Hydroquinazoline derivatives for the treatment of a disease or disorder, their uses, pharmaceutical composition, combination, and kit.

Description

Hydroquinazoline derivatives for the treatment of a disease or disorder. RELATED ORDERS

[001] This application claims the benefit and priority of U.S. Application No. 63 / 487,756, filed March 1, 2023, and U.S. Application No. 63 / 550,180, filed February 6, 2024, the entire contents of each of which are incorporated herein by reference in their entirety. BACKGROUND

[002] Heart failure is a major public health problem affecting more than 20 million patients worldwide and is associated with high morbidity. Natriuretic Peptide Receptor 1 (NPR1; also known as NPRA) is a guanylate cyclase receptor that is activated by Atrial Natriuretic Peptide (ANP), resulting in reduced blood pressure and blood volume. Binding to ANP induces dimerization and torsion of the receptor, which induces activation of the guanylate cyclase domain and conversion of GTP to cGMP. ANP is eliminated by NPR3, a natriuretic peptide receptor that lacks the guanylate cyclase domain, and degraded by Neutral Endopeptidase (NEP).

[003] It has been shown that increasing ANP through infusions can be beneficial for patients with chronic heart failure with reduced ejection fraction (pumping blood out by the heart) (Yoshimura et al., 2001, Can J Physiol Pharmacol 79(8):730-735). However, there is a need for oral agents that are able to supplement or replace existing therapies. SUMMARY

[004] In one aspect, the description refers to a compound of Formula (I): Petition 870260065188, dated 02 / 07 / 2026, p. 6 / 516 2 / 236 or a pharmaceutically acceptable salt thereof, where: A is NR1 or CR2R3; R1 and R2 are each independently H, (C3-C6)cycloalkyl, or (C6-Cw)aryl, wherein the (C6-Cw)aryl is optionally replaced by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl and (C3-C6)cycloalkyl; R3 is H or (C1-C6)alkyl; R4 is a (C6-Cw)aryl or a 5- or 6-membered heteroaryl comprising 1, 2, 3 or 4 heteroatoms selected from N, O and S, wherein the (C6-Cw)aryl or the 5- or 6-membered heteroaryl are each optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, oxo, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3C6)cycloalkyl, (C3-C6)cycloalkyl-(C1-C6)alkyl and (C1-C6)alkyl(C3C6)cycloalkyl; R6é NR8R9; R6 is selected from H, (C1-C6)alkyl, (C3C6)cycloalkyl and (C3-C6)cycloalkyl-(C1-C6)alkyl; R7 is (C3-C6)cycloalkyl or (C6-Cw)aryl, wherein the (C3C6)cycloalkyl and the (C6-C10)aryl are each optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H and HO2C(C1-C6)alkyl; R8 and R9 are, each one independently, H, (C1 Petition 870260065188, of 02 / 07 / 2026, page 7 / 516 3 / 236 C6)alkyl or a heterocycle with 3 to 6 members comprising 1 to 3 heteroatoms selected from N, O and S; or R8 and R9, together with the N to which they are attached, form a 3- to 10-membered heterocycle optionally comprising one or two additional heteroatoms selected from N, O, and S, wherein the 3- to 10-membered heterocycle is optionally substituted by one or more (e.g., 1, 2, 3, 4, or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl-(C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkyl-O-(C1-C6)alkyl, (C1-C6)hydroxyalkyl, (C1-C6)alkoxy, and a 3- to 7-membered heterocycle comprising one to two heteroatoms selected from N, O, and S; and Ra, Rb, Rce Rdsion, each independently H or (C1-C6)alkyl.

[005] In another aspect, the present invention relates to a pharmaceutical composition comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.

[006] In another aspect, the present invention relates to a combination comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutical agents.

[007] In another aspect, the present invention relates to a method for treating a disease or disorder comprising administering to a patient in need thereof a therapeutically effective amount of a compound of Formula I or a pharmaceutically acceptable salt thereof. In some embodiments, the disease or disorder is a cardiovascular disease or disorder. In some embodiments, the cardiovascular disease or disorder is selected from among hypertension, peripheral vascular disease, heart failure, Petition 870260065188, dated 02 / 07 / 2026, p. 8 / 516 4 / 236 Coronary artery disease (CAD), ischemic heart disease (IHD), mitral stenosis and regurgitation, angina, hypertrophic cardiomyopathy, diabetic cardiomyopathy, supraventricular and ventricular arrhythmias, cardiac dysrhythmia, atrial fibrillation (AF), new-onset atrial fibrillation, recurrent atrial fibrillation, cardiac fibrosis, atrial flutter, detrimental vascular remodeling, plaque stabilization, and myocardial infarction (MI). In some modalities, the disease or disorder is a disorder or disease associated with natriuretic peptide receptor activity.

[008] In another aspect, the present invention relates to a compound of Formula I, or a pharmaceutically acceptable salt thereof, for use as a medicament.

[009] In another aspect, the present invention relates to a compound of Formula I, or a pharmaceutically acceptable salt thereof, for use in the treatment of a disease or disorder.

[0010] In yet another aspect, the present invention relates to a compound of Formula I for use in the manufacture of a medicament to treat a disease or disorder.

[0011] In yet another aspect, the present invention relates to the use of a compound of Formula I, or a pharmaceutically acceptable salt thereof, in the treatment of a disease or disorder.

[0012] Other features and advantages of the description will be evident in the following detailed description and claims. DETAILED DESCRIPTION

[0013] In certain respects, the description provides substituted hydroquinazoline derivative compounds and pharmaceutical compositions thereof. In particular, such substituted compounds are useful as NPR1 activators and thus can be used to treat or prevent a disease or condition.

[0014] The details of the description are shown in the attached description below. Although similar or equivalent methods and materials Petition 870260065188, dated 02 / 07 / 2026, p. 9 / 516 5 / 236 those described in this document can be used in the practice or testing of the present invention; illustrative methods and materials are now described. Other features, objectives, and advantages of the description will become apparent from the description and claims. In the descriptive report and appended claims, singular forms also include the plural unless the context clearly dictates otherwise. Unless otherwise defined, all technical and scientific terms used in this document have the same meaning as commonly understood by a person of ordinary skill in the art to which the present invention pertains. All patents and publications cited in this descriptive report are incorporated herein by reference in their entirety. Compounds

[0015] In one respect, the description therefore provides a compound of Formula (I): or a pharmaceutically acceptable salt thereof, where: A is NR1 or CR2R3; R1 and R2 are each independently H, (C3-C6)cycloalkyl, or (C6-C1u)aryl, wherein the (C6-C1u)aryl is optionally replaced by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl and (C3-C6)cycloalkyl; R3 is H or (C1-C6)alkyl; R4 is a (C6-C10)aryl or a 5- or 6-membered heteroaryl comprising 1, 2, 3, or 4 heteroatoms selected from N, O, and Petition 870260065188, dated 02 / 07 / 2026, p. 10 / 516 6 / 236 S, wherein the 5- or 6-membered (C6-C10)aryl or heteroaryl are each optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, oxo, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3C6)cycloalkyl, (C3-C6)cycloalkyl-(C1-C6)alkyl and (C1-C6)alkyl(C3C6)cycloalkyl; R6é NR8R9; R6 is selected from H, (C1-C6)alkyl, (C3C6)cycloalkyl and (C3-C6)cycloalkyl-(C1-C6)alkyl; R7 is (C3-C6)cycloalkyl or (C6-Cw)aryl, wherein the (C3C6)cycloalkyl and the (C6-C10)aryl are each optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H and HO2C(C1-C6)alkyl; R8 and R9 are each independently H, (C1C6)alkyl or a 3- to 6-membered heterocycle comprising 1 to 3 heteroatoms selected from N, O, and S; or R8 and R9, together with the N to which they are attached, form a 3- to 10-membered heterocycle optionally comprising one or two additional heteroatoms selected from N, O, and S, wherein the 3- to 10-membered heterocycle is optionally substituted by one or more (e.g., 1, 2, 3, 4, or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl-(C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkyl-O-(C1-C6)alkyl, (C1-C6)hydroxyalkyl, (C1-C6)alkoxy, and a 3- to 7-membered heterocycle comprising one to two heteroatoms selected from N, O, and S; and Ra, Rb, Rce Rdsion, each independently H or (C1-C6)alkyl.

[0016] Unless otherwise specified, the term with Petition 870260065188, dated 02 / 07 / 2026, p. 11 / 516 7 / 236 of the present invention or compound of the present invention refers to compounds of Formula (I) thereof and to exemplified compounds and salts thereof, as well as all stereoisomers (including diastereomers and enantiomers), rotamers, tautomers and isotopically labeled compounds (including deuterium substitutions), as well as inherently formed chemical moieties.

[0017] Several embodiments of the description are described in this document. It will be recognized that the characteristics specified in each embodiment can be combined with other specified characteristics from other embodiments to provide other embodiments.

[0018] In some embodiments, A is NR1, and R1 is (C3C6)cycloalkyl or (C6-Cw)aryl, wherein (C6-Cw)aryl is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1C6)alkyl and (C3-C6)cycloalkyl. In some embodiments, A is NR1, and R1 is (C6-Cw)aryl which is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl and (C3-C6)cycloalkyl. In some embodiments, A is NR1, and R1 is (C6-Cw)aryl which is optionally replaced by one or more (e.g., 1, 2, 3, 4, or 5) substituents independently selected from halo and -CN. In some embodiments, A is NR1, and R1 is phenyl which is optionally replaced by 1 or 2 substituents independently selected from halo and -CN.In some embodiments, A is NR1, and R1 is phenyl which is optionally replaced by 1 substituent independently selected from halo and -CN. In some embodiments, A is NR1 and R1 is phenyl which is optionally replaced by 1 substituent independently selected from fluorine and -CN. Petition 870260065188, dated 02 / 07 / 2026, p. 12 / 516 8 / 236

[0019] In some modalities, A is NR1, and R1 is selected from CN In some modalities, A is NR1, and R1 is selected from-

[0020] In some embodiments, A is CR2R3, and R2 is (C6-C10)aryl, which is optionally substituted by one or more (e.g., 1, 2, 3, 4, or 5) substituents independently selected from halo, CN, -OH, -CO2H, (C1-C6)alkyl, and (C3-C6)cycloalkyl. In some embodiments, A is CR2R3, and R2 is (C6-Cw)aryl, which is optionally substituted by one or more (e.g., 1, 2, 3, 4, or 5) substituents independently selected from halo. In some embodiments, A is CR2R3, and R2 is phenyl which is optionally substituted by 1 or 2 substituents independently selected from halo. In some embodiments, A is CR2R3, and R2 is phenyl which is optionally substituted by 1 substituent selected from halo. In some embodiments, A is CR2R3, and R2 is phenyl which is optionally replaced by 1 substituent selected from among fluorine.

[0021] In some modes, A is CR2R3, and R2 is selected from

[0022] In some embodiments, A is CR2R3, and R3 is selected from H and -CH3.

[0023] In some embodiments, R4 is (C6-Cw)aryl or a heteroaryl with 5 or 6 members comprising 1, 2, 3 or 4 heteroatoms. Petition 870260065188, dated 02 / 07 / 2026, p. 13 / 516 9 / 236 members selected from N, O and S, wherein the (C6-C10)aryl is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, CO2H and (C1-C6)alkyl, and the 5- or 6-membered heteroaryl is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, oxo, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl, (C3C6)cycloalkyl-(C1-C6)alkyl and (C1-C6)alkyl(C3-C6)cycloalkyl.In certain embodiments, R4 is (C6-Cw)aryl or a 5- or 6-membered heteroaryl comprising 1 to 2 heteroatoms selected from N and S, wherein the (C6-Cw)aryl is optionally substituted by one or more (e.g., 1, 2, 3, 4 or 5) substituents independently selected from halo and (C1-C6)alkyl, and the 5- or 6-membered heteroaryl is optionally substituted by one or more (e.g., 1, 2, 3, 4 or 5) substituents independently selected from oxo, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl, and (C3C6)cycloalkyl-(C1-C6)alkyl.

[0024] In some embodiments, R4 is a 5- or 6-membered heteroaryl group comprising 1 to 2 heteroatoms selected from N and S, which is optionally substituted by one or more (e.g., 1, 2, 3, 4, or 5) substituents independently selected from oxo, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl, and (C3C6)cycloalkyl-(C1-C6)alkyl. In some embodiments, R4 is a 5-membered heteroaryl group comprising 1 to 2 heteroatoms selected from N and S, which is optionally substituted with one or more (e.g., 1, 2, 3, 4, or 5) substituents independently selected from oxo, (C1-C6)alkyl, (C1-C6)fluoroalkyl, (C3C6)cycloalkyl, and (C3-C6)cycloalkyl-(C1-C6)alkyl. In some embodiments, R4 is a 5-membered heteroaryl group comprising 1 to 2 heteroatoms selected from N and S, which is optionally substituted Petition 870260065188, dated 02 / 07 / 2026, p. 14 / 516 10 / 236 substituted by 1 or 2 substituents independently selected from (C1-C6)alkyl, (C1-C6)fluoroalkyl, (C3-C6)cycloalkyl and (C3-C6)cycloalkyl-(C1-C6)alkyl. In some embodiments, R4 is a 5-membered heteroaryl comprising 2 heteroatoms selected from N and S, which is optionally substituted by 1 or 2 substituents independently selected from (C1-C6)alkyl, (C1-C6)fluoroalkyl, (C3-C6)cycloalkyl and (C3-C6)cycloalkyl-(C1-C6)alkyl.

[0025] In certain embodiments, R4 is (C6-C10)aryl, which is optionally substituted by one or more (e.g., 1, 2, 3, 4 or 5) substituents independently selected from halo, oxo and (C1Ce)alkyl. In certain embodiments, R4 is phenyl, which is optionally substituted by 1 or 2 substituents independently selected from halo, oxo and (C1-C6)alkyl. In certain embodiments, R4 is (C6Cw)aryl, which is optionally substituted by one or more (e.g., 1, 2, 3, 4 or 5) substituents independently selected from halo.

[0026] In some modes, R4 is selected from L· Z^NXZ^NZ^N tll. LN,bF; , , , FZ^NS—\\ ' £ Z^N . \___ 5 \\ i Λ VN ? V7 x , , , % s / / 'n κι-N n'N NN * \ JN \ / / s-^ , , , , ηΓ) AND η \l_#, W , \= / and L / ^N ξ 'λ 1 des, R4 is selected from among x L / ^N \ \ \ \ \ , i \ N \ V , \ F\ An UZ^A \\ 1 « \\ ' s \\ ' VNX VNx N'Nx , , , FZ^N l / f í Zs 1 \ II . \ II 2 \ _J S-\ S-\ N\ , , , ^= / . In some modality- LZ^N i— . \N^CF3 , , , Petition 870260065188, of 02 / 07 / 2026, p. 15 / 516 11 / 236 LN 5 XX I In some modes, R4 is selected between '

[0027] In some embodiments, R5e NR8R9, and R8e R9, together with the N to which they are attached, form a 3-membered heterocycle optionally comprising 1 or 2 additional heteroatoms selected from N, O and S, wherein the 3- to 10-membered heterocycle is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3C6)cycloalkyl-(C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkyl-O-(C1C6)alkyl, (C1-C6)hydroxyalkyl, (C1-C6)alkoxy and a 3- to 7-membered heterocycle comprising 1 to 2 heteroatoms selected from N, O and S.

[0028] In some embodiments, R5e NR8R9, and R8e R9, together with the N to which they are attached, form a heterocycle with 3 a Petition 870260065188, dated 02 / 07 / 2026, p. 16 / 516 12 / 236 members comprising optionally 1 to 2 additional O heteroatoms, wherein the heterocycle with 3 to 10 members is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl-(C1-C6)alkyl, (C3C6)cycloalkyl, (C1-C6)alkyl-O-(C1-C6)alkyl, (C1-C6)hydroxyalkyl, (C1-C6)alkoxy and a heterocycle with 3 to 7 members comprising 1 to 2 heteroatoms selected from N, O and S.

[0029] In some embodiments, R5e NR8R9, and R8e R9, together with the N to which they are attached, form a heterocycle with 3 to 10 members optionally comprising 1 to 2 additional O heteroatoms, wherein the heterocycle with 3 to 10 members is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -OH, (C1-C6)alkyl, (C1C6)haloalkyl, (C3-C6)cycloalkyl, (C1-C6)alkyl-O-(C1-C6)alkyl, (C1C6)hydroxyalkyl, (C1-C6)alkoxy and a heterocycle with 3 to 7 members comprising a heteroatom selected from N, O and S.

[0030] In some embodiments, R5 and NR8R9, and R8 and R9, together with the N to which they are attached, form a 5- to 10-membered heterocycle optionally comprising 1 to 2 additional O heteroatoms, wherein the 5- to 10-membered heterocycle is optionally substituted by one or more (e.g., 1, 2, 3, 4, or 5) substituents independently selected from halo, -OH, (C1-C6)alkyl, (C1C6)haloalkyl, (C3-C6)cycloalkyl, (C1-C6)alkyl-O-(C1-C6)alkyl, (C1C6)hydroxyalkyl, (C1-C6)alkoxy, and a 3- to 7-membered heterocycle comprising a heteroatom selected from N and O. In some embodiments, the 5- to 10-membered heterocycle is optionally substituted by one or more (e.g., 1, 2, 3, 4 or 5) substituents independently selected from among fluorine, -OH, (C1-C6)alkyl, (C1-C6)fluoroalkyl, CH3O-(C1-C6)alkyl, (C1 Petition 870260065188, dated 02 / 07 / 2026, p. 17 / 516 13 / 236 Cs)hydroxyalkyl and a 5-membered heterocycle comprising a heteroatom selected from O. In some embodiments, the 5- to 10-membered heterocycle is optionally substituted by one or more (e.g., 1, 2, 3, 4, or 5) substituents independently selected from fluorine, -OH, -CH3, -CH2F, -CF2H, -CH2CH3, CH2OH, -OCH3, and -CH2OCH3. In some embodiments, the 5- to 10-membered heterocycle is optionally substituted by 1 or 2 substituents independently selected from fluorine, -OH, -CH3, CH2F, -CF2H, -CH2CH3, -CH2OH, -OCH3, and -CH2OCH3. In some embodiments, the 5- to 10-membered heterocycle is optionally replaced by 1 substituent independently selected from (C3-C6)cycloalkyl and a 5-membered heterocycle comprising a heteroatom selected from N and O.

[0031] In some modes, R5 is selected from among Petition 870260065188, dated 02 / 07 / 2026, p. 18 / 516 14 / 236 and In certain sports, R5 is selected. swimming among and In some modalities, R5 is selected. Petition 870260065188, dated 02 / 07 / 2026, p. 19 / 516 15 / 236 included among

[0032] In some embodiments, R5 is NR8R9, and R8 is selected from H and (C1-C6)alkyl. In some embodiments, R5 is NR8R9, and R9 is selected from H, (C1-C6)alkyl and a 3- to 6-membered heterocycle comprising an O heteroatom.

[0033] In some embodiments, R6 is selected from (C1-C4)alkyl, (C3-C5)cycloalkyl and (C3-C5)cycloalkyl-(C1-C4)alkyl. In certain embodiments, R6 is selected from -CH3, -CH2CH3, and

[0034] In some embodiments, R7 is selected from (C3C6)cycloalkyl or (C6-Cw)aryl, wherein the (C3-C6)cycloalkyl and (C6Cw)aryl are each optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CO2H and -CH2CO2H. In some embodiments, R7 is selected from (C5-C6)cycloalkyl or (C6-Cw)aryl, wherein the (C5C6)cycloalkyl and (C6-Cw)aryl are each optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CO2H and -CH2CO2H. Petition 870260065188, dated 02 / 07 / 2026, p. 20 / 516 16 / 236 selected separately from halo, -CO2H and -CH2CO2H. In some embodiments, R7 is selected from (C5-C6)cycloalkyl or (C6-Cw)aryl, wherein the (C5-C6)cycloalkyl and (C6-Cw)aryl are each optionally substituted by 1 or 2 substituents independently selected from fluorine, -CO2H and -CH2CO2H.

[0035] In certain modes, R7 is selected from oh and oh

[0036] In some modalities, Ra, Rb, Rce Rdsão, each independently, H or -CH3. In some modalities, Ra, Rb, Rce Rdsão, each, H. In some modalities, Ra, Rbe Rcsão, each, H. In some modalities, Raé H. In some modalities, Rbe Rcsão, each, H. In some modalities, Ra, Rb, Rce Rdsão, each, -CH3. In some preferred modalities, Rdé CH3.

[0037] In some embodiments, the description refers to a compound of Formula (I): or a pharmaceutically acceptable salt thereof, where: A is CR2R3; R2 is (C6-Cw)aryl, where (C6-Cw)aryl is optionally Petition 870260065188, dated 02 / 07 / 2026, p. 21 / 516 17 / 236 replaced by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl and (C3-C6)cycloalkyl; R3 is H or (C1-C6)alkyl; R4 is a 5- or 6-membered heteroaryl group comprising 1, 2, 3, or 4 heteroatoms selected from N, O, and S, wherein the 5- or 6-membered heteroaryl group is optionally substituted by one or more (for example, 1, 2, 3, 4, or 5) substituents independently selected from halo, -CN, -OH, -CO2H, oxo, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl-(C1-C6)alkyl, and (C1-C6)alkyl(C3-C6)cycloalkyl; R6é NR8R9; R6 is selected from H, (C1-C6)alkyl, (C3C6)cycloalkyl and (C3-C6)cycloalkyl-(C1-C6)alkyl; R7 is (C3-C6)cycloalkyl or (C6-Cw)aryl, wherein the (C3C6)cycloalkyl and (C6-Cw)aryl groups are each optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H and HO2C(C1-C6)alkyl; R8 and R9 are each independently H, (C1C6)alkyl or a 3- to 6-membered heterocycle comprising 1 to 3 heteroatoms selected from N, O, and S; or R8 and R9, together with the N to which they are attached, form a 3- to 10-membered heterocycle optionally comprising one or two additional heteroatoms selected from N, O, and S, wherein the 3- to 10-membered heterocycle is optionally substituted by one or more (e.g., 1, 2, 3, 4, or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl-(C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkyl-O-(C1-C6)alkyl, (C1-C6)hydroxyalkyl, (C1-C6)alkoxy, and a he Petition 870260065188, dated 02 / 07 / 2026, p. 22 / 516 18 / 236 terocycle with 3 to 7 members comprising 1 to 2 heteroatoms selected from N, O, and S; and Ra, Rb, Rce Rdsion, each independently H or (C1-C6)alkyl.

[0038] In some embodiments, the description refers to a compound of Formula (I): or a pharmaceutically acceptable salt thereof, where: A is CR2R3; R2 is phenyl, wherein the phenyl group is optionally replaced by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl and (C3-C6)cycloalkyl; R3 is H or (C1-C6)alkyl; R4 is a (C6-C10)aryl or a 5- or 6-membered heteroaryl comprising 1, 2, 3 or 4 heteroatoms selected from N, O and S, wherein the (C6-C6)aryl or the 5- or 6-membered heteroaryl are each optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, oxo, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3C6)cycloalkyl, (C3-C6)cycloalkyl-(C1-C6)alkyl and (C1-C6)alkyl(C3C6)cycloalkyl; R6é NR8R9; R6 is selected from H, (C1-C6)alkyl, (C3C6)cycloalkyl and (C3-C6)cycloalkyl-(C1-C6)alkyl; R7 is (C3-C6)cycloalkyl or (C6-Cw)aryl, where (C3 Petition 870260065188, dated 02 / 07 / 2026, p. 23 / 516 19 / 236 Cs)cycloalkyl and (C6-C10)aryl are each optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H and HO2C(C1-C6)alkyl; R8 and R9 are each independently H, (C1C6)alkyl or a 3- to 6-membered heterocycle comprising 1 to 3 heteroatoms selected from N, O, and S; or R8 and R9, together with the N to which they are attached, form a 3- to 10-membered heterocycle optionally comprising one or two additional heteroatoms selected from N, O, and S, wherein the 3- to 10-membered heterocycle is optionally substituted by one or more (e.g., 1, 2, 3, 4, or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl-(C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkyl-O-(C1-C6)alkyl, (C1-C6)hydroxyalkyl, (C1-C6)alkoxy, and a 3- to 7-membered heterocycle comprising one to two heteroatoms selected from N, O, and S; and Ra, Rb, Rce Rdsion, each independently H or (C1-C6)alkyl.

[0039] In some embodiments, the description refers to a compound of Formula (I): or a pharmaceutically acceptable salt thereof, where: A is CR2R3; R2 is phenyl, where the phenyl group is optionally replaced by one or more (e.g., 1, 2, 3, 4, or 5) independent substituents. Petition 870260065188, dated 02 / 07 / 2026, p. 24 / 516 20 / 236 selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl and (C3-C6)cycloalkyl; R3 is H or (C1-C6)alkyl; R4 is a (C6-C10)aryl or a 5- or 6-membered heteroaryl comprising 1, 2, 3 or 4 heteroatoms selected from N, O and S, wherein the (C6-C6)aryl or the 5- or 6-membered heteroaryl are each optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, oxo, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3C6)cycloalkyl, (C3-C6)cycloalkyl-(C1-C6)alkyl and (C1-C6)alkyl(C3C6)cycloalkyl; R6é NR8R9; R6 is selected from H, (C1-C6)alkyl, (C3C6)cycloalkyl and (C3-C6)cycloalkyl-(C1-C6)alkyl; R7 is (C3-C6)cycloalkyl or (C6-Cw)aryl, wherein the (C3C6)cycloalkyl and the (C6-C10)aryl are each optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H and HO2C(C1-C6)alkyl; R8 and R9 are each independently H, (C1C6)alkyl or a 3- to 6-membered heterocycle comprising 1 to 3 heteroatoms selected from N, O, and S; or R8 and R9, together with the N to which they are attached, form a 3- to 10-membered heterocycle optionally comprising one or two additional heteroatoms selected from N, O, and S, wherein the 3- to 10-membered heterocycle is optionally substituted by one or more (e.g., 1, 2, 3, 4, or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl-(C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkyl-O-(C1-C6)alkyl, (C1-C6)hydroxyalkyl, (C1-C6)alkoxy, and a he Petition 870260065188, dated 02 / 07 / 2026, p. 25 / 516 21 / 236 terocycle with 3 to 7 members comprising 1 to 2 heteroatoms selected from N, O, and S; and Ra, Rb, Rce Rdsion, each independently H or (C1-C6)alkyl.

[0040] In some embodiments, the description refers to a compound of Formula (I): or a pharmaceutically acceptable salt thereof, where: A is NR1; R1 is (C6-C10)aryl, wherein the (C6-C10)aryl is optionally replaced by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1C6)alkyl and (C3-C6)cycloalkyl; R3 is H or (C1-C6)alkyl; R4 is a (C6-Cw)aryl or a 5- or 6-membered heteroaryl comprising 1, 2, 3, or 4 heteroatoms selected from N, O, and S, wherein the (C6-Cw)aryl is optionally substituted by one or more (e.g., 1, 2, 3, 4, or 5) substituents independently selected from halo, -CN, -OH, -CO2H, and (C1-C6)alkyl, and the 5- or 6-membered heteroaryl is optionally substituted by one or more (e.g., 1, 2, 3, 4, or 5) substituents independently selected from halo, -CN, -OH, -CO2H, oxo, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl-(C1-C6)alkyl and (C1-C6)alkyl(C3-C6)cycloalkyl; R6é NR8R9; R6 is selected from (C1-C6)alkyl, (C3-C6)cycloalkyl and Petition 870260065188, dated 02 / 07 / 2026, p. 26 / 516 22 / 236 (C3-C6)cycloalkyl-(C1-C6)alkyl; R7 is (C3-C6)cycloalkyl or (C6-C10)aryl, wherein (C3C6)cycloalkyl and (C6-C10)aryl are each optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CO2H and HO2C-(C10C6)alkyl; R8 and R9, together with the N to which they are attached, form a 3- to 10-membered heterocycle optionally comprising one or two additional heteroatoms selected from N, O, and S, wherein the 3- to 10-membered heterocycle is optionally substituted by one or more (e.g., 1, 2, 3, 4, or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl-(C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkyl-O-(C1-C6)alkyl, (C1-C6)hydroxyalkyl, (C1-C6)alkoxy, and a 3- to 7-membered heterocycle comprising one to two heteroatoms selected from N, O, and S; and Ra, Rb, Rce Rdsion, each independently H or (C1-C6)alkyl.

[0041] In certain embodiments, the compound is a compound, or a pharmaceutically acceptable salt thereof, selected from: Table 1 Compound No. Structure Name 3-((R)-1-(((R)-4-(((R)-2(azepan-1-yl)-1-(1-methyl-1Hpyrazol-4-yl)ethyl)amino)-6-(3fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)bicyclo[1.1.1]pentane-1-carboxylic acid Petition 870260065188, dated 02 / 07 / 2026, page 27 / 516 23 / 236 Compound n° Structure Nome 2 / NN I Vo Ν NX> w OH Acid (1 R,4r)-4-((R)-1-(((R)-6-(3fluorophenyl)-6-methyl-4-(((R)-1-(1methyl-1H-pyrazol-4-yl)-2-((S)-3methylp peridin-1-yl)ethyl)amino)5,6,7,8-tetra-hydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic 3 / NN X HNXO Uro OH Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-(azepan-1-yl)-1-(1-methyl1H-pyrazol-4-yl)ethyl)amino)-6-(3fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic 4 OH MA FyK,..WN NU HNykÀ- 3Acid 3-((R)-1-(((R)-4-(((S)-2(azepan-1-yl)-1-(1-methyl-1 Hpyrazol-4-yl)ethyl)amino)-6-(3fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2- . il)(methyl)amino)propyl)bicyclo[1.1.1 ]pentane-1-carboxylic 5 / NN Yo ηνΛ-νΑ. Ν Ν γ xΗ Cr OH Acid (1 R,4r)-4-((R)-1-(((R)-6-(4fluorophenyl)-6-methyl-4-(((R)-1-(1methyl-1H-pyrazol-4-yl)-2-((S)-3methylp peridin-1-yl)ethyl)amino)5,6,7,8-tetra-hydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic Petition 870260065188, 02 / 07 / 2026, p. 28 / 5 24 / 2Compound n° Structure Name 6 \ NN λ Λ r-^7 F V7 Jd 1 / VL JL hn Π / έΠ NN^X\ 1 AyO OH 3Acid 3-((R)-1-(((R)-4-(((R)-2((1S,5S)-9- azabicyclo[3.3.1 ]nonan-9-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-(3-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2- yl)(methyl)amino)propyl)bicyclo[1.1.1 ]pentane-1-carboxylic 7 \ NN yo HNA-NA'·,, —ν n ><> Gold OH Acid (1R,4r)-4-((R)-1-(methyl((R)6-methyl-4-(((R)-1-(1-methyl-1 Hpyrazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)-6phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic 8 \ NN ___ J. À A ppi HN '' AAs / VxXn v L / k AANN^V\ 1 kAo OH 3Acid 3-((R)-1-(methyl((R)-6methyl-4-(((R)-1-(1-methyl-1Hpyrazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)-6phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)bicyclo[1.1.1 ]penta no-1-carboxylic acid 9 \ NN / AF >< íl Hpyrazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)bicyclo[1.1.1]pentane-1-carboxylic acid. Petition 870260065188, dated 02 / 07 / 2026, p. 29 / 516 25 / 236 Compound n° Structure Name 10 \|-N or xNH w OH Acid (1R,4r)-4-((R)-1-(((S)-4(((R)-2-((1S,5S)-9azabicycle[3.3.1 ]nonan-9-yl)-1-(1ethyl-1H-pyrazol-4-yl)ethyl)amino)-6(3-fluorophenyl)-5,6,7,8-tetrahydroquinazoline-2yl)amino)propyl)cyclo-hexane-1carboxylic 11\Ô \ NN OH χ 3-((R)-1-(((R)-4-((((R)-2((1S,5S)-9- azabicycle[3.3.1 ]nonan-9-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-(4-fluorotraphenylhydro)-quina,-5,6-2 il)(methyl)amino)propyl)bicycle[1.1.1 ]pentane-1-carboxyl 12 \ NN ___ J·,, Yll Ί k Jl· 1 . FN llM 1 ^γ.Ο OH 3Acid 3-((R)-1-(((R)-4-(((R)-2((S)-3-(fluoromethyl)piperidin-1-yl)- 1 -(1-methyl-1 H-pyrazol-4yl)ethyl)amino)-6-methyl-6-phenyl5,6,7,8-tetra-hydroquinazoline-2yl)(methyl)amino)propyl)bicycle[1.1.1 ]pentane-1-carboxylic 13 NN L Yo ΔΥ3 Δ 1 < — Ý 3-((R)-1-(((R)-4-(((R)-1(1-ethyl-1 H-pyrazol-4-yl)-2-((S)-3methylpiperidine-1-yl)ethyl)amino)-6(3-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-5,6,7,8-tetrahydroquinazolin- il)(methyl)amino)propyl)bicycle[1]pentane-1-carboxylic acid. Petition 870260065188, dated 02 / 07 / 2026, page 30 / 516 26 / 236 Compound No. Structure Name Acid (1R,4r)-4-((R)-1-(((R)-6-(4fluorophenyl)-4-(((R)-1-(1-methyl-1 Hpyrazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((1S,5S)-9azabicyclo[3.3.1 ]nonan-9-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-(3-fluorophen il)-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1carboxylic acid Acid (1R,4r)-4-((1R)-1-(((6R)-4(((1R)-2-(8azabicyclo[3.2.1 ]octan-8-yl)-1(1,5-dimethyl-1 H-pyrazol-4yl)ethyl)amino)-6-(3-fluorophenyl)5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((1S,5S)-9azabiciclo[3.3.1 ]nonan-9-yl)-1-(1ethyl-1H-pyrazol-4-yl)ethyl)amino)-6(3-fluorophenyl)-5,6,7,8-tetrahidroquinazolin-2yl)amino)propyl)ciclo-hexano-1carboxylico Petition 870260065188, 02 / 07 / 2026, pág. 31 / 516 27 / 236 Compound No. Structure Name Ácido (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((1S,5S)-9azabiciclo[3.3.1 ]nonan-9-yl)-1-(1ethyl-1H-pyrazol-4-yl)ethyl)amino)-6(3-fluorophenyl)-5,6,7,8-tetrahidroquinazolin-2yl)(metil)amino)propyl)ciclohexano-1-carboxylico Ácido (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((S)-3(fluorometil)piperidin-1-yl)-1-(1metil-1H-pirazol-4-yl)ethyl)amino)6-(3-fluorofen il)-5,6,7,8-tetrahidroquinazolin-2yl)(metil)amino)propyl)ciclohexano-1-carboxylico Acid (1 R,4r)-4-((R)-1-(((R)-6-(2fluorophenyl)-6-methyl-4-(((R)-1-(1methyl-1H-pyrazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1carboxylic (1S,4r)-1-fluoro-4-((S)-1(methyl((S)-4-(((S)-1-(1-methyl-1Hpyrazol-4-yl)-2-((R)-3methylpiperidin-1-yl)ethyl)amino)-6phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1carboxylic acid Petition 870260065188, dated 02 / 07 / 2026, page 32 / 516 28 / 236 Compound No. Structure Name (1R,4r)-4-((R)-1-(((R)-4(((R)-1-(1-isopropyl-1H-pyrazol-4yl)-2-((S)-3-methylpiperidin-1yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1carboxylic acid Acid (1R,4r)-4-((R)-1-(((R)-6-(3fluorophenyl)-4-(((R)-1-(1-methyl-1 Hpyrazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Acid (1R,4r)-4-((1R)-1-(((6R)-4(((1S)-2-(8azabicyclo[3.2.1 ]octan-8-yl)-1(2,4-dimethylthiazol-5-yl)ethyl)amino)6-(3-fluorophen il)-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1carboxylic acid 3Acid 3-((1 R)-1-(((6R)-4-(((1 R)2-(8-azabicyclo[3.2.1]octan-8-yl)1 -(1-methyl-1 H-pyrazol-4yl)ethyl)amino)-6-(4-fluorophenyl)5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)bicyclo[1.1.1]pentane-1-carboxylic acid Petition 870260065188, dated 02 / 07 / 2026, page 33 / 516 29 / 236 Compound No. Structure Name Acid (1 R,4r)-4-((1 R)-1-(((6R)-4(((1S)-2-(8azabiciclo[3.2.1 ]octan-8-yl)-1-(4methylthiazol-5-yl)ethyl)amino)-6-(3fluorophenyl)-5,6,7,8-tetrahidroquinazolin-2yl)amino)propyl)ciclo-hexano-1carboxylico 3Ácido 3-((R)-1-(((R)-4-(((R)-2((1S,5S)-9azabiciclo[3.3.1 ]nonan-9-yl)-1-(1metil-1H-pyrazol-4-yl)ethyl)amino)6-metil-6-fenil-5,6,7,8-tetrahidroquinazolin-2yl)(metil)amino)propyl)biciclo[1.1.1 ]pentane-1-carboxylico 3Ácido 3-((1 R)-1-(((6R)-4-(((1 R)2-(8-azabiciclo[3.2.1]octan-8-yl)1 -(1-metil-1 H-pyrazol-4yl)ethyl)amino)-6-methyl-6-phenyl5,6,7,8-tetra-hidroquinazolin-2yl)(methyl)amino)propyl)biciclo[1.1.1 ]pentano-1-carboxílico Ácido (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((1S,5S)-9azabiciclo[3.3.1 ]nonan-9-yl)-1-(1metil-1H-pirazol-4-yl)ethyl)amino)6-(3-fluorofen il)-5,6,7,8-tetrahidroquinazolin-2yl)(metil)amino)propyl)ciclohexano-1-carboxylico Petition 870260065188, 02 / 07 / 2026, pág. 34 / 516 30 / 236 Compound No. Structure Name Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-1-(1-ethyl-1 H-pyrazol-4-yl)-2(piperidin-1-yl)ethyl)amino)-6-(3fluorophenyl)-5,6,7,8-tetrahidroquinazolin-2yl)amino)propyl)ciclo-hexano-1carboxylico Ácido (1 R,4r)-4-((1 R)-1-(((6R)-4(((1R)-2-(8azabiciclo[3.2.1 ]octan-8-yl)-1-(1metil-1H-pirazol-4-il)ethyl)amino)6-(4-fluorofen il)-5,6,7,8-tetrahidroquinazolin-2il)(metil)amino)propil)ciclohexano-1-carboxylico Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-1-(1-methyl-1 H-pyrazol-4-yl)2-((S)-3-methylpiperidin-1yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2yl)amino)propyl)ciclo-hexano-1carboxylico (1 R,4r)-4-((1 R)-1-(((6R)-4(((1R)-2-(8azabicyclo[3.2.1 ]octan-8-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-(3-fluorophenyl)-5,6,7,8-tetrahidroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Petition 870260065188, 02 / 07 / 2026, pág. 35 / 516 31 / 236 Compound No. Structure Nome OH Ácido (1 R,4r)-4-((1 R)-1-(((6R)-4(((1R)-2-(8azabiciclo[3.2.1 ]octan-8-il)-1-(1metil-1H-pyrazol-4-yl)ethyl)amino)6-metil-6-fenil-5,6,7,8-tetrahydroquinazolin-2yl)ciclohexano-1-carboxílico (1 R,4r)-4-((R)-1-(((R)-6-(3fluorophenyl)-4-(((R)-2-((S)-3(methoxymethyl)piperidin-1-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)5,6,7,8-tetra-hydroquinazolin-2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid 3Acid 3-((S)-1-(((S)-4-(((R)-2((R)-3-(fluoromethyl)piperidin-1-yl)1 -(1-methyl-1H-pyrazol-4-yl)ethyl)amino)-6-methyl-6-phenyl5,6,7,8-tetra-hydroquinazolin-2-yl)(methyl)amino)propyl)bicyclo[1.1.1 ]pentane-1-carboxylic acid Ácido (1 R,4r)-4-((R)-1-(((S)-6-(3fluorofenil)-4-(((R)-1-fenil-2(piperidin-1-yl)ethyl)amino)-5,6,7,8tetra-hidroquinazolin-2yl)amino)propyl)ciclo-hexano-1carboxílico Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((1 R,3R,5R,7R)-2-azaadamantan-2-yl)-1-(1-ethyl-1 Hpyrazol-4-yl)ethyl)amino)-6-phenyl5,6,7,8-tetra-hydroquinazoline-2yl)amino)propyl)cyclo-hexano-1carboxylic Petition 870260065188, of 02 / 07 / 2026, p. 36 / 516 32 / 236 Compound n° Structure Name 39 / NN Λ À F Λ HNdNj-.„ xX N N'^YYO 1 LJX XX '''XYdH 2Acid 2-((1 R,4r)-4-((R)-1-(((R)6-(3-fluorophenyl)-4-(((R)-1-(1methyl-1H-pyrazol-4-yl)-2-((S)-3methylpiperidine-1-yl)ethyl)amino)- 5,6,7,8-tetra-hydroquinazolin-2yl)(methyl)amino)propyl)cyclohexyl)acetic 40 / NN Q hnYO% XX N Ν'ηΧ > 1 ur OH Acid (1 R,4r)-4-((R)-1-(methyl(1(R))4 H-pyrazol-4yl)-2-((S)-3-methylpiperidine-1yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic 41 Nl / / \ / Ά 1 dyde— N tide 3-((R)-1-(((R)-4-(((R)-2(9-azabicyclo[3.3.1 ]nonan-9-yl)-1(1-methyl-1H-pyrazol-4- il)ethyl)amino)-6-(2-fluorophenyl)5,6,7,8-tetra-hydroquinazoline-2yl)(methyl)amino)propyl)bicycl[1.1.1 ]pentane-1-carboxylic 42 NN^ A Xô Υ3ά χ(1 NN >Γ3 R)-1-(((6R)-4-(((1 R)2-(8-azabicyclo[3.2.1]octan-8-yl)1-(1-ethyl-1H-pyrazol-4yl)ethyl)amino)-6-(3-fluorophenyl)5,6,7,8-tetraline-2hydroquine il)(methyl)amino)propyl)bicycle[1 ]pentane-1-carboxylic 43 \ NN kj z\ x. 1 AA X HN^ / '| kl___ 1 . f XX A1 H NX-n 1 OH 3Acid 3-((S)-1-(((R)-4-(((R)-2((S)-3-(fluoromethyl)piperidin-1-yl)- 1 -(1-methyl-1 H-pyrazol-4yl)ethyl)amino)-6-methyl-6-phenyl5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)bicyclo[1.1.1]pentane-1-carboxylic acid. Petition 870260065188, dated 02 / 07 / 2026, page 37 / 516 33 / 236 Compound n° Structure Name 44 \ NN ___ XL JL hn '' 1 OH 3Acid 3-((R)-1-(methyl((R)-4(((R)-1-(1-methyl-1 H-pyrazol-4-yl)2-((S)-3-methylpiperidin-1yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazoline-2yl)amino)propyl)bicyclo[1.1.1 ]penta no-1-carboxylic acid 45 NN HN^O^u ^HH^H (1R,4r)-4-((R)-1-(((R)-4(((R)-1-(1-ethyl-1 H-pyrazol-4-yl)-2(piperidin-1-yl)ethyl)amino)-6-phenyl5,6,7,8-tetra-hydroquinazoline-2yl)amino)propyl hexacyclo-box-16\ NN ^Z. $ F ^ΊΓ . . 1 J. ^N^X / , l jl hn Ν N 'V! 1 OH 3Acid 3-((R)-1-(((R)-4-(((R)-1(1,5-dimethyl-1 H-pyrazol-4-yl)-2((S)-3-methylpiperidin-1yl)ethyl)amino)-6-(3-fluorophenyl)- 5,6,7,8-tetra-hydroquinazoline-2yl)(methyl)amino)propyl)bicyclo[1.1.1 ]pentane-1-carboxylic 47 \ NN Λ hn^O··, ^Cáv — N nX> Gold OH Acid (1R,4r)-4-((R)cyclopropyl(((R)-6-(3-fluorophenyl)4-(((R)-1-(1-methyl-1 H-pyrazole-4yl)-2-((S)-3-methylpiperidine-1yl)ethyl)amino)-5,6,7,8-tetrahydroquinazoline-2yl)(methyl)amino)methyl)cyclohexane-1-carboxylic 48 \ NN HN^O...Αάυ — ν Ν γη ' Oro OH Acid (1 R,4r)-4-((R)-1-(((R)-6-(2fluorophenyl)-4-(((R)-1-(1-methyl-1 Hpyrazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid. Petition 870260065188, dated 02 / 07 / 2026, page 38 / 516 34 / 236 Compound n° Structure Name 49 AIϊγ. H w OH Acid (1 R,4r)-4-((1 R)-1-(((6R)-4(((1R)-2-(8azabicycle[3.2.1 ]octan-8-yl)-1phenylethyl)amino)-6-phenyl-5,6,7,8tetra-hydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic 50 NN ó. XV OH Acid (1R,4r)-4-((R)-1-(((S)-4(((R)-1-(1-ethyl-1 H-pyrazol-4-yl)-2(piperidin-1-yl)ethyl)amino)-6-(3fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic 51 / NN _ Xr OH Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-(azepan-1-yl)-1-(1-methyl1H-pyrazol-4-yl)ethyl)amino)-6-phenyl5,6,7,8-tetra-hydroquinazolin-2propyloxyl)2cyclic-amino) \|-N Λ “Γ 11 W> 1 W OH Acid (1R,4r)-4-((R)-1-(((S)-4(((R)-2-((1S,5S)-9azabicycle[3.3.1 ]nonan-9-yl)-1-(1ethyl-1H-pyrazol-4-yl)ethyl)amino)-6(3-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic Petition 870260065188, dated 02 / 07 / 2026, p. 39 / 516 35 / 236 Compound n° Structure OR OH Nome Acid (1 R,4r)-4-((R)-1-(((R)-6-(3fluorophenyl)-4-(((R)-1-(1-methyl-6oxo-1,6-di-hydropyridin-3-yl)-2((S)-3-methylp iperidin-1yl)ethyl)amino)-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((S)-3(difluoromethyl)piperidin-1-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-(3-fluorophene il)-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic Acid (1R,4r)-4-((R)-1-((6-(3fluorophenyl)-4-(((R)-1-(1-methyl-1 Hpyrazol-4-yl)-2-(piperidin-1yl)ethyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2yl)amino)propyl)cyclo-hexane-1carboxylic (1R,4r)-4-((R)-1-(((R)-4(((R)-1-(1-methyl-1 H-pyrazol-4-yl)2-(piperidin-1-yl)ethyl)amino)-6phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic acid Petition 870260065188, 02 / 07 / 2026, p. 40 / 5 36 / 2 Compound No. Structure Name 57 / N'\ π c? Γ1 FX / NAAS rTl HN xx, NN Tf η ' Gold OH Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-(7azabicyclo[2.2.1 ]heptan-7-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-(3-fluorophenyl)-5,6,7,8-tetrahidroquinazolin-2yl)(methyl)amino)propyl)cyclohexano-1-carboxylic 58 / NN / / λ α Xo N Ν γΧ H x OH Ácido (1 R,4r)-4-((1 R)-1-(((6R)-4(((1R)-2-(2azabicycle[2.2.1 ]heptan-2-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-phenyl-5,6,7,8-tetrahidroquinazolin-2yl)amino)propyl)ciclo-hexano-1carboxílico 59 \ NN <7 >L χ—x / 7 L JL hn xCA < nn <X x OH Ácido (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((1S,5S)-9azabiciclo[3.3.1 ]nonan-9-il)-1-(1metil-1H-pirazol-4-il)etil)amino)6-fenil-5,6,7,8-tetrahidroquinazolin-2il)amino)propil)ciclo-hexano-1carboxílico 60 / N-N HN3'— xXx X° OH Ácido (1 R,4r)-4-((1 R)-1-(((6R)-4(((1R)-2-(8azabiciclo[3.2.1 ]octan-8-il)-1-(1metil-1H-pirazol-4-il)etil)amino)6-fenil-5,6,7,8-tetrahidroquinazolin-2il)amino)propil)ciclo-hexano-1carboxílico Petition 870260065188, dated 02 / 07 / 2026, p. 41 / 516 37 / 236 Compound n° Structure Name 61 / NN Z HN n bf η H ur° OH Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((3C,5R)-3,5dimethylpiperidin-1-yl)-1-(1-methyl1H-pyrazol-4-yl )ethyl)amino)-6-phenyl5,6,7,8-tetra-hydroquinazoline-2yl)amino)propyl)cyclo-hexane-1carboxylic 62 N-NZ Q HN^O roXvg ' Uro OH Acid (1 R,4r)-4-((1 R)-1-(((6R)-4(((1R)-2-(8azabiciclo[3.2.1 ]octane-8-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-(2-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexano-1-carboxylic acid 63 / NN ρ ρ UX γ ρ ρ γ γ (1R,4r)-4-((R)-1-(((R)-4(((R)-2-(7azabiciclo[2.2.1 ]heptan-7-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-(4-fluorophene yl)-5,6,7,8-tetrahydroquinazoline-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid 64 NN^ ΛΪΪΟ Ό ύο OH Acid (1R,4r)-4-((R)-1-(((R)-4-((R-1-()-1-(e) H-pyrazol-4-yl)-2((R)-2-methylpiperidin-1yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazoline-2yl)amino)propyl)cyclo-hexano-1carboxylic Petition 870260065188, of 02 / 07 / 2026, p. 42 / 516 38 / 236 Compound No. Structure Name Ácido (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((1S,5S)-9azabiciclo[3.3.1 ]nonan-9-yl)-1-(1ethyl-1H-pyrazol-4-yl)ethyl)amino)-6phenyl-5,6,7,8-tetrahidroquinazolin-2yl)amino)propyl)cyclo-hexano-1carboxílico Ácido (1 R,4r)-4-((R)-1-(methyl((R)6-methyl-4-(((R)-1-(1-methyl-1 Hpirazol-4-yl)-2-(piperidin-1yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2yl)amino)propyl)ciclo-hexano-1carboxylico 2Ácido 2-((1R,4r)-4-((R)-1(methyl((R)-4-(((R)-1-(1-methyl-1 Hpirazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)-6phenyl-5,6,7,8-tetrahidroquinazolin-2yl)amino)propyl)cyclo-hexyl)acetic acid (1 R,4r)-4-((1 R)-1-(((6R)-4(((1R)-2-(2azabicycle[2.2.1 ]heptan-2-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-methyl-6-phenyl-5,6,7,8-tetrahidroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Petition 870260065188, 02 / 07 / 2026, pág. 43 / 516 39 / 236 Compost No. Structure Name 3Acid 3-((1 S)-1-(((6R)-4-(((1 R)2-(8-azabicyclo[3.2.1]octan-8-yl)1 -(1-methyl-1 H-pyrazol-4yl)ethyl)amino)-6-methyl-6-phenyl5,6,7,8-tetra-hydroquinazolin-2yl)(methyl)amino)propyl)bicyclo[1.1.1]pentane-1-carboxylic Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-(7azabicyclo[2.2.1 ]heptan-7-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-methyl-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((5R,7R)-2-azaadamantan-2-yl)-1-(1-methyl-1 Hpyrazol-4-yl)ethyl)amino)-6-phenyl5,6,7,8-tetra-hydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic acid Acid (1 R,4r)-4-((R)-1-(((R)-6-(3fluorophenyl)-4-(((R)-2-((S)-3(hydroxymethyl)piperidin-1-yl)-1-(1methyl-1H-pyr azol-4-yl)ethyl)amino)5,6,7,8-tetra-hydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic Petition 870260065188, dated 02 / 07 / 2026, p. 44 / 516 40 / 236 Compound n° Structure Nome 73 ,N=\ A, hnÃnX XÚX Ν N i W OH Acid (1R,4r)-4-((R)-1-(((R)-4(((S)-2-((S)-3-methylpiperidin-1-yl)1-(4-methylthiazol-5-yl)ethyl)amino)-6phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic 74 \ NN Γ / 7 à ,n—\7 C jL hn L II 1x4 N 1 OH 3Acid 3-(1-(((R)-4-(((R)-2((1S,5S)-9- azabicyclo[3.3.1 ]nonan-9-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)-1l3propyl)bicyclo[1.1.1 ]pentane-1carboxylic 75 / NN Ó. X — / A / AZ 1 A OH Acid (1R,4r)-4-((R)-1-(((S)-6-(3fluorophenyl)-4-(((R)-1-(1-methyl-1 Hpyrazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)5,6,7,8-tetra-hydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic 76 \|-N Λ Ã-Ο·-. — iAi'Y''- OH Acid (1R,4r)-4-((R)-1-((4-(((R)1-(1-ethyl-1 H-pyrazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)-6(3-fluorophenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2yl)amino)propyl)cyclo-hexane-1carboxylic Petition 870260065188, dated 02 / 07 / 2026, page 45 / 516 41 / 236 Compound No. Structure Name 3Acid 3-((1 R)-1-(((6R)-4-(((1 S)2-(8-azabicyclo[3.2.1]octan-8-yl)1-(2-methylthiazol-5-yl)ethyl)amino)-6(3-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)bicyclo[1.1.1 ]pentane-1-carboxylic acid Acid (1R,4r)-4-((1 R)-1-(((6R)-4(((1R)-2-(3azabicyclo[4.1.0]heptan-3-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic Acid (1R,4r)-4-((1R)-1-(((6R)-4(((1R)-1-(1-ethyl-1H-pyrazol-4-yl)-2((1R,5S)-3-hydroxy-9azabicyclo[3.3.1 ]nonan-9yl)ethyl)amino)-6-(3-fluorophenyl)5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid (1R,4r)-4-((1R)-1-((4(((1R)-2-(8azabicyclo[3.2.1 ]octan-8-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-(4-fluorophenyl)-5,6,7,8-tetrahydropirido[4,3-d]pyrimidin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Petition 870260065188, 02 / 07 / 2026, pág. 46 / 516 42 / 236 Compound No. Structure Name Acid (1 R,4r)-4-((1 R)-1-(((6R)-4(((1S)-2-(8azabiciclo[3.2.1 ]octan-8-yl)-1-(2methylthiazol-5-yl)ethyl)amino)-6-(3fluorophenyl)-5,6,7,8-tetrahidroquinazolin-2yl)(methyl)amino)propyl)cyclohexano-1-carboxylic acid Ácido (1S,4s)-1-fluorc-4-((R)-1(metil((R)-4-(((S)-1-(1-metil-1 Hpirazol-4-yl)-2-((S)-3metilpiperidin-1-yl)ethyl)amino)-6fenil-5,6,7,8-tetrahidroquinazolin-2yl)amino)propyl)ciclo-hexano-1carboxylic acid Ácido (1R,4r)-4-((R)-1-(((R)-4((R)-2-((S)-3(metoximetil)piperidin-1-il)-1-(1metil-1H-pirazol-4-il)ethyl)amino)6-phenyl-5,6,7,8-tetrahydroquinazolin-2il)(metil)amino)propyl)cyclohexano-1-carboxylic Ácido (1R,4r)-4-((R)-1-(((R)-4(((R)-1-(1-metil-1 H-pirazol-4-il)2-((R)-3-metilpiperidin-1il)etil)amino)-6-fenil-5,6,7,8-tetrahidroquinazolin-2il)amino)propyl)ciclo-hexano-1carboxílico Petition 870260065188, dated 02 / 07 / 2026, p. 47 / 516 43 / 236 Compound no. Structure Name 85 H ΑΛ / OH 1f O (1R,4r)-4-((R)-1-(((R)-6phenyl-4-(((R)-1-phenyl-2-(pyrrolidin1-yl)ethyl)amino)-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1carboxylic acid 86 íA NNY 1 H w OH Acid (1 R,4r)-4-((1 R)-1-(((6R)-4(((1R)-2-(2azabicyclo[2.2.1 ]heptan-2-yl)-1-(4fluorophenyl)ethyl)amino)-6-phenyl5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1carboxylic 87 / NN η A XX N Ί 1 OH Acid 88 W \ / N / -\ H-pyrazol-3yl)ethyl)amino)-6-(3-fluorophenyl)5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Petition 870260065188, dated 02 / 07 / 2026, page 48 / 516 44 / 236 Compound No. Extrutura Nome 3Ácido 3-((R)-1-(((R)-4-(((R)-2((1S,5S)-9azabiciclo[3.3.1 ]nonan-9-il)-1(1,5-dimetil-1 H-pirazol-4il)etil)amino)-6-(3-fluorofenil)5,6,7,8-tetra-hidroquinazolin-2il)(metil)amino)propyl)biciclo[1.1.1 ]pentano-1-carboxylico Ácido (1R,4r)-4-((R)-1-(((R)-4(((R)-1-(1-metil-1 H-pirazol-4-il)2-((R)-2-metilpiperidin-1il)etil)amino)-6-fenil-5,6,7,8-tetrahidroquinazolin-2il)amino)propyl)ciclo-hexano-1carboxílico Ácido (1R,4r)-4-((R)-1-(((R)-4((R)-1-(1-etil-1H-pirazol-4-il)-2(piperidin-1-yl)ethyl)amino)-6-(3fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2il)(methyl)amino)propyl)cyclohexano-1-carboxylic Ácido (1R,4r)-4-((R)-1-(((R)-4((R)-2-((1S,5S)-9azabiciclo[3.3.1 ]nonan-9-il)-1-(1etil-1H-pirazol-4-yl)etil)amino)-6phenyl-5,6,7,8-tetrahydroquinazolin-2il)(methyl)amino)propyl)cyclohexano-1-carboxyilo Petition 870260065188, dated 02 / 07 / 2026, p. 49 / 516 45 / 236 Compost No. Structure Name (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((S)-3(hydroxymethyl)piperidin-1-yl)-1-(1-methyl-1H-pyrazol-4-yl)ethyl)amino)6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-(azepan-1-yl)-1-(1-ethyl-1Hpyrazol-4-yl)ethyl)amino)-6-phenyl5,6,7,8-tetra-hydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-(3,3-dimethylpiperidin-1-yl)1-(1-methyl-1H-pyrazol-4-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)amino)propyl)cyclohexane-1-carboxylic acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((R)-2-ethylpiperidin-1-yl)-1(1-methyl-1H-pyrazol-4-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)amino)propyl)cyclohexane-1-carboxylic acid (1R,4r)-4-((R)-1-(((R)-4(((R)-1-(1-cyclopropyl-1H-pyrazol4-yl)-2-(piperidin-1-yl)ethyl)amino)6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Petition 870260065188, dated 02 / 07 / 2026, p. 50 / 516 46 / 236 Compound No. Structure Name 98 / NN £[ J HN — — n ιι γ^ > 1 w OH Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((1 R,3R,5R,7R)-2-azaadamantan-2-methyl-1-1-1-1 Hpyrazol-4-yl)ethyl)amino)-6-phenyl5,6,7,8-tetra-hydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic 99 OA ð H LJ·., / OH 1f o Acid (1R,4r)-4-((R)-1-((6-(3fluorophenyl)-4-(((R)-1-phenyl-2(pyrrolidin-1-yl)ethyl)amino)-5,6,7,8tetra-hydropyrido[4,3-d]pyrimidin2-yl)amino)propyl-cyclo-hexanocarbon-100^N^ hn-—OHA OH Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-1-(1-isopropyl-1 H-pyrazol-4yl)-2-(piperidin-1-yl)ethyl)amino)-6phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexano-1carboxylic 101 / NN η Αθ' A / inc 1 A OH Acid (1 R,4r)-4-((R)-1-(methyl((S)4-(((R)-1-(1-methyl-1 H-pyrazol-4yl)-2-((S)-3-methylpiperidin-1yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexano-1carboxylic acid 102 / NN 77 Λ A XÔ 1 < 1 XXOH Acid ( R,4r)-4-((1 R)-1-(((6R)-4(((1R)-2-(8azabiciclo[3.2.1 ]octan-8-yl)-1(1,3-dimethyl-1H-pyrazol-4yl)ethyl)amino)-6-(3-fluorophenyl)5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid. Petition 870260065188, dated 02 / 07 / 2026, page 51 / 516 47 / 236 Compound No. Structure Name 103 104 105 Acid (1 R,4r)-4-((1 R)-1-(((6R)-4(((1R)-2-(8azabicyclo[3.2.1 ]octan-8-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-1-(1-ethyl-1 H-pyrazol-4-yl)-2((R)-2-(hydroxymethyl)piperidin-1yl)ethyl)amino)-6-(3-fluorophenyl)5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Acid (1R,4r)-4-((1R)-1-(((6R)-4(((1S)-2-(8azabicyclo[3.2.1 ]octan-8-yl)-1-(1methyl-1H-pyrazol-3-yl)ethyl)amino)6-(3-fluorophen il)-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Acid (1R,4r)-4-((R)-1-((6-(2fluorophenyl)-4-(((R)-1-(1-methyl-1 Hpyrazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)5,6,7,8-tetrahydropyrido[4,3d]pyrimidin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Petition 870260065188, dated 02 / 07 / 2026, page 52 / 516 48 / 236 Compound n° Structure Name 107 J yo — N η Uro OH Acid (1R,4r)-4-((1R)-1-(((6R)-4((1-(1-(fluoromethyl)-1 H-pyrazol-4yl)-2-((S)-3-methylpiperidin-1yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic 108 O / / ____1 ,nV L JL HN N Ν γη w OH Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((1S,5S)-9azabicyclo[3.3.1 ]nonan-9-yl)-1phenylethyl)amino)-6-phenyl-5,6,7,8tetra-hydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic 109 ( NN ηνΥνΧ^ L JL 1 ° Ζπχ — Ν Ν TX Oy OH Acid (1R,4r)-4-((1R)-1-(((6R)-4(((1R)-1-(1-ethyl-1). H-pyrazol-4-yl)-2(2-oxa-7-azaspiro[4,5]decan-7yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic 110 / NN XI ργχ hn^nCX 1 X OH Acid (1R,4r)-4-((R)-1-((6-(4fluorophenyl)-4-(((R)-1-(1-methyl-1 Hpyrazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)5,6,7,8-tetra-hydropyrido[4,3d]pyrimidin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic Petition 870260065188, dated 02 / 07 / 2026, p. 53 / 516 49 / 236 Compound No. Structure Name 111 N=^ Λ XÔ NN 1 tDk,OH O 3Acid 3-((1 R)-1-(((6R)-4-(((1 S)2-(8-azabicyclo[3.2.1]octan-8-yl)1-(2,4-dimethylthiazol-5yl)ethyl)amino)-6-(3-fluorophenyl)5,6,7,8-tetra-hydroquinazolin-2yl)(methyl)amino-1ocarboxyl][propylno1.1)bi 112 0 X / N—Ç / 7 p |Ί HN NN YY ' Gold OH Acid (1 R,4r)-4-((1 R)-1-(((6R)-4(((1 R)-2-((1 R,5S)-3-hydroxy-9azabicycle[3.3.1 ]nonan-9-yl)-1phenylethyl)amino)-6-phenyl-5,6,7,8tetra-hydroquinazoline-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic 113 ,N=\ A Xô xXa< nn 1 yX(1Xjoh 3 -ACID R)-1-(((6R)-4-(((1 S)2-(8-azabicyclo[3.2.1]octan-8-yl)1-(4-methylthiazol-5-yl)ethyl)amino)-6(3-fluorophenyl)-5,6,7,8-tetra- 2-hydroquinazolin il)(methyl)amino)propyl)bicycle[1 ]pentane-1-carboxylic 114 ZN=\ / -x / íx y L JL hn ^UÍAÂ^ N nX> H x OH Acid (1R,4r)-4-((R)-1-(((R)-4(((S)-1-(4-methylthiazol-5-yl)-2(piperidin-1-yl)ethyl)amino)-6-phenyl5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1carboxylic acid 115 n & moox o Acid (1R,4r)-4-((R)-1-(((S)-6phenyl-4-(((R)-1-phenyl-2-(pyrrolidin1-yl)ethyl)amino)-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1carboxylic. Petition 870260065188, dated 02 / 07 / 2026, p. 54 / 516 50 / 236 Compound n° Structure Name 116 NN A hÃ-0 ^^ζ'ΆΊι n A OH Acid (1R,4r)-4-((R)-1-(((S)-4(((R)-1-(1-ethyl-1). H-pyrazol-4-yl)-2(piperidin-1-yl)ethyl)amino)-6-(3fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic 117 ”~\|-N / 0H / A ry F Λ / 1 A zAZ Ν N > HW OH Acid (1R,4r)-4-((1R)-1-(((6R)-4(((1R)-1-(1-ethyl-1H-pyrazol-4-yl)-2((1R,5S)-3-hydroxy-9azabicyclo[3.3.1 ]nonan-9yl)ethyl)amino)-6-(3-fluorophenyl)5,6,7,8-tetra-hydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic 118 / NN hn^O VcA A ^^ N Νη 1 w OH Acid (1 R,4r)-4-((R)-1-(methyl((R)4-(((R)-1-(1-methyl-1 H-pyrazol-4yl)-2-(piperidin-1-yl)ethyl)amino)-6phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic 119 Ν V XS ^x hnAnJ XXa Or OH Acid (1R,4r)-4-((R)-1-(((R)-4(((S)-1-(2-methylthiazol-5-yl)-2(piperidin-1-yl)ethyl)amino)-6-phenyl5,6,7,8-tetra-hydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic Petition 870260065188, 02 / 07 / 2026, p. 55 / 5 51 / 2 Composite n° Structure Name 120 \ NN hnAO. v ''' / ήΑι'ΎΤ 1 w OH Acid (1R,4r)-4-((R)cyclopropyl(methyl((R)-4-(((R)-1-(1methyl-1H-pyrazol-4-yl)-2-((S)-3methylpiperidine- 1-yl)ethyl)amino)-6phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)methyl)cyclo-hexane-1carboxylic 121 / NN p, HH^'CT χών, Ν Ν IH kA / OH ΊΓ O Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-1-(1-methyl-1 H-pyrazol-4-yl)2-(4-methylpiperidin-1yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic 122 NN Q λΦ ^uò. A w OH Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((1R,4S)-2azabicyclo[2.2.1 ]heptan-2-yl)-1-(1ethyl-1H-pyrazol-4-yl)ethyl)amino)-6phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic 123 / NN p, hn^Q ^UÍAXk AND OH Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-1-(1-methyl-1 H-pyrazol-4-yl)2-((S)-2-methylpiperidin-1yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic Petition 870260065188, 02 / 07 / 2026, p. 56 / 5 52 / 236 Compost No. 124 Structure Name 125 126 127 Acid (1R,4r)-4-((R)-1-((6-(3fluorophenyl)-4-(((R)-1-(1-methyl-1 Hpyrazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)5,6,7,8-tetra-hydropyrido[4,3d]pyrimidin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic (1 R,4r)-4-((R)-1-(methyl((R)4-(((R)-1-(1-methyl-1 H-pyrazol-4yl)-2-((R)-3-methylpiperidin-1yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic acid (1R,4r)-4-((R)-1-(((R)-4(((R)-1-(1-ethyl-1H-pyrazol-4-yl)-2(6-azaspiro[3,5]nonan-6yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic acid Acid (1 R,4r)-4-((1 R)-1-(((6R)-4(((1S)-2-(8azabicyclo[3.2.1 ]octan-8-yl)-1-(2methylthiazol-4-yl)ethyl)amino)-6-(3fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1carboxylic Petition 870260065188, dated 02 / 07 / 2026, page 57 / 516 53 / 236 Compound No. Structure Name 128 129 130 131 Acid (1 R,4r)-4-((1 R)-1-(((6R)-4(((1R)-2-(2azabicyclo[2.2.1 ]heptan-2-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((S)-3-hydroxypiperidin-1yl)-1-(1-methyl-1H-pyrazol-4yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Acid (1S,4r)-4-((S)-1-(((S)-6-(3fluorophenyl)-6-methyl-4-(((R)-1-(1methyl-1H-pyrazol-4-yl)-2-((R)-3methylpiperidin-1-yl)ethyl)amino)5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1carboxylic (1R,4r)-4-((R)-1-((6-phenyl-4(((R)-1-phenyl-2-(pyrrolidin-1-yl)ethyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)amino)propyl)cyclohexane-1-carboxylic acid Petition 870260065188, dated 02 / 07 / 2026, page 58 / 516 54 / 236 Compound No. Structure Name 132 133 134 135 Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((1S,5S)-9azabicyclo[3.3.1 ]nonan-9-yl)-1-(1isopropyl-1 H-pyrazol-4yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1carboxylic acid Acid (1R,4r)-4-((R)-(((R)-4(((R)-2-((1S,5S)-9azabicyclo[3.3.1 ]nonan-9-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)(cyclopropyl)methyl)c cyclohexane-1-carboxylic acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((S)-3-methoxypiperidin-1yl)-1-(1-methyl-1H-pyrazol-4yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-1-(1-ethyl-1 H-pyrazol-4-yl)-2((S)-2-(hydroxymethyl)piperidin-1yl)ethyl)amino)-6-(3-fluorophenyl)5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Petition 870260065188, dated 02 / 07 / 2026, page 59 / 516 55 / 236 Compound No. 136 137 138 139 Structure Name (1R,4r)-4-((1R)-1-(((6R)-4(((1R)-2-(2azabicyclo[2.2.1 ]heptan-2-yl)-1phenylethyl)amino)-6-phenyl-5,6,7,8tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-(4,4-difluoroazepan-1-yl)1-(1-ethyl-1H-pyrazol-4yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1carboxylic acid Acid (1 R,4r)-4-((1 R)-1-(((6R)-4(((1 R)-2-((1 R,5S)-6-hydroxy-3azabicyclo[3.1. 1 ]heptan-3-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid (1R,4r)-4-((1R)-2-cyclopropyl-1-((6-phenyl-4-(((R)-1-phenyl-2-(pyrrolidin-1-yl)ethyl)amino)5,6,7,8-tetrahydroquinazoline-2-yl)amino)ethyl)cyclohexane-1-carboxylic acid Petition 870260065188, dated 02 / 07 / 2026, page 60 / 516 56 / 236 Compound No. 140 Structure Name 142 143 3Acid 3-(1-(((R)-4-(((S)-1-(1,3dimethyl-1H-pyrazol-5-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)-6phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)-1l3propyl)bicyclo[1.1.1 ]pentane-1carboxylic Acid (1R,4r)-4-((R)-1-(((S)-6-(2fluorophenyl)-4-(((R)-1-(1-methyl-1 Hpyrazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)5,6,7,8-tetra-hydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-(4-fluoropiperidin-1-yl)-1(1-methyl-1H-pyrazol-4yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((1S,5S)-9azabicyclo[3.3.1 ]nonan-9-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic Petition 870260065188, 02 / 07 / 2026, p. 61 / 5 57 / 2 Composite n° 144 145 146 147 148 Structure Name Acid (1 R,4r)-4-((1 R)-1-(((6R)-4(((1R)-2-(3-fluoro-3methylpiperidin-1-yl)-1-(1-methyl-1Hpyrazol-4-yl)ethyl)amino)-6-phenyl5,6,7,8-tetra-hydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic (1 R,4r)-4-((R)-1-(methyl((R)4-(((R)-1-(1-methyl-1 H-pyrazol-4yl)-2-(4-methylpiperidin-1yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic acid (1 R,4r)-4-((R)-1-(methyl((R)6-phenyl-4-(((R)-1-phenyl-2(pyrrolidin-1-yl)ethyl)amino)-5,6,7,8tetra-hydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic acid (1R,4r)-4-((R)-1-(((R)-4(((R)-1-(1-(cyclopropylmethyl)-1 Hpyrazol-4-yl)-2-(piperidin-1-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid (1R,4r)-4-((R)-1-(((R)-4(((R)-1-(1-ethyl-6-oxo-1,6-dihydropyridin-3-yl)-2-(piperidin-1yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Petition 870260065188, dated 02 / 07 / 2026, p. 62 / 516 58 / 236 Compound No. Structure Name 149 150 152 (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((R)-2(hydroxymethyl)piperidin-1-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-(4,4-difluoroazepan-1-yl)1 -(1-methyl-1H-pyrazol-4yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-(4-methoxypiperidin-1-yl)-1(1-methyl-1H-pyrazol-4yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1carboxylic Acid (1 R,4r)-4-((R)-1-((6-cyclohexyl-4-(((R)-1-(1-methyl-1Hpyrazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)5,6,7,8-tetrahydropyrido[4,3d]pyrimidin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic Petition 870260065188, dated 02 / 07 / 2026, page 63 / 516 59 / 236 Compound No. Structure Name 153 154 155 156 157 4Acid 4-((R)-1-(((R)-4-(((R)-2((1S,5S)-9azabicyclo[3.3.1 ]nonan-9-yl)-1-(1ethyl-1H-pyrazol-4-yl)ethyl)amino)-6(3-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2yl)amino)ethyl)benzoic (1R,4r)-4-((R)-1-(((R)-4(((R)-1-(1-ethyl-1 H-pyrazol-4-yl)-2(4-hydroxypiperidin-1yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid 3Acid 3-((R)-1-(((R)-6-(3fluorophenyl)-4-(((S)-1-(1-methyl-1 Hpyrazol-5-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)5,6,7,8-tetra-hydroquinazolin-2yl)(methyl)amino)propyl)bicyclo[1.1.1 ]pentane-1-carboxylic acid (1R,4r)-4-((1R)-1-(((6R)-4(((1R)-2-(3-fluoropiperidin-1-yl)-1(1-methyl-1H-pyrazol-4yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid (1R,4r)-4-((R)-1-((6-(3fluorophenyl)-4-(((R)-1-(1-methyl-1Hpyrazol-4-yl)-2-(piperidin-1yl)ethyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Petition 870260065188, dated 02 / 07 / 2026, page 64 / 516 60 / 236 Compound No. Structure Name 158 159 160 (1S,4r)-4-((1S)-1-((6-phenyl4-(((R)-1-phenyl-2-(pyrrolidin-1yl)ethyl)amino)-5,6,7,8-tetrahydroquinazolin-2yl)amino)ethyl)cyclohexane-1carboxylic acid 161 162 44-((R)-1-(((R)-6-phenyl-4(((R)-1-phenyl-2-(pyrrolidin-1yl)ethyl)amino)-5,6,7,8-tetrahydroquinazolin-2yl)amino)ethyl)benzoic acid (1R,4r)-4-((1R)-1-(((6R)-4(((1R)-2-(2azabicyclo[2.2.1 ]heptan-2-yl)-1phenylethyl)amino)-6-phenyl-5,6,7,8tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1carboxylic acid Acid (1R,4r)-4-((R)-1-(((R)-6-(3fluorophenyl)-4-(((S)-1-(1-methyl-1 Hpyrazol-5-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Acid (1 R,4r)-4-((1 R)-1-(((6R)-4(((1 R)-1-(1-ethyl-1 H-pyrazol-4-yl)-2(2-oxa-7-azaspiro[4.5]decan-7yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Petition 870260065188, dated 02 / 07 / 2026, page 65 / 516 61 / 236 Composto n° Estrutura Nome 163 ^NN Λ Ã F = ü HN''—N—Άη AoA a. nn τη Oro OH Ácido (1R,4r)-4-((R)-1-(((R)-4(((R)-1-(1-etil-1 H-pirazol-4-il)-2((S)-3-hidroxipiperidin-1il)etil)amino)-6-(3-fluorofenil)5,6,7,8-tetra-hidroquinazolin-2il)(metil)amino)propyl)ciclohexano-1-carboxílico 164 rS z- / a \ iy= / Ácido (1 R,4r)-4-((1 R)-1-(((6R)-4(((1S)-2-(8azabiciclo[3.2.1 ]octan-8-yl)-1-(1methyl-1H-pyrazol-5-yl)ethyl)amino)6-(3-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic 165 OQ hnAA — NN ηρ η H LA , XOH lí o (1R,4r)-4-((R)-1-(((R)-4(((R)-2-(dimethylamino)-1phenylethyl)amino)-6-phenyl-5,6,7,8tetra-hydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic acid 166 O Ξ H HN^Ny^ AA--yAN \ k—o H U-γΟ OH (1R,4r)-4-((R)-1-(((R)-6phenyl-4-(((R)-1-pheny acid l-2-((tetrahydro-2H-pyran-4yl)amino)ethyl)amino)-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic 167 FF~Í~F NN hnà / O xAG ^'Tl Ν^ΤΊ Uro OH Acid (1 R,4r)-4-((R)-1-(methyl((R)6-phenyl-4-(((R)-2-(piperidin-1-yl)-1(1-(2,2,2-trifluoroethyl)-1 H-pyrazol4-yl)ethyl)amino)-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclo-hexane-1carboxylic. Petition 870260065188, 02 / 07 / 2026, p. 66 / 5 62 / 2 Compound No. Structure Name 168 \-N 1 ,nv HN OH 4Ácido 4-((R)-1-(((R)-4-(((R)-2((1S,5S)-9azabiciclo[3.3.1 ]nonan-9-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-phenyl-5,6,7,8-tetra- hidroquinazolin-2-yl)amino)ethyl)-2fluorobenzoico 169 \“N o XX HN —nn ηρ η ' L___ OH Ácido (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((1R,5S)-3-oxa-9azabiciclo[3.3.1 ]nonan-9-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)6-phenyl-5,6,7,8-tetrahidroquinazolin-2yl)(methyl)amino)propyl)cyclohexano-1-carboxylic acid 170 \-N Λ \\ Cl ΑΊ à -------- a 1 OH Ácido (1R,4r)-4-((R)-1-((6-(3chlorophenyl)-4-(((R)-1-(1-methyl-1 Hpyrazol-4-yl)-2-((S)-3metilpiperidin-1-yl)ethyl)amino)5,6,7,8-tetra-hidroprido[4,3d]pirimidin-2yl)(methyl)amino)propyl)cyclohexano-1-carboxylic acid 171 ^NN hnÃ-nO χΑ OH 4Ácido 4-((R)-1-(((R)-4-(((R)-1(1-isopropyl-1 H-pyrazol-4-yl)-2(piperidin-1-yl)ethyl)amino)-6-phenyl5,6,7,8-tetra-hidroquinazolin-2yl)amino)ethyl)benzoic acid Petition 870260065188, 02 / 07 / 2026, pág. 67 / 516 63 / 236 Compound No. Structure Name 172 173 174 175 3Ácido 3-((R)-1-(((R)-4-(((S)-2((1R,5R)-9azabiciclo[3.3.1 ]nonan-9-yl)-1-(1metil-1H-pyrazol-5-yl)ethyl)amino)6-fenil-5,6,7,8-tetrahidroquinazolin-2il)(metil)amino)propyl)biciclo[1.1.1 ]pentane-1-carboxylic Ácido (1 R,4r)-4-((R)-1-(methyl((R)4-(((R)-2-methyl-1-(1-methyl-1 Hpirazol-4-yl)-2-(piperidin-1yl)propyl)amino)-6-phenyl-5,6,7,8tetra-hidroquinazolin-2yl)amino)propyl)ciclo-hexano-1carboxylico Acid (1R,4r)-4-((R)-1-((6-(3cyanophenyl)-4-(((R)-1-(1-methyl-1 Hpirazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)5,6,7,8-tetra-hidropyrido[4,3d]pyrimidin-2yl)(methyl)amino)propyl)ciclohexano-1-carboxylico Acid (1R,4r)-4-((1R)-1-(((6R)-4(((1R)-2-(3-(fluoromethyl)piperidin1-yl)-1-(1-methyl-1 H-pyrazol-4yl)ethyl)amino)-6-(3-fluorophenyl)5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1carboxylic acid Petition 870260065188, dated 02 / 07 / 2026, page 68 / 516 64 / 236 Compound No. Structure Name 177 178 179 Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((1R,6S)-2azabicyclo[4.1.0]heptan-2-yl)-1-(1methyl-1H-pyrazol-4-yl )ethyl)amino)6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((1S,6R)-2azabicyclo[4.1.0]heptan-2-yl)-1-(1methyl-1H-pyrazol-4-yl )ethyl)amino)6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((R)-3-ethyl-3hydroxypiperidin-1-yl)-1-(1-methyl1H-pyrazol-4-yl)ethyl)amino)-6-phenyl5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((3R,4R)-4-hydroxy-3methylpiperidin-1-yl)-1-(1-methyl-1Hpyrazol-4-yl )ethyl)amino)-6-phenyl5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Petition 870260065188, dated 02 / 07 / 2026, page 69 / 516 65 / 236 Compound No. Structure Name 180 (1R,4r)-4-((R)-1-(methyl((R)4-(((R)-1-(1-methyl-1H-pyrazol-4yl)-2-(5-azaspiro[2,5]octan-5yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1carboxylic acid 181 182 (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((R)-3-methoxypyrrolidin-1yl)-1-(1-methyl-1H-pyrazol-4yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((R)-3-hydroxy-3methylpiperidin-1-yl)-1-(1-methyl-1Hpyrazol-4-yl)ethyl)amino)-6-phenyl5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic 183 184 Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((3R,5R)-3-methoxy-5methylpiperidin-1-yl)-1-(1-methyl-1Hpyrazol-4-yl) ethyl)amino)-6-phenyl5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Acid (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((3S,5S)-3-methoxy-5methylpiperidin-1-yl)-1-(1-methyl-1Hpyrazol-4-yl) ethyl)amino)-6-phenyl5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid Petition 870260065188, dated 02 / 07 / 2026, page 70 / 516 66 / 236 Compound No. Structure Name 185 186 Acid (1R,4r)-4-((R)-1-(((R)-4(((S)-1-(3-fluoro-1-methyl-1Hpyrazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)-6phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic (1R,4r)-4-((R)-1-(((R)-4(((R)-2-((S)-3-hydroxy-3-methylpiperidin-1-yl)-1-(1-methyl-1Hpyrazol-4-yl)ethyl)amino)-6-phenyl5,6,7,8-tetra-hydroquinazolin-2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid

[0042] As used in this document, the terms salt or salts refer to an acid addition salt or a basic addition salt of a compound of the present invention. Salts include in particular pharmaceutically acceptable salts. The term pharmaceutically acceptable salts refers to salts that retain the biological efficacy and properties of the compounds of this description and that are typically not biologically or otherwise undesirable. In many cases, the compounds of the present invention have the capacity to form acidic and / or basic salts by virtue of the presence of amino and / or carboxyl groups or groups similar thereto. When both a basic group and an acidic group are present in the same molecule, the compounds of the present invention can also form internal salts, for example, zwitterionic molecules.

[0043] Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and organic acids.

[0044] The inorganic acids from which salts can be derived Petition 870260065188, dated 02 / 07 / 2026, page 71 / 516 67 / 236 of these include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and similar substances.

[0045] Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, toluenesulfonic acid, sulfosalicylic acid and the like.

[0046] Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases.

[0047] Inorganic bases from which salts can be derived include, for example, ammonium salts and metals from columns I to XII of the periodic table. In certain embodiments, salts are derived from sodium, potassium, ammonium, calcium, magnesium, iron, silver, zinc, and copper; particularly suitable salts include ammonium, potassium, sodium, calcium, and magnesium salts.

[0048] Organic bases from which salts can be derived include, for example, primary, secondary and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins and the like. Certain organic amines include isopropylamine, benzathine, choline, diethanolamine, diethylamine, lysine, meglumine, piperazine and tromethamine.

[0049] In another aspect, the present invention provides compounds of the present invention in the form of acetate, ascorbate, adipate, aspartate, benzoate, besylate, bromide / bromide hydrochloride, bicarbonate / carbonate, bisulfate / sulfate, camphorsulfonate, caprate, chloride / hydrochloride, chlorophyllonate, citrate, ethandisulfonate, fumarate, gluceptate, gluconate, glucuronate, glutamate, glutarate, glycolate, hippurate, iodide hydrochloride / iodide, isethionate, lactate, lactobionate, lauryl sulfate, malate, salts. Petition 870260065188, dated 02 / 07 / 2026, page 72 / 516 68 / 236 maleate, malonate, mandelate, mesylate, methyl sulfate, mucate, naphthoate, napsylate, nicotinate, nitrate, octadecanoate, oleate, oxalate, palmitate, pamoate, phosphate / hydrogen phosphate / dihydrogen phosphate, polygalacturonate, propionate, sebacate, stearate, succinate, sulfosalicylate, sulfate, tartrate, tosylate, trifenatate, trifluoroacetate or xinafoate.

[0050] Any formula provided herein is intended to represent both unlabeled and isotopically labeled forms of the compounds. Isotopically labeled compounds have structures illustrated by the formulas provided herein, except that one or more atoms are replaced by an atom having a selected atomic mass or mass number. Isotopes that may be incorporated into compounds of the description include, for example, isotopes of hydrogen.

[0051] Additionally, the incorporation of certain isotopes, particularly deuterium (i.e., 2H or D), can lead to certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements or an improvement in the therapeutic index or tolerability. Deuterium in this context is understood to be a substituent for a compound of the present invention. The deuterium concentration can be defined by the isotopic enrichment factor. The term isotopic enrichment factor, as used herein, means the ratio between the isotopic abundance and the natural abundance of a specific isotope.If a substituent in a compound of the present invention is denoted as deuterium, such compound has an isotopic enrichment factor for each designated deuterium atom of at least 3500 (52.5% deuterium incorporation in each designated deuterium atom), at least 4000 (60% deuterium incorporation), or at least 4500 (67.5% deuterium incorporation). Petition 870260065188, dated 02 / 07 / 2026, page 73 / 516 69 / 236 deuterium), at least 5000 (75% deuterium incorporation), at least 5500 (82.5% deuterium incorporation), at least 6000 (90% deuterium incorporation), at least 6333.3 (95% deuterium incorporation), at least 6466.7 (97% deuterium incorporation), at least 6600 (99% deuterium incorporation), or at least 6633.3 (99.5% deuterium incorporation). It should be understood that the term isotopic enrichment factor can be applied to any isotope in the same way as described for deuterium.

[0052] Other examples of isotopes that may be incorporated into compounds of the description include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine, such as 3H, 11C, 13C, 14C, 15N, 18F, 31P, 32P, 35S, 36Cl, 123I, 124I, 125I, respectively. Consequently, it should be understood that the description includes compounds incorporating one or more of any of the isotopes mentioned above, which include, for example, radioactive isotopes such as 3H and 14C, or those in which non-radioactive isotopes such as 2H and 13C are present. Such isotopically labeled compounds are useful in metabolic studies (with 14C), kinetic reaction studies (with, for example, 2H or 3H), detection or visualization techniques, such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT), including drug or substrate distribution assays in tissues or in the radioactive treatment of patients.In particular, a labeled or isotopically labeled compound may be particularly desirable for PET or SPECT studies. The isotopically labeled compounds of the present invention can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described in the accompanying Examples and Preparations using an appropriate isotopically labeled reagent in place of the unlabeled reagent. Petition 870260065188, dated 02 / 07 / 2026, page 74 / 516 70 / 236 previously used.

[0053] Any asymmetric atom (e.g., carbon or similar) of the compound (or compounds) of the present invention may be present in a racemic or enantiomerically enriched configuration, for example, (R)-, (S)- or (R,S)-. In certain embodiments, each asymmetric atom has at least 50% enantiomeric excess, at least 60% enantiomeric excess, at least 70% enantiomeric excess, at least 80% enantiomeric excess, at least 90% enantiomeric excess, at least 95% enantiomeric excess or at least 99% enantiomeric excess in the (R) or (S) configuration. Substituents on atoms with unsaturated double bonds may, if possible, be present in the cis (Z) or trans (E) form.

[0054] Thus, as used in the present document, a compound of the present invention may be in the form of one of the possible stereoisomers, rotamers, atropisomers, tautomers or mixtures thereof, for example, as substantially pure geometric stereoisomers (cis or trans), diastereomers, optical isomers (antipodes), racemates or mixtures thereof.

[0055] Any mixtures resulting from stereoisomers can be separated based on the physicochemical differences of the constituents, into pure or substantially pure geometric or optical isomers, diastereomers, racemates, for example, by chromatography and / or fractional crystallization.

[0056] Any racemates resulting from compounds of the present invention or from intermediates can be resolved at the optical antipodes by known methods, for example, by separating the diastereomeric salts thereof, obtained with an optically active acid or base, and releasing the optically active acidic or basic compound. In particular, a basic chemical moiety can, Petition 870260065188, dated 02 / 07 / 2026, p. 75 / 516 71 / 236 thus, be used for the resolution of the compounds of the present invention at their optical antipodes, for example, by fractional crystallization of a salt formed with an optically active acid, for example, tartaric acid, dibenzoyl tartaric acid, diacetyl tartaric acid, di-O,O'-p-tolyl tartaric acid, mandelic acid, malic acid or camphor-10-sulfonic acid. The racemic compounds of the present invention or racemic intermediates can also be resolved by chiral chromatography, for example, high-performance liquid chromatography (HPLC) with the use of a chiral adsorbent. Pharmaceutical Compositions

[0057] In another aspect, the present invention provides a pharmaceutical composition comprising a compound of the present invention, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers. In a further embodiment, the composition comprises at least two pharmaceutically acceptable carriers, such as those described herein.

[0058] In some embodiments, a pharmaceutical composition further comprises at least one additional pharmaceutically active agent. In some embodiments, the additional pharmaceutically active agent is selected from an ACE (angiotensin-converting enzyme) inhibitor, an angiotensin receptor blocker (ARB), a neprilysin inhibitor, a beta-blocker, a diuretic, a calcium channel blocker, a cardiac glycoside, a sodium-glucose cotransporter 2 (SGLT2i) inhibitor, or combinations thereof.

[0059] The pharmaceutical composition may be formulated for particular routes of administration, such as oral administration, parenteral administration (e.g., by injection, infusion, transdermal or topical administration) and rectal administration. Topical administration may also refer to inhalation or intranasal application. The composition Petition 870260065188, dated 02 / 07 / 2026, page 76 / 516 72 / 236 Pharmaceutical compositions of the present invention may be manufactured in a solid form (including, without limitation, capsules, tablets, pills, granules, powders or suppositories) or in a liquid form (including, without limitation, solutions, suspensions or emulsions). Tablets may be film-coated or enteric-coated according to methods known in the art. Typically, the pharmaceutical compositions are gelatin tablets or capsules comprising the active ingredient together with one or more of the following: a) diluents, for example, lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and / or glycine; b) lubricants, for example, silica, talc, stearic acid, its magnesium or calcium salt and / or polyethylene glycol; for tablets also c) binders, for example, magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidone; if desired d) disintegrants, for example, starches, agar, alginic acid or its sodium salt, or effervescent mixtures; and e) absorbents, colorants, flavorings and sweeteners.

[0060] Liquid compositions, particularly injectable ones, can, for example, be prepared by dissolution, dispersion, etc. For example, the disclosed compound is dissolved in or mixed with a pharmaceutically acceptable solvent such as, for example, water, saline solution, aqueous dextrose, glycerol, ethanol and the like, to form an injectable isotonic solution or suspension. Proteins, such as albumin, chylomicron particles or serum proteins, can be used to solubilize the disclosed compounds.

[0061] The disclosed compounds can also be formulated as a suppository which can be prepared from emulsions or Petition 870260065188, dated 02 / 07 / 2026, page 77 / 516 73 / 236 greasy suspensions; using polyalkylene glycols, such as propylene glycol, as carriers.

[0062] Parenteral injectable administration is generally used for subcutaneous, intramuscular, or intravenous injections and infusions. Injectables may be prepared in conventional forms such as liquid solutions or suspensions, or in solid forms to be dissolved in liquid before injection.

[0063] The compositions can be prepared according to conventional mixing, granulation or coating methods, respectively, and the present pharmaceutical compositions may contain from about 0.1% to about 99%, from about 5% to about 90%, or from about 1% to about 20% of the disclosed compound by weight or volume.

[0064] The dosage regimen using the disclosed compound is selected according to a variety of factors including type, species, age, weight, sex and medical condition of the patient; the severity of the condition being treated; the route of administration; the renal or hepatic function of the patient; and the particular disclosed compound used. A physician or veterinarian of ordinary skill in the art can readily determine and prescribe the effective amount of the drug needed to prevent, counteract or halt the progression of the condition.

[0065] The pharmaceutical composition or combination of the present invention may, for example, be in a unit dosage of approximately 11,000 mg of active ingredient(s) for an individual weighing approximately 50-70 kg. In one embodiment, the compositions are in the form of a tablet that can be scored. The therapeutically effective dosage of a compound, pharmaceutical composition, or combinations thereof, is dependent on the individual's species, body weight, age, and individual condition, disorder or disease, or its severity being treated. Petition 870260065188, dated 02 / 07 / 2026, page 78 / 516 74 / 236 Methods of use

[0066] In yet another aspect, the present invention relates to a method for treating or preventing a disease or disorder comprising administering to a patient in need thereof an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0067] In another aspect, the present invention relates to a method for treating a disease or disorder comprising administering to a patient in need thereof an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein the disease or disorder is a cardiovascular disease or disorder.

[0068] In certain modalities, the cardiovascular disease or disorder is selected from among hypertension, peripheral vascular disease, heart failure, coronary artery disease (CAD), ischemic heart disease (IHD), mitral stenosis and regurgitation, angina, hypertrophic cardiomyopathy, diabetic cardiomyopathy, supraventricular and ventricular arrhythmias, cardiac dysrhythmia, atrial fibrillation (AF), new-onset atrial fibrillation, recurrent atrial fibrillation, cardiac fibrosis, atrial flutter, detrimental vascular remodeling, plaque stabilization, and myocardial infarction (MI). In some modalities, heart failure is selected from heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), heart failure after acute myocardial infarction, or acute decompensated heart failure. In some Petition 870260065188, dated 02 / 07 / 2026, page 79 / 516 75 / 236 but modalities, hypertrophic cardiomyopathy is ventricular hypertrophy. In some modalities, hypertension is selected from resistant hypertension, hypertensive heart disease, pulmonary hypertension, pulmonary arterial hypertension, isolated systolic hypertension, resistant hypertension, and pulmonary arterial hypertension. In some modalities, hypertension is selected from resistant hypertension and hypertensive heart disease.

[0069] In some modalities, the disease or disorder is preeclampsia, asthma, glaucoma, a renal disorder, and / or cytokine release syndrome in an individual requiring such treatment. In some modalities, the renal disorder is selected from among: diabetic renal failure, non-diabetic renal failure, renal failure, diabetic nephropathy, non-diabetic nephropathy, acute kidney injury, contrast-induced nephropathy, nephrotic syndrome, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, renal vascular hypertension, diabetic retinopathy and end-stage renal disease (ESRD), endothelial dysfunction, diastolic dysfunction, renal fibrosis, and polycystic kidney disease (PKD).

[0070] In some modalities, the disease or disorder is a disorder or disease associated with natriuretic peptide receptor activity.

[0071] In another aspect, the present invention relates to the use of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition described herein for the manufacture of a medicament for use in treating a disease or disorder disclosed herein.

[0072] In another aspect, the present invention relates to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition described herein for use as a medicament. Petition 870260065188, dated 02 / 07 / 2026, p. 80 / 516 76 / 236

[0073] Another aspect of the present invention relates to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition described herein for use in the treatment of a disease or disorder disclosed herein. In some embodiments, the disease or disorder is a cardiovascular disease or disorder (for example, a cardiovascular disease or disorder as disclosed herein).

[0074] In another aspect, the present invention relates to the use of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition described herein in the treatment of a disease or disorder disclosed herein.

[0075] The compounds disclosed in the description can be administered in amounts effective in treating or preventing a disorder and / or preventing its development in individuals. Combination Therapy

[0076] The compounds described can be administered in therapeutically effective amounts in combination therapy with one or more pharmaceutically active agents (pharmaceutical combinations) or modalities, for example, non-drug therapies. The compounds of the present invention can be administered simultaneously with, or before or after, one or more other pharmaceutically active agents. The compound of the present invention can be administered separately, by the same route of administration or by a different route of administration, or together in the same pharmaceutical composition as the other agents. A pharmaceutically active agent is, for example, a chemical compound, peptide, antibody, antibody fragment or nucleic acid, which is therapeutically active or enhances therapeutic activity when administered to a patient. Petition 870260065188, dated 02 / 07 / 2026, page 81 / 516 77 / 236 in combination with a compound of the present invention.

[0077] In one embodiment, the description provides a product comprising a compound of the present invention and at least one pharmaceutically active agent as a combined preparation for simultaneous, separate or sequential use as disclosed herein. Products provided as a combined preparation include a composition comprising the compound of the present invention and the other pharmaceutically active agent (or agents) together in the same pharmaceutical composition as described herein or the compound of the present invention and the other pharmaceutically active agent (or agents) in separate form, for example, in the form of a kit.

[0078] In another aspect, the description includes a compound of Formula (I), or a pharmaceutically acceptable salt thereof, for use in a combination therapy.

[0079] Another aspect of the description refers to pharmaceutical compositions comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable carrier and one or more pharmaceutically acceptable agents. The pharmaceutically acceptable carrier may additionally include an excipient, a diluent or a surfactant.

[0080] Combination therapy involves administering the compounds in question in additional combination with other biologically active ingredients. For example, the compounds in question may be used in combination with other pharmaceutically active agents, preferably compounds that have the ability to enhance the effect of the compounds in question. The compounds in question may be administered simultaneously (as a single preparation or a separate preparation) or sequentially to another drug therapy or treatment modality. In general, a combination therapy Petition 870260065188, dated 02 / 07 / 2026, p. 82 / 516 78 / 236 refers to the administration of two or more medications during a single cycle or course of therapy.

[0081] Additional exemplary pharmaceutically active agents that may be used in combination with the compounds described include, but are not limited to, an ACE (angiotensin-converting enzyme) inhibitor, an angiotensin receptor blocker (ARB), a neprilysin inhibitor, a beta-blocker, a diuretic, a calcium channel blocker, a cardiac glycoside, a sodium-glucose cotransporter 2 (SGLT2i) inhibitor, or combinations thereof.As a non-limiting set of examples, a compound, or a pharmaceutically acceptable salt thereof, described herein may be combined with an additional pharmaceutically active agent selected from enalapril, benazepril, captopril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril, valsartan, azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, sacubitril, bisoprolol, carvedilol, propranolol, metoprolol, metoprolol tartrate, metoprolol succinate, thiazide diuretics, loop diuretics, potassium-sparing diuretics, amlodipine, clevidipine, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nisoldipine, verapamil, a digitalis glycoside, canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and combinations thereof.Exemplary diuretics and digitalis glycosides include, but are not limited to, chlorthalidone, hydrochlorothiazide, indapamide, metolazone, bumetanide, ethacrynic acid, furosemide, torsemide, amiloride, eplerenone, spironolactone, triamterene, digoxin, and combinations thereof. In some embodiments, a compound, or a pharmaceutically acceptable salt thereof, described herein may be combined with an angiotensin-neprilysin receptor (ARNi) inhibitor, such as a combination of sacubitril and valsartan (e.g., Entresto®). In some mo. Petition 870260065188, dated 02 / 07 / 2026, page 83 / 516 79 / 236 dalities, a compound, or a pharmaceutically acceptable salt thereof, described herein may be combined with one or more of the following: a corticosteroid (for example, an inhaled corticosteroid such as fluticasone, budesonide, mometasone, beclomethasone, ciclesonide or fluticasone furoate; or an oral or intravenous corticosteroid such as prednisone or methylprednisolone), a leukotriene modifier (for example, montelukast, zafirlukast or zileuton), a bronchodilator (for example, a long-acting beta-agonist (for example, salmeterol or formoterol), a short-acting beta-agonist (for example, albuterol or levalbuterol), theophylline or ipratropium) or combinations thereof (for example, a combination of fluticasone and salmeterol, a combination of budesonide and formoterol or a (combination of formoterol and mometasone).In some embodiments, a compound, or a pharmaceutically acceptable salt thereof, described herein may be combined with one or more of a beta-adrenergic receptor antagonist (e.g., timolol, levobunolol, metipranolol, carteolol or betaxolol), a carbonic anhydrase inhibitor (e.g., acetazolamide, dorzolamide, brinzolamide or methazolamide), an alpha 2-adrenergic receptor agonist (e.g., brimonidine or apraclonidine), a parasympathomimetic (e.g., cholinomimetics such as pilocarpine), a prostaglandin analogue (e.g., latanoprost, latanoprosteno bunode, travoprost, bimatoprost or tafluprost), a rho kinase inhibitor (e.g., netarsudil or ripasudil) or combinations thereof (e.g., a combination of rho kinase inhibitor and latanoprost).

[0082] Combination therapy is intended to encompass the administration of these therapeutic agents in a sequential manner, where each therapeutic agent is administered at a different time and in any order, or in alternation and in any order, as well Petition 870260065188, dated 02 / 07 / 2026, page 84 / 516 80 / 236 such as the administration of these therapeutic agents, or at least two of the therapeutic agents, in a substantially simultaneous manner. Substantially simultaneous administration may be achieved, for example, by administering to the individual a single capsule containing a fixed proportion of each therapeutic agent or in multiple single capsules for each of the therapeutic agents. Sequential or substantially simultaneous administration of each therapeutic agent may be effected by any appropriate route including, without limitation, oral routes, intravenous routes, intramuscular routes and direct absorption through mucous membrane tissues. The therapeutic agents may be administered by the same route or by different routes. For example, a first therapeutic agent of the selected combination may be administered by intravenous injection, while the other therapeutic agents of the combination may be administered orally.Alternatively, for example, all therapeutic agents may be administered orally, or all therapeutic agents may be administered by intravenous injection. The sequence in which the therapeutic agents are administered is not strictly critical. Method of Synthesis of the Compounds (I stopped at page 59)

[0083] The compounds of the present invention can be produced by a variety of methods, including standard chemistry. Suitable synthetic routes are represented in the Schemes given below.

[0084] Compounds of Formula (I) can be prepared by methods known in the art of organic synthesis as set out in part by the following synthesis schemes. In the schemes described below, it is understood that protecting groups for sensitive or reactive groups are used when necessary in accordance with general principles or chemistry. The protecting groups are handled according to standard methods of organic synthesis (TW Greene and Petition 870260065188, dated 02 / 07 / 2026, page 85 / 516 81 / 236 PGM Wuts, Protective Groups in Organic Synthesis, Third Edition, Wiley, New York, USA, 1999). These groups are removed at a convenient stage of compound synthesis using methods that are readily apparent to those skilled in the art. The selection processes, as well as the reaction conditions and the order of their execution, should be consistent with the preparation of compounds of Formula (I).

[0085] Those skilled in the art will recognize whether a stereocenter exists in the compounds of Formula (I). Consequently, the present invention includes both possible stereoisomers (unless specified in the synthesis) and includes not only racemic compounds, but the individual enantiomers and / or diastereomers as well. When it is desired that a compound be a single enantiomer or diastereomer, the same can be obtained by stereospecific synthesis or by resolution of the final product or any convenient intermediate. Resolution of the final product, an intermediate, or a starting material can be effected by any suitable method known in the art. See, for example, Stereochemistry of Organic Compounds by EL Eliel, SH Wilen, and LN Mander (Wiley-Interscience, 1994).

[0086] The compounds described in this document can be produced from commercially available starting materials or synthesized using known organic, inorganic and / or enzymatic processes. General reaction schemes 1 where A, Raa Rde R4a R7 are defined in this document (Petition 870260065188, dated 02 / 07 / 2026, page 86 / 516). 82 / 236 ra a Formula (I).

[0087] A general scheme for preparing compounds of Formula (I) is described in General Reaction Scheme IIa: CO cross-coupling step, for example: DIPEA, MeCN, 80 °C, 40 h; Ib, CN cross-coupling step, for example: DIPEA, MeCN, 100 °C, 72 h; Ic, CN cross-coupling step followed by hydrolysis, for example: DIPEA, i-PrOH, 110 °C, 48 h, purification, then treated with aqueous 4 N NaOH solution in THF / MeOH. Step Ia: a compound of formula INT-(II) can be prepared by reacting a compound of formula INT-(I) with 2,3,5,6-tetrafluorophenol and a base, such as DIPEA, in a suitable solvent, such as MeCN, at a temperature of 80 °C for 40 hours followed by flash column chromatography. A compound of formula INT-(I) can be prepared by any known suitable method, including, for example, the methods shown for preparing Intermediates 1 to 5 in Examples 1 to 5 below. Step I.b: a compound of formula INT-(III) can be prepared by reacting compounds of formulas INT-(II) and INT-(VI) (see, for example, Intermediates 6 to 8 for exemplary preparations) based on, such as DIPEA, a suitable solvent, such as MeCN, at a temperature of 100 °C for 72 hours followed by flash column chromatography. Step Ic: a compound of formula (I) can be prepared by the following sequence: a reaction of compounds of formula INT-(III) and INT-(VII) (see, for example, Intermediate 9 for an exemplary preparation) based on, such as DIPEA, a suitable solvent, such as i-PrOH, was carried out at a temperature of 110 °C for 40 hours followed by flash column chromatography or used as crude material after concentration; The above material can then be treated with a base, such as NaOH in THF / MeOH / water, followed by reverse phase purification to generate a compound of formula (I). Petition 870260065188, dated 02 / 07 / 2026, p. 87 / 516 83 / 236 General reaction schemes II: where A, Raa Rde R4a R7 are defined in this document for Formula (I).

[0088] A general scheme for preparing compounds of Formula (I) is described in General Reaction Scheme II: II.a: CN cross-coupling step, for example: DIPEA, MeCN, 70 °C, 3 h; II.b, CN cross-coupling step followed by hydrolysis, for example: DIPEA, MeCN, 160 °C, 48 h in a microwave reactor, purification, then treated with aqueous 4 N NaOH solution in THF / MeOH. Step II.a: a compound of formula INT-(V) can be prepared by reacting compounds of formula INT-(I) with INT-(VII) (see, for example, Intermediate 9 for an exemplary preparation) and base, such as DIPEA, in a suitable solvent, such as MeC, at a temperature of 70 °C for 3 hours followed by flash column chromatography. A compound of formula INT-(I) can be prepared by any known suitable method, including, for example, the methods shown for preparing Intermediates 1 to 5 in Examples 1 to 5 below. Step II.b: a compound of formula (I) can be prepared by following the sequence: a reaction of the compounds of formulas INT-(V) and INT-(VI) (see, for example, Intermediates 6 to 8 for exemplary preparations) with a base, such as DIPEA, in a suitable solvent, such as i-PrOH, was carried out at a temperature of 160 °C for 480 hours followed by flash column chromatography or used as crude material after concentration; the above material can then be treated with a base, such as NaOH in THF / MeOH / water, followed by reverse phase purification to generate a compound of Formula (I). Petition 870260065188, dated 02 / 07 / 2026, p. 88 / 516 84 / 236 Definitions

[0089] Terms not specifically defined in this document should be given the meanings that would be given to them by a person skilled in the art in light of the description and context. For the purpose of interpreting this descriptive report, the following definitions will apply unless otherwise specified, and, where appropriate, terms used in the singular will also include the plural and vice versa.

[0090] It should be noted that, as used in this document and the accompanying claims, the singular forms of a, an, or include plural referents unless the context clearly indicates otherwise. Thus, for example, reference to the pharmaceutical formulation includes reference to one or more pharmaceutical formulations; and so forth.

[0091] The term alkoxy, as used herein, refers to an alkyl group, preferably a lower alkyl group, having an oxygen bonded to it, for example, -O(alkyl). Representative alkoxy groups include, without limitation, methoxy, ethoxy, propoxy, tert-butoxy and the like. Representative substituted alkoxy groups include, but are not limited to, —OCF and the like.

[0092] An alkyl or alkane group is a non-aromatic hydrocarbon with a straight or branched chain that is fully saturated. Typically, a straight or branched alkyl group has from 1 to about 20 carbon atoms, preferably from 1 to about 10, unless otherwise defined. Examples of straight and branched alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, pentyl, and octyl. A straight or branched C1-C2 alkyl group is also called a lower alkyl group.

[0093] The term aril, as used in this document, Petition 870260065188, dated 02 / 07 / 2026, p. 89 / 516 85 / 236 includes single-ring aromatic groups in which each ring atom is carbon. Preferably, the ring is a 5- to 7-membered ring, more preferably a 6-membered ring. The term aryl also includes polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjacent rings where at least one of the rings is aromatic, for example, the other cyclic rings may be cycloalkyls, cycloalkenyls, cycloalkynyls, aryls, heteroaryls and / or heterocyclyls. Aryl groups include, without limitation, phenyl, biphenyl, naphthyl, anthracenyl, phenalenyl, phenanthrenyl, indanyl, indenyl, tetrahydronaphthalenyl, tetrahydrobenzoanulenyl and the like.

[0094] The term Cx-Cy, when used in conjunction with a chemical moiety such as acyl, acyloxy, alkyl, alkenyl, alkynyl, or alkoxy, is intended to include groups containing doxay carbons in the chain. For example, the term Cx-Cyalkyl refers to substituted or unsubstituted saturated hydrocarbon groups, including straight-chain alkyl and branched-chain alkyl groups containing doxay carbons in the chain. Co-alkyl indicates a hydrogen on which the group is in a terminal position, a bond if internal. The terms C2-Cyalkenyl and C2-Cyalkinyl refer to substituted or unsubstituted unsaturated aliphatic groups analogous in length and possible substitutions to the alkyls described above, but containing at least one double or triple bond, respectively.

[0095] The terms carbocycle and carbocyclic, as used in this document, refer to a saturated or unsaturated ring in which every atom of the ring is carbon. The term carbocycle includes both aromatic and non-aromatic carbocycles. Non-aromatic carbocycles include cycloalkane rings, in which all carbon atoms are saturated, and cycloalkene rings, which contain at least one double bond. Carbocycle includes monocyclic rings Petition 870260065188, dated 02 / 07 / 2026, p. 90 / 516 86 / 236 cycles with 5 to 7 members and bicyclics with 8 to 12 members. Each ring of a bicyclic carbocycle can be selected from saturated, unsaturated, and aromatic rings. Carbocycle includes bicyclic molecules in which one, two, three, or more atoms are shared between the two rings. The term fused carbocycle refers to a bicyclic carbocycle in which each of the rings shares two adjacent atoms with the other ring. Each ring of a fused carbocycle can be selected from saturated, unsaturated, and aromatic rings. In an exemplary embodiment, an aromatic ring, for example, phenyl, can be fused to a saturated or unsaturated ring, for example, cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated, and aromatic bicyclic rings, as permitted by valence, is included in the definition of carbocyclic.

[0096] A cycloalkyl group is a cyclic hydrocarbon that is fully saturated. Cycloalkyl includes monocyclic and bicyclic rings. Typically, a monocyclic cycloalkyl group has from 3 to about 10 carbon atoms, more typically 3 to 8 carbon atoms, unless otherwise defined. The second ring of a bicyclic cycloalkyl may be selected from saturated, unsaturated, and aromatic rings. Cycloalkyl includes bicyclic molecules in which one, two, three, or more atoms are shared between the two rings. The term fused cycloalkyl refers to a bicyclic cycloalkyl in which each of the rings shares two adjacent atoms with the other ring. The second ring of a fused bicyclic cycloalkyl may be selected from saturated, unsaturated, and aromatic rings.

[0097] The term cycloalkyl-alkyl, as used in this document, refers to an alkyl group substituted by a cycloalkyl group.

[0098] The term alkyl-cycloalkyl, as used herein Petition 870260065188, dated 02 / 07 / 2026, page 91 / 516 87 / 236 document, refers to a cycloalkyl group substituted by an alkyl group.

[0099] The terms halo and halogen, as used in this document, mean halogen and include chlorine, fluorine, bromine and iodine.

[00100] Haloalkyl, as used herein, refers to an alkyl group substituted with one or more (e.g., 1, 2, 3, 4, 5 or 6) halogens. Examples of haloalkyl groups include, but are not limited to, trifluoromethyl, difluoromethyl, pentafluoroethyl, trichloromethyl, etc. Fluoroalkyl, as used herein, refers to an alkyl group substituted with one or more (e.g., 1, 2, 3, 4, 5 or 6) fluoro groups.

[00101] The terms heteroaryl and heteroryl include single-ring aromatic structures, substituted or unsubstituted, preferably 5- to 7-membered rings, more preferably 5- to 6-membered rings, whose ring structures include at least one heteroatom, preferably one to four heteroatoms, more preferably one or two heteroatoms. The terms heteroaryl and heteroryl also include polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjacent rings, wherein at least one of the rings is heteroaromatic, for example, the other cyclic rings may be cycloalkyls, cycloalkenyls, cycloalkynyls, aryls, heteroaryls and / or heterocyclyls.Os grupos heteroarila incluem, porém sem limitação, furila, tienila, pirrolila, piridila, Nóxido de piridila, pirazolila, pyrimidinila, imidazolila, isoxazolila, oxazolila, oxadiazolila, pirazinila, indolila, tiofen-2-ila, quinolila, benzopiranila, isotiazolila, tiazolila, tiadiazol, indazol, benzimidazolila, tieno[3,2b]tiofeno, triazolila, triazinila, imidazo[1,2-b]pirazolila, furo[2,3c]piridinila, imidazo[1,2-a]piridinila, indazolila, pirrolo[2,3-c]piridinila, pirrolo[3,2-c]piridinila, pirazolo[3,4-c]piridinila, tieno[3,2-c]piridinila, tiePetição 870260065188, de 02 / 07 / 2026, pág. 92 / 516. 88 / 236 no[2,3-c]pyridinyl, thieno[2,3-b]pyridinyl, benzothiazolyl, indolyl, indolinyl, indolinonyl, di-hydrobenzothiophenyl, di-hydrobenzofuranyl, benzofuran, chromanyl, thiochromanyl, tetra-hydroquinolinyl, dihydrobenzothiazine, di-hydrobenzoxanil, quinolinyl, isoquinolinyl, 1,6naphthyridinyl, benzo[de]isoquinolinyl, pyrido[4,3-b][1,6]naphthyridinyl, thieno[2,3-b]pyrazinyl, quinazolinyl, tetrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, isoindolyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[3,4-b]pyridinyl, pyrrolo[3,2-b]pyridinyl, imidazo[5,4-b]pyridinyl, pyrrolo[1,2-a]pyridinyl, tetra-hydropyrrolo[1,2-a]pyrimidinyl, 3,4-di-hydro-2HY2-pyrrolo[2,1-b]pyrimidine, dibenzo[b,d]thiophene, pyridin-2-one, furo[3,2c]pyridinyl, furo[2,3-c]pyridinyl, 1H-pyrido[3,4-b][1,4]thiazinyl, benzooxazolyl, benzoisoxazolyl, furo[2,3-b]pyridinyl, benzothiophenyl, 1,5naphthyridinyl, furo[3,2-b]pyridine, [1,2,4]triazolo[l,5-a]pyridinyl, benzo[1,2,3]triazolyl, imidazo[1,2-a]pyrimidinyl,[1,2,4]triazolo[4,3b]pyridazinyl, benzo[c][1,2,5]thiadiazolyl, benzo[c][1,2,5]oxadiazole, 1,3di-hydro-2H-benzo[d]imidazol-2-one, . 3,4-di-hydro-2H-pyrazolo[1,5b][1,2]oxazinyl, 4,5,6,7-tetra-hydropyrazolo[1,5-a]pyridinyl, thiazolo[5,4 d]thiazolyl, imidazo[2,1-b][1,3,4]thiadiazolyl, thieno[2,3-b]pyrrolyl, 3Hindolyl, indolinyl, indolinonyl, di-hydrobenzothiophenyl, dihydrobenzofuran, chromanyl, thiochromanil, tetra-hydroquinolinyl, dihydrobenzothiazine,3,4-di-hydro-lH-isoquinolinyl, 2,3-dihydrobenzofuran, indolinyl, indolyl e di-hydrobenzoxanil.,

[00102] The term heteroatom, as used in the present document, means an atom of any element other than carbon or hydrogen. The preferred heteroatoms are nitrogen, oxygen and enxophre.

[00103] The terms heterocyclyl, heterocycle and heterocyclic refer to substituted or unsubstituted non-aromatic ring structures, preferably rings with 3 to 10 members, more preferably rings with 3 to 7 members, whose ring structures include Petition 870260065188, dated 02 / 07 / 2026, p. 93 / 516 89 / 236 in at least one heteroatom, preferably one to four heteroatoms, more preferably one or two heteroatoms. The terms heterocyclyl, heterocycle, and heterocyclic also include polycyclic ring systems that have two or more cyclic rings in which two or more carbons are common to two adjacent rings, wherein at least one of the rings is heterocyclic, for example, the other cyclic rings may be cycloalkyls, cycloalkenyls, cycloalkynyls, aryls, heteroaryls, and / or heterocyclyls. Polycyclic ring systems may be fused or bridged. Heterocyclyl groups include, for example, piperidine, piperazine, pyrrolidine, morpholine, lactones, lactams, aza-adamantane, and the like. Heterocyclyl groups may also be substituted by oxo groups. For example, heterocyclyl encompasses both pyrrolidine and pyrrolidinone.

[00104] As used in this document, the term oxo refers to a carbonyl group. When an oxo substituent occurs on an otherwise saturated group, such as with a cycloalkyl group substituted with oxo (e.g., 3-oxo-cyclobutyl), the substituted group is still considered a saturated group. When a group is referred to as being substituted by an oxo group, this may mean that a carbonyl chemical moiety (i.e., —C(=O)—) replaces a methylene unit (i.e., —CH2—).

[00105] The term optionally substituted means that a given chemical moiety (e.g., an alkyl group) may be (but is not required to be) attached to other substituents (e.g., heteroatoms). For example, an optionally substituted alkyl group may be a fully saturated alkyl chain (e.g., a pure hydrocarbon). Alternatively, the same optionally substituted alkyl group may have substituents other than hydrogen, where the substituents are as defined herein. Optionally substituted, as used in Petition 870260065188, dated 02 / 07 / 2026, p. 94 / 516 90 / 236 of this document also refers to replaced or not replaced, the meaning of which is described below.

[00106] The term substituted means that the specified group or chemical moiety bears one or more suitable substituents wherein the substituents can attach to the specified group or chemical moiety at one or more positions. For example, an aryl substituted by a cycloalkyl may indicate that the cycloalkyl attaches to an aryl atom by bonding or fusion to the aryl and shares two or more common atoms.

[00107] The term not substituted means that the specified group does not carry substitutes.

[00108] A patient or individual is a mammal, for example, a human being, mouse, rat, guinea pig, dog, cat, horse, cow, pig, or non-human primate, such as a monkey, chimpanzee, baboon, or rhesus monkey. In certain modalities, the individual is a primate. In still other modalities, the individual is a human being.

[00109] The terms pharmaceutically effective amount, therapeutically effective amount, or effective quantity mean an amount of a compound as described that, when administered to a patient who needs it, is sufficient to effect treatment for disease states, conditions, or disorders for which the compounds are useful. Such an amount would be sufficient to induce the biological or medical response of a tissue, system, or patient that is sought by a researcher or physician. The amount of a compound as described that constitutes a therapeutically effective amount will vary depending on factors such as the compound and its biological activity, the composition used for administration, the time of administration, the route of administration, the rate of excretion of the compound, the duration of treatment, the type of disease, or Petition 870260065188, dated 02 / 07 / 2026, page 95 / 516 91 / 236 disorder being treated and its severity, drugs used in combination with or coincidentally with the compounds described, and the patient's age, body weight, general health, sex, and diet. Such a therapeutically effective amount can be routinely determined by an individual of ordinary skill in the art who has taken note of their own knowledge, prior art, and this description.

[00110] As used in this document, the term pharmaceutical composition refers to a compound of the description, or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer or tautomer thereof, together with at least one pharmaceutically acceptable carrier, in a form suitable for oral or parenteral administration.

[00111] Carrier encompasses carriers, excipients and diluents and means a material, composition or vehicle, such as a solid or liquid charge, diluent, excipient, solvent or encapsulation material, involved in carrying or transporting a pharmaceutical agent from one organ, or part of the body, to another organ, or part of the body of an individual.

[00112] An individual needs treatment if that individual would benefit biologically, medically, or in quality of life from such treatment (preferably a human being).

[00113] As used in this document, the terms inhibit, inhibition, or that which inhibits refer to the reduction or suppression of a particular condition, symptom, disorder, or disease, or a significant decrease in the baseline activity of a biological activity or process.

[00114] As used in this document, the term treat, treating, or treatment of any disease or disorder refers to alleviating or improving the disease or disorder (i.e., slowing or halting the development of the disease or at least one of the symptoms). Petition 870260065188, dated 02 / 07 / 2026, p. 96 / 516 92 / 236 clinical aspects of the same) or alleviate or improve at least one physical parameter or biomarker associated with the disease or disorder, including those that may not be discernible to the patient.

[00115] As used in this document, the terms prevent, that prevents, or prevention of any disease or disorder refer to the prophylactic treatment of the disease or disorder; or delaying the onset or progression of the disease or disorder.

[00116] Pharmaceutically acceptable means that the substance or composition must be chemically and / or toxicologically compatible with the other ingredients comprising a formulation and / or the mammal that is treated with it.

[00117] Disorder means and is used interchangeably with the terms disease, condition or illness, unless otherwise indicated.

[00118] To administer, administering or administration means to directly administer a disclosed compound, or a pharmaceutically acceptable salt of the disclosed compound or composition, to an individual or to administer a prodrug derivative, or analogue of the compound or of the pharmaceutically acceptable salt of the compound or composition, to the individual, which may form an equivalent amount of active compound within the individual's body.

[00119] Compounds of the present invention, Compounds of Formula (I), compounds of the description and equivalent expressions (unless specifically identified otherwise) refer to compounds of Formula (I) as described herein including the salts, particularly pharmaceutically acceptable salts thereof, where the context thereof permits, as well as all stereoisomers (including diastereomers and enantiomers), rotamers, tautomers and isotopically identified compounds (including deuterium (D) substitutions). Petition 870260065188, dated 02 / 07 / 2026, page 97 / 516 93 / 236

[00120] In a specific embodiment, the term about or approximately means within 20%, preferably within 10%, and most preferably within 5% of a given value or range. Examples

[00121] The description is further illustrated by the following examples and summary schemes which should not be construed as limiting the spirit or scope of the present invention to the specific procedures described herein. It should be understood that the examples are provided to illustrate certain embodiments and that no limitation to the scope of the description is thereby intended. It should further be understood that it is possible to resort to various other embodiments, modifications and equivalents thereof which may be suggested to those skilled in the art without departing from the spirit of the present invention and / or the scope of the appended claims.

[00122] The compounds of the present invention can be prepared by methods known in the art of organic synthesis. In all methods, it is understood that protecting groups for sensitive or reactive groups can be used when necessary in accordance with general principles of chemistry. The protecting groups are handled according to standard methods of organic synthesis (TW Green and PGM Wuts (1999) Protective Groups in Organic Synthesis, 3rd edition, John Wiley & Sons). These groups are removed at a convenient stage of compound synthesis using methods that are readily apparent to those skilled in the art.

[00123] Unless otherwise noted, reagents and solvents were used as received from commercial suppliers. Nuclear magnetic resonance (NMR) spectra were obtained on a Bruker Avance spectrometer or a 400 MHz spectrometer. Petition 870260065188, dated 02 / 07 / 2026, page 98 / 516 94 / 236 Varian Oxford unless otherwise noted. NMR spectra are given in ppm (δ), and coupling constants, J, are reported in Hertz. Tetramethylsilane (TMS) was used as an internal standard. Chemical shifts are reported in ppm relative to dimethyl sulfoxide (δ 2.50), methanol (δ 3.31), chloroform (δ 7.26), or other solvent as indicated in the NMR spectral data. A small amount of the dry sample (2-5 mg) is dissolved in an appropriate deuterated solvent (1 ml). Mass spectra (ESIMS) were collected using a Waters system (Acquity UPLC and a Micromass ZQ mass spectrometer) or Agilent-1260 Infinity (6120 Quadrupole); all masses reported are am / z of the original protonated ions unless otherwise noted. The chemical names were generated using CambridgeSoft's ChemBioDraw Ultra v14.

[00124] Temperatures are given in degrees Celsius. As used in this document, unless otherwise specified, the term ambient temperature or ambient temperature means a temperature of 15 degrees Celsius to 30 degrees Celsius, as well as 20 degrees Celsius to 30 degrees Celsius, as well as 20 degrees Celsius to 25 degrees Celsius. Unless otherwise mentioned, all evaporations are carried out under reduced pressure, typically between about 15 mm Hg and 100 mm Hg (= 20-133 mbar). The structure of the final products, intermediates and starting materials is confirmed by standard analytical methods, e.g., microanalysis and spectroscopic characteristics, e.g., MS, IR, NMR. The abbreviations used are those conventional in the art.

[00125] All starting materials, building blocks, reagents, acids, bases, dehydrating agents, solvents and catalysts used to synthesize the compounds of the present invention in Petition 870260065188, dated 02 / 07 / 2026, page 99 / 516 95 / 236 conventions are commercially available or can be produced by organic synthesis methods known to a person of ordinary skill in the art. Example 1 - Intermediate 1: 2,4-dichloro-6-phenyl 1-5,6,7,8-tetrahydroquinazoline Step 3 Stage pjco1 Peak 2 |nt. 1Alnt1B

[00126] Step 1: To a stirred solution of diethyl carbonate (2110.0 ml, 17.0 mol, 5.0 eq) in tetrahydrofuran (2,4 I) at room temperature, NaH (165 g, 4.1 mol, 1.2 eq, 60% dispersion in mineral oil) was added in portions. The resulting mixture was heated to 80 °C, and then the solution of 4-phenylcyclohexanone (600.0 g, 3.4 mol) in tetrahydrofuran (2,4 I) was added dropwise over 1 h. The reaction mixture was then stirred at 80 °C for 1 h and rapidly cooled with saturated aqueous solution of NhUCI (1,2 I) at 0 °C and then extracted with EtOAc (3 x 5.0 I). The combined organic layer was dried with anhydrous sodium sulfate, filtered, and then concentrated to obtain a crude residue, which was purified by silica gel column chromatography with heptane / EtOAc = 100 / 1 to produce the desired compound ethyl 2-oxo-5-phenylcyclohexane-1-carboxylate (771.8 g, purity: 64.5%, 86.4% crude yield) as a colorless liquid.1H NMR (400 MHz, DMSO) δ 7.42 - 7.05 (m, 5H), 4.19 - 4.10 (m, 2H), 2.84 2.66 (m, 1H), 2.52 - 2.43 (m, 2H), 2.41 - 2.27 (m, 1H), 2.17 (ddd, J = 33.6, 21.5, 2.3 Hz, 2H), 1.93 - 1.75 (m, 2H), 1.26 - 1.12 (m, 3H).

[00127] Step 2: To a solution of ethyl 2-oxo-5-phenylcyclohexane-1-carboxylate (700.0 g, 2.8 mol, 1.0 eq) and urea (341 g, 5.7 mol, Petition 870260065188, dated 02 / 07 / 2026, p. 100 / 516 96 / 236 2.0 eq) in ethanol (12.5 l) at room temperature, sodium methoxide (1570.0 ml, 20% in methanol, 5.7 mol, 2.0 eq) was added. The resulting reaction mixture was stirred at 80 °C for 16 h. The reaction was monitored by HPLC. The reaction mixture was cooled to room temperature. The precipitated solid was filtered, washed with tert-butyl methyl ether (1 l x 3) and dried to obtain 6-phenyl-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione as a dirty white solid (510 g, purity: 98.6%, 74% yield). 1H NMR (400 MHz, DMSO) δ 7.47 - 7.01 (m, 5H), 5.43 (s, 1H), 2.81 - 2.64 (m, 1H), 2.57 (d, J = 4.6 Hz, 1H), 2.43 - 2.22 (m, 2H), 2.11 (dd, J = 15.5, 10.6 Hz, 1H), 1.88 (d, J = 10.3 Hz, 1H), 1.77 (dt, J = 11.7, 6.2 Hz, 1H).

[00128] Step 3: To a mixture of 6-phenyl-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione (500.0 g, 2.1 mol, 1.0 eq) in POCh (2.0 L, 4.0 V), N,N-diisopropylethylamine (266 g, 2.1 mol, 1.0 eq) was added by dropwise over 30 min at room temperature under a nitrogen atmosphere. After the addition, the resulting mixture was heated to 120 °C and stirred for 16 h. The reaction was monitored by HPLC. The reaction mixture was cooled to 25 °C in air and diluted with dichloromethane (2.0 L). The diluted suspension was concentrated under vacuum to remove most of the POCh. The residue was dissolved in dichloromethane (6.0 l), and then the residual POCh was rapidly cooled by adding ice water (10.0 l) at 0 °C.The aqueous phase was extracted with dichloromethane (3.0 l) again, dried with anhydrous Na2SO4, and the filtrate was concentrated to obtain crude residue, which was purified by silica gel column with heptane / EtOAc = 20 / 1 to produce the desired product 2,4-dichloro-6-phenyl-5,6,7,8-tetrahydroquinazoline (266.0 g, purity: 99.2%, 46% yield) as a yellow solid. LCMS: m / z = 257.00 [M+H]+; 1H NMR (400 MHz, DMSO) δ 7.46 - 7.02 (m, 5H), 3.17 - 2.88 (m, 4H), 2.75 (dd, J = 16.9, 11.0 Hz, 1H), 2.14 -1.90 (m, 2H). Petition 870260065188, dated 02 / 07 / 2026, page 101 / 516 97 / 236

[00129] Step 4: Racemic 2,4-Dichloro-6-phenyl-5,6,7,8-tetrahydroquinazoline (266.0 g) was purified by chiral SFC (Chiralcel OJ-H, flow rate: 4 ml / min, cosolvent: 40%, methanol, injected volume: 2 pl, outlet pressure: 100 bar, temperature: 35 °C) to yield 105.0 g, 99.7% ee of (R)-2,4-dichloro-6-phenyl-5,6,7,8-tetrahydroquinazoline and 105.0 g, 98.6% ee of (S)-2,4-dichloro-6-phenyl 5,6,7,8-tetrahydroquinazoline. The absolute stereochemistry was determined by small molecule X-ray crystallography. Example 2 - Intermediate 2: 2,4-dichloro-6-methyl-6-phenyl-5,6,7,8-tetrahydroquinazoline

[00130] Step 1: A solution of 2-phenylpropanal (430 g, 3.20 mol, 430 ml, 1 eq) in toluene (1.50 L), PPAS'hW (121 g, 640 mmol, 0.2 eq) and but-3-en-2-one (336 g, 4.81 mol, 400 ml, 1.5 eq) was heated to 25 °C. The mixture was stirred at 80 °C for 16 h. The TLC (petroleum ether / ethyl acetate = 10 / 1, Rf / reactant = 0.45, Rf / product = 0.45) indicated that the starting material had disappeared, and new points had formed. The reaction mixture (total 860 g) was combined and cooled to room temperature and added to water (5.00 L) slowly. The mixture was extracted with EtOAc (5.00 L). The organic layer was washed with a saturated solution of K2CO3 (3.00 L), brine (3.00 L), Petition 870260065188, dated 02 / 07 / 2026, p. 102 / 516 98 / 236 dried with Na2SO4, filtered and concentrated. The product was used directly in the next step. 1-Methyl-2,3-dihydro-[1,1'-biphenyl]-4(1H)-one (1.20 kg, crude) was obtained as a yellow oil.

[00131] Step 2: To a solution of 1-methyl-2,3-dihydro-[1,1'-biphenyl]4(1H)-one (200 g, 1.07 mol, 1 eq, crude) in EtOAc (1.00 l), Pd / C (20.0 g, 107 mmol, 10% purity, 0.1 eq) was added under a N2 atmosphere. The mixture was degassed and purged with H2 (0.34 MPa (50 psi)) 3 times. The mixture was stirred at 40 °C for 12 h. The TLC (petroleum ether / ethyl acetate = 10 / 1, Rf / reagent = 0.45, Rf / product = 0.65) indicated that the starting material disappeared, and new points were formed. The reaction mixture was filtered, and the cake was washed with EtOAc (600 ml x 3). The filtrate was concentrated. The product was purified by silica gel column chromatography (SiO2, petroleum ether / ethyl acetate = 10 / 1). 4-Methyl-4-phenylcyclohexan-1-one (438 g, 2.33 mol, 54.1% yield) was obtained as a yellow oil. 1H NMR (400 MHz CDCl3) δ 7.50 - 7.45 (m, 2H), 7.44 - 7.37 (m, 2H), 7.30 - 7.24 (m, 1H), 2.59 - 2.47 (m, 2H), 2.44 - 2.28 (m, 4H), 2.03 1.91 (m, 2H), 1.35 (s, 3H).

[00132] Step 3: To a solution of 4-methyl-4-phenylcyclohexan-1-one (608 g, 5.15 mol, 624 ml, 5 eq) in THF (1.16 l), NaH (49.4 g, 1.24 mol, 60% purity, 1.2 eq) was added slowly at 20 °C. A solution of diethyl carbonate (194 g, 1.03 mol, 1 eq) in THF (388 ml) was added dropwise at 80 °C over 0.5 h. The mixture was stirred at 80 °C for 1 h. The TLC (petroleum ether / ethyl acetate = 10 / 1, Rf / reagent = 0.40, Rf / product = 0.55) indicated that the starting material had disappeared, and a new endpoint had been formed. The reaction mixture was rapidly cooled with saturated NH4Cl (2 l) and extracted with EtOAc (400 ml). The organic layer was separated, washed with brine (700 ml x 2), dried with Na2SO4, filtered, and concentrated. The product was purified by silica gel column chromatography (SiO2, ether of Petition 870260065188, dated 02 / 07 / 2026, p. 103 / 516 99 / 236 petroleum). Ethyl 5-Methyl-2-oxo-5-phenylcyclohexane-1-carboxylate (325 g, 1.25 mol, 60.5% yield) was obtained as a yellow oil. 1H NMR, (400 MHz CDCb) δ 7.32 - 7.22 (m, 4H), 7.19 - 7.10 (m, 1H), 4.22 (q, J = 7.2 Hz, 2H), 4.07 (q, J = 7.2 Hz, 1H), 2.82 - 2.70 (m, 1H), 2.29 (br d, J = 16.4 Hz, 1H), 2.25 - 2.17 (m, 1H), 2.06 - 2.00 (m, 2H), 1.82 - 1.73 (m, 1H), 1.33 - 1.23 (m, 6H).

[00133] Step 4: To a mixture of ethyl 5-methyl-2-oxo-5-phenylcyclohexane-1-carboxylate (295 g, 1.13 mol, 1 eq) in EtOH (2.95 l), urea (136 g, 2.27 mol, 121 ml, 2 eq) and NaOMe (122 g, 2.27 mol, 2 eq) were slowly added. The mixture was stirred at 80 °C for 12 h. HPLC indicated that ~7.2% of the starting material remained, and ~77.5% of the desired peak was detected at 220 nm. The reaction mixture was concentrated to remove most of the ethanol. The product was triturated with MTBE (1.50 l) at 20 °C for 0.5 h. 6-Methyl-6-phenyl-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione (210 g, crude) was obtained as a white solid and used directly in the next step.

[00134] Step 5: To a mixture of 6-methyl-6-phenyl-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione (200 g, 780 mmol, 1 eq) in dioxane (2.00 l), Et3N (236 g, 2.34 mol, 325 ml, 3 eq) was added and followed by POCl3 (1.20 kg, 7.80 mol, 725 ml, 10 eq) by dropwise addition at 0-5 °C over 0.5 h. The mixture was stirred at 125 °C for 5 h. LCMS indicated that the reagent disappeared, and the new peak with the desired mass was detected. The reaction mixture was concentrated under reduced pressure and diluted with CH2Cl2 (3.00 l). The mixture was added to a saturated solution of NaHCO3 (5.00 L) and stirred at 20–40 °C for 0.5 h. The mixture was filtered with Celite. The organic layer was separated, washed with brine (1.00 L), dried with Na2SO4, filtered, and concentrated. The product was purified by silica gel column chromatography (SiO2, petroleum ether / ethyl acetate = 10 / 1 to 5 / 1). 2,4-Dichloro-6-methyl-6-phenyl-5,6,7,8-tetrahydroquinazoline (65.0 g, 220 mmol, 28.3% Petition 870260065188, dated 02 / 07 / 2026, page 104 / 516 (100 / 236 yield, 99.6% purity) was obtained as a yellow solid. LCMS: RT = 0.862 min, MS (ESI) m / z = 292.9 [M+H]+; 1H NMR (400 MHz CDCl3) δ 7.35 - 7.20 (m, 5H), 3.38 - 3.34 (m, 1H), 2.93 - 2.86 (m, 1H), 2.87 - 2.80 (m, 1H), 2.60 (dd, J = 2.8, 5.2 Hz, 1H), 2.34 - 2.31 (m, 1H), 2.01 - 1.97 (m, 1H), 1.43 (s, 3H).

[00135] Step 6: The chiral separation of 2,4-dichloro-6-methyl-6-phenyl-5,6,7,8-tetrahydroquinazoline (65.0 g, 221 mmol, 1 eq) was performed by SFC (column: DAICEL CHIRALPAK AY (250 mm x 50 mm, 10 pm); mobile phase: [0.1% NH3-H2O EtOH]; B%: 15% - 15%, 2.2; 2105 min). The product was concentrated. (R)-2,4-dichloro-6-methyl-6-phenyl-5,6,7,8tetrahydroquinazoline (27.0 g) eluted as Peak 1 and (S)-2,4-dichloro-6methyl-6-phenyl-5,6,7,8-tetrahydroquinazoline (24.0 g) eluted as Peak 2 and obtained as a yellow oil. Example 3 - Intermediate 3: 2,4-dichloro-6-(3-fluorophenyl)-6-methyl 5,6,7,8-tetrahydroquinazoline Peak 2 Int. 3B Petition 870260065188, dated 02 / 07 / 2026, p. 105 / 516 101 / 236

[00136] Step 1: To a solution of 1-(3-fluorophenyl)ethan-1-one (100 g, 723.91 mmol) in THF (1 l), t-BuOK (130 g, 1160 mmol) was added at 20 °C. The reaction mixture was stirred at 20 °C for 1 h. Then, a solution of (methoxymethyl)triphenylphosphonium chloride (372 g, 1090 mmol) in THF (1 l) was added dropwise at 0 °C. The reaction was allowed to cool to 20 °C and stirred for 16 h. The TLC (petroleum ether / ethyl acetate = 10 / 1) showed that the starting material was consumed, and a new principal point was formed. The reaction mixture was poured into petroleum ether (2 l) and then filtered. The filter was filtered through a silica filter and concentrated under vacuum to produce the desired product (E)-1-fluoro-3-(1-methoxyprop-1-en-2-yl)benzene (100 g, 602 mmol, 83.26% yield) as a yellow oil which was used directly in the next step.

[00137] Step 2: To a solution of (E)-1-fluoro-3-(1-methoxyprop-1en-2-yl)benzene (150 g, 902.57 mmol) in THF (1.5 l), a solution of HBr (663 g, 2170.71 mmol, in AcOH) in H2O (300 ml) was added dropwise at 0 °C. The reaction was allowed to cool to 40 °C after the addition was complete and stirred for 3 h. The TLC (petroleum ether / ethyl acetate = 10 / 1, Rf = 0.3) showed that the starting material was consumed, and a new endpoint was formed. The reaction mixture was separated, and the aqueous phase was extracted by EtOAc (100 ml x 2). The combined organic layer was washed with brine, dried with anhydrous Na2SO4, filtered, and concentrated under vacuum to generate 2-(3-fluorophenyl)propanal (150 g, crude) which was used directly in the next step.

[00138] Step 3: To a solution of 2-(3-fluorophenyl)propanal (140 g, crude) in toluene (1200 ml), but-3-en-2-one (96 g, 1380.25 mmol) and pTsOH^H2O (35 g, 184.01 mmol) were added at 25 °C. The mixture was stirred at 80 °C for 16 h. TLC (petroleum ether / ethyl acetate = 10 / 1) showed that the starting material was completely consumed. Petition 870260065188, dated 02 / 07 / 2026, p. 106 / 516 102 / 236 and a principal spot was formed. The reaction mixture was concentrated to remove toluene. The residue was purified by silica gel column chromatography (SiO2 (1000 g, 1000 mesh), petroleum ether to petroleum ether / ethyl acetate = 2 / 1), and then the desired fraction was concentrated to produce 3'-fluoro-1-methyl-2,3-dihydro-[1,1'-biphenyl]-4(1H)-one (120 g, 579.61 mmol, 98.65% purity, 48.09% yield over two steps). LCMS: m / z = 205.2 [M+H]+, RT = 0.883 min; 1H NMR (400 MHz, DMSO-d6) δ = 7.41 (dt, J = 6.7, 8.0 Hz, 1H), 7.28 - 7.20 (m, 2H), 7.15 - 7.07 (m, 2H), 6.03 (d, J = 10.1 Hz, 1H), 2.43 - 2.33 (m, 1H), 2.29 - 2.19 (m, 1H), 2.16 - 2.08 (m, 2H), 1.53 - 1.49 (m, 3H).

[00139] Step 4: To a solution of 3'-fluoro-1-methyl-2,3-dihydro[1,1'-biphenyl]-4(1H)-one (60 g, 293.76 mmol) in MeOH (600 ml), Pd / C (62 g, 58.75 mmol, 10% carbon) was added. The mixture was purged and degassed with H2 three times. The mixture was stirred at 25 °C for 16 h. The reaction mixture was filtered to remove Pd / C, and the filtrate was concentrated under vacuum. The residue was purified by silica gel column chromatography (PE to PE / EA = 2 / 1) and concentrated to yield 4-(3-fluorophenyl)-4-methylcyclohexan-1-one (37.5 g, 62% yield, 88% purity). LCMS: RT = 0.909 min, m / z = 207.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 7.45 - 7.37 (m, 1H), 7.36 - 7.29 (m, 2H), 7.09 - 7.01 (m, 1H), 2.40 - 2.29 (m, 4H), 2.19 - 2.11 (m, 2H), 1.98 - 1.89 (m, 2H), 1.30 (s, 3H).

[00140] Step 5: To a solution of 4-(3-fluorophenyl)-4-methylcyclohexan-1-one (100 g, 848.46 mmol) and NaH (8.14 g, 87.27 mmol, 60%) in THF (200 ml), a solution of diethyl carbonate (35 g, 169.69 mmol) was added dropwise at 80 °C under a N2 atmosphere. The mixture was stirred at 80 °C for 3 h. The reaction mixture was poured into HCl (200 ml, 1 N) and extracted with EtOAc (50 ml x 3). The combined organic layer was washed with brine (30 ml x 3), dried Petition 870260065188, dated 02 / 07 / 2026, p. 107 / 516 103 / 236 with anhydrous Na2SO4, filtered and concentrated under vacuum to produce the desired product ethyl 5-(3-fluorophenyl)-5-methyl-2-oxocyclohexane-1-carboxylate (30 g, 56% yield, 88.11% purity) as a yellow oil. LCMS: RT = 1.063 min, m / z = 279.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.32 - 7.41 (m, 1 H), 7.11 7.20 (m, 2 H), 7.02 (td, J = 8.28, 2.26 Hz, 1 H), 4.23 (q, J = 7.03 Hz, 2 H), 2.69 (br d, J = 15.94 Hz, 1 H), 2.47 - 2.56 (m, 1 H), 2.20 - 2.36 (m, 2 H), 2.03 - 2.16 (m, 1 H), 1.84 - 1.98 (m, 1 H); 1.73 - 1.84 (m, 1 H), 1.12 - 1.31 (m, 6 H).

[00141] Step 6: To a solution of 5-(3-fluorophenyl)-5-methyl-2-oxocyclohexane-1-carboxylate (30 g, 107.79 mmol) in EtOH (300 ml), urea (13 g, 215.58 mmol) and NaOMe (12 g, 215.58 mmol) were added. The mixture was stirred at 80 °C for 16 h, and the mixture was filtered to yield 6-(3-fluorophenyl)-6-methyl-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione (35 g, crude) as a yellow solid which was used directly in the next step. LCMS: RT = 0.806 min, m / z = 275.2 [M+H]+.

[00142] Step 7: To a solution of 6-(3-fluorophenyl)-6-methyl-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione (30 g, 109.49 mmol) and TEA (2.2 g, 16.41 mmol, 2.2 ml) in dioxane (200 ml), POCh (84 g, 546.87 mmol, 50.8 ml) was added dropwise at 0 °C. The mixture was heated to 125 °C and stirred for 3 h, and the reaction mixture was concentrated under vacuum. The residue was purified by flash chromatography (column: 300 g SiO2, PE and EA conditions), and the product fractions were concentrated under vacuum to yield 2,4-dichloro-6-(3-fluorophenyl)6-methyl-5,6,7,8-tetrahydroquinazoline (27 g, 80.7% yield) as a yellow oil. LCMS: RT=1.028 min, m / z = 311.2 [M+H]+.

[00143] Step 8: The racemate 2,4-dichloro-6-(3-fluorophenyl)-6-methyl-5,6,7,8-tetrahydroquinazoline (64 g, 205.78 mmol) was separated by SFC (column: DAICEL CHIRALPAK AY-H (250 mm · 30 mm, 10 µm)). Petition 870260065188, dated 02 / 07 / 2026, page 108 / 516 104 / 236 Condition: 0.1% NHβ·HζO EtOH, initial B%: 20% to final B%: 20%). The solution was concentrated under vacuum for rendering.

[00144] (R)-2,4-dichloro-6-(3-fluorophenyl)-6-methyl-5,6,7,8-tetrahydroquinazoline (14.6 g, 45.65 mmol, 22.20% yield, 94.7% purity). LCMS: RT = 1.034 min, m / z = 312.2 [M+H]+, SFC: RT = 0.905 min; 1H NMR (400 MHz, DMSO-d6) δ = 7.41 - 7.30 (m, 1H), 7.20 (br d, J = 11.4 Hz, 1H), 7.13 (br d, J = 7.8 Hz, 1H), 7.09 - 6.98(m, 1H), 3.21 (br d, J = 17.5 Hz, 1H), 3.00 - 2.78 (m, 2H), 2.59-2.52 (m, 1H), 2.40 - 2.16 (m, 1H), 2.11 - 1.89 (m, 1H), 1.34 (s, 3H)

[00145] (S)-2,4-dichloro-6-(3-fluorophenyl)-6-methyl-5,6,7,8-tetrahydroquinazoline (11.2 g, 36.01 mmol, 17.50% yield, 99.3% purity). LCMS: RT = 1.034 min, m / z = 312.2 [M+H]+, SFC: RT = 0.905 min; 1H NMR (400 MHz, DMSO-d6) δ = 7.35 (dt, J = 6.6, 8.0 Hz, 1H), 7.20 (td, J = 2.2, 11.4 Hz, 1H), 7.13 (dd, J = 0.9, 8.0 Hz, 1H), 7.08 - 7.00 (m, 1H), 3.21 (d, J = 17.7 Hz, 1H), 3.05 - 2.81(m, 2H), 2.58 - 2.53 (m, 1H), 2.37 - 2.19 (m, 1H), 2.00 (ddd, J = 6.1, 8.2, 13.9 Hz, 1H), 1.36 -1.27 (m, 3H). Example 4 - Preparation of Intermediate 4: 2,4-dichloro-6-(3-fluorophenyl)-5,6,7,8-tetrahydroquinazoline Petition 870260065188, dated 02 / 07 / 2026, p. 109 / 516 105 / 236

[00146] Step 1: The stirred suspension of 1-fluoro-3-iodobenzene (140 g, 630 mmol, 74.0 ml, 1.00 eq), 4,4,5,5-tetramethyl-2-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)-1,3,2-dioxaborolane (149 g, 561 mmol, 0.89 eq) and CS2CO3 (308 g, 945 mmol, 1.50 eq) in dioxane (1200 ml OH (300 ml) (8 / 2)) was degassed with argon for 15 min. Then, Pd(dppf)Cl2*CH2Cl2 (29.8 g, 36.5 mmol, 0.058 eq) was added and degassed again for 5 min. Then, The reaction mixture was heated to 70 °C for 16 h. The TLC (petroleum ether / ethyl acetate = 10 / 1, reagent Rf = 0.50, new point Rf = 0.34) showed that the starting material was completely consumed, and a new point was detected. The reaction mixture was concentrated under reduced pressure to remove dioxane. The residue was diluted with H2O (1.5 L) and extracted with EtOAc (1.5 L x 2). The combined organic layers were washed with brine (2 L x 2), dried with Na2SO4, filtered, and concentrated under reduced pressure to yield a residue.The residue was purified by column chromatography (SiO2, petroleum ether / acetate). Petition 870260065188, dated 02 / 07 / 2026, page 110 / 516 106 / 236 ethyl =1 / 0 to 5 / 1) to generate 8-(3-fluorophenyl)-1,4-dioxaspiro[4,5]dec-7ene (137 g, 584 mmol, 92.7% yield) as a brown oil. LCMS: MS (ESI) m / z = 235.2 [M+H]+; 1H NMR: (400 MHz, DMSOd6) δ 7.52 - 7.45 (m, 1H), 7.40 - 7.31 (m, 2H), 7.23 - 7.15 (m, 1H), 6.26 - 6.21 (m, 1H), 4.06 - 4.02 (m, 4H), 2.76 - 2.55 (m, 3H), 1.97 - 1.89 (m, 2H), 1.33 - 1.27 (m, 1H), 1.23 - 1.19 (m, 1H).

[00147] Step 2: To a solution of 8-(3-fluorophenyl)-1,4-dioxaspiro[4,5]dec-7-ene (80.0 g, 341 mmol, 1.00 eq) in EtOH (880 ml), Pd / C (8.00 g, 10% purity) was added under a N2 atmosphere. The suspension was degassed and purged with H2 3 times. The mixture was stirred under H2 (0.103 MPa (15 psi)) at 20 °C for 12 h. TLC (petroleum ether / ethyl acetate = 10 / 1, reagent Rf = 0.35, new point Rf = 0.42) showed that the starting material was consumed, and a new point was detected. The reaction mixture was filtered through a Celite filter and washed with excess EtOH (1 l) and EtOAc (1 l). The filtrate was concentrated to obtain the desired compound. The residue was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 5 / 1) to yield 8-(3-fluorophenyl)-1,4-dioxaspiro[4,5]decane (74.4 g, 314 mmol, 92.2% yield) as a colorless oil.LCMS: MS (ESI) m / z = 237.1 [M+H]+, 1H NMR: δ 7.36 - 7.27 (m, 1H), 7.11 - 6.92 (m, 3H), 3.92 - 3.85 (m, 4H), 2.68 - 2.57 (m, 1H), 1.82 1.70 (m, 4H), 1.69 (s, 4H).

[00148] Step 3: To a solution of 8-(3-fluorophenyl)-1,4-dioxaspiro[4,5]decane (74.4 g, 314 mmol, 1.00 eq) in dioxane (620 ml) / H2O (310 ml) (2 / 1), HCl (12 M, 309 ml, 11.7 eq) was added. The mixture was stirred at 20 °C for 3 h. LCMS showed that the starting material was consumed, and the desired compound was detected. The reaction mixture was concentrated under reduced pressure to remove dioxane. The residue was extracted with EtOAc (500 ml x 2), and the combined organic layers were washed with saturated NaHCO3 (500 ml and Petition 870260065188, dated 02 / 07 / 2026, page 111 / 516 107 / 236 brine 500 ml, dried with anhydrous Na2SO4, filtered and concentrated under reduced pressure to generate a residue. The crude product 4-(3-fluorophenyl)cyclohexan-1-one (64.5 g, crude) was used in the next step without further purification as a colorless oil. LCMS: product RT = 0.836 min, MS (ESI) m / z = 193.2 [M+H]+; 1H NMR: (400 MHz, DMSO-d6) δ 7.38 - 7.30 (m, 1H), 7.17 - 7.10 (m, 2H), 7.06 - 6.98 (m, 1H), 3.15 - 3.04 (m, 1H), 2.63 - 2.52 (m, 2H), 2.31 - 2.21 (m, 2H), 2.12 2.02 (m, 2H), 1.96 - 1.80 (m, 2H).

[00149] Step 4: To a stirred solution of diethyl carbonate (245 g, 2.08 mol, 251 ml, 5.00 eq) in THF (400 ml) at 25 °C, NaH (19.9 g, 498 mmol, 60.0% purity, 1.20 eq) was added in portions. The resulting mixture was heated to 80 °C, and then a solution of 4(3-fluorophenyl)cyclohexan-1-one (79.9 g, 415 mmol, 1.00 eq) in THF (400 ml) was added dropwise over ~20 min. The reaction mixture was then stirred at 80 °C for 30 min. LCMS showed that the starting material was consumed, and the desired compound was detected. The reaction mixture was rapidly cooled with a saturated solution of NH4Cl (1 l) and extracted with EtOAc (1 l x 2). The combined organic layer was washed with a saturated solution of NaHCO3 (800 ml) and brine (600 ml), dried with anhydrous Na2SO4, and concentrated under reduced pressure.The residue was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 1 / 0 to 10 / 1, Rf at desired point = 0.33) to generate ethyl 5-(3-fluorophenyl)-2-oxocyclohexane-1-carboxylate (65.3 g, 247 mmol, 59.4% yield) as a light yellow oil. LCMS product RT = 1.005 min, MS (ESI) m / z = 265.2 [M+H]+; 1H NMR: (400 MHz, DMSO-d6) δ 7.40 - 7.29 (m, 1H), 7.19 - 7.09 (m, 2H), 7.08 - 6.97 (m, 1H), 4.21 (br s, 3H), 2.88 - 2.69 (m, 1H), 2.49 - 2.41 (m, 1H), 2.35 - 2.04 (m, 2H), 2.01 - 1.92 (m, 1H), 1.90 1.80 (m, 1H), 1.77 - 1.41 (m, 1H), 1.22 - 1.17 (m, 3H).

[00150] Step 5: To a stirred solution of 5-(3-fluorophenyl)-2 Petition 870260065188, dated 02 / 07 / 2026, page 112 / 516 Ethyl oxocyclohexane-1-carboxylate (75.0 g, 283 mmol, 1.00 eq) was added to 1680 ml of EtOH, followed by urea (34.0 g, 567 mmol, 30.4 ml, 2.00 eq) and then NaOMe (30.6 g, 567 mmol, 2.00 eq). The reaction mixture was heated to 80 °C for 16 h. LCMS showed that the starting material was consumed, and the desired compound was detected. The reaction mixture was filtered, the solid was washed with MBTE (900 ml) and water (500 ml), and concentrated under reduced pressure to yield a residue. The crude product 6-(3-fluorophenyl)-5,6,7,8-tetrahydroquinazoline2,4(1H,3H)-dione (48.5 g, crude) was used in the next step without further purification as a white solid.

[00151] LCMS: product RT = 0.777 min, MS (ESI) m / z = 261.0 [M+H]+; 1H NMR: (400 MHz, DMSO-d6) δ 7.39 - 7.28 (m, 1H), 7.15 7.06 (m, 2H), 7.04 - 6.96 (m, 1H), 2.84 - 2.70 (m, 1H), 2.60 - 2.52 (m, 1H), 2.44 - 2.37 (m, 1H), 2.34 - 2.25 (m, 1H), 2.18 - 2.05 (m, 1H), 1.94 1.84 (m, 1H), 1.82 - 1.71 (m, 1H).

[00152] Step 6: To a stirred suspension of 6-(3-fluorophenyl)5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione (44.0 g, 169 mmol, 1.00 eq) in dioxane (1760 ml), TEA (5.65 g, 55.7 mmol, 7.77 ml, 0.33 eq) was added, followed by POCb (259 g, 1.69 mol, 157 ml, 10.0 eq) (by dropwise) at 0 °C, and the reaction mixture was heated to 130 °C for 3 h. LCMS showed that the starting material was consumed, and the desired compound was detected. The reaction mixture was concentrated under reduced pressure to remove the solvent. The residue was slowly diluted with H2O (300 ml) and adjusted to pH 7 with saturated NaHCO3 (700 ml), then extracted with EtOAc (1 L x 3), dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure to yield a residue. The crude product was triturated with MTBE (20 ml 3 times) at 25 °C for 2 h to yield 2,4-dichloro-6-(3-fluorophenyl)-5,6,7,8tetrahydroquinazoline (24.5 g, 82.4 mmol, 48.7% yield) as a yellow solid.LCMS: product RT = 1,020 min, MS (ESI) m / z. Petition 870260065188, dated 02 / 07 / 2026, page 113 / 516 109 / 236 = 296.7 [M+H]+; 1H NMR: (400 MHz, CHLOROFORM-d) δ 7.38 7.30 (m, 1H), 7.09 - 7.03 (m, 1H), 7.01 - 6.93 (m, 2H), 3.22 - 2.96 (m, 4H), 2.79 - 2.67 (m, 1H), 2.30 - 2.19 (m, 1H), 2.08 - 1.92 (m, 1H).

[00153] Step 7: Racemic 2,4-dichloro-6-(3-fluorophenyl)-5,6,7,8-tetrahydroquinazoline was purified by SFC (column: DAICEL CHIRALCEL OJ (250 mm * 30 mm, 10 µm); mobile phase: [0.1 % NH3^H2O MeOH]; B %: 30 % - 30 %, 2.8 min; 1100 min) to yield:

[00154] (R)-2,4-dichloro-6-(3-fluorophenyl)-5,6,7,8-tetrahydroquinazoline (10.6 g, >99 % ee): LCMS: product RT = 1.047 min, MS (ESI) m / z = 297.2 [M+H]+; 1H NMR: (400 MHz, CHLOROFORM-d) δ 7.37 - 7.30 (m, 1H), 7.08 - 7.03 (m, 1H), 7.03 - 6.93 (m, 2H), 5.32 - 5.30 (m, 1H), 3.20 - 2.98 (m, 4H), 2.80 - 2.69 (m, 1H), 2.29 - 2.20 (m, 1H), 2.06 - 1.94 (m, 1H) as a yellow solid.

[00155] (S)-2,4-Dichloro-6-(3-fluorophenyl)-5,6,7,8-tetrahydroquinazoline (12.0 g, >99% ee): LCMS: RT = 1.005 min, MS (ESI) m / z = 296.7 [M+H]+; 1H NMR: (400 MHz, CHLOROFORM-d) δ 7.39 - 7.31 (m, 1H), 7.08 - 7.03 (m, 1H), 7.03 - 6.94 (m, 2H), 3.20 - 2.97 (m, 4H), 2.79 - 2.69 (m, 1H), 2.29 - 2.20 (m, 1H), 2.07 - 1.94 (m, 1H) as a yellow solid. Example 5 - Preparation of Intermediate 5: (R)-2,4-dichloro-6-(4-fluorophenyl)-5,6,7,8-tetrahydroquinazoline Petition 870260065188, dated 02 / 07 / 2026, p. 114 / 516 110 / 236 Br Overnight PdCí2(dppf).CH2Cl2 Na2CO3, 90 °C Pd-C,[H] TFA, DCM days Step 1 NaH, O it goes up to 75 °C EtO OEt h Urea NaOMe / MeOH °C, 20 h POCh, TEA Step Step 5 Step THE 1,4-dioxane, 125 °C h Chiral separation by SFC Peak 1 Int. 5 Step

[00156] Step 1: 4,5,5-tetramethyl-2-(1,4-dioxaspiro[4,5]dec-7-en-8yl)-1,3,2-dioxaborolane (10 g, 37.6 mmol), 1-bromo-4-fluorobenzene (7.89 g, 45.1 mmol), and Na2COs (15.93 g, 150 mmol) were mixed in 1,4-dioxane (150 ml) and water (37.5 ml). The mixture was degassed with nitrogen for 5 min. PdCbídppfj.ChLCb adduct (1.534 g, 1.879 mmol) was added, and the reaction was heated to 90 °C overnight. LCMS showed that the reaction was complete. The crude product was cooled to room temperature, diluted with EtOAc, and filtered through Celite (the Celite was washed with EtOAc). The filtrate was concentrated and purified on a 120 2x silica column, 0-20% EtOAc in heptane to yield 8-(4-fluorophenyl)-1,4-dioxaspiro[4,5]dec-7-ene (7.33 g, 31.3 mmol, 83% yield) as a white solid. LCMS (basic): RT = 1.03 min; MS m / z = 387.2 [M+H]+.

[00157] Step 2: A solution of 8-(4-fluorophenyl)-1,4-dioxaspiro[4,5]dec-7-ene (3.67 g, 15.67 mmol) in EtOH (50 ml) was aspirated and filled with nitrogen three times. 50% moist Pd-C (1.667 g, 1.567 mmol) was added. A 1 atm hydrogen flask was connected via an adapter. The reaction flask was aspirated. Petition 870260065188, dated 02 / 07 / 2026, page 115 / 516 111 / 236 flask was filled with hydrogen three times. The reaction was stirred at room temperature under hydrogen for 1 h. LCMS showed that the reaction was complete. The flask was aspirated to remove hydrogen, filtered through Celite (washed with DCM), and concentrated to produce 8-(4-fluorophenyl)-1,4-dioxaspiro[4,5]decane (3.3 g, 13.97 mmol, 89% yield) as a white solid. The material was used as is in the next step. LCMS (basic): Rt = 1.08 min; MS not observed. TLC: Rf = 0.6, 1:1 EtOAc / heptane.

[00158] Step 3: To a solution of 8-(4-fluorophenyl)-1,4-dioxaspiro[4,5]decane (4.63 g, 19.59 mmol) in DCM (15 ml), TFA (30.2 ml, 392 mmol) was added. The resulting mixture was stirred at room temperature for 2 days. LCMS showed that the reaction was incomplete. More TFA (12 ml) was added. The reaction was continued for one more day. The mixture was concentrated, diluted with EtOAc, and washed with saturated NaHCO3, water, and brine. It was then dried with Na2SO4 and concentrated using a rotary evaporator. The residue was purified by chromatography (120 g silica gel column, 0-50% EtOAc / heptane; the product exited the column at ~30% EtOAc / heptane) to yield 4-(4-fluorophenyl)cyclohexan-1-one (3.1 g, 16.13 mmol, 82% yield) as a colorless oil. LCMS (basic): RT = 0.93 min; MS m / z = 192.5 [M+H]+.

[00159] Step 4: To a stirred solution of diethyl carbonate (19.60 ml, 162 mmol) in anhydrous THF (20 ml), NaH was added in mineral oil (0.776 g, 19.41 mmol). A solution of 4-(4-fluorophenyl)cyclohexan-1-one (3.11 g, 16.18 mmol) in anhydrous THF (10 ml) was added. The reaction was stirred at room temperature for 30 min before being heated to 75 °C and stirred under nitrogen for 1.5 h. TLC showed no further SMs, instead a new main peak. LCMS showed a new main peak and almost no other SMs. The reaction was cooled to 0 °C, then rapidly cooled with Petition 870260065188, dated 02 / 07 / 2026, p. 116 / 516 112 / 236 ml of saturated NH4Cl was extracted with 150 ml of EtOAc. The organic phase was washed with brine and dried with sodium sulfate. It was then concentrated by rotary evaporator and purified by ISCO (120 g silica gel column, 0-20% EtOAc in heptane), yielding ethyl 5-(4-fluorophenyl)-2-oxocyclohexane-1-carboxylate (2.5 g, 9.46 mmol, 58.5% yield). LCMS (basic): RT = 1.28 min, MS m / z = 265.2 [M+H]+. TLC: Rf = 0.80, 1:1 EtOAc / heptane. The product contained minor impurities. It was used as is in the next step.

[00160] Step 5: To a solution of ethyl 5-(4-fluorophenyl)-2-oxocyclohexane-1-carboxylate (4.25 g, 16.08 mmol) in MeOH (40 ml), urea (1.931 g, 32.2 mmol) and NaOMe (1.737 g, 32.2 mmol) were added. The mixture was heated to 75 °C in the presence of nitrogen for 20 h; LCMS showed that the reaction was complete (LCMS: RT = 0.74 min, MS m / z = 261.1 [M+H]+). White precipitates were observed. The reaction was cooled to room temperature, and the precipitate was filtered and washed with Et2O and dried to produce the desired product 6-(4-fluorophenyl)-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione (2.5 g, 59.4% yield). LCMS (basic): RT = 0.74 min, MS m / z = 261.1 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 7.36 - 7.21 (m, 2H), 7.11 (t, J = 8.8 Hz, 2H), 2.75 (dtd, J = 14.3, 7.7, 3.5 Hz, 1H), 2.55 (dd, J = 15.8, 5.0 Hz, 1H), 2.45 - 2.21 (m, 2H), 2.09 (dd, J = 16.0, 10.9 Hz, 1H), 1.95 - 1.82 (m, 1H), 1.73 (td, J = 11.9, 5.4 Hz, 1H).

[00161] Step 6: To a stirred suspension of 6-(4-fluorophenyl)5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione (2.5 g, 9.61 mmol) and TEA (3.21 ml, 23.05 mmol) in 1,4-dioxane (10 ml) at 0 °C, POCl3 (8.95 ml, 96 mmol) was added dropwise over 10 min. The resulting reaction mixture was stirred at 125 °C for 23 h (dark precipitates were observed). LCMS showed that the reaction was complete. The crude product was cooled and concentrated under pressure. Petition 870260065188, dated 02 / 07 / 2026, page 117 / 516 113 / 236 induced to remove excess 1,4-dioxane and POCh. The residue obtained was poured into ice water and stirred for ~30 min. The mixture was extracted with EtOAc and DCM. The separated organic layers were washed with saturated medium NaHCO3, brine, concentrated and purified by ISCO (120 g silica gel column, 0-50% EtOAc in heptane) to produce the racemic product (1.51 g, 4.83 mmol, 50.3% yield) as a beige-colored solid. This material was separated by chiral SFC (column: DAICEL CHIRALCEL OJ (250 mm * 30 mm, 10 µm); mobile phase: [0.1% NH3·H2O MeOH]; B%: 30% - 30%, 2.8 min; 1100 min) to produce the enantiomeric product (R)-2,4-dichloro-6-(4-fluorophenyl)-5,6,7,8-tetrahydroquinazoline (peak 1, 630 mg, 42% yield). LCMS (basic): RT = 1.20 min, MS = 299.3 [M+H]+; 1H NMR (400 MHz, Methylene Chloride-d2) δ 7.37 - 7.23 (m, 2H), 7.17 - 7.05 (m, 2H), 3.23 - 2.97 (m, 4H), 2.82 - 2.68 (m, 1H), 2.23 (ddq, J = 13.7, 5.8, 2.9 Hz, 1H), 2.11 - 1.91 (m, 1H). Example 6 - Preparation of Intermediate 6: (R)-3-(1-(methylamino)propyl)bicyclo[1.1.1-l-pentane-1-carboxylate hydrochloride the Step 3 Step 4

[00162] Step 1: To an acid solution 3 Petition 870260065188, dated 02 / 07 / 2026, page 118 / 516 114 / 236 (methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (253.0 g, 1.5 mol, 1.0 eq) in anhydrous THF (2500.0 ml), a complex of boranomethyl sulfide (2232.0 ml, 2.0 mol / l, 4.5 mol, 3.0 eq) at 0 °C was added dropwise, and the reaction mixture was stirred at 0 °C for 2 h. The reaction was monitored by GC. The reaction mixture was rapidly cooled with MeOH (750.0 ml) until no bubbles were generated at 25 °C. The mixture was concentrated under reduced pressure at 45 °C. The residue was dissolved in MTBE (5060.0 ml, 20 V), washed with aqueous saturated NaCl (759.0 ml χ 2) and dried with anhydrous Na2SO4, filtered and concentrated under reduced pressure to yield methyl 3(hydroxymethyl)bicyclo[1.1.1]pentane-1-carboxylate (255.0 g, GC purity: 98.8%, gross yield: 100%) as a light yellow solid. 1H NMR (300 MHz, CDCl3) δ 3.75 (s, 2H), 3.67 (s, 3H), 1.96 (dd, J = 9.2, 5.7 Hz, 6H).

[00163] Step 2: To a solution of methyl 3(hydroxymethyl)bicyclo[1.1.1]pentane-1-carboxylate (255.0 g gross, 1.5 mol, 1.0 eq) in dry DCM (2500.0 ml), NaHCO3 (250.0 g, 3.0 mol, 2 eq) and DMP (753.3 g, 1.8 mol, 1.2 eq) at 0 °C were added, and the mixture was warmed to 25 °C and stirred for 2 h. The reaction was monitored by GC. The reaction mixture was filtered through a Celite filter, and the filter cake was washed with DCM (1000.0 ml χ 3). The combined organic layers were concentrated under reduced pressure. The residue was diluted with EtOAc (5100.0 ml) and washed with aqueous saturated sodium thiosulfate (500.0 ml χ2) and aqueous saturated NaHCO3 (500.0 ml), dried with anhydrous Na2SO4, filtered, and concentrated. The residue was purified by column spectroscopy with heptane / EA = 10 / 1 to yield methyl 3-formylbicyclo[1.1.1]pentane-1-carboxylate (187.0 g, purity: 83.4%, gross yield: 70.2%) as a white solid. 1H NMR (300 MHz, CDCl3) δ 9.60 (s, 1H), 3.71 (s, 3H), 2.32 (s, 6H).

[00164] Step 3: To a mixture of 3-formylbicyclo[1.1.1]pentane-1 Petition 870260065188, dated 02 / 07 / 2026, page 119 / 516 115 / 236 methyl carboxylate (180.0 g, 1.3 mol, 1.0 eq) in DCM (1800.0 ml, 10 V) was added, (R)-(+)-2-methyl-2-propanesulfinamide (156.8 g, 1.3 mol, 1.0 eq) at 25 °C, and the mixture was stirred for 72 h. The reaction was monitored by GC. The reaction mixture was diluted with H2O (900.0 ml) and separated. The aqueous phase was extracted with DCM (2700.0 ml, 15 V), and the combined organic phases were washed with aqueous saturated NaCl (500.0 ml), dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The mixture was purified by column spectroscopy with heptane / EA = 5 / 1 to yield (R,E)-3-(((tert-butylsulfinyl)imino)methyl)bicyclo[1.1.1]pentane-1-carboxylate methyl (210.0 g, purity: 59.2 %), containing 40.8 % of (R)-2-methylpropane-2-sulfinamide (crude yield 63.0 %) as a dirty white solid which was used in the next step directly without further purification. 1H NMR (300 MHz, CDCl3) δ 7.97 (s, 1H), 3.68 (s, 3H), 2.28 (s, 6H), 1.16 (s, 9H).

[00165] Step 4: To a solution of (R,E)-3-(((tert-butylsulfinyl)imino)methyl)bicyclo[1.1.1]pentane-1-carboxylate methyl (200.0 g, 0.77 mol, 1.0 eq) in dry THF (1600.0 ml), ethyl magnesium bromide (777.0 ml, 1.5 mol, 2 mol / l, 2.0 eq) at -78 °C was added dropwise, and the mixture was stirred for 2 h. The reaction was monitored by HPLC. The reaction mixture was abruptly cooled with aqueous saturated NH4Cl (1200.0 ml) at -78 °C. The reaction mixture was then warmed to 25 °C. The mixture was extracted with EtOAc (3000.0 ml x 2), and the combined organic layers were dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography with heptane / EA = 3 / 1 to the crude product as a yellow oil. The crude product was purified by preparative HPLC to yield 27.0 g of (S)-3-(1-((tert-butylsulfinyl)amino)-113propyl)bicyclo[1.1.1]pentane-1-carboxylate with 93.9% purity and 81.0 g of (R)-3-(1-((tert-butylsulfinyl)amino)-113 Petition 870260065188, dated 02 / 07 / 2026, p. 120 / 516 116 / 236 propyl)bicyclo[1.1.1]pentane-1-carboxylate methyl with 97.2% purity. 1H NMR (300 MHz, CDCl3) δ 3.65 (d, J = 8.7 Hz, 3H), 3.11 (td, J = 8.3, 4.5 Hz, 1H), 2.87 (d, J = 7.7 Hz, 1H), 1.99 (qd, J = 9.6, 1.8 Hz, 6H), 1.55 (ddd, J = 14.1, 7.4, 4.5 Hz, 1H), 1.41 - 1.25 (m, 1H), 1.25 - 1.11 (m, 9H), 0.93 (t, J = 7.4 Hz, 3H).

[00166] Step 5: To a solution of (R)-3-(1-((tert-butylsulfinyl)amino)-113-propyl)bicyclo[1.1.1]pentane-1-carboxylate methyl (63.0 g, 0.21 mol, 1.0 eq) in dry THF (0.7 l), LiHMDS (2 M, 210.0 ml, 0.42 mol, 2.0 eq) was added at 0 °C under N2, and the reaction mixture was stirred for 0.5 h at 0 °C. Then, MeI (59.6 g, 0.42 mol, 2.0 eq) was added dropwise at 0 °C, and the mixture was warmed to 25 °C and stirred for 2 h. The reaction was monitored by HPLC. The reaction mixture was rapidly cooled with ice-cold water (1200.0 ml). The mixture was extracted with EtOAc (1000.0 ml χ 3), and the combined organic phases were washed with aqueous saturated NaCl (500.0 ml), dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure to yield (R)-3-(1-((tert-butylsulfinyl)(methyl)amino)-113propyl)bicyclo[1.1.1]pentane-1-carboxylate (55.0 g, purity: 82.1%, gross yield: 83.2%).1H NMR (300 MHz, CDCl3) δ 3.66 (s, 3H), 3.11 (dd, J = 8.7, 6.6 Hz, 1H), 2.49 (s, 3H), 2.13 (dd, J = 9.5, 1.8 Hz, 3H), 2.00 (dd, J = 9.5, 1.8 Hz, 3H), 1.62 - 1.46 (m, 2H), 1.23 (dd, J = 9.0, 5.2 Hz, 2H), 1.23 - 1.11 (m, 9H), 0.98 (t, J = 7.4 Hz, 3H).

[00167] Step 6: Methyl (R)-3-(1-((tert-butylsulfinyl)(methyl)amino)-113propyl)bicyclo[1.1.1]pentane-1-carboxylate (55.0 g, 182.5 mmol, 1.0 eq) was added to 4 M HCl in 1,4-dioxane (467.0 ml, 1.8 mol, 10.0 eq) at 0 °C, and the mixture was warmed to 25 °C and stirred for 2 h. The reaction was monitored by HPLC. The reaction mixture was concentrated under reduced pressure and exchanged with MTBE (110.0 ml χ2). The residue was triturated with MTBE / EtOAc (50 / 1, 165.0 ml) at 25 °C for 2 h. Petition 870260065188, dated 02 / 07 / 2026, p. 121 / 516 117 / 236 The mixture was filtered, and the filter cake was ground with MTBE (275.0 mL, 5 V) at 25 °C for 2 h. The mixture was filtered, and the filter cake was dried to yield methyl (R)-3-(1-(methylamino)propyl)bicyclo[1.1.1]pentane-1-carboxylate hydrochloride (25.5 g, yield: 59.8%) as a white solid. 1H NMR (300 MHz, MeOD) δ 3.70 (s, 2H), 3.20 - 3.07 (m, 1H), 2.73 (s, 3H), 2.19 (dd, J = 4.4, 1.3 Hz, 6H), 1.75 (t, J = 7.6 Hz, 2H), 1.07 (t, J = 7.5 Hz, 3H). Example 7 - Preparation of Intermediate 7: methyl (1R,4r)-4((R)-1-(methylamino)propyl)cyclohexane-1-carboxylate hydrochloride

[00168] Step 1: A solution of (1r,4r)-4-(methoxycarbonyl)cyclohexane-1-carboxylic acid (140 g, 751 mmol, 1 eq) in CH2Cl2 (700 ml) was added to DMF (549 mg, 7.52 mmol, 578 µl, 0.01 eq) under a nitrogen atmosphere. The reaction was cooled to 0 °C, and then (COCl)2 (101 g, 796 mmol, 69.7 ml, 1.06 eq) was added dropwise. The reaction was stirred at 25 °C for 10 h. Pd(dppf)Cb (16.5 g, 22.5 mmol, 0.03 eq) was added to the reaction, followed by THF (700 ml). The mixture was then cooled to 0 °C, and a solution of ZnEt2 (1 M, 902 ml, 1.2 eq) was added slowly at 0 °C. After the addition, the mixture was stirred at 25 °C for 10 h. The TLC (petroleum ether / ethyl acetate = 5 / 1, Rf / reagent = 0.20, Rf / new point = 0.55) showed that 0 material was consumed, and 0 a new point was formed. The reaction mixture was rapidly cooled by the addition of chilled saturated NH4Cl (1000 ml) and extracted with CH2Cl2 (600 ml x 3), the combined organic layers were washed with brine (1000 ml). Petition 870260065188, dated 02 / 07 / 2026, page 122 / 516 118 / 236 dried, filtered and concentrated under reduced pressure to generate a residue. The residue was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 4 / 1 to 1 / 4) to obtain a product (1r,4r)-4-propionylcyclohexane-1-carboxylate methyl (170 g, 514 mmol, 68.4% yield, 60.0% purity) was obtained as a light yellow oil. 1H NMR (400 MHz, CDCl3) δ 3.60 (s, 3H), 2.44 - 2.36 (m, 1H), 2.30 - 2.14 (m, 2H), 2.04 - 1.93 (m, 4H), 1.92 - 1.84 (m, 1H), 1.82 -1.69 (m, 3H), 1.68 - 1.61 (m, 1H), 1.45 - 1.35 (m, 1H), 1.33 (br d, J = 10.4 Hz, 1H), 1.45 - 1.30 (m, 1H), 1.33 - 1.24 (m, 1H), 1.23 1.15 (m, 1H), 1.00 - 0.92 (m, 1H).

[00169] Step 2: To a solution of (1R,4r)-4-propionylcyclohexane-1-carboxylate methyl (340 g, 1.71 mol, 1 eq), Ti(OEt)4 (782 g, 3.43 mol, 711 ml, 2 eq) and (R)-2-methylpropane-2-sulfinamide (228 g, 1.89 mol, 1.1 eq) were added. The mixture was stirred at 75 °C for 5 h. The TLC (petroleum ether / ethyl acetate = 5 / 1, Rf / reagent = 0.45, Rf / new point = 0.20) showed that the material was consumed, and the desired point was formed. The reaction was cooled to 25 °C and diluted with 800 ml of EtOAc and rapidly cooled with H2O (229 g). The resulting suspension was vigorously shaken and filtered through a short plug and Celite. The cake solid was washed with EtOAc (1500 ml x 2). The filtrate was concentrated under vacuum to obtain a residue. The residue was purified by column chromatography (SiO2, petroleum ether / ethyl acetate = 1 / 0 to 0 / 1) to obtain a product (230 g crude).The product was then purified by preparative HPLC (Phenomenex luna c18 250 mm * 100 mm * 10 µm; mobile phase: [water (NH4HCO3 10 mM) - ACN], B%: 45.0% - 65.0%, 20 minutes) to generate the desired product (1R,4r)-4-((E)-1-(((R)-tert-butylsulfinyl)imino)propyl)cyclohexane-1-carboxylate ethyl (98.0 g, 304 mmol, 17.7% yield, 98.0% purity) as a light yellow oil. LCMS: RT = 0.938 min, m / z = 316.3 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 4.08 (q, J = 7.2 Hz, 2H), 2.78 - 2.57 (m, 1H), 2.32 - 2.14 (m, 2H),. Petition 870260065188, dated 02 / 07 / 2026, p. 123 / 516 119 / 236 2.08 - 1.97 (m, 2H), 1.95 - 1.78 (m, 2H), 1.85 - 1.77 (m, 1H), 1.53 - 1.28 (m, 4H), 1.24 - 1.11 (m, 13H).

[00170] Step 3: To a solution of (1R,4r)-4-((E)-1-(((R)-tert-butylsulfinyl)imino)propyl)cyclohexane-1-carboxylate ethyl (96.0 g, 304 mmol, 1 eq) and Ti(OEt)4 (208 g, 912 mmol, 189 ml, 3 eq) in THF (960 ml) and EtOAc (240 ml), NaBH4 (34.5 g, 912 mmol, 3 eq) was added at -78 °C. The resulting mixture was continued and stirred at -78 °C for 2 h (removed from the bath at -78 °C and placed in an ice bath). Then, the mixture was stirred at 0 °C for 2 h. The reaction was cooled again to -78 °C and then rapidly cooled with NH4Cl (137 ml). The mixture was allowed to cool to 25 °C and filtered; the cake was washed with EtOAc (1000 ml x 2). The combined organic layers were concentrated under vacuum to obtain a residue.The residue was purified by preparative HPLC (Phenomenex luna C18 (250 * 70 mm, 10 µm), mobile phase: [water (NH4HCO3 10 mM)-ACN], B %: 45 % - 70 %, 20 min) to generate the desired product (1R,4r)-4-((R)-1-(((R)-tert-butylsulfinyl)amino)propyl)cyclohexane-1-carboxylate ethyl (58.0 g, 178 mmol, 58.7 % yield, 97.8 % purity) as a light yellow oil. LCMS: RT = 0.886 min, m / z = 318.2 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 4.03 (q, J = 7.2 Hz, 2H), 3.02 (d, J = 7.6 Hz, 1H), 2.95 - 2.86 (m, 1H), 2.22 - 2.09 (m, 1H), 2.02 - 1.90(m, 2H), 1.84 - 1.74 (m, 1H), 1.70 (br d, J = 12.8 Hz, 1H), 1.56 - 1.43 (m, 2H), 1.43 - 1.28 (m, 3H), 1.22 - 1.10 (m, 12H), 1.06 - 0.93 (m, 1H), 0.85 (t, J = 7.2 Hz, 3H).

[00171] Step 4: To a solution of (1R,4r)-4-((R)-1-(((R)-tert-butylsulfinyl)amino)propyl)cyclohexane-1-carboxylate ethyl (55.0 g, 173 mmol, 1 eq) in THF (1100 ml) at -70 °C, LiHMDS (1 M, 207 ml, 1.2 eq) was added, and then the mixture was stirred at 0 °C for 30 min. At 0 °C, CH3I (122 g, 866 mmol, 53.9 ml, 5 eq) was added, and the reaction mixture was slowly warmed to 25 °C for 2 h. LCMS showed that the material Petition 870260065188, dated 02 / 07 / 2026, p. 124 / 516 120 / 236 was consumed, and the desired point was formed. The reaction mixture was rapidly cooled by the addition of chilled saturated NH4Cl (300 ml), extracted with EtOAc (300 ml x 3). The combined organic layers were washed with brine (300 ml), dried with Na2SO4, filtered, and concentrated under reduced pressure to yield a residue. The residue was purified by column chromatography (SO2, petroleum ether / ethyl acetate = 1 / 0 to 0 / 1) to yield the desired product (1R,4r)-4-((R)-1-(((R)-tert-butylsulfinyl)(methyl)amino)propyl)cyclohexane-1-carboxylate ethyl (32.0 g, 90.7 mmol, 52.3% yield, 94.0% purity) as a yellow oil. LCMS: RT = 0.978 min, m / z = 332.3 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 4.12 - 4.00 (m, 2H), 2.74 (td, J = 8.8, 4.0 Hz, 1H), 2.48 - 2.40 (m, 3H), 2.23 - 2.08 (m, 1H), 2.06 - 1.92 (m, 3H), 1.80 (br d, J = 12.8 Hz, 1H), 1.72 - 1.62 (m, 1H), 1.58 - 1.46 (m, 1H), 1.44 - 1.27 (m, 3H), 1.24 - 1.10 (m, 11H), 1.07 - 0.88 (m, 5H).

[00172] Step 5: To a solution of ethyl (1R,4r)-4-((R)-1-(((R)-tert-butylsulfinyl)(methyl)amino)propyl)cyclohexane-1-carboxylate (64.0 g, 193 mmol, 1 eq) in MeOH (448 ml), HCl / MeOH (4 M, 448 ml, 9.28 eq) at 0 °C was added, the resulting mixture was continued and stirred at 25 °C for 5 h. LCMS showed that the material was consumed, and the desired product was formed. The reaction mixture was concentrated to obtain a product as a yellow oil. Then, the product was dissolved in EtOAc / MTBE (1 / 10, 220 ml) and concentrated to obtain a product as a white solid. The product was triturated with MTBE (100 ml) at 25 °C for 10 minutes to obtain methyl (1R,4r)-4-((R)1-(methylamino)propyl)cyclohexane-1-carboxylate hydrochloride (36.2 g, 144 mmol, 75.0% yield).LCMS: RT = 0.341 min, m / z = 213.9 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 9.49 - 8.92 (m, 2H), 3.63 (s, 3H), 2.68 (t, J = 5.2 Hz, 4H), 2.38 - 2.21 (m, 1H), 2.13 - 2.02 (m, 2H), 1.97 - 1.84 (m, 2H), 1.83 - 1.72 (m, 3H), 1.53 - 1.38 (m, 3H), 1.37 1.24 (m, 1H), 1.12 - 1.04 (m, 3H). Petition 870260065188, dated 02 / 07 / 2026, p. 125 / 516 121 / 236 Example 8 - Preparation of Intermediate 8: (1R,4r)-4-((R)-1-aminopropyl)cyclohexane-1-carboxylate methyl

[00173] Ethyl (1R,4r)-4-((R)-1-(((R)-tert-butylsulfinyl)amino)propyl)cyclohexane-1-carboxylate (75 g, 236 mmol) was dissolved in MeOH (400 ml). HCl in MeOH (295 ml, 4 mol / l in MeOH) was added at 0 °C. The resulting mixture was continued and stirred at 0 °C for 2 h. The reaction was concentrated under vacuum. The residue was triturated with MTBE (800 ml) to generate methyl (1R,4r)-4-((R)-1-aminopropyl)cyclohexane-1-carboxylate (40.6 g, 203 mmol, yield: 93.7%) as a white solid. LCMS: RT = 0.215 min, m / z = 200.2 [M+H]+; 1H NMR (400MHz, DMSO-d6) δ 8.18 - 7.83 (m, 3H), 3.59 (s, 3H), 2.91 - 2.76 (m, 1H), 2.30-2.17 (m, 1H), 1.93 (br s, 2H), 1.72 (brs, 2H), 1.65-1.44 (m, 3H), 1.29 (br s, 2H), 1.11 (s, 2H), 0.91 (t, J = 7.4 Hz, 3H). Example 9 - General method for the synthesis of amine intermediates. Preparation of Intermediate 9. b--L9 Ϊ 3

[00174] Step 1: (S)-3-methylpiperidine hydrochloride (3.19 g, 23.50 mmol), (R)-2-((tert-butoxycarbonyl)amino)-2-(1-methyl-1H-pyrazol-4-yl)acetic acid (5 g, 19.59 mmol) and EtsN (10.92 ml, 78 mmol) were dissolved in DCM (75 ml). The solution was cooled to 0 °C, and T3P (50% in EtOAc) (23.56 ml, 39.2 mmol) was added slowly. The solution Petition 870260065188, dated 02 / 07 / 2026, p. 126 / 516 122 / 236 became obscured, and the mixture was stirred at room temperature for 2 h. LC-MS indicated complete reaction. The reaction mixture was partitioned between EtOAc and water, the organic phase was washed with water, saturated NaHCO3 solution, brine, and dried with MgSO4. The solid was removed by filtration and concentrated under reduced pressure. The crude material was purified by ISCO combi-flash chromatography (ELSD detection), eluting with a 20-100% EtOAc gradient in heptane, using a 120 g silica column loaded with DCM. The fractions containing the product were combined, concentrated under reduced pressure, and dried under vacuum overnight to yield tert-butyl ((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1-yl)-2-oxoethyl)carbamate as a white solid (6.16 g, 93%). MS m / z = 337.1 [M+H]+.

[00175] Step 2: To a solution of tert-butyl ((R)-1-(1-methyl-1H-pyrazol-4-yl)-2((S)-3-methylpiperidin-1-yl)-2-oxoethyl)carbamate (2.46 g, 7.31 mmol) in THF (18.28 ml), BH3.DMS (2 M in THF) (18.28 ml, 36.6 mmol, 5.0 equiv.) at 0 °C was added. The mixture was then warmed to 25 °C and stirred overnight. LC-MS indicated that all the starting material was consumed. The reaction mixture was rapidly cooled with MeOH until no further bubbles were observed. The mixture was stirred for 30 min, then concentrated. The residue was diluted with MeOH (10 ml), then pyridine (5.91 ml, 73.1 mmol) was added to the solution. The resulting solution was stirred at room temperature for 2 days.The mixture was concentrated and diluted with MeOH for purification by reversed-phase column chromatography (20-80% MeCN / water with 0.1% NH4OH modifier, 150 g ISCO gold C18 column) and lyophilization drying to yield tert-butyl ((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1yl)ethyl)carbamate as a colorless oil (1.83 g, 78% yield). MS m / z = 323.3 [M+H]+. Petition 870260065188, dated 02 / 07 / 2026, p. 127 / 516 123 / 236

[00176] Step 3: To a solution of tert-butyl ((R)-1-(1-methyl-1H-pyrazol-4-yl)2-((S)-3-methylpiperidin-1-yl)ethyl)carbamate (1.64 g, 5.09 mmol) in MeOH (10 ml), a solution of HCl (6.36 ml, 25.4 mmol, 4 N in dioxane) was added. The reaction was stirred at room temperature for 4 h. The reaction mixture was concentrated under reduced pressure and dried under vacuum overnight to yield (R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)amine dihydrochloride as a pale clear solid in quantitative yield. MS m / z = 223.3 [M+H]+. Example 10 - Preparation of Intermediate 10: (3R,5R)-3-methoxy-5-methylpiperidine aMel, NaH A ] HCl / k OH ÔhfH|k Ί, · \ II — \ II I MeOH—— O O1।Step 1Step 2 Int. 10

[00177] Step 1: To a solution of tert-butyl (3R,5R)-3-hydroxy-5-methylpiperidine-1-carboxylate (4500.0 mg, 1 Eq, 20.902 mmol) in THF (104 ml), NaH (2.090 g, 60 wt%, 2.5 Eq, 52 mmol) was added at 0°C. Then, the reaction mixture was stirred at 0°C for 0.5 h, and Mel (7.42 g, 3.27 ml, 2.5 Eq, 52 mmol) was added dropwise. The mixture was stirred at 25°C for a further 1.5 h. LCMS showed that a main peak with the desired mass was detected. The mixture was rapidly cooled with saturated NH4Cl (100 ml) and extracted with EtOAc (100 ml*2). The combined organic phase was dried with anhydrous Na2SÜ4, filtered, and concentrated to yield residue. The residue was purified by silica gel flash chromatography (ISCO®; 80 g SepaFlash® Silica Flash column, 0-100% EtOAc / heptane eluent), and the eluent was concentrated to yield the desired product as a colorless oil. LCMS m / z [M-55]+= 174.2.

[00178] Step 2: To a solution of (3R,5R)-3-methoxy-5-methylpiperidine-1-carboxylate tert-butyl (4.4 g, 1 Eq, 19 mmol) in Petition 870260065188, dated 02 / 07 / 2026, page 128 / 516 124 / 236 MeOH (50 ml) was added to HCl (4 N in dioxane) (3.5 g, 24 ml, 4000 molar, 5 Eq, 96 mmol) at 0 °C. Then, the reaction mixture was stirred at room temperature for 2 h, and LC-MS indicated that all the SM was consumed. The mixture was concentrated under reduced pressure to yield a colorless oil. The crude product was used in the next step without further purification. LC-MS m / z [M+H]+= 130.1. Example 11 - Preparation of Intermediate 11: 2-((tert-butoxycarbonyl)amino)-2-(3-fluoro-1-methyl-1H-pyrazol-4-yl)acetic acid HCl, THF / H2O Step 2 Boc2O, NaHCO3 THF Step 3 4N NaOH THF / MeOH Step

[00179] Stage 1: To a solution of ethyl 2-((diphenylmethylene)amino)acetate (1.25 g, 4.68 mmol) 4-bromo-3-fluoro-1-methyl-1H-pyrazole (0.92 g, 5.14 mmol) in toluene (30 ml), K3PO4 (2.98 g, 14.03 mmol) and Pd(t-BusP)2 (0.24 g, 0.468 mmol) were added at 25 °C under N2. Then, the mixture was stirred at 100 °C for 16 h. LCMS showed that the desired mass was detected. The reaction mixture was poured into H2O (50 ml), and the aqueous layer was extracted with EA (50 ml*3). The combined organic phase was dried with Na2SO4, filtered, and concentrated. The residue was purified by silica gel flash chromatography (ISCO®; 40 g SepaFlash® Silica Flash column, 0-100% ethyl acetate / petroleum ether gradient eluent at 100 ml / min), then concentrated to yield 2-((diphenylmethylene)amino)-2-(3-fluoro-1-methyl-1H-pyrazol-4-yl)ethyl acetate (250 mg, 60% pu). Petition 870260065188, dated 02 / 07 / 2026, p. 129 / 516 125 / 236 prayer) like a yellow oil. LCMS m / z [M+H]+ = 366.0.

[00180] Step 2: To a solution of 2-((diphenylmethylene)amino)-2-(3fluoro-1-methyl-1H-pyrazol-4-yl)ethyl acetate (250 mg, 0.41 mmol, 60% purity) in dioxane (2 ml), 4 M HCl / dioxane (2 ml) was added. The resulting mixture was stirred at 25 °C for 4 h. LCMS showed that the desired mass was detected. H2O (4 ml) was added to the mixture and then extracted with PE (4 ml*3). The aqueous phase (0.41 mmol, in H2O (4 ml)) was carried over to the next step without further purification. The combined organic phase was discarded. LCMS m / z [M+H]+= 202.1.

[00181] Step 3: To a mixture of ethyl 2-amino-2-(3-fluoro-1-methyl-1H-pyrazol-4-yl)acetate (0.41 mmol, in H2O (4 ml)) in THF (4 ml), NaHCO3 (345 mg, 4.10 mmol) and Boc2O (179 mg, 0.82 mmol) were added. The resulting mixture was stirred at 25 °C for 16 h. LCMS showed that the desired mass was detected. The mixture was extracted with EA (15 ml*3). The combined organic product was dried with anhydrous Na2SO4, filtered, and concentrated to yield ethyl 2-((tert-butoxycarbonyl)amino)-2-(3-fluoro-1-methyl-1H-pyrazol-4-yl)acetate (200 mg, crude) as a yellow oil. LCMS m / z [M-55]+= 246.2.

[00182] Step 4: A solution of 2-((tert-butoxycarbonyl)amino)-2(3-fluoro-1-methyl-1H-pyrazol-4-yl)ethyl acetate (200 mg, crude) in 4 M THF / MeOH / NaOH = 2:1:1 (4 ml) was stirred at 40 °C for 1 h. LCMS showed that the desired mass was detected. The reaction mixture was concentrated to generate the residue. The residue was added to H2O (4 ml) and extracted with PE (4 ml*3). The aqueous phase was adjusted to pH~5 with 1 N HCl and extracted with EA (5 ml*3). The combined organic product was dried with anhydrous Na2SO4, filtered, and concentrated to yield 2-((tert-butoxycarbonyl)amino)-2-(3-fluoro-1-methyl-1H-pyrazol-4yl)acetic acid (110 mg, crude) as a yellow gum. Example 12: Synthesis of (1R,4r)-4-((R)-1-(((R)-6-(2-fluorophenyl)-4(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)amino acid. Petition 870260065188, dated 02 / 07 / 2026, p. 130 / 516 126 / 236 5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclohexane-1carboxylic acid (Compound 48) and (1R,4r)-4-((R)-1-(((S)-6-(2fluorophenyl)-4-(((R)-1 -(1-methyl-1 H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1yl)ethyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid (Compound 141) Petition 870260065188, dated 02 / 07 / 2026, page 131 / 516 127 / 236

[00183] Step 1: To a flask containing 4,4,5,5-tetramethyl-2-(1,4-dioxaspiro[4,5]dec-7-en-8-yl)-1,3,2-dioxaborolane (5 g, 18.79 mmol), 1-fluoro-2-iodobenzene (5 g, 22.54 mmol), and sodium carbonate (7.96 g, 75 mmol), dioxane (75 ml) and water (18.75 ml) were added. The reaction mixture was degassed with nitrogen for 5 min, and then PdCb(dppf).CH2Cb adduct (0.767 g, 0.939 mmol) was added and heated to 90 °C overnight. The reaction was monitored with LCMS and cooled to room temperature. The reaction was diluted with EtOAc and filtered through Celite and washed with EtOAc. The filtrate was concentrated and purified by chromatography (40 g, silica gel, 0-20% EtOAc in heptane) to yield 8-(2-fluorophenyl)-1,4-dioxaspiro[4,5]dec-7-ene (4.26 g, 18.18 mmol, 97% yield).LCMS: m / z = 235.2 [M+H]+; 1H NMR (400 MHz, Chloroform-d) δ 7.26 - 7.17 (m, 1H), 7.11 (ddd, J = 7.3, 5.1,2.0 Hz, 1H), 7.05 - 6.88 (m, 2H), 5.83 - 5.67 (m, 1H), 3.96 (s, 4H), 2.57 (ddt, J = 6.3, 3.9, 1.9 Hz, 2H), 2.40 (q, J = 2.6 Hz, 2H), 1.84 (t, J = 6.5 Hz, 2H).

[00184] Step 2: To a solution of 8-(2-fluorophenyl)-1,4-dioxaspiro[4,5]dec-7-ene (4.26 g, 18.18 mmol) in MeOH (100 ml), Pd / C (10%, 1.355 g) was added and washed with hydrogen three times. The resulting solution was stirred under a hydrogen flask for 16 h. The mixture was washed with nitrogen and filtered through Celite. The filtrate was concentrated to produce the desired product 8-(2-fluorophenyl)1,4-dioxaspiro[4,5]decane, which was carried to the next step as such. LCMS: m / z = 237 [M+H]+; 1H NMR (400 MHz, Chloroform-d) δ 7.37 - 7.24 (m, 1H), 7.18 (tdd, J = 7.4, 5.1, 1.8 Hz, 1H), 7.10 (td, J = 7.6, 1.4 Hz, 1H), 7.06 - 6.95 (m, 1H), 4.01 (s, 4H), 3.03 - 2.86 (m, 1H), 1.96 - 1.65 (m, 9H).

[00185] Step 3: The crude 8-(2-fluorophenyl)-1,4-dioxaspiro[4,5]decane residue was dissolved in DCM (15 ml), and TFA (28.0 ml, 364 mmol) was added at room temperature. The mixture was Petition 870260065188, dated 02 / 07 / 2026, p. 132 / 516 128 / 236 stirred at room temperature for 2 days. LCMS showed a single peak of the desired product. The mixture was concentrated, diluted with EtOAc and washed with saturated aqueous solution of sodium bicarbonate, water, brine, dried with sodium sulfate and concentrated. The residue was purified by chromatography (silica gel, 120 g, 0-50% EtOAc / heptane) to yield 4-(2-fluorophenyl)cyclohexan-1-one (3.6 g, 98% yield). 1H NMR (400 MHz, Chloroform-d) δ 7.61 - 7.22 (m, 2H), 7.10 (dt, J = 26.2, 8.5 Hz, 2H), 3.61 - 3.28 (m, 1H), 2.82 - 2.44 (m, 4H), 2.44 - 2.17 (m, 2H), 2.17 - 1.87 (m, 2H).

[00186] Step 4: NaH (1.032 g, 25.8 mmol) was added to diethyl carbonate (23.45 ml, 194 mmol) at room temperature in portions. 4-(2-Fluorophenyl)cyclohexan-1-one (3.1 g, 16.13 mmol) was then added in portions to the reaction mixture. When the reaction was heated to 60 °C, the foam formed rose. The reaction was cooled, and THF (20 ml) was used for rinsing. The mixture was heated to 75 °C for 2 h. The reaction was allowed to cool to room temperature and then neutralized with 2 M aqueous HCl solution. The resulting mixture was extracted with EtOAc (2 x 50 ml). The combined organic layers were dried with sodium sulfate, filtered, and concentrated. The residue was purified by chromatography (80 g, silica gel, EtOAc / heptane 0-30%) to yield ethyl 5-(2-fluorophenyl)-2-oxocyclohexane-1-carboxylate (2.6 g, 54.9% yield). LCMS: m / z = 263 [MH]+.

[00187] Step 5: To a flask containing ethyl 5-(2-fluorophenyl)-2-oxocyclohexane-1-carboxylate (2.3 g, 8.70 mmol) and urea (1.045 g, 17.40 mmol), NaOMe (0.940 g, 17.40 mmol) and MeOH (volume: 20 mL) were added. The mixture was heated to 70 °C for 16 h. The reaction was cooled to room temperature, and the precipitate was filtered, washed with Et2O, and dried to yield 6-(2-fluorophenyl)-5,6,7,8-tetrahydroquinazoline-2,4-diol (2.1 g, 93% yield). LCMS: m / z = Petition 870260065188, dated 02 / 07 / 2026, p. 133 / 516 129 / 236 261.1 [M+H]+; 1H NMR (400 MHz, Methanol-d4) δ 8.57 (s, 1H), 7.34 (td, J = 7.6, 1.9 Hz, 1H), 7.24 (tdd, J = 7.3, 5.2, 1.8 Hz, 1H), 7.18 - 7.11 (m, 1H), 7.11 - 6.96 (m, 1H), 3.19 (tq, J = 9.0, 4.6 Hz, 1H), 2.75 (dd, J = 16.2, 5.3 Hz, 1H), 2.69 - 2.49 (m, 2H), 2.45 - 2.30 (m, 1H), 2.00 (dq, J = 10.9, 5.4Hz, 2H).

[00188] Step 6: To a solution of 6-(2-fluorophenyl)-5,6,7,8-tetrahydroquinazoline-2,4-diol (2.1 g, 8.07 mmol) and Et3N (2.68 ml, 19.36 mmol) in dioxane (8 ml) at 0°C, POCh (7.52 ml, 81 mmol) was slowly added. The mixture was heated to 97°C for 40 h. The reaction mixture was concentrated and poured into ice-cold water and stirred for 30 min. The mixture was extracted with EtOAc (4 x 100 ml) until no product remained in the aqueous layer. The organic layers were combined and concentrated. The residue that was purified by chromatography (silica gel, 120 g, 0-30% EtOAc / heptane) yielded 2,4-dichloro-6-(2-fluorophenyl)-5,6,7,8-tetrahydroquinazoline (0.4 g, 17% yield). LCMS: m / z = 297 [M+H]+; 1H NMR (400 MHz, Methanol-d4) δ 7.46 7.25 (m, 2H), 7.25 - 7.04 (m, 2H), 3.85 - 3.68 (m, 1H), 3.47 - 3.36 (m, 1H), 3.20 - 2.94 (m, 2H), 2.83 (ddd, J = 17.7, 11.3, 1.5 Hz, 1H), 2.25 2.05 (m, 2H).

[00189] Step 7: A solution of 2,4-dichloro-6-(2-fluorophenyl)5,6,7,8-tetrahydroquinazoline (0.4 g, 1.346 mmol), 2,3,5,6-tetrafluorophenol (0.268 g, 1.615 mmol) and DIPEA (0.306 ml, 1.750 mmol) in CH3CN (2 ml) was stirred at 80 °C for 40 h. The residue was purified by chromatography (120 g, silica gel, 0-7%, then 7% EtOAc / heptane constant) to yield 2-chloro-6-(2-fluorophenyl)-4(2,3,5,6-tetrafluorophenoxy)-5,6,7,8-tetrahydroquinazoline (560 mg, 97% yield). LCMS: m / z = 427.1 [M+H]+; 1H NMR (400 MHz, Methanol-d4) δ 7.58 - 7.46 (m, 1H), 7.46 - 7.38 (m, 1H), 7.31 (tdd, J = 7.0, 5.1, 1.6 Hz, 1H), 7.20 (t, J = 7.3 Hz, 1H), 7.13 (dd, J = 10.8, 8.2 Hz, 1H), 3.46 (ddd, J = 11.4, 6.1, 2.5 Hz, 1H), 3.22 (dd, J = 17.3, 4.9 Petition 870260065188, dated 02 / 07 / 2026, p. 134 / 516 130 / 236 Hz, 1H), 3.13 - 2.99 (m, 2H), 2.90 (dd, J = 17.3, 11.2 Hz, 1H), 2.22 (tt, J = 8.9, 4.0 Hz, 2H).

[00190] Step 8: 2-chloro-6-(2-fluorophenyl)-4-(2,3,5,6-tetrafluorophenoxy)-5,6,7,8-tetrahydroquinazoline (280 mg, 0.656 mmol), (1R,4r)-4-((R)-1-(methylamino)propyl)cyclohexane-1-carboxylate methyl (263 mg, 0.919 mmol) in anhydrous acetonitrile (volume: 0.4 ml) in a 5 ml microwaveable flask, DIPEA (0.458 ml, 2.62 mmol) was added. The resulting mixture was heated to 100 °C for 72 h. The reaction mixture was purified by chromatography (40 g, silica gel, 0-10% EtOAc / heptane) to yield methyl (1R,4r)-4-((1R)-1-((6-(2-fluorophenyl)-4-(2,3,5,6-tetrafluorophenoxy)-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylate (176 mg, 44% yield).LCMS: m / z = 604,3 [M+H]+; RMN de1H (400 MHz, Metanol-d4) δ 7,36 (s, 1H), 7,30 (td, J = 7,6, 1,8 Hz, 1H), 7,16 (tdd, J = 7,3, 5,1, 1,8 Hz, 1H), 7,07 (td, J = 7,6, 1,4 Hz, 1H), 7,03 - 6,93 (m, 1H), 3,74 (s, 1H), 3,54 (s, 3H), 2,95 (dd, J = 16,2, 5,2 Hz, 1H), 2,76 (d, J = 17,6 Hz, 4H), 2,62 (dd, J = 16,2, 11,3 Hz, 1H), 2,06 (s, 5H), 1,90 - 1,67 (m, 3H), 1,55 - 1,12 (m, 6H), 0,45 - 0,68 (m, 5H).

[00191] Step 9: A solution of (R)-1-(1-methyl-1H-pyrazol-4-yl)-2((S)-3-methylpiperidin-1-yl)ethan-1-amine (103 mg, 0.350 mmol), (1R,4r)4-((1R)-1-((6-(2-fluorophenyl)-4-(2,3,5,6-tetrafluorophenoxy)-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylate methyl (176 mg, 0.292 mmol) and DIPEA (0.204 ml, 1.166 mmol) in isopropanol (0.25 ml) in a chemical glass pressure vessel (20 ml) was stirred at 110 °C for 2 days. 100 mg of (R)-1-(1-methyl-1H-pyrazol-4-yl)2-((S)-3-methylpiperidin-1-yl)ethan-1-amine (100 mg, 0.34 mmol) and DIPEA (0.2 mL, 1.16 mmol) were added and heated at 105 °C for 2 days. The mixture was concentrated under vacuum, and the residue was purified by chromatography (40 g, silica gel, 0-85% EtOAc / DCM) to yield (1R,4r)-4-((1R)-1-((6-(2-fluorophenyl)-4-(((R)-1-(1-methyl-1H-pyrazol Petition 870260065188, dated 02 / 07 / 2026, page 135 / 516 131 / 236 4-yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)amino)-5,6,7,8-tetra-hidroquinazolin2-yl)(methyl)amino)propyl)cyclo-hexane-1-carboxylate methyl (0.1 g, 52 % yield). LCMS: m / z = 660.4 [M+H]+.

[00192] Step 10: To a solution of (1R,4r)-4-((1R)-1-((6-(2-fluorophenyl)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylate methyl (100 mg, 0.152 mmol) in MeOH (2 ml) and water (0.5 ml), NaOH (4 M aqueous solution, 0.379 ml, 1.515 mmol) was added and stirred at 50 °C for 30 min.The reaction mixture was purified by chiral separation using SFC (2.0 x 25.0 cm ChromegaChiral CC4 column from ES Industries, methanol / acetonitrile (1:3) with 30 mM ammonium acetate, 65% cosolvent at 70 g / min, 100 bar, 25 °C) to yield (1R,4r)-4-((R)-1-(((R)-6-(2-fluorophenyl)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid (21 mg, 20% yield) and acid (1R,4r)-4-((R)-1-(((S)-6-(2fluorophenyl)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidi n-1yl)ethyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid (19 mg, 18% yield).

[00193] Acid (1 R,4r)-4-((R)-1-(((R)-6-(2-fluorophenyl)-4-(((R)-1-(1methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidine- 1-yl)ethyl)amino)-5,6,7,8tetra-hydroquinazolin-2-yl)(methyl)amino)propyl)cyclo-hexane-1-carboxylic: LCMS: m / z = 646.5[M+H]+; NMR de1H (400 MHz, DMSO-d6) δ 7.53 7.37 (m, 2H), 7.37 - 7.25 (m, 2H), 7.19 (q, J = 10.1, 8.6 Hz, 2H), 6.13 (d, J = 7.5 Hz, 1H), 5.31 (s. 1H), 4.49 (s, 1H), 3.75 (s, 3H), 3.18 (s, 2H), 2.89 - 2.58 (m, 7H), 2.29 (dd, J = 23.7, 10.7 Hz, 2H), 2.09 (s, 3H), 2.03 - 1.46 (m, 12H), 1.25 (t, J = 41.8 Hz, 6H), 1.02 - 0.46 (m, 7H).

[00194] Acid (1R,4r)-4-((R)-1-(((S)-6-(2-fluorophenyl)-4-(((R)-1-(1). methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)amino)-5,6,7,8tetra-hydroquinazolin-2-yl)(methyl)amino)propyl)cyclo-hexane-1-carboxylic: Petition 870260065188, 02 / 07 / 2026, p. 136 / 5 132 / 2 LCMS: m / z = 646.5 [M+H]+; RMN de1H (400 MHz, DMSO-d6) δ 7.54 7.40 (m, 2H), 7.40 - 7.23 (m, 2H), 7.19 (q, J = 8.6, 7.7 Hz, 2H), 6.14 (s, 1H), 5.31 (s, 1H), 4.50 (s, 1H), 3.75 (s, 3H), 3.18 (s, 2H), 2.71 (q, J = 24.6, 23.9 Hz, 7H), 2.31 (d, J = 15.6 Hz, 2H), 2.09 (s, 3H), 1.91 (s, 6H), 1.79 - 1.44 (m, 6H), 1,25 (t, J = 40.5 Hz, 6H), 0.98 - 0.63 (m, 7H). Example 13: Síntese de ácido (1R,4r)-4-((R)-1-(metil((R)-4-(((R)-1-(1metil-1H-pirazol-4-il)-2-((S)-3-metilpiperidin-1-il) etil)amino)-6-fenil5,6,7,8-tetra-hydroquinazolin-2-il)amino)propil)ciclo-hexano-1carboxílico (Compost 40)

[00195] Step 1: A solution of (R)-2,4-dichloro-6-phenyl-5,6,7,8-tetrahydroquinazoline (1265 mg, 4.53 mmol), (R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1-yl)ethan-1-amine dihydrochloride (1338 mg, 4.53 mmol) and DIPEA (2769 μL, 15.86 mmol) in MeCN (volume: 22 ml) was stirred at 70 °C for 3 h. MeCN was removed under reduced pressure, then the residue was extracted with EtOAc / water. The combined organic layer was washed with brine, dried with Na2SÜ4 and concentrated. The residue was purified by flash column chromatography (0-20% MeOH (NH30.1 N) / DCM) to yield (R)-2-chloro-N-((R)1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)-6-phenyl-5,6,7,8-tetrahydroquinazolin-4-amine as a pale clear solid (949 mg, 45%). MS: m / z = 465.1 [M+H]+.

[00196] Step 2: A solution of (R)-2-chloro-N-((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)-6-phenyl-5,6,7,8-tetrahydroquinazoline-4-amine (920 mg, 1.98 mmol), (1R,4r)-4-((R)-1 Petition 870260065188, dated 02 / 07 / 2026, p. 137 / 516 133 / 236 (methylamino)propyl)cyclohexane-1-carboxylate methyl (844 mg, 3.96 mmol) and DIPEA (1.727 ml, 9.89 mmol) in MeCN (4 ml) was heated to 160 °C in a microwave reactor for 2 days. The reaction mixture was diluted with EtOAc, washed with brine, dried with Na2SO4, and concentrated. The residue was purified using flash column chromatography (0-20% MeOH (0.1 N NH3) / DCM) to yield (1R,4r)-4-((R)1-(methyl((R)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)amino)propyl)cyclohexane-1-carboxylate methyl as a pale clear solid (832 mg, 65%). MS: m / z = 642.4 [M+H]+.

[00197] Step 3: To a solution of (1R,4r)-4-((R)-1-(methyl((R)-4(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)amino)propyl)cyclohexane-1-carboxylate methyl (832 mg, 1.296 mmol) in THF (6 ml) and MeOH (3 ml), NaOH (4 N aqueous solution) (1.620 ml, 6.48 mmol) was added. The resulting suspension was stirred at 50 °C for 30 min, then the solvent was removed under reduced pressure, and then diluted with DMSO. The suspension was purified by reversed-phase column chromatography. (Column 150 g ISCO gold C-18, 20-70% MeCN / water, with 0.1% NH4OH as modifier). The pure fractions were combined, and freeze-drying yielded a sodium salt of (1R,4r)-4-((R)-1-(methyl((R)-4(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)amino)propyl)cyclohexane-1-carboxylic acid as a white solid (445 mg, 43%).MS: m / z = 628.5 [M+H]+; 1H NMR (400 MHz, Methanol-d4) δ 7.49 (s, 1H), 7.40 (s, 1H), 7.38 - 7.30 (m, 4H), 7.25 - 7.19 (m, 1H), 5.49 (s, 1H), 4.54 (s, 1H), 3.86 (s, 3H), 3.05 - 2.94 (m, 2H), 2.93 - 2.82 (m, 5H), 2.78 - 2.71 (m, 3H), 2.64 (dd, J = 12.8, 5.3 Hz, 1H), 2.47 - 2.36 (m, 1H), 2.16 - 1.95 (m, 5H), 1.94 - 1.62 (m, 7H), 1.58 - 1.25 (m, 6H), 1.06 - 0.84 (m, 5H), 0.79 (t, J = 7.2 Hz, 4H). Petition 870260065188, dated 02 / 07 / 2026, p. 138 / 516 134 / 236

[00198] The following compounds were produced using the above procedure or modifications to the above procedure using the corresponding intermediates. Table 2 128 136 LCMS m / z [M+H]+ = 666,6, RMN de1H (400 MHz, MeOD) δ 7,40 (s, 1H), 7,30 (s, 1H), 7,28 - 7,17 (m, 5H), 7,16 - 6,99 (m, 1H), 5,17 (s, 1H), 3,75 (s, 3H), 2,96 - 2,53 (m, 9H), 2,37 (s, 1H), 2,13 1,10 (m, 29H), 0,90 - 0,58 __________(m, 3H).__________ LCMS m / z [M+H]+= 626,4, RMN de1H (400 MHz, Metanol-d4) δ 7,61 - 6,81 (m, 7H), 5,61 (d, J = 169,9 Hz, 1H), 4,37 (s, 1H), 3,73 (d, J = 8,9 Hz, 4H), 2,98 - 2,13 (m, 11H), 2,08 - 1,05 (m, 20H), 1,02 - 0,32 (m, 5H). LCMS m / z [M+H]+= 622,3, RMN de1H (400 MHz, MeOD) δ 7,19 - 6,93 (m, 10H), 4,96 (s, 1H), 4,11 (s, 1H), 2,74 (dd, J = 29,1, 13,1 Hz, 4H), 2,55 (s, 6H), 2,43 - 2,13 (m, 3H), 2,01 - 0,97 (m, 22H), 0,84 (d, J = 39,5 Hz, 2H). Petição 870260065188, de 02 / 07 / 2026, pág. 139 / 516 135 / 236 LCMS m / z [M+H]+ = 664,3, RMN de1H (400 MHz, Metanol-d4) δ 7,49 (s, 1H), 7,39 (s, 1H), 7,33 (td, J = 8,0, 6,1 Hz, 1H), 7,17 (dt, J = 7,8, 1,2 Hz, 1H), 7,10 (dt, J = 10,5, 2,1 Hz, 1H), 6,97 - 6,91 (m, 1H), 5,47 (s, 1H), 4,52 (s, 1H), 4,41 - 4,12 (m, 2H), 3,85 (s, 3H), 3,09 (t, J = 5,6 Hz, 2H), 3,03 - 2,87 (m, 4H), 2,78 - 2,70 (m, 3H), 2,65 (dd, J = 12,8, 5,5 Hz, 1H), 2,47 2,35 (m, 1H), 2,10 (td, J = 10,8, 2,7 Hz, 2H), 2,05 - 1,94 (m, 4H), 1,85 - 1,62 (m, 7H), 1,60 - 1,23 (m, 6H), 1,10 (dd, J = 11,2, 8,5 Hz, 1H), 0,94 (d, J = 12,7 Hz, 1H), 0,77 (t, J = 7,2 Hz, 3H), 0,65 (d, J = 13,3 Hz, 1H). LCMS m / z [M+H]+= 662,4, RMN de1H (400 MHz, Metanol-d4) δ 7,37 (s, 1H), 7,32 - 7,19 (m, 2H), 7,07 (d, J = 7,8 Hz, 1H), 7,00 (dt, J = 10,5, 2,1 Hz, 1H), 6,83 (td, J = 8,3, 2,3 Hz, 1H), 5,34 (s, 1H), 4,40 (s, 1H), 3,74 (s, 3H), 3,32 (dd, J = 10,7, 5,7 Hz, 1H), 3,28 - 3,23 (m, 1H), 2,97 - 2,76 (m, 4H), 2,71 (s, 3H), 2,68 - 2,58 (m, 3H), 2,57 - 2,47 (m, 1H), 2,35 2,25 (m, 1H), 2,03 - 1,54 (m, 12H), 1,48 - 1,13 (m, 6H), 0,97 - 0,77 (m, 2H), 0,70 Petição 870260065188, de 02 / 07 / 2026, pág. 140 / 516 136 / 236 ________0,49 (m, 4H).________ LCMS m / z [M+H]+ = 646,3, RMN de1H (400 MHz, Metanol-d4) δ 7,40 (s, 1H), 7,30 (s, 1H), 7,23 (td, J = 8,0, 6,1 Hz, 1H), 7,07 (dt, J = 7,8, 1,3 Hz, 1H), 7,00 (dt, J = 10,4, 2,1 Hz, 1H), 6,88 - 6,80 (m, 1H), 5,38 (s, 1H), 4,42 (s, 1H), 3,75 (s, 3H), 2,76 (d, J = 14,5 Hz, 7H), 2,69 - 2,50 (m, 4H), 2,35 (dd, J = 15,7, 10,8 Hz, 1H), 2,01 (d, J = 13,1 Hz, 1H), 1,96 - 1,83 (m, 4H), 1,82 - 1,50 (m, 7H), 1,49 1,14 (m, 6H), 0,89 - 0,73 (m, 5H), 0,72 - 0,64 (m, 3H), 0,59 - 0,49 (m, 1H) LCMS m / z [M+H]+= 644,4, RMN de1H (400 MHz, Metanol-d4) δ 7,36 (d, J = 2,9 Hz, 1H), 7,30 - 7,18 (m, 5H), 7,12 - 7,06 (m, 1H), 5,32 (s, 1H), 4,40 (s, 1H), 3,74 (s, 3H), 3,31 (dd, J = 10,8, 5,7 Hz, 1H), 3,26 - 3,23 (m, 1H), 2,94 - 2,67 (m, 7H), 2,66 2,58 (m, 3H), 2,56 - 2,47 (m, 1H), 2,37 - 2,26 (m, 1H), 2,02 - 1,54 (m, 12H), 1,48 1,12 (m, 6H), 0,98 - 0,80 (m, 2H), 0,73 - 0,47 (m, 4H). Petição 870260065188, de 02 / 07 / 2026, pág. 141 / 516 137 / 236 101 103 LCMS m / z [M+H]+ = 628,4, RMN de1H (400 MHz, Metanol-d4) δ 7,49 (s, 1H), 7,40 (s, 1H), 7,36 - 7,29 (m, 4H), 7,24 - 7,17 (m, 1H), 5,47 (s, 1H), 4,52 (s, 1H), 3,85 (s, 3H), 3,08 - 2,92 (m, 2H), 2,91 - 2,81 (m, 5H), 2,79 2,59 (m, 4H), 2,46 (dd, J = 15,8, 10,7 Hz, 1H), 2,14 2,07 (m, 1H), 2,05 - 1,93 (m, 4H), 1,92 - 1,61 (m, 7H), 1,58 - 1,24 (m, 6H), 1,04 0,83 (m, 5H), 0,79 (t, J = 7,2 Hz, 3H), 0,71 - 0,55 (m, 1H). LCMS m / z [M+H]+= 640,4, RMN de1H (400 MHz, Metanol-d4) δ 7,38 (s, 1H), 7,29 (s, 1H), 7,26 - 7,19 (m, 4H), 7,10 (tt, J = 7,2, 1,9 Hz, 1H), 5,17 (s, 1H), 4,38 (s, 1H), 3,74 (s, 3H), 3,17 (s, 2H), 2,94 - 2,84 (m, 1H), 2,74 (d, J = 16,3 Hz, 5H), 2,63 (dt, J = 10,6, 5,4 Hz, 3H), 2,42 2,25 (m, 1H), 1,99 (d, J = 13,1 Hz, 1H), 1,88 (s, 5H), 1,80 - 1,46 (m, 8H), 1,44 1,15 (m, 8H), 0,82 (d, J = 13,2 Hz, 1H), 0,65 (t, J = 7,2 Hz, 3H), 0,54 (s, 1H). Petição 870260065188, de 02 / 07 / 2026, pág. 142 / 516 138 / 236 118 129 LCMS m / z [M+H]+ = 614,3, RMN de1H (400 MHz, Metanol-d4) δ 7,46 (s, 1H), 7,42 - 7,27 (m, 5H), 7,24 - 7,15 (m, 1H), 5,46 (s, 1H), 4,53 (s, 1H), 3,84 (s, 3H), 3,02 - 2,93 (m, 1H), 2,90 - 2,67 (m, 7H), 2,65 - 2,34 (m, 6H), 2,13 1,93 (m, 4H), 1,91 - 1,69 (m, 3H), 1,65 - 1,22 (m, 11H), 0,92 (d, J = 12,5 Hz, 1H), 0,83 - 0,57 (m, 4H). LCMS m / z [M+H]+= 658,9, RMN de1H (400 MHz, Metanol-d4) δ 7,37 (s, 1H), 7,28 (s, 1H), 7,26 - 7,16 (m, 4H), 7,10 (t, J = 6,9 Hz, 1H), 5,33 (s, 1H), 4,42 (s, 2H), 3,74 (s, 3H), 3,18 - 3,01 (m, 5H), 2,95 - 2,47 (m, 11H), 2,32 (t, J = 13,5 Hz, 1H), 2,13 - 1,62 (m, 10H), 1,56 (d, J = 11,6 Hz, 2H), 1,49 - 1,10 (m, 6H), 0,92 (d, J = 10,9 Hz, 2H), 0,67 (t, J = 7,2 Hz, 3H). LCMS m / z [M+H]+= 630,4, RMN de1H (400 MHz, Metanol-d4) δ 7,52 (s, 1H), 7,46 - 7,28 (m, 5H), 7,28 - 7,17 (m, 1H), 5,43 (s, 1H), 3,87 (s, 3H), 3,63 (d, J = 10,0 Hz, 1H), 3,08 - 2,62 (m, 10H), 2,48 (d, J = 13,9 Hz, 1H), 2,20 - 1,14 (m, 17H), 0,96 (s, 1H), 0,80 (t, J = 7,3 Hz, 3H), 0,65 (s, 1H). Sinal para 3H oculto sob picos de solvente. Petição 870260065188, de 02 / 07 / 2026, pág. 143 / 516 139 / 236 134 145 LCMS m / z [M+H]+ = 644,5, RMN de1H (400 MHz, Metanol-d4) δ 7,41 (s, 1H), 7,33 - 7,21 (m, 5H), 7,19 - 7,09 (m, 1H), 5,31 (s, 1H), 4,44 (d, J = 33,6 Hz, 1H), 3,76 (s, 3H), 3,16 (s, 3H), 2,90 (ddt, J = 8,9, 5,5, 3,2 Hz, 1H), 2,79 (s, 3H), 2,77 - 2,65 (m, 4H), 2,59 (dd, J = 12,9, 5,2 Hz, 2H), 2,36 (t, J = 13,5 Hz, 1H), 2,25 - 1,57 (m, 12H), 1,54 - 1,11 (m, 8H), 0,84 (d, J = 13,2 Hz, 1H), 0,69 (t, J = 7,2 Hz, 3H), 0,50 (d, J = 13,1 Hz, 1H). LCMS m / z [M+H]+= 628,3, RMN de1H (400 MHz, Metanol-d4) δ 7,38 (s, 1H), 7,31 - 7,17 (m, 5H), 7,15 - 7,07 (m, 1H), 5,36 (s, 1H), 4,42 (s, 1H), 3,75 (s, 3H), 2,81 (t, J = 11,2 Hz, 4H), 2,74 (s, 3H), 2,65 (q, J = 6,8, 6,2 Hz, 3H), 2,54 (dd, J = 12,9, 4,8 Hz, 1H), 2,31 (t, J = 13,5 Hz, 1H), 2,17 - 1,59 (m, 9H), 1,52 (d, J = 12,9 Hz, 2H), 1,46 - 0,97 (m, 8H), 0,82 (d, J = 6,5 Hz, 4H), 0,66 (t, J = 7,1 Hz, 3H), 0,54 (d, J = 13,4 Hz, 1H). Petição 870260065188, de 02 / 07 / 2026, pág. 144 / 516 140 / 236 LCMS m / z [M+H]+ = 656,4, RMN de1H (400 MHz, Metanol-d4) δ 7,54 (s, 1H), 7,44 (s, 1H), 7,38 - 7,29 (m, 2H), 7,05 (t, J = 8,8 Hz, 2H), 5,41 (s, 1H), 4,73 (s, 1H), 3,84 (s, 3H), 2,92 (m, 6H), 2,83 2,68 (m, 3H), 2,47 - 2,37 (m, 1H), 2,15 - 1,42 (m, 24H), 0,81 (t, J = 7,4 Hz, 3H). LCMS m / z [M+H]+= 646,4, RMN de1H (400 MHz, Metanol-d4) δ 7,47 (s, 1H), 7,42 7,27 (m, 3H), 7,11 - 6,98 (m, 2H), 5,48 (s, 1H), 4,52 (s, 1H), 3,84 (s, 3H), 3,05 - 2,78 (m, 7H), 2,73 (dd, J = 10,4, 5,0 Hz, 3H), 2,63 (dd, J = 12,7, 5,1 Hz, 1H), 2,37 (t, J = 13,2 Hz, 1H), 2,12 - 1,20 (m, 18H), 1,03 - 0,81 (m, 5H), 0,76 (t, J = 7,2 Hz, 4H) LCMS m / z [M+H]+= 659,0, RMN de1H (400 MHz, Metanol-d4) δ 7,44 (s, 1H), 7,33 (td, J = 7,9, 5,9 Hz, 1H), 7,16 (d, J = 7,8 Hz, 1H), 7,09 (dt, J = 10,3, 2,2 Hz, 1H), 6,93 (td, J = 8,4, 2,5 Hz, 1H), 5,47 (s, 1H), 4,74 (s, 1H), 3,23 (d, J = 15,9 Hz, 2H), 3,01 (s, 1H), 2,85 (d, J = 15,7 Hz, 5H), 2,73 (q, J = 5,7, 5,1 Hz, 3H), 2,62 (s, 3H), 2,43 (dd, J = 15,4, 10,9 Hz, 1H), 2,11 (d, J = 13,2 Hz, 1H), 1,96 (s, 3H), 1,87 - 1,19 (m, 16H), Petição 870260065188, de 02 / 07 / 2026, pág. 145 / 516 141 / 236 0,79 (t, J = 7,2 Hz, 3H). LCMS m / z [M+H]+ = 675,3, RMN de1H (400 MHz, MeOD) δ 7,42 (s, 1H), 7,34 (td, J = 8,0, 6,0 Hz, 1H), 7,17 (d, J = 7,7 Hz, 1H), 7,11 (d, J = 10,5 Hz, 1H), 6,95 (td, J = 8,5, 2,6 Hz, 1H), 5,41 (s, 1H), 4,40 (s, 1H), 3,08 - 2,34 (m, 16H), 2,21 - 0,38 (m, 26H). LCMS m / z [M+H]+= 673,4, RMN de1H (400 MHz, MeOD) δ 7,48 (d, J = 9,9 Hz, 2H), 7,25 (td, J = 7,9, 5,9 Hz, 1H), 7,08 (d, J = 7,8 Hz, 1H), 7,02 (dt, J = 10,3, 2,2 Hz, 1H), 6,87 (td, J = 8,5, 2,6 Hz, 1H), 6,46 (d, J = 9,1 Hz, 1H), 5,13 - 4,88 (m, 1H), 4,48 4,12 (m, 1H), 3,45 (s, 3H), 3,01 - 2,60 (m, 11H), 2,59 2,29 (m, 2H), 2,18 - 0,99 (m, 18H), 1,02 - 0,51 (m, 9H), 0,34 (d, J = 13,5 Hz, 1H). LCMS m / z [M+H]+= 672,5, RMN de1H (400 MHz, MeOD) δ 7,24 (td, J = 7,9, 5,9 Hz, 1H), 7,08 (d, J = 7,8 Hz, 1H), 7,01 (dt, J = 10,6, 2,1 Hz, 1H), 6,85 (td, J = 8,5, 2,6 Hz, 1H), 5,87 (s, 1H), 5,38 (s, 1H), 4,45 - 4,18 (m, 1H), 3,78 - 3,42 (m, 5H), 3,16 3,05 (m, 1H), 3,01 - 2,86 (m, 1H), 2,85 - 2,54 (m, 6H), 2,49 - 2,28 (m, 1H), 2,24 Petição 870260065188, de 02 / 07 / 2026, pág. 146 / 516 142 / 236 105 111 113 1,09 (m, 26H), 0,98 (t, J = 12,4 Hz, 1H), 0,88 - 0,32 (m, 4H). LCMS m / z [M+H]+ = 658,6, RMN de1H (400 MHz, MeOD) δ 7,48 (s, 1H), 7,25 (q, J = 7,4 Hz, 1H), 7,06 (dd, J = 25,3, 9,0 Hz, 2H), 6,94 - 6,80 (m, 1H), 6,06 (s, 1H), 5,43 (s, 1H), 4,45 - 4,15 (m, 1H), 3,77 (s, 3H), 3,67 - 3,41 (m, 1H), 3,01 - 2,87 (m, 1H), 2,85 - 2,61 (m, 6H), 2,44 (t, J = 13,5 Hz, 1H), 2,24 - 1,02 (m, 25H), 0,78 (d, J = 13,4 Hz, 1H), 0,66 (t, J = 7,3 Hz, 3H), 0,41 (d, J = 13,7 Hz, _____________1H)._____________ LCMS m / z [M+H]+= 673,4, RMN de1H (400 MHz, MeOD) δ 7,25 (td, J = 8,0, 6,1 Hz, 1H), 7,07 (d, J = 7,7 Hz, 1H), 7,01 (dt, J = 10,6, 2,1 Hz, 1H), 6,95 - 6,79 (m, 1H), 5,26 (s, 1H), 4,63 (s, 1H), 3,02 - 2,88 (m, 1H), 2,89 2,57 (m, 9H), 2,49 (s, 3H), 2,44 - 2,22 (m, 4H), 2,18 1,10 (m, 21H), 0,75 (q, J = 6,3 Hz, 3H). LCMS m / z [M+H]+= 659,5, RMN de1H (400 MHz, MeOD) δ 8,68 (s, 1H), 7,26 (td, J = 7,9, 6,0 Hz, 1H), 7,07 (s, 1H), 7,02 (dt, J = 10,3, 2,0 Hz, 1H), 6,87 (td, J = 8,6, 2,6 Hz, 1H), 5,57 - 5,28 (m, 1H), Petição 870260065188, de 02 / 07 / 2026, pág. 147 / 516 143 / 236 148 4,66 - 4,40 (m, 1H), 3,03 2,92 (m, 1H), 2,92 - 2,76 (m, 5H), 2,77 - 2,59 (m, 3H), 2,49 - 2,35 (m, 4H), 2,15 1,27 (m, 22H), 0,55 - 0,25 (m, 3H). LCMS m / z [M+H]+ = 655,4, RMN de1H (400 MHz, MeOD) δ 7,59 - 7,38 (m, 2H), 7,32 - 7,17 (m, 4H), 7,19 7,01 (m, 1H), 6,42 (d, J = 9,3 Hz, 1H), 4,94 - 4,82 (m, 1H), 4,25 (t, J = 9,0 Hz, 1H), 3,90 (ddd, J = 45,2, 13,3, 6,8 Hz, 2H), 2,90 (ddt, J = 8,2, 5,4, 2,9 Hz, 1H), 2,78 - 2,53 (m, 7H), 2,40 (ddt, J = 35,1, 14,8, 7,7 Hz, 6H), 2,12 - 1,68 (m, 6H), 1,63 - 1,14 (m, 15H), 1,08 - 0,75 (m, 2H), 0,45 0,13 (m, 3H). LCMS m / z [M+H]+= 656,5, RMN de1H (400 MHz, MeOD) δ 7,39 (s, 1H), 7,37 7,24 (m, 2H), 7,21 - 7,10 (m, 1H), 7,10 - 7,02 (m, 1H), 6,97 (dd, J = 10,8, 8,0 Hz, 1H), 5,10 (s, 1H), 4,65 (s, 2H), 3,73 (s, 3H), 3,13 - 2,95 (m, 1H), 2,96 - 2,50 (m, 9H), 2,31 (dd, J = 15,2, 11,0 Hz, 1H), 2,05 - 1,26 (m, 22H), 0,71 (t, J = 7,3 Hz, 3H). Petição 870260065188, de 02 / 07 / 2026, pág. 148 / 516 144 / 236 138 169 LCMS m / z [M+H]+ = 668,7, RMN de1H (400 MHz, DMSO) δ 7,51 (s, 1H), 7,42 7,31 (m, 5H), 7,26 - 7,16 (m, 1H), 6,18 - 6,08 (m, 1H), 5,11 - 4,96 (m, 1H), 4,49 4,30 (m, 1H), 4,04 (q, J = 7,2 Hz, 2H), 2,96 - 2,80 (m, 3H), 2,80 - 2,58 (m, 7H), 2,39 2,23 (m, 1H), 2,01 - 1,58 (m, 13H), 1,56 - 1,45 (m, 2H), 1,45 - 1,06 (m, 14H), 0,89 0,78 (m, 1H), 0,65 (t, J = 7,3 __________Hz, 4H).__________ LCMS m / z [M+H]+= 642,8, RMN de1H (400 MHz, DMSO) δ 7,47 (s, 1H), 7,39 7,28 (m, 5H), 7,29 - 7,15 (m, 1H), 6,20 (d, J = 7,7 Hz, 1H), 5,40 - 5,26 (m, 1H), 4,61 4,42 (m, 1H), 3,88 - 3,71 (m, 4H), 3,07 - 2,94 (m, 2H), 2,93 - 2,82 (m, 2H), 2,80 2,70 (m, 5H), 2,67 - 2,55 (m, 3H), 2,37 - 2,19 (m, 3H), 2,05 - 1,56 (m, 8H), 1,42 0,97 (m, 8H), 0,92 - 0,79 (m, 1H), 0,74 - 0,57 (m, 4H). LCMS m / z [M+H]+= 656,3, RMN de1H (400 MHz, DMSO) δ 7,46 (s, 1H), 7,39 7,28 (m, 5H), 7,26 - 7,18 (m, 1H), 6,17 - 6,04 (m, 1H), 5,12 - 4,97 (m, 1H), 4,47 4,32 (m, 1H), 3,74 (s, 3H), 3,71 - 3,57 (m, 3H), 2,99 2,84 (m, 4H), 2,74 - 2,57 (m, Petição 870260065188, de 02 / 07 / 2026, pág. 149 / 516 145 / 236 5H), 2,38 - 2,20 (m, 3H), 1,98 - 1,55 (m, 11H), 1,52 0,95 (m, 9H), 0,91 - 0,70 (m, 1H), 0,63 (t, J = 7,1 Hz, 3H). LCMS m / z [M+H]+ = 630,3, RMN de1H (400 MHz, DMSO-d6) δ 7,50 (s, 1H), 7,41 - 7,29 (m, 2H), 7,20 (d, J = 7,8 Hz, 2H), 7,09 - 6,98 (m, 1H), 6,16 (d, J = 7,4 Hz, 1H), 5,26 (br s, 1H), 4,82 (br s, 1H), 3,75 (s, 3H), 2,97 2,91 (m, 1H), 2,86 - 2,82 (m, 1H), 2,80 (s, 3H), 2,75 - 2,70 (m, 1H), 2,68 - 2,63 (m, 4H), 2,59 (m, 1H), 2,53 (m, 1H), 2,31 - 2,23 (m, 1H), 1,95 1,86 (m, 2H), 1,81 - 1,67 (m, 6H), 1,48 (br s, 10H), 0,73 (t, J = 7,3 Hz, 3H). LCMS m / z [M+H]+= 630,3, RMN de1H (400 MHz, DMSO-d6) δ 7,59 - 7,44 (m, 1H), 7,42 - 7,27 (m, 2H), 7,23 - 7,14 (m, 2H), 7,08 7,01 (m, 1H), 6,18 (br s, 1H), 5,22 (br s, 1H), 4,76 (br s, 1H), 3,75 (s, 3H), 2,96 - 2,92 (m, 1H), 2,85 - 2,82 (m, 1H), 2,79 (s, 3H), 2,67 - 2,64 (m, 4H), 2,59 (m, 1H), 2,53 (m, 3H), 2,26 (br dd, J = 11,5, 14,9 Hz, 1H), 1,99 - 1,90 (br s, 2H), 1,84 - 1,77 (m, 6H), 1,48 (br s, 10H), 0,74 - 0,60 (m, 3H). Petição 870260065188, de 02 / 07 / 2026, pág. 150 / 516 146 / 236 LCMS m / z [M+H]+ = 642,6, RMN de 1H (400 MHz, DMSO-d6) δ 7,51 (s, 1H), 7,44 - 7,37 (m, 2H), 7,37 7,27 (m, 3H), 7,22 - 7,13 (m, 1H), 6,28 (br d, J = 7,5 Hz, 1H), 5,58 - 5,24 (m, 1H), 4,52 - 4,38 (m, 1H), 3,79 (s, 3H), 2,89 - 2,70 (m, 4H), 2,69 (br s, 3H), 2,62 - 2,54 (m, 1H),2,41 - 2,32 (m, 2H), 2,22 - 2,08 (m, 2H), 2,03 1,78 (m, 6H), 1,76 - 1,55 (m, 6H), 1,45 - 1,24 (m, 8H), 1,23 - 1,02 (m, 2H), 0,90 0,80 (m, 5H), 0,74 - 0,53 (m, 4H) LCMS m / z [M+H]+=626,6, RMN de1H (400 MHz, DMSO-d6) δ 7,55 (s, 1H), 7,41 - 7,33 (m, 3H), 7,29 (br t, J = 7,6 Hz, 2H), 7,21 - 7,12 (m, 1H), 6,32 (br d, J = 7,6 Hz, 1H), 5,61 - 5,29 (m, 1H), 4,77 (br s, 1H), 3,78 (s, 3H), 2,92 - 2,64 (m, 7H), 2,61 2,54 (m, 1H), 2,44 - 2,33 (m, 2H), 2,23 - 2,02 (m, 2H), 2,00 - 1,81 (m, 2H), 1,80 1,50 (m, 10H), 1,48 - 1,36 (m, 3H), 1,26 (s, 3H), 0,89 0,62 (m, 7H). Petição 870260065188, de 02 / 07 / 2026, pág. 151 / 516 147 / 236 LCMS m / z [M+H]+ = 644,6, RMN de1H (400 MHz, DMSO-d6) δ 7,56 (br s, 1H), 7,42 - 7,34 (m, 3H), 7,33 7,27 (m, 2H), 7,21 - 7,13 (m, 1H), 6,31 (br d, J =7,3 Hz, 1H), 5,66 - 5,23 (m, 1H), 4,76 (br s, 1H), 4,46 - 4,35 (m, 1H), 4,34 - 4,22 (m, 1H), 4,21 - 4,12 (m, 1H), 3,78 (s, 3H), 2,93 (br d, J = 8,9 Hz, 1H), 2,84 - 2,66 (m, 6H), 2,60 (br dd, J = 7,1, 12,3 Hz, 2H), 2,45 - 2,31 (m, 2H), 2,27 - 2,17 (m, 1H), 2,162,03 (m, 2H), 2,00 - 1,83 (m, 3H), 1,81 - 1,64 (m, 5H), 1,59 (br d, J = 10,0 Hz, 2H), 1,52 - 1,37 (m, 3H), 1,33 1,21 (m, 3H), 1,09 - 0,96 (m, 1H), 0,72 (br t, J = 6,6 Hz, ____________3H).____________ LCMS m / z [M+H]+= 644,6. RMN de1H (400 MHz, DMSO-d6) δ 12,50 - 12,06 (m, 1H), 7,76 - 7,57 (m, 1H), 7,47 - 7,33 (m, 2H), 7,31 7,17 (m, 2H), 7,13 - 7,00 (m, 1H), 5,03 - 4,68 (m, 1H), 4,07 (q, J = 7,3 Hz, 2H), 3,84 - 3,34 (m, 6H), 3,20 - 2,61 (m, 8H), 2,59 - 2,52 (m, 3H), 2,33 -2,22 (m, 1H), 2,01 1,47 (m, 13H), 1,32 (t, J = 7,3 Hz, 3H), 0,93 - 0,65 m, 6H). Petition 870260065188, dated 02 / 07 / 2026, p. 152 / 516 148 / 236 LCMS m / z [M+H]+ = 672,6, RMN de1H (400 MHz, DMSO-d6) δ 7,40 - 7,32 (m, 1H), 7,28 (s, 1H), 7,18 (br d, J = 7,8 Hz, 2H), 7,07 - 6,98 (m, 1H), 6,11 (br d, J = 6,1 Hz, 1H), 5,31 - 4,97 (m, 1H), 4,51 - 4,42 (m, 1H), 3,65 (br s, 3H), 3,18 (br d, J = 3,1 Hz, 1H), 3,06 (br s, 1H), 2,95 2,89 (m, 2H), 2,72 (s, 3H), 2,61 (br dd, J = 3,3, 14,7 Hz, 5H), 2,34 - 2,22 (m, 2H), 2,19 (s, 3H), 1,99 - 1,87 (m, 4H), 1,85 - 1,75 (m, 4H), 1,72 - 1,53 (m, 3H), 1,51 1,44 (m, 4H), 1,40 - 1,20 (m, 8H), 1,16 - 1,10 (m, 1H), 0,69 (br t, J = 7,0 Hz, 3H). LCMS m / z [M+H]+= 686,7, RMN de1H (400 MHz, DMSO-d6) δ 7,50 (br s, 1H), 7,41 - 7,29 (m, 2H), 7,18 (br d, J = 8,2 Hz, 2H), 7,04 (br t, J = 8,1 Hz, 1H), 6,23 - 6,02 (m, 1H), 5,29 - 4,92 (m, 1H), 4,57 - 4,37 (m, 1H), 4,03 (q, J = 7,0 Hz, 2H), 3,01 - 2,81 (m, 4H), 2,80 - 2,55 (m, 8H), 2,36 - 2,26 (m, 1H), 2,07 1,73 (m, 12H), 1,73 - 1,48 (m, 4H), 1,44 - 1,21 (m, 11H), 1,15 - 1,03 (m, 1H), 0,83 (br d, J = 10,9 Hz, 1H), 0,74 - 0,48 (m, 4H). Petição 870260065188, de 02 / 07 / 2026, pág. 153 / 516 149 / 236 LCMS m / z [M+H]+ = 646,6, RMN de 1H (400 MHz, DMSO-d6) δ 7,47 (s, 1H), 7,39 - 7,28 (m, 5H), 7,26 7,17 (m, 1H), 6,30 - 6,12 (m, 1H), 5,59 - 5,38 (m, 1H), 4,59 (br t, J = 9,2 Hz, 1H), 3,74 (s, 3H), 2,95 - 2,59 (m, 11H), 2,26 - 2,16 (m, 1H), 1,98 - 1,84 (m, 4H), 1,84 1,58 (m, 7H), 1,57 - 1,30 (m, 6H), 1,26 - 1,02 (m, 2H), 0,80 (br d, J = 6,1 Hz, 4H), 0,70 (br t, J = 6,0 Hz, 3H). LCMS m / z [M+H]+= 642,6, RMN de1H (400 MHz, DMSO-d6) δ 7,52 (br s, 1H), 7,42 - 7,26 (m, 3H), 7,15 (t, J = 8,9 Hz, 2H), 6,31 - 6,07 (m, 1H), 5,34 - 5,00 (m, 1H), 4,90 - 4,68 (m, 1H), 3,74 (s, 3H), 3,18 (br s, 2H), 3,08 (br s, 1H), 2,94 - 2,87 (m, 1H), 2,79 (s, 3H), 2,64 - 2,55 (m, 4H), 2,31 - 2,21 (m, 1H), 1,93 - 1,63 (m, 10H), 1,58 1,39 (m, 7H), 1,35 - 1,29 (m, 1H), 1,23 (br s, 2H), 0,72 (br t, J = 7,3 Hz, 3H). LCMS m / z [M+H]+= 652,6, RMN de1H (400 MHz, DMSO-d6) δ 7,62 - 7,51 (m, 1H), 7,45 - 7,33 (m, 3H), 7,33 - 7,24 (m, 2H), 7,22 7,14 (m, 1H), 6,35 - 6,15 (m, 1H), 5,36 - 4,99 (m, 1H), 4,68 (br d, J = 7,8 Hz, 1H), Petição 870260065188, de 02 / 07 / 2026, pág. 154 / 516 150 / 236 3,77 (s, 3H), 2,92 (br d, J = 6,5 Hz, 2H), 2,80 - 2,71 (m, 6H), 2,45 - 2,39 (m, 2H), 2,26 - 2,16 (m, 1H), 2,11 2,04 (m, 1H), 1,97 - 1,80 (m, 8H), 1,77 - 1,59 (m, 6H), 1,53 (br s, 2H), 1,48 - 1,37 (m, 6H), 1,26 (s, 3H), 0,76 0,64 (m, 3H).________ LCMS m / z [M+H]+ = 638,6, RMN de1H (400 MHz, DMSO-d6) δ 7,56 (br s, 1H), 7,45 - 7,35 (m, 3H), 7,31 (br t, J = 7,6 Hz, 2H), 7,23 - 7,13 (m, 1H), 6,38 (br s, 1H), 5,11 (br d, J = 3,9 Hz, 1H), 4,73 (br t, J = 6,7 Hz, 1H), 3,78 (s, 3H), 3,21 (br s, 2H), 3,12 (br s, 2H), 2,85 - 2,72 (m, 4H), 2,70 - 2,58 (m, 3H), 2,41 (br d, J = 16,0 Hz, 2H), 2,28 2,15 (m, 1H), 2,13 - 2,04 (m, 1H), 1,94 - 1,81 (m, 3H), 1,77 - 1,68 (m, 3H), 1,67 1,59 (m, 3H), 1,52 (br d, J = 8,4 Hz, 2H), 1,49 - 1,40 (m, 3H), 1,37 (br d, J = 6,7 Hz, 1H), 1,27 (s, 5H), 0,71 (br t, J = 6,6 Hz, 3H). LCMS m / z [M+H]+= 672,7, RMN de1H (400 MHz, DMSO-d6) δ 7,60 - 7,42 (m, 1H), 7,41 - 7,27 (m, 2H), 7,19 (br d, J = 7,8 Hz, 2H), 7,09 - 6,99 (m, 1H), 6,16 (br d, J = 6,4 Hz, 1H), 5,31 4,89 (m, 1H), 4,61 - 4,29 (m, Petição 870260065188, de 02 / 07 / 2026, pág. 155 / 516 151 / 236 1H), 3,74 (s, 3H), 3,44 (br d, J = 7,1 Hz, 1H), 3,00 - 2,91 (m, 1H), 2,87 (br d, J = 6,6 Hz, 2H), 2,71 (s, 5H), 2,66 2,56 (m, 2H), 2,34 - 2,27 (m, 1H), 2,00 - 1,69 (m, 12H), 1,66 - 1,56 (m, 1H), 1,50 (br d, J = 5,4 Hz, 2H), 1,45 1,20 (m, 8H), 1,16 - 1,02 (m, 1H), 0,89 - 0,75 (m, 1H), 0,70 - 0,60 (m, 3H), 0,58 0,38 (m, 1H). LCMS m / z [M+H]+ = 658,6, RMN de1H (400 MHz, DMSO-d6) δ 7,57 - 7,43 (m, 1H), 7,42 - 7,30 (m, 3H), 7,15 (t, J = 8,9 Hz, 2H), 6,26 - 6,06 (m, 1H), 5,32 - 4,97 (m, 1H), 4,57 - 4,36 (m, 1H), 3,74 (s, 3H), 3,19 - 3,05 (m, 2H), 2,97 - 2,86 (m, 1H), 2,71 (s, 3H), 2,61 - 2,56 (m, 3H), 2,30 - 2,22 (m, 1H), 2,06 - 1,98 (m, 1H), 1,94 1,75 (m, 7H), 1,74 - 1,68 (m, 1H), 1,66 - 1,42 (m, 7H), 1,39 - 1,17 (m, 8H), 1,17 1,07 (m, 1H), 0,91 - 0,78 (m, 1H), 0,66 (br t, J = 7,2 Hz, 3H), 0,57 - 0,43 (m, 1H). Petição 870260065188, de 02 / 07 / 2026, pág. 156 / 516 152 / 236 LCMS m / z [M+H]+ = 658,6, RMN de 1H (400 MHz, DMSO-d6) δ 7,46 (s, 1H), 7,42 - 7,29 (m, 2H), 7,19 (br d, J = 8,1 Hz, 2H), 7,11 6,97 (m, 1H), 6,24 (br d, J = 6,6 Hz, 1H), 5,02 (br d, J = 6,4 Hz, 1H), 4,61 - 4,34 (m, 1H), 3,74 (s, 3H), 3,17 - 3,04 (m, 2H), 2,99 - 2,88 (m, 1H), 2,71 (s, 3H), 2,65 - 2,51 (m, 6H), 2,32 - 2,18 (m, 1H), 2,03 - 1,85 (m, 4H), 1,83 1,68 (m, 4H), 1,66 - 1,44 (m, 6H), 1,43 - 1,17 (m, 7H), 1,16 - 1,02 (m, 1H), 0,92 0,75 (m, 1H), 0,69 - 0,60 (m, 3H), 0,56 - 0,41 (m, 1H). LCMS m / z [M+H]+= 654,6, RMN de1H (400 MHz, DMSO-d6) δ 7,49 (s, 1H), 7,43 - 7,37 (m, 2H), 7,37 7,27 (m, 3H), 7,24 - 7,15 (m, 1H), 6,46 - 6,18 (m, 1H), 5,39 - 4,91 (m, 1H), 4,57 4,33 (m, 1H), 3,77 (s, 3H), 3,23 - 3,05 (m, 2H), 2,81 (br d, J = 16,0 Hz, 1H), 2,74 2,61 (m, 5H), 2,47 - 2,36 (m, 3H), 2,26 - 2,03 (m, 3H), 1,96 - 1,75 (m, 6H), 1,73 1,44 (m, 8H), 1,36 - 1,23 (m, 9H), 1,14 - 1,02 (m, 1H), 0,90 - 0,77 (m, 1H), 0,71 0,61 (m, 3H), 0,53 - 0,39 (m, 1H). Petição 870260065188, de 02 / 07 / 2026, pág. 157 / 516 153 / 236 LCMS m / z [M+H]+ = 676,6, RMN de 1H (400 MHz, DMSO-d6) δ 7,45 (s, 1H), 7,40 - 7,27 (m, 2H), 7,20 (br d, J = 7,8 Hz, 2H), 7,08 6,99 (m, 1H), 6,20 - 6,05 (m, 1H), 5,55 - 5,22 (m, 1H), 4,59 - 4,38 (m, 1H), 3,74 (s, 3H), 3,19 - 3,13 (m, 4H), 3,13 - 3,05 (m, 1H), 2,98 2,84 (m, 2H), 2,78 - 2,69 (m, 3H), 2,69 - 2,59 (m, 3H), 2,56 (br d, J = 4,4 Hz, 1H), 2,52 (d, J = 1,9 Hz, 2H), 2,32 - 2,22 (m, 1H), 2,05 -1,95 (m, 2H), 1,95 - 1,78 (m, 5H), 1,74 (br dd, J = 9,0, 9,9 Hz, 2H), 1,66 - 1,48 (m, 3H), 1,47 - 1,20 (m, 5H), 1,19 1,05 (m, 1H), 0,99 - 0,81 (m, 2H), 0,68 (br t, J = 6,8 Hz, 3H), 0,62 - 0,49 (m, 1H). LCMS m / z [M+H]+= 644,6, RMN de1H (400 MHz, DMSO-d6) δ 7,58 - 7,50 (m, 1H), 7,34 (br d, J = 7,7 Hz, 3H), 7,31 - 7,24 (m, 2H), 7,22 - 7,11 (m, 1H), 6,43 6,23 (m, 1H), 5,44 - 5,18 (m, 1H), 4,82 - 4,64 (m, 1H), 4,47 - 4,13 (m, 2H), 3,77 (s, 3H), 3,17 (s, 1H), 2,85 - 2,66 (m, 6H), 2,43 - 2,28 (m, 3H), 2,25 - 1,97 (m, 5H), 1,92 1,72 (m, 7H), 1,61 (br d, J = 8,2 Hz, 2H), 1,53 - 1,37 (m, 3H), 1,35 - 1,22 (m, 3H), Petição 870260065188, de 02 / 07 / 2026, pág. 158 / 516 154 / 236 1,12 - 1,01 (m, 1H), 0,62 (br d, J = 1,5 Hz, 3H). LCMS m / z [M+H]+ = 660,6, RMN de1H (400 MHz, DMSO-d6) δ 7,54 - 7,44 (m, 1H), 7,40 - 7,33 (m, 1H), 7,30 (s, 1H), 7,19 (br d, J = 7,8 Hz, 2H), 7,08 - 6,99 (m, 1H), 6,22 - 6,05 (m, 1H), 5,55 - 5,25 (m, 1H), 4,59 4,44 (m, 1H), 3,75 (s, 3H), 2,99 - 2,88 (m, 1H), 2,81 (br d, J = 8,2 Hz, 1H), 2,72 (s, 3H), 2,66 - 2,58 (m, 3H), 2,57 - 2,54 (m, 3H), 2,29 2,19 (m, 1H), 2,04 (br d, J = 6,7 Hz, 2H), 1,97 - 1,84 (m, 3H), 1,82 - 1,70 (m, 2H), 1,68 - 1,57 (m, 4H), 1,56 1,46 (m, 3H), 1,43 - 1,21 (m, 4H), 0,90 (br t, J = 8,9 Hz, 2H), 0,85 - 0,74 (m, 5H), 0,68 (br t, J = 6,7 Hz, 4H). LCMS m / z [M+H]+= 656,6, RMN de1H (400 MHz, DMSO-d6) δ 7,56 (br s, 1H), 7,44 - 7,29 (m, 2H), 7,24 7,13 (m, 2H), 7,09 - 6,97 (m, 1H), 6,30 - 6,14 (m, 1H), 5,30 - 5,10 (m, 1H), 4,89 4,66 (m, 1H), 4,03 (q, J = 7,3 Hz, 2H), 3,19 - 3,08 (m, 3H), 2,96 - 2,91 (m, 1H), 2,79 (s, 3H), 2,64 - 2,59 (m, 3H), 2,36 - 2,21 (m, 2H), 1,94 (br s, 1H), 1,85 - 1,65 (m, 8H), 1,61 - 1,42 (m, 7H), 1,41 Petição 870260065188, de 02 / 07 / 2026, pág.159 / 516. 155 / 236 1,10 (m, 7H), 0,72 (br t, J = 7,2 Hz, 3H). LCMS m / z [M+H]+ = 644,3, RMN de1H (400 MHz, DMSO-d6) δ 7,66 (br d, J = 1,9 Hz, 1H), 7,49 - 7,27 (m, 5H), 7,21 (br t, J = 6,0 Hz, 1H), 6,07 - 5,34 (m, 1H), 4,75 (br s, 1H), 4,58 - 4,02 (m, 3H), 3,79 (s, 4H), 3,54 (br d, J = 9,4 Hz, 2H), 3,18 2,59 (m, 9H), 2,48 - 2,34 (m, 1H), 2,24 - 2,06 (m, 2H), 2,01 - 1,60 (m, 10H), 1,59 1,44 (m, 2H), 1,38 - 1,05 (m, 4H), 0,75 (br s, 3H). LCMS m / z [M+H]+= 644,6, RMN de1H (400 MHz, DMSO-d6) δ 7,43 - 7,27 (m, 2H), 7,19 (br d, J = 7,6 Hz, 2H), 7,08 - 7,01 (m, 1H), 6,57 - 6,03 (m, 1H), 5,87 5,18 (m, 1H), 4,99 - 4,70 (m, 1H), 3,66 (s, 3H), 2,98 - 2,77 (m, 6H), 2,65 - 2,57 (m, 4H), 2,27 - 2,12 (m, 4H), 2,02 1,72 (m, 10H), 1,70 - 1,35 (m, 6H), 0,96 - 0,64 (m, 7H). LCMS m / z [M+H]+= 686,7, RMN de1H (400 MHz, DMSO-d6) δ 7,62 - 7,50 (m, 1H), 7,41 - 7,32 (m, 2H), 7,23 - 7,15 (m, 2H), 7,08 7,00 (m, 1H), 6,20 - 6,04 (m, 1H), 5,28 - 4,96 (m, 1H), 4,58 - 4,36 (m, 1H), 4,03 (q, J = 7,2 Hz, 2H), 3,03 - 2,82 Petição 870260065188, de 02 / 07 / 2026, pág. 160 / 516 156 / 236 (m, 4H), 2,81 - 2,57 (m, 7H), 2,36 - 2,28 (m, 1H), 2,04 1,75 (m, 12H), 1,75 - 1,57 (m, 2H), 1,55 - 1,35 (m, 7H), 1,30 (br t, J = 7,3 Hz, 5H), 1,26 - 1,02 (m, 2H), 0,91 0,77 (m, 1H), 0,72 - 0,45 (m, 4H). LCMS m / z [M+H]+ = 682,6, RMN de1H (400 MHz, DMSO-d6) δ 7,47 (s, 1H), 7,42 - 7,27 (m, 2H), 7,21 (br d, J = 7,9 Hz, 2H), 7,09 7,01 (m, 1H), 6,18 (br d, J = 7,3 Hz, 1H), 6,06 - 5,74 (m, 1H), 5,58 - 5,28 (m, 1H), 4,62 - 4,42 (m, 1H), 3,75 (s, 3H), 3,00 - 2,84 (m, 2H), 2,81 - 2,67 (m, 5H), 2,64 2,56 (m, 2H), 2,32 - 2,23 (m, 1H), 2,08 - 1,78 (m, 9H), 1,77 - 1,57 (m, 4H), 1,43 1,22 (m, 5H), 1,20 - 1,07 (m, 2H), 0,96 - 0,80 (m, 1H), 0,73 - 0,51 (m, 4H). LCMS m / z [M+H]+= 658,6, RMN de1H (400 MHz, DMSO-d6) δ 7,56 - 7,40 (m, 2H), 7,38 - 7,25 (m, 2H), 7,24 - 7,14 (m, 2H), 6,32 6,05 (m, 1H), 5,34 - 4,96 (m, 1H), 4,61 - 4,35 (m, 1H), 3,75 (s, 3H), 3,26 - 3,00 (m, 4H), 2,73 (s, 3H), 2,65 - 2,56 (m, 6H), 2,36 - 2,26 (m, 1H), 2,13 - 1,86 (m, 5H), 1,85 1,68 (m, 4H), 1,66 - 1,45 (m, Petição 870260065188, de 02 / 07 / 2026, pág. 161 / 516 157 / 236 6H), 1,40 - 1,19 (m, 7H), 1,17 - 1,05 (m, 1H), 0,91 0,80 (m, 1H), 0,74 - 0,63(m, 3H), 0,61 - 0,38 (m, 1H). LCMS m / z [M+H]+ = 644,4, RMN de1H (400 MHz, DMSO-d6) δ 7,47 - 7,23 (m, 3H), 7,15 (br t, J = 8,7 Hz, 2H), 6,21 (br d, J = 7,3 Hz, 1H), 5,39 - 4,93 (m,1H), 4,67 - 4,34 (m, 1H), 3,74 (s, 3H), 3,24 - 3,13 (m, 3H), 2,98 2,86 (m, 2H), 2,81 - 2,64 (m, 5H), 2,63 - 2,57 (m, 2H), 2,34 - 2,18 (m, 2H), 2,05 1,97 (m, 1H), 1,94 - 1,80 (m, 4H), 1,75 - 1,67 (m, 1H), 1,58 (br d, J = 6,1 Hz, 4H), 1,40 - 1,26 (m, 3H), 1,19 (br d, J = 9,9 Hz, 4H), 1,14 1,07 (m, 1H), 0,95 - 0,77 (m, 2H), 0,67 (br t, J = 7,1 Hz, 3H), 0,57 - 0,42 (m, 1H).LCMS m / z [M+H]+= 628,6, RMN de1H (400 MHz, DMSO-d6) δ 7,48 (br s, 1H), 7,43 - 7,26 (m, 5H), 7,23 7,12 (m, 1H), 6,40 - 6,13 (m, 1H), 5,45 - 5,19 (m, 1H), 4,50 - 4,38 (m, 1H), 3,77 (s, 3H), 2,86 - 2,78 (m, 2H), 2,73 - 2,64 (m, 6H), 2,43 (br d, J = 1,7 Hz, 3H), 2,33 (br d, J = 3,5 Hz, 2H), 2,22 - 2,08 (m, 3H), 1,96 - 1,80 (m, 4H), 1,71 - 1,61 (m, 2H), 1,47 (br s, 4H), 1,40 - 1,23 (m, 9H),. Petição 870260065188, de 02 / 07 / 2026, pág. 162 / 516 158 / 236 0,89 - 0,74 (m, 2H), 0,70 0,58 (m, 3H). LCMS m / z [M+H]+= 642,6, RMN de 1H (400 MHz, DMSO-d6) δ 7,45 (s, 1H), 7,39 - 7,27 (m, 5H), 7,26 7,17 (m, 1H), 6,13 (br d, J = 7,2 Hz, 1H), 5,49 - 5,33 (m, 1H), 4,67 - 4,42 (m, 1H), 3,74 (s, 3H), 3,57 (s, 1H), 2,93 - 2,79 (m, 3H), 2,72 (br s, 3H), 2,67 - 2,62 (m, 2H), 2,35 - 2,24 (m, 2H), 2,10 2,01 (m, 3H), 1,94 - 1,85 (m, 3H), 1,82 - 1,71 (m, 2H), 1,67 - 1,58 (m, 3H), 1,51 (br d, J = 5,1 Hz, 3H), 1,38 1,32 (m, 3H), 1,24 (br s, 5H), 0,90 (br d, J = 9,4 Hz, 1H), 0,85 (br t, J = 6,8 Hz, 2H), 0,79 (br d, J = 6,5 Hz, 3H), 0,68 (br t, J =6,8 Hz, 3H). LCMS m / z [M+H]+= 640,6, RMN de1H (400 MHz, DMSO-d6) δ 7,46 (s, 1H), 7,42 - 7,27 (m, 5H), 7,23 7,13 (m, 1H), 6,37 - 6,18 (m, 1H), 5,33 - 5,00 (m, 1H), 4,61 - 4,37 (m, 1H), 3,76 (s, 3H), 3,19 (br d, J = 9,7 Hz, 3H), 2,88 - 2,76 (m, 4H), 2,73 - 2,63 (m, 4H), 2,39 2,32 (m, 1H), 2,27 (br s, 1H), 2,23 - 2,03 (m, 4H), 1,91 1,75 (m, 4H), 1,71 - 1,46 (m, 6H), 1,39 - 1,23 (m, 8H), 1,19 (br d, J = 8,9 Hz, Petição 870260065188, de 02 / 07 / 2026, pág. 163 / 516 159 / 236 2H),1,12 - 1,02 (m, 1H), 0,90 - 0,78 (m, 1H), 0,71 - 0,59 (m, 3H). LCMS m / z [M+H]+= 638,5, RMN de1H (400 MHz, DMSO-d6) δ 7,77 - 7,61 (m, 1H), 7,48 - 7,26 (m, 5H), 7,20 (br t, J = 7,3 Hz, 1H), 6,17 - 5,65 (m, 1H), 4,98 4,59 (m, 1H), 4,01 - 3,77 (m, 5H), 3,70 - 3,49 (m, 2H), 3,01 - 2,75 (m, 4H), 2,60 (br dd, J = 4,5, 10,0 Hz, 2H), 2,29 - 2,05 (m, 5H), 2,02 1,71 (m, 8H), 1,69 - 1,35 (m, 9H), 1,33 - 1,21 (m, 3H), 0,74 (br s, 3H). LCMS m / z [M+H]+= 640,6, RMN de1H (400 MHz, DMSO-d6) δ 7,45 (s, 1H), 7,40 (br d, J = 7,6 Hz, 2H), 7,34 - 7,26 (m, 3H), 7,21 7,16 (m, 1H), 6,53 - 6,11 (m, 1H), 5,43 - 4,91 (m, 1H), 4,54 - 4,27 (m, 1H), 3,76 (s, 3H), 3,25 - 3,16 (m, 2H), 2,86 - 2,74 (m, 2H), 2,68 2,64 (m, 3H), 2,40 - 2,30 (m, 4H), 2,23 - 2,06 (m, 3H), 1,91 - 1,84 (m, 2H), 1,83 1,73 (m, 2H), 1,63 (br d, J = 2,3 Hz, 5H), 1,36 - 1,14 (m, 12H), 1,09 - 1,02 (m, 1H), 0,90 - 0,78 (m, 1H), 0,71 0,57 (m, 3H), 0,52 - 0,38 (m, 1H). Petição 870260065188, de 02 / 07 / 2026, pág. 164 / 516 160 / 236 LCMS m / z [M+H]+= 626,6, RMN de1H (400 MHz, DMSO-d6) δ 7,42 (br d, J = 2,8 Hz, 1H), 7,39 - 7,31 (m, 4H), 7,28 (s, 1H), 7,22 (dt, J = 2,8, 5,5 Hz, 1H), 6,13 5,98 (m, 1H), 5,16 (br d, J = 7,5 Hz, 1H), 4,61 - 4,38 (m, 1H), 3,74 (s, 3H), 2,94 - 2,84 (m, 1H), 2,72 (s, 3H), 2,62 2,53 (m, 4H), 2,46 - 2,39 (m, 2H), 2,32 - 2,18 (m, 2H), 2,09 - 1,76 (m, 8H), 1,76 1,45 (m, 4H), 1,41 - 1,18 (m, 4H), 1,17 - 1,05 (m, 1H), 0,95 - 0,79 (m, 3H), 0,68 (br t, J = 6,5 Hz, 3H), 0,58 - 0,37 (m, 2H), 0,19 - 0,08 (m, 1H). LCMS m / z [M+H]+= 702,6, RMN de1H (400 MHz, DMSO-d6) δ 7,60 - 7,47 (m, 1H), 7,42 - 7,29 (m, 2H), 7,23 - 7,14 (m, 2H), 7,10 7,00 (m, 1H), 6,42 - 5,97 (m, 1H), 5,37 - 4,96 (m, 1H), 4,60 - 4,34 (m, 2H), 4,25 4,09 (m, 1H), 4,07 - 4,00 (m, 2H), 3,78 (br d, J = 2,1 Hz, 1H), 2,98 - 2,81 (m, 4H), 2,72 (s, 3H), 2,64 - 2,57 (m, 2H), 2,29 - 2,05 (m, 2H), 2,03 - 1,77 (m, 6H), 1,76 1,54 (m, 6H), 1,53 - 1,46 (m,1H), 1,44 - 1,23 (m, 9H), 1,22 - 0,98 (m, 4H), 0,93 0,78 (m, 1H), 0,71 - 0,70 (m, 1H), 0,73 - 0,63 (m, 2H), Petição 870260065188, de 02 / 07 / 2026, pág. 165 / 516 161 / 236 0,62 - 0,51 (m, 1H). LCMS m / z [M+H]+= 646,6, RMN de1H (400 MHz, DMSO-d6) δ 7,53 (br s, 1H), 7,38 - 7,28 (m, 5H), 7,21 (dt, J = 2,8, 5,9 Hz, 1H), 6,19 5,92 (m, 1H), 5,58 - 5,42 (m, 1H), 4,96 - 4,70 (m, 1H), 3,76 - 3,72 (m, 3H), 3,17 (s, 1H), 2,96 - 2,83 (m, 2H), 2,80 - 2,72 (m, 5H), 2,64 2,60 (m, 2H), 2,20 - 2,06 (m, 3H), 1,99 - 1,83 (m, 3H), 1,82 - 1,71 (m, 2H), 1,69 1,32 (m, 13H), 1,30 - 1,21 (m, 1H), 0,84 - 0,76 (m, 4H), 0,69 (br t, J = 7,2 Hz, 3H). LCMS m / z [M+H]+= 670,6, RMN de1H (400 MHz, DMSO-d6) δ 7,40 - 7,32 (m, 1H), 7,29 (s, 1H), 7,18 (br d, J = 7,9 Hz, 2H), 7,07 - 7,00 (m, 1H), 6,08 - 5,95 (m, 1H), 5,33 - 4,99 (m, 1H), 4,84 4,70 (m, 1H), 3,66 (s, 3H), 2,97 - 2,81 (m, 3H), 2,78 (s, 3H), 2,73 (br s, 2H), 2,65 2,57 (m, 2H), 2,28 - 2,21 (m, 1H), 2,18 (s, 3H), 2,01 - 1,60 (m, 16H), 1,50 - 1,32 (m, 8H), 0,78 - 0,66 (m, 3H). Petição 870260065188, de 02 / 07 / 2026, pág. 166 / 516 162 / 236 102 LCMS m / z [M+H]+= 646,7, RMN de1H (400 MHz, DMSO-d6) δ 8,25 (s, 1H), 7,49 (s, 1H), 7,41 - 7,30 (m, 2H), 7,20 (br d, J = 7,9 Hz, 2H), 7,08 - 7,00 (m, 1H), 6,21 (br d, J = 7,4 Hz, 1H), 5,52 - 5,25 (m, 1H), 4,60 4,42 (m, 1H), 4,06 - 3,99 (m, 2H), 2,98 - 2,8 (m, 2H), 2,72 (s, 3H), 2,70 - 2,62 (m, 2H), 2,61 - 2,55 (m, 2H), 2,39 (br s, 4H), 2,31 - 2,23 (m, 1H), 2,02 - 1,80 (m, 5H), 1,76 1,57 (m, 2H), 1,44 (br s, 4H), 1,35 (br d, J = 4,1 Hz, 3H), 1,32 - 1,27 (m, 4H), 1,26 1,08 (m, 2H), 1,07 - 0,80 (m, 2H), 0,74 - 0,50 (m, 4H). LCMS m / z [M+H]+= 672,6, RMN de1H (400 MHz, DMSO-d6) δ 7,55 - 7,29 (m, 2H), 7,19 (br d, J = 7,9 Hz, 2H), 7,05 (br t, J = 8,1 Hz, 1H), 6,09 (br d, J = 6,0 Hz, 1H), 4,96 (br d, J = 6,2 Hz, 1H), 4,59 - 4,38 (m, 1H), 3,67 (s, 3H), 3,18 - 3,03 (m, 4H), 3,00 - 2,88 (m, 2H), 2,71 (s, 3H), 2,60 (br dd, J = 4,5, 16,2 Hz, 3H), 2,36 - 2,19 (m, 2H), 2,11 (s, 3H), 1,98 1,84 (m, 4H), 1,84 - 1,81 (m, 1H), 1,73 - 1,59 (m, 2H), 1,56 - 1,39 (m, 5H), 1,36 1,17 (m, 7H), 1,14 - 1,02 (m, 1H), 0,95 - 0,80 (m, 1H), Petição 870260065188, de 02 / 07 / 2026, pág. 167 / 516 163 / 236 104 107 0,69 (br t, J = 6,7 Hz, 3H), 0,53 - 0,33 (m, 1H). LCMS m / z [M+H]+= 676,7, 0,82 min; RMN de1H (400 MHz, DMSO-d6) δ 7,50 (s, 1H), 7,42 - 7,30 (m, 2H), 7,19 (br d, J = 7,9 Hz, 2H), 7,08 - 6,97 (m, 1H), 6,26 (br d, J = 7,8 Hz, 1H), 5,41 5,21 (m, 1H), 4,56 - 4,46 (m, 1H), 4,03 (q, J = 7,3 Hz, 2H), 3,49 (td, J = 5,0, 10,4 Hz, 2H), 3,01 - 2,87 (m, 3H), 2,75 - 2,70 (m, 3H), 2,62 (br dd, J = 4,8, 10,7 Hz, 2H), 2,38 (br d, J = 7,0 Hz, 1H), 2,30 - 2,22 (m, 2H), 2,01 1,78 (m, 6H), 1,71 - 1,49 (m, 4H), 1,43 - 1,18 (m, 14H), 1,12 - 1,02 (m, 1H), 0,91 0,81 (m, 1H), 0,74 - 0,53 (m, ____________4H).____________ LCMS m / z [M+H]+= 646,6, RMN de1H (400 MHz, DMSO-d6) δ 7,98 (br s, 1H), 7,76 - 7,67 (m, 1H), 7,37 (br d, J = 4,3 Hz, 5H), 7,29 7,23 (m, 1H), 6,21 - 6,13 (m, 1H), 6,08 - 5,99 (m, 1H), 4,58 - 4,26 (m, 1H), 3,78 3,65 (m, 2H), 3,63 - 3,58 (m, 1H), 2,90 (br s, 5H), 2,82 2,71 (m, 4H), 2,45 - 2,29 (m, 2H), 2,03 - 1,91 (m, 5H), 1,87 - 1,80 (m, 2H), 1,76 (br s, 5H), 1,52 - 1,38 (m, 3H), 1,36 - 1,22 (m, 3H), 1,20 Petição 870260065188, de 02 / 07 / 2026, pág. 168 / 516 164 / 236 135 140 1,11 (m, 1H), 1,09 - 0,94 (m, 3H), 0,87 (br d, J = 5,9 Hz, 3H), 0,70 (br s, 3H). LCMS m / z [M+H]+= 676,5, RMN de1H (400 MHz, DMSO-d6) δ 7,74 (s, 1H), 7,49 - 7,45 (m, 1H), 7,40 7,29 (m, 2H), 7,23 - 7,18 (m, 2H), 7,09 - 7,00 (m, 1H), 6,29 - 6,13 (m, 1H), 5,34 5,28 (m, 1H), 4,07 - 4,01 (m, 2H), 3,26 - 3,22 (m, 3H), 2,74 - 2,70 (m, 2H), 2,03 1,97 (m, 4H), 1,90 - 1,82 (m, 3H), 1,59 - 1,48 (m, 4H), 1,37 - 1,34 (m, 2H), 1,32 (br d, J = 4,4 Hz, 3H), 1,29 (br d, J = 7,3 Hz, 5H), 1,23 (br s, 13H), 0,86 - 0,82 (m, 2H), 0,69 - 0,65 (m, 2H). LCMS m / z [M+H]+= 626,6, RMN de1H (400 MHz, DMSO-d6) δ 7,37 - 7,28 (m, 4H), 7,25 - 7,18 (m, 1H), 6,32 (br d, J = 7,5 Hz, 1H), 5,92 (s, 1H), 5,54 - 5,29 (m, 1H), 4,87 - 4,74 (m, 1H), 3,66 (s, 3H), 2,91 - 2,75 (m, 5H), 2,74 - 2,68 (m, 1H), 2,64 - 2,58 (m, 3H), 2,52 2,52 (m, 2H), 2,23 (br dd, J = 11,9, 15,1 Hz, 1H), 2,05 (s, 3H), 1,97 - 1,86 (m, 3H), 1,80 (br d, J = 8,4 Hz, 3H), 1,70 (br d, J = 6,7 Hz, 3H), 1,67 - 1,55 (m, 2H), 1,53 1,42 (m, 4H), 1,38 - 1,21 (m, Petição 870260065188, de 02 / 07 / 2026, pág. 169 / 516 165 / 236 144 155 1H), 0,83 - 0,65 (m, 7H). LCMS m / z [M+H]+= 646,7, RMN de1H (400 MHz, DMSO-d6) δ 12,21 - 11,44 (m, 1H), 7,47 (br s, 1H), 7,34 (br d, J = 4,3 Hz, 5H), 7,27 7,17 (m, 1H), 5,38 - 5,17 (m, 1H), 4,46 (br s, 1H), 3,74 (s, 3H), 2,99 - 2,83 (m, 1H), 2,82 - 2,69 (m, 4H), 2,65 2,55 (m, 3H), 2,38 - 2,19 (m, 3H), 2,11 - 1,78 (m, 6H), 1,75 - 1,48 (m, 5H), 1,44 1,07 (m, 9H), 1,01 - 0,76 (m, 2H), 0,69 (br s, 3H), 0,60 0,46 (m, 1H). LCMS m / z [M+H]+= 630,3, RMN de1H (400 MHz, DMSO-d6) δ 12,68 - 11,64 (m, 1H), 7,37 (dt, J = 6,5, 7,9 Hz, 1H), 7,27 (d, J = 1,4 Hz, 1H), 7,23 - 7,17 (m, 2H), 7,08 - 7,00 (m, 1H), 6,37 (br d, J = 7,8 Hz, 1H), 6,17 (d, J = 1,8 Hz, 1H), 5,85 - 5,35 (m, 1H), 4,84 (br t, J = 6,9 Hz, 1H), 3,77 (s, 3H), 3,00 - 2,89 (m, 1H), 2,88 - 2,83 (m, 1H), 2,80 (s, 3H), 2,75 - 2,60 (m, 5H), 2,59 - 2,55 (m, 1H), 2,53 (br d, J = 2,0 Hz, 1H), 2,31 - 2,18 (m, 1H), 2,00 1,88 (m, 3H), 1,85 - 1,79 (m, 3H), 1,77 - 1,65 (m, 3H), 1,63 - 1,55 (m, 1H), 1,55 1,42 (m, 4H), 1,38 - 1,25 (m, 1H), 0,85 - 0,69 (m, 7H). Petição 870260065188, de 02 / 07 / 2026, pág. 170 / 516 166 / 236 161 163 LCMS m / z [M+H]+= 646,6, RMN de1H (400 MHz, DMSO-d6) δ 7,42 - 7,31 (m, 1H), 7,25 (d, J = 1,5 Hz, 1H), 7,19 (br d, J = 7,8 Hz, 2H), 7,07 - 7,00 (m, 1H), 6,32 (br d, J = 7,5 Hz, 1H), 6,14 (s, 1H), 5,52 - 5,40 (m, 1H), 4,43 (br t, J = 9,2 Hz, 1H), 3,78 (s, 3H), 2,96 - 2,83 (m, 2H), 2,72 (s, 4H), 2,68 - 2,57 (m, 4H), 2,31 - 2,20 (m, 1H), 2,13 - 2,00 (m, 1H), 1,97 1,88 (m, 4H), 1,81 (br d, J = 9,5 Hz, 2H), 1,75 - 1,56 (m, 4H), 1,49 (br d, J = 2,9 Hz, 2H), 1,41 - 1,21 (m, 5H), 1,19 - 1,05 (m, 1H), 1,03 0,88 (m, 1H), 0,79 (br d, J = 6,4 Hz, 4H), 0,71 (br t, J = 6,9 Hz, 3H), 0,65 (br d, J = 3,9 Hz, 1H), 0,56 - 0,41 (m, 1H). LCMS m / z [M+H]+= 662,5, RMN de1H (400 MHz, DMSO-d6) δ 7,62 - 7,49 (m, 1H), 7,41 - 7,28 (m, 2H), 7,20 (br d, J = 8,6 Hz, 2H), 7,04 (br t, J = 8,9 Hz, 1H), 6,20 (br d, J = 7,5 Hz, 1H), 5,47 - 5,30 (m, 1H), 4,60 4,42 (m, 1H), 4,03 (q, J = 6,6 Hz, 2H), 2,99 - 2,86 (m, 2H), 2,84 - 2,63 (m, 8H), 2,63 2,57 (m, 3H), 2,34 - 2,17 (m, 2H), 2,04 - 1,69 (m, 10H), 1,58 - 1,52 (m, 1H), 1,41 Petição 870260065188, de 02 / 07 / 2026, pág. 171 / 516 167 / 236 164 172 1,17 (m, 9H), 1,10 - 0,85 (m, 4H), 0,56 (br t, J = 6,7 Hz, 2H). LCMS m / z [M+H]+= 658,6, RMN de1H (400 MHz, DMSO-d6) δ 12,19 - 11,72 (m, 1H), 7,38 (q, J = 7,4 Hz, 1H), 7,27 - 7,15 (m, 3H), 7,05 (dt, J = 1,7, 8,2 Hz, 1H), 6,35 (br d, J = 6,0 Hz, 1H), 6,21 - 6,08 (m, 1H), 5,19 (br d, J = 6,0 Hz, 1H), 4,38 (br t, J = 8,5 Hz, 1H), 3,84 (s, 3H), 3,14 (br s, 1H), 3,05 - 2,85 (m, 2H), 2,77 - 2,69 (m, 3H), 2,69 - 2,60 (m, 4H), 2,33 2,22 (m, 1H), 2,14 - 1,62 (m, 10H), 1,60 - 0,92 (m, 15H), 0,71 (br t, J = 7,0 Hz, 2H), 0,47 - 0,31 (m, 1H). LCMS m / z [M+H]+= 638,6, RMN de1H (400 MHz, DMSO-d6) δ 7,43 - 7,28 (m, 4H), 7,27 - 7,15 (m, 2H), 6,24 (br d, J = 7,6 Hz, 1H), 6,15 (s, 1H), 5,52 - 5,14 (m, 1H), 4,88 - 4,64 (m, 1H), 3,80 (s, 3H), 2,95 (br d, J = 6,2 Hz, 2H), 2,93 - 2,81 (m, 2H), 2,78 (s, 3H), 2,69 (br s, 3H), 2,63 (br d, J = 4,3 Hz, 1H), 2,56 (br s, 1H), 2,31 2,21 (m, 1H), 1,97 - 1,87 (m, 3H), 1,83 (br d, J = 13,1 Hz, 3H), 1,77 (br d, J = 6,4 Hz, 4H), 1,70 (br d, J = 7,7 Hz, 3H), 1,46 (br d, J = 6,4 Hz, Petição 870260065188, de 02 / 07 / 2026, pág. 172 / 516 168 / 236 173 4H), 1,42 - 1,32 (m, 4H), 0,72 (br t, J = 6,4 Hz, 3H). LCMS m / z [M+H]+ = 642,7, RMN de1H (400 MHz, DMSO-d6) δ 7,92 - 7,82 (m, 1H), 7,64 - 7,52 (m, 1H), 7,39 (br d, J = 7,5 Hz, 4H), 7,28 (br d, J = 8,1 Hz, 1H), 5,81 - 5,72 (m, 1H), 4,46 4,21 (m, 1H), 3,79 (s, 3H), 3,63 - 3,54 (m, 1H), 2,96 2,85 (m, 6H), 2,08 (s, 3H), 1,98 - 1,80 (m, 8H), 1,74 1,63 (m, 4H), 1,48 - 1,39 (m, 6H), 1,32 - 1,22 (m, 6H), 1,20 - 1,13 (m, 3H), 1,00 0,85 (m, 2H), 0,74 - 0,67 (m, ____________3H).____________ LCMS m / z [M+H]+= 656,40, RMN de1H (300 MHz, METANOL-d4) δ ppm 7,54 (s, 1 H), 7,44 (s, 1 H), 7,38 - 7,28 (m, 1 H), 7,21 - 7,07 (m, 2 H), 7,01 - 6,88 (m, 1 H), 5,53 - 5,27 (m, 1 H), 4,78 - 4,65 (m, 1 H), 3,84 (s, 3 H), 3,14 2,88 (m, 6 H), 2,86 - 2,75 (m, 4 H), 2,53 - 2,28 (m, 1 H), 2,23 - 1,98 (m, 9 H), 1,90 1,53 (m, 13 H), 1,31 (br d, J = 11,71 Hz, 1 H), 0,93 - 0,68 (m, 3 H). Petição 870260065188, de 02 / 07 / 2026, pág. 173 / 516 169 / 236 LCMS m / z [M+H]+ = 630,45, RMN de1H (400 MHz, METANOL- d4) δ ppm 7,53 (s, 1 H), 7,42 (s, 1 H), 7,38 - 7,29 (m, 1 H), 7,17 (br d, J = 7,82 Hz, 1 H), 7,11 (br d, J = 10,17 Hz, 1 H), 7,00 - 6,92 (m, 1 H), 5,63 (br d, J = 5,48 Hz, 2 H), 4,10 (q, J = 7,30 Hz, 2 H), 3,84 (s, 3 H), 3,09 2,87 (m, 6 H), 2,85 - 2,64 (m, 4 H), 2,43 - 2,39 (m, 2 H), 2,25 - 1,93 (m, 6 H), 1,89 1,55 (m, 8 H), 1,24 (t, J = 7,24 Hz, 3 H), 0,96 - 0,77 (m, 4 H) LCMS m / z [M+H]+= 612,60, RMN de1H (400 MHz, METANOL-d4) δ ppm 7,53 (s, 1 H), 7,41 (s, 1 H), 7,37 - 7,28 (m, 4 H), 7,24 - 7,20 (m, 1 H) 5,60 (br d, J = 4,30 Hz, 1 H), 4,85 - 4,76 (m, 1 H) 3,83 (s, 3 H), 2,96 (s, 6 H), 2,81 (br d, J = 8,22 Hz, 7 H), 2,44 - 2,40 (m, 2 H), 2,21 - 1,94 (m, 5 H) 1,92 - 1,56 (m, 11 H) 1,00 - 0,76 (m, 4 H) LCMS m / z [M+H]+= 658,40, RMN de1H (400 MHz, METANOL- d4) δ ppm 7,46 (br s, 1 H), 7,40 - 7,29 (m, 2 H), 7,17 (br d, J = 7,43 Hz, 1 H), 7,11 (br d, J = 10,17 Hz, 1 H), 7,01 - 6,89 (m, 1 H), 5,46 - 5,30 (m, 1 H), 4,10 (q, J = 7,30 Hz, 1 H), 3,89 - 3,71 Petição 870260065188, de 02 / 07 / 2026, pág. 174 / 516 170 / 236 (m, 4 H), 3,10 - 2,90 (m, 5 H), 2,89 - 2,60 (m, 5 H), 2,48 - 2,34 (m, 1 H), 2,26 - 1,92 (m, 6 H), 1,89 - 1,62 (m, 6 H), 1,60 - 1,17 (m, 5 H), 1,12 - 0,56 (m, 8 H), 0,39 (br s, 2 H) 97 n-n'^ / γ hnÃ-O Aá x OH LCMS m / z [M+H]+ = 644,45, RMN de 1H (400 MHz, METANOL- d4) δ 8,52 (br s, 1 H), 7,59 (br s, 1 H), 7,39 (br s, 1 H), 7,37 - 7,29 (m, 3 H), 7,26 - 7,18 (m, 1 H) 5,59 - 5,49 (m, 1 H) 4,57 - 4,46 (m, 1 H) 3,76 - 3,53 (m, 2 H) 3,09 2,35 (m, 14 H) 2,22 - 1,76 (m, 7 H) 1,71 - 1,24 (m, 12 H) 1,01 (br d, J = 5,70 Hz, 4 H), 0,78 (br t, J = 7,02 Hz, 3 H) 112 o AH A / N—xX L JL hn1 ΧγΟ OH LCMS m / z [M+H]+ = 665,90, RMN de 1H (400 MHz, METANOL- d4) δ ppm 8,53 (s, 1 H), 7,34 - 7,42 (m, 6 H), 7,23 - 7,33 (m, 4 H), 4,99 (br dd, J = 9,21,4,82 Hz, 1 H), 4,27 (br t, J = 9,21 Hz, 1 H), 3,93 4,04 (m, 1 H), 3,13 - 3,23 (m, 1 H), 2,96 - 3,12 (m, 3 H), 2,70 - 2,91 (m, 7 H), 2,56 2,68 (m, 2 H), 2,14 - 2,39 (m, 5 H), 2,01 - 2,12 (m, 2 H), 1,69 - 2,00 (m, 6 H), 1,61 (br d, J = 12,28 Hz, 2 H), 1,26 1,50 (m, 7 H),1,06 - 1,24 (m, 4 H)., Petição 870260065188, de 02 / 07 / 2026, pág. 175 / 516 171 / 236 120 LCMS m / z [M+H]+ = 640,65, RMN de1H (400 MHz, METANOL-d4) δ ppm 7,42 (br s, 1 H), 7,28 - 7,37 (m, 5 H), 7,17 - 7,23 (m, 1 H), 5,34 (br d, J = 2,63 Hz, 1 H), 3,73 3,92 (m, 4 H), 2,91 - 3,06 (m, 4 H), 2,77 - 2,89 (m, 2 H), 2,66 - 2,76 (m, 3 H), 2,61 2,57 (m, 1 H), 2,41 - 2,37 (m, 1 H), 2,14 - 2,26 (m, 1 H), 1,91 - 2,13 (m, 5 H), 1,58 1,87 (m, 7 H), 1,52 (br d, J = 8,77 Hz, 2 H), 1,43 (br dd, J = 13,59, 2,63 Hz, 1 H), 1,32 (br d, J = 11,84 Hz, 2 H), 0,77 - 1,07 (m, 6 H), 0,71 (br s, 2 H), 0,33 (br d, J = 6,58 Hz, 2 H). 133 LCMS m / z [M+H]+= 676,70, RMN de1H (400 MHz, METANOL-d4) δ ppm 8,53 (s, 1H), 7,49 (br s, 1H), 7,37 (br s, 1H), 7,33 (br d, J = 3,1 Hz, 4H), 7,22 (dt, J = 2,9, 5,6 Hz, 1H), 5,19 (br s, 1H), 3,85 (s, 3H), 3,76 - 3,58 (m, 1H), 3,51 - 3,44 (m, 1H), 3,40 (br s, 1H), 3,16 - 2,90 (m, 5H), 2,90 - 2,63 (m, 4H), 2,61 2,34 (m, 2H), 2,20 - 2,12 (m, 3H), 2,10 - 1,88 (m, 8H), 1,86 - 1,71 (m, 2H), 1,62 (br s, 5H), 1,46 - 1,32 (m, 2H), 1,29 (br d, J = 4,4 Hz, 2H), 1,06 - 0,86 (m, 2H), 0,84 0,73 (m, 1H), 0,56 (br d, J = Petição 870260065188, de 02 / 07 / 2026, pág. 176 / 516 172 / 236 146 147 150 13,6 Hz, 1H), 0,40 (br s, 2H). LCMS m / z [M+H]+ = 596,2, RMN de1H (300 MHz, METANOL-d4) δ ppm 7,26 7,41 (m, 9 H), 7,17 - 7,24 (m, 1 H), 5,34 (br d, J = 7,90 Hz, 1 H), 4,37 (br t, J = 9,55 Hz, 1 H), 2,67 - 3,09 (m, 10 H), 2,42 - 2,59 (m, 1 H), 1,72 2,11 (m, 8 H), 1,53 - 1,63 (m, 1 H), 1,21 - 1,48 (m, 10 H), 1,09 - 1,18 (m, 2 H), 0,80 (br t, J = 6,91 Hz, 3 H). LCMS m / z [M+H]+= 654.30, RMN de1H (400 MHz, METANOL-d4) δ ppm 7,61 (br s, 1 H) 7,41 (br s, 1 H) 7,29 7,38 (m, 4 H) 7,18 - 7,27 (m, 1 H) 5,58 (br d, J = 3,07 Hz, 1 H) 4,50 - 4,66 (m, 1 H) 3,96 (br d, J = 7,02 Hz, 2 H) 2,95 - 3,06 (m, 2 H) 2,90 (s, 3 H) 2,37 - 2,84 (m, 10 H) 1,75 - 2,18 (m, 8 H) 1,43 1,69 (m, 8 H) 1,20 - 1,35 (m, 4 H) 0,79 (br t, J = 7,23 Hz, 3 H) 0,51 - 0,63 (m, 2 H) 0,36 (q, J = 4,82 Hz, 2 H). LCMS m / z [M+H]+= 664,6, RMN de1H (400 MHz, METANOL- d4) δ ppm 7,49 (br s, 1 H), 7,39 (br s, 1 H), 7,27 7,36 (m, 4 H), 7,22 (br dd, J = 5,92, 2,41 Hz, 1 H), 5,33 (br d, J = 4,38 Hz, 1 H), 4,49 (br d, J = 11,40 Hz, 1 H), 2,63 - 3,04 (m, 13 H), 2,39 Petição 870260065188, de 02 / 07 / 2026, pág. 177 / 516 173 / 236 154 156 2,51 (m, 1 H), 1,94 - 2,16 (m, 9 H), 1,76 - 1,92 (m, 3 H), 1,63 - 1,73 (m, 2 H), 1,21 1,55 (m, 7 H), 0,87 - 1,01 (m, 1 H), 0,77 (br t, J = 7,02 Hz, H), 0,66 - 0,62 (m, 1 H) LCMS m / z [M+H]+ = 644,3, RMN de1H (300 MHz, METANOL- d4) δ ppm 7,57 (s, 1 H), 7,42 (s, 1 H), 7,38 - 7,30 (m, 4 H), 7,24 (dt, J=5,76, 2,71 Hz, 1 H), 5,54 - 5,50 (m, 1 H), 4,52 (br t, J = 9,21 Hz, 1 H), 4,13 (q, J = 7,24 Hz, 2 H), 3,69 - 3,56 (m, 1 H), 3,12 - 2,16 (m, 12 H), 2,57 - 2,23 (m, 3 H) , 2,20 - 1,73 (m, 10 H), 1,65 - 1,24 (m, 11 H), 0,80 (br t, J = 7,24 Hz, 3 H). LCMS m / z [M+H]+= 632,70, RMN de1H (400 MHz, METANOL-d4) δ ppm 8,54 (s, 1 H), 7,52 (br s, 1 H), 7,40 (br s, 1 H), 7,38 - 7,29 (m, 4 H), 7,28 - 7,20 (m, 1 H), 5,44 (br dd, J = 8,55, 4,60 Hz, 1 H), 4,61 (br s, 1 H), 4,50 (br s, 2 H), 2,97 - 3,08 (m, 1 H), 2,65 - 2,97 (m, 7 H), 2,41 - 2,60 (m, 4 H), 2,11 - 2,22 (m, 2 H), 1,96 - 2,10 (m, 3 H), 1,72 - 1,95 (m, 5 H), 1,63 (br d, J = 8,33 Hz, 2 H), 1,36 - 1,56 (m, 5 H), 1,20 - 1,35 (m, 3 H), 0,89 - 1,05 (m, 1 H), 0,81 (br t, J = 7,02 Hz, 3 H), 0,57 (br d, J = 13,59 Hz, 1 H). Petição 870260065188, de 02 / 07 / 2026, pág. 178 / 516 174 / 236 162 167 LCMS m / z [M+H]+ = 683,90, RMN de1H (400 MHz, METANOL-d4) δ ppm 7,56 (br s, 1 H), 7,42 (br s, 1 H), 7,38 7,29 (m, 4 H), 7,27 - 7,20 (m, 1 H), 5,46 - 5,33 (m, 1 H), 4,64 - 4,47 (m, 2 H), 4,21 4,07 (m, 2 H), 3,78 - 3,59 (m, 3 H), 3,53 (br d, J = 8,33 Hz, 1 H), 3,39 (br d, J = 9,21 Hz, 1 H), 3,07 - 2,96 (m, 2 H), 2,91 (s, 3 H), 2,87 - 2,77 (m, 3 H), 2,74 - 2,59 (m, 3 H), 2,54 - 2,26 (m, 5 H), 2,14 (br d, J = 10,96 Hz, 1 H), 2,09 1,68 (m, 7 H), 1,65 - 1,35 (m, 11 H), 0,80 (br t, J = 7,02 Hz, _____________3 H)._____________ LCMS m / z [M+H]+= 681,95, RMN de1H (400 MHz, METANOL-d4) δ ppm 7,68 (br s, 1 H), 7,53 (br s, 1 H), 7,29 7,39 (m, 4 H), 7,17 - 7,27 (m, 1 H), 5,56 (br s, 1 H), 4,46 4,68 (m, 1 H), 2,92 - 3,07 (m, 3 H), 2,89 (s, 3 H), 2,67 2,83 (m, 4 H), 2,40 - 2,66 (m, 5 H), 2,08 - 2,18 (m, 1 H), 1,74 - 2,07 (m, 6 H), 1,25 1,67 (m, 12 H), 0,90 (br s, 1 H), 0,78 (br t, J = 7,02 Hz, 3 H), 0,66 - 0,59 (m, 1 H). Petição 870260065188, de 02 / 07 / 2026, pág. 179 / 516 175 / 236 149 LCMS m / z [M+H]+ = 638,85, RMN de1H (400 MHz, METANOL-d4) δ = 7,51 (s, 1H), 7,43 (s, 1H), 7,37 - 7,26 (m, 4H), 7,22 - 7,18 (m, 1H), 5,48 - 5,19 (m, 2H), 4,82 4,70 (m, 1H), 3,83 (s, 3H), 3,54 - 3,40 (m, 1H), 3,32 3,32 (m, 1H), 3,25 - 3,21 (m, 1H), 3,17 - 3,04 (m, 1H), 2,32 - 2,26 (m, 2H), 2,89 (s, 3H), 2,81 (br d, J = 6,3 Hz, 1H), 2,77 - 2,67 (m, 2H), 2,55 - 2,33 (m, 2H), 2,13 2,06 (m, 1H), 2,04 - 1,96 (m, 4H), 1,95 - 1,87 (m, 1H), 1,78 (br d, J = 8,2 Hz, 2H), 1,71 (br s, 2H), 1,66 (br s, 1H), 1,62 - 1,50 (m, 5H), 1,28 (br d, J = 3,9 Hz, 2H), 1,04 (br d, J = 6,7 Hz, 1H), 0,89 (br s, 1H), 0,80 (t, J = 7,4 Hz, 2H). LCMS m / z [M+H-16]+= 628,45, RMN de1H (400 MHz, METANOL-d4) δ ppm 7,50 (br s, 1 H), 7,41 (br s, 1 H), 7,37 - 7,27 (m, 4 H), 7,24 - 7,16 (m, 1 H), 5,50 (br d, J = 4,38 Hz, 1 H), 4,64 - 4,49 (m, 1 H), 2,96 (br d, J = 11,40 Hz, 3 H), 2,85 (br s, 3 H), 2,79 - 2,65 (m, 3 H), 2,56 - 2,38 (m, 3 H), 2,14 - 1,78 (m, 8 H), 1,70 - 1,24 (m, 14 H), 1,10 (br d, J = 6,58 Hz, 3 H), 1,01 - 0,90 (m, 1 H), 0,78 Petição 870260065188, de 02 / 07 / 2026, pág. 180 / 516 176 / 236 (br t, J = 7,02 Hz, 3 H). 116 125 LCMS m / z [M+H]+ = 646,6, RMN de1H (400 MHz, DMSO-d6) δ 7,50 (s, 1H), 7,41 - 7,31 (m, 2H), 7,20 (br d, J = 7,9 Hz, 2H), 7,08 7,00 (m, 1H), 6,15 (br d, J = 7,3 Hz, 1H), 5,30 (br d, J = 6,1 Hz, 1H), 4,57 - 4,43 (m, 1H), 4,08 - 3,99 (m, 2H), 2,99 - 2,88 (m, 1H), 2,72 (s, 3H), 2,66 2,57 (m, 2H), 2,52 - 2,51 (m, 2H), 2,37 (br s, 4H), 2,29 2,21 (m, 1H), 2,09 - 1,78 (m, 6H), 1,75 - 1,53 (m, 2H), 1,43 (br s, 4H), 1,38 - 1,33 (m, 3H), 1,33 1,19 (m, 6H), 1,18 - 1,05 (m, 1H), 0,93 - 0,81 (m, 1H), 0,76 - 0,50 (m, 4H) LCMS m / z [M+H]+= 628,3, RMN de1H (400 MHz, Metanol-d4) δ 7,36 (s, 1H), 7,31 7,17 (m, 5H), 7,13 - 7,05 (m, 1H), 5,34 (s, 1H), 4,43 (s, 1H), 3,74 (s, 3H), 2,91 - 2,67 (m, 7H), 2,66 - 2,58 (m, 3H), 2,50 (dd, J = 12,8, 5,2 Hz, 1H), 2,37 - 2,24 (m, 1H), 2,02 - 1,83 (m, 5H), 1,75 (t, J = 17,7 Hz, 2H), 1,51 (ddd, J = 40,3, 25,2, 13,3 Hz, 7H), 1,26 (dt, J = 38,3, 12,2 Hz, 4H), 0,91 - 0,72 (m, 5H), 0,71 - 0,51 (m, 4H). Petição 870260065188, de 02 / 07 / 2026, pág. 181 / 516 177 / 236 143 175 LCMS m / z [M+H]+ = 654,7, RMN de1H (400 MHz, MeOD) δ 7,52 (s, 1H), 7,40 (s, 1H), 7,38 - 7,28 (m, 4H), 7,22 (dq, J = 5,6, 2,5 Hz, 1H), 5,28 (br s, 1H), 4,43 (br s, 1H), 3,85 (s, 3H), 3,23 3,07 (br m, 1H), 3,07 - 2,61 (m, 9H), 2,59 - 2,34 (m, 1H), 2,30 - 1,15 (m, 24H), 1,02 0,83 (m, 1H), 0,83 - 0,67 (m, 3H), 0,68 - 0,43 (m, 1H). LCMS m / z [M+H]+= 650,6, RMN de1H (400 MHz CD3OD) δ 7,42 (s, 1H), 7,30 (s, 1H), 7,27 - 7,18 (m, 1H), 7,10 - 6,95 (m, 1H), 6,91 6,80 (m, 1H), 5,52 (s, 1H), 4,25 (s, 1H), 4,21 - 4,03 (m, 2H), 3,74 (s, 3H), 2,98 - 2,51 (m, 9H), 2,36 - 2,22 (m, 1H), 2,10 - 1,74 (m, 10H), 1,65 1,52 (m, 4H), 1,51- 1,11 (m, 6H), 1,07 - 0,86 (m, 3H), 0,83 (t, J = 7,2 Hz, 3H).

[00199] Exemplo 14: Síntese de ácido (1R,4r)-4-((R)-1-((6-fenil-4(((R)-1-fenil-2-(pirrolidin-1-il)etil)amino)-5,6,7,8-tetra-hidropirido[4,3d]pirimidin-2-il)amino)propil)ciclo-hexano-1-carboxílico (Composto 131) Petição 870260065188, de 02 / 07 / 2026, pág. 182 / 516 178 / 236

[00200] Step 1: (R)-1-phenyl-2-(pyrrolidin-1-yl)ethan-1-amine (230 mg, 0.874 mmol) and DIPEA (0.763 ml, 4.37 mmol) were combined with MeCN (3 ml), and then 2,4-dichloro-6-phenyl-5,6,7,8-tetrahydropyrido[4,3d]pyrimidine (245 mg, 0.874 mmol) was added in portion. The reaction was stirred at 70 °C overnight, at which point LCMS indicated the formation of the desired product. The same was concentrated under reduced pressure. The crude material was purified directly by combiflash chromatography ISCO (24 grams, 0-20 % (0.1 % ammonia in MeOH / DCM)) to provide the desired product (R)-2-chloro-6-phenyl-N-(1-phenyl-2-(pyrrolidin-1-yl)ethyl)-5,6,7,8-tetrahydropyrido[4,3d]pyrimidin-4-amine (163 mg, 0.376 mmol, 43 % yield). MS: m / z = 434.1 [M+H]+.

[00201] Step 2: To a microwave flask containing ethyl (1R,4r)-4-((R)-1-aminopropyl)cyclohexane-1-carboxylate (159 mg, 0.636 mmol) and ethyl (1R,4r)-4-((R)-1-aminopropyl)cyclohexane-1-carboxylate (138 mg, 0.318 mmol), MeCN (0.7 ml, ratio: 1.000) and 2,2,2-trifluoroethanol (0.700 ml, ratio: 1.000) were added. The reaction was heated in a microwave reactor at 175 °C for 2 h, at which time LCMS indicated the formation of the desired product. The reaction mixture was diluted with EtOAc, washed with saturated NaHCO3, brine, dried with MgSO4, and concentrated under reduced pressure to give the crude product. This was purified by combiflash chromatography (12 gram, 0-10% (0.1% ammonia in MeOH / DCM)) to... Petition 870260065188, dated 02 / 07 / 2026, page 183 / 516 179 / 236 provide the desired product (1R,4r)-4-((R)-1-((6-phenyl-4-(((R)-1-phenyl-2(pyrrolidin-1-yl)ethyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2yl)amino)propyl)cyclohexane-1-carboxylate ethyl (20 mg, 0.033 mmol, 10.3% yield). MS: m / z = 611.3 [M+H]+.

[00202] Step 3: To a flask containing ethyl (1R,4r)-4-((R)-1-((6-phenyl-4(((R)-1-phenyl-2-(pyrrolidin-1-yl)ethyl)amino)-5,6,7,8-tetrahydropyrido[4,3d]pyrimidin-2-yl)amino)propyl)cyclohexane-1-carboxylate (20 mg, 0.033 mmol), THF (1 ml, ratio: 2), MeOH (0.500 ml, ratio: 1.000), and then 3.75 N NaOH (0.087 ml, 0.327 mmol) were added. The mixture was stirred at 60 °C for 1 h, at which point LCMS indicated the formation of the desired product. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resulting residue was diluted with ACN, water, and MeOH, and purified by basic preparative HPLC (25-50% acetonitrile / water, 5 mM NH4OH, wavelength 393 nm, lower limit).The desired fractions were combined and lyophilized to provide the desired acid product (1R,4r)-4-((R)-1-((6-phenyl-4-(((R)-1-phenyl-2-(pyrrolidin-1-yl)ethyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)amino)propyl)cyclohexane-1-carboxylic acid (9.3 mg, 0.014 mmol, 44.1% yield). MS: m / z = 583.2 [M+H]+; 1H NMR (400 MHz, Methanol-d4) δ 7.31 - 7.00 (m, 10H), 6.76 (tt, J = 7.2, 1.0 Hz, 1H), 5.33 (dd, J = 10.7, 3.9 Hz, 1H), 4.13 - 3.88 (m, 2H), 3.66 - 3.52 (m, 1H), 3.50 3.33 (m, 2H), 3.10 (dd, J = 12.7, 10.8Hz, 1H), 2.63 - 2.51 (m, 6H), 1.89 - 1.80 (m, 1H), 1.77 - 1.67 (m, 6H), 1.56 - 1.47 (m, 2H), 1.39 - 1.32 (m, 1H), 1.27 - 1.10 (m, 4H), 0.84 - 0.72 (m, 4H), 0.65 - 0.49 (m, 1H). Example 15: Synthesis of acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-(4fluoropiperidin-1-yl)-1-( 1 -methyl-1 H-pyrazol-4-yl)ethyl)amino)-6-phenyl-5,6,7,8tetrahydroquinazolin-2-yl)amino)propyl)cyclohexane-1-carboxylic acid (Compound 142) Petition 870260065188, dated 02 / 07 / 2026, p. 184 / 516 180 / 236 NN

[00203] Stage 1: tetrahydroquinazoline A solution of (R)-2,4-dichloro-6-phenyl-5,6,7,8 (740 mg, 2.65 mmol), 2-(4-fluoropiperidin-1-yl)-1-(1-methyl-1H-pyrazol-4-yl)ethan-1-amine bis-hydrochloride (720 mg, 3.18 mmol, prepared according to intermediate 8) and DIPEA (1.389 ml, 7.95 mmol) in MeCN (10 ml) was heated at 80 °C overnight, at which point LCMS indicated the formation of the desired product. The reaction mixture was concentrated under reduced pressure, partitioned between EtOAc and water. The organic phase was washed with saturated NaHCO3 solution, washed with brine, and dried with MgSO4. The solid was removed by filtration, and the resulting solution was concentrated under reduced pressure. The same was purified by combiflash chromatography ISCO (40 gram, 0-100 % (10 % MeOH in DCM / DCM)) to give the desired product (6R)-2-chloro-N-(2-(4f fluoropyridoxine-1-yl)-1-(1-methyl-1H-pyrazol-4-yl)ethyl l)-6-phen i I-5,6,7,8-tetrahydroquinazolin-4-amine (480 mg, 1.023 mmol, 38.6% yield). MS: m / z = 469.2 [M+H]+.

[00204] Step 2: To a microwave flask containing ethyl (1R,4r)-4((R)-1-aminopropyl)cyclohexane-1-carboxylate (213 mg, 0.853 mmol) and (6R)-2-chloro-N-(2-(4-fluoropiperidin-1-yl)-1-(1-methyl-1H-pyrazol-4-yl)ethyl)-6-phenyl-5,6,7,8-tetrahydroquinazoline-4-amine (200 mg, 0.426 mmol), MeCN (1 ml, ratio: 1.000) and 2,2,2-trifluoroethanol (1 ml, ratio: 1.000) were added. The reaction was heated in a microwave reactor at 165 °C for 1.5 h, at which point LCMS indicated Petition 870260065188, dated 02 / 07 / 2026, page 185 / 516 181 / 236 the formation of the desired product. The reaction mixture was diluted with EtOAc, washed with saturated NaHCO3, brine and dried with MgSO4 and concentrated under reduced pressure. The same was purified by combiflash chromatography ISCO (24 gram, 0-20 % (0.1 % ammonia in MeOH / DCM)) to give the desired product (1R,4r)-4-((1R)-1(((6R)-4-((2-(4-fluoropiperidin-1-yl)-1-(1-methyl-1H-pyrazol-4-yl)ethyl)amino)6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)amino)propyl)cyclohexane-1-carboxylate ethyl (109 mg, 0.169 mmol, 39.6 % yield). MS: m / z = 646.4 [M+H]+.

[00205] Step 3: To a flask containing (1R,4r)-4-((1R)-1-(((6R)-4((2-(4-fluoropiperidin-1-yl)-1-(1-methyl-1H-pyrazol-4-yl)ethyl)amino)-6-phenyl5,6,7,8-tetrahydroquinazolin-2-yl)amino)propyl)cyclohexane-1-carboxylate ethyl (109 mg, 0.169 mmol), THF (1 ml, ratio: 2), MeOH (0.500 ml, ratio: 1.000) and then 3.75 N NaOH (0.450 ml, 1.688 mmol) were added. The mixture was stirred at 60 °C for 1 h, at which point LCMS indicated the formation of the desired product. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resulting residue was diluted with ACN, water, and MeOH, and purified by basic preparative HPLC (15-40% acetonitrile / water, 5 mM NH4OH, wavelength 396, mass detector). The desired fractions were combined and lyophilized to provide the desired product (31 mg, 0.046 mmol, 27.2% yield).MS: m / z = 618.3 [M+H]+; 1H NMR (400 MHz, Methanol-d4) δ 7.42 (s, 1H), 7.30 (d, J = 0.8 Hz, 1H), 7.27 - 7.20 (m, 4H), 7.17 - 7.09 (m, 1H), 5.49 (dd, J = 9.7, 5.0 Hz, 1H), 4.63 - 4.44 (m, 1H), 3.74 (s, 3H), 2.97 - 2.78 (m, 2H), 2.70 -2.42 (m, 7H), 2.38 - 2.27 (m, 2H), 2.08 1.52 (m, 13H), 1.45 - 1.22 (m, 4H), 1.02 - 0.86 (m, 2H), 0.83 (t, J = 7.3 Hz, 3H).

[00206] The following compounds were produced using the above procedure or modifications to the above procedure with the Petition 870260065188, dated 02 / 07 / 2026, p. 186 / 516 182 / 236 use of the corresponding intermediaries. Table 3 LCMS m / z [M+H]+ = 642,4, RMN de1H (400 MHz, Metanol-d4) δ 7,62 (s, 1H), 7,50 - 7,40 (m, 1H), 7,38 7,30 (m, 4H), 7,24 (ddt, J = 8,6, 5,4, 2,6 Hz, 1H), 5,70 (dd, J = 10,0, 4,7 Hz, 1H), 4,51 - 4,40 (m, 1H), 3,89 (s, 1H), 3,14 - 2,93 (m, 3H), 2,91 - 2,59 (m, 5H), 2,42 (dd, J = 15,8, 11,0 Hz, 1H), 2,19 - 1,91 (m, 6H), 1,84 (t, J = 10,4 Hz, 2H), 1,77 - 1,60 (m, 5H), 1,60 - 1,30 (m, 11H), 1,18 - 0,98 (m, 2H), 0,95 (t, J = 7,3 Hz, 4H), 0,88 (d, J = 6,4 Hz, 3H). LCMS m / z [M+H]+= 614,4, RMN de1H (400 MHz, Metanol-d4) δ 7,42 (s, 1H), 7,29 (d, J = 4,8 Hz, 1H), 7,26 - 7,16 (m, 4H), 7,12 (tt, J = 6,2, 2,8 Hz, 1H), 5,55 (dd, J = 10,2, 4,9 Hz, 1H), 3,73 (s, 4H), 2,99 - 2,42 (m, 8H), 2,29 (dd, J = 15,9, 11,2 Hz, 1H), 2,03 - 1,10 (m, 18H), 1,04 - 0,52 (m, 9H). LCMS m / z [M+H]+= 666,5, RMN de1H (400 MHz, MeOD) δ 7,52 (s, 1H), 7,37 (s, 1H), 7,23 (q, J = 4,1 Hz, 4H), 7,11 (ddt, J = 8,4, 5,5, 2,6 Hz, 1H), 4,03 (q, J = 7,3 Hz, 2H), 3,71 (dt, J = 9,7, 4,9 Hz, 1H), 3,01 - 2,81 (m, 3H), 2,61 (dt, J = 15,8, 10,0 Hz, 3H), 2,35 (d, J = 13,4 Petição 870260065188, de 02 / 07 / 2026, pág. 187 / 516 183 / 236 Hz, 1H), 2,17 - 1,74 (m, 14H), 1,74 - 1,48 (m, 7H), 1,31 (t, J = 7,3 Hz, 8H), 0,82 (t, J = 7,3 Hz, 6H). LCMS m / z [M+H]+ = 614,4, RMN de1H (400 MHz, MeOD) δ 7,55 (s, 1H), 7,43 (s, 1H), 7,39 - 7,29 (m, 4H), 7,28 - 7,18 (m, 1H), 5,63 (dd, J = 9,8, 4,8 Hz, 1H), 4,14 (q, J = 7,3 Hz, 2H), 3,84 (s, 1H), 3,05 - 2,89 (m, 2H), 2,76 (dd, J = 15,8, 5,4 Hz, 2H), 2,70 - 2,55 (m, 4H), 2,54 - 2,36 (m, 3H), 2,15 1,91 (m, 5H), 1,82 (d, J = 12,9 Hz, 1H), 1,75 - 1,54 (m, 6H), 1,51 - 1,39 (m, 8H), 1,11 - 1,00 (m, 2H), 0,94 (t, J = 7,3 Hz, 3H). LCMS m / z [M+H]+= 612,4, RMN de1H (400 MHz, MeOD) δ 7,52 (d, J = 3,3 Hz, 1H), 7,42 (d, J = 4,1 Hz, 1H), 7,34 (d, J = 6,4 Hz, 3H), 7,21 (d, J = 7,1 Hz, 1H), 5,53 (s, 1H), 3,83 (d, J = 14,4 Hz, 4H), 3,55 (s, 1H), 2,96 (d, J = 10,8 Hz, 3H), 2,82 - 2,57 (m, 3H), 2,52 2,28 (m, 3H), 2,14 - 1,87 (m, 6H), 1,85 - 1,60 (m, 6H), 1,59 - 1,26 (m, 7H), 1,15 0,97 (m, 2H), 0,93 (t, J = 7,4 Hz, 3H). Petição 870260065188, de 02 / 07 / 2026, pág. 188 / 516 184 / 236 LCMS m / z [M+H]+ = 652,4, RMN de1H (400 MHz, Metanol-d4) δ 7,51 (dd, J = 40,1,8,4 Hz, 2H), 7,38 7,02 (m, 5H), 5,42 (s, 1H), 3,91 - 3,73 (m, 4H), 3,19 2,85 (m, 4H), 2,82 - 2,58 (m, 3H), 2,45 (dd, J = 15,8, 10,6 Hz, 1H), 2,25 - 1,53 (m, 21H), 1,49 - 1,24 (m, 4H), 1,09 (dtd, J = 18,9, 13,8, 13,4, 9,9 Hz, 2H), 0,83 (t, J = 7,5 Hz, 3H) LCMS m / z [M+H]+= 614.34, RMN de1H (400 MHz, MeOD) δ 7,42 (s, 1H), 7,37 7,22 (m, 5H), 7,13 (qt, J = 5,3, 2,8 Hz, 1H), 5,55 (s, 1H), 3,74 (s, 4H), 2,99 - 2,50 (m, 8H), 2,43 - 2,24 (m, 1H), 2,14 - 1,16 (m, 20H), 0,89 0,74 (m, 7H). LCMS m / z [M+H]+= 626,3, RMN de1H (400 MHz, Metanol-d4) δ 7,34 - 7,18 (m, 6H), 7,11 (tq, J = 6,4, 2,2 Hz, 1H), 7,02 - 6,90 (m, 2H), 5,24 (s, 1H), 3,59 (ddt, J = 9,1,6,1,2,9 Hz, 1H), 3,40 (s, 1H), 3,03 - 2,79 (m, 3H), 2,75 - 2,49 (m, 3H), 2,36 (q, J = 12,1, 10,9 Hz, 3H), 2,10 - 1,07 (m, 19H), 0,81 (t, J = 7,3 Hz, 5H). Petição 870260065188, de 02 / 07 / 2026, pág. 189 / 516 185 / 236 LCMS m / z [M+H]+ = 614,4, RMN de1H (400 MHz, MeOD) δ 7,48 (s, 1H), 7,40 (d, J = 0,8 Hz, 1H), 7,38 - 7,30 (m, 4H), 7,27 - 7,17 (m, 1H), 5,63 (dd, J = 10,2, 4,1 Hz, 1H), 3,85 (s, 4H), 3,19 (dd, J = 13,6, 10,3 Hz, 1H), 3,10 2,93 (m, 2H), 2,80 - 2,29 (m, 7H), 2,12 - 1,87 (m, 5H), 1,80 (d, J = 12,9 Hz, 1H), 1,75 - 1,56 (m, 5H), 1,55 1,26 (m, 7H), 1,17 - 0,98 (m, 5H), 0,93 (t, J = 7,3 Hz, 3H). LCMS m / z [M+H]+= 628,4, RMN de1H (400 MHz, Metanol-d4) δ 7,42 (s, 1H), 7,31 (s, 1H), 7,23 (d, J = 4,9 Hz, 4H), 7,18 - 7,07 (m, 1H), 5,42 (d, J = 8,2 Hz, 1H), 3,74 (s, 4H), 2,86 (tdd, J = 11,3, 5,2, 2,8 Hz, 1H), 2,77 2,51 (m, 4H), 2,45 (dd, J = 12,7, 5,5 Hz, 1H), 2,38 2,20 (m, 3H), 2,17 - 1,78 (m, 7H), 1,75 - 1,52 (m, 3H), 1,50 - 1,20 (m, 6H), 1,15 1,04 (m, 2H), 1,00 - 0,81 (m, 5H), 0,76 (d, J = 8,4 Hz, ____________6H).____________ LCMS m / z [M+H]+= 628,4, RMN de1H (400 MHz, MeOD) δ 7,55 - 7,24 (m, 6H), 6,98 (dt, J = 8,6, 4,2 Hz, 1H), 5,76 (s, 1H), 3,75 (d, J = 2,3 Hz, 4H), 3,06 - 2,84 (m, 2H), 2,63 - 2,16 (m, 2H), 2,16 - 0,48 (m, 34H). Petição 870260065188, de 02 / 07 / 2026, pág. 190 / 516 186 / 236 LCMS m / z [M+H]+ = 614,3, RMN de1H (400 MHz, MeOD) δ 7,50 (s, 1H), 7,43 (s, 1H), 7,39 - 7,30 (m, 4H), 7,21 (ddd, J = 8,5, 6,0, 2,2 Hz, 1H), 5,60 (dd, J = 7,6, 5,8 Hz, 1H), 3,85 (s, 4H), 3,11 - 2,81 (m, 4H), 2,77 2,33 (m, 6H), 2,17 - 1,88 (m, 5H), 1,81 (d, J = 12,9 Hz, 1H), 1,75 - 1,23 (m, 12H), 1,16 - 1,00 (m, 5H), 0,94 (t, J = 7,3 Hz, 3H). LCMS m / z [M+H]+= 623,0, RMN de1H (400 MHz, Metanol-d4) δ 7,39 - 7,27 (m, 8H), 7,27 - 7,19 (m, 2H), 5,13 (s, 1H), 4,65 (s, 1H), 3,59 (ddd, J = 10,0, 6,3, 3,8 Hz, 1H), 3,22 - 3,10 (m, 1H), 3,01 (tdd, J = 11,2, 5,3, 2,9 Hz, 1H), 2,81 (tq, J = 10,3, 5,1 Hz, 3H), 2,72 - 2,60 (m, 2H), 2,53 (dd, J = 15,5, 11,0 Hz, 1H), 2,15 - 2,06 (m, 1H), 2,06 - 1,88 (m, 4H), 1,83 1,51 (m, 9H), 1,47 - 1,14 (m, 8H), 0,90 (t, J = 7,3 Hz, 3H), 0,85 - 0,72 (m, 1H), 0,66 0,48 (m, 1H). LCMS m / z [M+H]+= 600,3, RMN de1H (400 MHz, DMSO-d6) δ 7,48 (s, 1H), 7,40 - 7,26 (m, 5H), 7,26 7,19 (m, 1H), 6,12 (d, J = 8,0 Hz, 1H), 5,81 (s, 1H), 5,40 (q, J = 7,6 Hz, 1H), 3,74 (s, 3H), 3,68 - 3,61 (m, 1H), 3,17 (s, 1H), 2,87 (tq, J = 9,0, 4,5 Hz, 1H), 2,70 2,52 (m, 3H), 2,48 - 2,32 (m, Petição 870260065188, de 02 / 07 / 2026, pág. 191 / 516 187 / 236 151 5H), 2,22 (dd, J = 15,6, 11,3 Hz, 1H), 1,94 - 1,84 (m, 2H), 1,78 (d, J = 12,7 Hz, 2H), 1,72 - 1,58 (m, 3H), 1,56 1,39 (m, 5H), 1,38 - 1,21 (m, 4H), 1,20 - 1,00 (m, 2H), 0,98 - 0,72 (m, 5H). LCMS m / z [M+H]+ = 626,4, RMN de1H (400 MHz, Metanol-d4) δ 7,50 (s, 1H), 7,41 (s, 1H), 7,35 - 7,28 (m, 4H), 7,23 - 7,17 (m, 1H), 5,46 - 5,34 (m, 1H), 3,84 3,74 (m, 4H), 3,29 - 3,25 (m, 2H), 2,97 (tdd, J = 11,2, 5,2, 2,7 Hz, 1H), 2,85 (q, J = 8,0, 7,4 Hz, 2H), 2,76 - 2,56 (m, 3H), 2,41 (dd, J = 15,5, 11,0 Hz, 1H), 2,12 - 1,86 (m, 7H), 1,81 - 1,53 (m, 8H), 1,47 1,30 (m, 7H), 1,10 - 0,95 (m, 2H), 0,91 (t, J = 7,3 Hz, 3H). LCMS m / z [M+H]+= 630,3, RMN de1H (400 MHz, Metanol-d4) δ 7,49 (s, 1H), 7,39 (s, 1H), 7,37 - 7,29 (m, 4H), 7,21 (tt, J = 6,4, 2,1 Hz, 1H), 5,57 (dd, J = 9,8, 4,9 Hz, 1H), 3,87 - 3,72 (m, 4H), 3,30 (s, 3H), 3,28 - 3,22 (m, 1H), 3,01 - 2,86 (m, 3H), 2,82 - 2,55 (m, 5H), 2,38 (dd, J = 14,8, 10,9 Hz, 2H), 2,24 (t, J = 10,6 Hz, 1H), 2,14 - 1,84 (m, 7H), 1,78 (d, J = 12,7 Hz, 1H), 1,71 - 1,61 (m, 2H), 1,58 - 1,24 (m, 6H), 1,10 - 0,95 (m, 2H), 0,92 (t, J = 7,3 Hz, 3H). Petição 870260065188, de 02 / 07 / 2026, pág. 192 / 516 188 / 236 121 LCMS m / z [M+H]+ = 628,4, RMN de1H (400 MHz, Metanol-d4) δ 7,41 (s, 1H), 7,30 (d, J = 0,8 Hz, 1H), 7,28 - 7,17 (m, 4H), 7,11 (ddd, J = 8,6, 5,7, 2,7 Hz, 1H), 5,53 (dd, J = 9,8, 4,9 Hz, 1H), 3,73 (s, 4H), 2,96 2,74 (m, 4H), 2,71 - 2,45 (m, 4H), 2,29 (dd, J = 15,7, 11,1 Hz, 1H), 2,07 - 1,77 (m, 5H), 1,60 (ddd, J = 44,7, 33,6, 11,2 Hz, 8H), 1,44 - 1,14 (m, 4H), 1,02 - 0,87 (m, 2H), 0,84 (t, J = 7,3 Hz, 3H), 0,75 (d, J = 5,7 Hz, 6H), 0,53 0,34 (m, 1H). LCMS m / z [M+H]+= 614,3, RMN de1H (400 MHz, Metanol-d4) δ 7,44 (s, 1H), 7,31 (s, 1H), 7,24 (q, J = 4,0, 2,9 Hz, 4H), 7,13 (td, J = 5,9, 2,8 Hz, 1H), 5,58 (s, 1H), 3,74 (s, 4H), 3,10 - 2,79 (m, 4H), 2,79 - 2,51 (m, 4H), 2,41 - 2,27 (m, 1H), 2,27 1,77 (m, 7H), 1,57 (d, J = 13,4 Hz, 5H), 1,50 - 0,90 (m, 9H), 0,83 (d, J = 6,5 Hz, ____________6H).____________ LCMS m / z [M+H]+= 582,8, RMN de1H (400 MHz, DMSO) δ 7,43 - 7,30 (m, 6H), 7,25 (t, J = 7,4 Hz, 3H), 7,16 (t, J = 7,2 Hz, 1H), 6,43 (d, J = 7,2 Hz, 1H), 5,87 (s, 1H), 5,25 (s, 1H), 3,61 (s, 1H), 2,91 (ddd, J = 14,7, 11,3, 7,4 Hz, 2H), 2,67 2,38 (m, 9H), 2,31 (dd, J = 15,7, 11,4 Hz, 1H), 2,03 Petição 870260065188, de 02 / 07 / 2026, pág. 193 / 516 189 / 236 115 119 1,85 (m, 3H), 1,79 (d, J = 14,6 Hz, 2H), 1,67 - 1,42 (m, 6H), 1,37 - 1,01 (m, 4H), 0,81 (t, J = 7,2 Hz, 5H). LCMS m / z [M+H]+ = 582,6, RMN de1H (400 MHz, DMSO) δ 7,42 - 7,30 (m, 6H), 7,30 - 7,20 (m, 3H), 7,16 (t, J = 7,2 Hz, 1H), 6,37 (d, J = 7,3 Hz, 1H), 5,79 (s, 1H), 5,26 (s, 1H), 3,61 (d, J = 8,5 Hz, 1H), 2,96 - 2,81 (m, 2H), 2,67 (dd, J = 15,7, 5,3 Hz, 1H), 2,61 - 2,36 (m, 6H), 2,25 (dd, J = 15,6, 11,3 Hz, 1H), 1,92 (td, J = 9,9, 4,9 Hz, 3H), 1,78 (d, J = 13,8 Hz, 2H), 1,69 - 1,40 (m, 7H), 1,37 - 1,05 (m, 5H), 0,93 - 0,51 (m, 5H). LCMS m / z [M+H]+= 617,4, RMN de1H (400 MHz, DMSO) δ 7,37 - 7,21 (m, 5H), 7,18 - 7,09 (m, 1H), 6,43 (s, 1H), 5,85 (s, 1H), 5,52 (s, 1H), 3,51 (s, 1H), 2,81 (s, 1H), 2,63 - 2,35 (m, 8H), 2,32 - 2,11 (m, 4H), 1,85 (s, 3H), 1,72 (s, 2H), 1,55 (s, 2H), 1,39 (d, J = 5,5 Hz, 5H), 1,26 (d, J = 33,9 Hz, 5H), 1,05 (s, 2H), 0,73 (t, J = 7,2 Hz, 5H). Petição 870260065188, de 02 / 07 / 2026, pág. 194 / 516 190 / 236 139 158 LCMS m / z [M+H]+ = 608,7, RT = 0,94 min (Método: A: 5 mM de hidróxido de amônio em água, B: 5 mM de hidróxido de amônio em ACN, pH 10,2, 50 °C, 2-98 % B. AcQuity UPLC BEH C18 1^m 2,1x 30 mm, 1 __________ml / min)__________ LCMS m / z [M+H]+= 568,4, RMN de1H (400 MHz, Metanol-d4) δ 7,42 - 7,16 (m, 10H), 5,55 - 5,33 (m, 1H), 3,82 (td, J = 9,3, 8,0, 5,7 Hz, 1H), 3,06 - 2,29 (m, 10H), 2,10 - 1,75 (m, 10H), 1,66 1,18 (m, 5H), 1,18 - 0,84 (m, 5H). LCMS m / z [M+H]+= 675,6, RMN de1H (400 MHz, MeOD) δ 7,25 (td, J = 8,1, 6,1 Hz, 1H), 7,10 - 7,04 (m, 1H), 7,00 (dt, J = 10,3, 2,2 Hz, 1H), 6,86 (td, J = 8,6, 2,7 Hz, 1H), 5,65 - 5,24 (m, 1H), 3,86 - 3,58 (m, 1H), 2,95 (dddd, J = 11,3, 8,3, 5,2, 2,7 Hz, 1H), 2,77 (d, J = 7,0 Hz, 2H), 2,73 - 2,54 (m, 3H), 2,48 (s, 3H), 2,43 - 2,25 (m, 4H), 2,14 - 1,12 (m, 24H), 1,00 (qt, J = 12,7, 6,4 Hz, 2H), 0,64 (t, J = 7,3 Hz, 3H). Petição 870260065188, de 02 / 07 / 2026, pág. 195 / 516 191 / 236 114 LCMS m / z [M+H]+ = 661,4, RMN de1H (400 MHz, MeOD) δ 8,81 (s, 1H), 7,35 (td, J = 8,0, 6,1 Hz, 1H), 7,17 (d, J = 7,9 Hz, 1H), 7,11 (dt, J = 10,3, 2,2 Hz, 1H), 7,02 6,91 (m, 1H), 5,45 (s, 1H), 3,83 - 3,58 (m, 1H), 3,23 3,14 (m, 1H), 3,11 - 2,98 (m, 1H), 2,95 - 2,61 (m, 5H), 2,56 - 2,38 (m, 4H), 2,24 1,81 (m, 7H), 1,81 - 1,50 (m, 8H), 1,50 - 1,17 (m, 8H), 0,93 (t, J = 7,3 Hz, 4H), 0,82 - 0,54 (m, 1H). LCMS m / z [M+H]+= 631,5, RMN de1H (400 MHz, MeOD) δ 8,69 (s, 1H), 7,29 7,19 (m, 4H), 7,12 (dt, J = 5,8, 2,9 Hz, 1H), 5,45 (dd, J = 9,5, 5,3 Hz, 1H), 3,56 (ddd, J = 10,2, 6,6, 4,0 Hz, 1H), 2,99 - 2,26 (m, 12H), 2,08 - 1,09 (m, 18H), 1,00 0,69 (m, 8H), 0,70 - 0,49 (m, _____________1H).____________ LCMS m / z [M+H]+= 617,5, RMN de1H (400 MHz, MeOD) δ 8,68 (s, 1H), 7,29 7,19 (m, 4H), 7,14 (dt, J = 6,1,3,2 Hz, 1H), 5,69 (s, 1H), 3,70 (s, 1H), 2,90 (ddt, J = 8,3, 5,3, 2,5 Hz, 1H), 2,82 (dd, J = 12,9, 9,7 Hz, 1H), 2,75 - 2,28 (m, 12H), 1,96 (dtd, J = 31,6, 13,0, 7,8 Hz, 5H), 1,83 - 1,66 (m, 2H), 1,58 - 1,15 (m, 11H), 1,10 0,91 (m, 2H), 0,63 (t, J = 7,3 Hz, 3H). Petição 870260065188, de 02 / 07 / 2026, pág. 196 / 516 192 / 236 127 159 160 LCMS m / z [M+H]+ = 661,4, RMN de1H (400 MHz, MeOD) δ 7,35 (td, J = 8,0, 6,1 Hz, 1H), 7,26 - 7,15 (m, 2H), 7,11 (dt, J = 10,3, 2,2 Hz, 1H), 6,96 (td, J = 8,5, 2,6 Hz, 1H), 5,61 (s, 1H), 3,72 (ddd, J = 9,8, 6,0, 3,8 Hz, 1H), 3,61 - 3,38 (m, 2H), 3,25 - 2,98 (m, 3H), 2,92 2,58 (m, 6H), 2,57 - 2,40 (m, 1H), 2,24 - 1,90 (m, 7H), 1,90 - 1,22 (m, 15H), 1,19 0,97 (m, 2H), 0,75 (s, 3H). LCMS m / z [M+H]+= 562,6, RMN de1H (400 MHz, DMSO) δ 7,77 (d, J = 8,1 Hz, 2H), 7,39 - 7,27 (m, 6H), 7,27 - 7,18 (m, 1H), 7,17 6,97 (m, 5H), 6,40 (d, J = 8,3 Hz, 1H), 5,29 (d, J = 7,1 Hz, 1H), 5,00 (t, J = 7,3 Hz, 1H), 2,96 - 2,76 (m, 3H), 2,66 - 2,53 (m, 3H), 2,49 2,40 (m, 3H), 2,29 - 2,07 (m, 1H), 2,00 - 1,74 (m, 2H), 1,72 - 1,56 (m, 4H), 1,38 (d, J = 7,0 Hz, 3H). LCMS m / z [M+H]+= 607,8, RMN de1H (400 MHz, MeOD) δ 7,34 - 7,16 (m, 8H), 7,12 (dtd, J = 4,7, 2,6, 1,3 Hz, 2H), 5,15 (dd, J = 10,0, 4,1 Hz, 1H), 3,56 (ddd, J = 9,7, 5,8, 4,0 Hz, 1H), 3,32 (s, 1H), 2,97 - 2,71 (m, 4H), 2,71 - 2,35 (m, 4H), 2,26 (dd, J = 19,3, 8,5 Hz, 2H), 2,11 - 0,87 (m, 20H), 0,50 (t, J = 7,2 Hz, 3H). Petição 870260065188, de 02 / 07 / 2026, pág. 197 / 516 193 / 236 LCMS m / z [M+H]+ = 638,4, RMN de 1H (400 MHz, MeOD) δ 7,60 (td, J = 7,8, 2,9 Hz, 1H), 7,37 (s, 1H), 7,34 - 7,24 (m, 4H), 7,24 7,14 (m, 1H), 7,14 - 6,92 (m, 3H), 5,47 (s, 1H), 5,14 - 4,93 (m, 1H), 3,75 (s, 3H), 3,63,1 (Sinais para 5H sobrepõem o pico de solvente de MeOD), 3,04 - 2,83 (m, 1H), 2,82 - 2,53 (m, 3H), 2,39 2,27 (m, 1H), 2,26 - 1,86 (m, 8H), 1,87 - 1,54 (m, 5H), 1,49 (d, J = 6,9 Hz, 3H). LCMS m / z [M+H]+= 640,5, RMN de1H (400 MHz, DMSO) δ 7,51 (s, 1H), 7,37 - 7,28 (m, 5H), 7,27 - 7,17 (m, 1H), 6,04 (s, 1H), 5,71 (s, 1H), 5,29 - 5,14 (m, 1H), 3,75 (s, 3H), 3,67 - 3,60 (m, 1H), 2,95 - 2,82 (m, 3H), 2,76 - 2,70 (m, 2H), 2,64 2,52 (m, 2H), 2,36 - 2,22 (m, 1H), 1,99 - 1,73 (m, 10H), 1,72 - 1,62 (m, 3H), 1,55 1,45 (m, 3H), 1,45 - 1,34 (m, 4H), 1,34 - 1,21 (m, 3H), 1,20 - 1,05 (m, 2H), 0,98 0,81 (m, 2H), 0,75 (t, J = 7,2 __________Hz, 3H).__________ LCMS m / z [M+H]+= 654,7, RMN de1H (400 MHz, DMSO) δ 7,54 (s, 1H), 7,42 - 7,30 (m, 5H), 7,27 - 7,15 (m, 1H), 6,03 (s, 1H), 5,70 (s, 1H), 5,16 (q, J = 7,2 Hz, 1H), 4,03 (q, J = 7,2 Hz, 2H), 3,63 (s, 1H), 2,91 - 2,79 (m, 3H), 2,73 (s, 2H), 2,68 Petição 870260065188, de 02 / 07 / 2026, pág. 198 / 516 194 / 236 100 108 2,55 (m, 2H), 2,36 - 2,18 (m, 1H), 2,00 - 1,74 (m, 10H), 1,68 - 1,60 (m, 3H), 1,56 1,47 (m, 3H), 1,44 - 1,37 (m, 4H), 1,35 - 1,24 (m, 6H), 1,17 - 1,06 (m, 2H), 0,96 0,74 (m, 5H). LCMS m / z [M+H]+ = 628,6, RMN de1H (400 MHz, DMSO) δ 7,53 (s, 1H), 7,41 - 7,29 (m, 5H), 7,27 - 7,16 (m, 1H), 6,12 (s, 1H), 5,78 (s, 1H), 5,49 - 5,39 (m, 1H), 4,49 - 4,29 (m, 1H), 3,78 3,63 (m, 1H), 2,95 - 2,85 (m, 1H), 2,75 - 2,66 (m, 2H), 2,61 - 2,52 (m, 3H), 2,45 2,37 (m, 3H), 2,29 - 2,19 (m, 1H), 2,02 - 1,78 (m, 5H), 1,74 - 1,64 (m, 2H), 1,56 1,39 (m, 5H), 1,37 - 1,28 (m, 10H), 1,25 - 1,11 (m, 3H), 1,04 - 0,91 (m, 2H), 0,81 (t, J = 7,2 Hz, 3H). LCMS m / z [M+H]+= 636,7, RMN de1H (400 MHz, DMSO) δ 7,42 - 7,30 (m, 6H), 7,29 - 7,21 (m, 3H), 7,19 - 7,08 (m, 1H), 6,32 (s, 1H), 5,69 (s, 1H), 5,09 - 4,84 (m, 1H), 3,08 - 2,86 (m, 2H), 2,82 - 2,52 (m, 5H), 2,45 2,28 (m, 2H), 2,01 - 1,58 (m, 12H), 1,55 - 1,31 (m, 10H), 1,30 - 0,83 (m, 5H), 0,78 (t, J = 7,3 Hz, 3H). Petição 870260065188, de 02 / 07 / 2026, pág. 199 / 516 195 / 236 153 LCMS m / z [M+H]+ = 652,3, RMN de 1H (400 MHz, MeOD) δ 7,94 - 7,84 (m, 2H), 7,36 (s, 1H), 7,29 (dd, J = 7,8, 3,8 Hz, 3H), 7,14 - 7,08 (m, 1H), 7,08 - 7,01 (m, 1H), 6,92 (ddd, J = 11,0, 8,4, 4,2 Hz, 2H), 5,48 (s, 2H), 5,29 5,23 (m, 1H), 5,07 - 5,01 (m, 1H), 4,03 - 3,92 (m, 2H), 3,21 - 2,82 (m, 5H), 2,76 2,56 (m, 3H), 2,36 - 2,25 (m, 1H), 2,14 - 1,85 (m, 9H), 1,68 - 1,54 (m, 5H), 1,47 (dd, J = 7,0, 1,2 Hz, 3H), 1,31 (td, J = 7,3, 1,0 Hz, ____________3H).____________ LCMS m / z [M+H]+= 608,6, RMN de1H (400 MHz, DMSO) δ 7,76 (d, J = 8,1 Hz, 2H), 7,38 - 7,12 (m, 9H), 6,62 (s, 1H), 6,12 (d, J = 8,4 Hz, 1H), 5,45 - 5,34 (m, 1H), 5,10 - 4,98 (m, 1H), 4,41 4,23 (m, 1H), 2,92 - 2,77 (m, 1H), 2,68 - 2,56 (m, 2H), 2,54 (s, 3H), 2,48 - 2,30 (m, 5H), 2,25 - 2,12 (m, 1H), 1,96 - 1,78 (m, 2H), 1,54 1,18 (m, 14H). LCMS m / z [M+H]+= 646,3, RMN de1H (400 MHz, DMSO-d6) δ 7,52 (s, 1H), 7,41 - 7,27 (m, 2H), 7,25 7,12 (m, 2H), 7,00 (dt, J = 2,1,8,4 Hz, 1H), 6,46 - 6,22 (br s, 1H), 6,11 (br s, 1H), 5,45 (q, J = 7,4 Hz, 1H), 3,76 (s, 3H), 3,69 - 3,59 (m, 1H), 2,85 (br d, J = 9,4 Hz, 1H), 2,81 - 2,70 (m, 2H), Petição 870260065188, de 02 / 07 / 2026, pág. 200 / 516 196 / 236 2,70 - 2,63 (m, 1H), 2,61 2,54 (m, 1H), 2,54 - 2,51 (m, 2H), 2,45 - 2,31 (m, 2H), 2,19 - 2,08 (m, 1H), 2,07 2,00 (m, 1H), 1,95 (m, 1H), 1,92 - 1,78 (m, 3H), 1,72 1,59 (m, 4H), 1,58 - 1,50 (m, 2H), 1,48 - 1,40 (m, 1H), 1,37 - 1,22 (m, 5H), 1,20 1,06 (m, 2H), 1,00 - 0,86 (m, 2H), 0,85 - 0,72 (m, 7H). LCMS m / z [M+H]+= 632,5 , RMN de1H (400 MHz, DMSO-d6) δ 7,46 (s, 1H), 7,40 - 7,33 (m, 1H), 7,33 7,31 (m, 1H), 7,19 (d, J = 7,8 Hz, 1H), 7,14 (br d, J = 10,5 Hz, 1H), 7,01 (dt, J = 1,9, 8,6 Hz, 1H), 5,81 (br d, J = 7,6 Hz, 1H), 5,36 - 5,27 (m, 2H), 3,76 (s, 3H), 3,75 3,68 (m, 1H), 3,03 - 2,93 (m, 2H), 2,92 - 2,76 (m, 3H), 2,69 (br t, J = 5,1 Hz, 4H), 2,66 - 2,58 (m, 2H), 2,33 (br dd, J = 11,2, 15,2 Hz, 1H), 2,09 - 1,98 (m, 2H), 1,89 (br dd, J = 6,2, 11,8 Hz, 3H), 1,74 (br t, J = 12,8 Hz, 2H), 1,52 (br s, 8H), 1,46 - 1,33 (m, 2H), 1,33 - 1,18 (m, 2H), 1,08 - 0,95 (m, 2H), 0,86 (t, J = 7,3 Hz, 3H). Petição 870260065188, de 02 / 07 / 2026, pág. 201 / 516 197 / 236 LCMS m / z [M+H]+= 646,6, RMN de 1H (400 MHz, DMSO-d6) δ 7,53 (s, 1H), 7,38 (m, 2H), 7,34 (s, 1H), 7,11 (t, J = 8,8 Hz, 2H), 6,37 (br s, 1H), 6,20 (br s, 1H), 5,44 (q, J = 7,1 Hz, 1H), 3,77 (s, 3H), 3,65 (br s, 1H), 2,85 (br d, J = 10,3 Hz, 1H), 2,81 -2,61 (m, 3H), 2,57 (br dd, J = 7,5, 12,2 Hz, 2H), 2,44 - 2,30 (m, 2H), 2,19 1,88 (m, 4H), 1,87 - 1,77 (m, 3H), 1,74 - 1,50 (m, 6H), 1,49 - 1,28 (m, 4H), 1,25 (s, 3H), 1,21 - 1,06 (m, 2H), 1,02 - 0,87 (m, 2H), 0,81 (br d, J = 6,4 Hz, 6H) LCMS m / z [M+H]+= 672,7, RMN de1H (400 MHz, DMSO-d6) δ 7,55 (br s, 1H), 7,40 - 7,33 (m, 2H), 7,20 7,15 (m, 2H), 7,07 - 7,00 (m, 1H), 6,22 - 6,02 (m, 1H), 5,20 - 5,13 (m, 1H), 4,03 (q, J = 7,2 Hz, 2H), 3,00 - 2,90 (m, 2H), 2,90 - 2,83 (m, 2H), 2,72 (br s, 2H), 2,63 - 2,54 (m, 3H), 2,43 (br d, J = 1,6 Hz, 1H), 2,28 (br dd, J = 11,2, 15,0 Hz, 1H), 2,04 1,89 (m, 4H), 1,84 (br dd, J = 6,3, 11,7 Hz, 8H), 1,65 (br d, J = 0,9 Hz, 2H), 1,54 1,45 (m, 3H), 1,43 - 1,33 (m, 5H), 1,30 (t, J = 7,3 Hz, 4H), 1,24 - 1,13 (m,2H), 0.98 0.87 (m, 2H), 0.80 (t, J = 7.2 Hz, 3H)., Petition 870260065188, dated 02 / 07 / 2026, p. 202 / 516 198 / 236 LCMS m / z [M+H]+= 658,4, RMN de 1H (400 MHz, DMSO-d6) δ 7,49 (s, 1H), 7,42 - 7,34 (m, 1H), 7,31 (s, 1H), 7,19 (br d, J = 7,8 Hz, 2H), 7,08 - 7,00 (m, 1H), 6,27 - 5,88 (m, 2H), 5,14 (q, J = 7,0 Hz, 1H), 3,74 (s, 3H), 3,62 (br dd, J = 1,3, 3,6 Hz, 2H), 3,00 - 2,80 (m, 4H), 2,73 (br s, 2H), 2,66 - 2,54 (m, 2H), 2,34 - 2,21 (m, 1H), 2,10 - 1,76 (m, 11H), 1,65 (br d, J = 8,8 Hz, 2H), 1,57 1,46 (m, 3H), 1,45 - 1,35 (m, 4H), 1,34 - 1,25 (m, 2H), 1,24 - 1,09 (m, 2H), 0,92 (br dd, J = 1,6, 7,1 Hz, 2H), 0,80 (br t, J = 7,2 Hz, 3H) LCMS m / z [M+H]+= 672,7, RMN de1H (400 MHz, DMSO-d6) δ 7,54 (br s, 1H), 7,40 - 7,31 (m, 2H), 7,19 (d, J = 7,7 Hz, 2H), 7,08 - 7,00 (m, 1H), 6,22 - 6,00 (m, 1H), 5,98 - 5,77 (m, 1H), 5,16 (q, J = 7,2 Hz, 1H), 4,03 (q, J = 7,3 Hz, 2H), 2,99 - 2,90 (m, 2H), 2,72 (br s, 3H), 2,63(br d, J = 5,3 Hz, 2H), 2,59 (br d, J = 4,9 Hz, 2H), 2,26 (br dd, J = 12,0, 14,7 Hz, 1H), 1,99 - 1,89 (m, 4H), 1,89 1,77 (m, 8H),1,70 - 1,60 (m, 2H), 1,54 - 1,35 (m, 8H), 1,30 (t, J = 7,3 Hz, 5H), 1,22 - 1,12 (m, 2H), 0,98 - 0,87 (m, 2H), 0,79 (t, J = 7,3 Hz, 3H)., Petição 870260065188, de 02 / 07 / 2026, pág. 203 / 516 199 / 236 LCMS m / z [M+H]+= 646,3, RMN de 1H (400 MHz, DMSO-d6) δ 7,55 (s, 1H), 7,35 (s, 1H), 7,30 - 7,23 (m, 1H), 7,19 - 7,04 (m, 3H), 6,40 - 6,25 (m, 1H), 6,08 5,85 (m, 1H), 5,44 (q, J = 7,6 Hz, 1H), 3,78 (s, 3H), 3,69 - 3,61 (m, 1H), 2,85 (br d, J = 15,8 Hz, 2H), 2,78 (br d, J = 10,5 Hz, 1H), 2,71 2,65 (m, 1H), 2,61 - 2,56 (m, 1H), 2,53 (d, J = 1,9 Hz, 1H), 2,45 - 2,37 (m, 2H), 2,36 - 2,31 (m, 1H), 2,30 2,21 (m, 1H), 2,10 - 1,98 (m, 2H), 1,97 - 1,90 (m, 1H), 1,89 - 1,78 (m, 3H), 1,72 1,60 (m, 4H), 1,59 - 1,51 (m, 2H), 1,46 (dt, J = 4,0, 6,9 Hz, 1H), 1,36 (s, 3H), 1,34 1,26 (m, 1H), 1,25 - 1,07 (m, 2H), 1,00 - 0,88 (m, 2H), 0,86 - 0,72 (m, 7H). LCMS m / z [M+H]+= 632,6, RMN de1H (400 MHz, DMSO-d6) δ 7,54 - 7,49 (m, 1H), 7,40 - 7,33 (m, 1H), 7,31 (s, 1H), 7,20 (d, J = 7,6 Hz, 2H), 7,07 - 7,00 (m, 1H), 6,19 - 6,10 (m, 1H), 5,93 5,75 (m, 1H), 5,47 - 5,38 (m, 1H), 4,07 - 3,99 (m, 2H), 3,71 - 3,64 (m, 1H), 2,96 2,90 (m, 1H), 2,70 - 2,64 (m, 2H), 2,39 (br s, 4H), 2,30 2,17 (m, 2H), 2,00 - 1,80 (m, 6H), 1,72 - 1,63 (m, 2H), 1,42 (br d, J = 4,4 Hz,6H), 1,37 - 1,28 (m, 8H), 1,22 1,14 (m, 2H), 1,00 - 0,91 (m, Petição 870260065188, de 02 / 07 / 2026, pág. 204 / 516 200 / 236 117 130 2H), 0,83 - 0,78 (m, 3H). LCMS m / z [M+H]+= 688,6, RMN de1H (400 MHz, DMSO-d6) δ 7,53 (br d, J = 7,5 Hz, 1H), 7,42 - 7,30 (m, 2H), 7,19 (br d, J = 9,3 Hz, 2H), 7,09 - 7,00 (m, 1H), 6,27 - 6,08 (m, 1H), 5,29 5,16 (m, 1H), 4,43 - 4,26 (m, 1H), 4,09 - 3,99 (m, 2H), 3,80 - 3,73 (m, 1H), 3,69 3,64 (m, 1H), 2,94 (br s, 2H), 2,83 - 2,77 (m, 2H), 2,61 (br d, J = 4,2 Hz, 4H), 2,30 - 2,15 (m, 3H), 2,15 2,01 (m, 4H), 1,95 - 1,83 (m, 4H), 1,79 - 1,65 (m, 4H), 1,56 - 1,44 (m, 2H), 1,34 1,28 (m, 5H), 1,23 - 1,11 (m, 4H), 1,09 - 0,94 (m, 4H), 0,83 - 0,75 (m, 3H). LCMS m / z [M+H]+= 646,3, RMN de1H (400 MHz, DMSO-d6) δ 7,63 - 7,48 (m, 1H), 7,43 - 7,25 (m, 2H), 7,23 - 7,09 (m, 2H), 7,00 (dt, J = 2,3, 8,4 Hz, 1H), 6,53 6,21 (m, 1H), 6,12 - 5,86 (m, 1H), 5,52 - 5,38 (m, 1H), 3,76 (s, 3H), 3,69 - 3,61 (m, 1H), 2,90 - 2,70 (m, 4H), 2,59 - 2,55 (m, 1H), 2,54 2,52 (m, 2H), 2,40 - 2,30 (m, 2H), 2,13 - 1,95 (m, 4H), 1,91 - 1,80 (m, 3H), 1,72 (br d, J = 11,9 Hz, 2H), 1,67 1,58 (m, 2H), 1,55 (br d, J = 3,1 Hz, 1H), 1,50 - 1,40 (m, 2H), 1,39 - 1,25 (m, 4H), 1,24 - 1,13 (m, 2H), 1,08 0,91 (m, 2H), 0,89 - 0,70 (m, Petição 870260065188, de 02 / 07 / 2026, pág. 205 / 516 201 / 236 ____________7H).____________ LCMS m / z [M+H]+ = 614,2, RMN de 1H (400 MHz, DMSO-d6) δ ppm 8,53 (s, 1 H), 7,41 - 7,34 (m, 6 H) 7,29 - 7,14 (m, 2 H) 7,02 - 6,97 (m, 1 H) 5,38 (br d, J=2,63 Hz, 1 H) 3,70 (brs, 1H), 3,07 - 2,99 (m, 2 H), 2,88 - 2,50 (m, 9 H) 2,16 - 1,98 (m, 4 H), 1,84 - 1,25 (m, 14 H) 0,93 (t, J=6,8 Hz, 3H), 0,84 - 0,81 (m, 1 H) 0,58 - 0,56 ___________(m, 1 H).___________ LCMS m / z [M+H]+= 632,70, RMN de1H (400 MHz, DMSO-d6 ) δ ppm 7,53 (br s, 1H), 7,40 - 7,33 (m, 1H), 7,32 (s, 1H), 7,19 (d, J = 7,7 Hz, 2H), 7,08 - 7,00 (m, 1H), 6,26 - 6,08 (m, 1H), 5,99 5,72 (m, 1H), 5,47 - 5,37 (m, 1H), 4,07 - 3,97 (m, 2H), 3,73 - 3,63 (m, 2H), 2,97 2,86 (m, 2H), 2,68 - 2,63 (m, 1H), 2,60 - 2,55 (m, 2H), 2,45 - 2,42 (m, 2H), 2,38 (br s, 4H), 2,27 - 2,19 (m, 1H), 2,07 - 1,98 (m, 1H), 1,96 1,88 (m, 2H), 1,87 - 1,81 (m, 2H), 1,74 - 1,63 (m, 2H), 1,42 (br d, J = 4,6 Hz, 4H), 1,37 - 1,28 (m, 7H), 1,26 1,15 (m, 2H), 1,01 - 0,88 (m, 2H), 0,85 - 0,78 (m, 3H). Petição 870260065188, de 02 / 07 / 2026, pág. 206 / 516 202 / 236 109 LCMS m / z [M+H]+ = 614,40, RMN de1H (400 MHz, METANOL-d4) δ ppm 7,53 (s, 1H), 7,42 (s, 1H), 7,35 - 7,32 (m, 4H), 7,24 - 7,21 (m, 1H), 5,06 (br s, 1H), 3,85 (s, 3H), 3,02 - 2,98 (m, 3H), 2,83 2,73 (m, 6H), 2,48 - 2,42 (m, 1H), 2,23 - 1,98 (m, 7H), 2,14 - 1,93 (m, 5H), 1,82 1,31 (m, 10H), 1,09 - 0,92 __________(m,5H)__________ LCMS m / z [M+H]+= 628,00, RMN de1H (400 MHz, METANOL- d4) δ ppm 7,60 (s, 1 H), 7,44 (s, 1 H), 7,29 - 7,39 (m, 4 H), 7,19 - 7,27 (m, 1 H), 5,71 - 5,82 (m, 1 H), 4,14 (q, J = 7,45 Hz, 2 H), 3,86 (br s, 1 H), 3,38 (br s, 1 H), 3,14 (br s, 1 H), 3,01 (br s, 2 H), 2,53 - 2,90 (m, 5 H), 2,35 - 2,51 (m, 2 H), 1,88 2,19 (m, 5 H), 1,59 - 1,86 (m, 6 H), 1,46 - 1,58 (m, 3 H), 1,32 - 1,45 (m, 6 H), 1,17 (br d, J = 6,14 Hz, 2 H), 1,00 - 1,10 (m, 2 H), 0,95 (br t, J = 7,23 Hz, 4 H). LCMS m / z [M+H]+= 669,80, RMN de1H (400 MHz, METANOL-d4) δ ppm 7,55 (s, 1 H), 7,43 (s, 1 H), 7,28 - 7,37 (m, 4 H), 7,24 - 7,20 (m, 1 H), 5,54 - 5,49 (m, 1 H), 4,13 (q, J = 7,31 Hz, 2 H), 3,82 (br s, 1 H), 3,59 - 3,77 (m, 2 H), 3,52 (br d, J = 8,77 Hz, 2 H), 3,33 - 3,43 (m, 1 H), 2,92 - 3,04 (m, 1 H), 2,56 - 2,86 (m, 5 H), 2,31 Petição 870260065188, de 02 / 07 / 2026, pág. 207 / 516 203 / 236 122 126 2,51 (m, 3 H), 2,21 (s, 2 H), 1,87 - 2,13 (m, 6 H), 1,26 1,85 (m, 14 H), 1,01 - 1,11 (m, 2 H), 0,94 (t, J = 7,45 __________Hz, 3 H).__________ LCMS m / z [M+H]+ = 625,90, RMN de1H (400 MHz, METANOL-d4) δ ppm 7,63 (br s, 1 H), 7,45 - 7,55 (m, 1 H), 7,29 - 7,39 (m, 4 H), 7,23 (br d, J = 5,70 Hz, 1 H), 5,68 5,90 (m, 2 H), 4,57 - 4,77 (m, 1 H), 4,15 (q, J = 7,02 Hz, 2 H), 3,86 (br s, 2 H), 3,45 - 3,63 (m, 2 H), 3,06 3,26 (m, 2 H), 2,98 (br s, 2 H), 2,54 - 2,88 (m, 5 H), 2,33 - 2,51 (m, 1 H), 1,59 2,20 (m, 11 H), 1,21 - 1,57 (m, 8 H), 1,04 (br d, J = 4,38 Hz, 1 H), 0,95 (br t, J = 7,23 __________Hz, 2 H).__________ LCMS m / z [M+H]+= 653,75, RMN de1H (300 MHz, METANOL- d4) δ ppm 7,60 (d, J = 7,24 Hz, 1 H) 7,44 (d, J = 6,58 Hz, 1 H) 7,27 - 7,38 (m, 4 H) 7,19 - 7,26 (m, 1 H) 5,58 (br s, 1 H) 4,12 (qd, J = 7,24, 1,97 Hz, 1 H) 3,89 (br s, 1 H) 2,86 - 3,10 (m, 2 H) 2,60 - 2,84 (m, 5 H) 2,29 2,58 (m, 5 H) 1,61 - 2,21 (m, 14 H) 1,31 - 1,58 (m, 11 H) 0,77 - 1,23 (m, 5 H) Petição 870260065188, de 02 / 07 / 2026, pág. 208 / 516 204 / 236 137 165 166 LCMS m / z [M+H]+ = 664,35, RMN de1H (400 MHz, METANOL- d4) δ ppm 8,53 (s, 1 H), 7,58 (s, 1 H), 7,42 (s, 1 H), 7,35 - 7,31 (m, 4 H), 7,16 - 7,26 (m, 1 H), 5,54 (br s, 1 H), 4,12 (q, J = 7,16 Hz, 2 H), 3,88 (br d, J = 2,19 Hz, 1 H), 2,94 - 3,06 (m, 2 H), 2,55 - 2,93 (m, 9 H), 2,38 2,52 (m, 1 H), 1,88 - 2,20 (m, 9 H), 1,60 - 1,86 (m, 5 H), 1,26 - 1,57 (m, 6 H), 0,87 - 1,14 (m, 5 H) LCMS m / z [M+H]+= 556,30, RMN de1H (400 MHz, METANOL- d4) δ ppm 8,51 (br s, 1 H), 7,37 - 7,35 (m, 7H), 7,28 - 7,25 (m, 2H), 5,46 5,38 (m, 1H), 3,78 - 3,76 (m, 1H), 3,12 - 2,62 (m, 8H), 2,52 - 2,50 (m, 2H), 2,38 2,32 (m, 5H), 2,14 - 1,98 (m, 3H), 1,89 - 1,26 (m, 9H), 0,96 - 0,92 (m, 3H). LCMS m / z [M+H]+= 612,30, RMN de1H (400 MHz, METANOL-d4) δ ppm 8,51 (s, 1 H), 7,44 - 7,29 (m, 9 H), 7,27 (br d, J = 6,58 Hz, 1 H), 5,36 (br d, J = 3,95 Hz, 1 H), 3,94 (br d, J = 12,28 Hz, 2 H), 3,77 (br s, 1 H), 3,45 3,36 (m, 2 H), 3,25 - 3,12 (m, 1 H), 3,10 - 2,96 (m, 2 H), 2,93 - 2,63 (m, 4 H), 2,61 - 2,48 (m, 1 H), 2,24 1,95 (m, 4 H), 1,92 - 1,66 (m, 4 H), 1,64 - 1,17 (m, 9 H), 0,95 (br t, J = 7,23 Hz, 3 H), 0,84 (br s, 1 H), 0,55 (br Petição 870260065188, de 02 / 07 / 2026, pág. 209 / 516 205 / 236 132 d, J = 11,84 Hz, 1 H) LCMS m / z [M+H]+ = 627,90, RMN de1H (METANOL-d4) δ 7,61 (s, 1H), 7,45 (s, 1H), 7,30-7,39 (m, 4H), 7,24 7,22 (m, 1H), 5,65 (brs, 1H), 4,14 (q, J = 7,3 Hz, 2H), 3,11 - 3,15 (m, 3H), 3,00 2,71 (m, 8H), 2,49 - 2,42 (m, 2H), 2,12 - 1,95 (m, 6H), 1,83 - 1,63 (m, 8H), 1,55 1,49 (m, 2H), 1,47 - 1,42 (m, 2H), 1,40 - 1,31 (m, 3H), 1,11 - 1,02 (m, 3H), 0,97 0,91 (m, 3H). LCMS m / z [M+H]+= 668,5, RMN de1H (400 MHz, DMSO) δ 7,50 (s, 1H), 7,26 (d, J = 4,6 Hz, 5H), 7,15 (tt, J = 5,5, 3,1 Hz, 1H), 6,02 (s, 1H), 5,87 (s, 1H), 5,11 (q, J = 7,3 Hz, 1H), 4,32 (p, J = 6,6 Hz, 1H), 3,58 (s, 1H), 2,81 (t, J = 6,8 Hz, 3H), 2,65 (s, 2H), 2,53 (td, J = 13,4, 5,7 Hz, 2H), 2,20 (dd, J = 15,4, 11,1 Hz, 1H), 2,00 1,70 (m, 11H), 1,71- 1,55 (m, 2H), 1,42 (q, J = 7,6 Hz, 3H), 1,37 - 1,23 (m, 13H), 1,22 - 1,05 (m, 2H), 0,95 0,79 (m, 2H), 0,73 (t, J = 7,2 Hz, 3H). Petição 870260065188, de 02 / 07 / 2026, pág. 210 / 516 206 / 236 176 177 LCMS m / z [M+H]+ = 626,5, RMN de 1H (400 MHz, DMSO-d6) δ = 7,58 - 7,43 (m, 1H), 7,38 - 7,26 (m, 5H), 7,25 - 7,18 (m, 1H), 6,20 6,08 (m, 1H), 5,70 - 5,47 (m, 1H), 4,54 - 4,41 (m, 1H), 3,75 (s, 3H), 2,92 - 2,80 (m, 2H), 2,74 - 2,69 (m, 3H), 2,65 - 2,55 (m, 2H), 2,47 2,43 (m, 1H), 2,30 - 2,18 (m, 2H), 2,17 - 2,09 (m, 1H), 2,07 (s, 1H), 2,03 - 1,77 (m, 5H), 1,73 - 1,59 (m, 3H), 1,50 - 1,33 (m, 3H), 1,32 1,21 (m, 5H), 1,20 - 1,05 (m, 2H), 1,01 - 0,91 (m, 1H), 0,90 - 0,72 (m, 2H), 0,71 0,60 (m, 3H), 0,37 - 0,10 (m, ____________2H).____________ LCMS m / z [M+H]+= 626,5, RMN de1H (400 MHz, DMSO-d6) δ = 7,56 - 7,41 (m, 1H), 7,39 - 7,27 (m, 5H), 7,25 - 7,17 (m, 1H), 6,18 6,04 (m, 1H), 5,63 - 5,37 (m, 1H), 4,56 - 4,42 (m, 1H), 3,75 (s, 3H), 2,97 - 2,85 (m, 2H), 2,74 - 2,68 (m, 3H), 2,65 - 2,54 (m, 2H), 2,46 2,40 (m, 1H), 2,31 - 2,22 (m, 1H), 2,21 - 2,09 (m, 2H), 2,04 - 1,89 (m, 2H), 1,87 1,76 (m, 3H), 1,67 (br s, 3H), 1,45 - 1,21 (m, 8H), 1,19 - 1,02 (m, 2H), 0,99 0,92 (m, 1H), 0,88 - 0,79 (m, 1H), 0,71 - 0,63 (m, 3H), 0,63 - 0,51 (m, 1H), 0,30 0,11 (m, 2H). Petição 870260065188, de 02 / 07 / 2026, pág. 211 / 516 207 / 236 178 179 LCMS m / z [M+H]+ = 658,4, RMN de 1H (400 MHz, DMSO-d6) δ = 7,58 - 7,40 (m, 1H), 7,39 - 7,25 (m, 5H), 7,25 - 7,18 (m, 1H), 6,17 5,98 (m, 1H), 5,51 - 5,12 (m, 1H), 4,60 - 4,36 (m, 1H), 3,74 (s, 3H), 2,91 - 2,82 (m, 1H), 2,78 - 2,68 (m, 3H), 2,68 - 2,57 (m, 3H), 2,57 2,51 (m, 3H), 2,45 - 2,32 (m, 2H), 2,31 - 2,13 (m, 2H), 2,11 - 1,99 (m, 1H), 1,97 1,79 (m, 3H), 1,79 - 1,58 (m, 4H), 1,56 - 1,46 (m, 1H), 1,45 - 0,97 (m, 10H), 0,92 0,77 (m, 1H), 0,76 - 0,60 (m, 6H), 0,59 - 0,44 (m, 1H). LCMS m / z [M+H]+= 644,5, RMN de1H (600 MHz, DMSO) δ 11,86 (d, J = 248,6 Hz, 1H), 11,27 (s, 1H), 10,04 (s, 1H), 8,26 (s, 1H), 7,60 (s, 1H), 7,40 (s, 1H), 7,39 - 7,31 (m, 4H), 7,26 (ddd, J = 8,7, 5,1, 3,5 Hz, 1H), 5,70 (s, 1H), 4,40 (s, 2H), 3,78 (s, 4H), 3,50 (s, 2H), 3,35 (d, J = 14,5 Hz, 2H), 3,27 (d, J = 11,9 Hz, 1H), 3,18 (d, J = 12,3 Hz, 1H), 3,05 (d, J = 23,9 Hz, 1H), 2,97 - 2,65 (m, 6H), 2,43 - 2,23 (m, 1H), 2,16 1,80 (m, 5H), 1,72 (d, J = 13,5 Hz, 3H), 1,60 (p, J = 15,8 Hz, 1H), 1,43 (d, J = 11,9 Hz, 2H), 1,37 - 1,22 (m, 2H), 1,16 (q, J = 12,5 Hz, 1H), 1,03 - 0,78 (m, 5H), 0,72 (d, J = 23,2 Hz, 3H), Petição 870260065188, de 02 / 07 / 2026, pág. 212 / 516 208 / 236 180 181 0,46 (d, J = 14,0 Hz, 1H) LCMS m / z [M+H]+ = 640,5, RMN de1H (400 MHz CD3OD) δ 7,27 (s, 1H), 7,17 (s, 1H), 7,14- 7,05 (m, 4H), 7,04-6,93 (m, 1H), 5,04 (s, 1H), 4,23 (s, 1H), 3,59 (s, 3H), 2,84-2,71 (m, 1H), 2,69-2,14 (m, 12H), 2,15 1,95 (m, 2H), 1,94 - 1,58 (m, 7H), 1,56 -1,31 (m, 5H), 1,29-0,97 (m, 7H), 0,94 0,61 (m, 3H), 0,308 (t, J = ________7,2 Hz, 3H).________ LCMS m / z [M+H]+= 630,5, RMN de1H (400 MHz, DMSO-d6 ) δ = 7,54 - 7,42 (m, 1H), 7,38 - 7,27 (m, 5H), 7,25 - 7,18 (m, 1H), 6,23 6,12 (m, 1H), 5,50 - 5,19 (m, 1H), 4,60 - 4,44 (m, 1H), 3,81 (br s, 1H), 3,74 (s, 3H), 3,12 (s, 3H), 2,95 - 2,85 (m, 1H), 2,84 - 2,74 (m, 2H), 2,72 (s, 2H), 2,70 - 2,65 (m, 1H), 2,65 - 2,56 (m, 3H), 2,54 (br s, 2H), 2,47 - 2,40 (m, 2H), 2,31 - 2,20 (m, 1H), 2,01 - 1,80 (m, 6H), 1,77 1,54 (m, 3H), 1,42 - 1,06 (m, 5H), 0,95 - 0,80 (m, 1H), 0,73 - 0,63 (m, 3H), 0,63 0,49 (m, 1H). Petição 870260065188, de 02 / 07 / 2026, pág. 213 / 516 209 / 236 182 183 LCMS m / z [M+H]+ = 644,4, RMN de 1H (400 MHz, DMSO) δ 7,46 (s, 1H), 7,38 - 7,29 (m, 5H), 7,22 (ddt, J = 8,6, 5,2, 3,2 Hz, 1H), 6,13 (d, J = 7,3 Hz, 1H), 5,23 (d, J = 7,4 Hz, 1H), 4,47 (t, J = 10,3 Hz, 1H), 3,74 (s, 3H), 2,87 (tt, J = 10,5, 4,6 Hz, 1H), 2,72 (s, 3H), 2,61 (dtd, J = 31,0, 13,8, 6,1 Hz, 5H), 2,39 (s, 1H), 2,23 (dq, J = 22,6, 12,5 Hz, 4H), 2,01 (d, J = 11,4 Hz, 1H), 1,90 (s, 3H), 1,81 (d, J = 11,4 Hz, 1H), 1,72 (d, J = 12,3 Hz, 1H), 1,64 (s, 1H), 1,54 (s, 1H), 1,31 (t, J = 19,9 Hz, 7H), 1,13 (t, J = 12,8 Hz, 1H), 1,03 (s, 3H), 0,87 (d, J = 13,4 Hz, 1H), 0,69 (t, J = 7,2 Hz, 3H), 0,55 (t, J = 12,7 __________Hz, 1H).__________ LCMS m / z [M+H]+= 658,3, RMN de1H (400 MHz, DMSO-d6) δ = 7,56 - 7,41 (m, 1H), 7,39 - 7,27 (m, 5H), 7,26 - 7,19 (m, 1H), 6,25 6,08 (m, 1H), 5,55 - 5,11 (m, 1H), 4,62 - 4,39 (m, 1H), 3,74 (s, 3H), 3,08 (s, 3H), 2,94 - 2,83 (m, 1H), 2,83 2,69 (m, 4H), 2,68 - 2,51 (m, 7H), 2,35 - 2,12 (m, 2H), 1,98 - 1,75 (m, 7H), 1,74 1,51 (m, 3H), 1,40 - 1,01 (m, 6H), 0,89 - 0,74 (m, 4H), 0,68 (br t, J = 6,8 Hz, 3H), 0,58 - 0,40 (m, 1H) Petição 870260065188, de 02 / 07 / 2026, pág. 214 / 516 210 / 236 184 185 LCMS m / z [M+H]+ = 658,5, RMN de1H (400 MHz, DMSO-d6) δ = 11,91 (br s, 1H), 7,56 - 7,44 (m, 1H), 7,42 - 7,29 (m, 5H), 7,26 7,19 (m, 1H), 6,24 - 6,11 (m, 1H), 5,53 - 5,12 (m, 1H), 4,64 - 4,38 (m, 1H), 3,74 (s, 3H), 3,07 (s, 3H), 2,93 - 2,82 (m, 1H), 2,79 - 2,57 (m, 8H), 2,57 - 2,51 (m, 2H), 2,49 2,45 (m, 1H), 2,34 - 2,14 (m, 2H), 2,03 - 1,77 (m, 7H), 1,77 - 1,56 (m, 3H), 1,46 1,20 (m, 4H), 1,19 - 1,04 (m, 2H), 0,93 - 0,82 (m, 1H), 0,78 (br d, J = 6,0 Hz, 3H), 0,68 (br s, 1H), 0,59 - 0,41 __________(m,1H)__________ LCMS m / z [M+H]+= 646,4, RMN de1H (400 MHz, DMSO-d6) δ = 11,88 (br s, 1H), 7,50 - 7,38 (m, 1H), 7,37 - 7,29 (m, 4H), 7,26 7,18 (m, 1H), 6,20 (br s, 1H), 5,49 - 5,21 (m, 1H), 4,57 - 4,45 (m, 1H), 3,63 (s, 3H), 2,94 - 2,84 (m, 1H), 2,83 - 2,77 (m, 1H), 2,72 (s, 3H), 2,71 - 2,67 (m, 1H), 2,66 - 2,62 (m, 1H), 2,61 2,58 (m, 1H), 2,57 - 2,52 (m, 2H), 2,47 - 2,43 (m, 1H), 2,30 - 2,21 (m, 1H), 2,10 1,99 (m, 1H), 1,94 - 1,79 (m, 5H), 1,76 - 1,68 (m, 1H), 1,67 - 1,56 (m, 3H), 1,55 1,46 (m, 2H), 1,41 - 1,22 (m, 5H), 1,21 - 1,08 (m, 1H), 1,02 - 0,92 (m, 1H), 0,83 0,75 (m, 4H), 0,74 - 0,64 (m, Petição 870260065188, de 02 / 07 / 2026, pág. 215 / 516 211 / 236 3H), 0,60 - 0,44 (m, 1H) LCMS m / z [M+H]+ = 644,4, RMN de1H (400 MHz, DMSO) δ 8,18 (s, 1H), 7,46 (s, 1H), 7,37 - 7,28 (m, 5H), 7,22 (ddd, J = 8,6, 5,3, 3,3 Hz, 1H), 6,20 (d, J = 7,0 Hz, 1H), 5,23 - 5,17 (m, 1H), 4,45 (t, J = 10,2 Hz, 1H), 3,74 (s, 3H), 2,37 - 2,29 (m, 1H), 2,26 (d, J = 13,0 Hz, 2H), 2,13 (d, J = 10,6 Hz, 1H), 2,05 - 1,85 (m, 4H), 1,80 (d, J = 11,6 Hz, 1H), 1,55 (s, 1H), 1,40 - 1,20 (m, 7H), 1,13 (t, J = 12,4 Hz, 1H), 1,03 (d, J = 8,8 Hz, 3H), 0,88 (q, J = 12,5 Hz, 1H), 0,68 (t, J = 7,1 Hz, 3H), 0,51 (q, J = 12,5 Hz, 1H), 2,88 (s, 1H), 2,72 (s, 3H), 2,70 - 2,52 (m, 5H), 2,41 (s, 1H), 1,71 (d, J = 12,9 Hz, 1H), 1,65 (s, 1H). Exemplo 16: Síntese de ácido (1R,4r)-4-((R)-1-((6-ciclo-hexil-4-(((R)-1(1 -metil-1 H-pirazol-4-il)-2-((S)-3-metilpiperidin-1-il)etil)amino)-5,6,7,8tetra-hidropirido[4,3-d]pirimidin-2-il)(metil)amino)propil)ciclo-hexano-1carboxílico (Composto 152) Petição 870260065188, de 02 / 07 / 2026, pág. 216 / 516 212 / 236

[00207] Step 1: A solution of tert-butyl 2,4-dichloro-7,8-dihydropyrido[4,3d]pyrimidine-6(5H)-carboxylate (3 g, 9.86 mmol), LiOH (0.828 g, 19.73 mmol) in THF (24 ml, ratio: 2) and water (12 ml, ratio: 1.000) was stirred at 65 °C for 4.5 h, at which time LCMS indicated the formation of the desired product. A solution of HCl (2N) was added to neutralize the reaction. The reaction mixture was diluted with EtOAc, washed with water, brine and dried with Na2SO4 and concentrated under reduced pressure to give the crude product. The same was purified by ISCO combiflash chromatography (80 gram, 0-100% EtOAc / DCM) to give the desired product 2-chloro-4-hydroxy-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-tert-butyl carboxylate (1.15 g, 4.02 mmol, 40.8% yield). MS: m / z = 286.0 [M+H]+.

[00208] Step 2: A microwaveable flask containing 2-chloro-4 Petition 870260065188, dated 02 / 07 / 2026, page 217 / 516 213 / 236 hydroxy-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-tert-butyl carboxylate (600 mg, 2,100 mmol), methyl (1R,4r)-4-((R)-1(methylamino)propyl)cyclohexane-1-carboxylate hydrochloride (661 mg, 2,310 mmol) in anhydrous CH3CN (3.5 ml) and DIPEA (1.467 ml, 8.40 mmol) was irradiated at 150 °C for 3.5 h, at which point LCMS indicated the formation of the desired product. The crude product was filtered to remove precipitates and concentrated. The same was purified by ISCO combiflash chromatography (40 grams, 0-10% MeOH / DCM) to give the desired product 4-hydroxy-2-(((R)-1-((1r,4R)-4(methoxycarbonyl)cyclohexyl)propyl)(methyl)amino)-7,8-dihydropyrido[4,3d]pyrimidine-6(5H)-tert-butyl carboxylate (405 mg, 0.876 mmol, 41.7% yield). MS: m / z = 463.3 [M+H]+.

[00209] Step 3: To a solution of 4-hydroxy-2-(((R)-1-((1r,4R)-4(methoxycarbonyl)cyclohexyl)propyl)(methyl)amino)-7,8-dihydropyrido[4,3d]pyrimidine-6(5H)-carboxylate tert-butyl (400 mg, 0.865 mmol) in MeOH (1.667 ml), 4 N HCl in dioxane (2.162 ml, 8.65 mmol) was added and stirred at room temperature for 1.5 h, at which time LCMS indicated the formation of the desired product. The reaction mixture was concentrated under reduced pressure and azeotropated twice with DCM. The resulting residue was dried under vacuum for several hours to give the desired product (1R,4r)-4-((R)-1-((4-hydroxy-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylate methyl (351 mg, 0.880 mmol, 100% yield). MS: m / z = 363.2 [M+H]+.

[00210] Step 4: Cyclohexanone (0.016 ml, 0.153 mmol) and (1R,4r)-4-((R)-1-((4-hydroxy-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylate methyl (60.9 mg, 0.168 mmol) followed by DCE (1.5 ml) under N2 were added to a flask. This was stirred for 15 min, and then sodium triacetoxyborohydride (64.8 mg, 0.306 mmol) was added and stirring continued. Petition 870260065188, dated 02 / 07 / 2026, page 218 / 516 214 / 236 overnight, at which point LCMS showed incomplete reaction. Two more eq of cyclohexanone were added and stirred for 15 min. Then, two eq of sodium triacetoxyborohydride were added and stirred for another 1 h, at which point LCMS indicated the formation of the desired product. This was directly purified by combiflash chromatography ISCO (24 grams, 0-30% MeOH / DCM) to give the desired product (1R,4r)-4-((R)-1-((6-cyclohexyl-4-hydroxy-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylate (57.5 mg, 0.129 mmol, 85% yield). MS: m / z = 445.3 [M+H]+.

[00211] Step 5: To a solution of (1R,4r)-4-((R)-1-((6-cyclohexyl-4-hydroxy-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylate (57.5 mg, 0.129 mmol) in anhydrous ACN (0.3 ml) in a microwaveable flask, POClA (0.036 ml, 0.388 mmol) was added dropwise at room temperature. The reaction mixture was heated to 80 °C for 60 min, at which point LCMS indicated the formation of the desired product. It was diluted with EtOAc and rapidly cooled by the careful addition of saturated aqueous NaHCO3 solution. Two phases were separated, and the aqueous phase was extracted twice with EtOAc, dried with Na2SO4, and concentrated. It was further dried under high vacuum to give the desired product (1R,4r)-4-((R)-1-((4-chloro-6-cyclohexyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylate methyl (60 mg, 0.130 mmol, 100% yield). MS: m / z = 463.2 [M+H]+.

[00212] Step 6: To a microwaveable flask containing (1R,4r)-4((R)-1-((4-chloro-6-cyclohexyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylate methyl (60 mg, 0.130 mmol), (R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1yl)ethan-1-amine (38.3 mg, 0.130 mmol) in CH3CN (0.5 ml), HCl in Petition 870260065188, dated 02 / 07 / 2026, page 219 / 516 215 / 236 dioxane (0.032 ml, 0.130 mmol) was added and irradiated at 120 °C in MW for 7 h followed by further heating at 130 °C for 1 h, at which point LCMS indicated ~35% formation of the desired product. The reaction mixture was concentrated under vacuum. The same was further dried under high vacuum to give the desired crude product (1R,4r)-4-((R)-1-((6-cyclohexyl-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)3-methylpiperidin-1-yl)ethyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylate methyl (84 mg, 0.052 mmol, 40% yield). MS: m / z = 649.4 [M+H]+.

[00213] Step 7: To a flask containing (1R,4r)-4-((R)-1-((6-cyclohexyl-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1yl)ethyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylate methyl (84 mg, 0.052 mmol), THF (0.4 ml, ratio: 2) and MeOH (0.200 ml, ratio: 1.000) were added, followed by 4 M NaOH (0.065 ml, 0.259 mmol). The mixture was stirred at 50 °C for 1.5 h, at which point LCMS indicated the formation of the desired product. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resulting residue was diluted with MeOH and purified by basic preparative HPLC (25-50% acetonitrile / water, 5 mM NH4OH, wavelength 396, mass detector).The desired fractions were combined and lyophilized to provide the desired acid product (1R,4r)-4-((R)-1-((6-cyclohexyl-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)3-methylpiperidin-1-yl)ethyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid (10 mg, 0.014 mmol, 27.9% yield). LCMS: m / z = 635.5 [M+H]+; 1H NMR (400 MHz, Methanol-d4) δ 7.45 (s, 1H), 7.36 (s, 1H), 5.46 (s, 1H), 4.47 (s, 1H), 3.82 (s, 3H), 3.54 - 3.37 (m, 2H), 2.92 - 2.74 (m, 8H), 2.68 - 2.62 (m, 2H), 2.53 - 2.45 (m, 1H), 2.04 - 1.91 (m, 5H),1.88 - 1.59 (m, 11H), 1.51 - 1.20 (m, 11H), 0.92 - 0.67 (m, 9H). Petition 870260065188, dated 02 / 07 / 2026, page 220 / 516 216 / 236 Example 17: Synthesis of acid (1R,4r)-4-((R)-1-(((R)-6-(3-fluorophenyl)-4(((R)-1 -(1-methyl-1 H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)amino)5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclohexane-1carboxylic acid (Compound 23)

[00214] Step 1: A solution of (R)-2,4-dichloro-6-(3-fluorophenyl)5,6,7,8-tetrahydroquinazoline (10 g, 33.7 mmol), 2,3,5,6-tetrafluorophenol (6.71 g, 40.4 mmol) and DIPEA (7.64 ml, 43.7 mmol) in CH3CN (volume: 50 ml) was stirred at 80 °C for 40 h. The mixture was concentrated, and EtOAc (200 ml) was added, and washed with saturated aqueous NaHCO3 solution, water and brine, dried with Na2SO4 and concentrated. LCMS showed some product in the aqueous layer; a 6 N aqueous HCl solution was used to neutralize to pH = 4 and extracted with EtOAc (200 ml). The organic layer was dried with Na2SO4 and concentrated. The residue was purified by chromatography (2 x 330 g, silica gel, 0-5% with 5% constants of EtOAc / heptane) to produce the desired product. 1H NMR (400 MHz, DMSO-d6) δ 8.01 (tt, J = 10.9, 7.3 Hz, 1H), 7.40 (td, J = 8.0, 6.0 Hz, 1H), 7.33 - 7.18 (m, 2H), Petition 870260065188, dated 02 / 07 / 2026, p. 221 / 516 217 / 236 7,08 (td, J = 9,1, 8,7, 2,6 Hz, 1H), 3,24 - 2,91 (m, 4H), 2,85 (dd, J = 16,6, 11,1 Hz, 1H), 2,10 (td, J = 8,0, 7,3, 3,4 Hz, 2H).

[00215] Step 2: (R)-2-chloro-6-(3-fluorophenyl)-4-(2,3,5,6-tetrafluorophenoxy)-5,6,7,8-tetrahydroquinazoline (8.6 g, 20.15 mmol), (1R,4r)-4-((R)-1-(methylamino)propyl)cyclohexane-1-carboxylate methyl (8.08 g, 28.2 mmol) in anhydrous acetonitrile (volume: 12 ml), DIPEA (14.08 ml, 81 mmol) was added in a 100 ml pressure reactor. The resulting mixture was heated to 100 °C for 72 h. The reaction mixture was diluted with EtOAc (250 ml) and washed with saturated aqueous NaHCO3 solution, water and brine, then dried with Na2SO4 and concentrated.The residue was purified by flash chromatography (330 g, silica gel, 0-10% EtOAc / heptane; product eluting at ~9% EtOAc / heptane); 1H NMR (400 MHz, DMSO-d6) δ 8.06 - 7.91 (m, 1H), 7.38 (td, J = 7.8, 6.0 Hz, 1H), 7.23 (dd, J = 10.1, 2.8 Hz, 2H), 7.06 (td, J = 8.8, 2.2 Hz, 1H), 3.69 (s, 1H), 3.58 (s, 3H), 3.08 (dt, J = 10.7, 6.0 Hz, 1H), 2.95 (dd, J = 16.1, 5.0 Hz, 1H), 2.89 - 2.71 (m, 4H), 2.65 (dd, J = 15.8, 11.5Hz, 1H), 2.04 (tt, J = 10.8, 5.2 Hz, 2H), 1.80 (dd, J = 34.3, 12.7 Hz, 2H), 1.55 - 1.10 (m, 5H), 0.92 - 0.77 (m, 2H), 0.59 - 0.43 (m, 3H).

[00216] Step 3: A solution of (R)-1-(1-methyl1H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1-yl)ethan-1-amine bischloride (1.174 g, 3.98 mmol), (1R,4r)-4-((R)-1-(((R)-6-(3-fluorophenyl)-4-(2,3,5,6tetrafluorophenoxy)-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylate methyl (2 g, 3.31 mmol) in iPrOH (volume: 3 ml) and DIPEA (2.315 ml, 13.25 mmol) was stirred at 110 °C for 3 days. To the mixture, EtOAc (100 ml) was added and washed with a saturated solution of NaHCO3 and brine, dried with Na2SO4 and concentrated. The residue was purified using flash column chromatography (0-25% EtOAc / heptane to remove SM by elution, 40-85% EtOAc / DCM to remove the product by elution). Petition 870260065188, dated 02 / 07 / 2026, p. 222 / 516 218 / 236 silica column 120, 1 injection) to generate the desired product (1R,4r)4-((R)-1-(((R)-6-(3-fluorophenyl)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)3-methylpiperidin-1-yl)ethyl)amino)-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylate methyl as a pale clear solid (1.25 g). LCMS: m / z = 660.4 [M+H]+.

[00217] Step 4: To a solution of (1R,4r)-4-((R)-1-(((R)-6-(3-fluorophenyl)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylate methyl (1.05 g, 1.591 mmol) in MeOH (volume: 12 ml, ratio: 2.000) and water (volume: 6 ml, ratio: 1.000), NaOH (4 M, 3.98 ml, 15.91 mmol) was added and stirred at 50 °C for 30 min, and the mixture was half concentrated and directly loaded to be purified by column chromatography. Reverse phase. (120 g ISCO gold C-18 column, 10 to 60% MeCN / water, with 0.1% NH4OH as a modifier to produce 0.77 g of (1R,4r)-4-((R)-1-(((R)-6-(3-fluorophenyl)-4(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)amino)5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid.LCMS: m / z = 646.7 [M+H]+; 1H NMR (400 MHz, Methanol-d4) δ 7.39 (s, 1H), 7.35 - 7.17 (m, 2H), 7.12 - 6.96 (m, 2H), 6.84 (td, J = 8.6, 2.7 Hz, 1H), 5.41 (d, J = 9.5 Hz, 1H), 4.39 (s, 1H), 3.73 (s, 3H), 3.01 - 2.82 (m, 3H), 2.77 (s, 4H), 2.66 (dq, J = 15.9, 10.7, 8.1 Hz, 4H), 2.42 - 2.19 (m, 1H), 2.10 - 1.50 (m, 12H), 1.50 - 1.05 (m, 6H), 0.94 0.73 (m, 5H), 0.67 (t, J = 7.2 Hz, 3H), 0.50 (d, J = 12.7 Hz, 1H).

[00218] The following compounds were produced using the above procedure or modifications to the above procedure using the corresponding intermediates. Petition 870260065188, dated 02 / 07 / 2026, p. 223 / 516 219 / 236 Table 4 LCMS m / z [M+H]+ = 646,4, RMN de 1H (400 MHz, MeOD) δ 7,41 (s, 1H), 7,36 7,19 (m, 5H), 7,13 (ddd, J = 8,5, 5,5, 2,5 Hz, 1H), 5,51 5,23 (m, 1H), 4,55 - 4,32 (m, 1H), 4,30 - 4,00 (m, 2H), 3,75 (s, 3H), 2,97 - 2,61 (m, 10H), 2,56 (dd, J = 12,9, 5,3 Hz, 1H), 2,48 - 2,24 (m, 1H), 2,12 - 1,65 (m, 10H), 1,65 - 1,52 (m, 2H), 1,52 - 1,10 (m, 6H), 1,10 - 0,77 (m, 2H), 0,69 (t, J = 7,3 Hz, 3H), 0,53 (d, J = 12,7 Hz, 1H). LCMS m / z [M+H]+= 644,3, RMN de1H (400 MHz, DMSO) δ 7,54 - 7,18 (m, 3H), 7,13 (d, J = 8,6 Hz, 2H), 6,97 (t, J = 8,6 Hz, 1H), 6,34 - 5,86 (m, 1H), 5,40 - 4,87 (m, 1H), 4,63 - 4,26 (m, 1H), 3,68 (s, 3H), 2,97 - 2,80 (m, 2H), 2,76 - 2,49 (m, 8H), 2,31 - 2,05 (m, 2H), 2,00 - 1,39 (m, 11H), 1,16 (dd, J = 39,4, 22,6 Hz, 9H), 0,77 (d, J = 12,0 Hz, 1H), 0,60 (t, J = 7,3 Hz, 4H). Example 18: Synthesis of acid (1R,4r)-4-((R)-1-((6-(3-fluorophenyl)-4(((R)-1-( 1 -methyl-1 H-pyrazol-4-yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)amino)5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid (Compound 55) Petition 870260065188, dated 02 / 07 / 2026, page 224 / 516 220 / 236

[00219] Step 1: To a solution of 1-bromo-3-fluorobenzene (30 g, 209.52 mmol) and 1,4-dioxa-8-azaspiro[4,5]decane (73.33 g, 419.04 mmol) in toluene (500 ml), t-BuONa (40.27 g, 139.68 mmol), Sphos (8.60 g, 20.95 mmol) and Pd2(dba)s (9.59 g, 10.48 mmol) were added at 25 °C under N2. Then, the mixture was stirred at 110 °C for 16 h before being degassed three times with N2. LCMS showed that the desired mass was detected. The reaction mixture was poured into H2O (1000 ml) and acidified with 3 N HCl to adjust pH = 1, then extracted with EtOAc (800 ml x 2). The aqueous phase was adjusted to pH = 7-8 by the addition of NaHCO3. Extracted with EtOAc (800 ml x 3), the combined organic phase was dried with anhydrous Na2SO4, filtered, and concentrated to Petition 870260065188, dated 02 / 07 / 2026, p. 225 / 516 221 / 236 produce 8-(3-fluorophenyl)-1,4-dioxa-8-azaspiro[4,5]decane (42 g, 91.28% purity) as a yellow oil. LCMS: RT = 0.651 min, m / z = 238.1 [M+H]+.

[00220] Step 2: To a solution of 8-(3-fluorophenyl)-1,4-dioxa-8-azaspiro[4,5]decane (42 g, 177.01 mmol) in dioxane / H2O (450 ml, V / V = 2 / 1), concentrated HCl (150 ml) was added at 25 °C. Then, the mixture was stirred at 60 °C for 24 h. TLC (petroleum ether / ethyl acetate = 5 / 1) showed that most of the starting material (Rf = 0.5) was consumed, and a major point (Rf = 0.4) was detected. The reaction mixture was poured into H2O (1000 ml) and basified with 6 N NaOH solution to adjust to pH = 7-8. The mixture was extracted with EtOAc (1000 ml x 3). The combined organic phase was dried with anhydrous Na2SO4, filtered, and concentrated. The residue was purified by combiflash silica gel column chromatography (from PE to 50% EA) and concentrated to yield 1-(3-fluorophenyl)piperidin-4-one (20 g, 95% purity) as a colorless oil. LCMS: RT = 0.723 min, m / z = 194.0 [M+H]+.

[00221] Step 3: To a solution of diethyl carbonate (36.68 g, 310.53 mmol) in THF (60 ml), NaH (2.98 g, 60%, 74.53 mmol) was added in portions. Then, the mixture was heated to 80 °C, and a solution of 1-(3-fluorophenyl)piperidin-4-one (12 g, 62.11 mmol) in THF (60 ml) was added to the mixture by dropwise. The reaction mixture was stirred at 80 °C for 2 h. The TLC (petroleum ether / ethyl acetate = 5 / 1) showed that the starting material (Rf = 0.4) was completely consumed, and a principal spot (Rf = 0.8) was detected. The reaction mixture was rapidly cooled with a saturated NH4Cl solution (300 ml) and extracted with EtOAc (200 ml x 3). The combined organic phase was dried with anhydrous Na2SO4, filtered, and concentrated. The residue was purified by combiflash silica gel column chromatography (from PE to 50% EA) and concentrated to produce 1-(3Petition 870260065188, dated 02 / 07 / 2026, page 226 / 516 222 / 236 fluorophenyl)-4-oxopiperidine-3-carboxylate ethyl (8.0 g, 80% purity) as a colorless oil. LCMS: RT = 0.927 min, m / z = 266.0 [M+H]+.

[00222] Step 4: To a solution of 1-(3-fluorophenyl)-4-oxopiperidine-3-carboxylate ethyl (4 g, 15.08 mmol) in EtOH (100 ml), urea (1.81 g, 30.16 mmol) and NaOMe (1.63 g, 30.16 mmol) were added at 25 °C. Then, the mixture was stirred at 80 °C for 16 h. LCMS showed that a main peak with the desired mass was detected. The precipitate was filtered and dried under reduced pressure to yield 6-(3-fluorophenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine2,4(1H,3H)-dione (1.2 g, 87% purity) as a yellow solid. LCMS: RT = 0.683 min, m / z = 262.0 [M+H]+.

[00223] Step 5: To a solution of 6-(3-fluorophenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-2,4(1H,3H)-dione (1.2 g, 4.59 mmol) in dioxane (10 ml), POCh (7 ml) was added at 25 °C. Then, the reaction mixture was heated to 125 °C and stirred for 16 h. LCMS showed that a main peak with the desired mass was detected. The reaction mixture was concentrated under reduced pressure to remove POCl3. Then, the residue was diluted with EA (50 ml) and washed with saturated NaHCO3 solution (50 ml x 2). The combined organic phase was dried with anhydrous Na2SO4, filtered, and concentrated. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10 / 1 - petroleum ether / ethyl acetate = 2 / 1) and concentrated to yield 2,4-dichloro-6-(3-fluorophenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (400 mg, 87% purity) as a yellow solid. LCMS: RT = 0.910 min, m / z = 297.9 [M+H]+.

[00224] Step 6: To a solution of 2,4-dichloro-6-(3-fluorophenyl)5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (150 mg, 0.503 mmol) and 1-(1-methyl-1H-pyrazol-4-yl)-2-(piperidin-1-yl)ethan-1-amine bichloride hydrochloride (212 mg, 0.603 mmol) in MeCN (2 ml), DPIEA (325 mg, 2.52 mmol) was added. The mixture was then stirred at 80 °C for 4 h. LCMS showed Petition 870260065188, dated 02 / 07 / 2026, page 227 / 516 223 / 236 that a main peak with the desired mass was detected. The reaction mixture was diluted with H2O (5 ml) and extracted with ethyl acetate (3 ml x 3). The combined organic phase was dried with anhydrous Na2SO4, filtered, and concentrated. The residue was purified by silica gel column chromatography (from petroleum ether to ethyl acetate) and concentrated to yield 2-chloro-6-(3-fluorophenyl)-N-(1-(1-methyl-1H-pyrazol-4yl)-2-(piperidin-1-yl)ethyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine (100 mg, 96% purity) as a yellow solid. LCMS: RT = 0.731 min, m / z = 470.1 [M+H]+.

[00225] Step 7: To a solution of 2-chloro-6-(3-fluorophenyl)-N-(1-(1-methyl-1H-pyrazol-4-yl)-2-(piperidin-1-yl)ethyl)-5,6,7,8-tetrahydropyrido[4,3d]pyrimidin-4-amine (100 mg, 0.425 mmol) in ACN (0.5 ml), DPIEA (82 mg, 0.638 mmol) and methyl (1R,4r)-4-((R)-1-aminopropyl)cyclohexane-1-carboxylate hydrochloride (100 mg, 0.212 mmol) were added at 25 °C. Then, the mixture was stirred at 160 °C for 10 h under microwave. LCMS showed that the starting material was completely consumed, and a main peak with the desired mass was detected. The reaction mixture was diluted with H2O (5 ml) and extracted with EtOAc (3 ml x 3). The combined organic phase was dried with anhydrous Na2SO4, filtered, and concentrated.The residue was purified by preparative TLC (EA) to yield (1R,4r)-4-((1R)-1-((6-(3-fluorophenyl)-4-((1-(1-methyl-1H-pyrazol-4-yl)-2-(piperidin-1-yl)ethyl)amino)-5,6,7,8-tetrahydropyrido[4,3d]pyrimidin-2-yl)amino)propyl)cyclohexane-1-carboxylate methyl (120 mg, 82% purity) as a yellow oil. LCMS: RT = 0.724 min, m / z = 633.3 [M+H]+.

[00226] Step 8: To a solution (1R,4r)-4-((1R)-1-((6-(3fluorophenyl)-4-((1-(1-methyl-1H-pyrazol-4-yl)-2-(piperidin-1-yl)ethyl)amino)5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)amino)propyl)cyclohexane1-methyl carboxylate (100 mg, 0.158 mmol) in THF / H2O (1 ml, V / V=1 / 1), UOH-HaO (33 mg, 0.790 mmol) was added at 25 °C. En Petition 870260065188, dated 02 / 07 / 2026, p. 228 / 516 224 / 236. The mixture was stirred at 25 °C for 4 h. LCMS showed that the starting material was completely c...

Claims

CLAIMS 1. Compound characterized in that it has Formula (I): (I) or a pharmaceutically acceptable salt thereof, wherein: A is NR1 or CR2R3; R1 and R2 are each independently H, (C3C6)cycloalkyl, or (C6-Cw)aryl, wherein (C6-Cw)aryl is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl and (C3-C6)cycloalkyl; R3 is H or (C1-C6)alkyl; R4 is (C6-Cw)aryl or a 5- or 6-membered heteroaryl comprising 1, 2, 3 or 4 heteroatoms selected from N, O and S, wherein the (C6-Cw)aryl or the 5- or 6-membered heteroaryl are each optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, oxo, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3C6)cycloalkyl, (C3-C6)cycloalkyl-(C1-C6)alkyl and (C1-C6)alkyl(C3C6)cycloalkyl; R5 is NR8R9;R6 is selected from H, (C1-C6)alkyl, (C3C6)cycloalkyl and (C3-C6)cycloalkyl-(C1-C6)alkyl; R7 is (C3-C6)cycloalkyl or (C6-Cw)aryl, wherein (C3C6)cycloalkyl and (C6-C10)aryl are each optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H and HO2C(C1-C6)alkyl; R8 and R9 are each independently H, (C1C6)alkyl or a 3- to 6-membered heterocycle comprising 1 to 3 heteroatoms selected from N, O and S;or R8 and R9, together with the N to which they are attached, form a heterocycle with 3 to 10 members comprising optionally 1 or 2 additional heteroatoms selected from N, O and S, wherein the heterocycle with 3 to 10 members is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl, (C1C6)haloalkyl, (C3-C6)cycloalkyl-(C1-C6)alkyl, (C3-C6)cycloalkyl, (C1C6)alkyl-O-(C1-C6)alkyl, (C1-C6)hydroxyalkyl, (C1-C6)alkoxy and a heterocycle with 3 to 7 members comprising 1 to 2 heteroatoms selected from N, O and S; Ra, Rb, Rc, and Rd are each independently H or (C1-C6) alkyl.

2. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that A is NR1, and R1 is (C3-C6)cycloalkyl or (C6-C10)aryl, wherein the (C6-C10)aryl is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl and (C3-C6)cycloalkyl.

3. A compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that A is NR1 and R1 is (C6-Cw)aryl, which is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl and (C3-C6)cycloalkyl. Petition 870250075165, dated 25 / 08 / 2025, p. 516 / 551 3 / 33 4. A compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, characterized in that A is NR1, and R1 is (C6-Cw)aryl, which is optionally replaced by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo and -CN.

5. A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, characterized in that A is NR1, and R1 is phenyl, which is optionally replaced by 1 or 2 substituents independently selected from halo and -CN.

6. Compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that A is NR1, and R1 is selected from: CN 7. Compound according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that A is CR2R3, and R2 is (C6-Cw)aryl, which is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-C6)alkyl and (C3-C6)cycloalkyl.

8. A compound according to any one of claims 1 or 7, or a pharmaceutically acceptable salt thereof, characterized in that A is CR2R3, and R2 is (C6-Cw)aryl, which is optionally replaced by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo.

9. Compound, according to any one of claims 1, 7 and 8, or a pharmaceutically acceptable salt thereof, characterized in that A is CR2R3, and R2 is phenyl, which is optionally substituted by 1 or 2 substituents independently selected from among halo.

10. A compound according to any one of claims 1 and 7 to 9, or a pharmaceutically acceptable salt thereof, characterized in that A is CR2R3, and R2 is selected from: FA\ / F TI LI and ^ / , 11. A compound according to any one of claims 1 and 7 to 10, or a pharmaceutically acceptable salt thereof, characterized in that A is CR2R3, and R3 is selected from H and -CH3.

12. A compound according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, characterized in that R4 is a (C6-C1o)aryl or a 5- or 6-membered heteroaryl comprising 1, 2, 3 or 4 heteroatoms selected from N, O and S, wherein the (C6-Cw)aryl is optionally substituted with one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H and (C1Cs)alkyl, and the 5- or 6-membered heteroaryl is optionally substituted with one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, oxo, (C1C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl-(C1C6)alkyl and (C1-C6)alkyl(C3-C6)cycloalkyl.

13. Compound, according to any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, characterized in that R4 is (C6-Cw)aryl or a 5- or 6-membered heteroaryl comprising 1 to 2 heteroatoms selected from N and S, wherein the (C6-Cw)aryl is optionally substituted by one or more (e.g., 1, 2, 3, 4 or 5) independent substituents. Petition 870250075165, dated 08 / 25 / 2025, p. 518 / 551 5 / 33 selected from halo and (C1-C6)alkyl, and the 5- or 6-membered heteroaryl is optionally substituted by one or more (e.g., 1, 2, 3, 4 or 5) substituents independently selected from oxo, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl and (C3-C6)cycloalkyl-(C1-C6)alkyl.

14. A compound according to any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, characterized in that R4 is a 5- or 6-membered heteroaryl comprising 1 to 2 heteroatoms selected from N and S, which is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from oxo, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl and (C3-C6)cycloalkyl(C1-C6)alkyl.

15. A compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt thereof, characterized in that R4 is a 5-membered heteroaryl comprising 1 to 2 heteroatoms selected from N and S, which is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from oxo, (C1-C6)alkyl, (C1-C6)fluoroalkyl, (C3-C6)cycloalkyl and (C3-C6)cycloalkyl(C1-C6)alkyl.

16. A compound according to any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, characterized in that R4 is (C6-C1o)aryl, which is optionally replaced by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo.

17. Compound, according to any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, characterized in that R4 is selected from: Petition 870250075165, dated 08 / 25 / 2025, p. 519 / 551 6 / 33 18. A compound according to any one of claims 1 to 17, or a pharmaceutically acceptable salt thereof, characterized in that R5 is NR8R9, and R8 and R9, together with the N to which they are attached, form a 3- to 10-membered heterocycle optionally comprising 1 or 2 additional heteroatoms selected from N, O, and S, wherein the 3- to 10-membered heterocycle is optionally substituted by one or more (for example, 1, 2, 3, 4, or 5) substituents independently selected from halo, -CN, OH, -CO2H, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl-(C1C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkyl-O-(C1-C6)alkyl, (C1C6)hydroxyalkyl, (C1-C6)alkoxy and a heterocycle with 3 to 7 members comprising 1 to 2 heteroatoms selected from N, O, and S.

19. A compound according to any one of claims 1 to 18, or a pharmaceutically acceptable salt thereof, characterized in that R5 is NR8R9, and R8 and R9, together with the N to which they are attached, form a heterocycle with 3 to 10 members, optionally comprising 1 to 2 additional O heteroatoms, wherein the heterocycle with 3 to 10 members is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CN, -OH, -CO2H, (C1-Cs)alkyl, (C1-Cs)haloalkyl, (C3-C6)cycloalkyl-(C1-Cs)alkyl, (C3Cejcycloalkyl, (C1-C6)alkyl-O-(C1-C6)alkyl, (C1-C6)hydroxyalkyl, (C1-C6)alkoxy and a heterocycle with 3 to 7 members comprising 1 to 2 heteroatoms selected from N, O and S.

20. A compound according to any one of claims 1 to 19, or a pharmaceutically acceptable salt thereof, characterized in that R5 is NR8R9, and R8 and R9, together with the N to which they are attached, form a 3- to 10-membered heterocycle optionally comprising 2 additional O heteroatoms, wherein the 3- to 10-membered heterocycle is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -OH, (C1-C6)alkyl, (C1C6)haloalkyl, (C3-C6)cycloalkyl, (C1-C6)alkyl-O-(C1-C6)alkyl, (C1C6)hydroxyalkyl, (C1-C6)alkoxy and a 3- to 7-membered heterocycle comprising a heteroatom selected from N, O and St.

21. A compound according to any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof, characterized in that R5 is NR8R9, and R8 and R9, together with the N to which they are attached, form a 5 to 10-membered heterocycle optionally comprising 1 to 2 additional O heteroatoms, wherein the 5 to 10-membered heterocycle is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -OH, (C1-C6)alkyl, (C1C6)haloalkyl, (C3-C6)cycloalkyl, (C1-C6)alkyl-O-(C1-C6)alkyl, (C1Ce)hydroxyalkyl, (C1-C6)alkoxy and a 3 to 7-membered heterocycle comprising a heteroatom selected from N and O.

22. Compound according to claim 21, or a pharmaceutically acceptable salt thereof, characterized in that the 5- to 10-membered heterocycle is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) independent substituents selected from among fluorine, -OH, (C1-C6)alkyl, (C1-C6)fluoroalkyl, CH3O-(C1-C6)alkyl, (C1-C6)hydroxyalkyl and a 5-membered heterocycle comprising a heteroatom selected from O.

23. A compound according to claim 21 or 22, or a pharmaceutically acceptable salt thereof, characterized in that the 5- to 10-membered heterocycle is optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from fluorine, -OH, -CH3, -CH2F, CF2H, CH2CH3, -CH2OH, -OCH3 and -CH2OCH3.

24. Compound, according to any one of claims 1 to 23, or a pharmaceutically acceptable salt thereof, characterized in that R5 is selected from: Petition 870250075165, dated 08 / 25 / 2025, pp. 522 / 551 9 / 33 25. Compound according to any one of claims 1 to 17, or a pharmaceutically acceptable salt thereof, characterized in that R5 is NR8R9, and R8 is selected from H and (C1-C6)alkyl.

26. A compound according to any one of claims 1 to 17 and 25, or a pharmaceutically acceptable salt thereof, characterized in that R5 is NR8R9, and R9 is selected from H, (C1-C6)alkyl and a 3- to 6-membered heterocycle comprising an O heteroatom.

27. A compound according to any one of claims 1 to 26, or a pharmaceutically acceptable salt thereof, characterized in that R6 is selected from (C1-C4)alkyl, (C3-C5)cycloalkyl and (C3-C5)cycloalkyl-(C1-C4)alkyl.

28. A compound according to any one of claims 1 to 27, or a pharmaceutically acceptable salt thereof, characterized in that R6 is selected from -CH3, -CH2CH3, X and X.

29. A compound according to any one of claims 1 to 28, or a pharmaceutically acceptable salt thereof, characterized in that R7 is selected from (C3-C6)cycloalkyl or (C6-Cw)aryl, wherein the (C3-C6)cycloalkyl and (C6-Cw)aryl groups are each optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CO2H and -CH2CO2H. Petition 870250075165, dated 08 / 25 / 2025, pp. 523 / 551 10 / 33 30. A compound according to any one of claims 1 to 28, or a pharmaceutically acceptable salt thereof, characterized in that R7 is selected from (C5-C6)cycloalkyl or (C6-Cw)aryl, wherein the (C5-C6)cycloalkyl and (C6-Cw)aryl groups are each optionally substituted by one or more (for example, 1, 2, 3, 4 or 5) substituents independently selected from halo, -CO2H and -CH2CO2H.

31. A compound according to any one of claims 1 to 28, or a pharmaceutically acceptable salt thereof, characterized in that R7 is selected from (C5-C6)cycloalkyl or (C6-Cw)aryl, wherein the (C5-C6)cycloalkyl and (C6-Cw)aryl groups are each optionally substituted by 1 or 2 substituents independently selected from fluorine, -CO2H and -CH2CO2H.

32. A compound according to any one of claims 1 to 31, or a pharmaceutically acceptable salt thereof, characterized in that R7 is selected from: oh and oh.

33. A compound according to any one of claims 1 to 32, or a pharmaceutically acceptable salt thereof, characterized in that Ra, Rb, Rc and Rd are each independently H or -CH3.

34. A compound according to any one of claims 1 to 32, or a pharmaceutically acceptable salt thereof, characterized in that Ra is H.

35. Compound, according to any of the claims Petition 870250075165, dated 08 / 25 / 2025, pp. 524 / 551 11 / 33 tions 1 to 32, or a pharmaceutically acceptable salt thereof, characterized in that Rb and Rc are each H.

36. A compound according to any one of claims 1 to 32, or a pharmaceutically acceptable salt thereof, characterized in that Rd is -CH3.

37. Compound, or pharmaceutically acceptable salt thereof, characterized in that it is selected from: 3-((R)-1-(((R)-4-(((R)-2-(azepam-1-yl)-1-(1-methyl-1H-pyrazol-4yl)ethyl)amino)-6-(3-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)bicyclo[1.1.1]pentane-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((R)-6-(3-fluorophenyl)-6-methyl-4-(((R)-1-(1-methyl1H-pyrazol-4-yl)-2-((S)-3-methylp iperidin-1-yl)ethyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)amino)propyl)cyclohexane-1-carboxylic acid; (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-(azepan-1-yl)-1-(1-methyl-1Hpyrazol-4-yl)ethyl)amino)-6-(3-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1-carboxylic acid; 3-((R)-1-(((R)-4-(((S)-2-(azepan-1-yl)-1-(1-methyl-1H-pyrazol-4yl)ethyl)amino)-6-(3-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)bicyclo[1.1.1]pentane-1-carboxylic acid;ácido (1R,4r)-4-((R)-1-(((R)-6-(4-fluorofenil)-6-metil-4-(((R)-1-(1-metil1H-pirazol-4-il)-2-((S)-3-metilpiperidin-1-il)etil)amino)-5,6,7,8-tetrahidroquinazolin-2-il)amino)propil)ciclo-hexano-1-carboxylico; acid 3-((R)-1-(((R)-4-(((R)-2-((1S,5S)-9-azabicyclo[3.3.1]nonan-9-yl)-1(1-methyl-1H-pyrazol-4-yl)ethyl)amino)-6- (3-fluorophenyl)-5,6,7,8-tetrahidroquinazolin-2-yl)(methyl)amino)propyl)bicyclo[1.1.1]pentane-1carboxylic acid; (1R,4r)-4-((R)-1-(methyl((R)-6-methyl-4-(((R)-1-(1-methyl-1H-pyrazol4-yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)amino)propyl)cyclo-hexano-1-carboxylic acid; acid 3-((R)-1-(methyl((R)-6-methyl-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2 Request 870250075165, dated 25 / 08 / 2025, pág. 525 / 551 12 / 33 ((S)-3-methylpiperidin-1-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)amino)propyl)bicyclo[1.1.1]pentane-1-carboxylic acid;acid 3-((R)-1-(((R)-6-(3-fluorophenyl)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2((S)-3-methylpiperidin-1-yl)et il)amino)-5,6,7,8-tetra-hidroquinazolin-2yl)(methyl)amino)propyl)bicyclo[1.1.1]pentane-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((S)-4-(((R)-2-((1S,5S)-9azabiciclo[3.3.1]nonan-9-yl)-1-(1-ethyl-1H-pyrazol-4-yl)et il)amino)-6-(3fluorophenyl)-5,6,7,8-tetra-hidroquinazolin-2-yl)amino)propyl)ciclo-hexano1-carboxylico; acid 3-((R)-1-(((R)-4-(((R)-2-((1S,5S)-9-azabicyclo[3.3.1]nonan-9-yl)-1(1-methyl-1H-pyrazol-4-yl)ethyl)amino)-6- (4-fluorophenyl)-5,6,7,8-tetrahidroquinazolin-2-yl)(methyl)amino)propyl)bicyclo[1.1.1]pentane-1carboxylic acid; 3-((R)-1-(((R)-4-(((R)-2-((S)-3-(fluorometil)piperidin-1-yl)-1-(1metil-1H-pyrazol-4-il)etil)amino)-6-metil-6-fenil-5,6,7,8-tetrahidroquinazolin-2-yl)(metil)amino)propyl)biciclo[1.1.1]pentane-1-carboxylico acid;3-((R)-1-(((R)-4-(((R)-1-(1-ethyl-1H-pyrazol-4-yl)-2-((S)-3metilpiperidin-1-il)etil)amino)-6-(3-fluorofenil)-5,6,7,8-tetrahidroquinazolin-2-yl)(metil)amino)propyl)biciclo[1.1.1]pentane-1carboxylic acid; ácido (1R,4r)-4-((R)-1-(((R)-6-(4-fluorofenil)-4-(((R)-1-(1-metil-1Hpirazol-4-il)-2-((S)-3-metilpiperidin-1-il)etil)amino)-5,6,7,8-tetrahidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((1S,5S)-9azabicyclo[3.3.1]nonan-9-yl)-1-(1-methyl-1H-pyrazol-4-yl)et il)amino)-6-(3fluorophenyl)-5,6,7,8-tetra-hidroquinazolin-2-yl)amino)propyl)ciclo-hexano1-carboxylico; acid (1R,4r)-4-((1 R)-1-(((6R)-4-(((1R)-2-(8-azabiciclo[3.2.1 ]octan-8-yl)1-(1,5-dimethyl-1H-pyrazol-4-yl)ethyl)amino)-6-(3-fluorophenyl)-5,6,7,8-tetra Petição 870250075165, dated 25 / 08 / 2025, pág. 526 / 551 13 / 33 hidroquinazolin-2-yl)(methyl)amino)propyl)ciclo-hexano-1-carboxílico;acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((1S,5S)-9azabiciclo[3.3.1]nonan-9-yl)-1-(1-ethyl-1H-pyrazol-4-yl)et il)amino)-6-(3fluorophenyl)-5,6,7,8-tetra-hidroquinazolin-2-yl)amino)propyl)ciclo-hexano1-carboxylico; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((1S,5S)-9azabicyclo[3.3.1]nonan-9-yl)-1-(1-ethyl-1H-pyrazol-4-yl)ethyl)a mino)-6-(3fluorophenyl)-5,6,7,8-tetra-hidroquinazolin-2-yl)(methyl)amino)propyl)cyclohexano-1-carboxylic acid; ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((S)-3-(fluorometil)piperidin-1-il)1 -(1-metil-1H-pirazol-4-il)etil)amino)-6-(3-fluorofenil)-5,6,7,8-tetrahidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1-carboxylico; ácido (1R,4r)-4-((R)-1-(((R)-6-(2-fluorofenil)-6-metil-4-(((R)-1-(1-metil1H-pirazol-4-il)-2-((S)-3-metilpiperidin-1-il)etil)amino)-5,6,7,8-tetrahidroquinazolin-2-il)amino)propil)ciclo-hexano-1-carboxylico;acid (1S,4r)-1-fluoro-4-((S)-1-(methyl((S)-4-(((S)-1-(1-methyl-1H-pyrazol-4yl)-2-((R)-3-methylpiperidin-1 -yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)amino)propyl)cyclo-hexane-1-carboxylic; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-isopropyl-1H-pyrazol-4-yl)-2-((S)3-methylpiperidin-1-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hydroquinazolin-2yl)amino)propyl)cyclo-hexane-1-carboxylic; (1R,4r)-4-((R)-1-(((R)-6-(3-fluorophenyl)-4-(((R)-1-(1-methyl-1Hpyrazol-4-yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid; (1R,4r)-4-((1 R)-1-(((6R)-4-(((1S)-2-(8-azabicyclo[3.2.1 ]octan-8-yl)1-(2,4-dimethylthiazol-5-yl)ethyl)amino)-6-(3-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2-yl)amino)propyl)cyclohexane-1-carboxylic acid;acid 3-((1R)-1-(((6R)-4-(((1R)-2-(8-azabicyclo[3.2.1]octan-8-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)-6- (4-fluorophenyl)-5,6,7,8-tetrahydroquinazoline-2-yl)(methyl)amino)propyl)bicycle[1.1.1]pentane-1Petition 870250075165, dated 08 / 25 / 2025, p. 527 / 551 14 / 33 carboxyl; acid (1R,4r)-4-((1 R)-1-(((6R)-4-(((1S)-2-(8-azabicycle[3.2.1 ]octan-8-yl)1-(4-methylthiazol-5-yl)ethyl)amino)-6-(3-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2-yl)amino)propyl)cyclo-hexane-1-carboxylic; acid 3-((R)-1-(((R)-4-((((R)-2-((1S,5S)-9-azabicyclo[3.3.1]nonan-9-yl)-1(1-methyl-1H-pyrazol-4-yl)ethyl)amino)-6 -methyl-6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)bicycle[1.1.1]pentane-1carboxylic; acid 3-((1R)-1-(((6R)-4-(((1R)-2-(8-azabiciclo[3.2.1]octan-8-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)-6-m ethyl-6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)bicycle[1.1.1]pentane-1carboxylic;acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((1S,5S)-9azabicyclo[3.3.1]nonan-9-yl)-1-(1-methyl-1H-pyrazol-4-yl)ethyl) amino)-6-(3fluorophenyl)-5,6,7,8-tetra-hidroquinazolin-2-yl)(methyl)amino)propyl)cyclohexano-1-carboxylic acid; ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-ethyl-1H-pyrazol-4-yl)-2-(piperidin1-yl)ethyl)amino)-6-(3-fluorofenil)-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)cyclo-hexano-1-carboxylic acid; ácido (1R,4r)-4-((1 R)-1-(((6R)-4-(((1R)-2-(8-azabiciclo[3.2.1 ]octan-8-yl)1 -(1-metil-1H-pirazol-4-il)etil)amino)-6-(4-fluorofenil)-5,6,7,8-tetrahidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1-carboxylico; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl l)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)ciclo-hexano-1-carboxylic acid;ácido (1R,4r)-4-((1 R)-1-(((6R)-4-(((1R)-2-(8-azabiciclo[3.2.1 ]octan-8-yl)1 -(1-metil-1H-pirazol-4-il)etil)amino)-6-(3-fluorofenil)-5,6,7,8-tetrahidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1-carboxylico; ácido (1R,4r)-4-((1 R)-1-(((6R)-4-(((1R)-2-(8-azabiciclo[3.2.1 ]octan-8-il)1 -(1-metil-1H-pirazol-4-il)etil)amino)-6-metil-6-fenil-5,6,7,8-tetra Petição 870250075165, de 25 / 08 / 2025, pág. 528 / 551 15 / 33 hidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1-carboxílico; acid (1R,4r)-4-((R)-1-(((R)-6-(3-fluorophenyl)-4-(((R)-2-((S)-3(methoxymethyl)piperidin-1-yl)-1-(1-methyl-1H-pyr azol-4-yl)ethyl)amino)-5,6,7,8tetra-hidroquinazolin-2-yl)(methyl)amino)propyl)ciclo-hexano-1-carboxylic acid; 3-((S)-1-(((S)-4-(((R)-2-((R)-3-(fluorometil)piperidin-1-yl)-1-(1metil-1H-pyrazol-4-il)etil)amino)-6-metil-6-fenil-5,6,7,8-tetrahidroquinazolin-2-yl)(metil)amino)propyl)biciclo[1.1.1]pentane-1-carboxylico acid;acid (1R,4r)-4-((R)-1-(((S)-6-(3-fluorophenyl)-4-(((R)-1-phenyl-2-(piperidin1-yl)ethyl)amino)-5,6,7,8-tetra-hydroquinazolin-2-yl-amino-cyclohexypropyl-1) acid (1R,4r)-4-((R)-1-(((R)-4-((((R)-2-((1R,3R,5R,7R)-2-azaadamantan-2-yl)-1-(1-ethyl-1H-pyrazol-4-yl )ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)amino)propyl)cyclo-hexane-1-carboxylic; acid 2-((1R,4r)-4-((R)-1-(((R)-6-(3-fluorophenyl)-4-(((R)-1-(1-methyl-1Hpyrazol-4-yl)-2-((S)-3-methylpipe ridin-1-yl)ethyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclo-hexyl)acetic; acid (1R,4r)-4-((R)-1-(methyl((R)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2((S)-3-methylpiperidin-1-yl)e til)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)amino)propyl)cyclo-hexane-1-carboxylic; acid 3-((R)-1-(((R)-4-(((R)-2-(9-azabiciclo[3.3.1]nonan-9-yl)-1-(1-methyl1H-pyrazol-4-yl)ethyl)amino)-6-(2-f luophenyl)-5,6,7,8-tetra-hydroquinazolin2-yl)(methyl)amino)propyl)bicyclo[1.1.1]pentane-1-carboxylic;3-((1R)-1-(((6R)-4-(((1R)-2-(8-azabicyclo[3.2.1]octan-8-yl)-1-(1ethyl-1H-pyrazol-4-yl)ethyl)amino)-6-(3-fluorophenyl)-5,6,7,8-tetrahidroquinazolin-2-yl)(methyl)amino)propyl)bicyclo[1.1.1]pentane-1carboxylic acid; ácido 3-((S)-1-(((R)-4-(((R)-2-((S)-3-(fluorometil)piperidin-1-il)-1-(1metil-1H-pirazol-4-il)etil)amino)-6-metil-6-fenil-5,6,7,8-tetrahidroquinazolin-2-il)(metil)amino)propil)biciclo[1.1.1]pentano-1Petição 870250075165, de 25 / 08 / 2025, pág. 529 / 551 16 / 33 carboxílico; acid 3-((R)-1-(methyl((R)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amin o)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)bicyclo[1.1.1]pentane-1-carboxylic acid; (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-ethyl-1H-pyrazol-4-yl)-2-(piperidin1-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)ciclo-hexano-1-carboxylic acid;3-((R)-1-(((R)-4-(((R)-1-(1,5-dimetil-1H-pyrazol-4-yl)-2-((S)-3metilpiperidin-1-il)ethyl)amino)-6-(3-fluorofenil)-5,6,7,8-tetrahidroquinazolin-2-yl)(metil)amino)propyl)biciclo[1.1.1]pentane-1-carboxylic acid; ácido (1R,4r)-4-((R)-ciclopropyl(((R)-6-(3-fluorophenyl)-4-(((R)-1-(1-metil1H-pirazol-4-yl)-2-((S)-3-metilpiperidin-1-il)etil)amino)-5,6,7,8-tetrahidroquinazolin-2-il)(metil)amino)metil)ciclo-hexano-1-carboxylic acid; ácido (1R,4r)-4-((R)-1-(((R)-6-(2-fluorofenil)-4-(((R)-1-(1-metil-1Hpirazol-4-il)-2-((S)-3-metilpiperidin-1-il)etil)amino)-5,6,7,8-tetrahidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((1 R)-1-(((6R)-4-(((1R)-2-(8-azabiciclo[3.2.1 ]octan-8-yl)1-phenylethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)ciclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((S)-4-(((R)-1-(1-ethyl-1H-pyrazol-4-yl)-2-(piperidin1-yl)ethyl)amino)-6- (3-fluorophenyl)-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)ciclo-hexano-1-carboxylic acid;ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-(azepan-1-yl)-1-(1-metil-1Hpirazol-4-il)etil)amino)-6-fenil-5,6,7,8-tetra-hidroquinazolin-2il)amino)propil)ciclo-hexano-1-carboxylico; acid (1R,4r)-4-((R)-1-(((S)-4-(((R)-2-((1S,5S)-9azabicyclo[3.3.1]nonan-9-yl)-1-(1-ethyl-1H-pyrazol-4-yl)ethyl)a mino)-6-(3fluorophenyl)-5,6,7,8-tetra-hidroquinazolin-2-yl)(methyl)amino)propyl)cyclohexano-1-carboxylic acid; Petition 870250075165, 08 / 25 / 2025, pág. 530 / 551 17 / 33 ácido (1R,4r)-4-((R)-1-(((R)-6-(3-fluorofenil)-4-(((R)-1-(1-metil-6-oxo1,6-di-hidropirin-3-il)-2-((S)-3-metilpiperidin-1-il)etil)amino)-5,6,7,8tetra-hidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1-carboxylico; ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((S)-3-(difluorometil)piperidin-1-il)1 -(1-metil-1H-pirazol-4-il)etil)amino)-6-(3-fluorofenil)-5,6,7,8-tetrahidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1-carboxylico;acid (1R,4r)-4-((R)-1-((6-(3-fluorophenyl)-4-(((R)-1-(1-methyl-1H-pyrazol-4yl)-2-(piperidin-1-yl)ethyl )amino)-5,6,7,8-tetra-hidropyrido[4,3-d]pyrimidin-2yl)amino)propyl)ciclo-hexano-1-carboxylico; (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2(piperidin-1-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)ciclo-hexano-1-carboxylic acid; ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-(7-azabiciclo[2.2.1]heptan-7-yl)-1(1-metil-1H-pirazol-4-il)etil)amino)-6-(3-fluorofenil)-5,6,7,8-tetrahidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1-carboxylico; acid (1R,4r)-4-((1R)-1-(((6R)-4-(((1R)-2-(2-azabicyclo[2.2.1]heptan-2yl)-1-(1-methyl-1H-pyrazol-4-yl )ethyl)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)amino)propyl)ciclo-hexano-1-carboxylic acid; ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((1S,5S)-9azabiciclo[3.3.1]nonan-9-yl)-1-(1-metil-1H-pirazol-4-il)etil)amino)-6-fenil5,6,7,8-tetra-hidroquinazolin-2-il)amino)propil)ciclo-hexano-1carboxylic;ácido (1R,4r)-4-((1 R)-1-(((6R)-4-(((1R)-2-(8-azabiciclo[3.2.1 ]octan-8-yl)1 -(1-metil-1H-pirazol-4-il)etil)amino)-6-fenil-5,6,7,8-tetrahidroquinazolin-2-il)amino)propil)ciclo-hexano-1-carboxylico; ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((3S,5R)-3,5-dimetilpiperidin-1-il)1 -(1-metil-1H-pirazol-4-il)etil)amino)-6-fenil-5,6,7,8-tetrahidroquinazolin-2-il)amino)propyl)ciclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((1 R)-1-(((6R)-4-(((1R)-2-(8-azabiciclo[3.2.1 ]octan-8-yl)1 -(1-methyl-1H-pyrazol-4-yl)ethyl)amino)-6-(2-fluorophenyl)-5,6,7,8-tetra Request 870250075165, dated 25 / 08 / 2025, pág. 531 / 551 18 / 33 hidroquinazolin-2-yl)(methyl)amino)propyl)ciclo-hexano-1-carboxílico; ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-(7-azabiciclo[2.2.1]heptan-7-yl)-1(1-metil-1H-pirazol-4-il)etil)amino)-6-(4-fluorofenil)-5,6,7,8-tetrahidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1-carboxylico;acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-ethyl-1H-pyrazol-4-yl)-2-((R)-2methylpiperidin-1-yl)ethyl )amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)ciclo-hexano-1-carboxylico; ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((1S,5S)-9azabiciclo[3.3.1]nonan-9-yl)-1-(1-ethyl-1H-pyrazol-4-yl)ethyl)amino)-6-phenyl5,6,7,8-tetra-hidroquinazolin-2-yl)amino)propyl)cyclo-hexano-1carboxylic acid; acid (1R,4r)-4-((R)-1-(methyl((R)-6-methyl-4-(((R)-1-(1-methyl-1H-pyrazol-4yl)-2-(piperidin-1-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)cyclo-hexano-1-carboxylic acid; acid 2-((1R,4r)-4-((R)-1-(methyl((R)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2((S)-3-methylpiperidin-1 -yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)amino)propyl)cyclo-hexyl)acetic acid; acid (1R,4r)-4-((1R)-1-(((6R)-4-(((1R)-2-(2-azabicyclo[2.2.1]heptan-2yl)-1-(1-methyl-1H-pyrazol-4-yl)ethyl)am ino)-6-methyl-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)(methyl)amino)propyl)ciclo-hexano-1-carboxylic acid;acid 3-((1S)-1-(((6R)-4-((((1R)-2-(8-azabicyclo[3.2.1]octan-8-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)-6-m ethyl-6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)bicycle[1.1.1]pentane-1carboxylic; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-(7-azabicyclo[2.2.1]heptan-7-yl)-1(1-methyl-1H-pyrazol-4-yl)ethyl)ami no)-6-methyl-6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclo-hexane-1-carboxylic; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((5R,7R)-2-aza-adamantan-2-yl)1 -(1-methyl-1H-pyrazol-4-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)amino)propyl)cyclo-hexane-1-carboxylic; Petition 870250075165, dated 8 / 25 / 2025, p. 532 / 551 19 / 33 acid (1R,4r)-4-((R)-1-(((R)-6-(3-fluorophenyl)-4-(((R)-2-((S)-3(hydroxymethyl)piperidin-1-yl)-1-(1-methyl-1H-pi razol-4-yl)ethyl)amino)-5,6,7,8tetra-hydroquinazolin-2-yl)(methyl)amino)propyl)cyclo-hexane-1-carboxylic;(1R,4r)-4-((R)-1-(((R)-4-(((S)-2-((S)-3-methylpiperidin-1-yl)-1-(4methylthiazol-5-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hydroquinazolin-2yl)amino)propyl)cyclo-hexane-1-carboxylic acid; acid 3-(1-(((R)-4-(((R)-2-((1S,5S)-9-azabicyclo[3.3.1]nonan-9-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)-6- phenyl-5,6,7,8-tetra-hydroquinazolin-2yl)(methyl)amino)-113-propyl)bicyclo[1.1.1]pentane-1-carboxylic; acid (1R,4r)-4-((R)-1-(((S)-6-(3-fluorophenyl)-4-(((R)-1-(1-methyl-1Hpyrazol-4-yl)-2-((S)-3-methylpiperidin -1-yl)ethyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclo-hexane-1-carboxylic; acid (1R,4r)-4-((R)-1-((4-(((R)-1-(1-ethyl-1H-pyrazol-4-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)-6-(3- fluorophenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)amino)propyl)cyclo-hexane-1-carboxylic;3-((1R)-1-(((6R)-4-(((1S)-2-(8-azabicyclo[3.2.1]octan-8-yl)-1-(2metilthiazol-5-yl)ethyl)amino)-6-(3-fluorofenil)-5,6,7,8-tetra-hidroquinazolin2-yl)(metil)amino)propyl)biciclo[1.1.1]pentane-1-carboxylic acid; acid (1R,4r)-4-((1R)-1-(((6R)-4-(((1R)-2-(3-azabicyclo[4.1.0]heptan-3yl)-1-(1-methyl-1H-pyrazol-4-yl)ethyl l)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)(methyl)amino)propyl)ciclo-hexano-1-carboxylic acid; ácido (1R,4r)-4-((1R)-1-(((6R)-4-(((1 R)-1-(1-ethyl-1H-pyrazol-4-yl)-2((1R,5S)-3-hidróxi-9-azabiciclo[3.3.1]nonan-9-yl)ethyl)amino)-6-(3fluorofenil)-5,6,7,8-tetra-hidroquinazolin-2-yl)(metil)amino)propil)ciclohexano-1-carboxylico; ácido (1R,4r)-4-((1 R)-1-((4-(((1R)-2-(8-azabiciclo[3.2.1]octan-8-yl)-1-(1metil-1H-pirazol-4-il)etil)amino)-6-(4-fluorofenil)-5,6,7,8-tetrahidropirido[4,3-d]pirimidin-2-yl)(metil)amino)propyl)ciclo-hexano-1carboxylic acid;acid (1R,4r)-4-((1 R)-1-(((6R)-4-(((1S)-2-(8-azabiciclo[3.2.1 ]octan-8-yl) Request 870250075165, dated 25 / 08 / 2025, pág. 533 / 551 20 / 33 1-(2-methylthiazol-5-yl)ethyl)amino)-6-(3-fluorophenyl)-5,6,7,8-tetrahidroquinazolin-2-yl)(methyl)amino)propyl)cyclo-hexano-1-carboxylic acid; acid (1S,4s)-1-fluoro-4-((R)-1-(methyl((R)-4-(((S)-1-(1-methyl-1H-pyrazol4-yl)-2-((S)-3-methylpiperidin-1 -yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)amino)propyl)ciclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((S)-3-(methoxymethyl)piperidin-1 -yl)1 -(1-methyl-1H-pyrazol-4-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)(methyl)amino)propyl)ciclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((R)-3methylpiperidin-1-yl)ethyl l)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)ciclo-hexano-1-carboxylic acid;(1R,4r)-4-((R)-1-(((R)-6-phenyl-4-(((R)-1-phenyl-2-(pyrrolidin-1yl)ethyl)amino)-5,6,7,8-tetra-hydroquinazolin-2-yl)amino)propyl)cyclohexane-1-carboxylic acid; (1R,4r)-4-((1R)-1-(((6R)-4-(((1R)-2-(2-azabicyclo[2.2.1]heptan-2yl)-1-(4-fluorophenyl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hydroquinazolin-2yl)amino)propyl)cyclo-hexane-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((S)-3-(fluoromethyl)piperidin-1 -yl)1 -(1-methyl-1H-pyrazol-4-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclo-hexane-1-carboxylic; acid (1R,4r)-4-((1 R)-1-(((6R)-4-(((1S)-2-(8-azabicyclo[3.2.1 ]octan-8-yl)1-(1,5-dimethyl-1H-pyrazol-3-yl)ethyl)amino)-6-(3-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclo-hexane-1-carboxylic; acid 3-((R)-1-(((R)-4-(((R)-2-((1S,5S)-9-azabicyclo[3.3.1]nonan-9-yl)-1(1,5-dimethyl-1H-pyrazol-4-yl)ethyl)amino)- 6-(3-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)bicyclo[1.1.1]pentane-1carboxylic;acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((R)-2methylpiperidin-1-yl)ethyl l)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)ciclo-hexano-1-carboxylic acid; Petition 870250075165, 08 / 25 / 2025, pág. 534 / 551 21 / 33 ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-ethyl-1H-pyrazol-4-yl)-2-(piperidin1-yl)ethyl)amino)-6-(3-fluorofenil)-5,6,7,8-tetra-hidroquinazolin-2yl)(metil)amino)propil)ciclo-hexano-1-carboxylico; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((1S,5S)-9azabicyclo[3.3.1]nonan-9-yl)-1-(1-ethyl-1H-pyrazol-4-yl)e tyl)amino)-6-phenyl5,6,7,8-tetra-hidroquinazolin-2-yl)(methyl)amino)propyl)ciclo-hexano-1carboxylico; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((S)-3-(hidroximethyl)piperidin-1 -yl)1 -(1-methyl-1H-pyrazol-4-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)(methyl)amino)propyl)ciclo-hexano-1-carboxylic acid;(1R,4r)-4-((R)-1-(((R)-4-(((R)-2-(azepan-1-yl)-1-(1-ethyl-1H-pyrazol4-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)ciclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-(3,3-dimethylpiperidin-1-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)cyclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((R)-2-ethylpiperidin-1-yl)-1-(1-methyl1H-pyrazol-4-yl)ethyl )amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)ciclo-hexano-1-carboxylico; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-cyclopropyl-1H-pyrazol-4-yl)-2(piperidin-1-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)(methyl)amino)propyl)cyclo-hexano-1-carboxylic acid; ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((1R,3R,5R,7R)-2-azaadamantan-2-yl)-1-(1-metil-1H-pirazol-4-il)etil)amino)-6-fenil-5,6,7,8tetra-hidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1-carboxylico;(1R,4r)-4-((R)-1-((6-(3-fluorophenyl)-4-(((R)-1-phenyl-2-(pyrrolidin-1yl)ethyl)amino)-5,6,7,8-tetra-hidropyrido[4,3-d]pyrimidin-2yl)amino)propyl)ciclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-isopropyl-1H-pyrazol-4-yl)-2(piperidin-1-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2Petição 870250075165, dated 08 / 25 / 2025, pág. 535 / 551 22 / 33 il)amino)propyl)ciclo-hexano-1-carboxylico; acid (1R,4r)-4-((R)-1-(methyl((S)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2((S)-3-methylpiperidin-1-yl)e tyl)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)amino)propyl)ciclo-hexano-1-carboxylic acid; ácido (1R,4r)-4-((1 R)-1-(((6R)-4-(((1R)-2-(8-azabiciclo[3.2.1 ]octan-8-yl)1-(1,3-dimetil-1H-pirazol-4-il)etil)amino)-6-(3-fluorofenil)-5,6,7,8-tetrahidroquinazolin-2-yl)(metil)amino)propil)ciclo-hexano-1-carboxylico;(1R,4r)-4-((1 R)-1-(((6R)-4-(((1R)-2-(8-azabicyclo[3.2.1 ]octan-8-yl)1 -(1-methyl-1H-pyrazol-4-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclo-hexane-1-carboxylic acid; (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-ethyl-1H-pyrazol-4-yl)-2-((R)-2(hydroxymethyl)piperidin-1-yl)ethyl)amino)-6-(3-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclo-hexane-1-carboxylic acid; (1R,4r)-4-((1 R)-1-(((6R)-4-(((1S)-2-(8-azabicyclo[3.2.1 ]octan-8-yl)1 -(1-methyl-1H-pyrazol-3-yl)ethyl)amino)-6-(3-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclo-hexane-1-carboxylic acid; (1R,4r)-4-((R)-1-((6-(2-fluorophenyl)-4-(((R)-1-(1-methyl-1H-pyrazol-4yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)amino)-5,6,7,8-tetra-hydropyrido[4,3d]pyrimidin-2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid;(1R,4r)-4-((1R)-1-(((6R)-4-((1-(1-(fluorometil)-1H-pirazol-4-yl)-2((S)-3-metilpiperidin-1-il)etil)amino)-6-fenil-5,6,7,8-tetrahidroquinazolin-2-yl)(metil)amino)propil)ciclo-hexano-1-carboxylic acid; ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((1S,5S)-9azabiciclo[3.3.1]nonan-9-yl)-1-feniletil)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)amino)propyl)cyclo-hexano-1-carboxílico; ácido (1R,4r)-4-((1R)-1-(((6R)-4-(((1R)-1-(1-ethyl-1H-pyrazol-4-yl)-2-(2oxa-7-azaspiro[4,5]decan-7-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)amino)propyl)cyclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((R)-1-((6-(4-fluorophenyl)-4-(((R)-1-(1-methyl-1H-pyrazol-4yl)-2-((S)-3-methylpiperidin-1-yl)ethyl)amino)-5,6,7,8-tetra-hidropyrido[4,3 Request 870250075165, dated 08 / 25 / 2025, pág. 536 / 551 23 / 33 d]pyrimidin-2-yl)(methyl)amino)propyl)cyclo-hexano-1-carboxylic acid;3-((1R)-1-(((6R)-4-(((1S)-2-(8-azabicyclo[3.2.1]octan-8-yl)-1-(2,4dimetilthiazol-5-yl)ethyl)amino)-6-(3-fluorofenil)-5,6,7,8-tetrahidroquinazolin-2-yl)(metil)amino)propyl)biciclo[1.1.1]pentane-1-carboxylic acid; acid (1R,4r)-4-((1R)-1-(((6R)-4-(((1R)-2-((1R,5S)-3-hidróxi-9azabiciclo[3.3.1]nonan-9-yl)-1-phenylethyl )amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)(methyl)amino)propyl)ciclo-hexano-1-carboxylic acid; 3-((1R)-1-(((6R)-4-(((1S)-2-(8-azabicyclo[3.2.1]octan-8-yl)-1-(4metilthiazol-5-yl)ethyl)amino)-6-(3-fluorofenil)-5,6,7,8-tetra-hidroquinazolin2-yl)(metil)amino)propyl)biciclo[1.1.1]pentane-1-carboxylic acid; (1R,4r)-4-((R)-1-(((R)-4-(((S)-1-(4-methylthiazol-5-yl)-2-(piperidin-1yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2-yl)amino)propyl)cyclohexano-1-carboxylic acid; (1R,4r)-4-((R)-1-(((S)-6-phenyl-4-(((R)-1-phenyl-2-(pyrrolidin-1yl)ethyl)amino)-5,6,7,8-tetra-hidroquinazolin-2-yl)amino)propyl)cyclohexano-1-carboxylic acid;ácido (1R,4r)-4-((R)-1-(((S)-4-(((R)-1-(1-ethyl-1H-pyrazol-4-yl)-2-(piperidin1-yl)ethyl)amino)-6-(3-fluorophenyl)-5,6,7,8-tetra-hidroquinazolin-2yl)(metil)amino)propil)ciclo-hexano-1-carboxylico; ácido (1R,4r)-4-((1R)-1-(((6R)-4-(((1 R)-1-(1-ethyl-1H-pyrazol-4-yl)-2((1R,5S)-3-hidróxi-9-azabiciclo[3.3.1]nonan-9-yl)ethyl)amino)-6-(3fluorofenil)-5,6,7,8-tetra-hidroquinazolin-2-yl)amino)propyl)cyclo-hexano1-carboxílico; (1R,4r)-4-((R)-1-(methyl((R)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2(piperidin-1-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)ciclo-hexano-1-carboxylic acid; (1R,4r)-4-((R)-1-(((R)-4-(((S)-1-(2-methylthiazol-5-yl)-2-(piperidin-1yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2-yl)amino)propyl)cyclohexano-1-carboxylic acid;Petition 870250075165, 08 / 25 / 2025, pág. 537 / 551 24 / 33 acid (1R,4r)-4-((R)-cyclopropyl(methyl((R)-4-(((R)-1-(1-methyl-1H-pyrazol-4yl)-2-((S)-3-methylpiperidin-1 -yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)amino)methyl)ciclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-(4methylpiperidin-1-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)cyclo-hexano-1-carboxylic acid; ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((1R,4S)-2azabiciclo[2.2.1]heptan-2-yl)-1-(1-ethyl-1H-pyrazol-4-yl)ethyl)amino)-6-phenyl5,6,7,8-tetra-hidroquinazolin-2-yl)amino)propyl)cyclo-hexano-1carboxílico; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-((S)-2methylpiperidin-1-yl)ethyl l)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)ciclo-hexano-1-carboxylic acid;acid (1R,4r)-4-((R)-1-((6-(3-fluorophenyl)-4-(((R)-1-(1-methyl-1H-pyrazol-4yl)-2-((S)-3-methylpiperidin-1-yl)et il)amino)-5,6,7,8-tetra-hidropyrido[4,3d]pyrimidin-2-yl)(methyl)amino)propyl)cyclo-hexano-1-carboxylic acid; (1R,4r)-4-((R)-1-(methyl((R)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2((R)-3-methylpiperidin-1-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)amino)propyl)cyclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-ethyl-1H-pyrazol-4-yl)-2-(6azaspiro[3,5]nonan-6-yl)ethyl )amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin2-yl)amino)propyl)ciclo-hexano-1-carboxylico; acid (1R,4r)-4-((1 R)-1-(((6R)-4-(((1S)-2-(8-azabiciclo[3.2.1 ]octan-8-yl)1-(2-methylthiazol-4-yl)ethyl)amino)-6-(3-fluorophenyl)-5,6,7,8-tetrahidroquinazolin-2-yl)amino)propyl)cyclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((1R)-1-(((6R)-4-(((1R)-2-(2-azabicyclo[2.2.1]heptan-2yl)-1-(1-methyl-1H-pyrazol-4-yl)ethyl l)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)(methyl)amino)propyl)ciclo-hexano-1-carboxylic acid;acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((S)-3-hidroxipiperidin-1-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2 Petição 870250075165, dated 25 / 08 / 2025, pág. 538 / 551 25 / 33 il)(methyl)amino)propyl)ciclo-hexano-1-carboxylico; acid (1S,4r)-4-((S)-1-(((S)-6-(3-fluorophenyl)-6-methyl-4-(((R)-1-(1-methyl1H-pyrazol-4-yl)-2-((R)-3-methylp hyperidin-1-yl)ethyl)amino)-5,6,7,8-tetrahidroquinazolin-2-yl)amino)propyl)ciclo-hexano-1-carboxylic acid; (1R,4r)-4-((R)-1-((6-phenyl-4-(((R)-1-phenyl-2-(pyrrolidin-1yl)ethyl)amino)-5,6,7,8-tetra-hidropyrido[4,3-d]pyrimidin-2yl)amino)propyl)ciclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((1S,5S)-9azabicyclo[3.3.1]nonan-9-yl)-1-(1-isopropyl-1H-pyrazol- 4-yl)ethyl)amino)-6phenyl-5,6,7,8-tetra-hidroquinazolin-2-yl)amino)propyl)ciclo-hexano-1carboxylico;acid (1R,4r)-4-((R)-(((R)-4-(((R)-2-((1S,5S)-9-azabicyclo[3.3.1]nonan9-yl)-1-(1-methyl-1H-pyrazol-4-yl)ethyl)am ino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)(methyl)amino)(cyclopropyl)methyl)cyclo-hexano-1carboxylic acid; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((S)-3-methoxypiperidin-1-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)a mino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)(methyl)amino)propyl)ciclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-ethyl-1H-pyrazol-4-yl)-2-((S)-2(hidroxymethyl)piperidin-1-yl)ethyl)ami no)-6-(3-fluorophenyl)-5,6,7,8-tetrahidroquinazolin-2-yl)(methyl)amino)propyl)ciclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((1R)-1-(((6R)-4-(((1R)-2-(2-azabiciclo[2.2.1]heptan-2yl)-1-phenylethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)(methyl)amino)propyl)ciclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-(4,4-difluoroazepan-1-yl)-1-(1-ethyl1H-pyrazol-4-yl)ethyl) amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)ciclo-hexano-1-carboxylico;ácido (1R,4r)-4-((1R)-1-(((6R)-4-(((1R)-2-((1R,5S)-6-hidróxi-3azabiciclo[3.1.1]heptan-3-il)-1-(1 -metil-1H-pirazol-4-il)etil)amino)-6fenil-5,6,7,8-tetra-hidroquinazolin-2-il)(metil)amino)propil)ciclo-hexanoPetição 870250075165, de 25 / 08 / 2025, pág. 539 / 551 26 / 33 1-carboxílico; (1R,4r)-4-((1 R)-2-cyclopropyl-1-((6-phenyl-4-(((R)-1-phenyl-2-(pyrrolidin1-yl)ethyl)amino)-5,6,7,8-tetra-hidroquinazolin-2-yl)amino)ethyl)cyclohexano-1-carboxylic acid; acid 3-(1-(((R)-4-(((S)-1-(1,3-dimethyl-1H-pyrazol-5-yl)-2-((S)-3methylpiperidin-1-yl)ethyl)amino)-6-phenes 1-5,6,7,8-tetra-hidroquinazolin-2yl)(methyl)amino)-113-propyl)bicyclo[1.1.1]pentane-1-carboxylic acid; ácido (1R,4r)-4-((R)-1-(((S)-6-(2-fluorofenil)-4-(((R)-1-(1-metil-1Hpirazol-4-il)-2-((S)-3-metilpiperidin-1-il)etil)amino)-5,6,7,8-tetrahidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1-carboxylic acid;ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-(4-fluoropiperidin-1-yl)-1-(1-metil1H-pirazol-4-il)etil)amino)-6-fenil-5,6,7,8-tetra-hidroquinazolin-2il)amino)propil)ciclo-hexano-1-carboxylico; ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((1S,5S)-9azabiciclo[3.3.1]nonan-9-yl)-1-(1-metil-1H-pirazol-4-il)etil)amino)-6-fenil5,6,7,8-tetra-hidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1carboxylico; ácido (1R,4r)-4-((1R)-1-(((6R)-4-(((1R)-2-(3-fluoro-3-metilpiperidin-1-il)1 -(1-metil-1H-pirazol-4-il)etil)amino)-6-fenil-5,6,7,8-tetrahidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1-carboxylico; acid (1R,4r)-4-((R)-1-(methyl((R)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-(4methylpiperidin-1-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)cyclo-hexano-1-carboxylic acid; (1R,4r)-4-((R)-1-(methyl((R)-6-phenyl-4-(((R)-1-phenyl-2-(pyrrolidin-1yl)ethyl)amino)-5,6,7,8-tetra-hidroquinazolin-2-yl)amino)propyl)cyclohexano-1-carboxylic acid;(1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-(cyclopropylmethyl)-1H-pyrazol-4yl)-2-(piperidin-1-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid; (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-ethyl-6-oxo-1,6-dihydropyridine-3 Petition 870250075165, dated 08 / 25 / 2025, page 540 / 551 27 / 33 yl)-2-(piperidin-1-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazoline-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((R)-2-(hydroxymethyl)piperidin-1-yl)1 -(1-methyl-1H-pyrazol-4-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2-yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid; (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-(4,4-difluoroazepan-1-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid;acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-(4-methoxipiperidin-1-yl)-1-(1-methyl1H-pyrazol-4-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)cyclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((R)-1-((6-cyclo-hexyl-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)2-((S)-3-methylpiperidin-1-yl)ethyl )amino)-5,6,7,8-tetra-hidropyrido[4,3d]pyrimidin-2-yl)(methyl)amino)propyl)cyclo-hexano-1-carboxylic acid; acid 4-((R)-1-(((R)-4-(((R)-2-((1S,5S)-9-azabicyclo[3.3.1]nonan-9-yl)-1(1-ethyl-1H-pyrazol-4- yl)ethyl)amino)-6-(3-fluorophenyl)-5,6,7,8-tetrahidroquinazolin-2-yl)amino)ethyl)benzoic acid; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-ethyl-1H-pyrazol-4-yl)-2-(4hidroxypiperidin-1-yl)ethyl)ami no)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)(methyl)amino)propyl)ciclo-hexano-1-carboxylic acid; acid 3-((R)-1-(((R)-6-(3-fluorophenyl)-4-(((S)-1-(1-methyl-1H-pyrazol-5-yl)-2((S)-3-methylpiperidin-1-yl)et il)amino)-5,6,7,8-tetra-hidroquinazolin-2yl)(methyl)amino)propyl)bicyclo[1.1.1]pentane-1-carboxylic acid;(1R,4r)-4-((1R)-1-(((6R)-4-(((1R)-2-(3-fluoropiperidin-1-yl)-1-(1-methyl-1H-pyrazol-4-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid; (1R,4r)-4-((R)-1-((6-(3-fluorophenyl)-4-(((R)-1-(1-methyl-1H-pyrazol-4yl)-2-(piperidin-1-yl)ethyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2yl)(methyl)amino)propyl)cyclohexane-1-carboxylic acid; (1S,4r)-4-((1S)-1-((6-phenyl-4-(((R)-1-phenyl-2-(pyrrolidin-1-yl)ethyl)amino)-5,6,7,8-tetrahydroquinazolin-2-yl)amino)ethyl)cyclohexane-1-carboxylic acid; 4-((R)-1-(((R)-6-phenyl-4-(((R)-1-phenyl-2-(pyrrolidin-1-yl)ethyl)amino)5,6,7,8-tetrahydroquinazolin-2-yl)amino)ethyl)benzoic acid; (1R,4r)-4-((1R)-1-(((6R)-4-(((1R)-2-(2-azabicyclo[2.2.1]heptan-2yl)-1-phenylethyl)amino)-6-phenyl-5,6,7,8-tetrahydroquinazolin-2yl)amino)propyl)cyclohexane-1-carboxylic acid;ácido (1R,4r)-4-((R)-1-(((R)-6-(3-fluorofenil)-4-(((S)-1-(1-metil-1Hpirazol-5-il)-2-((S)-3-metilpiperidin-1-il)etil)amino)-5,6,7,8-tetrahidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1-carboxylic acid; (1R,4r)-4-((1R)-1-(((6R)-4-(((1R)-1-(1-ethyl-1H-pyrazol-4-yl)-2-(2oxa-7-azaspiro[4,5]decan-7-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)(methyl)amino)propyl)cyclo-hexano-1-carboxylic acid; ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-1-(1-ethyl-1H-pyrazol-4-yl)-2-((S)-3hidroxipiperidin-1-yl)ethyl)amino)-6-(3-fluorofenil)-5,6,7,8-tetrahidroquinazolin-2-yl)(metil)amino)propil)ciclo-hexano-1-carboxylico; acid (1R,4r)-4-((1 R)-1-(((6R)-4-(((1S)-2-(8-azabiciclo[3.2.1 ]octan-8-yl)1 -(1-methyl-1H-pyrazol-5-yl)ethyl)amino)-6-(3-fluorophenyl)-5,6,7,8-tetrahidroquinazolin-2-yl)(methyl)amino)propyl)cyclo-hexano-1-carboxylic acid; (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-(dimethylamino)-1-phenylethyl)amino)6-phenyl-5,6,7,8-tetra-hidroquinazolin-2-yl)amino)propyl)ciclo-hexano-1carboxylic acid;acid (1R,4r)-4-((R)-1-(((R)-6-phenyl-4-(((R)-1-phenyl-2-((tetra-hidro-2Hpiran-4-yl)amino)ethyl)amino)-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)ciclo-hexano-1-carboxylico; ácido (1R,4r)-4-((R)-1-(metil((R)-6-fenil-4-(((R)-2-(piperidin-1-yl)-1-(1(2,2,2-trifluoroetil)-1H-pirazol-4-il)etil)amino)-5,6,7,8-tetrahidroquinazolin-2-il)amino)propil)ciclo-hexano-1-carboxylic acid; acid 4-((R)-1-(((R)-4-(((R)-2-((1S,5S)-9-azabiciclo[3.3.1]nonan-9-yl)-1(1-methyl-1H-pyrazol-4-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolinPetition 870250075165, dated 25 / 08 / 2025, pág. 542 / 551 29 / 33 2-yl)amino)ethyl)-2-fluorobenzoic acid; ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((1R,5S)-3-oxa-9azabiciclo[3.3.1]nonan-9-yl)-1-(1-metil-1H-pirazol-4-il)etil)amino)-6-fenil5,6,7,8-tetra-hidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1carboxylico;ácido (1R,4r)-4-((R)-1-((6-(3-chlorofenil)-4-(((R)-1-(1-metil-1H-pirazol-4il)-2-((S)-3-methylpiperidin-1-yl)etil)amino)-5,6,7,8-tetra-hidropirido[4,3d]pyrimidin-2-il)(methyl)amino)propyl)cyclo-hexano-1-carboxylo; ácido 4-((R)-1-((R)-4-(((R)-1-(1-isopropyl-1H-pirazol-4-il)-2-(piperidin-1yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)benzoico; ácido 3-((R)-1-(((R)-4-(((S)-2-((1R,5R)-9-azabiciclo[3.3.1]nonan-9-il)-1(1-metil-1H-pirazol-5-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin2-il)(metil)amino)propyl)biciclo[1.1.1]pentano-1-carboxilo; ácido (1R,4r)-4-((R)-1-(metil((R)-4-(((R)-2-metil-1-(1-metil-1H-pirazol-4il)-2-(piperidin-1-yl)propyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)amino)propyl)cyclo-hexano-1-carboxylo; ácido (1R,4r)-4-((R)-1-((6-(3-cyanophenyl)-4-(((R)-1-(1-metil-1H-pirazol-4il)-2-((S)-3-methylpiperidin-1-yl)etil)amino)-5,6,7,8-tetra-hidropirido[4,3d]pyrimidin-2-il)(methyl)amino)propyl)cyclo-hexano-1-carboxylo;ácido (1R,4r)-4-((1R)-1-(((6R)-4-(((1R)-2-(3-(fluorometil)piperidin-1 -il)1 -(1-metil-1H-pirazol-4-il)etil)amino)-6-(3-fluorofenil)-5,6,7,8-tetrahidroquinazolin-2-il)amino)propil)ciclo-hexano-1-carboxylico; ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((1R,6S)-2azabiciclo[4.1.0]heptan-2-yl)-1-(1 -metil-1H-pirazol-4-il)etil)amino)-6fenil-5,6,7,8-tetra-hidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano1-carboxílico; ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((1S,6R)-2azabiciclo[4.1.0]heptan-2-yl)-1-(1 -metil-1H-pirazol-4-il)etil)amino)-6fenil-5,6,7,8-tetra-hidroquinazolin-2-il)(metil)amino)propil)ciclo-hexanoPetição 870250075165, de 25 / 08 / 2025, pág. 543 / 551 30 / 33 1-carboxílico; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((R)-3-ethyl-3-hidroxipiperidin-1 -yl)1 -(1-methyl-1H-pyrazol-4-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)(methyl)amino)propyl)ciclo-hexano-1-carboxylic acid;ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((3R,4R)-4-hidróxi-3metilpiperidin-1-il)-1-(1-metil-1H-pirazol-4-il)etil)amino)-6-fenil-5,6,7,8tetra-hidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1-carboxylico; (1R,4r)-4-((R)-1-(methyl((R)-4-(((R)-1-(1-methyl-1H-pyrazol-4-yl)-2-(5azaspiro[2,5]octan-5-yl)ethyl)amino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin2-yl)amino)propyl)cyclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((R)-3-methoxipyrrolidin-1-yl)-1-(1methyl-1H-pyrazol-4-yl)ethyl)a mino)-6-phenyl-5,6,7,8-tetra-hidroquinazolin-2yl)(methyl)amino)propyl)ciclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((R)-3-hidróxi-3-methylpiperidin-1yl)-1-(1-methyl-1H-pyrazol-4-yl)et il)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)(methyl)amino)propyl)ciclo-hexano-1-carboxylic acid;ácido (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((3R,5R)-3-metóxi-5metilpiperidin-1-il)-1-(1-metil-1H-pirazol-4-il)etil)amino)-6-fenil-5,6,7,8tetra-hidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1-carboxylic acid; acid (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((3S,5S)-3-methoxy-5methylpiperidin-1-yl)-1-(1-methyl-1H-pyrazol-4-yl) ethyl)amino)-6-phenyl-5,6,7,8tetra-hidroquinazolin-2-yl)(methyl)amino)propyl)ciclo-hexano-1-carboxylic acid; ácido (1R,4r)-4-((R)-1-(((R)-4-(((S)-1-(3-fluoro-1-metil-1H-pirazol-4-il)-2((S)-3-metilpiperidin-1-il)etil)amino)-6-fenil-5,6,7,8-tetrahidroquinazolin-2-il)(metil)amino)propil)ciclo-hexano-1-carboxylic acid; and acidic (1R,4r)-4-((R)-1-(((R)-4-(((R)-2-((S)-3-hidróxi-3-methylpiperidin-1yl)-1-(1-methyl-1H-pyrazol-4-yl)et il)amino)-6-phenyl-5,6,7,8-tetrahidroquinazolin-2-yl)(methyl)amino)propyl)ciclo-hexano-1-carboxylic acid.; 38. Pharmaceutical composition characterized in that it comprises a compound, as defined in any of claims 1 to 37, or a pharmaceutically acceptable salt thereof and one or more (for example, 1, 2, 3, 4 or 5) pharmaceutically acceptable carriers.

39. Pharmaceutical composition according to claim 38, characterized in that it further comprises an additional pharmaceutically active agent.

40. Pharmaceutical composition, according to claim 39, characterized in that the additional pharmaceutically active agent is selected from an ACE (angiotensin-converting enzyme) inhibitor, an angiotensin receptor blocker (ARB), a neprilysin inhibitor, a beta-blocker, a diuretic, a calcium channel blocker, a cardiac glycoside, a sodium-glucose cotransporter 2 (SGLT2i) inhibitor, an angiotensin-neprilysin receptor inhibitor (ARNi), a corticosteroid, a leukotriene modifier, a bronchodilator, a beta-adrenergic receptor antagonist, a carbonic anhydrase inhibitor, an alpha 2-adrenergic receptor agonist, a parasympathomimetic, a prostaglandin analogue, a rho kinase inhibitor, and combinations thereof.

41. Use of a compound, as defined in any one of claims 1 to 37, or of a pharmaceutically acceptable salt thereof, characterized in that it is for the manufacture of a medicament, composition, combination and / or kit for treating or preventing a disease or disorder.

42. Use according to claim 41, characterized in that the disease or disorder is a cardiovascular disease or disorder.

43. Use, according to claim 42, characterized in that the cardiovascular disease or disorder is selected from among hypertension, peripheral vascular disease, heart failure, Petition 870250075165, dated 08 / 25 / 2025, pp. 545 / 551 32 / 33 coronary artery disease (CAD), ischemic heart disease (IHD), mitral stenosis and regurgitation, angina, hypertrophic cardiomyopathy, diabetic cardiomyopathy, supraventricular and ventricular arrhythmias, cardiac dysrhythmia, atrial fibrillation (AF), new-onset atrial fibrillation, recurrent atrial fibrillation, cardiac fibrosis, atrial flutter, detrimental vascular remodeling, plaque stabilization, and myocardial infarction (MI).

44. Use according to claim 43, characterized in that the heart failure is selected from heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), heart failure following acute myocardial infarction, or acute decompensated heart failure.

45. Use, according to claim 41, characterized in that the disease or disorder is pre-eclampsia, asthma, glaucoma, a kidney disorder and / or cytokine release syndrome in an individual who needs such treatment.

46. ​​Use according to claim 41, characterized in that the disease or disorder is a disorder or disease associated with natriuretic peptide receptor activity.

47. Combination, characterized in that it comprises a compound, as defined in any one of claims 1 to 37, or an acceptable pharmaceutical salt thereof, and / or a pharmaceutical composition, as defined in any one of claims 38 to 40, in combination with one or more additional active pharmaceutical agents.

48. Kit, characterized in that it comprises: (a) a compound, as defined in any one of claims 1 to 37, or an acceptable pharmaceutical salt thereof, and / or (b) a pharmaceutical composition, as defined in any one of claims 38 to 40, and / or Petition 870250075165, dated 08 / 25 / 2025, pp. 546 / 551 33 / 33 (c) a combination, as defined in claim 47; and (d) instructions for administration.

49. Invention, characterized in any of its embodiments or in any applicable category of claim, for example, of product or process or use encompassed by the matter initially described, disclosed or illustrated in the patent application, for example: Method for treating or preventing a disease or disorder comprising administering to a patient in need thereof a therapeutically effective amount of a compound, as defined in any of the preceding claims, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition, as defined in any of the preceding claims; and / or Compound of Formula I or a pharmaceutically acceptable salt thereof for the treatment of a disease or disorder; and / or Compound of Formula I for the manufacture of a medicament, composition, combination and / or kit for the treatment of a disease or disorder;and / or a composition comprising a compound of Formula I or a pharmaceutically acceptable salt thereof for the treatment of a disease or disorder.