoline-9-carboxamida; N-(1-cyanocyclopropyl)-3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-1-(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1a]isoquinoline-9-carboxamida; N-(1-cyanocyclobutyl)-3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-1-propyl-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9carboxamide; 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]- N-(3-cyanooxetan-3-yl)-8-methoxy-1-propyl-5,6-di-hydropyrrolo[2,1- a ]isoquinoline-9carboxamide;3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]- N-(3-cyanooxetan-3-yl)-8-methoxy-1-(2-thienyl)-5,6-di-hidropyrrolo[2,1- a ]isoquinolina-9carboxamida; N-(1-cyanocyclobutyl)-3-[(2R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-1-thiazol-5-yl-5,6-di-hidropyrrolo[2,1- a ]isoquinolina-9carboxamida; Petition 870260076443, of 31 / 07 / 2026, pág. 494 / 508 37 / 49 (R )-3-(2-cyano-2-methylazetidine-1-carbonyl)-8-methoxy-N-(1methyl-2-oxo-1,2-di-hydropyridin-3-yl)-1-(2,2,2-trifluoroethyl)-5,6-dihydropyrrolo[2,1-a]isoquinoline-9-carboxamida; (R )-3-(2-cyano-2-methylazetidine-1-carbonyl)-8-methoxy-N-(2oxo-1,2-di-hydropyridin-3-yl)-1-(2,2,2-trifluoroethyl)-5,6-dihydropyrrolo[2,1a]isoquinoline-9-carboxamida; N-(1-cyanocyclobutyl)-8-methoxy-3-((S)-2-methyl-2-((R)-2,2,2trifluoro-1-hidroxyethyl)pyrrolidine-1-carbonyl)-1-(1,3,4-thiadiazol-2-yl)-5,6-dihidropyrrolo[2,1-a]isoquinoline-9-carboxamida;(R )-3-(2-cyano-2-methylazetidine-1-carbonyl)-N-(1-cyanocyclobutyl)-8-methoxy-1-(thiophen-2-yl)-5,6-dihydropyrrolo[2,1a]isoquinoline-9-carboxamide; N-(1-cyanocyclobutyl)-3-((R )-2-((R )-1-hydroxyethyl)-2methylpyrrolidine- 1-carbonyl)-8-methoxy-6-methyl-1-(thiophen-2-yl)-5,6-dihydropyrrolo[2,1-a]isoquinoline-9-carboxamide; 3-((R )-2-cyano-2-methylpyrrolidine-1-carbonyl)-N-(1-cyanocyclobutyl)-8-methoxy-6-methyl-1-(thiophen-2-yl)-5,6-dihydropyrrolo[2,1a]isoquinoline-9-carboxamide; (R )-N-(1-cyanocyclobutyl)-8-methoxy-5-methyl-3-((R )-2-methyl-2((S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidine-1-carbonyl)-1-(thiophen-2-yl)-5,6-dihydropyrrolo[2,1-a]isoquinoline-9-carboxamide; (5)-N-(1-cyanocyclobutyl)-3-((R )-2-((R )-1-hydroxyethyl)-2methylpyrrolidine-1-carbonyl)-8-methoxy-5-methyl-1-(thiophen-2-yl)-5,6-dihydropyrrolo[2,1-a]isoquinoline-9-carboxamide;(4 S)-N-(1-cyanocyclobutyl)-7-methoxy-4-methyl-3-((R )-2-methyl-2((S)-2,2,2-trifluoro-1-hidroxyethyl)pyrrolidine-1-carbonyl)-1-(thiophen-2-yl)-3a,5di-hidro-4H-cyclopenta[a]naphthalene-8-carboxamide; (5)-3-((R )-2-cyano-2-methylpyrrolidine-1-carbonyl)-N-(1cyanocyclobutyl)-8-methoxy-5-methyl-1-(thiophen-2-yl)-5,6-di-hidropyrrolo[2,1 Petição 870260076443, de 31 / 07 / 2026, pág. 495 / 508 38 / 49 a]isoquinoline-9-carboxamida; (R )-N-(1-cyanocyclobutyl)-8-methoxy-5-methyl-3-((R )-2-methyl-2((S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidine-1-carbonyl)-1-(2,2,2-trifluoroethyl)5,6-di-hydropyrrolo[2,1-a]isoquinoline-9-carboxamida; (1aR ,9bR )-N-(1-cyanocyclobutyl)-8-methoxy-3-((R )-2-methyl-2((S)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidine-1-carbonyl)-5-(thiophen-2-yl)-1a,9bdi-hydro-1H-cyclopropa[c]pyrrolo[2,1-a]isoquinoline-7-carboxamide; N-[2-(dimethylamino)-2-oxo-ethyl]-3-[(2 S)-2-ethyl-2-methylpyrrolidine-1-carbonyl]-8-methoxy-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1a ]isoquinoline-9-carboxamide;[(2 R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidin-1-yl]-[8-methoxy9-(1-methylpyrazol-3-yl)-1-(2-thienyl)-5,6-dihydropyrrolo[2,1- a ]isoquinolin-3yl]methanone; [8-methoxy-9-(1-methylpyrazol-3-yl)-1-(2-thienyl)-5,6-dihydropyrrolo[2,1 - a ]isoquinolin-3-yl]-[(2 R )-2-methyl-2-[(1 S')-2,2,2-trifluoro-1hydroxy-ethyl]pyrrolidin-1-yl]methanone; [(2 R )-2-[(1 S)-1-hydroxyethyl]-2-methyl-pyrrolidin-1-yl]-[8-methoxy9-(1-methylpyrazol-3-yl)-1-propyl-5,6-dihydropyrrolo[2,1- a ]isoquinolin-3yl]methanone; [1-(4-fluorophenyl)-8-methoxy-9-(1-methylpyrazol-3-yl)-5,6-dihydropyrrolo[2,1- a ]isoquinolin-3-yl]-[(2 S)-2-methyl-2-[(1 R )-2,2,2-trifluoro-1hydroxy-ethyl]pyrrolidin-1-yl]methanone; [1-(4-fluorophenyl)-8-methoxy-9-(1-methylpyrazol-3-yl)-5,6-dihidroxyrolo[2,1- a ]isoquinolin-3-yl]-[(2 R )-2-[(1 S)-1-hidroxyethyl]-2-methylpyrrolidin-1-yl]methanone; [1-(4-fluorophenyl)-8-methoxy-9-(1-methylpyrazol-3-yl)-5,6-dihidroxyrolo[2,1- a ]isoquinolin-3-yl]-[(2 R )-2-[(1 R )-1-hidroxyethyl]-2-methylpyrrolidin-1-yl]methanone;[1-(4-fluorophenyl)-8-methoxy-9-(1-methylpyrazol-3-yl)-5,6-di Petição 870260076443, de 31 / 07 / 2026, p. 496 / 508 39 / 49 hydropyrrolo[2,1-a]isoquinolin-3-yl]-[(25)-2-[(15)-1-hydroxyethyl]-2-methylpyrrolidin-1-yl]methanone; [(25)-2-[(15)-1-hydroxyethyl]-2-methylpyrrolidin-1-yl]-[8-methoxy9-(1-methylpyrazol-3-yl)-1-(2-thienyl)-5,6-dihydropyrrolo[2,1- a ]isoquinolin-3yl]methanone; [1-(4-fluorophenyl)-8-methoxy-9-(2-methyltetrazol-5-yl)-5,6-dihydropyrrolo[2,1- a ]isoquinolin-3-yl]-[(2 5)-2-methyl-2-[(1 R )-2,2,2-trifluoro-1hydroxyethyl]pyrrolidin-1-yl]methanone; [1-(4-fluorophenyl)-8-methoxy-9-(2-methyltetrazol-5-yl)-5,6-dihydropyrrolo[2,1 - a ]isoquinolin-3-yl]-[(2 5)-2-[1-hydroxypropyl]-2-methylpyrrolidin-1-yl]methanone; [1-(4-fluorophenyl)-8-methoxy-9-(2-methyltetrazol-5-yl)-5,6-dihydropyrrolo[2,1- a ]isoquinolin-3-yl]-[(2 S)-2-[(1 S)-1-hydroxyethyl]-2-methylpyrrolidin-1-yl]methanone;2-cyclopropyl(hydroxy)methyl)-2-methylpyrrolidin-1-yl)(1-(4fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di-hydropyrrolo[2,1a]isoquinolin-3-yl)methanone; (R )-3-(2-cyano-2-methylpyrrolidin-1-carbonyl)-N-(2cyanopropan-2-yl)-8-methoxy-1-(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1a]isoquinoline-9-carboxamide; N-(1-cyanocyclobutyl)-3-[(2R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy-1-(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1a ]isoquinoline-9-carboxamide; 3-[(2 R )-2-[(1 R )-1-hydroxyethyl]-2-methyl-pyrrolidine-1-carbonyl]8-methoxy-N-(1-methyl-2-oxo-3-pyridyl)-1-(2-thienyl)-5,6-di-hydropyrrolo[2,1a ]isoquinoline-9-carboxamide; 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy- N-(1methyl-2-oxo-3-pyridyl)-1-(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1a ]isoquinoline-9-carboxamide;Petition 870260076443, de 31 / 07 / 2026, pág. 497 / 508 40 / 49 3-[(2 R )-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-8-methoxy- N-(2oxo-1 H-pyridin-3-yl)-1-(2,2,2-trifluoroethyl)-5,6-di-hidropyrrolo[2,1a ]isoquinolina-9-carboxamida; 3-[(2R)-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-N-[(3R or S)3-cyanotetra-hydrofuran-3-yl]-8-methoxy-1-(2,2,2-trifluoroethyl)-5,6-dihydropyrrolo[2,1- a ]isoquinolina-9-carboxamida; 3-[(2R)-2-cyano-2-methyl-pyrrolidine-1-carbonyl]-N-[(3S or R)3-cyanotetra-hydrofuran-3-yl]-8-methoxy-1-(2,2,2-trifluoroethyl)-5,6-dihydropyrrolo[2,1- a ]isoquinolina-9-carboxamida; [1-(4-fluorophenyl)-8-methoxy-9-(2-methyltetrazol-5-yl)-5,6-dihydropyrrolo[2,1-a]isoquinolin-3-yl]-[(2R ou S)-4,4-difluoro-2-methyl-2-[(1 R ou S)-1-hydroxyethyl]pyrrolidin-1-yl]methanone; N-(1-cyanocyclobutyl)-3-[(2R )-2-[(1 R )-1-hydroxyethyl]-2-methylpyrrolidin-1-carbonyl]-8-methoxy-1-thiazol-5-yl-5,6-di-hydropyrrolo[2,1a]isoquinoline-9-carboxamide;N-(1-Cyanocyclobutyl)-8-methoxy-3-[(2R )-2-methyl-2-[(1 S)-2,2,2trifluoro-1-hydroxy-ethyl]pyrrolidine-1-carbonyl]-1-thiazol-5-yl-5,6-dihydropyrrolo[2,1-a ]isoquinoline-9-carboxamide; 2-ethyl-1-[8-methoxy-9-(1-methylpyrazol-3-yl)-1-(2-thienyl)-5,6-dihydropyrrolo[2,1-a ]isoquinoline-3-carbonyl]pyrrolidine-2-carbonitrila; rel -(2 R, 3 S)-3-hidroxi-1-[8-methoxy-9-(2-methyltetrazol-5-yl)-1propyl-5,6-di-hidropyrrolo[2,1- a ]isoquinoline-3-carbonyl]-2-methyl-pyrrolidine2-carbonitrila; rel -(2 R ,3 S)-1-[1-(4-fluorophenyl)-8-methoxy-9-(2-methyltetrazol-5yl)-5,6-di-hidropyrrolo[2,1- a ]isoquinoline-3-carbonyl]-3-hidroxi-2-methylpyrrolidine-2-carbonitrila; 2-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-propyl-5,6-dihydropyrrolo[2,1-a]isoquinolina-3-carbonyl)-2-azabiciclo[4.2.0]octano-1-carbonitrila; Petition 870260076443, of 31 / 07 / 2026, pág. 498 / 508 41 / 49 (1S,5S)-2-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-propyl-5,6dihydropyrrolo[2,1-a]isoquinolina-3-carbonyl)-5-methyl-2azabiciclo[3.2.0]heptane-1-carbonitrila;(2R ,4 5)-4-hydroxy-1-[8-methoxy-9-(2-methyltetrazol-5-yl)-1propyl-5,6-di-hydropyrrolo[2,1-a]isoquinolina-3-carbonyl]-2-methyl-pyrrolidine-2-carbonitrila; and (2R ,4 5)-1-[1-(4-fluorophenyl)-8-methoxy-9-(2-methyltetrazol-5-yl)5,6-di-hydropyrrolo[2,1-a]isoquinolina-3-carbonyl]-4-hydroxy-2-methylpyrrolidine-2-carbonitrila; (2R,4S)-4-hydroxy-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1(thiophen-2-yl)-5,6-di-hidroimidazo[5,1-a]isoquinolina-3-carbonyl)-2methylpyrrolidine-2-carbonitrila; (R)-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(thiophen-2-yl)5,6-di-hidroimidazo[5,1-a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila; (8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(thiophen-2-yl)-5,6-dihydroimidazo[5,1-a]isoquinolin-3-yl)((S)-2-methyl-2-((R)-3,3,3-trifluoro-1-hydroxypropyl)pyrrolidin-1-yl)methanone; (8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(thiophen-2-yl)-5,6-dihydroimidazo[5,1-a]isoquinolin-3-yl)((S)-2-methyl-2-((S)-3,3,3-trifluoro-1-hydroxypropyl)pyrrolidin-1-yl)methanone;(S)-N-(2-cyano-4,4,4-trifluorobutan-2-yl)-8-methoxy-N-methyl-9(2-methyl-2H-tetrazol-5-yl)-1-(thiophen-2-yl)-5,6-di-hidroimidazo[5,1a]isoquinolina-3-carboxamide; (2R,4S)-1-(1-(3,3-difluorocyclobutyl)-8-methoxy-9-(2-methyl-2Htetrazol-5-yl)-5,6-di-hidroimidazo[5,1-a]isoquinolina-3-carbonyl)-4-hidroxy-2methylpyrrolidine-2-carbonitrila; (R)-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(2,2,2trifluoroethyl)-5,6-di-hidroimidazo[5,1-a]isoquinolina-3-carbonyl)-2Petição 870260076443, de 31 / 07 / 2026, pág. 499 / 508 42 / 49 metilpirrolidina-2-carbonitrila; (8-methoxy-9-(1-methyl-1H-pyrazol-3-yl)-1-(thiophen-2-yl)-5,6-dihidroimidazo[5,1-a]isoquinoline-3-yl)((S)-2-methyl-2-((R)-2,2,2-trifluoro-1hidroxiethyl)pyrrolidin-1-yl)methanone; (8-methoxy-9-(1-methyl-1H-pyrazol-3-yl)-1-(thiophen-2-yl)-5,6-dihidroimidazo[5,1a]isoquinolin-3-yl)((R)-2-methyl-2-((S)-2,2,2-trifluoro-1hidroxiethyl)pyrrolidin-1-yl)methanone;(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(thiophen-2-yl)-5,6-dihidroimidazo[5,1-a]isoquinoline-3-yl)((S)-2-methyl-2-((R)-2,2,2-trifluoro-1hidroxiethyl)pyrrolidin-1-yl)methanone; (8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(thiophen-2-yl)-5,6-dihidroimidazo[5,1-a]isoquinoline-3-yl)((R)-2-methyl-2-((S)-2,2,2-trifluoro-1hidroxiethyl)pyrrolidin-1-yl)methanone; (R)-3-(2-cyano-2-methylpyrrolidine-1-carbonyl)-8-methoxy-N-(1methyl-2-oxo-1,2-di-hidropyridin-3-yl)-1-(thiophen-2-yl)-5,6-di-hidroimidazo[5,1a]isoquinolina-9-carboxamida; (R)-3-(2-cyano-2-methylpyrrolidine-1-carbonyl)-8-methoxy-N-(2oxo-1,2-di-hidropyridin-3-yl)-1-(thiophen-2-yl)-5,6-di-hidroimidazo[5,1a]isoquinolina-9-carboxamida; (8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-propyl-5,6-dihidropyrrolo[2,1-a]isoquinoline-3-yl)((S)-2-methyl-2-((S)-3,3,3-trifluoro-1hidroxypropyl)pyrrolidin-1-yl)methanone;((S)-2-((R)-1,2-di-hidroxi-2-methylpropyl)-2-methylpyrrolidin-1yl)(1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-dihidropyrrolo[2,1-a]isoquinoline-3-yl)methanone; (1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-dihidropyrrolo[2,1-a]isoquinoline-3-yl)((S)-2-methyl-2-((R)-3,3,3-trifluoro-1hidroxypropyl)pyrrolidin-1-yl)methanone; (1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-di Petição 870260076443, dated 31 / 07 / 2026, pág. 500 / 508 43 / 49 hydropyrrole[2,1-a]isoquinoline-3-yl)((S)-2-methyl-2-((S)-3,3,3-trifluoro-1hidroxypropyl)pyrrolidin-1-yl)methanone; (R)-3-(2-cyano-2-methylazetidine-1-carbonyl)-8-methoxy-N-(1methyl-2-oxo-1,2-di-hidropyridin-3-yl)-1-propyl-5,6-di-hidropyrrolo[2,1a]isoquinolina-9-carboxamida; (R)-3-(2-cyano-2-methylazetidine-1-carbonyl)-8-methoxy-N-(2oxo-1,2-di-hidropyridin-3-yl)-1-propyl-5,6-di-hidropyrrolo[2,1-a]isoquinolina-9-carboxamida;(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-propyl-5,6-dihidroimidazo[5,1-a]isoquinoline-3-yl)((S)-2-methyl-2-((R)-2,2,2-trifluoro-1hidroxiethyl)pyrrolidin-1-yl)methanone; (8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-propyl-5,6-dihidroimidazo[5,1-a]isoquinolin-3-yl) ((R)-2-methyl-2-((S)-2,2,2-trifluoro-1hidroxiethyl)pyrrolidin-1-yl)methanone; (R)-3-(2-cyano-2-methylazetidine-1-carbonyl)-1-isobutyl-8methoxy-N-(2-oxo-1,2-di-hydropyridin-3-yl)-5,6-di-hydropyrrolo[2,1a]isoquinoline-9-carboxamida; (R)-3-(2-cyano-2-methylazetidine-1-carbonyl)-1-isobutyl-8methoxy-N-(1-methyl-2-oxo-1,2-di-hydropyridin-3-yl)-5,6-di-hydropyrrolo[2,1a]isoquinoline-9-carboxamida; (8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(2,2,2-trifluoroethyl)5,6-dihydropyrrolo[2,1-a]isoquinolin-3-yl)((S)-2-methyl-2-((S)-3,3,3-trifluoro1-hydroxypropyl)pyrrolidin-1-yl)methanone; (R)-3-(2-cyano-2-methylazetidine-1-carbonyl)-8-methoxy-N-(1methyl-2-oxo-1,2-dihydropyridin-3-yl)-1-(2,2,2-trifluoroethyl)-5,6-dihydropyrrolo[2,1-a]isoquinoline-9-carboxamide;(1-(4-fluorophenyl)-8-methoxy-9-(1-methyl-1H-pyrazol-3-yl)-5,6-dihidroimidazo[5,1-a]isoquinolin-3-yl)((S)-2-methyl-2-((R)-2,2,2-trifluoro-1hidroxiethyl)pyrrolidin-1-yl)methanone; Petition 870260076443, 07 / 31 / 2026, pág. 501 / 508 44 / 49 (1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-dihydroimidazo[5,1-a]isoquinolin-3-yl)((S)-2-methyl-2-((R)-2,2,2-trifluoro-1hydroxyethyl)pyrrolidin-1-yl)methanone; (R)-3-(2-cyano-2-methylpyrrolidin-1-carbonyl)-1-(4fluorophenyl)-8-methoxy-N-(1-methyl-2-oxo-1,2-di-hydropyridin-3-yl)-5,6-dihydroimidazo[5,1-a]isoquinoline-9-carboxamide; (1-(3,5-difluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)5,6-di-hydropyrrolo[2,1-a]isoquinolin-3-yl)((S)-2-methyl-2-((S)-3,3,3-trifluoro1-hydroxypropyl)pyrrolidin-1-yl)methanone; {(S)-2-[(S)-3,3,3-trifluoro-1-hydroxypropyl]-2-methyl-1pyrrolidinyl}{11-methoxy-12-(2-methyl-2H-tetraazol-5-yl)-3-(2-thienyl)-6azatricyclo[7.4.0.02,6]trideca-1(13),2,4,9,11-pentaen-5-yl}methanone;(R)-1-(8-methoxy-9-(1-methyl-1H-pyrazol-3-yl)-1-(thiophen-2-yl)5,6-di-hydroimidazo[5,1-a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2carbonitrila; (R)-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(2-methylprop-1en-1-yl)-5,6-di-hydropyrrolo[2,1-a]isoquinolina-3-carbonyl)-2-methylazetidine-2carbonitrila; (S)-3-(1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)5,6-dihydropyrrolo[2,1-a]isoquinolina-3-carbonyl)-4-methyloxazolidine-4-carbonitrila; (S)-3-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-propyl-5,6-dihydropyrrolo[2,1-a]isoquinolina-3-carbonyl)-4-methyloxazolidine-4-carbonitrila; (R)-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-propyl-5,6-dihydroimidazo[5,1-a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila; (R)-1-(8-methoxy-9-(1-methyl-1H-pyrazol-3-yl)-1-(2,2,2trifluoroethyl)-5,6-dihydroimidazo[5,1-a]isoquinolina-3-carbonyl)-2methylpyrrolidine-2-carbonitrila;(R)-1-(1-(3,3-difluorocyclobutyl)-8-methoxy-9-( 1-methyl-1H Petição 870260076443, de 31 / 07 / 2026, pág. 502 / 508 45 / 49 pyrazol-3-yl)-5,6-di-hidroimidazo[5,1-a]isoquinolina-3-carbonyl)-2metilpirrolidina-2-carbonitrila; (S)-3-(8-methoxy-9-(2-metil-2H-tetrazol-5-yl)-1-(2,2,2trifluoroethyl)-5,6-di-hidropyrrolo[2,1-a]isoquinolina-3-carbonyl)-4metiloxazolidina-4-carbonitrila; (R)-1-(1-(4-fluorophenyl)-8-methoxy-9-(1-methyl-1H-pyrazol-3-yl)5,6-di-hidroimidazo[5,1-a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2carbonitrila; (R)-1-(1-(4-fluorophenyl)-8-methoxy-9-(1-methyl-1H-pyrazol-3-yl)5,6-di-hidroimidazo[5,1-a]isoquinolina-3-carbonyl)-2-methylazetidine-2carbonitrila; (R)-1-(1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)5,6-di-hydroimidazo[5,1-a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2carbonitrila; (R)-1-(1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)5,6-di-hydroimidazo[5,1-a]isoquinolina-3-carbonyl)-2-methylazetidine-2carbonitrila;(R)-3-(3-(2-cyano-2-methylpyrrolidine-1-carbonyl)-1-(4fluorophenyl)-8-methoxy-5,6-di-hidroimidazo[5,1-a]isoquinolin-9yl)picolinonitrila; (R)-3-(3-(2-cyano-2-methylazetidine-1-carbonyl)-1-(4fluorophenyl)-8-methoxy-5,6-di-hidroimidazo[5,1-a]isoquinolin-9yl)picolinonitrila; (R)-1-(9-(4,4-dimethyl-4,5-di-hydrooxazol-2-yl)-8-methoxy-1(thiophen-2-yl)-5,6-di-hydroimidazo[5,1-a]isoquinolina-3-carbonyl)-2methylpyrrolidine-2-carbonitrila; (R)-8-methoxy-5-methyl-3-((R)-2-methyl-2-((S)-2,2,2-trifluoro-1hydroxyethyl)pyrrolidine-1-carbonyl)-N-( 1-methyl-2-oxo-1,2-di-hydropyridin-3-yl)1-(2,2,2-trifluoroethyl)-5,6-di-hydropyrrolo[2,1-a]isoquinolina-9-carboxamide; Petition 870260076443, de 31 / 07 / 2026, pág. 503 / 508 46 / 49 3-((R)-3-((2R,4S)-2-cyano-4-hidroxy-2-metilpirrolidina-1carbonyl)-8-metoxy-5-metil-1-(2,2,2-trifluoroetil)-5,6-di-hidropirrolo[2,1a]isoquinolin-9-il)picolinonitrila;(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(2-methylprop-1-en-1yl)-5,6-di-hydropyrrolo[2,1-a]isoquinolin-3-yl)((S)-2-methyl-2-((S)-3,3,3trifluoro-1-hydroxypropyl)pyrrolidin-1-yl)methanone; (2R,4S)-4-hydroxy-1-(1-isobutyl-8-methoxy-9-(2-methyl-2Htetrazol-5-yl)-5,6-di-hydropyrrolo[2,1-a]isoquinolina-3-carbonyl)-2methylpyrrolidine-2-carbonitrila; (S)-N-(2-cyano-4,4,4-trifluorobutan-2-yl)-8-methoxy-N-methyl-9(2-methyl-2H-tetrazol-5-yl)-1-(2-methylprop- 1-en-1-yl)-5,6-dihydropyrrolo[2,1a]isoquinoline-3-carboxamida; (S)-N-(2-cyano-4,4,4-trifluorobutan-2-yl)-1-(2,2-difluoropropyl)-8-methoxy-N-methyl-9-(2-methyl-2H-tetrazol-5-yl)-5,6-dihydropyrrolo[2,1-a]isoquinoline-3-carboxamida; (S)-N-(2-cyano-4,4,4-trifluorobutan-2-yl)-8-methoxy-N-methyl-9(2-methyl-2H-tetrazol-5-yl)-1-(1,3,4-thiadiazol-2-yl)-5,6-di-hydropyrrolo[2,1a]isoquinoline-3-carboxamide;(S)-N-(2-cyano-4,4,4-trifluorobutan-2-yl)-1-(5-fluoropyridin-2yl)-8-methoxy-N-methyl-9-(2-methyl-2H-1,2,3-triazol-4-yl)-5,6-di-hydropyrrolo[2,1a]isoquinoline-3-carboxamide; ((R)-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(2-methylprop1-en-1-yl)-5,6-di-hydropyrrolo[2,1-a]isoquinoline-3-carbonyl)-2methylpyrrolidine-2-carbonitrila; (1-(tert-butyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-dihydroimidazo[5,1-a]isoquinolin-3-yl)((S)-2-methyl-2-((S)-3,3,3-trifluoro-1hydroxypropyl)pyrrolidin-1-yl)methanone; (R)-1-(1-isobutyl-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-dihydroimidazo[5,1-a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila; Petition 870260076443, de 31 / 07 / 2026, pág. 504 / 508 47 / 49 (R)-1-(1-(3,3-difluorocyclobutyl)-8-methoxy-9-(2-methyl-2Htetrazol-5-yl)-5,6-dihydroimidazo[5,1-a]isoquinolina-3-carbonyl)-2-methylpyrrolidine-2-carbonitrila;(1-isobutyl-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-dihidropyrrolo[2,1-a]isoquinoline-3-yl)((S)-2-methyl-2-((S)-3,3,3-trifluoro-1hidroxypropyl)pyrrolidin-1-yl)methanone; (1-(terc-butyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-dihidropyrrolo[2,1-a]isoquinoline-3-yl)((S)-2-methyl-2-((S)-3,3,3-trifluoro-1hidroxypropyl)pyrrolidin-1-yl)methanone; (1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-dihydroimidazo[5,1-a]isoquinolin-3-yl)((S)-2-methyl-2-((S)-2,2,2-trifluoro-1hydroxyethyl)pyrrolidin-1-yl)methanone; (2R,4S)-1-(1-(4-fluorophenyl)-8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-5,6-dihydroimidazo[5,1-a]isoquinoline-3-carbonyl)-4-hydroxy-2methylpyrrolidine-2-carbonitrila; (R)-1-(8-methoxy-9-(2-methyl-2H-tetrazol-5-yl)-1-(2-metilalil)5,6-di-hidropyrrolo[2,1-a]isoquinolina-3-carbonyl)-2-metilazetidina-2carbonitrila; ou um estereoisômero, tautomero ou sal farmaceuticamente aceitável do mesmo.; 44. Pharmaceutical composition, characterized in that it comprises the compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof, as defined in any one of claims 1 to 43, and a pharmaceutically acceptable carrier.

45. Method of modulating follicle-stimulating hormone receptor (FSHR) activity in a subject, characterized in that it comprises administering to a subject in need thereof the compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof, as defined in any of claims 1 to 43, or the composition, as defined in claim 44.

46. ​​A method for modulating follicle-stimulating hormone receptor (FSHR) activity in a biological sample, characterized in that it comprises bringing the biological sample into contact with the compound, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, as defined in any one of claims 1 to 43, or the composition, as defined in claim 44.

47. A method for treating a disease or disorder in a subject in need thereof, characterized in that it comprises administering to the subject a therapeutically effective amount of the compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof, as defined in any one of claims 1 to 43, or the composition, as defined in claim 44, optionally wherein the disease or disorder is a fertility disorder.

48. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof, as defined in any one of claims 1 to 43, or a composition, as defined in claim 44, characterized in that it is intended for use in modulating follicle-stimulating hormone receptor (FSHR) activity in a subject requiring such modulation.

49. A compound, stereoisomer, tautomer or pharmaceutically acceptable salt thereof, as defined in any one of claims 1 to 43, or a composition, as defined in claim 44, characterized in that it is intended for use in the treatment of a disease or disorder in a subject in need thereof, optionally wherein the disease or disorder is a fertility disorder.

50. Use of a pharmaceutically acceptable compound, stereoisomer, tautomer or salt thereof, as defined in any of claims 1 to 43, or a composition, as defined in claim 44, characterized in that it is intended for the preparation of a medicament to modulate follicle-stimulating hormone receptor (FSHR) activity in a subject.

51. Use of a pharmaceutically acceptable compound, stereoisomer, tautomer or salt thereof, as defined in any one of claims 1 to 43, or a composition, as defined in claim 44, characterized in that it is intended for the preparation of a medicament to treat a disease or disorder in a subject in need thereof, optionally wherein the disease or disorder is a fertility disorder.

52. Method, as defined in claim 47, compound for use, as defined in claim 49, or use, as defined in claim 51, characterized in that the disease or disorder is selected from hypogonadotropic hypogonadism, isolated idiopathic hypogonadotropic hypogonadism, Kallmann syndrome, idiopathic hypogonadotropic hypogonadism, craniopharyngiomas, combined pituitary hormone deficiency, fertile eunuch syndrome, abnormal beta subunit of LH, abnormal beta subunit of FSH, mass lesions, pituitary adenomas, cysts, metastatic cancer in the sella (breasts in women, lung and prostate in men), infiltrative lesions, hemochromatosis, sarcoidosis, histiocytosis, lymphoma, lymphocytic hypophysitis, meningitis, pituitary apoplexy, hyperprolactinemia, hypothyroidism, intentional (iatrogenic) secondary hypogonadism, empty sella, pituitary infarction, Sheehan's syndrome, anorexia nervosaCongenital adrenal hyperplasia and disorders related to GnRH deficiency.