A derivative of camptotechcin, a conjugate thereof, a method of preparation thereof, and its medical use.

Description

Camptothecin derivative, its conjugate, method of preparation and medical use. TECHNICAL FIELD

[001] The present invention relates to a new camptothecin derivative, a conjugate thereof, a method of preparation, a pharmaceutical composition containing this compound and its use in the preparation of antineoplastic drugs. BACKGROUND

[002] Antibody-drug conjugates (ADCs) are a relatively new class of anticancer drugs, developed to combine the selectivity of monoclonal antibodies with the cell-killing properties of cytotoxic agents. ADCs have attracted considerable interest as a novel therapeutic approach and continue to evolve. The design of ADCs involves linking monoclonal antibodies or antibody fragments to cytotoxic agents with biological activity via ligands. This leverages the specificity of antibodies for tumor cell surface antigens and the efficiency of cytotoxic substances, avoiding the drawbacks of low antibody efficacy and high toxicity of cytotoxic agents. This means that, compared to traditional chemotherapeutic drugs, ADCs can Petition 870260084912, dated 08 / 20 / 2026, page 9 / 1402 2 / 694 to more precisely target and destroy tumor cells while simultaneously reducing side effects on healthy cells. The linker in an ADC is not only the molecular part that establishes the covalent bond between the antibody and the small drug molecule, but also a key element in the design of targeted therapy. This involves several considerations: the addition of linkers should not induce aggregation; it should ensure acceptable pharmacokinetic (PK) properties; improve stability in the bloodstream; and allow for the effective release of active molecules at the targeted site.

[003] Camptothecin (CPT) is a pentacyclic quinoline alkaloid originally isolated from the wood and bark of the native Chinese tree Camptotheca acuminata. Camptothecin exhibits significant antitumor activity by inhibiting topoisomerase I. Topoisomerase I is an enzyme overexpressed in several tumor cell lines and is essential for DNA synthesis. Camptothecin binds to the Topo IDNA complex, stabilizing it and preventing the rejoining of broken DNA strands, which in turn blocks DNA replication and RNA synthesis. Due to its broad antitumor activity and unique mechanism of action, numerous efforts have been made to develop clinical analogs of camptothecin. Currently, only three analogs are available. Petition 870260084912, dated 08 / 20 / 2026, page 10 / 1402 3 / 694 market: Irinotecan (FDA approved in 1994, Pfizer Inc.), Topotecan (FDA approved in 2007, Novartis) and Belotecan (approved for marketing in South Korea in 2003, ChongKunDang Pharmaceuticals).

[004] However, both camptothecin and most of its derivatives exhibit low solubility and poor activity under physiological conditions, which limits the clinical development of camptothecin analogs. Therefore, the transformation of camptothecin into ADCs may overcome these limitations. Irinotecan is a prodrug, and its active metabolite, SN-38, has low solubility and a short half-life. Immunomedics has combined SN-38 as a cytotoxic agent with sacituzumab, which targets cancer cells expressing Trop-2, for the treatment of adult patients with metastatic triple-negative breast cancer (TNBC). The humanized sacituzumab govitecan-hziy lyophilized injection was approved by the FDA in April 2022 for treatment (US7999083 B2).

[005] The amino group of DX-8951f (hexatecane) contributes to its solubility, while the rigidity conferred by the cyclohexane ring favors the balance between the active form of the lactone and the inactive form of the hydroxy acid, thus increasing its activity. However, clinical trials did not achieve the expected results. Daiichi Sankyo used the Petition 870260084912, dated 08 / 20 / 2026, page 11 / 1402 4 / 694 amino-hydroxyacetylation to generate DXd, which is 2 to 4 times less active than exatecan (US 20210169852 A). DXd, linked to an anti-HER2 antibody via an enzyme-removable Gly-Gly-Phe-Gly tetrapeptide linker, yielded an ADC (Enhertu) that demonstrated great potential in treating HER2-expressing cancers in clinical settings. Consequently, Enhertu received accelerated FDA approval on December 20, 2019, for the treatment of unresectable or metastatic HER2-positive breast cancer in adults who have already received two or more anti-HER2 regimens for metastatic disease. Although the cyclohexane ring of DXd is believed to stabilize the biologically active lactone form, it introduces a chiral center, which complicates synthesis and SAR studies.To overcome this challenge, researchers at ImmunoGen developed a new series of camptothecin analogs with ring opening and elimination of the additional chiral center, introducing a group at position 7 for antibody conjugation. When conjugated with an anti-EGFR antibody (HuEGFR), the resulting ADC proved effective against EGFR-positive HSC-2 tumor xenograft models (US20210077482A1). Researchers at MediBoston applied a similar approach, deriving a functional group for antibody conjugation at position 9, incorporating a hydrophilic polypeptide linker, and obtained preliminary results. Petition 870260084912, dated 08 / 20 / 2026, page 12 / 1402 5 / 694 favorable clinical cases with the resulting ADC (WO 2021173773).

[006] Although camptothecin analogs exhibit good antitumor activity, especially when conjugated with humanized antibodies, providing excellent targeting and tumor elimination activity at lower effective doses, thus reducing toxicity and widening the therapeutic window, different types of camptothecin derivatives have very distinct half-lives, membrane permeability, and in vitro activity. Furthermore, their cytotoxicity against different cancer cells varies widely. Therefore, our goal is to design new structures to improve the activity and membrane permeability of camptothecin derivatives (i.e., enhance the bystander effect of camptothecin derivatives), thereby improving the killing of tumor cells with low or no antigen expression, in the hope of achieving specific clinical effects. SUMMARY

[007] One aspect of the present invention provides a compound represented by the general formula (A), or a pharmaceutically acceptable salt thereof: L-L2-Li-Dr (A) where: Petition 870260084912, dated 08 / 20 / 2026, p. 13 / 1402 6 / 694 Dr. is selected from among the following structures: R1 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl, alkynyl, cycloalkyl, -NRdRe, -(CH2U-OH, -(CH2) m-NRdRe, -OC(=O)NRf(CH2)m-OH, -OC(=O)NRf-(CH2)m-NRdRe, -(CH2) mC(=O)OH, -(CH2UC(=O)-NRdRe, -(CH2) mC(=O)NRf-(CH2) n-OH, -(CH2) mC(=O)NRf(CH2) n-NRdRe, -NRf-(CH2) m-OH, -NRf-(CH2) m-NRdRe, -O-(CH2) m-OH, O-(CH2) m-NRdRe, -NRfC(=O)O-(CH2) m-OH, -NRbC(=O)O-(CH2) m-NRdRe, -(CH2)m-NRfC(=O)O-(CH2)n-OH-, -(CH2)m-NRfC(=O)O-(CH2)n-NRdRe, (CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-OH, (CH2)m-NRfC(=O)-(CH2)n-NRdRe, -(CH2)m-NRfC(=O)-(CH2)n-OH, and (CH2)m-NRfC(=O)-G-(CH2)n-OH, wherein the alkyl, alkoxyl, alkenyl, alkynyl and cycloalkyl groups may be further substituted by one or more groups selected from halogen, deuterium, amino, alkyl and hydroxyl; Petition 870260084912, dated 08 / 20 / 2026, page 14 / 1402 7 / 694 R2 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl and alkynyl groups, wherein the alkyl, alkoxyl, alkenyl and alkynyl groups may be further replaced by one or more groups selected from halogen; R3 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl, alkynyl, CH2=, -NRdRe, -(CH2)m-OH, -(CH2)m-NRdRe, -OC(=O)NRf-(CH2)m-OH, OC(=O)NRf-(CH2)m-NRdRe, -(CH2)mC(=O)OH, -(CH2)mC(=O)-NRdRe, (CH2)mC(=O)NRf-(CH2)n-OH, -(CH2)mC(=O)NRf-(CH2)n-NRdRe, -NRf(CH2)m-OH, -NRf-(CH2)m-NRdRe, -NRf-C(=O)Rd, -NRf-C(=O)-(CH2)mRd, -NRfC(=O)O-(CH2)m-Rd, -O-(CH2)m-OH, -O-(CH2)m-NRdRe, NRfC(=O)O-(CH2)m-OH, -NRfC(=O)NRd-(CH2)m-OH, -NRfC(=O)NRd(CH2)mO-(CH2)n-OH, -NRfC(=O)O-(CH2)mO-(CH2)n-OH,NRfC(=O)NRd-(CH2)mO-(CH2)n-NRdRe, -NRfC(=O)O-(CH2)mO-(CH2)nNRdRe, -NRfC(=O)NRd-(CH2)m-NRdRe, -NRfC(=O)O-(CH2)m-NRdRe,(CH2)m-NRfC(=O)O-(CH2)n-OH, -(CH2)m-NRfC(=O)O-(CH2)n-NRdRe,(CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-OH,(CH2)m-NRfC(=O)-(CH2)n-NRdRe, and -(CH2)m-NRfC(=O)-(CH2)n-OH, wherein the alkyl, alkoxyl, alkenyl, and alkynyl groups may be further substituted by one or more groups selected from halogen, deuterium, amino,alkyl and hydroxyl; R4 is selected from hydrogen, halogen, hydroxyl, Petition 870260084912, dated 08 / 20 / 2026, page 15 / 1402 8 / 694 carboxyl, amino, cyano, alkyl, alkoxyl, alkenyl, alkynyl, cycloalkyl, -NRdRe, -(CH2)m-OH, -(CH2) m-NRdRe, OC(=O)NRf-(CH2) m-OH, -OC(=O)NRf-(CH2) m-NRdRe, -(CH2) mC(=O)OH, -(CH2) mC(=O)-NRdRe, -(CH2)mC(=O)NRf-(CH2)n-OH, -(CH2UC(=O)NRf-(CH2) n-NRdRe, -NRf-(CH2) m-OH, -NRf-(CH2) m-NRdRe, -O(CH2)m-OH, -O-(CH2) m-NRdRe, -NRfC(=O)O-(CH2) m-OH, -NRbC(=O)O(CH2)m-NRdRe, -(CH2)m-NRfC(=O)O-(CH2)n-OH-, -(CH2)m-NRfC(=O)O(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf(CH2)n-OH, -(CH2)m-NRfC(=O)-(CH2)n-NRdRe, -(CH2)m-NRfC(=O)(CH2)n-OH, and -(CH2)m-NRfC(=O)-G-(CH2)n-OH, wherein the alkyl, alkoxyl, alkenyl, alkynyl and cycloalkyl groups may be further substituted by one or more groups selected from halogen, deuterium, amino, alkyl and hydroxyl; the group -(CH2)m- may be further replaced by one or more halogen or deuterium groups; and G is selected from cycloalkylene, heterocycloalkene, heteroarylene, and arylene; R5 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl and alkynyl groups, wherein the alkyl, alkoxyl, alkenyl and alkynyl groups may be further replaced by one or more groups selected from halogen; R6 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl, and alkynyl. Petition 870260084912, dated 08 / 20 / 2026, page 16 / 1402 9 / 694 wherein the alkyl, alkoxyl, alkenyl and alkynyl groups may be further substituted by one or more groups selected from halogen; R7 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl and alkynyl groups, wherein the alkyl, alkoxyl, alkenyl and alkynyl groups may be further replaced by one or more groups selected from halogen; Rde Resão, each independently selected from between hydrogen and alkyl; Rf is selected from hydrogen, alkyl, -C(O)Rc, S(O)Rc, and -S(O)2Rc, with the alkyl group possibly being substituted by cycloalkyl; and Rc is selected from hydrogen, hydroxyl, and alkyl; Li is selected from a linkage, -(CH2)m-*, -O-*, NRa-*, -(CH2)mO-*, -(CH2)m-NRa-*, -OC(=O)NRb-(CH2)mO-*, OC(=O)NRb-(CH2)m-NRa-*, -(CH2)mC(=O)O-*, -(CH2)mC(=O)NRa-*, -(CH2)mC(=O)NRb-(CH2)nO-*, -(CH2)mC(=O)NRb-(CH2)n-NRa-*, NRb-(CH2)mO-*, -NRb-(CH2)m-NRa-*, -O-(CH2)mO-*, -O-(CH2)mNRa-*, -NRbC(=O)O-(CH2)mO-*, -NRbC(=O)O-(CH2)m-NRa-*, -(CH2)mNRbC(=O)O-(CH2)nO-*, -(CH2)m-NRbC(=O)O-(CH2)n-NRa-*, -(CH2)mOC(=O)NRb-(CH2)n-NRa-*, -(CH2)m-OC(=O)NRb-(CH2)nO-*, -(CH2)mNRbC(=O)-(CH2)n-NRa-*, and -(CH2)m-NRbC(=O)-(CH2)nO-*, where * represents the L2 binding site; Petition 870260084912, dated 08 / 20 / 2026, page 17 / 1402 10 / 694 Rae Rbsão, each independently selected from hydrogen, alkyl, -C(O)Rc, -S(O)Rc, and -S(O)2Rc, wherein the alkyl may be additionally substituted by cycloalkyl; and Rc is selected from hydrogen, hydroxyl, and alkyl; L2 is selected from a link where * is a connection point with Li; Oq'LAla L éL4L3 ou L3 is an amino acid residue formed by two or more amino acids, and L3 may optionally comprise one or more of the following structures, and Le is selected from one or more of the following structures: Petition 870260084912, dated 08 / 20 / 2026, page 18 / 1402 11 / 694 OH HO,J ° °H \ ^NH 1 / °τ; ho^ o HlX HO )- Xo HO vA HO OH OH 1 0? q 4 \ HO^ OH NH M / 0H / xo A HO )—< \ U S- HOJ V Zt4 HH HO pbb ^y=o Raa n<>ai n n-| λ w , 0 , or OM;jU / , each independently, selected between hydrogen and alkyl; . cXXp........yu L4 is 2 ; Zi is selected between a bond, -(CH2)p-, -(C2H4O)q-, Petition 870260084912, dated 08 / 20 / 2026, p. 19 / 1402 12 / 694 -(CH2)pC(O)NH-, -(CH2)pO-(CH2)pC(O)NH-, -(CH2) pC(O)-Le-NH-, -(CH2)pO-(CH2)pC(O)-L6-NH-, -C(O)NH-, -C(O)O-, -C(O)-,OC(O)-, -NH-, -O-, and -OC(O)NH-; m is an integer from 1 to 6; n is an integer from 1 to 6; s is an integer from 1 to 6; t is an integer from 0 to 10; if S2, S3, and S4 are each independently an integer from 0 to 10; preferably an integer from 0 to 8, or from 0 to 6; more preferably, from 0 to 4; even more preferably, from 0 to 2 or from 1 to 2; sã and s6 are, each independently, an integer from 1 to 6; ti is an integer from 1 to 6; t2 is an integer from 0 to 6; t3 is an integer from 1 to 6; t4 is an integer from 0 to 10; t5 is an integer from 0 to 10; p is an integer from 1 to 10; q is an integer from 1 to 10; and Q is a connecting unit. Petition 870260084912, dated 08 / 20 / 2026, p. 20 / 1402 13 / 694 with Zi being connected to Q.

[008] In a specific embodiment, in the compound represented by the general formula (A) or in its pharmaceutically acceptable salt, according to the present invention, Dr. is selected from among the following structures: Li is selected from -O-*, -NRa-*, -(CH2)mO-*, (CH2) m-NRa-*, -OC(=O)NRb-(CH2) mO-*, -OC(=O)NRb-(CH2) m-NRa-*, (CH2) mC(=O)O-*, -(CH2) mC(=O)NRa-*, -NRb-(CH2) mO-*, -NRb(CH2)m-NRa-*, -O-(CH2)mO-*, -O-(CH2)m-NRa-*, -NRbC(=O)O(CH2)mO-*, -NRbC(=O)O-(CH2)m-NRa-*, -(CH2) m-NRbC(=O)-(CH2) nNRa-*, and -(CH2) m-NRbC(=O)-(CH2) nO-*, being * a connecting point with L2; Ra is selected from between hydrogen and C1-C6 alkyl; Rbé is selected from hydrogen, alkyl, -C(O)Rc, S(O)Rc, and -S(O)2Rc, with Rc being selected from hydrogen, hydroxyl, and C1-C6 alkyl; m is an integer from 1 to 6; preferably, a Petition 870260084912, dated 08 / 20 / 2026, page 21 / 1402 14 / 694 is a whole number from 1 to 4; more preferably, from 1 to 2; n is an integer from 1 to 6; preferably from 1 to 4; most preferably from 1 to 2; R1 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-C6 alkynyl, wherein the C1-Ce alkyl, C1-Ce alkoxyl, C2-C6 alkenyl and C2-C6 alkynyl groups may be further substituted by one or more groups selected from halogen; C1-Ce alkyl and C1-Ce alkoxyl being preferred; R2 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-Ce alkynyl, wherein the C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-Ce alkynyl groups may be further substituted by one or more groups selected from halogen; halogen being the preferred group.

[009] In another specific embodiment, in the compound represented by the general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, Dr. is selected from among the following structures: Petition 870260084912, dated 08 / 20 / 2026, page 22 / 1402 15 / 694 Li is selected from -O-*, -NRa-*, -(CH2) mO-*, (CH2) m-NRa-*, -OC(=O)NRb-(CH2) mO-*, -OC(=O)NRb-(CH2) m-NRa-*, (CH2) mC(=O)O-*, -(CH2) mC(=O)NRa-*, -NRb-(CH2) mO-*, -NRb(CH2)m-NRa-*, -O-(CH2)mO-*, -O-(CH2)m-NRa-*, -NRbC(=O)O(CH2)mO-*, -NRbC(=O)O-(CH2)m-NRa-*, -(CH2) m-NRbC(=O)-(CH2) nNRa-*, and -(CH2) m-NRbC(=O)-(CH2) nO-*, being * a connecting point with L2; Ra is selected from between hydrogen and C1-C1 alkyl; Rbé selected from hydrogen, alkyl, -C(O)Rc, S(O)Rc, and -S(O)2Rc, with the alkyl group possibly being further substituted by cycloalkyl; and Rcé selected from hydrogen, hydroxyl, and C1-Ce alkyl. m is an integer from 1 to 6; preferably an integer from 1 to 4; more preferably, from 1 to 2; n is an integer from 1 to 6; preferably from 1 to 4; most preferably from 1 to 2; R1 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-C1 alkyl, C1-C1 alkoxyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, -NRdRe, -(CH2)m-OH, Petition 870260084912, dated 08 / 20 / 2026, page 23 / 1402 16 / 694 (CH2) m-NRdRe, -OC(=O)NRf-(CH2) m-OH, -OC(=O)NRf-(CH2) m-NRdRe, (CH2) mC(=O)OH, - (CH2) mC(=O) -NRdRe, - (CH2) mC(=O)NRf- (CH2) n-OH, - (CH2) mC(=O)NRf- (CH2) n-NRdRe, -NRf- (CH2) m-OH, -NRf- (CH2) m-NRdRe, -O-(CH2)m-OH, -O-(CH2)m-NRdRe, -NRfC(=O)O-(CH2)m-OH, NRbC(=O)O-(CH2) m-NRdRe, -(CH2) m-NRfC(=O)O-(CH2) n-OH-, -(CH2)mNRfC(=O)O-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)mOC(=O)NRf-(CH2)n-OH, -(CH2)m-NRfC(=O)-(CH2)n-NRdRe, -(CH2)mNRfC(=O)-(CH2)n-OH, and -(CH2)m-NRfC(=O)-G-(CH2)n-OH, wherein the C1-C1 alkyl, C1-C1 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl and C3-C6 cycloalkyl structures may be further substituted by one or more groups selected from halogen, deuterium, amino, C1-C1 alkyl and hydroxyl; with C1-C1 alkyl and C1-C1 alkoxy being the preferred options; the (CH2)m- group may optionally be replaced by one or more deuterium or halogen groups; and G is selected from cycloalkylene, heterocycloalkene, heteroarylene, and arylene. R2 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-Ce alkynyl, wherein the C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-Ce alkynyl groups may be further substituted by one or more groups selected from halogen; halogen being the preferred option; and Rd, Re, Rf, m, and en are defined as those of the general formula. Petition 870260084912, dated 08 / 20 / 2026, page 24 / 1402 17 / 694 (A)

[0010] In another specific embodiment, in the compound represented by the general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, Dr. is selected from among the following structures: Li is selected from a linkage, -(CH2)m-*, -O-*, (CH2)mO-*, -NRa-*, -(CH2) m-NRa-*, -NRb-(CH2)mO-*, -NRb-(CH2)mNRa-*, -O-(CH2) mO-*, -O-(CH2) m-NRa-*, -(CH2) m-OC(=O)NRb(CH2) n-NRa-*, -(CH2) m-OC(=O)NRb-(CH2) nO-*, -(CH2)m-NRbC(=O) (CH2) n-NRa-*, and -(CH2) m-NRbC(=O)-(CH2) nO-*, where * is a linkage location with L2; Ra is selected from between hydrogen and C1-C1 alkyl; Rbé selected from hydrogen, alkyl, -C(O)Rc, S(O)Rc, and -S(O)2Rc, with the alkyl group possibly being further substituted by cycloalkyl; and Rcé selected from hydrogen, hydroxyl, and C1-Ce alkyl. m is an integer from 1 to 6; preferably, an integer from 1 to 4; Petition 870260084912, dated 08 / 20 / 2026, page 25 / 1402 18 / 694 n is an integer from 1 to 6; preferably, an integer from 1 to 4; and R2 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-C6 alkynyl, wherein the C1-Ce alkyl, C1-Ce alkoxyl, C2-C6 alkenyl and C2-C6 alkynyl groups may be further substituted by one or more groups selected from halogen; halogen being the preferred group.

[0011] In another specific embodiment, in the compound represented by the general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, Dr. is selected from among the following structures: Li is selected from -O-*, where * is a linking location with L2; R2 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl, and C2-Ce alkynyl groups, where the C1-Ce alkyl and alkoxyl groups are... Petition 870260084912, dated 08 / 20 / 2026, page 26 / 1402 19 / 694 C1-C6, C2-C6 alkenyl and C2-C6 alkynyl groups may be further replaced by one or more groups selected from halogens; halogen being the preferred option; R3é selecionado entre hidrogênio, halogênio, hidroxila, amino, ciano, alquila C1-C6, alcoxila C1-C6, alquenila C2-C6, alquinila C2-C6, CH2=, -NRdRe, -(CH2)m-OH, -(CH2) m-NRdRe, OC(=O)NRf-(CH2) m-OH, -OC(=O)NRf-(CH2) m-NRdRe, -(CH2) m-C(=O)OH, -(CH2) m-C(=O)-NRdRe, -(CH2)m-C(=O)NRf-(CH2)n-OH, -(CH2)mC(=O)NRf-(CH2) n-NRdRe, -NR''-(CH) m-OH, -NRf-(CH2) m-NRdRe, -NRfC(=O)Rd, -NRf-C(=O)-(CH2)m-Rd, -NRfC(=O)O-(CH2)m-Rd, -O-(CH2)mOH, -O-(CH2)m-NRdRe, -NRfC(=O)O-(CH2)m-OH, -NRfC(=O)NRd-(CH2)mOH, -NRfC(=O)NRd-(CH2)m-O-(CH2)n-OH, -NRfC(=O)O-(CH2)m-O(CH2)n-OH, -NRfC(=O)NRd-(CH2)m-O-(CH2)n-NRdRe, -NRfC(=O)O(CH2)m-O-(CH2)n-NRdRe, -NRfC(=O)NRd-(CH2)m-NRdRe, -NRfC(=O)O(CH2)m-NRdRe, -(CH2)m-NRfC(=O)O-(CH2)n-OH, -(CH2)m-NRfC(=O)O(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf(CH2)n-OH, -(CH2)m-NRfC(=O)-(CH2)n-NRdRe, e -(CH2)m-NRfC(=O)(CH2)n-OH, sendo que os grupos alquila C1-C6, alcoxila C1-C6,C2-C6 alkenyl and C2-C6 alkynyl groups may be further substituted by one or more groups selected from halogen, deuterium, amino, C1-C6 alkyl, and hydroxyl; hydrogen or hydroxyl being the preferred options. R4 is selected from hydrogen, halogen, hydroxyl, Petition 870260084912, dated 08 / 20 / 2026, page 27 / 1402 20 / 694 carboxyl, amino, cyano, Ci-Ce alkyl, Ci-Ce alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, Ca-Ce cycloalkyl, -NRdRe, -(CH2U-OH, (CH2) m-NRdRe, -OC(=O)NRf-(CH2) m-OH, -OC(=O)NRf-(CH2) m-NRdRe, (CH2) mC(=O)OH, - (CH2) mC(=O) -NRdRe, - (CH2) mC(=O)NRf- (CH2) n-OH, - (CH2) mC(=O)NRf- (CH2) n-NRdRe, -NRf- (CH2) m-OH, -NRf- (CH2) m-NRdRe, -O-(CH2)m-OH, -O-(CH2)m-NRdRe, -NRfC(=O)O-(CH2)m-OH, NRbC(=O)O-(CH2) m-NRdRe, -(CH2) m-NRfC(=O)O-(CH2) n-OH-, -(CH2)mNRfC(=O)O-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)mOC(=O)NRf-(CH2)n-OH, -(CH2)m-NRfC(=O)-(CH2)n-NRdRe, -(CH2)mNRfC(=O)-(CH2)n-OH, and -(CH2)m-NRfC(=O)-G-(CH2)n-OH, where the Ci-Ce alkyl, Ci-Ce alkoxy, alkenyl C2-C6, C2-C6 alkynyl and Cycloalkyl Ca-Ce groups are optionally substituted by one or more groups selected from halogen, deuterium, amino, C1-Ce alkyl and hydroxyl; hydroxyl, C1-Ce alkyl and C1-Ce alkoxy are preferred; the -(CH2)m- group is optionally substituted by one or more deuterium or halogen groups;and G is selected from cycloalkylene, heterocycloylene, heteroarylene, and arylene; and; Rd, Re, Rf, m, en are defined as those of the general formula (A).

[0012] In another specific embodiment, in the compound represented by the general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, Petition 870260084912, dated 08 / 20 / 2026, page 28 / 1402 21 / 694 Dr. is selected from among the following structures: R3 Li is selected from -O-*, where * is a linking location with L2; R2 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-Ce alkynyl, wherein the C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-Ce alkynyl groups may be further substituted by one or more groups selected from halogen; halogen being the preferred option; R3 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl, C2-Ce alkynyl and CH2=, wherein the C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-Ce alkynyl groups may be further substituted by one or more groups selected from halogen; hydrogen and hydroxyl being the preferred options; and R4 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-C1 alkyl, C1-C1 alkoxyl, C2-C1 alkenyl and Petition 870260084912, dated 08 / 20 / 2026, page 29 / 1402 22 / 694 C2-Ce alkynyl, wherein the C1-Ce alkyl, C1-Ce alkoxyl, C2-C6 alkenyl and C2-C6 alkynyl groups may be further substituted by one or more halogen groups selected; hydroxyl, C1-Ce alkyl and C1-Ce alkoxyl being the preferred options.

[0013] In another specific embodiment, in the compound represented by the general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, Dr. is selected from among the following structures: Li is selected between -(CH2)mO-* and -(CH2)m-NRa-*, where * is a connection site with L2; m is an integer from 1 to 6; preferably, an integer from 1 to 4; Ra is selected from between hydrogen and C1-C1 alkyl; R5 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-C6 alkyl, C1-C6 alkoxyl, C2-C6 alkenyl, and C2-C6 alkynyl groups, wherein the C1-C6 alkyl, C1-C6 alkoxyl, C2-C6 alkenyl, and C2-C6 alkynyl groups may be further substituted by one or more other groups. Petition 870260084912, dated 08 / 20 / 2026, page 30 / 1402 23 / 694 selected from halogen; halogen being the preferred option; and R7 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-C6 alkynyl, wherein the C1-Ce alkyl, C1-Ce alkoxyl, C2-C6 alkenyl and C2-C6 alkynyl groups may be further substituted by one or more groups selected from halogen; hydroxyl and amino being the preferred options.

[0014] In another specific embodiment, in the compound represented by the general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, Dr. is selected from among the following structures: Li is selected from -O-*, where * is a linking location with L2; R5 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl, and C2-Ce alkynyl groups, where the C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl, and C2-Ce alkynyl groups can be Petition 870260084912, dated 08 / 20 / 2026, page 31 / 1402 24 / 694 additionally replaced by one or more groups selected from halogen; halogen being the preferred option; R6 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-C6 alkyl, C1-C6 alkoxyl, C2-C6 alkenyl, and C2-C6 alkynyl, wherein the C1-C6 alkyl, C1-C6 alkoxyl, C2-C6 alkenyl, and C2-C6 alkynyl groups may be further substituted by one or more groups selected from halogen; hydroxyl and amino being the preferred options; and R7 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-C6 alkyl, C1-C6 alkoxyl, C2-C6 alkenyl and C2-C6 alkynyl, wherein the C1-C6 alkyl, C1-C6 alkoxyl, C2-C6 alkenyl and C2-C6 alkynyl groups may be further substituted by one or more groups selected from halogen; hydroxyl and amino being the preferred options.

[0015] In a preferred embodiment, in the compound represented by the general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, Dr is selected from: Petition 870260084912, dated 08 / 20 / 2026, page 32 / 1402 25 / 694

[0016] In another preferred embodiment, in the compound represented by general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, when Li is selected from -NRa-*, -(CH2) m-NRa-*, OC(=O)NRb-(CH2) m-NRa-*, -(CH2) mC(=O)NRa-*, -(CH2) mC(=O)NRb(CH2) n-NRa-*, -NRb-(CH2) m-NRa-*, -O-(CH2) m-NRa-*, -NRbC(=O)O(CH2) m-NRa-*, -(CH2) m-NRbC(=O)O-(CH2) n-NRa-*, -(CH2)mOC(=O)NRb-(CH2)n-NRa-*, and -(CH2)m-NRbC(=O)-(CH2)n-NRa-*, where * is a binding site with L2, L2 is selected from a link or being * a link site with Li; and Ra, Rb, men are defined according to the general formula (A).

[0017] In another preferred embodiment, in the compound represented by the general formula (A), or in its salt Petition 870260084912, dated 08 / 20 / 2026, page 33 / 1402 26 / 694 pharmaceutically acceptable, according to the present invention, Li is selected from a bond, -O-*, -(CH2) mO-*, -NRa-*, -OC(=O)NRb-(CH2)mO-*, -(CH2) mC(=O)O-*, -(CH2UC(=O)NRb- (CH2) nO-*, -NRb-(CH2)mO-*, -O-(CH2)mO-*, NRbC(=O)O-(CH2)mO-*, -(CH2)m-NRbC(=O)O-(CH2)nO-*, -(CH2)mOC(=O)NRb-(CH2)nO-*, and -(CH2)m-NRbC(=O)-(CH2)nO-*, where * is a binding site with L2; L2 is selected from a link, linked to Li; and being a place Ra, Rb, men are defined according to the general formula (A).

[0018] In another preferred embodiment, in the compound represented by general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, L3 is an amino acid residue formed by two or more amino acids selected from phenylalanine, alanine, glycine, valine, leucine, isoleucine, tryptophan, tyrosine, histidine, lysine, citrulline, serine, threonine, cysteine, Petition 870260084912, dated 08 / 20 / 2026, page 34 / 1402 27 / 694 glutamic acid, glutamine, aspartic acid, asparagine, methionine and arginine, and L3 optionally comprises one or more of the following structures: Petition 870260084912, dated 08 / 20 / 2026, page 35 / 1402 28 / 694 preferably, wherein R, Raa, and Rbb are each independently selected from hydrogen and C1-C1 alkyl; s is an integer from 1 to 6; preferably, an integer from 2 to 6; more preferably, from 2 to 4; If they are, each independently, an integer from 1 to 6; preferably from 2 to 6; most preferably from 2 to 4; t is an integer from 0 to 10; preferably from 2 to 8; most preferably from 3 to 7; Petition 870260084912, dated 08 / 20 / 2026, p. 36 / 1402 29 / 694 ti is an integer from 1 to 6; preferably from 1 to 4; more preferably from 2 to 4; or even more preferably, 1 or 2; t2 is an integer from 1 to 6; preferably from 1 to 4; most preferably 0 or 2; ta is an integer from 1 to 6; preferably from 1 to 4; most preferably 1 or 2; t4 is an integer from 0 to 10; and t5 is an integer from 0 to 10.

[0019] In another embodiment, La is an amino acid residue formed by two or more amino acids selected from phenylalanine, alanine, glycine, valine, leucine, isoleucine, tryptophan, tyrosine, histidine, lysine, citrulline, serine, threonine, cysteine, glutamic acid, glutamine, aspartic acid, asparagine, methionine, and arginine. and La optionally comprises structures: HO. HO HO ' Petition 870260084912, dated 08 / 20 / 2026, p. 37 / 1402 30 / 694 or where R, Raa, Rbb, s, t, ti to ts, ss, and se are the same as defined previously.

[0020] In another preferred embodiment, in the compound represented by general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, L3 is ^Ib , ^la , or Lia, * represents the L2 binding site, and • represents the binding site with a carbonyl or methylene group; Lib and L'ib are each independently amino acid residues formed by one or more amino acids selected from phenylalanine, alanine, glycine, valine, leucine, isoleucine, tryptophan, tyrosine, histidine, lysine, citrulline, serine, threonine, cysteine, glutamic acid, Petition 870260084912, dated 08 / 20 / 2026, p. 38 / 1402 31 / 694 glutamine, aspartic acid, asparagine, methionine and arginine; L1a is a connection or is selected from one or more of the following structures: or Petition 870260084912, dated 08 / 20 / 2026, p. 39 / 1402 32 / 694 preferably or where R is selected from hydrogen and C1-C1 alkyl, preferably hydrogen; Raae Rbbsão each one selected independently from Ci-Ce alkyl; s is an integer from 1 to 6; preferably, an integer from 2 to 6; more preferably, from 2 to 4; Petition 870260084912, dated 08 / 20 / 2026, page 40 / 1402 33 / 694 S5 and if they are, each independently, an integer from 1 to 6; preferably from 2 to 6; most preferably from 2 to 4; t is an integer from 0 to 10; preferably from 2 to 8; most preferably from 3 to 7; ti is an integer from 1 to 6; preferably from 1 to 4; more preferably from 2 to 4; or even more preferably, 1 or 2; t2 is an integer from 0 to 6; preferably from 1 to 4; most preferably 1 or 2; ta is an integer from 1 to 6; preferably from 1 to 4; most preferably 1 or 2; t4 is an integer from 0 to 10; and t5 is an integer from 0 to 10.

[0021] In another embodiment There is ^Lib / / L1b^L'1b1a, ou1-13, * where * is a binding site with L2, and • a binding site with carbonyl or methylene; where Lib and L'ib are, each independently, amino acid residues formed by one or more amino acids selected from phenylalanine, alanine, glycine, valine, Petition 870260084912, dated 08 / 20 / 2026, p. 41 / 1402 34 / 694 leucine, isoleucine, tryptophan, tyrosine, histidine, lysine, citrulline, serine, threonine, cysteine, glutamic acid, glutamine, aspartic acid, asparagine, methionine and arginine; and Lia is a connection or is selected from one or more of the following structures: or where R, Raa, Rbb, s, t, ti to ts, ss, and se are the same as defined previously.

[0022] In another preferred embodiment, in the compound represented by the general formula (A), or in its pharmaceutically acceptable salt, according to the present Petition 870260084912, dated 08 / 20 / 2026, p. 42 / 1402 35 / 694 invention, L3 is selected from: Petition 870260084912, dated 08 / 20 / 2026, p. 43 / 1402 36 / 694 where Lib and L'ib are, each independently, Petition 870260084912, dated 08 / 20 / 2026, p. 44 / 1402 37 / 694 amino acid residues formed by one or more amino acids selected from phenylalanine, alanine, glycine, valine, leucine, isoleucine, tryptophan, tyrosine, histidine, lysine, citrulline, serine, threonine, cysteine, glutamic acid, glutamine, aspartic acid, asparagine, methionine and arginine; R is selected from between hydrogen and C1-C1 alkyl and is preferably hydrogen; Raae Rbbsão each one selected independently from Ci-Ce alkyl; s is an integer from 1 to 6; preferably, an integer from 2 to 6; more preferably, from 2 to 4; Ss and if are, each independently, an integer from 1 to 6; preferably from 2 to 6; most preferably from 2 to 4; t is an integer from 0 to 10; preferably from 2 to 8; most preferably from 3 to 7; ti is an integer from 1 to 6; preferably from 1 to 4; more preferably from 2 to 4; or even more preferably, 1 or 2; t2 is an integer from 1 to 6; preferably from 1 to 4; most preferably 0 or 2; ta is an integer from 1 to 6; preferably from 1 to 4; most preferably 1 or 2; Petition 870260084912, dated 08 / 20 / 2026, p. 45 / 1402 38 / 694 t4 is an integer from 0 to 10; t5 is an integer from 0 to 10; • It is a binding site with L2; and it is a binding site with carbonyl or methylene.

[0023] In another preferred embodiment, in the compound represented by general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, L3 is selected from: Petition 870260084912, dated 08 / 20 / 2026, p. 46 / 1402 39 / 694 where Lib and L'ib are each independently amino acid residues formed from one or more amino acids selected from phenylalanine, alanine, glycine, valine, leucine, isoleucine, tryptophan, tyrosine, histidine, lysine, Petition 870260084912, dated 08 / 20 / 2026, page 47 / 1402 40 / 694 citrulline, serine, threonine, cysteine, glutamic acid, glutamine, aspartic acid, asparagine, methionine and arginine; R is selected from between hydrogen and C1-C1 alkyl and is preferably hydrogen; Raae Rbbsão each one selected independently from Ci-Ce alkyl; Ss and if are, each independently, an integer from 1 to 6; preferably from 2 to 6; most preferably from 2 to 4; t is an integer from 0 to 10; preferably from 2 to 8; most preferably from 3 to 7; ti is an integer from 1 to 6; preferably from 1 to 4; more preferably from 2 to 4; or even more preferably, 1 or 2; t2 is an integer from 1 to 6; preferably from 1 to 4; most preferably 0 or 2; ta is an integer from 1 to 6; preferably from 1 to 4; most preferably 1 or 2; t4 is an integer from 0 to 10; ts is an integer from 0 to 10; • It is a binding site with L2; and it is a binding site with carbonyl or methylene. Petition 870260084912, dated 08 / 20 / 2026, p. 48 / 1402 41 / 694

[0024] In another preferred embodiment, in the compound represented by general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, Lib and L'ib are each independently amino acid residues formed by one or more amino acids selected from glycine, phenylalanine, citrulline, leucine, isoleucine, alanine, valine, asparagine, glutamine, arginine, glutamic acid and lysine; preferably, amino acid residues formed by two or more amino acids selected from glycine, phenylalanine, citrulline, valine, lysine, glutamine, glutamic acid, leucine and alanine.

[0025] In another preferred embodiment, in the compound represented by general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, Lib and L'ib are each independently selected from: -Gly-*, -Val-*, -Gly-Phe-Gly-*, -PheGly-*, -Gly-Val-Cit-*, -Val-Cit-*, -Gly-Val-Arg-*, -Val-Arg*, -Gly-Val-Ala-*, -Val-Ala-*, -Gly-Phe-*, -Phe-Gly-*, -GlyGly-Gly-*, Gly-Gly-*, -Gly-Val-Gly-*, -Gly-Ala-Gly-*, -GlyPhe-Cit-*, -Gly-Phe-Val-*, -Gly-Phe-Ala-*, -Gly-Phe-Lys-*, -Phe-Lys-*, -Gly-Val-*, -Gly-Cit-*, -Gly-Ala-*, -Gly-GlyLys-*, Gly-Lys'-*, -Ala-Ala-Ala-*, -Gln-Val-Ala-*, -Gln-ValCit-*, -Asp-Val-Ala-*, -Asp-Val-Cit-*, -Lys-Gly-Val-Ala-*, -Lys-Gly-Val-Cit-*, -Lys-Gly-Gly-Val-Ala-*, -Lys-Gly-GlyPetition 870260084912, of 08 / 20 / 2026, p. 49 / 1402 42 / 694 Val-Cit-*, Gly-Gly-Phe-Gly-*, -Lys-Gln-Val-Cit-*, -Lys-GlnVal-Ala-*, -Lys-Glu-Val-Cit-*, -Lys-Glu-Val-ALa-*, -LysAsp-Val-Cit-*, -Lys-Asp-Val-Ala-*, Glu-Val-Cit-*, Glu-ValAla-*, -Lys-Val-Ala-*, -Lys-Val-Cit-*, -Val-Lys-Gly-*, and Val-Lys*; preferably, -Gly-Phe-Gly-*, -Gly-Val-Cit-*, -Val-Cit-*, -Gly-Val-Ala-*, -Val-Ala-*, -Gly-Phe-Gly-*, Phe-Gly-*, -Gly-Phe-Lys-, -Phe-Lys-*, -Gln-Val-Ala-*, -GlnVal-Cit-*, -Asp-Val-Ala-*, -Lys-Gly-Val-Ala-*, -Lys-GlyVal-Cit-*, -Lys-Gly-Gly-Val-Ala-*, -Lys-Gly-Gly-Val-Cit-*, Gly-Gly-Phe-Gly-*, -Lys-Gln-Val-Cit-*, -Lys-Gln-Val-Ala-*, -Lys-Glu-Val-Cit-*, -Lys-Glu-Val-ALa-*, -Lys-Asp-Val-Cit-*, -Lys-Asp-Val-Ala-*, Glu-Val-Cit-*, Glu-Val-Ala-*, -Lys-ValAla-*, -Lys-Val-Cit-*, -Val-Lys-Gly-*, -Val-Lys-*, and -AspVal-Cit-*, where * represents the linkage point with L2.

[0026] In another preferred embodiment, in the compound represented by general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, L3 is selected from: Petition 870260084912, dated 08 / 20 / 2026, p. 50 / 1402 43 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 51 / 1402 44 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 52 / 1402 45 / 694 OH Petition 870260084912, dated 08 / 20 / 2026, p. 53 / 1402 46 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 54 / 1402 47 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 55 / 1402 48 / 694 • It is a connection point with L2; and Petition 870260084912, dated 08 / 20 / 2026, page 56 / 1402 49 / 694 is a carbonyl or methylene binding site.

[0027] In another preferred embodiment, in the compound represented by the general formula (A), or in its pharmaceutically acceptable salt, according to the present Invention, Q is selected from: THE preferably, °

[0028] In another preferred embodiment, in the compound represented by general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, Zi is selected from a linkage, -(CH2)p-, Petition 870260084912, 20 / 08 / 2026, p. 57 / 1402 50 / 694 (CH2)pC(O)NH-, -(CH2)pO-(CH2)pC(O)NH-, -(CH2) pC(O)-Le-NH-, -(CH2)pO-(CH2)pC(O)-L6-NH-, -C(O)NH-, -C(O)O-, -C(O)-, OC(O)-, and -OC(O)NH-, where p is an integer from 1 to 10; preferably an integer from 1 to 6; more preferably from 2 to 4; and even more preferably from 2 to 3; si, s2, s3, and s4 are each independently an integer from 0 to 10; preferably from 0 to 8 or from 0 to 6; more preferably from 0 to 4; even more preferably from 0 to 2, or from 1 to 2; is selected L6 s is an integer from 1 to 6; preferably, an integer from 2 to 6; more preferably, from 2 to 4; t is an integer from 0 to 10; preferably from 0 to 8; more preferably from 3 to 7; and L6 preferably Petition 870260084912, dated 08 / 20 / 2026, p. 58 / 1402 51 / 694

[0029] In another preferred embodiment, in the compound represented by general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, Zi is selected from among a linkage, -(CH2)p-, -(CH2)pC(O)NH-, -(CH2)pO-(CH2)pC(O)NH-, -C(O)NH-, -C(O)O-, -C(O)-, -OC(O)-, and -OC(O)NH-; if it is an integer from 0 to 6; preferably, an integer from 0 to 1; s2 is an integer from 0 to 6; preferably, an integer from 0 to 1; sa is 0; s 4 is 0; ep is an integer from 1 to 10; preferably from 1 to 6; more preferably from 2 to 4; and even more preferably from 2 to 3.

[0030] In another preferred embodiment, in the compound represented by the general formula (A), or in its pharmaceutically acceptable salt, according to the present Petition 870260084912, dated 08 / 20 / 2026, p. 59 / 1402 52 / 694 invention, Zi is selected from -(CH2) pC(O)NH-, -(CH2) pO-(CH2) pC(O)NH-, and -C(O)NH-; if it is an integer from 1 to 6; preferably, an integer from 2 to 6; S2 is an integer from 1 to 10; preferably, an integer from 2 to 10; S3 is 0; s 4 is 0; ep is an integer from 1 to 10; preferably from 1 to 6; more preferably from 2 to 4; and even more preferably from 2 to 3.

[0031] In another preferred embodiment, in the compound represented by general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, Q-L4- is selected from: Petition 870260084912, dated 08 / 20 / 2026, p. 60 / 1402 53 / 694 where: Zi is selected from -C(O)NH-, -C(O)O-, -C(O)-, OC(O)-, and -OC(O)NH-, preferably -C(O)NH-; p is an integer from 1 to 10; preferably, an integer from 1 to 6; more preferably, an integer from 2 to 4; and most preferably, an integer from 2 to 3. if is an integer from 0 to 6; integer from 0 to 1; sa is an integer from 1 to 10; preferably, an integer from 1 s is an integer from 0 s4 is an integer from 1 s7 is an integer from 1 s is a number a 8; integer from 0 to 6; a 1; The integer from 1 to 6; a 2; integer from 0 to 6; a 2; The integer from 1 to 4; preferably, one preferably, one preferably, one Petition 870260084912, dated 08 / 20 / 2026, page 61 / 1402 54 / 694 is an integer from 1 to 2; S9 is an integer from 1 to 10; preferably, an integer from 1 to 8; and sio is an integer from 1 to 4; preferably, an integer from 1 to 2.

[0032] In another preferred embodiment, in the compound represented by general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, L is selected from: Petition 870260084912, dated 08 / 20 / 2026, p. 62 / 1402 55 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 63 / 1402 56 / 694 o, e Petition 870260084912, dated 08 / 20 / 2026, p. 64 / 1402 57 / 694 OH OH OH in which, Lib is an amino acid residue formed by two or more amino acids selected from glycine, phenylalanine, citrulline, leucine, isoleucine, alanine, valine, asparagine, glutamine, arginine, glutamic acid and lysine; or, preferably, a residue formed by two or more amino acids selected from glycine, phenylalanine, citrulline, leucine, alanine, valine, glutamine, glutamic acid and lysine;more preferably, selected from: -Gly-*, -Val-*, -Gly-Phe-Gly-*, -Phe-Gly-*, -Gly-ValCit-*, -Val-Cit-*, -Gly-Val-Arg-*, -Val-Arg-*, -Gly-Val-Ala*, -Val-Ala-*, -Gly-Phe-*, -Phe-Gly-*, -Gly-Gly-Gly-*, GlyGly-*, -Gly-Val-Gly-*, -Gly-Ala-Gly-*, -Gly-Phe-Cit-*, -GlyPhe-Val-*, -Gly-Phe-Ala-*, -Gly-Phe-Lys-*, -Phe-Lys-*, -GlyVal-*, -Gly-Cit-*, -Gly-Ala-*, -Gly-Gly-Lys-*, Gly-Lys'-*, -Ala-Ala-Ala-*, -Gln-Val-Ala-*, -Gln-Val-Cit-*, -Asp-ValAla-*, -Asp-Val-Cit-*, -Lys-Gly-Val-Ala-*, -Lys-Gly-ValCit-*, -Lys-Gly-Gly-Val-Ala-*, -Lys-Gly-Gly-Val-Cit-*, GlyGly-Phe-Gly-*, -Lys-Gln-Val-Cit-*, -Lys-Gln-Val-Ala-*,; Petition 870260084912, dated 08 / 20 / 2026, page 65 / 1402 58 / 694 Lys-Glu-Val-Cit-*, -Lys-Glu-Val-ALa-*, -Lys-Asp-Val-Cit-*, -Lys-Asp-Val-Ala-*, Glu-Val-Cit-*, Glu-Val-Ala-*, -Lys-ValAla-*, -Lys-Val-Cit-*, -Val-Lys-Gly-*, and -Val-Lys-*; preferably, -Gly-Phe-Gly-*, -Gly-Val-Cit-*, -ValCit-*, -Gly-Val-Ala-*, -Val-Ala-*, -Gly-Phe-Gly-*, -Phe-Gly*, -Gly-Phe-Lys-, -Phe-Lys-*, -Gln-Val-Ala-*, -Gln-Val-Cit*, -Asp-Val-Ala-*, -Lys-Gly-Val-Ala-*, -Lys-Gly-Val-Cit-*, -Lys-Gly-Gly-Val-Ala-*, -Lys-Gly-Gly-Val-Cit-*, Gly-GlyPhe-Gly-*, -Lys-Gln-Val-Cit-*, -Lys-Gln-Val-Ala-*, -LysGlu-Val-Cit-*, -Lys-Glu-Val-ALa-*, -Lys-Asp-Val-Cit-*, Lys-Asp-Val-Ala-*, Glu-Val-Cit-*, Glu-Val-Ala-*, -Lys-ValAla-*, -Lys-Val-Cit-*, -Val-Lys-Gly-*, -Val-Lys-*, and -AspVal-Cit-*; • represents the connection point with L2; Zi is selected from -C(O)NH-, -C(O)O-, -C(O)-, OC(O)-, and -OC(O)NH-, preferably -C(O)NH-; p is an integer from 1 to 10; preferably, an integer from 1 to 6; if it is an integer from 0 to 6; preferably, an integer from 0 to 1; s2 is an integer from 1 to 6; preferably, an integer from 1 to 2; sa is an integer from 0 to 6; preferably, a Petition 870260084912, dated 08 / 20 / 2026, p. 66 / 1402 59 / 694 is an integer from 0 to 1; S4 is an integer from 1 to 6; preferably, an integer from 1 to 2; t is an integer from 0 to 10; ti is an integer from 1 to 6; preferably from 1 to 4; more preferably from 2 to 4; or even more preferably, 1 or 2; t2 is an integer from 0 to 6; preferably from 1 to 4; most preferably 1 or 2; and ta is an integer from 1 to 6; preferably from 1 to 4; most preferably 1 or 2.

[0033] In a preferred embodiment, in the compound represented by general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, Lib is an amino acid residue formed by one or more amino acids selected from glycine, phenylalanine, citrulline, leucine, isoleucine, alanine, valine, asparagine, glutamine, arginine, glutamic acid and lysine; or, preferably, an amino acid residue formed by two or more amino acids selected from glycine, phenylalanine, citrulline, leucine, alanine, valine, glutamine, glutamic acid and lysine; most preferably selected from -Gly-*, -Val-*, Petition 870260084912, dated 08 / 20 / 2026, page 67 / 1402 60 / 694 Gly-Phe-Gly-*, -Phe-Gly-*, -Gly-Val-Cit-*, -Val-Cit-*, -GlyVal-Arg-*, -Val-Arg-*, -Gly-Val-Ala-*, -Val-Ala-*, -Gly-Phe*, -Phe-Gly-*, -Gly-Gly-Gly-*, Gly-Gly-*, -Gly-Val-Gly-*, Gly-Ala-Gly-*, -Gly-Phe-Cit-*, -Gly-Phe-Val-*, -Gly-PheAla-*, -Gly-Phe-Lys-*, -Phe-Lys-*, -Gly-Val-*, -Gly-Cit-*, -Gly-Ala-*, -Gly-Gly-Lys-*, Gly-Lys’-*, -Ala-Ala-Ala-*, Gln-Val-Ala-*, -Gln-Val-Cit-*, -Asp-Val-Ala-*, -Asp-ValCit-*, -Lys-Gly-Val-Ala-*, -Lys-Gly-Val-Cit-*, -Lys-GlyGly-Val-Ala-*, -Lys-Gly-Gly-Val-Cit-*, Gly-Gly-Phe-Gly-*, Lys-Gln-Val-Cit-*, -Lys-Gln-Val-Ala-*, -Lys-Glu-Val-Cit-*, -Lys-Glu-Val-ALa-*, -Lys-Asp-Val-Cit-*, -Lys-Asp-Val-Ala-*, Glu-Val-Cit-*, Glu-Val-Ala-*, -Lys-Val-Ala-*, -Lys-Val-Cit*, -Val-Lys-Gly-*, and -Val-Lys-*;preferably, -GlyPhe-Gly-*, -Gly-Val-Cit-*, -Val-Cit-*, -Gly-Val-Ala-*, -ValAla-*, -Gly-Phe-Gly-*, -Phe-Gly-*, -Gly-Phe-Lys-, -Phe-Lys*, -Gln-Val-Ala-*, -Gln-Val-Cit-*, -Asp-Val-Ala-*, -Lys-GlyVal-Ala-*, -Lys-Gly-Val-Cit-*, -Lys-Gly-Gly-Val-Ala-*, Lys-Gly-Gly-Val-Cit-*, Gly-Gly-Phe-Gly-*, -Lys-Gln-Val-Cit*, -Lys-Gln-Val-Ala-*, -Lys-Glu-Val-Cit-*, -Lys-Glu-ValALa-*, -Lys-Asp-Val-Cit-*, -Lys-Asp-Val-Ala-*, Glu-Val-Cit*, Glu-Val-Ala-*, -Lys-Val-Ala-*, -Lys-Val-Cit-*, -Val-LysGly-*, -Val-Lys-*, and -Asp-Val-Cit-*.;

[0034] In another preferred embodiment, in the compound represented by the general formula (A), or in its salt Petition 870260084912, dated 08 / 20 / 2026, page 68 / 1402 61 / 694 pharmaceutically acceptable, according to the present invention, L'ib is an amino acid residue formed by one or more amino acids selected from glycine, phenylalanine, citrulline, leucine, isoleucine, alanine, valine, asparagine, glutamine, arginine, glutamic acid and lysine; or, preferably, an amino acid residue formed by two or more amino acids selected from glycine, phenylalanine, citrulline, leucine, aspartic acid, alanine, valine, glutamine, glutamic acid and lysine;most preferably selected from -Gly-*, -Val-*, -Gly-Phe-Gly-*, -Phe-Gly*, -Gly-Val-Cit-*, -Val-Cit-*, -Gly-Val-Arg-*, -Val-Arg-*, -Gly-Val-Ala-*, -Val-Ala-*, -Gly-Phe-*, -Phe-Gly-*, -GlyGly-Gly-*, Gly-Gly-*, -Gly-Val-Gly-*, -Gly-Ala-Gly-*, -GlyPhe-Cit-*, -Gly-Phe-Val-*, -Gly-Phe-Ala-*, -Gly-Phe-Lys-*, -Phe-Lys-*, -Gly-Val-*, -Gly-Cit-*, -Gly-Ala-*, -Gly-GlyLys-*, Gly-Lys'-*, -Ala-Ala-Ala-*, -Gln-Val-Ala-*, -Gln-ValCit-*, -Asp-Val-Ala-*, -Asp-Val-Cit-*, -Lys-Gly-Val-Ala-*, -Lys-Gly-Val-Cit-*, -Lys-Gly-Gly-Val-Ala-*, -Lys-Gly-GlyVal-Cit-*, Gly-Gly-Phe-Gly-*, -Lys-Gln-Val-Cit-*, -Lys-GlnVal-Ala-*, -Lys-Glu-Val-Cit-*, -Lys-Glu-Val-ALa-*, -LysAsp-Val-Cit-*, -Lys-Asp-Val-Ala-*, Glu-Val-Cit-*, Glu-ValAla-*, -Lys-Val-Ala-*, -Lys-Val-Cit-*, -Val-Lys-Gly-*, and -Val-Lys-*; preferably, -Gly-Phe-Gly-*, -Gly-ValCit-*, -Val-Cit-*, -Gly-Val-Ala-*, -Val-Ala-*, -Gly-Phe-Gly*, -Phe-Gly-*, -Gly-Phe-Lys-, -Phe-Lys-*, -Gln-Val-Ala-*, Petition 870260084912, dated 08 / 20 / 2026, page 69 / 1402; 62 / 694 Gln-Val-Cit-*, -Asp-Val-Ala-*, -Lys-Gly-Val-Ala-*, -LysGly-Val-Cit-*, -Lys-Gly-Gly-Val-Ala-*, -Lys-Gly-Gly-ValCit-*, Gly-Gly-Phe-Gly-*, -Lys-Gln-Val-Cit-*, -Lys-Gln-ValAla-*, -Lys-Glu-Val-Cit-*, -Lys-Glu-Val-ALa-*, -Lys-AspVal-Cit-*, -Lys-Asp-Val-Ala-*, Glu-Val-Cit-*, Glu-Val-Ala-*, -Lys-Val-Ala-*, -Lys-Val-Cit-*, -Val-Lys-Gly-*, -Val-Lys-*, and -Asp-Val-Cit-*.

[0035] In another preferred embodiment, in the compound represented by general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, Lib and L'ib are -Gly-* or -Val-*.

[0036] In another preferred embodiment, in the compound represented by general formula (A), or in its pharmaceutically acceptable salt, according to the present invention, the compound is selected from: Petition 870260084912, dated 08 / 20 / 2026, page 70 / 1402 63 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 71 / 1402 64 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 72 / 1402 65 / 694 OH OH LY-18B Petition 870260084912, dated 08 / 20 / 2026, p. 73 / 1402 66 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 74 / 1402 67 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 75 / 1402 68 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 76 / 1402 69 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 77 / 1402 70 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 78 / 1402 71 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 79 / 1402 72 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 80 / 1402 73 / 694 O Petition 870260084912, dated 08 / 20 / 2026, p. 81 / 1402 74 / 694 LY-34 Petition 870260084912, dated 08 / 20 / 2026, p. 82 / 1402 75 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 83 / 1402 76 / 694 LY-42A Petition 870260084912, dated 08 / 20 / 2026, p. 84 / 1402 77 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 85 / 1402 78 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 86 / 1402 79 / 694 OH OH Petition 870260084912, dated 08 / 20 / 2026, p. 87 / 1402 80 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 88 / 1402 81 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 89 / 1402 82 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 90 / 1402 83 / 694

[0037] Another aspect of the present invention provides a compound represented by the general formula (I) or a stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof; Petition 870260084912, dated 08 / 20 / 2026, p. 91 / 1402 84 / 694 (I) in which, R8 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl and alkynyl groups, wherein the alkyl, alkoxyl, alkenyl and alkynyl groups may be further replaced by one or more groups selected from halogen; R9 is selected from hydrogen, halogen, hydroxyl, carboxyl, cyano, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, -NRdRe, -(CH2U-OH, -(CH2) m-NRdRe, -OC(=O)NRf(CH2)m-OH, -OC(=O)NRf-(CH2)m-NRdRe, -(CH2) mC(=O)OH, -(CH2UC(=O)-NRdRe, -(CH2) mC(=O)NRf-(CH2) n-OH, -(CH2) mC(=O)NRf(CH2) n-NRdRe, -NRf-(CH2) m-OH, -NRf-(CH2) m-NRdRe, -O-(CH2) m-OH, O-(CH2) m-NRdRe, -NRfC(=O)O-(CH2) m-OH, -NRbC(=O)O-(CH2) m-NRdRe, -(CH2)m-NRfC(=O)O-(CH2)n-OH, -(CH2)m-NRfC(=O)O-(CH2)n-NRdRe, (CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-OH, (CH2)m-NRfC(=O)-(CH2)n-NRdRe, -(CH2)m-NRfC(=O)-(CH2)n-OH, and (CH2)m-NRfC(=O)-G-(CH2)n-OH, where alkyl, alkoxy, alkenyl, alkynyl, and cycloalkyl are optionally substituted by one or more groups selected from deuterium, halogen, Petition 870260084912, dated 08 / 20 / 2026, page 92 / 1402 85 / 694 amino, alkyl and hydroxyl; and the -(CH2)m- group is optionally replaced by one or more deuterium or halogen atoms; G is selected from cycloalkylene, heterocycloalkylene, heteroarylene, and arylene. R10 is selected from hydrogen, halogen, hydroxyl, cyano, alkyl, alkoxy, alkenyl, alkynyl, CH2=, -NRdRe, -(CH2)m-OH, -(CH2)m-NRdRe, -OC(=O)NRf-(CH2)m-OH, -OC(=O)NRf(CH2)m-NRdRe, -(CH2)mC(=O)OH, -(CH2)mC(=O)-NRdRe, -(CH2)mC(=O)NRf-(CH2)n-OH, -(CH2)mC(=O)NRf-(CH2)n-NRdRe, -NRf-(CH2)mOH, -NRf-(CH2)m-NRdRe, -NRf-C(=O)Rd, -NRf-C(=O)-(CH2)m-Rd, NRfC(=O)O-(CH2)m-Rd, -O-(CH2)m-OH, -O-(CH2)m-NRdRe, -NRfC(=O)O(CH2)m-OH, -NRfC(=O)NRd-(CH2)m-OH, -NRfC(=O)NRd-(CH2)mO(CH2)n-OH, -NRfC(=O)O-(CH2)mO-(CH2)n-OH, -NRfC(=O)NRd-(CH2)mO-(CH2)n-NRdRe, -NRfC(=O)O-(CH2)mO-(CH2)n-NRdRe, -NRfC(=O)NRd(CH2)m-NRdRe, -NRfC(=O)O-(CH2)m-NRdRe, -(CH2)m-NRfC(=O)O-(CH2)nOH, -(CH2)m-NRfC(=O)O-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)nNRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-OH, -(CH2)m-NRfC(=O)-(CH2)nNRdRe, and -(CH2)m-NRfC(=O)-(CH2)n-OH, wherein the alkyl, alkoxy, alkenyl and alkynyl groups are optionally replaced by one or more groups selected from halogens; Rde Resão, each independently selected from hydrogen and C1-C6 alkyl; Petition 870260084912, dated 08 / 20 / 2026, page 93 / 1402 86 / 694 Rf is selected from hydrogen, C1-Ce alkyl, -C(O)Rc, -S(O)Rc, and -S(O)2Rc, wherein the C1-Ce alkyl is optionally replaced by a C1-Ce cycloalkyl; and Rc is selected from hydrogen, hydroxyl, and C1-Ce alkyl; m is an integer from 1 to 6; en is an integer from 1 to 6.

[0038] In a preferred embodiment, in the compound represented by general formula (I), or in its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or even in its pharmaceutically acceptable salt, R8 is a halogen, preferably fluorine or chlorine.

[0039] In another preferred embodiment, in the compound represented by general formula (I), or in its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or in a mixture thereof, or even in its pharmaceutically acceptable salt, according to the present invention, R9 is selected from hydroxyl, C1-C1 alkyl, C1-C1 alkoxy, C1-C1 cycloalkyl, -NRdRe, -(CH2)m-OH, -(CH2)mNRdRe, -(CH2)m-NRbC(=O)O-(CH2)n-OH, -(CH2)m-OC(=O)NRf-(CH2)n-OH, -(CH2)m-NRfC(=O)-(CH2)n-OH, -O-(CH2)m-NRdRe, -O-(CH2)m-OH, and (CH2)m-NRfC(=O)-G-(CH2)n-OH; and -(CH2)m- is optionally replaced by one or more deuterium or halogen atoms.

[0040] G is selected from cycloalkylene, Petition 870260084912, dated 08 / 20 / 2026, page 94 / 1402 87 / 694 heterocycloalkylene, heteroarylene and arylene.

[0041] Rd and Re each independently, selected from hydrogen and Ci-Ce alkyl, or preferably hydrogen; Rfé selected between hydrogen and C1-C1e alkyl, preferably hydrogen; m is an integer from 1 to 6, preferably from 1 to 4; n is an integer from 1 to 6, preferably 1 or 2.

[0042] In another preferred embodiment, in the compound represented by general formula (I), or in its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or even in its pharmaceutically acceptable salt, according to the present invention, R10 is selected from hydrogen, hydroxyl, amino, -(CH2)m-OH, -OC(=O)NRf-(CH2)m-OH, -(CH2)mC(=O)OH, (CH2)mC(=O)NRf-(CH2)n-OH, -NRf-(CH2)m-OH, -NRfC(=O)O-(CH2)m-OH, -NRfC(=O)NRd-(CH2)m-OH, -NRfC(=O)NRd-(CH2)mO-(CH2)n-OH, NRfC(=O)O-(CH2)mO-(CH2) n-OH, -NRfC(=O)NRd- (CH2) mO- (CH2) nNRdRe, -NRfC(=O)O-(CH2) mO-(CH2) n-NRdRe, -NRfC(=O)NRd-(CH2) mNRdRe, and -NRfC(=O)O-(CH2)m-NRdRe; Each one independently, selected from Petition 870260084912, dated 08 / 20 / 2026, page 95 / 1402 88 / 694 hydrogen and C1-C1 alkyl, or preferably hydrogen; Rf is selected from hydrogen, C1-Ce alkyl, -C(O)Rc, -S(O)Rc, and -S(O)2Rc, wherein Rc is selected from hydrogen, hydroxyl, and C1-Ce alkyl; m is an integer from 1 to 6, preferably from 1 to 4, more preferably 1 or 2; en is an integer from 1 to 6, preferably 1 or 2.

[0043] In another preferred embodiment, in the compound represented by general formula (I), or in its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or even in its pharmaceutically acceptable salt, according to the present invention, R9 is selected from hydrogen, C1-C1 alkyl, C1-C1 alkoxy, hydroxyl, carboxyl, -NRdRe, -(CH2)m-OH, (CH2)m-NRdRe, -(CH2)m-NRfC(=O)O-(CH2)n-OH, -(CH2)m-OC(=O)NRf(CH2)n-OH, -(CH2)m-NRfC(=O)-(CH2)n-OH, -O-(CH2)m-NRdRe, and -O(CH2)m-OH; Rde Resão, each independently selected from hydrogen and C1-C1 alkyl; Rfé selected between hydrogen and C1-Ce alkyl; m is an integer from 1 to 6; en is an integer from 1 to 4, preferably 1 or Petition 870260084912, dated 08 / 20 / 2026, page 96 / 1402 89 / 694 2.

[0044] In another preferred embodiment, in the compound represented by general formula (I), or in its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or in a mixture thereof, or even in its pharmaceutically acceptable salt, according to the present invention, R10 is selected from hydrogen, hydroxyl, amino, CH2=, -(CH2U-OH, -OC(=O)NRf-(CH2) m-OH, -(CH2) mC(=O)OH, -(CH2) mC(=O)NRf-(CH2) n-OH, -NRf-(CH2) m-OH, -NRf-C(=O)Rd, -NRfC(=O)-(CH2) m-Rd, -NRfC(=O)O-(CH2) m-Rd, -NRf-C(=O)-(CH2) m-OH, and -NRfC(=O)O-(CH2)m-OH; Rde Resão, each independently selected from hydrogen and C1-C1 alkyl; Rf is selected from hydrogen, C1-Ce alkyl, -C(O)Rc, -S(O)Rc, and -S(O)2Rc, wherein the C1-Ce alkyl is optionally replaced by C3-C6 cycloalkyl; and Rc is selected from hydrogen, hydroxyl, and C1-Ce alkyl; m is an integer from 1 to 6; preferably an integer from 1 to 4 or an integer from 4 to 6; en is an integer from 1 to 4, preferably 1 or 2.

[0045] In another preferred embodiment, the compound represented by the general formula (I), or its Petition 870260084912, dated 08 / 20 / 2026, p. 97 / 1402 90 / 694 stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or a pharmaceutically acceptable salt thereof, according to this Petition 870260084912, dated 08 / 20 / 2026, p. 98 / 1402 91 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 99 / 1402 92 / 694 Petition 870260084912, dated 08 / 20 / 2026, pp. 100 / 1402 93 / 694 Petition 870260084912, dated 08 / 20 / 2026, pp. 101 / 1402 94 / 694 Petition 870260084912, dated 08 / 20 / 2026, p. 102 / 1402 95 / 694 Petition 870260084912, dated 08 / 20 / 2026, pp. 103 / 1402 96 / 694

[0046] Yet another aspect of the present invention relates to a compound represented by the general formula (II), or to a stereoisomer, tautomer, mesomer, racemate, Petition 870260084912, dated 08 / 20 / 2026, pp. 104 / 1402 97 / 694 enantiomer or diastereomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt of said compound; R11R12 (II) in which, R11 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl and alkynyl groups, and the alkyl, alkoxyl, alkenyl and alkynyl groups may be further replaced by one or more groups selected from halogen groups; R12 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxy, alkenyl, alkynyl, -NRdRe, -(CHa)m-OH, -(CH2)m-NRdRe, -OC(=O)NRf(CHa)m-OH, -OC(=O)NRf-(CH2)m-NRdRe, -(CH2)mC(=O)OH, -(CHa)mC(=O)-NRdRe, -(CH2)mC(=O)NRf-(CH2)n-OH, -(CH2)mC(=O)NRf(CH2)n-NRdRe, -NRf-(CH2)m-OH, -NRf-(CHa)m-NRdRe, -O-(CH2)m-OH, O-(CH2)m-NRdRe, -NRfC(=O)O-(CH2)m-OH, -NRbC(=O)O-(CHa) m-NRa-*, -(CH2) m-NRbC(=O)O-(CH2) nO-*, -(CH2) m-NRfC(=O)O-(CH2) n-NRdRe, (CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-OH, (CH2)m-NRfC(=O)-(CH2)n-NRdRe, and -(CH2)m-NRfC(=O)-(CH2)n-OH, Petition 870260084912, dated 08 / 20 / 2026, page 105 / 1402 98 / 694 wherein the alkyl, alkoxy, alkenyl and alkynyl groups are optionally replaced by one or more groups selected from halogens; R13 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxy, alkenyl, alkynyl, -NRdRe, -(CH2U-OH, -(CH2) m-NRdRe, -OC(=O)NRf(CH2)m-OH, -OC(=O)NRf-(CH2)m-NRdRe, -(CH2) mC(=O)OH, -(CH2UC(=O)-NRdRe, -(CH2) mC(=O)NRf-(CH2) n-OH, -(CH2) mC(=O)NRf(CH2) n-NRdRe, -NRf-(CH2) m-OH, -NRf-(CH2) m-NRdRe, -O-(CH2) m-OH, O-(CH2) m-NRdRe, -NRfC(=O)O-(CH2) m-OH, -NRbC(=O)O-(CH2) m-NRa-*, -(CH2) m-NRbC(=O)O-(CH2) nO-*, -(CH2) m-NRfC(=O)O-(CH2) n-NRdRe, (CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-OH, (CH2)m-NRfC(=O)-(CH2)n-NRdRe, and -(CH2)m-NRfC(=O)-(CH2)n-OH, wherein the alkyl, alkoxy, alkenyl and alkynyl groups are optionally replaced by one or more groups selected from halogens; Rde Resão, each independently selected from hydrogen and C1-C1 alkyl; Rf is selected from hydrogen, C1-Ce alkyl, -C(O)Rc, -S(O)Rc, and -S(O)2Rc, wherein Rc is selected from hydrogen, hydroxyl, and C1-Ce alkyl; m is an integer from 1 to 6; en is an integer from 1 to 6. Petition 870260084912, dated 08 / 20 / 2026, page 106 / 1402 99 / 694

[0047] In a preferred embodiment, in the compound represented by general formula (II), or in its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or in a mixture thereof, or even in its pharmaceutically acceptable salt, according to the present invention, R11 is selected from halogen, preferably fluorine or cyano.

[0048] In another embodiment preferably used, in the compound represented by general formula (II) or the stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer thereof, or a mixture thereof, or the pharmaceutically acceptable salt thereof, according to the present invention, Ri2 is selected from hydroxyl, amino, a C1-C1 alkyl, -(CH2U-OH, and -(CH2)m-NRdRe; Rde Resão each one selected independently between hydrogen and Ci-Ce alkyl; em is an integer from 1 to 6; preferably, an integer from 1 to 4.

[0049] In another preferred embodiment, in the compound represented by general formula (II), or in its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or in a mixture thereof, or even in its pharmaceutically acceptable salt, according to the present invention, R“ is selected between hydroxyl and amino. Petition 870260084912, dated 08 / 20 / 2026, page 107 / 1402 100 / 694

[0050] In another embodiment preferably used, in the compound represented by general formula (II) or the stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer thereof, or a mixture thereof, or the pharmaceutically acceptable salt thereof, according to the present invention, R13 is selected from hydroxyl and C1-C6 alkoxy.

[0051] In another preferred embodiment, the compound represented by general formula (II), or its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or even its pharmaceutically acceptable salt, according to the present invention, is selected from: Petition 870260084912, dated 08 / 20 / 2026, p. 108 / 1402 101 / 694 HO PY-29A

[0052] Yet another aspect of the present invention provides a ligand-drug conjugate represented by general formula (B) or a pharmaceutically acceptable salt thereof; Pc--L'--L2—L-,—Dr (B) where: Dr. is selected from among the following structures: Petition 870260084912, dated 08 / 20 / 2026, p. 109 / 1402 102 / 694 R1 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, -NRdRe, -(CH2U-OH, -(CH2) m-NRdRe, -OC(=O)NRf(CH2)m-OH, -OC(=O)NRf-(CH2)m-NRdRe, -(CH2) mC(=O)OH, -(CH2UC(=O)-NRdRe, -(CH2) mC(=O)NRf-(CH2) n-OH, -(CH2) mC(=O)NRf(CH2) n-NRdRe, -NRf-(CH2) m-OH, -NRf-(CH2) m-NRdRe, -O-(CH2) m-OH, O-(CH2) m-NRdRe, -NRfC(=O)O-(CH2) m-OH, -NRbC(=O)O-(CH2) m-NRdRe, -(CH2)m-NRfC(=O)O-(CH2)n-OH-, -(CH2)m-NRfC(=O)O-(CH2)n-NRdRe, (CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-OH, (CH2)m-NRfC(=O)-(CH2)n-NRdRe, -(CH2)m-NRfC(=O)-(CH2)n-OH, and (CH2)m-NRfC(=O)-G-(CH2)n-OH, wherein the alkyl, alkoxy, alkenyl, alkynyl, and cycloalkyl groups are optionally substituted by one or more groups selected from halogen, deuterium, amino, alkyl, and hydroxyl; the group -(CH2)m- is optionally replaced by one or more deuterium atoms or halogen groups;and G is selected from cycloalkylene, heterocycloalkylene, heteroarylene, and arylene; R2 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl, and alkynyl. Petition 870260084912, dated 08 / 20 / 2026, page 110 / 1402 103 / 694 wherein the alkyl, alkoxyl, alkenyl and alkynyl groups may be further substituted by one or more groups selected from halogen; R3 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl, alkynyl, CH2=, -NRdRe, -(CH2)m-OH, -(CH2)m-NRdRe, -OC(=O)NRf-(CH2)m-OH, OC(=O)NRf-(CH2)m-NRdRe, -(CH2)mC(=O)OH, -(CH2)mC(=O)-NRdRe, (CH2)mC(=O)NRf-(CH2)n-OH, -(CH2)mC(=O)NRf-(CH2)n-NRdRe, -NRf(CH2)m-OH, -NRf-(CH2)m-NRdRe, -NRf-C(=O)Rd, -NRf-C(=O)-(CH2)mRd, -NRfC(=O)O-(CH2)m-Rd, -O-(CH2)m-OH, -O-(CH2)m-NRdRe, NRfC(=O)O-(CH2)m-OH, -NRfC(=O)NRd-(CH2)m-OH, -NRfC(=O)NRd(CH2)mO-(CH2)n-OH, -NRfC(=O)O-(CH2)mO-(CH2)n-OH, NRfC(=O)NRd-(CH2)mO-(CH2)n-NRdRe, -NRfC(=O)O-(CH2)mO-(CH2)nNRdRe, -NRfC(=O)NRd-(CH2)m-NRdRe, -NRfC(=O)O-(CH2)m-NRdRe, (CH2)m-NRfC(=O)O-(CH2)n-OH, -(CH2)m-NRfC(=O)O-(CH2)n-NRdRe, (CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-OH, (CH2)m-NRfC(=O)-(CH2)n-NRdRe, and -(CH2)m-NRfC(=O)-(CH2)n-OH, wherein the alkyl, alkoxyl, alkenyl, and alkynyl groups may be further substituted by one or more groups selected from halogen, deuterium, amino,alkyl and hydroxyl; R4 is selected from hydrogen, halogen, hydroxyl, carboxyl, amino, cyano, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, -NRdRe, -(CH2)m-OH, Petition 870260084912, dated 20 / 08 / 2026, page 111 / 1402 104 / 694 (CH2) m-NRdRe, -OC(=O)NRf-(CH2) m-OH, -OC(=O)NRf-(CH2) m-NRdRe, (CH2) mC(=O)OH, - (CH2) mC(=O) -NRdRe, - (CH2) mC(=O)NRf- (CH2) n-OH, - (CH2) mC(=O)NRf- (CH2) n-NRdRe, -NRf- (CH2) m-OH, -NRf- (CH2) m-NRdRe, -O-(CH2) m-OH, -O-(CH2) m-NRdRe, -NRfC(=O)O-(CH2) m-OH, NRbC(=O)O-(CH2) m-NRdRe, -(CH2) m-NRfC(=O)O-(CH2) n-OH-, -(CH2)mNRfC(=O)O-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)mOC(=O)NRf-(CH2)n-OH, -(CH2)m-NRfC(=O)-(CH2)n-NRdRe, -(CH2)mNRfC(=O)-(CH2)n-OH, and -(CH2)m-NRfC(=O)-G-(CH2)n-OH, wherein the alkyl, alkoxy, alkenyl, alkynyl and cycloalkyl groups may optionally be replaced by one or more groups selected from halogen, deuterium, amino, alkyl and hydroxyl; the -(CH2)m- group may optionally be replaced by one or more deuterium or halogen atoms; and G is selected from cycloalkylene, heterocyclylene, heteroarylene, and arylene. R5 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl and alkynyl groups, wherein the alkyl, alkoxyl, alkenyl and alkynyl groups may be further replaced by one or more groups selected from halogen; R6 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl, and alkynyl groups, with the alkyl, alkoxyl, alkenyl, and alkynyl groups being able to be further replaced by one or more other groups. Petition 870260084912, dated 08 / 20 / 2026, page 112 / 1402 105 / 694 selected from halogen; R7 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl and alkynyl groups, wherein the alkyl, alkoxyl, alkenyl and alkynyl groups may be further replaced by one or more groups selected from halogen; Rde Resão, each independently selected from between hydrogen and alkyl; Rf is selected from hydrogen, alkyl, -C(O)Rc, S(O)Rc, and -S(O)2Rc, wherein the C1-Ce alkyl group may optionally be replaced by a C1-Ce cycloalkyl group; and Rc is selected from hydrogen, hydroxyl, and alkyl. Li is selected from a linkage, -(CRU-*, -O-*, NRa-*, -(CH2)mO-*, -(CH2)m-NRa-*, -OC(=O)NRb-(CH2)mO-*, OC(=O)NRb-(CH2)m-NRa-*, -(CH2)mC(=O)O-*, -(CH2)mC(=O)NRa-*, -(CH2)mC(=O)NRb-(CH2)nO-*, -(CH2)mC(=O)NRb-(CH2)n-NRa-*, NRb-(CH2)mO-*, -NRb-(CH2)m-NRa-*, -O-(CH2)mO-*, -O-(CH2)mNRa-*, -NRbC(=O)O-(CH2)mO-*, -NRbC(=O)O-(CH2)m-NRa-*, -(CH2)mNRbC(=O)O-(CH2)nO-*, -(CH2)m-NRbC(=O)O-(CH2)n-NRa-*, -(CH2)mOC(=O)NRb-(CH2)n-NRa-*, -(CH2)m-OC(=O)NRb-(CH2)nO-*, -(CH2)mNRbC(=O)-(CH2)n-NRa-*, and -(CH2)m-NRbC(=O)-(CH2)nO-*, where * indicates the point of attachment to L2; Rae Rbsão, each independently selected from hydrogen, alkyl, -C(O)Rc, -S(O)Rc, and -S(O)2Rc, being Petition 870260084912, dated 08 / 20 / 2026, pp. 113 / 1402 106 / 694 that the alkyl group can be additionally replaced by cycloalkyl; and Rc is selected from hydrogen, hydroxyl, and alkyl; L2 is selected from a 5 HH, O1, and H linkage with Li; OO L' is either V; vXN~· ¢( Q' is selected from °, ' 0 a. -ç a; , —, , , , —, , 0 9 HTj Í HIJ H, , O; where * is a linkage site with L4, and linkage with Pc; u ρρ°Λ* H, , where * is a linkage site O —-χH� N' -Λ?0-, , íl O 1 r\ μι Γ* 1 W υλ=Α° -* , o * , O , 0 HbQ^· , , and é is a linkage site Petition 870260084912, dated 08 / 20 / 2026, p. 114 / 1402 107 / 694 La is an amino acid residue formed by two or more amino acids, and La may optionally contain one or more of the following structures; and La is selected from one or more of the following structures: or where R, Ra, and Rbb are each independently selected from hydrogen and alkyl; Petition 870260084912, dated 08 / 20 / 2026, pp. 115 / 1402 108 / 694 L4 is Zi is selected from a bond, -(CH2)p-, -(C2H4O)q-, -(CH2)pC(O)NH-, -(CH2)pO-(CH2)pC(O)NH-, -(CH2) pC(O)-Le-NH-, -(CH2)pO-(CH2)pC(O)-L6-NH-, -C(O)NH-, -C(O)O-, -C(O)-,OC(O)-, -NH-, -O-, and -OC(O)NH-; m is an integer from 1 to 6; n is an integer from 1 to 6; s is an integer from 1 to 6; t is an integer from 0 to 10; if S2, S3, and S4 are each independently an integer from 0 to 10; preferably from 0 to 8 or from 0 to 6; more preferably from 0 to 4; even more preferably from 0 to 2, or from 1 to 2; sã and s6 are, each independently, an integer from 1 to 6; ti is an integer from 1 to 6; t2 is an integer from 0 to 6; t3 is an integer from 1 to 6; t4 is an integer from 0 to 10; ts is an integer from 0 to 10; Petition 870260084912, dated 08 / 20 / 2026, page 116 / 1402 109 / 694 p is an integer from 1 to 10; q is an integer from 1 to 10; v ranges from 1 to 10, being either a decimal or integer number; Pc is an antibody or an antigen-binding fragment derived from an antibody, or even a modified antibody; The modified antibody has a Pc'-((L5)wF)x structure where: 'Pc' is an antibody; L5 is a binding unit; w is 0 or 1; F is a clickable probe or a sulfhydryl group or a precursor thereof that can be attached to Q' after a reaction, such as a metal-free click reaction, and preferably F is an azide group; ex is an integer from 1 to 8; Zi is connected to Q'.

[0053] In a preferred embodiment, in the ligand-drug conjugate represented by general formula (B) or by the corresponding pharmaceutically acceptable salt, according to the present invention, La is selected from: Petition 870260084912, dated 08 / 20 / 2026, page 117 / 1402 110 / 694 Petition 870260084912, dated 08 / 20 / 2026, page 118 / 1402 111 / 694 o N'r / OH 7—\ PH «o / ° / —. OH HO ÒH Raa Ν' - / «5 YLlb^NAfL'i< H 0 HO. ho\oh η(Ατοη OH OH Ή OH OH HO^ OH / —( 0H HO )—( / HO HO J \ HO 'r / —\ θΗ HO OH / H ά '2 '3 , OH Âxyy tlH R '2 '3 , , HO. ho-Voh ΗΟ*η-ΟΗ O^N'R .. V-aY- e , , e oX / 4 NH / * xi / v / rr N π νΎ N-L1b YH g HX , Petition 870260084912, dated 08 / 20 / 2026, page 119 / 1402 112 / 694 where R is selected between hydrogen and C1-C1 alkyl, hydrogen being preferred. Raae Rbbsão each one selected independently from Ci-Ce alkyl; s is an integer from 1 to 6; preferably, an integer from 2 to 6; more preferably, from 2 to 4; If they are, each independently, an integer from 1 to 6; preferably from 2 to 6; most preferably from 2 to 4; t is an integer from 0 to 10; preferably from 2 to 8; most preferably from 3 to 7; ti is an integer from 1 to 6; preferably from 1 to 4; more preferably from 2 to 4; or even more preferably, 1 or 2; t2 is an integer from 1 to 6; preferably from 1 to 4; most preferably 0 or 2; ta is an integer from 1 to 6; preferably from 1 to 4; most preferably 1 or 2; t4 is an integer from 0 to 10; ts is an integer from 0 to 10; • represents the binding site with L2; It is a site of connection with a carbonyl or methylene group; Petition 870260084912, dated 08 / 20 / 2026, pp. 120 / 1402 113 / 694 Lib and L'ib are, each independently, amino acid residues formed by one or more amino acids selected from glycine, phenylalanine, citrulline, leucine, isoleucine, alanine, valine, asparagine, glutamine, arginine, glutamic acid and lysine; preferably, amino acid residues formed by two or more amino acids selected from glycine, phenylalanine, citrulline, valine, lysine, glutamine, glutamic acid, leucine and alanine; and preferably, Lib and L'ib are each independently selected from -Gly-*, -Val-*, -GlyPhe-Gly-*, -Phe-Gly-*, -Gly-Val-Cit-*, -Val-Cit-*, -Gly-ValArg-*, -Val-Arg-*, -Gly-Val-Ala-*, -Val-Ala-*, -Gly-Phe-*, -Phe-Gly-*, -Gly-Gly-Gly-*, Gly-Gly-*, -Gly-Val-Gly-*, -GlyAla-Gly-*, -Gly-Phe-Cit-*, -Gly-Phe-Val-*, -Gly-Phe-Ala-*, -Gly-Phe-Lys-*, -Phe-Lys-*, -Gly-Val-*, -Gly-Cit-*, -GlyAla-*, -Gly-Gly-Lys-*, Gly-Lys'-*, -Ala-Ala-Ala-*, -Gln-ValAla-*, -Gln-Val-Cit-*, -Asp-Val-Ala-*, and -Asp-Val-Cit-*;preferably, -Gly-Phe-Gly-*, -Gly-Val-Cit-*, -ValCit-*, -Gly-Val-Ala-*, -Val-Ala-*, -Gly-Phe-Gly-*, -Phe-Gly*, -Gly-Phe-Lys-, -Phe-Lys-*, -Gln-Val-Ala-*, -Gln-Val-Cit*, -Asp-Val-Ala-*, and -Asp-Val-Cit-, where * indicates the point of connection with L2.;

[0054] In a preferred embodiment, in the ligand-drug conjugate represented by the general formula (B) or by Petition 870260084912, dated 08 / 20 / 2026, pp. 121 / 1402 114 / 694 corresponding pharmaceutically acceptable salt, according to the present invention, L' the is selected from Where * indicates the connection point with L4, and is the connection point with Pc; L3 is an amino acid residue formed by two or more amino acids selected from glycine, phenylalanine, citrulline, leucine, isoleucine, alanine, valine, asparagine, glutamine, arginine, glutamic acid, and lysine; or, preferably, an amino acid residue formed by two or more amino acids selected from glycine, phenylalanine, citrulline, valine, lysine, glutamine, glutamic acid, leucine, and alanine; Petition 870260084912, dated 08 / 20 / 2026, pp. 122 / 1402 115 / 694 L4 is Zi is selected from among a linkage, -(CH2)p-, -(CH2)pC(O)NH-, -(CH2)pO-(CH2)pC(O)NH-, -(CH2)pC(O)-Le-NH-, (CH2)pO-(CH2)pC(O)-Le-NH-, -C(O)NH-, -C(O)O-, -C(O)-, OC(O)-, -NH-, -O-, and -OC(O)NH-; if it is an integer from 1 to 6; preferably, an integer from 2 to 6; S2 is an integer from 1 to 10; preferably, an integer from 2 to 10; S3 is 0; s4 is 0; p is an integer from 1 to 10; preferably, an integer from 1 to 6; more preferably, an integer from 2 to 4; and most preferably, an integer from 2 to 3. Le is selected from Petition 870260084912, dated 08 / 20 / 2026, pp. 123 / 1402 116 / 694 s is an integer from 1 to 6; preferably, an integer from 2 to 6; more preferably, from 2 to 4; t is an integer from 0 to 10; preferably from 0 to 8; most preferably from 3 to 7; and preferably L6 is

[0055] In a specific embodiment, in the ligand-drug conjugate represented by the general formula (B) or by its acceptable pharmaceutical salt, according to the present invention, There is Z2 and Z3 are each independently selected from -C(O)NH-, -C(O)O-, -C(O)-, -OC(O)-, -NH-, -O-, and OC(O)NH-, preferably -C(O)NH-; ri is an integer from 1 to 8; preferably, from Petition 870260084912, dated 08 / 20 / 2026, pp. 124 / 1402 117 / 694 to 6; more preferably, from 1 to 3; r2 is an integer from 1 to 6; preferably from 1 to 4; most preferably from 1 to 2; ra is an integer from 0 to 6; preferably from 0 to 4; most preferably from 0 to 2; r4 is an integer from 0 to 6; preferably from 0 to 4; most preferably from 0 to 2; and rs is an integer from 1 to 6; preferably from 1 to 4; most preferably from 1 to 2.

[0056] In another specific embodiment, in the ligand-drug conjugate represented by the general formula (B) or by its acceptable pharmaceutical salt according to the present invention, when w is 0, F is a sulfhydryl group; or, when w is 1, F is a clickable probe that can be connected to Q' after a reaction, such as a metal-free click reaction; and, preferably, F is an azide group.

[0057] In another specific embodiment, in the ligand-drug conjugate represented by the general formula (B) or by its acceptable pharmaceutical salt according to the present invention, Pc is a modified antibody, and the modified antibody has the following structure: Petition 870260084912, dated 08 / 20 / 2026, pp. 125 / 1402 118 / 694 where: 'Pc' is an antibody; Z2 and Z3 are each independently selected from -C(O)NH-, -C(O)O-, -C(O)-, -OC(O)-, -NH-, -O-, and OC(O)NH-, preferably -C(O)NH-; ri is an integer from 1 to 8; preferably from 1 to 6; most preferably from 1 to 3; r2 is an integer from 1 to 6; preferably from 1 to 4; more preferably from 1 to 2; r3 is an integer from 0 to 6; preferably from 0 to 4; most preferably from 0 to 2; r4 is an integer from 0 to 6; preferably from 0 to 4; most preferably from 0 to 2. rs is an integer from 1 to 6; preferably from 1 to 4; most preferably from 1 to 2.

[0058] In a preferred embodiment, in the ligand-drug conjugate represented by general formula (B) or by its acceptable pharmaceutical salt, according to the present invention, Pc is a modified antibody, and Pc-Q' is selected from: Petition 870260084912, dated 08 / 20 / 2026, pp. 126 / 1402 119 / 694 where Pc' is an antibody; Petition 870260084912, dated 08 / 20 / 2026, pp. 127 / 1402 120 / 694 Z2 and Z3 are each independently selected from -C(O)NH-, -C(O)O-, -C(O)-, -OC(O)-, -NH-, -O-, and OC(O)NH-, preferably -C(O)NH-; ri is an integer from 1 to 8; preferably from 1 to 6; most preferably from 1 to 3; r2 is an integer from 1 to 6; preferably from 1 to 4; most preferably from 1 to 2; r3 is an integer from 0 to 6; preferably from 0 to 4; most preferably from 0 to 2; r4 is an integer from 0 to 6; preferably from 0 to 4; most preferably from 0 to 2; and rs is an integer from 1 to 6; preferably from 1 to 4; most preferably from 1 to 2.

[0059] In a preferred embodiment, the ligand-drug conjugate represented by the general formula (B) or its acceptable pharmaceutical salt, selected from: HO, ho^Yoh xL _>OH HO*^ YO^N^t - <MM O H O H T-LY1 conforme a presente invenção, é / \Α^ρ Ο λ jTXj h 0 nCO N ]ÍT ,n^ A. H H A Ni N^ N ST 0 H n4 O=< / 0— > <0H 0^4 o —iv , Petition 870260084912, of 20 / 08 / 2026, p. 128 / 1402 121 / 694 YOUR. »OHkOH Ή H NH HN YOUR'*' THEIR N T-LY2 N F T-LY6 — v N H THEIR THEIR Pc· Petition 870260084912, of 20 / 08 / 2026, p. 129 / 1402 122 / 694 YOUR. HO*S*OHOH OH HO V01 l-LYo Ο Ο ΝΗΟ T-LY21C O O Petition 870260084912, dated 08 / 20 / 2026, pp. 130 / 1402 123 / 694 O T-LY22 'NO' H O o H o F Praça T-LY22AF — V H N T-LY-22C O Petition 870260084912, dated 08 / 20 / 2026, pp. 131 / 1402 124 / 694 Praça'· HN,,. T-LY22CC F the H N„ F the H F Petition 870260084912, dated 08 / 20 / 2026, pp. 132 / 1402 125 / 694 Petition 870260084912, dated 08 / 20 / 2026, pp. 133 / 1402 126 / 694 pc Petition 870260084912, dated 08 / 20 / 2026, pp. 134 / 1402 127 / 694 Praça F T-LY28B Praça T-LY28C Petition 870260084912, dated 08 / 20 / 2026, pp. 135 / 1402 128 / 694 Praça N H O Pc' o T-LY29B o o o T-LY29C V O O F T-LY33 Petition 870260084912, dated 08 / 20 / 2026, pp. 136 / 1402 129 / 694 Petition 870260084912, dated 08 / 20 / 2026, pp. 137 / 1402 130 / 694 Petition 870260084912, dated 08 / 20 / 2026, pp. 138 / 1402 131 / 694 Petition 870260084912, dated 08 / 20 / 2026, pp. 139 / 1402 132 / 694 HO NH THE OH OH T-LY46E Praça HQ OH QH OH I Q T-LY46G Q HN, \ HN,. NHQ -------'V Petition 870260084912, dated 08 / 20 / 2026, pp. 140 / 1402 133 / 694 Praça O T-LY47D N H N' H .O 'O' F O Praça O T-LY47E O Petition 870260084912, dated 08 / 20 / 2026, pp. 141 / 1402 134 / 694 O Praça HOHOOH O T-LY48C O ------!ν N H N H I-LY4BU F ο '-H·'N H O O, Petition 870260084912, dated 08 / 20 / 2026, page 142 / 1402 135 / 694 Praça □ T-LY49B □ ------!v , where v is from 1 to 10 and v is a decimal or an integer, Pc is an antibody or an antigen-binding fragment; 'Pc' is an antibody.

[0060] In some realizations in the conjugated link Petition 870260084912, of 20 / 08 / 2026, p. 143 / 1402 136 / 694 drug represented by general formula (B) or by its acceptable pharmaceutical salt, according to the present invention, the antibody is selected from: a murine antibody, a chimeric antibody, a humanized antibody, or a fully human antibody.

[0061] In other embodiments, in the ligand-drug conjugate represented by general formula (B) or in the pharmaceutically acceptable salt thereof, according to the present invention, the antibody or an antigen-binding fragment thereof is selected from anti-HER2 antibody (ErbB2), anti-EGFR antibody, anti-B7-H3 antibody, anti-c-Met antibody, anti-HER3 antibody (ErbB3), anti-HER4 antibody (ErbB4), anti-ROR1 antibody, anti-CLDN6 antibody, anti-CLDN9 antibody, anti-CLDN18 antibody.2, anti-NaPi-2b antibody, anti-TNF-α antibody, anti-ENPP3 antibody, anti-DLL3 antibody, anti-CD20 antibody, anti-CD22 antibody, anti-CD28 antibody, anti-CD30 antibody, anti-CD33 antibody, anti-CD37 antibody, anti-CD38 antibody, anti-CD44 antibody, anti-CD45 antibody, anti-CD47 antibody, anti-CD48 antibody, anti-CD56 antibody, anti-CD70 antibody, anti-CD73 antibody, anti-CD98 antibody, anti-CD105 antibody, anti-CEA antibody, anti-EphA2 antibody, anti-MUCI antibody, anti-Lewis Y antibody, anti-VEGFR antibody, anti-GPNMB antibody, antiPetição 870260084912, de 20 / 08 / 2026, p. 144 / 1402. 137 / 694 Integrin, anti-PSMA antibody, anti-Tenascin-C antibody, anti-SLC44A4 antibody, anti-CD79 antibody, anti-TROP-2 antibody, anti-CD79B antibody, anti-Mesothelin antibody, anti-Nectin-4 antibody, anti-TPBG antibody or a fragment of antigen binding.

[0062] In other embodiments, in the drug-linking conjugate represented by the general formula (B) or by its acceptable pharmaceutical salt, according to the present invention, the antibody or antigen-binding fragment is selected from Trastuzumab, Cetuximab, Pertuzumab, Nimotuzumab, Enoblituzumab, Emibetuzumab, Inotuzumab, Pinatuzumab, Brentuximab, Gemtuzumab, Bivatuzumab, Lorvotuzumab, or an antigen-binding fragment derived from any of these antibodies.

[0063] In other embodiments, the drug-binding conjugate represented by general formula (B) or its acceptable pharmaceutical salt, according to the present invention, is selected from: T-LY1 THE THE F U Petition 870260084912, dated 08 / 20 / 2026, pp. 145 / 1402 138 / 694 Trastuzumab Trastuzumab N =H N F T-LY6 Petition 870260084912, de 20 / 08 / 2026, pág. 146 / 1402 139 / 694 Trastuzumab Petition 870260084912, de 20 / 08 / 2026, pág. 147 / 1402 140 / 694 Trastuzumab OR THE THE T-LY22AD N OR The N,, The the F ---------'n, Trastuzumab THE T-LY22AF NIO N O' H THE The .N A Trastuzumab-- T-LY-22C Trastuzumab ,N o the T-LY22CC The New the F Petition 870260084912, dated 08 / 20 / 2026, pp. 148 / 1402 141 / 694 Trastuzumab F l-LYOZCU HH, IV, Trastuzumab F l-LYZZCt HN,_ Petition 870260084912, dated 08 / 20 / 2026, pp. 149 / 1402 142 / 694 Petition 870260084912, dated 08 / 20 / 2026, pp. 150 / 1402 143 / 694 Petition 870260084912, dated 08 / 20 / 2026, pp. 151 / 1402 144 / 694 Trastuzumab v Trastuzumab Trastuzumab Trastuzumab Trastuzumab T-LY29B N H NH Tratusumab T-LY29C Petition 870260084912, of 20 / 08 / 2026, p. 152 / 1402 145 / 694 Trastuzumab—J] S' Trastuzumab Ο NH H0 N Ό Ο Ο HN ο F T-LY33 Trastuzumab I-LY33A Trastuzumab ν Trastuzumab Trastuzumab Ο T-LY34C ObNHO OH hoA-oh Ο Ο OUR. OH OH A Yxoh ho hO Petition 870260084912, of 20 / 08 / 2026, p. 153 / 1402 146 / 694 Petition 870260084912, of 20 / 08 / 2026, p. 154 / 1402 147 / 694 Trastuzumab Trastuzumab ΗΟ £ Petition 870260084912, of 20 / 08 / 2026, p. 155 / 1402 148 / 694 Trastuzumab Ο Ο Ο ΗΟΗ<° ι ι^η ηο / ^Υιι Ύ ΟΗ ΟΗΟ T-LY44D Trastuzumab OH T-LY46D Trastuzumab NHO OH OH OH OH OH O .OH OH THEIR N H T-LY46E Petition 870260084912, of 20 / 08 / 2026, p. 156 / 1402 149 / 694 HQ Trastuzumab OH OH HQ HQ. OH Q T-LY46G H Ί. HN H N,„ Q Petition 870260084912, of 20 / 08 / 2026, p. 157 / 1402 150 / 694 Trastuzumab Trastuzumab I-LY4 / L THEIR THEIR Petition 870260084912, of 20 / 08 / 2026, p. 158 / 1402 151 / 694 ο HN ο Trastuzumab Trastuzumab Trastuzumab OH Ν H T-LY48B ------!ν C T.LY48C C Ι-ΙΥ4ΗΙ) T-LY48E NH H Ν NHC OH ΟΗ ο Trastuzumab Petition 870260084912, of 20 / 08 / 2026, p. 159 / 1402 152 / 694 Trastuzumab Trastuzumab T-LY5OA Trastuzumab □ □ I-LYNUd ,N. N. H, N. Trastuzumab N, where v is 'N' H N' H T-LY51A T-LY51B o 'N' H --------iv. HO ,N-.,.,.Λ THE N'0 H an integer or decimal number from 1 to, preferably, an integer from 2 to 8.

[0064] The present invention also relates to a pharmaceutical composition, which comprises the drug-ligand conjugate represented by general formula (B) or its acceptable pharmaceutical salt, as described in this invention, in combination with one or more acceptable pharmaceutical vehicles or excipients.

[0065] The present invention also relates to the use of the compound represented by the general formula (A) or its salt. Petition 870260084912, dated 08 / 20 / 2026, pp. 160 / 1402 153 / 694 acceptable pharmaceutical form, according to the present invention, in the preparation of a drug-ligand conjugate.

[0066] The present invention also relates to the use of the compound represented by general formula (I) or of its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or of its acceptable pharmaceutical salt, as described in the present invention, or to the use of the compound represented by general formula (II) or of its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or of its acceptable pharmaceutical salt, in the preparation of a ligand-drug conjugate.

[0067] The present invention also relates to the use of the drug-ligand conjugate or its acceptable pharmaceutical salt, or the pharmaceutical composition comprising it, as per the present invention, in the preparation of a medicament for the treatment of tumors or cancer, wherein the cancer is preferably breast cancer, ovarian cancer, soft tissue sarcoma, liposarcoma, lung cancer, non-small cell lung cancer, gastric cancer, melanoma, head and neck cancer, cervical cancer or prostate cancer.

[0068] The present invention also relates to the drug-ligand conjugate or to its acceptable pharmaceutical salt, or to Petition 870260084912, dated 08 / 20 / 2026, pp. 161 / 1402 154 / 694 pharmaceutical composition comprising, according to the present invention, for use in the treatment of tumors or cancers, wherein the cancer is preferably breast cancer, ovarian cancer, soft tissue sarcoma, liposarcoma, lung cancer, non-small cell lung cancer, gastric cancer, melanoma, head and neck cancer, cervical cancer or prostate cancer.

[0069] The present invention also relates to a method for treating tumors or cancers, comprising administering to a needy individual an effective amount of the drug-ligand conjugate or its acceptable pharmaceutical salt, or the pharmaceutical composition comprising it, as per the present invention, wherein the cancer is preferably breast cancer, ovarian cancer, soft tissue sarcoma, liposarcoma, lung cancer, non-small cell lung cancer, gastric cancer, melanoma, head and neck cancer, cervical cancer or prostate cancer.

[0070] The present invention also relates to the use of the compound represented by general formula (I) or of its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or of its acceptable pharmaceutical salt, or also to the compound represented by general formula (II) or of its stereoisomer, tautomer, Petition 870260084912, dated 08 / 20 / 2026, pp. 162 / 1402 155 / 694 mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or of an acceptable pharmaceutical salt thereof, or of the pharmaceutical composition comprising them, according to the present invention, for the preparation of a medicament intended for the treatment of tumors or cancers, wherein the cancer is preferably breast cancer, ovarian cancer, soft tissue sarcoma, liposarcoma, lung cancer, non-small cell lung cancer, gastric cancer, melanoma, head and neck cancer, cervical cancer or prostate cancer.

[0071] The present invention also relates to the compound represented by general formula (I) or to its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or to its acceptable pharmaceutical salt, or to the compound represented by general formula (II) or to its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or to its acceptable pharmaceutical salt, or even to the pharmaceutical composition comprising them, as per the present invention, for use in the treatment of tumors or cancers, wherein the cancer is preferably breast cancer, ovarian cancer, soft tissue sarcoma, liposarcoma, lung cancer, non-small cell lung cancer, gastric cancer, melanoma, head and neck cancer, cervical cancer Petition 870260084912, dated 08 / 20 / 2026, pp. 163 / 1402 156 / 694 or prostate cancer.

[0072] The present invention also relates to a method for treating tumors or cancers, comprising administering to a patient in need an effective amount of the compound represented by general formula (I) or of its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or of its acceptable pharmaceutical salt, or of the compound represented by general formula (II) or of its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or of its acceptable pharmaceutical salt, or of the pharmaceutical composition comprising them, as per the present invention, wherein the cancer is preferably breast cancer, ovarian cancer, soft tissue sarcoma, liposarcoma, lung cancer, non-small cell lung cancer, gastric cancer, melanoma, head and neck cancer, cervical cancer or prostate cancer. DETAILED DESCRIPTION

[0073] Unless otherwise defined, all technical and scientific terms used in this document have the same meanings generally understood by persons with common knowledge in the technical field to which this disclosure pertains. Although this disclosure may also be Petition 870260084912, dated 08 / 20 / 2026, pp. 164 / 1402 157 / 694 implemented or tested by means of any method and material similar or equivalent to those described in this document, the preferred methods and materials are described herein.

[0074] Unless otherwise indicated, the terms used in the description and claims have the following meanings.

[0075] The term linker unit (or linker fragment) refers to a chemical structural fragment or linkage that is connected to a ligand at one end and to a drug at the other end, and may also be connected to other linker units before binding to the drug.

[0076] The term ligand-drug conjugate refers to a structure in which the ligand is linked to a biologically active drug via a stable linker unit. In the present disclosure, the ligand-drug conjugate is preferably an antibody-drug conjugate (ADC), meaning that a monoclonal antibody or an antibody fragment is linked to a biologically active toxic drug, i.e., a camptothecin derivative, via the stable linker unit.

[0077] Examples of the three-letter and one-letter codes for amino acids used in this disclosure, as well as Petition 870260084912, dated 08 / 20 / 2026, pp. 165 / 1402 158 / 694 and their respective structures are presented in the following table: Table 1: Examples of the three-letter and one-letter codes for amino acids used in this publication, as well as their respective structures. Acronym Abbreviation Name Structure G Gly Glycine O H2N^oh A Ala Alanine 0 h'cY^oh nh2 V Val Valina ch3 0 HaC'^p^OH nh2 L Leu Leucine O Η3ογ^ΛΟΗ ch3 nh2 I Ile Isoleucine = 0 Η3θ^ΛΟΗ nh2 F Phe Phenylalanine 0 nh2 W Trp Tryptophan H UQ nh2 ^OH O Petition 870260084912, dated 08 / 20 / 2026, pp. 166 / 1402 159 / 694 Y Tyr Tyrosine 0 rj^Y^j^OH NH2 D Asp Aspartic acid 0 ηογΥοη 0 nh2 H His Histidine o hV NH2 N Asn Asparagine 0 Y'foH 0 nh2 E Glu Glutamic acid 0 o nh2 K Lys Lysine 0 nh2 Q Gln Glutamine O 0 H2N ^-^γ^ΟΗ nh2 M Met Methionine 0 nh2 R Arg Arginine HH< ,NH2 H2N, , NX / OH YY NH 0 S Ser Serine O HO^^y^OH nh2 T Thr Thrreonine OH O ^Y^OH nh2 Petition 870260084912, dated 08 / 20 / 2026, page 167 / 1402 160 / 694 C Cys Cysteine ​​O HS^Y^OH nh2 P Pro Proline / 'iOH HOC Cit Citrulline OO H2N NH nh2

[0078] The term antibody refers to immunoglobulins, which are tetrapeptide chain structures composed of two identical heavy chains and two identical light chains, connected by interchain disulfide bonds. The composition and amino acid sequence of the constant region of the immunoglobulin heavy chains differ from one another, resulting in differences in antigenicity. Thus, immunoglobulins can be classified into five types or isotypes, namely IgM, IgD, IgG, IgA, and IgE, with their corresponding heavy chains being the μ chain, the δ chain, the γ chain, the α chain, and the ε chain, respectively. The same class of Ig can be further divided into different subclasses based on differences in the amino acid composition of the hinge region and the number and position of the heavy chain disulfide bonds, such as IgG, which can be divided into IgG1, IgG2, IgG3, and IgG4.Light chains are classified as either κ-chain or λ-chain, based on their constant region. Each class of Ig can have either κ or λ chains. Petition 870260084912, dated 08 / 20 / 2026, pp. 168 / 1402 161 / 694

[0079] The heavy and light chains of antibodies have, near the N-terminal end, highly variable regions of about 110 amino acids, known as the variable region (Fv region). The remaining sequences, near the C-terminal end, are relatively stable and are called the constant region. The variable region includes three hypervariable regions (HVRs) and four relatively conserved structural regions (FRs). The three hypervariable regions determine the antibody's specificity and are also known as complementarity-determining regions (CDRs). Each light chain variable region (LCVR) and heavy chain variable region (HCVR) consists of three CDRs and four FRs arranged in the following sequence, from N-terminal to C-terminal: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The three CDRs in the light chain are designated LCDR1, LCDR2, and LCDR3, while the three CDRs in the heavy chain are designated HCDR1, HCDR2, and HCDR3.The CDR amino acid residues in the LCVR and HCVR regions of the antibodies or antigen-binding fragments described in this disclosure correspond in number and position to the known Kabat numbering scheme (LCDR1-3, HCDR2-3) or to the Kabat and Chothia numbering schemes (HCDR1).

[0080] The term “antigen-binding fragment” refers to one or more fragments of an antibody that maintains Petition 870260084912, dated 08 / 20 / 2026, pp. 169 / 1402 162 / 694 the ability to bind specifically to an antigen. It has been shown that fragments of a complete antibody can be used for the antigen-binding function of the antibody. Examples of binding fragments included in the “antigen-binding fragment” include: (i) Fab fragments, which are monovalent fragments consisting of the VL, VH, CL, and CH1 domains; (ii) F(ab')2 fragments, which are bivalent fragments that include two Fab fragments connected by disulfide bridges in the hinge region; (iii) Fd fragments consisting of the VH and CH1 domains; (iv) Fv fragments, which consist of the VH and VL domains of an antibody arm; (v) single-domain or dAb fragments, which consist of the VH domain; and (vi) isolated complementarity-determining regions (CDRs) or (vii) combinations of two or more isolated CDRs that may optionally be connected by synthetic linkers.Additionally, although the two domains of an Fv fragment, VL (variable region of the light chain) and VH (variable region of the heavy chain), are encoded by distinct genes, recombinant methods can be used to connect them via a synthetic linker, thus resulting in a single protein chain in which the VL and VH regions pair up to form a monovalent molecule (known as single-chain Fv (scFv)). These single-chain antibodies are also included within the scope of the term fragment-binding antibody. Petition 870260084912, dated 08 / 20 / 2026, pp. 170 / 1402 163 / 694 antigen. Such antibody fragments are obtained by means of conventional techniques known to experts in the field and are functionally tested in the same way as complete antibodies. The antigen-binding portions can be produced by recombinant DNA technology or by enzymatic or chemical cleavage of full-length immunoglobulins. The antibodies can be of various isotypes, such as IgG (e.g., subtypes IgG1, IgG2, IgG3, or IgG4), IgA1, IgA2, IgD, IgE, or IgM.

[0081] The term alkyl refers to a saturated aliphatic hydrocarbon group, which may be linear or branched, containing from 1 to 20 carbon atoms; preferably, an alkyl group containing from 1 to 12 carbon atoms; more preferably, from 1 to 10 carbon atoms; and, even more preferably, from 1 to 6 carbon atoms (including 1, 2, 3, 4, 5 or 6 carbons). Non-limiting examples include: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-amyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3 Petition 870260084912, dated 08 / 20 / 2026, pp. 171 / 1402 164 / 694 dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4methylhexyl, 5-methylhexyl, 2,3-dimethylpentyl, 2,4dimethylpentyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 2ethylpentyl, 3-ethylpentyl, n-octyl, 2,3-dimethylhexyl, 2,4dimethylhexyl, 2,5-dimethylhexyl, 2,2-dimethylhexyl, 3,3dimethylhexyl, 4,4-dimethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4ethylhexyl, 2-methyl-2-ethylpentyl, 2-methyl-3-ethylpentyl, nonnonyl, 2-methyl-2-ethylhexyl, 2-methyl-3-ethylhexyl, 2,2-diethylpentyl, n-decyl, 3,3-diethylhexyl, 2,2-diethylhexyl, various branched isomers of these isomers and the like. Preferably, the alkyl group is a short-chain alkyl containing from 1 to 6 carbon atoms.Non-limiting examples include: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-amyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, among others. The alkyl group may be substituted or unsubstituted, and, when substituted, the substituent may be attached at any available connection point. Preferred substituents include one or more of the following groups: alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, sulfhydryl. Petition 870260084912, dated 08 / 20 / 2026, pp. 172 / 1402 165 / 694 hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxyl, heterocycloalkoxyl, cycloalkylthio, heterocycloalkylthio and oxo.

[0082] The term alkoxy refers to -O-(alkyl) and -O-(unsubstituted cycloalkyl), where the alkyl or cycloalkyl group is defined as described above. Non-limiting examples of alkoxy groups include: methoxy, ethoxy, propoxy, butoxy, cyclopropoxy, cyclobutoxy, cyclopentyloxy and cyclohexyloxy. The alkoxy group may be optionally substituted or unsubstituted and, when substituted, the substituent is preferably one or more of the following groups: alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, sulfhydryl, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio and heterocycloalkylthio.

[0083] The term cycloalkyl refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent in which the cycloalkyl ring has from 3 to 20 carbon atoms; preferably from 3 to 12 carbon atoms; more preferably from 3 to 10 carbon atoms; and even more preferably from 3 to 8 carbon atoms (including 3, 4, 5, 6, 7 or 8 carbon atoms). Examples Petition 870260084912, dated 08 / 20 / 2026, page 173 / 1402 166 / 694 Non-limiting examples of monocyclic cycloalkyl groups include: cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cycloctyl, among others; and polycyclic cycloalkyl groups include spiral, fused and dotted structures.

[0084] The term heterocycloalkyl refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent containing from 3 to 20 atoms in the ring, of which one or more are heteroatoms selected from nitrogen, oxygen or S(O)m (where m is an integer 0, 1 or 2), excluding ring fragments containing -OO-, -OS- or -SS-, and the remaining ring atoms being carbon. Preferably, the heterocycloalkyl group includes from 3 to 12 atoms in the ring, containing from 1 to 4 heteroatoms (1, 2, 3 or 4 heteroatoms). More preferably still, the heterocyclic ring contains from 3 to 10 atoms in the ring (including 3, 4, 5, 6, 7, 8, 9 or 10 atoms). Non-limiting examples of monocyclic heterocycloalkyl groups include pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, among others. Polycyclic heterocycloalkyl groups include spiral, fused, and point-like structures. Petition 870260084912, dated 08 / 20 / 2026, pp. 174 / 1402 167 / 694

[0085] The term spiro-heterocycloalkyl refers to a polycyclic heterocyclic group in which monocyclic rings of 5 to 20 members share an atom (called the spiro atom), wherein one or more ring atoms are heteroatoms selected from nitrogen, oxygen, or S(O)m (where m is an integer from 0 to 2), and the remaining ring atoms are carbon. The spiro-heterocycloalkyl group may include one or more double bonds, but does not include any ring containing a fully conjugated π electronic system. The spiro-heterocycloalkyl group is preferably composed of rings of 6 to 14 members, and more preferably of 7 to 10 members. Spiroheterocycloalkyl groups are classified into monospiroheterocyclic, diespiroheterocyclic, and polyspiroheterocyclic groups, according to the number of spiro atoms shared between the rings, with monospiroheterocyclic and diespiroheterocyclic groups being preferred.The spiro-heterocycloalkyl group is most preferably a monospiro-heterocyclic group formed by 4 / 4-membered, 4 / 5-membered, 4 / 6-membered, 5 / 5-membered, or 5 / 6-membered rings. Non-limiting examples of spiro-heterocycloalkyl groups include: Petition 870260084912, dated 08 / 20 / 2026, page 175 / 1402 168 / 694

[0086] The term fused heterocyclic group refers to a polycyclic heterocyclic group of 5 to 20 members, in which each ring of the system shares a pair of adjacent atoms with another ring of the system, one or more rings may include one or more double bonds, but no ring has a fully conjugated π electronic system, one or more ring atoms are heteroatoms selected from nitrogen, oxygen, or S(O)m (m is an integer of 0, 1, or 2), and the other ring atoms are carbon. The fused heterocyclic group is preferably composed of 6 to 14 members, more preferably between 7 and 10 members (rings of 7, 8, 9, or 10 members). Fused heterocyclic groups can be classified as bicyclic, tricyclic, tetracyclic, or polycyclic groups, according to the number of constituent rings.Fused bicyclic or tricyclic heterocyclic groups are preferably used, and 5 / 5-membered or 5 / 6-membered fused bicyclic heterocyclic groups are more preferred. Non-limiting examples of fused heterocyclic groups include: Petition 870260084912, dated 08 / 20 / 2026, page 176 / 1402 169 / 694 H

[0087] The term “bridged heterocyclic group” refers to a 5- to 14-membered polycyclic heterocyclic group in which any two rings share two atoms that are not directly bonded and may include one or more double bonds, but neither ring has a fully conjugated π electronic system, one or more ring atoms are heteroatoms selected from nitrogen, oxygen, or S(O)m (m is an integer of 0, 1, or 2), and the other ring atoms are carbon. The bridged heterocyclic group is preferably composed of 6 to 14 members, with 7 to 10 members being more preferred (7-, 8-, 9-, or 10-membered rings). Bridged heterocyclic groups can be divided into bicyclic, tricyclic, tetracyclic, and polycyclic bridged heterocyclic groups according to the number of constituent rings. Heterocyclic groups with Petition 870260084912, dated 08 / 20 / 2026, page 177 / 1402 170 / 694 Bicyclic, tricyclic, or tetracyclic bridges are preferred, with bicyclic or tricyclic bridges being even more preferred. Non-limiting examples of bridging heterocyclic groups include:

[0088] The heterocyclic group ring may also be fused to an aryl, heteroaryl or cycloalkyl ring, and the ring attached to the main structure is the heterocyclic group and non-limiting examples include:

[0089] The heterocyclic group may be substituted or unsubstituted and, when substituted, the substituent is preferably one or more of the following groups: alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, sulfhydryl, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio and oxo.

[0090] The term aryl refers to a monocyclic group Petition 870260084912, dated 08 / 20 / 2026, pp. 178 / 1402 171 / 694 or fused polycyclic, consisting only of carbon atoms, with 6 to 14 members (i.e., rings sharing adjacent pairs of carbon atoms) and exhibiting a conjugated π electronic system or, preferably, a group with 6 to 10 members (rings of 6, 7, 8, 9 or 10 members), such as phenyl and naphthyl, with phenyl being the most preferred form. The aryl ring may be fused to a heteroaryl, heterocyclic or cycloalkyl ring, and the ring attached to the main structure is the aryl ring; non-limiting examples include:

[0091] The aryl group may be substituted or unsubstituted and, when substituted, the substituent is preferably one or more of the following groups: alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, sulfhydryl, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio and heterocycloalkylthio. Petition 870260084912, dated 08 / 20 / 2026, page 179 / 1402 172 / 694

[0092] The term heteroaryl refers to a heterocyclic aromatic system containing 1 to 4 heteroatoms (1, 2, 3, or 4 heteroatoms) and 5 to 14 atoms in the ring, with the heteroatoms being selected from oxygen, sulfur, and nitrogen. The heteroaryl group is preferably 5 to 10 members long (5, 6, 7, 8, 9, or 10-membered heteroaryl rings), with 5 or 6 members being more preferred, such as furan, thiophene, pyridine, pyrrole, N-alkylated pyrrole, pyrimidine, pyrazine, imidazole, tetrazole, among others. The heteroaryl ring may be fused to an aryl, heterocyclic, or cycloalkyl ring, with the ring attached to the main structure being the heteroaryl ring, and non-limiting examples include:

[0093] The heteroaryl group may be optionally substituted or unsubstituted, and, when substituted, the substituent(s) is / are preferably one or more of the following groups: alkyl, alkenyl, alkynyl, alkoxyl, alkylthio, alkylamino, halogen, sulfhydryl, hydroxyl, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, Petition 870260084912, dated 08 / 20 / 2026, pp. 180 / 1402 173 / 694 heteroaryl, cycloalkoxyl, heterocycloalkoxyl, cycloalkylthio and heterocycloalkylthio.

[0094] The term amino protecting group refers to a group used to protect the amino group during reactions in other parts of the molecule, ensuring that the amino group remains unchanged. Non-limiting examples include: 9-fluorenylmethoxycarbonyl, tert-butyloxycarbonyl, acetyl, benzyl, allyl, p-methoxybenzyl, among others. These groups may optionally be replaced by 1 to 3 substituents (1, 2 or 3 substituents) selected from halogen, alkoxy and nitro groups. The amino protecting group is preferably 9-fluorenylmethoxycarbonyl.

[0095] The term haloalkyl refers to an alkyl group substituted by one or more halogens, the alkyl being as defined above.

[0096] The term deuterated alkyl refers to an alkyl group substituted by one or more deuterium atoms, the alkyl being as defined above.

[0097] The term hydroxyalkyl refers to an alkyl group substituted by one or more hydroxyl groups, the alkyl being as defined above.

[0098] The term hydroxyl refers to the -OH group.

[0099] The term halogen refers to fluorine, chlorine, Petition 870260084912, dated 08 / 20 / 2026, pp. 181 / 1402 174 / 694 bromine or iodine.

[00100] The term amino refers to the -NH2 group.

[00101] The term nitro refers to the -NO2 group.

[00102] The term cyano refers to the -CN group.

[00103] The term amide refers to the C(O)N(alkyl) or (cycloalkyl) group, with alkyl and cycloalkyl groups defined as above.

[00104] The term carboxylic ester group refers to the -C(O)O(alkyl) or (cycloalkyl) group, with alkyl and cycloalkyl groups being defined as above.

[00105] This disclosure also includes several deuterated forms of the compounds of formula (I). Each hydrogen atom bonded to a carbon atom can be independently replaced by a deuterium atom. Qualified professionals in the field can consult the relevant literature to synthesize deuterated forms of the compounds of formula (I). In preparing deuterated forms of the compounds of formula (I), commercially available deuterated starting materials can be used, or these can be synthesized using conventional techniques with deuterated reagents, including, but not limited to: deuterated borane, tetrahydrofuran trideuterated borane, deuterated lithium aluminum hydride, deuterated iodoethane, Petition 870260084912, dated 08 / 20 / 2026, pp. 182 / 1402 175 / 694 deuterated iodomethane, among others.

[00106] The terms optionally or optionally mean that the event or circumstance described may or may not occur. This description includes both the case where the event or circumstance occurs and the case where it does not occur. For example, heterocyclic group optionally substituted by alkyl means that the alkyl group may or may not be present, covering both the scenario where the heterocyclic group is substituted by an alkyl group and the scenario where it is not.

[00107] The term substituted refers to the substitution of one or more hydrogen atoms in the group, preferably up to 5 hydrogen atoms, more preferably 1, 2 or 3 hydrogen atoms, by a corresponding number of substituents, independently. It is evident that the substituents are only in their possible chemical positions. Experts in the field can determine, with minimal effort (experimentally or theoretically), which substitutions are possible or not. For example, an amino or hydroxyl group with free hydrogen combined with a carbon atom with unsaturated bonds (such as ethylenic bonds) may be unstable.

[00108] The term pharmaceutical composition refers to Petition 870260084912, dated 08 / 20 / 2026, pp. 183 / 1402 176 / 694 a mixture containing one or more of the compounds described in this document, or their salts or physiologically / pharmaceutically acceptable prodrugs, together with other chemical components, such as physiologically / pharmaceutically acceptable vehicles and excipients. The purpose of the pharmaceutical composition is to facilitate the administration of the compound(s) to a biological organism, promote the absorption of the active ingredient and thus exert biological activity.

[00109] The term pharmaceutically acceptable salt refers to salts of the ligand-drug conjugates described herein, or to salts of the compounds mentioned in this document, that are safe and effective for use in mammalian organisms and that exhibit the desired biological activity. The disclosed ligand-drug conjugate contains at least one amino group and may form salts with acids. Non-limiting examples of pharmaceutically acceptable salts include: hydrochloride, hydrobromide, iodide, sulfate, bisulfate, citrate, acetate, succinate, ascorbate, oxalate, nitrate, sorbate, hydrophosphate, dihydrogen phosphate, salicylate, hydrogen citrate, tartrate, maleate, fumarate, formate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, and p-toluenesulfonate.

[00110] The term vehicle, as used in this disclosure, refers to a system capable of Petition 870260084912, dated 08 / 20 / 2026, pp. 184 / 1402 177 / 694 modify how a drug enters and distributes itself in the human body, control the drug release rate, and direct drug delivery to the target organ. Drug delivery and targeting systems can reduce drug degradation and loss, decrease side effects, and improve bioavailability. For example, polymeric surfactants that can be used as vehicles have a unique amphiphilic structure, allowing them to self-assemble into various types of aggregates. Preferred examples of these aggregates include micelles, microemulsions, gels, liquid crystals, vesicles, and the like. These aggregates have the ability to encapsulate drug molecules and exhibit good membrane permeability, making them excellent vehicles for drug delivery.

[00111] The term excipient refers to additional substances present in pharmaceutical formulations, besides the active ingredient, also known as auxiliary materials. For example, binders, diluents, disintegrants and lubricants in tablets; the matrix component in semi-solid formulations such as ointments and creams; and also preservatives, antioxidants, flavorings, flavor enhancers, co-solvents, emulsifiers, solubilizers, osmotic agents, colorants and similar substances in liquid formulations. Petition 870260084912, dated 08 / 20 / 2026, pp. 185 / 1402 178 / 694 all can be considered excipients.

[00112] Pharmaceutical compositions containing the active components may be formulated in forms suitable for oral administration, such as tablets, lozenges, troches, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, syrups or elixirs. Oral formulations may be prepared using any method known in the pharmaceutical field, and may include one or more ingredients selected from: sweeteners, flavorings, colorings and preservatives, in order to make the pharmaceutical formulations more attractive and palatable. Tablets contain appropriate active ingredients and excipients that are non-toxic and pharmaceutically acceptable for the preparation of tablets.These excipients may include inert excipients such as calcium carbonate, sodium carbonate, lactose, calcium phosphate, or sodium phosphate; granulating and disintegrating agents such as microcrystalline cellulose, cross-linked sodium carboxymethylcellulose, corn starch, or alginic acid; binders such as starch, gelatin, polyvinylpyrrolidone, or gum arabic; and lubricants such as magnesium stearate, stearic acid, or talc. These tablets may be uncoated or coated using known techniques to mask the taste of the tablet. Petition 870260084912, dated 08 / 20 / 2026, page 186 / 1402 179 / 694 drug or delay disintegration and absorption in the gastrointestinal tract, providing prolonged-release effects. For example, water-soluble agents can be used to mask odors, such as hydroxypropylmethylcellulose or hydroxypropylcellulose, or substances to prolong the release time, such as ethylcellulose or cellulose acetate butyrate.

[00113] Hard gelatin capsules, containing active ingredients mixed with inert solid diluents, such as calcium carbonate, calcium phosphate or kaolin, or soft gelatin capsules, containing active ingredients mixed with water-soluble vehicles, such as polyethylene glycol, or with oily solvents, such as peanut oil, liquid paraffin or olive oil, may also be used as oral pharmaceutical forms.

[00114] Aqueous suspensions contain active substances mixed with excipients suitable for the preparation of aqueous suspensions. Such excipients include suspending agents such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone and gum arabic; dispersing agents or wetting agents, which may be natural phospholipids such as lecithin, or condensation products of alkylene oxides with fatty acids, such as stearate. Petition 870260084912, dated 08 / 20 / 2026, p. 187 / 1402 180 / 694 polyoxyethylene; condensation products of ethylene oxide with long-chain fatty alcohols, such as heptadecaethyleneoxycetanol; or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol, such as polyoxyethylenated sorbitol monooleate, or with partial esters derived from fatty acids and hexitol anhydrides, such as polyoxyethylenated dehydrated sorbitan monooleate. Aqueous suspensions may contain one or more preservatives, such as ethylparaben or n-propylparaben, one or more colorants, one or more flavorings, and one or more sweeteners, such as sucrose, saccharin, or aspartame.

[00115] Oil suspensions can be prepared by suspending the active ingredients in vegetable oils, such as peanut oil, olive oil, sesame oil, or coconut oil, or in mineral oils, such as liquid paraffin. These oil suspensions may contain thickening agents, such as beeswax, hard paraffin, or cetyl alcohol. Sweeteners and flavorings may be added to prepare a palatable formulation. These compositions can be preserved by the addition of antioxidants, such as butylated hydroxyanisole or α-tocopherol.

[00116] Dispersible powders and granules for preparing aqueous suspensions by adding water provide the ingredient Petition 870260084912, dated 08 / 20 / 2026, pp. 188 / 1402 181 / 694 active ingredient in a mixture with dispersants or wetting agents, suspending agents, or one or more preservatives. Suitable dispersants, wetting agents, and suspending agents have been described previously. Other excipients, such as sweeteners, flavorings, and colorings, may also be added. These compositions can be preserved by the addition of antioxidants, such as ascorbic acid.

[00117] The pharmaceutical composition of the present invention can also be formulated in the form of an oil-in-water emulsion. The oil phase may consist of vegetable oils, such as olive oil or peanut oil, mineral oils, such as liquid paraffin, or mixtures of these oils. Suitable emulsifiers may be natural phospholipids, such as soy lecithin; esters or partial esters derived from fatty acids and hexitol anhydride, such as sorbitol monooleate; and condensation products of these partial esters with ethylene oxide, such as polyoxyethylened sorbitol monooleate. The emulsions may also contain sweeteners, flavorings, preservatives, and antioxidants. Syrups and elixirs may be prepared with sweeteners such as glycerin, propylene glycol, sorbitol, or sucrose. Such formulations may also include demulcents, preservatives, colorants, and antioxidants.

[00118] The pharmaceutical composition of the present Petition 870260084912, dated 08 / 20 / 2026, pp. 189 / 1402 The invention can also be formulated as a sterile aqueous solution for injection. Acceptable solvents and vehicles include water, Ringer's solution for injection, and isotonic sodium chloride solution. Sterile injectable preparations can also be formulated as sterile oil-in-water injectable microemulsions, in which the active ingredient is dissolved in the oil phase. For example, the active ingredient can be dissolved in a mixture of soybean oil and lecithin, and then this oil solution can be added to a mixture of water and glycerol to form a microemulsion. Injectable solutions or microemulsions can be administered to the patient by local injection in large volumes into the bloodstream, preferably maintaining a constant circulating concentration of the compound by continuous intravenous administration. Continuous intravenous infusion devices can be used for this purpose.

[00119] The pharmaceutical compositions of the present invention can also be formulated as sterile injectable suspensions in water or oil for intramuscular or subcutaneous administration. These suspensions can be formulated using suitable dispersants or wetting agents and suspending agents, as described above. Sterile injectable preparations also Petition 870260084912, dated 08 / 20 / 2026, pp. 190 / 1402 183 / 694 may be sterile solutions or suspensions in non-toxic diluents or solvents acceptable for parenteral use, such as solutions prepared in 1,3-butanediol. In addition, sterile fixed oils may be used as solvents or suspension media. For this purpose, any neutral fixed oil may be used, including synthetic mono- or diglycerides. Additionally, fatty acids, such as oleic acid, may be used in the preparation of injectable formulations.

[00120] It is common knowledge among experts in the field that drug dosage depends on several factors, including, but not limited to: the activity of the specific compound, the patient's age, weight, health condition, habits, diet, administration time, route of administration, excretion rate, and combination with other medications. Furthermore, the ideal therapeutic regimen, such as the treatment method and the daily dosage of the compound in the general formula or its pharmaceutically acceptable salt, can be validated according to conventional therapeutic protocols. BRIEF DESCRIPTION OF THE DRAWINGS

[00121] FIG. 1 shows a tumor growth curve of a mouse model bearing an NCI-N87 gastric cancer tumor in Test Example 3.

[00122] FIG. 2 shows a growth curve of Petition 870260084912, dated 08 / 20 / 2026, pp. 191 / 1402 184 / 694 tumor of a JIMT-1 mouse model of human breast cancer in Test Example 4.

[00123] FIG. 3A shows a growth inhibition curve of Her2-negative 468-luc cells in Test Example 6.

[00124] FIG. 3B shows a growth inhibition curve of Her2-positive N87 cells in Test Example 6.

[00125] FIG. 3C shows a growth inhibition curve of N87 cells and 468-luc cells under co-incubation in Test Example 6.

[00126] FIG. 4 and FIG. 5 show a weight change curve for rats after a single dose of 200 mg / kg in Test Example 7.

[00127] FIG. 6A and FIG. 6B show a tumor growth curve of a mouse model bearing an NCI-N87 gastric cancer tumor in Test Example 5. DETAILED DESCRIPTION OF ACHIEVEMENTS

[00128] The compounds of the present invention and their methods of preparation can be better understood through the following examples, which illustrate methods for preparing or using the compounds. However, it should be understood that these examples do not limit the scope of the present invention. Petition 870260084912, dated 08 / 20 / 2026, pp. 192 / 1402 185 / 694 invention. Variations of the invention, whether currently known or developed in the future, are considered to be within the scope of this disclosure and the claims.

[00129] The compounds of the present invention are prepared using convenient starting materials and general preparation steps. The present invention provides typical or preferred reaction conditions, such as reaction temperature, time, solvent, pressure, and molar ratios of reagents. However, unless expressly stated otherwise, other reaction conditions may also be adopted. Optimization conditions may vary depending on the specific reagents or solvents used, but in general, the steps and conditions necessary for reaction optimization can be determined.

[00130] Furthermore, protecting groups can be used in the invention to protect certain functional groups from unwanted reactions. The protecting groups suitable for various functional groups and their protection or deprotection conditions are widely known to those skilled in the art. For example, “Protective groups in Organic Synthesis” by TW Greene and GM Wuts (3rd edition, Wiley, New York, 1999, and references thereto) describes in detail the protection or deprotection of many protecting groups. Petition 870260084912, dated 08 / 20 / 2026, page 193 / 1402 186 / 694

[00131] The isolation and purification of compounds and intermediates are carried out by means of appropriate methods and steps, such as filtration, extraction, distillation, crystallization, column chromatography, preparative thin-layer chromatography, high-performance preparative liquid chromatography, or a combination of these methods based on specific needs. For specific methods of use, refer to the examples described in the present invention. Certainly, other similar methods of isolation and purification may also be adopted. Conventional methods (including physical constants and spectral data) may be used for characterization.

[00132] The compound's structure is determined by nuclear magnetic resonance (NMR) and / or mass spectrometry (MS). NMR shifts are given in units of 10-6 (ppm). NMR measurements are performed using a Bruker DPS 400 nuclear magnetic instrument. The assay solvents are deuterated dimethyl sulfoxide (DMSO-de), deuterated chloroform (CDCla), deuterated methanol (CD3OD), and deuterated water (D2O), with tetramethylsilane (TMS) as an internal standard.

[00133] MS measurements of small molecules are performed using an LC (Waters 2695) / MS (Quattro Premier XE) mass spectrometer (manufacturer: Waters) (detector Petition 870260084912, dated 08 / 20 / 2026, pp. 194 / 1402 187 / 694 photodiode array).

[00134] MS measurements of ADCs are performed using UPLC-MS (Thermo Fisher Scientific, Dionex UltiMate 3000 UPLC-Q Exactive MS; high-resolution mass spectrometer, Thermo Q EXACTIVE HF-X).

[00135] For the HIC analysis of ADC, an Agilent 1200 high-performance liquid chromatograph is used for HIC assays. The chromatographic column is a Thermo MAbPac HICButyl (5 µm, 4.6 x 100 mm). A mixed solution (pH 7.0) of 1.5 M ammonium sulfate and 25 mM phosphate and isopropanol (95:5) is used as mobile phase A, and the solution of 25 mM phosphate (pH 7.0) and isopropanol (80:20) is used as mobile phase B to perform gradient elution at a flow rate of 1.0 mL / min.

[00136] For the SEC analysis of ADC, an Agilent 1200 high-performance liquid chromatograph is used for SEC assays. The chromatographic column is a Waters BioResolve SEC mAb (2.5 µm, 7.8 x 300 mm), and PBS is used as the mobile phase for isocratic elution at a flow rate of 0.5 mL / min.

[00137] For ADC RP analysis, an Agilent 1200 high-performance liquid chromatograph is used for HIC assays. The chromatographic column is a Thermo MAbPac RP (4 µm, 3x100 mm). A 0.1% trifluoroacetic acid solution is used as mobile phase A, and acetonitrile, isopropanol, and acid are used as the chromatographic column. Petition 870260084912, dated 08 / 20 / 2026, pp. 195 / 1402 188 / 694 trifluoroacetic (80:20:0.1) is used as mobile phase B for gradient elution at a flow rate of 1.0 mL / min.

[00138] For preparative high-performance liquid chromatography, an LC6000 high-performance liquid chromatography (manufacturer: Beijing Chuangxintongheng Science & Technology Co., Ltd) is used. The chromatographic column used is the Daisogel C18 (10 µm, 100 Å, 30 mm x 250 mm). The mobile phase is composed of acetonitrile / water. The Orienda BRIX-2860 is used. The Phenomenex Luna C18 (250 x 50 mm x 10 µm) is used as the chromatographic column. The mobile phase is a mixture of water (0.225% trifluoroacetic acid) and acetonitrile.

[00139] The TLC silica gel plate uses Qingdao Marine Chemical GF254 silica gel plate. The specifications of silica gel plates used in thin-layer chromatography (TLC) are 0.20 mm to 0.25 mm, while the specifications of preparative thin-layer chromatography separation and purification products are 0.5 mm.

[00140] Silica gel of 100 to 200 mesh, 200 to 300 mesh and 300 to 400 mesh (Qingdao Marine Chemical) is commonly used as a carrier in column chromatography.

[00141] The known starting materials mentioned in this invention can be synthesized by methods already known in the literature or acquired in stores. Petition 870260084912, dated 08 / 20 / 2026, page 196 / 1402 189 / 694 online and companies such as Beijing Ouhe, Sigma, J&K Scientific, Yishiming, BePharm Ltd., InnoChem, Energy Chemical, Bidepharm, ChemExpress, Yilai Biotechnology, BirdoTech, among others.

[00142] Unless otherwise specified in the examples, all reactions are conducted under a nitrogen atmosphere.

[00143] An argon atmosphere or nitrogen atmosphere means that a reaction flask is connected to an argon flask or a nitrogen flask with a volume of approximately 1L.

[00144] Reaction solvents, organic solvents or inert solvents refer to solvents that do not participate in the reaction under the conditions described, including benzene, toluene, acetonitrile, tetrahydrofuran (THF), dimethylformamide (DMF), chloroform, dichloromethane, ether, methanol, N-methylpyrrolidone (NMP), pyridine, and the like. Unless otherwise specified in the embodiments, the term solution refers to an aqueous solution.

[00145] The chemical reactions described in the present invention are generally carried out under atmospheric pressure. The reaction temperatures range from -78 °C to 200 °C. The reaction time and conditions are, for example, under standard atmospheric pressure, a temperature of -78 °C to 200 °C, and a duration of approximately 1 to 24 hours. If the reaction lasts from one day Petition 870260084912, dated 08 / 20 / 2026, page 197 / 1402 190 / 694 to the other, the reaction time will generally be 16 hours. In the examples, unless otherwise specified, the reaction temperature is room temperature, i.e., 20 °C to 30 °C.

[00146] The progress of the reactions in the examples is monitored by thin-layer chromatography (TLC). The development solvent systems used in the reactions are: A: Dichloromethane and methanol system, B: Petroleum ether and ethyl acetate system, C: Acetone. The volumetric ratio of the solvents is adjusted according to the polarity of the compounds.

[00147] The eluent systems used in column chromatography for the purification of compounds and the development solvent systems used in thin-layer chromatography include: A: Dichloromethane and methanol system, B: Petroleum ether and ethyl acetate system. The volumetric ratio of the solvents is adjusted according to the polarity of the compounds, and small amounts of basic or acidic reagents, such as triethylamine and trifluoroacetic acid, may be added for adjustment.

[00148] Unless otherwise defined, all professional and scientific terms used in this document have the same meanings as they are commonly known by Petition 870260084912, dated 08 / 20 / 2026, pp. 198 / 1402 191 / 694 experts in the field. Furthermore, any methods and materials similar or equivalent to those described may be applied to the methods of the present invention.

[00149] The compounds of the present invention are prepared in accordance with the exemplary procedures provided in this document, as well as with modifications known to those skilled in the art. Preparation Examples Example Preparation 1: Preparation of (9R)-9-ethyl-5-fluoro-1,9-dihydroxy-4-methyl-1,2,3,9,12,15-hexahydro OH,13H-benzo[de]pyrano[3',4:6,7]indolizino[1,2 — b]quinoline-10,13-dione (PY-1)

[00150] NaNCç (270 mg, 3.91 mmol) was added to a 25 mL three-necked flask, then 6 mL of water was added for dissolution, followed by 1 mL of glacial acetic acid, and then a solution of acetic acid (3 Petition 870260084912, dated 08 / 20 / 2026, page 199 / 1402 A solution of 192 / 694 mL of glacial acetic acid and 3 mL of water) containing exatecane mesylate (ChemExpress, 100 mg, 0.188 mmol) was slowly added to the previously prepared NaNO2 solution, and the reaction was conducted for 1.5 hours at room temperature. The reaction solution was filtered to collect a solid, the solid was dried to obtain a reddish-brown solid, the reddish-brown solid was isolated and purified by high-performance liquid chromatography (Oriendo, BRIX-2860; column: Phenomenex Luna C18 250 x 50 mm x 10 gm; mobile phase: water (0.5% formic acid)-acetonitrile, eluted 40% to 80%) and lyophilized, to obtain 12 mg of reddish powder with a yield of 14%.

[00151] LCMS (ESI): m / z, 437.1[M+1]+.

[00152] 1H NMR (400 MHz, DMSO-d6) δ 7.75 (d, J = 11.0 Hz, 1H), 7.31 (s, 1H), 6.50 (s, 1H), 6.04- 5.83 (m, 1H), 5.48-5.29 (m, 4H), 5.16 (d, J = 5.6 Hz, 1H), 3.23 (dd, J = 13.4, 8.6 Hz, 2H), 3.09-2.98 (m, 1H), 2.37 (s, 3H), 2.02 (dd, J = 16.4, 6.8 Hz, 1H), 1.86 (dq, J = 14.0, 7.2 Hz, 2H), 0.88 (t, J = 7.3 Hz, 3H). Example Preparation 2: Preparation of (9S)-9-ethyl-5fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15hexahydro-1H,12H-benzo[de]pyrano[3,,4,:6,7]indolizino[1,2b]quinolin-1-yl(2-hydroxyethyl)carbamate (PY-1AB) Petition 870260084912, dated 08 / 20 / 2026, p. 200 / 1402 193 / 694 Step 1: Preparation of (9S)-9-ethyl-5-fluoro-9-hydroxy4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3,,4,:6,7]indolizino[1,2-b]quinolin-1yl(4-nitrophenyl carbonate) (PY-1D)

[00153] Compound PY-1 (40.0 mg, 0.09 mmol, 1.0 equivalent) and triethylamine (27.3 mg, 0.27 mmol, 3.0 equivalents) were dissolved in dichloromethane (5 mL). 4-Nitrophenyl chloroformate (36.2 mg, 0.18 mmol, 2.0 equivalents) was added to the solution at 0 °C, and then the mixture was heated to 35 °C and stirred for 3 hours. After the reaction, the solution was cooled to room temperature and then concentrated, obtaining a crude yellow solid (60 mg crude product; purity: 49.3%; 0.05 mmol; yield: Petition 870260084912, dated 08 / 20 / 2026, page 201 / 1402 194 / 694 55.6%).

[00154] LCMS: RT = 0.909 min, MS (ESI) m / z =602.1 [M+H]+. Step 2: Preparation of (9S)-9-ethyl-5-fluoro-9-hydroxy4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3,,4,:6,7]indolizino[1,2-b]quinolin-1-yl(2hydroxyethyl)carbamate (PY-1AB)

[00155] Compound PY-1D (0.05 mmol, 1.0 equivalent) and triethylamine (10.1 mg, 0.1 mmol, 2.0 equivalents) were dissolved in dichloromethane (5 mL), ethanolamine (31.4 mg, 0.04 mmol, 1.1 equivalents) was added to the solution at 0 °C, and the mixture was then stirred for 3 hours at 25 °C. The reaction solution was cooled and concentrated to obtain a crude product, which was purified by reversed-phase chromatography (column: Welch Xtimate C18, 150 x 30 mm x 5 µm; mobile phase: [water(FA)-ACN]; gradient: 6%-46% B for 25 min) to obtain the target product PY-1AB (2.23 mg, 0.004 mmol, yield: 8.00%) as a white solid.

[00156] LCMS: RT = 1.197 min, MS (ESI) m / z = 524.2 [M+H]+.

[00157] 1HNMR (400MHz, DMSO-d6) δ ppm 7.81 (d,J = 10.8 Hz, 1 H), 7.45 (t, J = 5.6 Hz, 1 H), 7.33 (s, 1 H), 6.52 (s, 1 H), 6.27 (s, 1 H), 5.44 - 5.24 (m, 4 H), 4.70(t, J = 5.6Hz, 1H), 3.48-3.44 (m, 2H), 3.22-3.12 (m, 4H), Petition 870260084912, dated 08 / 20 / 2026, p. 202 / 1402 195 / 694 2.40 (s, 3 H), 2.20-2.17 (m, 1 H), 1.91-1.86 (m, 2 H), 1.271.22 (m, 1 H), 0.88 (t, J = 7.2 Hz, 3 H). Example Preparation 3: Preparation of (9S)-9-ethyl-5-fluoro-9-hydroxy-1-(hydroxymethyl)-4-methyl-1,2,3,9,12,15-hexahydro-10H,13H-benzo[de]pyrano[3',4':6,7]indolizino[1,2b]quinoline-10,13-dione (PY-2) and (S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-1-methylene-1,2,3,9,12,15-hexahydro-10H,13H-benzo[de]pyrano[3,,4,:6,7]indolizino[1,2b]quinoline-10,13-dione (PY-2b) Step 1: Preparation of (E)-N-(3-fluoro-7 (hydroxymethylene)-4-methyl-8-oxo-5,6,7,8 tetrahydronaphthalene-1-yl)acetamide (PY-22)

[00158] N-(3-fluoro-4-methyl-8-oxo-5,6,7,8 Petition 870260084912, dated 08 / 20 / 2026, p. 203 / 1402 196 / 694 tetrahydronaphthalene-1-yl)acetamide (PY-21) (1.0 g, 4.25 mmol, 1.0 equivalent) was dissolved in THF (20 mL) in a 100 mL three-necked flask and cooled to 0 °C in an ice bath. t-BuOK (12.75 mmol, 1 M, 12.75 mL, 3 eq) was added slowly, maintaining the system at 0 °C under stirring for 30 minutes. Then, ethyl formate (787 mg, 10.63 mmol, 2.5 eq) was added to the reaction system, which was then stirred for 2 hours. After this period, ammonium chloride (20 mL) was added for cooling, and the reaction system was extracted with ethyl acetate, dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the yellow solid compound (E)-N-(3-fluoro-7(hydroxymethylene)-4-methyl-8-oxo-5,6,7,8tetrahydronaphthalene-1-yl)acetamide (1.22 g; yield: 95%).

[00159] LCMS(ESI): m / z, 264.1[M+1]+. Step 2: Preparation of N-(3-fluoro-7-(hydroxymethyl)-4-methyl-8-oxy-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY23)

[00160] PtO2 (69.00 mg, 303.90 gmol, 0.2 equivalent) was added to a solution of the compound (E)-N-(3-fluoro-7(hydroxymethylene)-4-methyl-8-oxo-5,6,7,8tetrahydronaphthalene-1-yl)acetamide (PY-22) (400 mg, 1.52 mmol, 1.0 equivalent) in methanol (50 mL) under a nitrogen atmosphere, the nitrogen gas being replaced by Petition 870260084912, dated 08 / 20 / 2026, page 204 / 1402 197 / 694 gaseous hydrogen three times, the reaction system reacted under a hydrogen atmosphere for 24 hours (40 °C), the remaining raw materials were detected, PtO2 (69.00 mg, 303.90 gmol, 0.2 eq) was added again and the reaction system reacted further under a hydrogen atmosphere for 24 hours. The reaction system was filtered, the filtrate was concentrated under reduced pressure, the residue was purified by silica gel column chromatography (eluent: ethyl acetate / n-hexane = 1:20-1:5) obtaining the yellow solid compound N-(3-fluoro-7-(hydroxymethyl)-4-methyl-8-oxy-5,6,7,8tetrahydronaphthalene-1-yl)acetamide (324 mg, yield: 63%).

[00161] LCMS(ESI):m / z, 266.1[M+1]+. Step 3: Preparation of 8-amino-6-fluoro-2(hydroxymethyl)-5-methyl-3,4-dihydronaphthalene-1(2H)-one (PY-24)

[00162] SOCl2 (2.71 mmol, 1 M / L, 2.71 mL, 4.0 equivalents) was added to a solution of the compound N-(3fluoro-7-(hydroxymethyl)-4-methyl-8-oxy-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-23) (180 mg, 0.68 g / mol, 1.0 equivalent) in anhydrous MeOH (15 mL) under an ice bath. After the addition, the system was replaced three times with nitrogen gas and stirred at 50 °C for 60 minutes. The reaction system was concentrated under reduced pressure and the residue was purified by preparative high-performance liquid chromatography (Oriendo, BRIX-2860; Petition 870260084912, dated 08 / 20 / 2026, page 205 / 1402 198 / 694 column: Phenomenex Luna C18 250 χ 50 mm χ 10 pm; mobile phase: water (0.225% trifluoroacetic acid - acetonitrile, eluted 40% to 80%) yielding the light yellow solid compound 8amino-6-fluoro-2-(hydroxymethyl)-5-methyl-3,4-dihydronaphthalene-1(2H)-one (28.5 mg, yield: 25%).

[00163] LCMS(ESI): m / z, 264.1[M+1]+.

[00164] 1H NMR (400 MHz, DMSO-d6) δ 7.43 (brs, 2H), 6.35 (d, J = 12.0 Hz, 1H), 3.74 (dd, J = 10.8, 4.4 Hz, 1H), 3.60 (dd, J = 10.8, 7.2 Hz, 1H), 2.90 (dt, J = 17.2, 4.8 Hz, 1H), 2.75-2.54 (m, 2H), 2.18-2.08 (m, 1H), 1.98 (s, 3H), 1.84-1.79 (m, 1H). Step 4: Preparation of (9S)-9-ethyl-5-fluoro-9-hydroxy1-(hydroxymethyl)-4-methyl-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3,,4,:6,7]indolizino[1,2-b]quinoline-10,13dione (PY-2) and (S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-1 methylene-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3,,4,:6,7]indolizino[1,2-b]quinoline-10,13dione (PY-2b)

[00165] (S)-4-ethyl-4-hydroxy-7,8-dihydro-1Hpyrano[3,4-f]indolizino-3,6,10(4H)-trione (26 mg, 98.5 pmol, 1.0 equivalent) and PPTS (5 mg, 19.70 pmol, 0.2 equivalent) were added to a solution of the compound 8-amino-6fluoro-2-(hydroxymethyl)-5-methyl-3,4-dihydro-naphthalene1(2H)-one (22 mg, 98.5 pmol, 1.0 equivalent) in xylene (5 Petition 870260084912, dated 08 / 20 / 2026, page 206 / 1402 199 / 694 mL). After the addition, the gaseous nitrogen displacement was performed three times and the reaction system was stirred at 140 °C for 3 hours. The reaction system was concentrated under reduced pressure and the residue was purified by preparative high-performance liquid chromatography (Oriendo, BRIX-2860; column: Phenomenex Luna C18 250 x 50 mm x 10 µm; mobile phase: water (0.225% trifluoroacetic acid)-acetonitrile, 40% to 80%) to obtain a yellow solid PY-2 (3.42 mg, yield: 7%) and a dark brown, sticky solid PY-2b (5.31 mg, yield: 10%). PY-2:

[00166] LCMS(ESI): m / z, 451.2[M+1]+.

[00167] 1H NMR (400 MHz, DMSO-d6) δ 11.80 (s, 1H), 8.14 (s, 1H), 7.17 (d, J = 12.4 Hz, 1H), 6.73 (s, 1H), 6.46 (s, 1H), 6.11 (d, J = 2.0 Hz, 1H), 5.61 (d, J = 2.0 Hz, 1H), 5.36 (s, 1H), 4.73 (d, J = 2.4 Hz, 1H), 2.95 (t, J = 6.8 Hz, 2H), 2.79 (t, J = 6.8 Hz, 2H), 2.25 - 2.03 (m, 5H), 2.00 (d, J = 2.0 Hz, 1H), 1.86-1.76 (m, 2H), 0.85 (t, J = 7.2 Hz, 3H). PY-2b:

[00168] LCMS(ESI): m / z, 433.2[M+1]+.

[00169] 1H NMR (400 MHz, CDCla) δ 7.67 (d, J = 10.8 Hz, 1H), 7.62 (s, 1H), 5.77-5.70 (m, 3H), 5.38-5.30 (m, 3H), 3.77 (s, 1H), 3.22-3.19 (m, 2H), 2.85-2.82 (m, 2H), 2.41 (s, Petition 870260084912, dated 08 / 20 / 2026, p. 207 / 1402 200 / 694 3H), 1.96 - 1.82 (m, 2H), 1.04 (t, J= 8.0 Hz, 3H). Example of Preparation 4: Preparation of (IS,9S)-9-ethyl5-fluoro-9-hydroxy-l-((2-hydroxymethyl)amino)-4-methyl1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13dione (PY-4)

[00170] Exatecan mesylate (ChemExpress) (50 mg, 114.82 pmol) was dissolved in DMF (2 mL), and then ethylene oxide (1 mL, 1.15 mL) and glacial acetic acid (3.45 mg, 57.41 pmol) were added to the solution and the reaction system was stirred at 90 °C for 16 hours. After the reaction, the solution was cooled to room temperature, 20 mL of water were added to the system, and extraction was performed with ethyl acetate (20 mL χ³). After being combined, the organic phases were rinsed with saturated brine, dried with anhydrous Na₂SU₄, and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography. Petition 870260084912, dated 08 / 20 / 2026, page 208 / 1402 201 / 694 high-efficiency preparative liquid (Oriendo, BRIX-2860; column: Phenomenex Luna C18, 250 x 50 mm x 10 μm; mobile phase: water (0.225% trifluoroacetic acid) - acetonitrile, elution 40% to 80%), 1 drop of hydrochloric acid was added to the resulting solution, and the mixture was lyophilized to obtain the yellow solid compound PY-4 (5.82 mg, yield: 21%).

[00171] LCMS: [M+H]+= 480.9.

[00172] 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 0.72 - 0.83 (t, J=14.7 Hz, 3H), 1.72 - 1.85 (m, 2H), 2.13-2.22 (s, 3H), 2.43-2.56 (m, 1H), 2.80- 3.06 (m, 2H), 3.18 - 3.31 (s, 2H), 3.31-3.40 (m, 1H), 3.74-3.82 (m, 2H), 5.08-5.13 (s, 1H), 5.18 - 5.41 (m, 4H), 7.10 -7.14 (s, 1H), 7.15-7.21 (s, 1H). Example Preparation 5: Preparation of 2-hydroxyethyl((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxy-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3',4:6,7]indolizino[1,2-b]quinolin-1-yl)carbamate (PY-4Car) Petition 870260084912, dated 08 / 20 / 2026, page 209 / 1402 202 / 694 Step 1: Preparation of (IS,9S)-9-ethyl-5-fluoro-9hydroxy-1-isocyanate-4-methyl-1,2,3,9,12,15-hexahydro1 OH,13H-benzo[de]pyrano[3',4:6,7]indolizino[1,2 — b]quinoline-10,13-dione (4Car2)

[00173] At 0 °C, three equivalents of triethylamine (14 mg, 0.14 mmol) and one equivalent of tryphosgene (14 mg, 0.046 mmol) were added to a solution of exatecan mesylate (20 mg, 0.046 mmol) in dichloromethane (2 mL), and the reaction system was stirred at 0 °C for three hours. After the reaction, the system was concentrated under reduced pressure, yielding 20 mg of crude product, and the crude product was used directly for the next reaction. Step 2: Preparation of 2-hydroxyethyl((11,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxy-2,3,9,10,13,15hexahydro-1H,12H-benzo[de]pyrano[3',4:6,7]indolizino[1,2— b]quinolin-l-yl)carbamate (PY-4Car)

[00174] The compound (IS,9S)-9-ethyl-5-fluoro-9hydroxy-1-isocyanate-4-methyl-1,2,3,9,12,15-hexahydro10H, 13H-benzo[de]pyrano[3',4:6,7]indolizino[1,2 — b]quinoline-10,13-dione (4Car2) (20 mg, 0.043 mmol) was Petition 870260084912, dated 08 / 20 / 2026, page 210 / 1402 203 / 694 was dissolved in 1 mL of dichloromethane, then 10 equivalents of ethylene glycol (27 mg, 0.43 mmol) were added dropwise, and the reaction system was stirred for 3 hours at room temperature. The reaction system was concentrated under reduced pressure. The residue was purified by preparative reversed-phase liquid chromatography (Oriendo, BRIX-2860; column: Phenomenex Luna C18, 250 x 50 mm x 10 gm; mobile phase: water (0.225% trifluoroacetic acid) - acetonitrile, with elution from 40% to 80%), yielding 6.5 mg of a yellow solid compound PY-4Car.

[00175] LCMS: m / z = 524.2 [M+1]+.

[00176] 1H NMR (400 MHz, DMSO-d6) δ 8.43 (s, 1 H), 8.00 (d, J = 8.4 Hz, 1 H), 7.78 (d, J = 10.8 Hz, 1 H), 7.31 (s, 1 H), 6.55 (s, 1 H), 5.43 (s, 2 H), 5.24 (d, J = 7.20 Hz, 2 H), 4.81 (t, J = 5.2 Hz, 1 H), 3.97-4.17 (m, 2 H), 3.61 (d, J=3.6 Hz, 2 H), 3.02-3.18 (m, 2 H), 2.30-2.41 (m, 3 H), 2.05 - 2.28 (m, 2H), 1.75-1.94 (m, 2H), 0.87 (t, J = 7. 2Hz, 3H). Example of Preparation 6: Preparation of 4-hydroxybutyl((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3,4,6,7]indolizino[1,2-b]quinolin-1-yl)carbamate (PY-4Car2) Petition 870260084912, dated 08 / 20 / 2026, p. 211 / 1402 204 / 694 PY4CM2» Step 1: Preparation of 4-((tert-butyl dimethylsilyl)oxy)butyl(4-nitrophenyl)carbonate (PY-4car2-b)

[00177] N,N-diisopropylethylamine (2.43 mL, 14.68 mmol, 3 equivalents) was added to a solution of 4-((tert-butyl-dimethylsilyl)oxy)butyl-1-ol (1 g, 4.89 mmol, 1 equivalent) and bis(p-nitrobenzyl carbonate) (2.98 g, 9.79 mmol, 2 equivalents) in N,N-dimethylformamide (15 mL), and the mixture was stirred at room temperature overnight. The reaction solution was concentrated, diluted with dichloromethane (10 mL), and the organic phase was washed three times with water (10 mL) and once with saturated brine (10 mL). Then, the organic phase was dried with anhydrous sodium sulfate, filtered, and concentrated. The residue obtained was Petition 870260084912, dated 08 / 20 / 2026, page 212 / 1402 205 / 694 purified by silica gel column chromatography (eluents: ethyl acetate / petroleum = 1:10, dichloromethane / petroleum = 40%) to obtain the product 4((tert-butyl-dimethylsilyl)oxy)butyl(4-nitrophenyl)carbonate (PY-4car2-b) (1.63 g, yield = 90.2%).

[00178] LCMS(ESI): m / z, 370[M+H]+. Step 2: Preparation of 4-((tert-butyldimethylsilyl)oxy)butyl((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3,4,6,7]indolizino[1,2-b]quinolin-1-yl)carbamate (PY-4car2-d)

[00179] Triethylamine (20.92 pL, 150.48 pmol, 4 equivalents), the compound PY-4car2-b (18.1 mg, 48.92 pmol, 1.3 equivalents) and 1-hydroxybenzotriazole (2.4 mg, 18.81 pmol, 0.5 equivalents) were added to a solution of exatecane (20 mg, 37.62 pmol, 1 equivalent, mesylate, ChemExpress) and N,N-diisopropylethylamine (6.22 pL, 37.62 pmol, 1 equivalent) in dichloromethane (6 mL). The resulting solution was then stirred for 48 hours at room temperature and then concentrated, and the residue was purified by high-performance liquid chromatography (preparative chromatography manufacturer: Oriendo, model: BRIX-2860, column: Welch Xtimate C18). 250 x 30 mm x 10 µm; mobile phase: water (0.225% HCOOH) and acetonitrile; elution ratio of Petition 870260084912, dated 08 / 20 / 2026, page 213 / 1402 206 / 694 acetonitrile: 50% to 60%), to obtain a target compound PY4car2-d (15 mg, yield = 59.8%).

[00180] LCMS(ESI): m / z, 666[M+H]+. Step 3: Preparation of 4-hydroxybutyl((1S,9S)-9-ethyl5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15hexahydro-1H,12H-benzo[de]pyrano[3,,4,:6,7]indolizino[1,2b]quinolin-1-yl)carbamate (PY-4Car2)

[00181] Triethylamine trihydrofluoride (14.69 pL, 90.12 pmol, 4 equivalents) was added to a solution of the compound PY-4car2-d (15 mg, 22.53 pmol, 1 equivalent) in tetrahydrofuran (3 mL) under an ice bath. The resulting solution was stirred for 5 minutes and then kept under stirring at room temperature (25 °C) overnight. The residue was purified by preparative reversed-phase chromatography (preparative chromatography manufacturer: SHIMADZU, model: LC-20AP, column: YMC-Triart Prep C18 250 x 30 mm x 10 µm, mobile phase: water (0.225% HCOOH)-acetonitrile, acetonitrile elution ratio: 20% to 55%) to obtain a target compound PY-4Car2 (3.77 mg, yield = 30.34%).

[00182] LCMS(ESI): m / z, 552[M+H]+.

[00183] 1H NMR (400 MHz, DMSO-de) δ 7.91 (d, J = 8.8 Hz, 1H), 7.78 (d, J = 10.8 Hz, 1H), 7.31 (s, 1H), 6.51 (s, 1H), 5.42 (s, 2H), 5.24 (d, J = 4.2 Hz, 2H), 4.41 (t, J = Petition 870260084912, dated 08 / 20 / 2026, p. 214 / 1402 207 / 694 5.2 Hz, 1H), 4.15-4.03 (m, 2H), 3.43 (q, J = 6.2 Hz, 2H), 3.29 - 3.06 (m, 3H), 2.38 (d, J = 1.8 Hz, 3H), 2.25-2.08 (m, 2H), 1.93-1.81 (m, 2H), 1.65 (p, J = 6.8 Hz, 2H), 1.50 (p, J = 6.6 Hz, 2H), 0.87 (t, J = 7.2 Hz, 3H).19F NMR (377 MHz, DMSO-d 6) δ -111.37. Example of Preparation 7: Preparation of 3-hydroxypropyl((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[d]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-1-yl)carbamate (PY-4Car3C) Petition 870260084912, dated 08 / 20 / 2026, p. 215 / 1402 208 / 694 TBSO HY Step 1: Preparation of the compound 3-((tert-butyldimethylsilyl)oxy)propyl(4-nitrophenyl)carbonate

[00184] Bis(p-nitrobenzyl carbonate) (1.28 g, 852.31 pL, 4.20 mmol, 2 equivalents) and DIPEA (543.14 mg, 694.55 pL, 4.20 mmol, 2 equivalents) were added to a solution of 3-((tert-butyldimethylsilyl)oxy)propanol (400 mg, 2.10 mmol, 1 equivalent) in DMF (5 mL) at 0 °C, and the resulting solution was stirred at room temperature (25 °C) for 16 hours. Then, the reaction solution was added to 60 mL of water and extracted with ethyl acetate three times (20 mL of ethyl acetate for each extraction), and the organic phases were combined, washed with brine (60 mL), dried with anhydrous sodium sulfate, and filtered. The filtrate was evaporated to dryness. Petition 870260084912, dated 08 / 20 / 2026, page 216 / 1402 209 / 694 to obtain the crude product, which was subsequently purified by silica gel column chromatography (elution: ethyl acetate / petroleum = 1:30-1:20), resulting in a light yellow oily compound, 3-((tert-butyldimethylsilyl)oxy)propyl(4-nitrophenyl)carbonate (740 mg, yield: 99.07%).

[00185] 1H NMR (400 MHz, Chloroform-d) δ 8.30-8.26 (m, 2H), 7.40-7.35 (m, 2H), 4.41 (t, J = 6.4 Hz, 2H), 3.76 (t, J = 5.9 Hz, 2H), 1.99-1.93 (m, 2H), 0.90 (s, 9H), 0.07 (s, 6H). Step 2: Preparation of the PY-4Car 3C-a compound

[00186] HOBt (10.17 mg, 99.96%, 6.78 pL, 75.24 pmol, 1 equivalent) and DIPEA (29.17 mg, 99%, 37.31 pL, 225.73 pmol, 3 equivalents) were added to a solution of the compound 3-((tert-butyl-dimethylsilyl)oxy)propyl(4-nitrophenyl)carbonate (32.10 mg, 90.29 pmol, 1.2 equivalents) and exatecan mesylate (40 mg, 75.24 pmol, 1 equivalent) in DMF (2 mL), and after the addition, the resulting solution was stirred at room temperature (25 °C) for 1 hour, and analysis by LC-MS indicated that the reaction was complete. The reaction solution was purified by high-performance liquid chromatography (preparative chromatography manufacturer: Oriendo, model: BRIX-2860, column: Welch Xtimate C18 150 x 21.2 mm x 5 µm, mobile phase: water (0.225% HCOOH)-acetonitrile). Petition 870260084912, dated 08 / 20 / 2026, page 217 / 1402 210 / 694 a water elution ratio: 50% to 80%) and the reaction solution was lyophilized to obtain a light yellow solid compound PY-4Car 3C-a (45 mg, yield: 91.75%).

[00187] LCMS: m / z = 652.3 [M+1]+; Rt = 3,098 min. Step 3: Preparation of the PY-4Car 3C compound

[00188] Triethylamine trihydrofluoride (499.70 mg, 98%, 505.26 pL, 3.04 mmol, 50 eq) was added to a solution of the compound PY-4Car3C-a (45 mg, 60.75 pmol, 1 eq) in THF (2 mL) at room temperature and, after the addition, the reaction solution was stirred at 40 °C for 10 hours. LC-MS analysis indicated that the reaction was complete. The reaction solution was purified by high-performance liquid chromatography (preparative chromatography manufacturer: SHIMADZU, model: LC-20AP, column: Welch Xtimate C18 250 x 30 mm x 10 µm, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution ratio: 30% to 60%) and the reaction solution was lyophilized to obtain a yellow solid compound PY-4Car3C (27.40 mg, yield: 83.90%, purity: 98.19%).

[00189] LCMS: m / z = 538.2 [M+1]+; Rt = 1,508 min.

[00190] 1H NMR (400 MHz, DMSO-dβ) δ 7.92 (d, J = 8.8 Hz, 1H), 7.77 (d, J = 10.9 Hz, 1H), 7.30 (s, 1H), 6.52 (s, 1H), 5.42 (s, 2H), 5.23 (d, J = 6.4 Hz, 3H), 4.51 (s, 1H), 4.20-4.15 (m, 1H), 4.13-4.05 (m, 1H), 3.50 (t, J = 6.4 Hz, 2H), 3.23 (s, 1H), 3.14-3.07 (m, 1H), 2.37 (d, J = 1.8 Hz, Petition 870260084912, dated 08 / 20 / 2026, p. 218 / 1402 211 / 694 3H), 2.24-2.09 (m, 2H), 1.92-1.82 (m, 2H), 1.76 (p, J = 6.5 Hz, 2H), 0.87 (t, J = 7.3 Hz, 3H). Example Preparation 8: Preparation of (1S,9S)-9-ethyl5-fluoro-9-hydroxy-1-(2-hydroxyethyl)(methyl)amino)-4-methyl 1,2,3,9,12,15-hexahydro-10H,13H benzo[de]pyrano[3',4:6,7]indolizino[1,2-b]quinoline-10,13dione (PY-5)

[00191] The compound (1S,9S)-9-ethyl-5-fluoro-9-hydroxy-1-((2-hydroxymethyl)amino)-4-methyl-1,2,3,9,12,15-hexahydro-10H,13H-benzo[de]pyrano[3,,4,:6,7]indolizino[1,2b]quinoline-10,13-dione (PY-4) (25 mg, 52.14 pmol) was dissolved in methanol (2 mL), then paraformaldehyde (7.83 mg, 260.69 pmol) and glacial acetic acid (626.19 pg, 10.43 pmol) were added to the solution, and the reaction system was stirred at 60 °C for two hours. Sodium cyanoborohydride (16.38 mg, 260.69 pmol) was added and the reaction system was stirred at 30 °C for 16 hours. The reaction solution was then cooled to the desired temperature. Petition 870260084912, dated 08 / 20 / 2026, page 219 / 1402 212 / 694 ambient, 20 mL of saturated ammonium chloride solution were added to the system and ethyl acetate was used for extraction (20 mL χ 3). After being combined, the organic phases were rinsed with saturated brine, dried with anhydrous Na2SO4 and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by high-performance preparative liquid chromatography (Oriendo, BRIX-2860; column: Phenomenex Luna C18 250 χ 50 mm χ 10 pm; mobile phase: water (0.225% trifluoroacetic acid)-acetonitrile, eluted from 40% to 80%), to obtain a solution of the purified product, 1 drop of hydrochloric acid was added to the solution and the mixture was lyophilized to obtain a yellow solid PY-5 (7.63 mg, yield: 29.65%).

[00192] LCMS: [M+H]+= 494.8.

[00193] 2.57-2.69 (s, 3H), 2.933.15 (m, 2H), 3.19-3.31 (m, 1H), 3.34-3.42 (m, 1H), 3.783.92 (m, 2H), 5.08-5.44 (m, 4H), 7.12-7.14 (s, 1H), 7,147.18 (d, J=10.4 Hz, 1H). Example Preparation 9: Preparation of N-(1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4:6,7]indolizino[1,2b]quinoline-1-yl)-N-(2-hydroxyethyl)formamide (PY-6A1) Petition 870260084912, dated 08 / 20 / 2026, p. 220 / 1402 213 / 694

[00194] Acetic anhydride (63.87 mg, 625.65 pmol) was added dropwise to a solution of acetic acid (31.31 mg, 521.38 pmol) in anhydrous tetrahydrofuran (1 mL), and the reaction system was maintained at 50 °C for 1 hour. A solution of the compound (1S,9S)-9-ethyl-5-fluoro-9-hydroxy-1-((2-hydroxymethyl)amino)4-methyl-1,2,3,9,12,15-hexahydro-10H,13H benzo[de]pyrano[3,,4,:6,7]indolizino[1,2-b]quinolin-10,13dione (PY-4) (100 mg, 208.55 pmol) in anhydrous tetrahydrofuran (5 mL) was added to the reaction system, and the reaction system was reacted at 20 °C for 4 hours. 20 mL of water were added to the reaction system, and ethyl acetate was used for extraction (20 mL χ 3). After being combined, the organic phases were rinsed with saturated brine, dried with anhydrous Na2SO4, and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by high-performance preparative liquid chromatography (Oriendo, BRIX-2860; column: Phenomenex Luna C18). Petition 870260084912, dated 08 / 20 / 2026, p. 221 / 1402 214 / 694 250 χ 50 mm χ 10 pm; mobile phase: water (0.225% trifluoroacetic acid)-acetonitrile, eluted from 40% to 80%), the resulting solution was lyophilized to obtain a white solid compound PY-6A1 (4.02 mg, 7.92 pmol, yield: 3.80%).

[00195] LCMS: [M+H]+= 508.2.

[00196] 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 0.77-0.95 (t, J=0.9Hz, 3H), 1.75-1.91 (m, 2H), 2.15-2.33 (m, 1H), 2.322.39 (s, 3H), 2.94-3.14 (m, 2H), 3.40-3.66 (m, 2H), 4.67-5.30 (m, 3H), 5.31-5.57 (m, 3H), 6.46-6.51 (s, 1H), 7.26-7.30 (s, 1H), 7.71-7.82 (m, 1H), 8.11-8.29 (d, J=44.6 Hz, 1H). Example Preparation 10: Preparation of N-(1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4:6,7]indolizino[1,2b]quinoline-1-yl)-N-(2-hydroxyethyl)acetamide (PY-6A2)

[00197] Three triethylamine equivalents (12 mg, A solution of 0.12 mmol) and an equivalent of acetyl chloride (3.27 mg, 41.70 pmol) were added to a solution of the compound. Petition 870260084912, dated 08 / 20 / 2026, page 222 / 1402 215 / 694 (1S,9S)-9-ethyl-5-fluoro-9-hydroxy-1-((2-hydroxymethyl)amino) 4-methyl-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3,,4,:6,7]indolizino[1,2-b]quinolin-10,13dione (PY-4) (20 mg, 0.04 mmol) in dichloromethane (1 mL), maintained at 0 °C, and the reaction system was then stirred at 0 °C for two hours. The reaction solution was concentrated under reduced pressure. The residue was purified by high-performance liquid chromatography (Oriendo, BRIX-2860; column: Phenomenex Luna C18 250 x 50 mm x 10 µm; mobile phase: water (0.225% trifluoroacetic acid)-acetonitrile, eluted from 40% to 80%), to obtain a white solid compound PY-6A2 (3.25 mg, 15%).

[00198] LCMS(ESI): m / z, 522.2 [M+1]+.

[00199] 1H NMR (400 MHz, DMSO-d6) δ 8.13 (s, 1 H) 7.75 (br d, J = 9.6 Hz, 1 H) 7.25-7.38 (m, 1 H) 6.52 (s, 1 H) 5.30-5.53 (m, 4 H) 4.04 - 4.33 (m, 2 H) 2.85-3.19 (m, 5 H) 2.29-2.41 (m, 4 H) 2.03-2.23 (m, 5 H) 1.83-1.95 (m, 2 H) 0.87 (t, J = 7.2 Hz, 3 H). Example of Preparation 11: Preparation of N-(1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4:6,7]indolizino[1,2b]quinoline-1-yl)-N-(2-hydroxyethyl)methanesulfonamide (PY6B1) Petition 870260084912, dated 08 / 20 / 2026, p. 223 / 1402 216 / 694

[00200] Three equivalents of triethylamine (12 mg, 0.12 mmol) and one equivalent of methanesulfonyl chloride (5 mg, 0.04 mmol) were added to a solution of the compound (1S,9S)-9-ethyl-5-fluoro-9-hydroxy-1-((2-hydroxymethyl)amino)4-methyl-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3,,4,:6,7]indolizino[1,2-b]quinolin-10,13dione (PY-4) (20 mg, 0.04 mmol) in dichloromethane (1 mL), maintained at 0 °C, and the reaction system was then stirred at 0 °C for two hours. The reaction solution was concentrated under reduced pressure. The residue was purified by high-performance liquid chromatography (Oriendo, BRIX-2860; column: Phenomenex Luna C18 250 x 50 mm x 10 gm; mobile phase: water (0.225% trifluoroacetic acid)-acetonitrile, eluted from 48% to 80%), to obtain a white solid compound PY-6B1 (1.3 mg, yield: 15%).

[00201] LCMS(ESI): m / z, 558.2 [M+1]+.

[00202] 1H NMR (400 MHz, DMSO-d6) δ 8.22 (d, J = 13.6 Petition 870260084912, dated 08 / 20 / 2026, page 224 / 1402 217 / 694 Hz, 1 H) 7.70-7.81 (m, 1H), 7.28-7.35 (m, 1H) 6.55 (d, J = 1.6 Hz, 1 H), 5.43 (s, 3 H) 4.15-4.37 (m, 1 H), 2.80-3.11 (m, 4 H) 2.63-2.70 (m, 1 H), 2.27-2.40 (m, 6 H), 2.01-2.24 (m, 2 H) 1.53-1.95 (m, 4 H), 0.80-0.94 (m, 3 H). Example of Preparation 12: Preparation of (S)-9-ethyl-5fluoro-9-hydroxy-4-(3-hydroxypropyl)-1,2,3,9,12,15hexahydro-10H,13H-benzo[de]pyrano[3',4:6,7]indolizino[1,2b]quinoline-10,13-dione (PY-8) Petition 870260084912, dated 08 / 20 / 2026, p. 225 / 1402 218 / 694 Step 1: Preparation of 1-bromo-3-fluoro-2-methoxy-5-nitrobenzene (PY-82)

[00203] Concentrated sulfuric acid (30 mL) was added to a solution of 2-fluoro-1-methoxy-4-nitrobenzene (PY-81) (50 g, 292 mmol) and NBS (57.2 g, 321 mmol) in acetic acid (500 mL) and the resulting solution was stirred overnight at 120 °C. The reaction solution was concentrated, allowed to stand to precipitate a milky white solid and filtered, and a filter cake was washed with water and ethanol and dried to obtain the compound PY-82 (58 g, yield: 79%).

[00204] LCMS(ESI): m / z, 249.9 [M+H]+.

[00205] 1H NMR (400 MHz, DMSO-d6) δ 8.34-8.23 (m, 2H), 4.07 (d, J = 3.2 Hz, 3H). Step 2: Preparation of 3-bromo-5-fluoro-4-methoxyaniline (PY-83)

[00206] Concentrated hydrochloric acid (3.34 mL, 0.55 equiv.) and 83 mL of water were sequentially added to a solution of the compound 1-bromo-3-fluoro-2-methoxy-5-nitrobenzene (PY-82) (50 g, 200 mmol) and ferrous powder (55.85 g, 1 mol) in ethanol (500 mL), and the resulting solution was stirred overnight at 80 °C. The reaction solution was filtered through diatomaceous earth and concentrated under reduced pressure, and the residue was isolated and purified by silica gel column chromatography (PE: EA = 3:1) to obtain the compound PY-83 (40 g, Petition 870260084912, dated 08 / 20 / 2026, p. 226 / 1402 219 / 694 income: 90%).

[00207] LCMS(ESI): m / z, 219.9 [M+H]+.

[00208] 1H NMR (400 MHz, DMSO-d6) δ 6.59 (t, J = 2.0 Hz, 1H), 6.41 (dd, J = 13.2, 2.6 Hz, 1H), 5.40 (s, 2H), 3.67 (s, 3H). Step 3: Preparation of N-(3-bromo-5-fluoro-4-methoxyphenyl)acetamide (PY-84)

[00209] Acetyl chloride (4 mL, 1.2 equiv.) was added to a solution of the compound 3-bromo-5-fluoro-4-methoxyaniline (PY-83) (10.0 g, 45.4 mmol) and triethylamine (13.9 mL, 2.2 equiv.) in dichloromethane (500 mL) and the resulting solution was stirred overnight at 25 °C. The reaction was stopped using 150 mL of saturated ammonium chloride, then 3 χ 80 mL of dichloromethane were added for extraction, the organic phase was washed with 80 mL of saturated sodium chloride solution and concentrated under reduced pressure, and the residue was isolated and purified by silica gel column chromatography (PE: EA = 3:1) to obtain the compound PY-84 (10 g, yield: 84%).

[00210] LCMS(ESI): m / z, 264.0 [M+H]+. Step 4: Preparation of ethyl (Z)-4-(5-acetamido-3-fluoro-2-methoxyphenyl)butyl-3-enoate (PY-85)

[00211] DIPEA (60 mL, 6.0 equiv.) and ethyl crotonate Petition 870260084912, dated 08 / 20 / 2026, page 227 / 1402 220 / 694 (1.5 equiv., 10.89 mL) were sequentially added to a solution of the compound N-(3-bromo-5-fluoro-4-methoxyphenyl)acetamide (PY-84) (15 g, 57.23 mmol) and Pd(tBuaP)2 (1.46 g, 0.05 equiv.) in toluene (200.0 mL) and the resulting solution was stirred overnight at 13 °C. The reaction mixture was concentrated directly under reduced pressure and the residue was isolated and purified by silica gel column chromatography (PE:EA = 1:2) to obtain the compound PY-85 (7.9 g, yield: 46%).

[00212] LCMS(ESI): m / z, 296.1 [M+H]+. Step 5: Preparation of ethyl 4-(5-acetamido-3-fluoro-2-methoxyphenyl)butyrate (PY-86)

[00213] Palladium on carbon (0.1 equiv., 2.88 g) was added to a solution of the compound ethyl (Z)-4-(5-acetamido-3-fluoro-2-methoxyphenyl)butyl-3-enoate (PY-85) (8.0 g, 27.08 mmol) in methanol (100.0 mL) and the resulting solution was reacted at 50 °C overnight. The reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure and dried to obtain a crude compound PY-86, which was used directly for the following reaction.

[00214] LCMS(ESI): m / z, 298.1 [M+H]+. Step 6: Preparation of 4-(5-acetamido-3-fluoro-2-methoxyphenyl)butyric acid (PY-87) Petition 870260084912, dated 08 / 20 / 2026, p. 228 / 1402 221 / 694

[00215] Lithium hydroxide (3 equiv., 1.93 g) was added to a mixed solvent of ethyl 4-(5-acetamido-3-fluoro-2-methoxyphenyl)butyrate (PY-86) (8 g, 26 mmol) in methanol, tetrahydrofuran, and water (120 mL) (mixture in a 1:1:1 ratio), and the resulting solution was allowed to react overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and then ethyl acetate (2 x 80 mL) was used to extract impurities and remove the organic phase. Next, concentrated hydrochloric acid was added to the aqueous phase to adjust the pH value to 1, and then it was extracted with ethyl acetate (3 χ 80 mL), the organic phases were combined, dried with anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure to obtain the compound PY-87 (3.8 g, yield: 70%).

[00216] LCMS(ESI): m / z 270.1 [M+H]+; 292.1 [M+Na]+.

[00217] 1H NMR (400 MHz, DMSO-d6) δ 12.07 (s, 1H), 9.99 (s, 1H), 7.50 (dd, J = 13.6, 2.4 Hz, 1H), 7.09-7.03 (m, 1H), 3.77 (d, J = 1.2 Hz, 3H), 2.63-2.53 (m, 2H), 2.25 (t, J = 7.2 Hz, 2H), 2.02 (s, 3H), 1.75 (dq, J = 9.2, 7.2 Hz, 2H). Step 7: Preparation of N-(3-fluoro-4-methoxy-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-88)

[00218] A solution of the compound 4-(5-acetamidoacetyl) Petition 870260084912, dated 20 / 08 / 2026, page 229 / 1402 222 / 694 3-fluoro-2-methoxyphenyl)butyric acid (PY-87) (1 g, 3.71 mmol) in PPA (polyphosphoric acid) was stirred for 3 hours at 95 °C. The reaction mixture was added to ice-cold water, washed with water, then extracted with ethyl acetate (3 χ² 30 mL), dried with anhydrous sodium sulfate, and then filtered and concentrated under reduced pressure. The residue was purified by high-performance liquid chromatography (Oriendo, BRIX2860; column: Phenomenex Luna C18 250 χ² 50 mm χ² 10 gm; mobile phase: water (0.225% trifluoroacetic acid)-acetonitrile, eluted 45% to 85%) and lyophilized to obtain compound PY-88 (110 mg, yield: 11%).

[00219] LCMS(ESI): m / z, 252.1 [M+H]+; 274.0 [M+Na]+.

[00220] 1H NMR (400 MHz, DMSO-d6) δ 12.05 (s, 1H), 8.37 (d, J = 14.8 Hz, 1H), 3.81 (d, J = 1.2 Hz, 3H), 2.95 (t, J = 6.0 Hz, 2H), 2.66 (dd, J = 7.2, 5.6 Hz, 2H), 2.16 (s, 3H), 1.99 (q, J = 6.4 Hz, 2H). Step 8: Preparation of N-(3-fluoro-4-hydroxy-8-oxy-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-89)

[00221] The compound N-(3-fluoro-4-methoxy-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-88) (1.3 g) was dissolved in DCE (20 mL), 5 equivalents of AlCla were added, and the resulting solution was stirred at 60 °C for 5 hours. 100 mL of water was added for dilution, and the resulting solution was extracted with acetate. Petition 870260084912, dated 08 / 20 / 2026, pp. 230 / 1402 223 / 694 ethyl, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain 910 mg of the yellow solid compound PY-89.

[00222] LCMS(ESI): m / z, 238.0 [M+1]+. Step 9: Preparation of 4-acetamido-2-fluoro-5-oxy-5,6,7,8-tetrahydronaphthalene-1-yltrifluoromethanesulfonate (PY-810)

[00223] The compound N-(3-fluoro-4-hydroxy-8-oxy5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-89) (0.9 g) was dissolved in DCM (20 mL), 3 equivalents of triethylamine and 3 equivalents of trifluoromethanesulfonic anhydride were added, the resulting solution was stirred at room temperature for 3 hours and concentrated under reduced pressure, and the residue was isolated and purified by silica gel column chromatography (ethyl acetate / hexane = 1:5) to obtain 0.9 g of yellow solid compound PY-810.

[00224] LCMS(ESI): m / z, 370.1 [M+1]+. Step 10: Preparation of N-(4-(3-(benzyloxy)propyl-1-alkynyl-1-yl)-3-fluoro-8-oxy-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-811)

[00225] The compound 4-acetamido-2-fluoro-5-oxy5,6,7,8-tetrahydronaphthalene-1-yltrifluoromethanesulfonate Petition 870260084912, dated 08 / 20 / 2026, p. 231 / 1402 224 / 694 (PY-810) (420 mg) was dissolved in DMF (10 mL) and 2 equivalents of triethylamine, 3 equivalents of propargyl benzyl ether, 0.2 equivalents of Pd(PPha)2Cl2 and 0.1 equivalents of CuI were added. The resulting solution was stirred at 80 °C for 12 hours under a nitrogen atmosphere. The resulting solution was diluted with 100 mL of water, extracted with ethyl acetate, dried with anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by preparative high-performance liquid chromatography (Oriendo, BRIX-2860; column: Phenomenex Luna C18 250 x 50 mm x 10 gm; mobile phase: water (0.225% trifluoroacetic acid)-acetonitrile, eluted from 45% to 85%), to obtain 250 mg of the yellow solid compound PY811.

[00226] LCMS(ESI): m / z, 366.1 [M+1]+. Step 11: Preparation of N-(3-fluoro-4-(3-hydroxypropyl)-8-oxy-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-812)

[00227] The compound N-(4-(3-(benzyloxy)propyl-1-alkynyl-1-yl)-3-fluoro-8-oxy-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-811) (250 mg) was dissolved in MeOH (10 mL), 0.1 equivalents of palladium on carbon were added, and the resulting solution was stirred at room temperature for 12 hours under a hydrogen atmosphere. A Petition 870260084912, dated 08 / 20 / 2026, page 232 / 1402 The resulting 225 / 694 solution was filtered and the filtrate was concentrated under reduced pressure to obtain 150 mg of the yellow solid compound PY-812.

[00228] LCMS(ESI): m / z, 280.2 [M+1]+. Step 12: Preparation of 8-amino-6-fluoro-5-(3-hydroxypropyl)-3,4-dihydronaphthalene-1(2H)-one (PY-813)

[00229] The compound N-(3-fluoro-4-(3-hydroxypropyl)-8oxy-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-812) (150 mg) was dissolved in 6N HCl (2 mL) and EtOH (2 mL), and the resulting solution was stirred at 60 °C for 3 hours, filtered, and concentrated under reduced pressure to obtain 125 mg of the yellow solid compound PY-813.

[00230] LCMS(ESI): m / z, 238.1 [M+1]+. Step 13: Preparation of (S)-9-ethyl-5-fluoro-9-hydroxy-4-(3-hydroxypropyl)-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4:6,7]indolizino[1,2-b]quinoline-10,13dione (PY-8)

[00231] The compound 8-amino-6-fluoro-5-(3-hydroxypropyl)-3,4-dihydronaphthalene-1(2H)-one (PY-813) (125 mg, 0.53 mmol) and 1.1 equivalents of (S)-4-ethyl-4-hydroxy7,8-dihydro-1H-pyrano[3,4-f]indolizino-3,6,10(4H)-trione (ChemExpress, 152 mg, 0.58 mmol) were dissolved in 10 mL of xylene and 0.3 equivalents of PPTS were added. Petition 870260084912, dated 08 / 20 / 2026, page 233 / 1402 226 / 694 (pyridinium p-toluenesulfonate) (40 mg, 0.16 mmol). The resulting solution was stirred at 120 °C for 12 hours under a nitrogen atmosphere. The resulting solution was concentrated under reduced pressure. The residue was isolated and purified by high-performance liquid chromatography (Oriendo, BRIX-2860; column: Phenomenex Luna C18 250 x 50 mm x 10 µm; mobile phase: water (0.225% trifluoroacetic acid)acetonitrile, eluted 45% to 85%) and lyophilized to obtain a yellow solid compound PY-8 (42 mg, yield: 17%).

[00232] LCMS(ESI): m / z, 456.2 [M+1]+.

[00233] 1H NMR (400 MHz, DMSO-d6) δ 7.72 (d, J = 11.2 Hz, 1H), 7.30 (s, 1H), 6.51 (s, 1H), 5.43 (s, 2H), 5.24 (s, 2H), 4.60 (t, J = 5.2 Hz, 1H), 3.49 (q, J = 6.0 Hz, 2H), 3.16 (t, J = 6.0 Hz, 4H), 2.87 (t, J = 8.0 Hz, 2H), 2.08 (t, J = 6.0 Hz, 2H), 1.88-1.87 (m, 2H), 1.69 (p, J = 6.4 Hz, 2H), 0.88 (t, J = 7.2 Hz, 3H). Example of Preparation 13: Preparation of (S)-9-ethyl-5fluoro-9-hydroxy-4-propyl-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13dione (PY-8B) PY-8B Petition 870260084912, dated 08 / 20 / 2026, p. 234 / 1402 227 / 694 Step 1: Preparation of N-(3-bromo-5-fluorophenyl)acetamide (PY-8a)

[00234] 3-bromo-5-fluoroaniline (50 g, 0.263 mol) was dissolved in dichloromethane (700 mL), triethylamine (53.2 g, 0.526 mol) was added at room temperature, acetic anhydride (40.3 g, 0.395 mol) was added slowly dropwise under an ice-cold water bath, and after addition, the resulting solution reacted at room temperature for 2 hours. Water (400 mL) was added, and then the aqueous phase was extracted with dichloromethane (200 mL), the organic phases were combined, washed sequentially with saturated sodium chloride solution (300 mL χ2), dried with anhydrous sodium sulfate and filtered, the filtrate was concentrated under pressure. Petition 870260084912, dated 08 / 20 / 2026, p. 235 / 1402 228 / 694 reduced and the residue was pulverized with n-heptane and filtered to obtain N-(3-bromo-5-fluorophenyl)acetamide (54 g, yield: 88.4%). Step 2: Preparation of tert-butyl (E)-4-(3-acetamido5-fluorophenyl)but-3-enoate (PY-8b)

[00235] N-(3-bromo-5-fluorophenyl)acetamide (PY-8a) (54g, 0.2327 mol) was dissolved in N,N-dimethylformamide (700 mL), bis(tri-tert-butylphosphine)palladium (5.97g, 11.64 mmol), tris(o-methylphenyl)phosphorus (7.07g, 23.27 mmol), N-methyldicyclohexylamine (100g, 0.5119 mol) and tert-butyl 3-butenoate (66.1g, 0.4654 mol) were added sequentially, nitrogen shift was performed three times and then the resulting solution reacted at 100 °C for 16 hours.Ethyl acetate (600 mL) and water (1 L) were added for extraction, then the aqueous phase was extracted with ethyl acetate (300 mL), the organic phases were combined, washed sequentially with saturated sodium chloride solution (500 mL χ 2), dried with anhydrous sodium sulfate, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography with an ethyl acetate / n-heptane (0%-30%) eluent system to obtain tert-butyl (E)-4-(3acetamido-5-fluorophenyl)but-3-enoate (65 g, yield: 95.3%). Petition 870260084912, dated 08 / 20 / 2026, p. 236 / 1402 229 / 694 Step 3: Preparation of tert-butyl 4-(3-acetamido-5-fluorophenyl)butyrate (PY-8c)

[00236] tert-butyl(E)-4-(3-acetamido-5-fluorophenyl)but-3-enoate (PY-8b) (65 g, 0.2218 mol) was dissolved in methanol (1.3 L), nitrogen substitution was performed once, then Pd / C (33 g, 0.3101 mol) was added and, after the addition, nitrogen substitution was performed again, hydrogen substitution twice, and the resulting solution was left to react at room temperature for 16 hours. The resulting solution was filtered, the filtrate was concentrated under reduced pressure, and the residue was purified by reversed-phase chromatography with an acetonitrile / purified water eluent system (0%-90%) to obtain tert-butyl 4-(3-acetamido-5-fluorophenyl)butyrate (PY-8c) (55 g, yield: 84%). Step 4: Preparation of tert-butyl 4-(5-acetamido-2-bromo-3-fluorophenyl)butyrate (PY-8d)

[00237] 4-(3-acetamido-5-fluorophenyl) tert-butyl butyrate (PY-8c) (55 g, 0.1864 mol) was dissolved in N,N-dimethylformamide (600 mL). NBS (36.5 g, 0.2051 mol) was added in different batches under an ice-cold water bath, and after addition, the resulting solution was stirred at room temperature for 1 hour. Then, acetate was added. Petition 870260084912, dated 08 / 20 / 2026, page 237 / 1402 230 / 694 ethyl (300 mL) and water (400 mL) for extraction, then the aqueous phase was extracted with ethyl acetate (100 mL) once, the organic phases were combined, washed sequentially with saturated sodium chloride solution (300 mL χ 2), dried with anhydrous sodium sulfate and filtered, the filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography with an ethyl acetate / n-heptane eluent system (0%-30%) to obtain tert-butyl 4-(5-acetamido-2-bromo-3-fluorophenyl)butyrate (59 g, yield: 84.6%). Step 5: Preparation of 4-(5-acetamido-2-bromo-3-fluorophenyl)butyric acid (PY-8e)

[00238] tert-butyl 4-(5-acetamido-2-bromo-3-fluorophenyl)butyrate (PY-8d) (59 g, 0.1577 mol) was dissolved in dichloromethane (300 mL), HCl / dioxane (400 mL, 1.6 mol) was added dropwise in an ice water bath and, after the addition, the resulting solution reacted at room temperature for 16 hours and was filtered, and the filtrate was concentrated under reduced pressure to obtain 4-(5-acetamido-2-bromo-3-fluorophenyl)butyric acid (42 g, yield: 83.7%). Step 6: Preparation of N-(4-bromo-3-fluoro-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-8g)

[00239] 4-(5-acetamido-2-bromo-3-acid Petition 870260084912, dated 20 / 08 / 2026, page 238 / 1402 231 / 694 fluorophenyl)butyric acid (PY-8e) (42 g, 0.1321 mol) and Eaton's reagent (210 g) were added to a 1 L three-necked flask, the nitrogen was replaced 3 times, and the resulting solution was reacted at 85 °C for 1 hour. The reaction solution was slowly added dropwise to water (2 L) in an ice-cold water bath and filtered. The filter cake was washed with water, and then the filtrate was concentrated and dried under reduced pressure and subsequently purified by silica gel column chromatography with an ethyl acetate / dichloromethane (0%-30%) eluent system to obtain a crude product (30 g). Next, the crude product was pulverized with an ethyl acetate (10 mL) / petroleum ether (100 mL) system and filtered to obtain N-(4-bromo-3-fluoro-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (20 g, yield: 50.4%).

[00240] LCMS(ESI): m / z, 300.0 [M+H]+.

[00241] 1H NMR (400 MHz, CDCla) δ 12.35 (s, 1H), 8.61 (d, J = 11.6 Hz, 1H), 3.07 (t, J = 6.0 Hz, 2H), 2.69 (dd, J = 7.2 Hz, 2H), 2.24 (s, 3H), 2.11 (p, J = 6.4 Hz, 2H). Step 7: Preparation of N-(4-(3-(benzoyloxy)propyl-1-alkynyl-1-yl)-3-fluoro-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-8h)

[00242] N-(4-bromo-3-fluoro-8-oxo-5,6,7,8tetrahydronaphthalene-1-yl)acetamide (PY-8g) (1.8 g, 6.0 mmol) Petition 870260084912, dated 08 / 20 / 2026, p. 239 / 1402 232 / 694 was dissolved in anhydrous DMF (50 mL) in a nitrogen atmosphere, (prop-2-en-1-oxy)methyl)benzene (4.34 mL, 29.99 mmol), copper iodide (228.4 mg, 1.2 mmol), dichlorobis(triphenylphosphine)palladium (841.9 mg, 1.2 mmol) and triethylamine (3.33 mL, 23.99 mmol) were added sequentially, hydrogen shift was performed three times, and then the resulting mixture was heated to 100 °C and stirred for reaction for 16 hours. The reaction solution was concentrated to dryness and the residue was purified by silica gel column chromatography (eluents: ethyl acetate / n-hexane = 1:20-1:5) to obtain the compound PY-8h (1.0 g, yield: 45.6%) as a yellow solid.

[00243] LCMS: m / z = 366.1 [M+1]+; Rt = 1.108. Step 8: Preparation of N-(3-fluoro-8-oxo-4-propyl-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-8i)

[00244] The compound PY-8h (2.5 g, 6.84 mmol) was dissolved in methanol (20 mL) and tetrahydrofuran (20 mL), palladium was added over charcoal (4.0 g), hydrogen displacement was performed three times, and the resulting mixture was heated to 45 °C and stirred for 4 hours. After filtration, the reaction solution was concentrated directly, and the crude product was used directly for the next reaction. Petition 870260084912, dated 08 / 20 / 2026, pages 240 / 1402 233 / 694

[00245] LCMS: m / z = 264.1 [M+1]+; Rt = 1,056. Step 9: Preparation of 8-amino-6-fluoro-5-propyl-3,4-dihydronaphthalene-1(2H)-one (PY-8j)

[00246] Compound PY-8i (1.91 g, 6.84 mmol) was dissolved in 6M hydrochloric acid (20 mL) and ethanol (20 mL), and the resulting mixture was heated to 60 °C and stirred for 1 hour. The reaction solution was concentrated to dryness, and the crude product was used directly for the next reaction. Step 10: Preparation of (S)-9-ethyl-5-fluoro-9-hydroxy-4-propyl-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13-dione (PY-8B)

[00247] Compound PY-8j (960 mg, 1.0 eq) and (S)-4-ethyl-4-hydroxy-7,8-dihydro-1H-pyrano[3,4-f]indolizino3,6,10(4H)-trione (PY-8f) (ChemExpress, 1.17 g, 1.1 eq) were dispersed in toluene (25 mL) in a nitrogen atmosphere, pyridinium p-toluenesulfonate (508 mg, 0.5 eq) was added, and the resulting mixture was heated to 120 °C and stirred for 16 hours to react. The reaction solution was concentrated, and the residue was purified by silica gel column chromatography (eluents: dichloromethane / methanol = 10:1) to obtain compound PY-8B (340 mg, yield: 18%) as a brown solid. Petition 870260084912, dated 08 / 20 / 2026, pp. 241 / 1402 234 / 694

[00248] LCMS: m / z =449.2 [M+H]+; Rt = 3,313 min.

[00249] 1H NMR (400 MHz, DMSO-d6) δ 7.72 (d, J = 11.4 Hz, 1H), 7.30 (s, 1H), 6.52 (s, 1H), 5.43 (s, 2H), 5.23 (s, 2H), 3.15 (q, J = 5.6 Hz, 4H), 2.81 (t, J = 7.7 Hz, 2H), 2.08 (t, J = 5.9 Hz, 2H), 1.94-1.78 (m, J = 7.1 Hz, 2H), 1.58 (h, J = 7.4 Hz, 2H), 0.97 (t, J = 7.3 Hz, 3H), 0.88 (t, J = 7.3 Hz, 3H). Example of Preparation 14: Preparation of (S)-9-ethyl-5fluoro-9-hydroxy-4-(2-hydroxyethoxy)-1,2,3,9,12,15-hexahydro10H,13H-benzo[de]pyrano[3',4':6,7]indolizino[1,2b]quinoline-10,13-dione (PY-9)

[00250] 1 equivalent of tetrabutylammonium bromide (TBAB) (15.3 mg), 0.2 equivalents of palladium chloride catalyst (1.7 mg), 250 mL of ethylene oxide, and 2.5 equivalents of potassium carbonate (16.4 mg) were added separately to 2 mL of aqueous solution of compound PY-13 (20 mg). The reaction solution reacted at 25 °C for 16 hours, and the reaction solution was subjected to Petition 870260084912, dated 08 / 20 / 2026, p. 242 / 1402 235 / 694 preparative high-performance liquid chromatography (preparative chromatography manufacturer: SHIMADZU, model: LC-20AP, column: Welch Xtimate C18 250 χ 30 mm χ 10 gm, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution ratio: 12% to 42%) and lyophilized to obtain a crude product of a white solid compound PY-9. The white solid compound was subsequently isolated and purified by thin-layer chromatography to obtain 3.03 mg of the compound PY-9.

[00251] LCMS(ESI): m / z, 467.2 [M+H]+.

[00252] 1H NMR (400 MHz, DMSO-dβ) δ 7.83 (d, J = 12.5 Hz, 1H), 7.29 (s, 1H), 6.51 (s, 1H), 5.43 (s, 2H), 5.25 (s, 2H), 4.93 (t, J = 5.4 Hz, 1H), 4.14 (t, J = 4.9 Hz, 2H), 3.73 (q, J = 5.1 Hz, 2H), 3.16 (dt, J = 11.1, 6.1 Hz, 4H), 2.02 (dt, J = 12.6, 6.6 Hz, 2H), 1.86 (h, J = 7.0 Hz, 2H), 0.88 (t, J = 7.3 Hz, 3H);19F NMR (377 MHz, DMSO-d β)δ 123.40. Example of Preparation 15: Preparation of (S)-9-ethyl-5fluoro-9-hydroxy-4-(hydroxymethyl)-1,2,3,9,12,15-hexahydro10H,13H-benzo[de]pyrano[3',4':6,7]indolizino[1,2b]quinoline-10,13-dione (PY-10) PY-10 Petition 870260084912, dated 08 / 20 / 2026, p. 243 / 1402 236 / 694 Step 1: Preparation of 8-amino-5-bromo-6-fluoro-3,4-dihydroonaphthalene-1(2H)-one (PY-10b)

[00253] 6N HCl (6 mL) was added to a solution of compound PY-8g (2g, 6.66 mmol, 1 eq) in ethanol (6 mL), the reaction solution was stirred at 80 °C for 3 hours, and the reaction solution was cooled to room temperature, concentrated under reduced pressure, diluted with 20 mL of water and adjusted with a sodium bicarbonate solution until the pH was neutral, then the mixture was extracted with dichloromethane (30 mL x 3), and the organic phases were combined, washed with saturated brine (30 mL), dried with anhydrous sodium sulfate and concentrated under reduced pressure to obtain a crude compound 8-amino-5-bromo-6-fluoro-3,4-dihydronaphthalene-1(2H)-one (PY-10b) (1.52 g, yield: 88%; purity: 91%) as a yellow solid.

[00254] LCMS(ESI): m / z, 258 [M+1]+, 260 [M+1]+. Step 2: Preparation of (S)-4-bromo-9-ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15-hexahydro-10H,13H Preparation 870260084912, dated 20 / 08 / 2026, page 244 / 1402 237 / 694 benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13 dione (PY-10d)

[00255] Compound PY-8f (1.55 g, 5.89 mmol, 1 eq) and PPTS (1.48 g, 5.89 mmol, 1 eq) were added to a solution of compound PY-10b (1.52 g, 5.89 mmol, 1 eq) in toluene (20 mL), the reaction solution was stirred at 120 °C for 16 hours in a nitrogen atmosphere and the residue was purified by silica gel column chromatography (dichloromethane: methanol = 10:1), to obtain a yellow solid compound PY-10d (1.3 g, yield: 45%; purity: 88%).

[00256] LCMS(ESI): m / z, 485 [M+H]+, 487 [M+H]+. Step 3: Preparation of (S)-9-ethyl-5-fluoro-9-hydroxy-4(hydroxymethyl)-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13dione (PY-10)

[00257] (Tributylstannyl)methanol (2.84 g, 8.84 mmol, 3.3 eq) and Xphos Pd G2 (210.77 mg, 267.87 pmol, 0.1 eq) were added to a solution of compound PY-10d (1.30 g, 2.68 mmol, 1 eq) in dioxane (5 mL), respectively, and the reaction solution was stirred at 90 °C for 16 hours in a nitrogen atmosphere, concentrated under reduced pressure, and diluted with water and dichloromethane (50 mL / 50 mL). A solid precipitated, the reaction solution was filtered, a filter cake was collected separately, and a filtrate was extracted with Petition 870260084912, dated 08 / 20 / 2026, page 245 / 1402 238 / 694 dichloromethane (50 mL χ 3), the organic phases were combined, then washed with saturated brine (50 mL), dried with anhydrous sodium sulfate and concentrated under reduced pressure, and the residue and filter cake were purified by silica gel column chromatography (dichloromethane: methanol = 10:1) to obtain the yellow solid compound PY-10 (649 mg, yield: 55.5%, purity: 100%).

[00258] LCMS (ESI): m / z, 437 [M+H]+. Example of Preparation 16: Preparation of (S)-9-ethyl-5-fluoro-9-hydroxy-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3,4,6,7]indolizino[1,2b]quinoline-4-carboxylic acid (PY-10A) and (S)-9-ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15-hexahydro-10H,13H-benzo[de]pyrano[3',4':6,7]indolizino[1,2b]quinoline-10,13dione (PY-10B) PY-10B nh2o PY-10-3 Petition 870260084912, dated 08 / 20 / 2026, p. 246 / 1402 239 / 694 Step 1: Preparation of N-(3-fluoro-4-formyl-8-oxo5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-10-1)

[00259] H2SO4 (4.34 g, 44.21 mmol, 5.2 eq) was added to a solution of N-(3-fluoro-4-methyl-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (2 g, 8.5 mmol, 1.0 eq) and MnO2 (11.09 g, 127.52 mmol, 15 eq) in chloroform (100 mL) at 0 °C, and the reaction solution was gradually cooled to room temperature and reacted for 16 hours. After filtration, the reaction solution was adjusted with a saturated sodium bicarbonate solution until the pH was neutral, extracted with dichloromethane (30 mL x 3), and concentrated to obtain a crude yellow-brown solid product (2.1 g) to be used directly in the next step without purification.

[00260] LCMS(ESI): m / z, 250.1 [M+1]+. Step 2: Preparation of 4-acetamido-2-fluoro-5-oxo-5,6,7,8-tetrahydronaphthalene-1-carboxylic acid (PY-10-2)

[00261] Dimethylbutadiene (1.55 g, 22.07 mmol, 10 eq) was added to a solution of the compound N-(3-fluoro-4-formyl-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (1.1 g, 2.21 mmol, 1 eq), sodium chlorite (1.20 g, 13.24 mmol, 6 eq) and monobasic sodium phosphate (534 mg, 4.41 mmol, 2 eq) in methanol / water = 1 / 1 (30 mL) at 25 °C. The reaction solution was stirred at 50 °C for 2 hours. Saturated aqueous sodium bicarbonate solution was added to adjust the Petition 870260084912, dated 08 / 20 / 2026, p. 247 / 1402 240 / 694 pH 8, the reaction solution was extracted with dichloromethane (30 mL x 3) to recover the raw materials, then the aqueous phase was adjusted with 2N HCl to adjust the pH to 2, and the aqueous phase was extracted with ethyl acetate (30 mL x 3) and concentrated to obtain the compound PY-10-2 (324 mg, yield: 55.36%).

[00262] LCMS (ESI): m / z, 266.0[M+1]+. Step 3: Preparation of 4-amido-2-fluoro-5-oxo-5,6,7,8-tetrahydronaphthalene-1-carboxylic acid (PY-10-3)

[00263] The compound 4-acetamido-2-fluoro-5-oxo-5,6,7,8-tetrahydronaphthalene-1-carboxylic acid (415 mg, 1.67 mmol, 1 eq) was added to a solution of NaOH (5 M, 15 mL), the reaction solution was stirred at 80 °C for 2 hours, adjusted with dilute 2N hydrochloric acid to adjust the pH to 2 and extracted with ethyl acetate (30 mL x 3), and the organic phase was concentrated to obtain the compound PY-10-3 (320 mg, yield: 85.6%).

[00264] LCMS (ESI): m / z: 224.0[M+1]+. Step 4: Preparation of (S)-9-ethyl-5-fluoro-9-hydroxy10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3,,4,:6,7]indolizino[1,2-b]quinoline-4carboxylic acid (PY-10A) and acid (S)-9-ethyl-5-fluoro-9-hydroxy1,2,3,9,12,15-hexahydro-10H,13H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13-dione (PY-10B) Petition 870260084912, dated 08 / 20 / 2026, pp. 248 / 1402 241 / 694

[00265] The compounds 4-amido-2-fluoro-5-oxo-5,6,7,8-tetrahydronaphthalene-1-carboxylic acid (364.64 mg, 1.43 mmol, 1 eq), (S)-4-ethyl-4-hydroxy-7,8-dihydro-1Hpyrano[3,4-f]indolizino-3,6,10(4H)-trione (377.42 mg, 1.43 mmol, 1 eq) and PPTS (360.29 mg, 1.43 mmol, 1 eq) were dissolved in a toluene solution (15 mL), the reaction solution was stirred at 120 °C for 16 hours, and after removal of the solvent under reduced pressure, the residue was purified by silica gel column chromatography (eluents: dichloromethane / methanol = 10:1-5:1) to obtain a crude product of a brown oily compound, and then the crude product was isolated by preparative high-performance liquid chromatography (preparative chromatography manufacturer: Oriendo, model: Lab311-DJ-R2, column: YMC-Triart Prep C18 250 χ 30 mm χ 10 μm, mobile phase: water (0.225% HCOOH)acetonitrile, water elution ratio: 30% to 60%) and lyophilized, to obtain compound PY-10A (18.19 g, yield: 2.82%), LCMS (ESI): m / z: 451.1[M+1]+; and a compound PY-10B (46 mg, yield: 7.9%), LCMS (ESI): m / z: 407.1[M+1]+. Example of Preparation 17: Preparation of (S)-(9-ethyl-5-fluoro-9-hydroxy-10,13-dioxy-2,3,9,10,13,15-hexahydro-1H,12H-benzo[d]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-4-yl)methyl(2-hydroxyethyl)carbamate (PY-10Car) Petition 870260084912, dated 08 / 20 / 2026, pp. 249 / 1402 242 / 694 PY-10 Car-a H0^NH2 Step 1: Preparation of (S)-(9-ethyl-5-fluoro-9-hydroxy10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-4yl)methyl(4-nitrophenyl)carbonate (PY-10 Cara)

[00266] Compound PY-10 (8.0 mg, 0.018 mmol, 1.0 eq), bis(4-nitrophenyl)carbonate (44.6 mg, 0.147 mmol, 8.0 eq) and N,N-diisopropylethylamine (28.4 mg, 0.220 mmol, 12.0 eq) were added to a solution of N,N-dimethylformamide (2 mL) at room temperature and the reaction solution was stirred at 50 °C for 16 hours. LC-MS analysis indicated that the reaction was complete. The reaction solution was concentrated under reduced pressure and purified with a dichloromethane / methanol developing agent system (15 / 1) from a thin-layer chromatography plate to obtain a yellow oily compound PY-10 Car-a (18 mg, overweighted, no yield calculated).

[00267] LCMS (ESI): m / z, 602.3 [M+H]+. Step 2: Preparation of (S)-(9-ethyl-5-fluoro-9-hydroxy Petition 870260084912, dated 08 / 20 / 2026, page 250 / 1402 243 / 694 10,13-dioxy-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[d]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-4yl)methyl(2-hydroxyethyl)carbamate (PY-10Car)

[00268] The compound PY-10 Car-a (18.0 mg, impure), aminoethanol (1.83 mg, 0.030 mmol) and N,N-diisopropylethylamine (11.6 mg, 0.090 mmol) were added to a solution of N,N-dimethylformamide (1 mL) at room temperature and the reaction solution was stirred at 25 °C for 0.5 hours. LC-MS analysis indicated that the reaction was complete. The reaction solution was purified by high-performance liquid chromatography (preparative chromatography manufacturer: Luna, model: Lab311-ISCO-R4, column: Phenomenex Luna C18 250 x 50 mm x 10 pm, mobile phase: water (0.225% HCOOH)acetonitrile, water elution ratio: 12% to 42%) and the eluate was lyophilized to obtain a white solid product PY-10 Car (4.14 mg, 7.56 pmol, two-step yield: 42%).

[00269] LCMS (ESI): m / z, 524.2 [M+H]+.

[00270] 1H NMR (400 MHz, DMSO-d6) δ 7.79 (d, J = 11.2 Hz, 1H), 7.32 (s, 1H), 7.19 (t, J = 5.6 Hz, 1H), 6.54 (s, 1H), 5.44 (s, 2H), 5.27 (d, J = 4.4 Hz, 3H), 4.63 (t, J = 5.6 Hz, 1H), 3.30 - 3.23 (m, 5H), 3.18 (s, 2H), 3.04 (q, J = 6.0 Hz, 2H), 2.08 (s, 2H), 1.86 (dt, J = 15.2, 7.2 Hz, 2H), 0.87 (t, J = 7.2 Hz, 3H). Petition 870260084912, dated 08 / 20 / 2026, p. 251 / 1402 244 / 694 Example of Preparation 18: Preparation of (S)-9-ethyl-5fluoro-9-hydroxy-4-methoxy-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4:6,7]indolizino[1,2-b]quinoline-10,13dione (PY-11) Step 1: Preparation of 8-amino-6-fluoro-5-methoxy-3,4-dihydronaphthalene-1(2H)-one (PY-111)

[00271] A solution of the compound N-(3-fluoro-4-methoxy-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-88) (100 mg) in HCl (7N, 10 mL) was stirred at 100 °C for 2 hours. Saturated NaHCO3 solution (10 mL) was slowly added to quench the reaction and adjust the pH to neutral (pH 7). The reaction solution was extracted with ethyl acetate (3 χ² 30 mL), the organic phases were combined, dried with anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure to obtain a yellow solid compound PY-111 (66 mg, 79%).

[00272] LCMS (ESI): m / z, 210.1 [M+H]+. Petition 870260084912, dated 08 / 20 / 2026, page 252 / 1402 245 / 694 Step 2: Preparation of (S)-9-ethyl-5-fluoro-9-hydroxy-4-methoxy-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4:6,7]indolizino[1,2-b]quinoline-10,13dione (PY-11)

[00273] PPTS (0.67 eq, 16 mg) and (S)-4-ethyl-4-hydroxy-7,8-dihydro-1H-pyrano[3,4-f]indolizino-3,6,10(4H)-trione (1 eq, 25 mg) were added to a solution of the compound 8-amino-6-fluoro-5-methoxy-3,4-dihydronaphthalene-1(2H)-one (PY111) (20 mg) in toluene (10 mL) and the reaction solution was subjected to 140 °C for 16 hours. The reaction solution was concentrated under reduced pressure to remove the toluene and 5 mL of DMF were added. The resulting mixture was purified by preparative high-performance liquid chromatography (Orendo, BRIX-2860; column: Phenomenex Luna C18 250 χ 50 mm χ 10 pm; mobile phase: water (0.225% trifluoroacetic acid)-acetonitrile, eluted from 45% to 85%), to obtain a white solid compound PY-11 (8.4 mg, yield: 20%).

[00274] LCMS (ESI): m / z, 437.2 [M+H]+.

[00275] 1H NMR (400 MHz, DMSO-d6) δ 7.85 (d, J = 12.5 Hz, 1H), 7.30 (s, 1H), 6.52 (s, 1H), 5.43 (s, 2H), 5.25 (s, 2H), 3.94 (s, 3H), 3.14 (dt, J = 11.2, 6.0 Hz, 4H), 2.05 (q, J = 6.4, 5.8 Hz, 2H), 1.88 (dq, J = 14.4, 7.2 Hz, 2H), 0.88 (t, J = 7.2 Hz, 3H). Petition 870260084912, dated 08 / 20 / 2026, p. 253 / 1402 246 / 694 Preparation Example 19: Preparation of (1S,9S)-1amino-9-ethyl-5-fluoro-9-hydroxy-4-methoxy-1,2,3,9,12,15hexahydro-1OH,13H-benzo[de]pyrano[3',4:6,7]indolizino[1,2—b]quinoline-10,13-dione and (IR,9S)-1-amino-9-ethyl-5-fluoro-9hydroxy-4-methoxy-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4:6,7]indolizino[1,2-b]quinoline-10,13dione (PY-12A and PY-12B) FY-12A and PY-12B Step 1: Preparation of (E)-N-(3-fluoro-7-(hydroxyimino)-4-methoxy-8-oxy-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-121)

[00276] 3 equivalents of tetrahydrofuran solution of potassium tert-butoxide and tert-butyl nitrite were added separately to 10 mL of tetrahydrofuran solution of the compound N-(3-fluoro-4-methoxy-8-oxo Petition 870260084912, dated 08 / 20 / 2026, p. 254 / 1402 247 / 694 5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-88) (200 mg) was added to the reaction solution at 0 °C. The reaction solution was stirred at 0 °C for 1 hour, diluted with 30 mL of water, and extracted with 10 mL of ethyl acetate three times. The organic phases were combined, dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative high-performance liquid chromatography (Oriendo, BRIX-2860; column: Phenomenex Luna C18 250 χ 50 mm χ 10 pm; mobile phase: water (0.225% trifluoroacetic acid)-acetonitrile, eluted from 45% to 85%), to obtain 250 mg of the yellow solid compound PY-121.

[00277] LCMS (ESI): m / z, 281.1 [M+1]+. Step 2: Preparation of N,N'-(3-fluoro-4-methoxy-8-oxy-5,6,7,8-tetrahydronaphthalene-1,7-diacyl)diacetamide (PY-122)

[00278] 1 mL of acetic anhydride and 2 mL of acetic acid were added to the compound (E)-N-(3-fluoro-7(hydroxyimino)-4-methoxy-8-oxy-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-121) (180 mg) at room temperature, zinc powder (35 mg) was added, and the reaction solution was stirred for 4 hours at room temperature. The reaction solution was concentrated under reduced pressure, diluted with 100 mL of water, extracted with ethyl acetate, dried with anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography. Petition 870260084912, dated 08 / 20 / 2026, p. 255 / 1402 248 / 694 high-efficiency preparative liquid (Oriendo, BRIX-2860; column: Phenomenex Luna C18 250 x 50 mm x 10 μm; mobile phase: water (0.225% trifluoroacetic acid)-acetonitrile, eluted from 45% to 85%), to obtain 250 mg of the white solid compound PY-122.

[00279] LCMS (ESI): m / z, 309.1 [M+1]+. Step 3: Preparation of N-(8-amino-6-fluoro-5-methoxy-1-oxy-1,2,3,4-tetrahydronaphthalene-2-yl)acetamide (PY-123)

[00280] The compound N,N'-(3-fluoro-4-methoxy-8-oxy5,6,7,8-tetrahydronaphthalene-1,7-diacyl)diacetamide (PY-122) (150 mg) was dissolved in 6N HCl (2 mL) and EtOH (2 mL), and the resulting solution was stirred at 60 °C for 3 hours. The reaction solution was concentrated under reduced pressure to obtain 115 mg of crude product, and the crude product was used directly for the next reaction.

[00281] LCMS (ESI): m / z, 267.1 [M+1]+. Step 4: Preparation of N-(9S)-9-ethyl-5-fluoro-9-hydroxy-4-methoxy-10,13-dioxy-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3',4:6,7]indolizino[1,2-b]quinoline-1yl)acetamide (PY-124)

[00282] 1 equivalent of (S)-4-ethyl-4-hydroxy-7,8-dihydro-1H-pyrano[3,4-f]indolizino-3,6,10(4H)-trione (ChemExpress) (92 mg) and 0. 5 equivalents of PPTS (24 mg) Petition 870260084912, dated 08 / 20 / 2026, p. 256 / 1402 249 / 694 were added to a solution of the compound N-(8-amino-6-fluoro-5-methoxy-1-oxy-1,2,3,4-tetrahydronaphthalene-2-yl)acetamide (PY-123) (80 mg) in toluene and the reaction solution was stirred at 120 °C for 12 hours. The reaction solution was concentrated under reduced pressure. The residue was purified by high-performance liquid chromatography (Oriendo, BRIX-2860; column: Phenomenex Luna C18 250 x 50 mm x 10 µm; mobile phase: water (0.225% trifluoroacetic acid)acetonitrile, eluted 45% to 85%), to obtain 55 mg of a yellow solid mixture PY-124.

[00283] LCMS (ESI): m / z, 494.2 [M+1]+. Step 5: Preparation of (1S,9S)-1-amino-9-ethyl-5-fluoro9-hydroxy-4-methoxy-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4:6,7]indolizino[1,2-b]quinoline-10,13dione and (1R,9S)-1-amino-9-ethyl-5-fluoro-9-hydroxy-4-methoxy1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4:6,7]indolizino[1,2-b]quinoline-10,13dione (PY-12A and PY-12B)

[00284] N-(9S)-9-ethyl-5-fluoro-9-hydroxy-4-methoxy-10,13-dioxy-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3',4:6,7]indolizino[1,2-b]quinoline-1-yl)acetamide (PY-124) (55 mg) was dissolved in 3 mL of 6N HCl, and the resulting solution was stirred at 85 °C for 5 hours. The reaction solution was concentrated under reduced pressure. The Petition 870260084912, dated 08 / 20 / 2026, page 257 / 1402 250 / 694 residue was purified by high-performance liquid chromatography (Oriendo, BRIX-2860; column: Phenomenex Luna C18 250 x 50 mm x 10 gm; mobile phase: water (0.225% HCOOH)acetonitrile, eluted from 45% to 85%) and lyophilized, to obtain separately a compound PY-12A (4.55 mg) and a compound PY12B (6.24 mg).

[00285] PY-12A (LC-MS retention time: 0.651 min): LCMS (ESI): m / z, 452.2 [M+1]+, Rt=0.651.

[00286] 1H NMR (400 MHz, DMSO-d6) δ 7.87 (d, J = 12.4 Hz, 1H), 7.30 (s, 1H), 6.53 (s, 1H), 5.62 (d, J = 19.2 Hz, 1H), 5.46 - 5.29 (m, 3H), 4.38 (s, 1H), 3.95 (s, 3H), 3.28 - 3.03 (m, 4H), 2.08 (s, 2H), 1.87 (dd, J = 9.2, 7.2 Hz, 2H), 0.87 (t, J = 7.2 Hz, 3H).

[00287] PY-12B (LC-MS retention time: 0.677 min): LCMS (ESI): m / z, 452.2 [M+1]+, Rt=0.677.

[00288] 1H NMR (400 MHz, DMSO-d6) δ 8.66 (s, 2H), 8.01 (d, J = 12.4 Hz, 1H), 7.34 (s, 1H), 6.57 (s, 1H), 5.90 (d, J = 19.2 Hz, 1H), 5.60-5.30 (m, 3H), 5.08 (s, 1H), 4.00(d, J = 1.2 Hz, 3H), 3.15 (t, J = 12.8 Hz, 3H), 2.12 (t,J = 13.6 Hz, 1H), 1.97-1.76 (m, J = 7.2 Hz, 2H), 0.87 (t,J = 7.2 Hz, 3H). Example of Preparation 20: Preparation of (S)-9-ethyl-5-fluoro-4,9-dihydroxy-1,2,3,9,12,15-hexahydro-10H,13H Preparation 870260084912, dated 20 / 08 / 2026, page 258 / 1402 251 / 694 benzo[de]pyrano[3',4:6,7]indolizino[1,2-b]quinoline-10,13dione (PY-13) PY-132 PY-13 Step 1: Preparation of N-(3-fluoro-4-hydroxy-8-oxy 5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-131)

[00289] 3 equivalents of AlCla were added to a solution of the compound N-(3-fluoro-4-methoxy-8-oxo-5,6,7,8tetrahydronaphthalene-1-yl)acetamide (PY-88) (200 mg) in DCM, and the reaction solution reacted at 60 °C for 2 hours. A saturated solution of NaHCOa (10 mL) was added slowly to quench the reaction and further adjust the pH value to 3 to 4. The reaction solution was extracted with ethyl acetate (3 χ 30 mL), the organic phases were combined, dried with anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure to obtain a yellow solid compound PY-131 (130 mg, 68%).

[00290] LCMS (ESI): m / z, 238.0 [M+H]+, 260.1 [M+Na]. Step 2: Preparation of 8-amino-6-fluoro-5-hydroxyl-3,4-Petition 870260084912, dated 08 / 20 / 2026, page 259 / 1402 252 / 694 dihydronaphthalene-1(2H)-one (PY-132)

[00291] A solution of the compound N-(3-fluoro-4-hydroxyl-8-oxy-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-131) (70 mg) in HCl (12N, 3.5 mL) was stirred at 100 °C for 16 hours. A saturated solution of NaHCO3 (10 mL) was slowly added to quench the reaction and further adjust the pH value to 3 to 4, and the reaction solution was extracted with ethyl acetate (3 χ 30 mL). The organic phases were combined, dried with anhydrous sodium sulfate and filtered, the filtrate was concentrated under reduced pressure and 5 mL of MeCN were added. The resulting solution was isolated by preparative high-performance liquid chromatography (Oriendo, BRIX-2860; column: Phenomenex Luna C18 250 χ 50 mm χ 10 pm; mobile phase: water (0.225% trifluoroacetic acid)-acetonitrile, eluted from 45% to 85%), to obtain a yellow solid compound PY-132 (12 mg, 20%).

[00292] LCMS (ESI): m / z, 196.1 [M+H]+. Step 3: Preparation of (S)-9-ethyl-5-fluoro-4,9-dihydroxy-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4:6,7]indolizino[1,2-b]quinoline-10,13dione (PY-13)

[00293] PPTS (0.67 eq, 12.9 mg) and (S)-4-ethyl-4-hydroxy-7,8-dihydro-1H-pyrano[3,4-f]indolizino-3,6,10(4H)trione (1 eq, 20.2 mg) were added to a solution of Petition 870260084912, dated 08 / 20 / 2026, page 260 / 1402 253 / 694 8-amino-6-fluoro-5-hydroxyl-3,4-dihydronaphthalene-1(2H)-one (PY-132) (15 mg) in toluene (10 mL) and the reaction solution was reacted at 140 °C for 16 hours. The toluene was removed under reduced pressure and 5 mL of DMF were added. The resulting mixture was purified by preparative high-performance liquid chromatography (Orendo, BRIX-2860; column: Phenomenex Luna C18 250 x 50 mm x 10 µm; mobile phase: water (0.225% HCOOH)-acetonitrile, eluted 45% to 85%), to obtain a white solid compound PY-13 (3.2 mg).

[00294] LCMS (ESI): m / z, 423.1 [M+H]+.

[00295] 1H NMR (400 MHz, DMSO-d6) δ 7.77 (d, J = 11.9 Hz, 1H), 7.26 (s, 1H), 6.50 (s, 1H), 5.42 (s, 2H), 5.22 (s, 2H), 3.11 (t, J = 6.1 Hz, 2H), 3.03 (t, J = 6.2 Hz, 2H), 2.01 (q, J = 6.2 Hz, 2H), 1.87 (dq, J = 14.5, 7.1 Hz, 2H), 0.87 (t, J = 7.3 Hz, 3H). Example of Preparation 21: Preparation of (S)-4,11-diethyl-8,10-difluoro-4,9-dihydroxy-1,12-dihydro-14Hpyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H)-dione (PY-14) Petition 870260084912, dated 08 / 20 / 2026, p. 261 / 1402 254 / 694 PY-14-f Step 1: Preparation of 1-(2,4-difluoro-3-methoxyphenyl)propyl-1-one (PY-14-c)

[00296] N-BuLi (1.07 g, 10.41 mL, 16.65 mmol, 1.2 eq, 1.60 M) was added slowly, dropwise, to the compound 1,3-difluoro-2-methoxybenzene (PY-14-a) (2 g, 13.88 mmol, 1 eq) in 20 mL of anhydrous THF at -70 °C. The reaction solution was stirred for half an hour at the same temperature. Then, the compound N-methoxy-N-methylpropionamide (PY-14-b) (4.55 g, 34.69 mmol, 2.5 eq) was added. The reaction solution was stirred further at -70 °C for half an hour. The low-temperature bath was removed, the temperature was raised to 25 °C, and the reaction solution was stirred for 16 hours. LCMS showed that a product was generated and, at room temperature, 5 mL of saturated ammonium chloride solution were used to quench the reaction, then 3 × 10 mL of ethyl acetate were used to extract the organic phase, the organic phase was washed with saturated brine, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure, and the residue was purified by Petition 870260084912, dated 08 / 20 / 2026, p. 262 / 1402 255 / 694 silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to obtain a light yellow oily target compound (1.6 g, yield: 54%).

[00297] LCMS (ESI): m / z, 214.9 [M+H]+. Step 2: Preparation of 1-(2,4-difluoro-3-methoxy-6-nitrophenyl)propyl-1-one (PY-14-d)

[00298] Fuming nitric acid (699.74 mg, 95%, 474.82 pL, 10.55 mmol, 0.96 eq) was added slowly, dropwise, to 22 mL of 1-(2,4-difluoro-3-methoxyphenyl)propyl-1-one solution (2.20 g, 10.99 mmol, 1 eq) in H2SO4 at -40 °C and the reaction solution was stirred for 1 hour at temperature. The reaction solution was added to ice water, the reaction flask was washed with 10 mL of absolute ethanol, 100 mL of DCM were added to extract the organic phase, the organic phase was washed with saturated brine, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) and dried, to obtain a light yellow oily compound 1-(2,4-difluoro-3-methoxy-6-nitrophenyl)propyl-1-one (1.2 g, yield: 34%).

[00299] LCMS (ESI): m / z, 246.1 [M+H]+.

[00300] 1H NMR (400 MHz, DMSO-d a) δ 8.24 - 8.13 (m, 1H), 4.16 (t, J = 2.1 Hz, 3H), 2.89 - 2.81 (m, 2H), 1.14 (t, Petition 870260084912, dated 08 / 20 / 2026, p. 263 / 1402 256 / 694 J = 7.1 Hz, 3H). Step 3: Preparation of 1-(6-amino-2,4-difluoro-3-methoxyphenyl)propyl-1-one (PY-14-e)

[00301] Iron powder (250.57 mg, 31.88 pL, 4.49 mmol, 5.5 eq), water (339.85 mg, 339.85 pL, 18.86 mmol, 23.12 eq) and concentrated hydrochloric acid (16.36 mg, 37.39 pL, 448.65 pmol, 0.55 eq, 12 M) were added separately to 10 mL of 1-(2,4-difluoro-3-methoxy-6-nitrophenyl)propyl-1-one (Py-14-d) solution (200 mg, 815.73 pmol, 1 eq) in absolute ethanol, and the reaction solution was stirred at 80 °C for 16 hours in a nitrogen atmosphere. The reaction solution was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (eluents: petroleum ether: ethyl acetate = 10:1) to obtain a white solid compound 1-(6-amino-2,4-difluoro-3-methoxyphenyl)propyl-1-one (141 mg, yield: 80%).

[00302] LCMS (ESI): m / z, 216.1 [M+H]+. Step 4: Preparation of 1-(6-amino-2,4-difluoro-3-hydroxyphenyl)propyl-1-one (PY-14-f)

[00303] Three equivalents of AlClA (557.61 mg, 4.18 mmol, 3 eq) were added to 10 mL of 1-(6-amino-2,4-difluoro-3-methoxyphenyl)propyl-1-one (Py14-e) solution (300 mg, 1.39 mmol, 1 eq) in DCM, and the reaction solution was stirred at 70 °C for 4 hours in an atmosphere of Petition 870260084912, dated 08 / 20 / 2026, page 264 / 1402 257 / 694 nitrogen. The reaction was stopped with 100 mL of saturated ammonium chloride solution, and then the organic phase was extracted with 2 x 100 mL of DCM, washed with saturated brine, dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a yellow solid crude product of the compound 1-(6-amino-2,4-difluoro-3-hydroxyphenyl)propyl-1-one (165 mg, crude product yield not calculated).

[00304] LCMS (ESI): m / z, 202.0 [M+H]+.

[00305] 1H NMR (400 MHz, DMSO-d6) δ 9.06 (s, 1H), 6.42 (dd, J = 13.0, 2.1 Hz, 1H), 3.45 (s, 2H), 2.87-2.82 (m, 2H), 1.05 (t, J = 7.2 Hz, 3H). Step 5: Preparation of (S)-4,11-diethyl-8,10-difluoro4,9-dihydroxy-1,12-dihydro-14Hpyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H)-dione (PY-14)

[00306] PPTS (25.11 mg, 99.92 pmol, 0.67 eq) and (S)-4-ethyl-4-hydroxy-7,8-dihydro-1H-pyrano[3,4-f]indolizino3,6,10(4H)-trione (ChemExpress) (30 mg, 149.13 pmol, 1 eq) were added separately to 10 mL of a solution of 1-(6-amino-2,4-difluoro-3-hydroxyphenyl)propyl-1-one (PY-14-f) (30 mg, 149.13 pmol, 1 eq) in toluene, and the reaction solution was stirred at 130 °C for 16 hours in a nitrogen atmosphere. The reagent was purified by chromatography. Petition 870260084912, dated 08 / 20 / 2026, p. 265 / 1402 258 / 694 high-performance liquid preparative (preparative chromatography manufacturer: SHIMADZU, model: LC-20AP, column: YMC-Triart Prep C18 250 x 30 mm x 10 μm, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution ratio: 12% to 42%) and lyophilized to obtain a yellow solid (35.55 mg, 55.65%).

[00307] LCMS (ESI): m / z, 429.1 [M+H]+.

[00308] 1H NMR (400 MHz, DMSO-d6) δ 7.84 (d, J =11.4 Hz, 1H), 7.26 (s, 1H), 6.52 (s, 1H), 5.43 (s, 2H), 5.31 (s, 2H), 3.22 - 3.15 (m, 2H), 1.86 (hept, J = 7.1 Hz, 2H),1.32 (t, J = 7.4 Hz, 3H), 0.87 (t, J = 7.3 Hz, 3H). Example of Preparation 22: Preparation of (S)-4(aminomethyl)-9-ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15hexahydro-10H,13H-benzo[de]pyrano[3',4':6,7]indolizino[1,2b]quinoline-10,13-dione (PY-16) OH 7 O Petition 870260084912, dated 08 / 20 / 2026, page 266 / 1402 259 / 694 ΡΥ-10-1 Step 1: Preparation of N-(4-((benzylamino)methyl)-3-fluoro-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY 16d)

[00309] NaBH(OAc)3 (2.06 g, 9.79 mmol, 2 eq) was added to a solution of the compound N-(3-fluoro-4-formyl-8oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (1.22 g, 8.5 mmol, 1 eq) and benzylamine (642.29 pL) in DCM (110 mL). The reaction solution was stirred for 12 hours at room temperature. Water (100 mL) was added to quench the reaction, the reaction solution was extracted with DCM (50 mL) three times, the organic phases were combined, washed with saturated brine (100 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (eluents: ethyl acetate / petroleum ether = 1 / 5-1 / 2) to obtain a brown oily substance N-(4-((benzylamino)methyl)-3-fluoro-8-oxo5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-16d) (499.5 mg, yield: 30%). Petition 870260084912, dated 08 / 20 / 2026, page 267 / 1402 260 / 694

[00310] LCMS (ESI): m / z, 341[M+H]+. Step 2: Preparation of 8-amino-5-((benzylamino)methyl)6-fluoro-3,4-dihydronaphthalene-1(2H)-one (PY-16e)

[00311] 6N HCl (3 mL) and EtOH (3 mL) were added to the compound N-(4-((benzylamino)methyl)-3-fluoro-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (499.5 mg, 1.47 mmol, 1 eq), the reaction solution was stirred at 60 °C for 3 hours and concentrated under reduced pressure, to obtain a crude brown oily product 8-amino-5-((benzylamino)methyl)6-fluoro-3,4-dihydronaphthalene-1(2H)-one (PY-16e) (517.9 mg).

[00312] LCMS (ESI): m / z, 341[M+H]+. Step 3: Preparation of (S)-4-((benzylamino)methyl)-9-ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-10,13dione (PY-16g)

[00313] PPTS (305.35 mg, 1.22 mmol, 1 eq) was added to a solution of the compound 8-amino-5((benzylamino)methyl)-6-fluoro-3,4-dihydronaphthalene-1(2H)-one (517.9 mg, 1.22 mmol, 1 eq) and the compound (S)-4-ethyl-4-hydroxy-7,8-dihydro-1H-pyrano[3,4-f]indolizino-3,6,10(4H)trione (ChemExpress) (319.87 mg, 1.22 mmol, 1 eq) in toluene (15 mL) and the reaction solution was stirred at 120 °C for 12 hours. Water (100 mL) was added to quench the reaction, then the reaction solution was extracted with DCM (50 mL) three Petition 870260084912, dated 08 / 20 / 2026, p. 268 / 1402 261 / 694 times, the organic phases were combined, washed with saturated brine (100 mL), dried with anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (eluents: dichloromethane / methanol = 12 / 1-11 / 1) to obtain a brown oily substance (S)-4-((benzylamino)methyl)-9-ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline10,13-dione (PY-16g) (466 mg, yield: 73%).

[00314] LCMS (ESI): m / z, 526[M+H]+. Step 4: Preparation of (S)-4-(aminomethyl)-9-ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13dione (PY-16)

[00315] Pd / C (100 mg, 939.67 gmol, 2.27 eq) and Pd(OH)2 (100 mg, 712.1 gmol, 1.72 eq) were added to a solution of the compound (S)-4-((benzylamino)methyl)-9-ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13dione (21 8 mg, 414.78 gmol, 1 eq) in MeOH (10 mL) under a hydrogen atmosphere. The reaction solution was stirred at room temperature for 5 hours, filtered with diatomaceous earth to remove Pd / C, and then concentrated to obtain the brown solid product (S)-4-(aminomethyl)-9-ethyl-5-fluoro-9 Petition 870260084912, dated 08 / 20 / 2026, page 269 / 1402 262 / 694 hydroxy-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10, 13-dione (PY-16) (296.6 mg, yield: 82%).

[00316] LCMS (ESI): m / z, 436[M+H]+.

[00317] 1H NMR (400 MHz, DMSO-d6) δ 8.27 (s, 1H), 7.75 (d, J = 11.2 Hz, 1H), 7.31 (s, 1H), 6.54 (s, 1H), 5.44 (s, 2H), 5.24 (s, 2H), 4.00 19F NMR (377 MHz, DMSO-d β) δ-113.60. Example of Preparation 23: Preparation of 2-hydroxyethyl (S)-((9-ethyl-5-fluoro-9-hydroxy-10,13-dioxo-2,3,9,10,13,15 hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2b]quinoline-4-yl)methyl)carbamate (PY-16Car) Step 1: Preparation of 2-((third Petition 870260084912, of 08 / 20 / 2026, page 270 / 1402 263 / 694 butyldimethylsilyl)oxy)ethyl(4-nitrophenyl)carboxylate (PY 16Carb)

[00318] 2-(tert-butyldimethylsilyloxy)ethanol (2.0 g, 11.34 mmol, 1.0 eq) was added to a solution of bis(4-nitrophenyl)carbonate (NPC) (5.18 g, 17.01 mmol, 1.5 eq) and N,N-diisopropylethylamine (DIPEA, 4.40 g, 34.03 mmol, 3.0 eq) in tetrahydrofuran (120 mL) at 0 °C, and the reaction solution was stirred at 25 °C for 16 hours. The reaction solution was concentrated under reduced pressure and purified by silica gel column chromatography with an ethyl acetate / petroleum ether (0%-10%) eluent system to obtain the yellow oily compound PY-16Carb (2.70 g, 7.91 mmol, yield: 70%).

[00319] 1H NMR (400 MHz, CHCla-d) δ 8.28 (d, J = 9.2 Hz, 2H), 7.38 (d, J = 9.2 Hz, 2H), 4.36 (dd, J = 5.6, 4.1 Hz, 2H), 3.91 (dd, J = 5.6, 4.1 Hz, 2H), 0.91 (s, 9H), 0.10 (s, 6H). Step 2: Preparation of 2-((tertbutyldimethylsilyl)oxy)ethyl(S)-((9-ethyl-5-fluoro-9-hydroxy10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4yl)methyl)carbamate (PY-16Carc)

[00320] Compound 2-((tertbutyldimethylsilyl)oxy)ethyl(4-nitrophenyl)carboxylate (35.75 Petition 870260084912, dated 08 / 20 / 2026, page 271 / 1402 264 / 694 mg, 0.105 mmol, 1.2 eq) and compound (S)-4-(aminomethyl)-9-ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13dione (38.0 mg, 0.087 mmol, 1.0 eq) and N,N-diisopropylethylamine (33.84 mg, 0.262 mmol, 3.0 eq) were added to a solution of N,N-dimethylformamide (2 mL) at room temperature, and the reaction solution was stirred at 25 °C for 1 hour. The reaction solution was used directly for the next step.

[00321] LCMS (ESI): m / z, 638.3 [M+H]+. Step 3: Preparation of 2-hydroxyethyl (S)-((9-ethyl-5fluoro-9-hydroxy-10,13-dioxo-2,3,9,10,13,15-hexahydro1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2b]quinoline-4-yl)methyl)carbamate (PY-16Car)

[00322] MeOH (2 mL) and 4 N hydrochloric acid were added to the reaction solution in the previous step, and the resulting solution was stirred at 25 °C for 1 hour. The reaction solution was purified by high-performance liquid chromatography (preparative chromatography manufacturer: Luna, model: Lab311-ISCO-R4, Phenomenex Luna C18 (250x50 mmx10 µm) was used as the chromatographic column, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution rate: 12% to 42%), and the eluate was lyophilized to obtain a white solid product PY 16Car (20.4 mg, 0.039 mmol, yield in Petition 870260084912, dated 08 / 20 / 2026, page 272 / 1402 265 / 694 two stages: 45%).

[00323] LCMS (ESI): m / z, 524.2 [M+H]+.

[00324] 1H NMR (400 MHz, DMSO-de) δ 7.73 (d, J = 11.2 Hz, 1H), 7.65 (t, J = 5.6 Hz, 1H), 7.31 (s, 1H), 6.52 (s, 1H), 5.43 (s, 2H), 5.24 (s, 2H), 4.71 (t, J = 5.2 Hz, 1H), 4.43 (d, J = 5.2 Hz, 2H), 3.96 (t, J = 5.2 Hz, 2H), 3.52 (q, J = 5.2 Hz, 2H), 3.24 (t, J = 6.0 Hz, 2H), 3.15 (t, J = 6.4Hz, 2H), 2.12 - 2.02 (m, 2H), 1.87 (hept, J = 7.2 Hz, 2H), 0.88 (t, J = 7.2 Hz, 3H). Example of Preparation 24: Preparation of (S)-4-(2-aminoethoxy)-9-ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15hexahydro-10H,13H-benzo[d]pyrano[3',4':6,7]indolizino[1,2b]quinoline-10,13-dione (PY-17) Step 1: Preparation of (S)-(2-((9-ethyl-5-fluoro-9hydroxy-10,13-dioxy-2,3,9,10,13,15-hexahydro-1H,12H benzo[d]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-4yl)oxy)ethyl)tert-butyl carbamate (PY-17-a)

[00325] Potassium carbonate (10.7 mg, 77.26 pmol, Petition 870260084912, dated 08 / 20 / 2026, p. 273 / 1402 266 / 694 2.0 eq) was added to a solution of compound PY-13 (41 mg, 38.63 gmol, 1.0 eq) in DMF and the resulting solution was stirred at 25 °C for half an hour, then (2-bromoethyl) tert-butyl carbamate (21.6 mg, 91.6 gmol, 2.5 eq) was added at the same temperature and the reaction solution was stirred at 25 °C for 16 hours. The reagent was purified by preparative high-performance liquid chromatography (preparative chromatography manufacturer: SHIMADZU, model: LC-20AP, column: YMC-Triart Prep C18 250 χ 30 mm χ 10 gm, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution ratio: 12% to 42%) and lyophilized to obtain a gray solid compound PY-17-a (5 mg, yield: 23%).

[00326] LCMS (ESI): m / z, 566.2 [M+H]+. Step 2: Preparation of (S)-4-(2-aminoethoxy)-9-ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[d]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13dione (PY-17)

[00327] 0.5 mL of TFA were added slowly, dropwise, to 5 mL of solution of compound PY-17-a (7 mg, 12.38 gmol, 1.0 eq) in DCM under an ice-cold water bath, and the reaction solution was heated naturally to 25 °C under an ice-cold water bath and stirred for 16 hours. The reagent was purified by preparative high-performance liquid chromatography (preparative chromatography manufacturer: Petition 870260084912, dated 08 / 20 / 2026, page 274 / 1402 267 / 694 SHIMADZU, model: LC-20AP, column: YMC-Triart Prep C18 250 χ 30 mm χ 10 μm, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution ratio: 12% to 42%) and lyophilized, to obtain a white solid compound PY-17 (1.97 mg, yield: 34%).

[00328] LCMS (ESI): m / z, 466.2 [M+H]+.

[00329] 1H NMR (400 MHz, DMSO-d6) δ 8.06 (s, 3H), 7.90 (d, J = 12.3 Hz, 1H), 7.30 (s, 1H), 6.52 (s, 1H), 5.44 (s, 2H), 5.27 (s, 2H), 4.27 (t, J = 5.1 Hz, 2H), 3.17 (t, J = 6.1 Hz, 5H), 2.06 (t, J = 6.2 Hz, 2H), 1.87 (p, J = 6.8 Hz, 2H), 0.88 (t, J = 7.3 Hz, 3H). Example of Preparation 25: Preparation of (S)-9-ethyl-5fluoro-9-hydroxy-4-(2-hydroxyethyl)-1,2,3,9,12,15-hexahydro10H,13H-benzo[de]pyrano[3',4':6,7]indolizino[1,2b]quinoline-10,13-dione (PY-18) Petition 870260084912, dated 08 / 20 / 2026, p. 275 / 1402 268 / 694 Step 1: Preparation of N-(4-(2-(benzyloxy)ethyl)-3-fluoro-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY18c)

[00330] 3.3 equivalents of potassium compound (2(benzyloxy)ethyl)trifluoroborate (532 mg), 3 equivalents of potassium carbonate, 30 mg of palladium acetate and 88 mg of S-Phos ligand were added sequentially and separately to a mixed solution of compound N-(4-bromo-3fluoro-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (200 mg) in 12.5 mL of toluene and water (volume ratio: 4:1) in a nitrogen atmosphere. The reaction solution was stirred at 100 °C for 16 hours in a nitrogen atmosphere and concentrated under reduced pressure, and then the residue was purified by silica gel column chromatography (eluents: ethyl acetate / n-hexane = 1:20-1:8) to obtain 140 mg of the white solid compound N-(4-(2-(benzoyloxy)ethyl) Petition 870260084912, dated 08 / 20 / 2026, p. 276 / 1402 269 / 694 3-fluoro-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-18c) (yield: 59%).

[00331] LCMS (ESI): m / z, 356 [M+1]+.

[00332] 1H NMR (400 MHz, DMSO-dβ) δ 12.26 (s, 1H), 8.29 (d, J = 13.3 Hz, 1H), 5.10 (t, J = 5.3 Hz, 1H), 4.50 (dd, J = 5.4, J = .2 Hz), 2 Hz 3.10 (t, J = 6.2 Hz, 2H), 2.67 (dd, J = 7.3, J =5.8 Hz, 2H), 2.16 (s, 3H), 1.99 (p, J = 6.3 Hz, 2H). Step 2: Preparation of N-(3-fluoro-4-(2-hydroxyethyl)-8oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-18d)

[00333] 0.25 equivalents of Pd / C catalyst and 0.25 equivalents of Pd(OH)2 catalyst were added separately to a solution of the compound N-(4-(2-(benzoyloxy)ethyl)-3-fluoro-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (140 mg) in 10 mL of methanol, and the reaction solution was allowed to react at 25 °C for 16 hours in a hydrogen atmosphere. After filtering the catalysts, the reaction solution was concentrated under reduced pressure and dried to obtain a pale solid crude product of a compound N-(3-fluoro-4-(2-hydroxyethyl)-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-18d) (100 mg, yield of crude product not calculated).

[00334] LCMS (ESI): m / z, 266 [M+H]+, 288 [M+Na]+. Petition 870260084912, dated 08 / 20 / 2026, page 277 / 1402 270 / 694 Step 3: Preparation of 8-amino-6-fluoro-5-(2-hydroxyethyl)-3,4-dihydronaphthalene-1(2H)-one (PY-18e)

[00335] 4 mL of 6N HCl were added to the compound N(3-fluoro-4-(2-hydroxyethyl)-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (80 mg) and the reaction solution was maintained at 40 °C for 3 hours. The reaction solution was cooled to room temperature, diluted with water and adjusted with dilute 2N hydrochloric acid to adjust the pH value to 3-5, then ethyl acetate was used to extract the organic phase, the organic phase was then washed with saturated brine, then dried with anhydrous sodium sulfate and concentrated under reduced pressure, to obtain 30 mg of the yellow solid compound 8-amino-6-fluoro-5(2-hydroxyethyl)-3,4-dihydronaphthalene-1(2H)-one (Py-18e) (yield: 37%).

[00336] LCMS (ESI): m / z, 224 [M+H]+. Step 4: Preparation of (S)-9-ethyl-5-fluoro-9-hydroxy-4(2-hydroxyethyl)-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13dione (PY-18)

[00337] 0.67 equivalents of PPTS (18.8 mg) and 1 equivalent of the compound (S)-4-ethyl-4-hydroxy-7,8-dihydro1H-pyrano[3,4-f]indolizino-3,6,10(4H)-trione (29.4 mg) (ChemExpress) were added separately to a solution Petition 870260084912, dated 08 / 20 / 2026, page 278 / 1402 271 / 694 of the compound 8-amino-6-fluoro-5-(2-hydroxyethyl)-3,4-dihydronaphthalene-1(2H)-one in 5 mL of toluene in a nitrogen atmosphere, and the reaction solution was stirred at 130 °C for 16 hours and isolated by preparative high-performance liquid chromatography (preparative chromatography manufacturer: SHIMADZU, model: LC-20AP, column: Synergi MaxRP 280 χ 30 mm χ 10 μm, mobile phase: water (0.225% HCOOH)acetonitrile, water elution ratio: 12% to 42%) and lyophilized, to obtain 6.0 mg of a yellow solid compound. (S)-9-ethyl-5-fluoro-9-hydroxy-4-(2-hydroxyethyl)1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13dione (PY-18) (yield: 12%).

[00338] LCMS (ESI): m / z, 451 [M+H]+.

[00339] 1H NMR (400 MHz, DMSO-d6) δ 7.71 (dd, J = 11.3, 6.3 Hz, 1H), 7.33 - 7.28 (m, 1H), 6.54 (s, 1H), 5.43 (s, 2H), 5.23 (d, J = 11.2 Hz, 2H), 4.88 (t, J = 5.3 Hz, 1H), 3.61 (d, J = 6.5 Hz, 2H), 3.20 - 3.12 (m, 4H), 3.01 (d, J = 6.6 Hz, 2H), 2.07 (s, 2H), 1.87 (hept, J = 7.0 Hz, 2H), 0.88 (t, J = 7.3 Hz, 3H).19F NMR (377 MHz, DMSO-dβ) δ -112.5. Example of Preparation 26: Preparation of (S)-4-(3-aminopropyl)-9-ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15hexahydro-10H,13H-benzo[de]pyrano[3',4':6,7]indolizino[1,2b]quinoline-10,13-dione (PY-19) Petition 870260084912, dated 08 / 20 / 2026, p. 279 / 1402 272 / 694 Step 1: Preparation of mixed intermediates of (S,E)(3-(9-ethyl-5-fluoro-9-hydroxy-10,13-dioxy-2,3,9,10,13,15hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2b]quinolin-4-yl)allyl)tert-butyl carbamate (PY-19c) and (S,E) carbamate (PY 19c')

[00340] 0.1 equivalents of bis(tert-butylphosphine) palladium (2.1 mg), 0.2 equivalents of tri(o-tolyl)-phosphine (2.5 mg), 6 equivalents of DIPEA (41 pL) and 2.5 equivalents of tert-butyl allylcarbamate compound (17.8 mg) were added separately to a solution of the compound (S)-4-bromo-9-ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15-hexahydro10H,13H-benzo[de]pyrano[3',4':6,7]indolizino[1,2] Petition 870260084912, dated 20 / 08 / 2026, page 280 / 1402 273 / 694 b ]quinoline-10,13-dione (20 mg) in 5 mL of toluene. The reaction solution was stirred at 120 °C for 16 hours, the reaction solution was concentrated, then purified by silica gel column chromatography (eluents: dichloromethane / methanol = 20:1-10:1) and concentrated under reduced pressure to obtain 10 mg of compounds (S,E)-(3-(9-ethyl-5-fluoro-9-hydroxy-10,13-dioxy-2,3,9,10,13,15-hexahydro1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin4-yl)allyl)tert-butyl carbamate (PY-19c) and (S,E)-(3-(9-ethyl5-fluoro-9-hydroxy-10,13-dioxy-2,3,9,10,13,15-hexahydro1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin4-yl)prop-1-en-1-yl)tert-butyl carbamate (PY-19c') as a mixture (yield: 43%; purity: 77%). Step 2: Preparation of tert-butyl (S)-(3-(9-ethyl-5-fluoro-9hydroxy-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4yl)propyl)carbamate (PY- 19d)

[00341] 0.25 equivalents of Pd / C (14.2 mg) and 0.25 equivalents of Pd(OH)2 (9.4 mg) were added separately to a solution of the mixture (S,E)-(3-(9-ethyl-5-fluoro-9-hydroxy-10,13-dioxy-2,3,9,10,13,15-hexahydro1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin4-yl)allyl)tert-butyl carbamate (PY-19c) and (S,E)-(3-(9-ethyl-5-fluoro-9-hydroxy-10,13-dioxy-2,3,9,10,13,15-hexahydroPetition 870260084912, of 20 / 08 / 2026, page 281 / 1402 274 / 694 tert-butyl 1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2b]quinoline-4-yl)prop-1-en-1-yl)carbamate (PY-19c') (30 mg) in 5 mL of methanol. The reaction solution was stirred at 25 °C for 16 hours in a hydrogen atmosphere and, after filtration, the reaction solution was concentrated under reduced pressure, yielding 19.6 mg of crude product of the compound (S)-(3-(9-ethyl-5-fluoro-9-hydroxy10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4yl)propyl)tert-butyl carbamate (PY-19d) (yield: 65%), which was used directly for the next reaction.

[00342] LCMS (ESI): m / z, 564.3 [M+1]+. Step 3: Preparation of (S)-4-(3-aminopropyl)-9-ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13dione (PY-19)

[00343] 0.8 mL of TFA were slowly added to a solution of the compound (S)-(3-(9-ethyl-5-fluoro-9-hydroxy-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4yl)propyl)carbamate tert-butyl (16.3 mg, purity: 82%) in 2.4 mL of dichloromethane under an ice-water bath condition, and the reaction solution was naturally heated to 25 °C and stirred for 16 hours. The reaction solution was Petition 870260084912, dated 08 / 20 / 2026, page 282 / 1402 275 / 694 concentrated under reduced pressure and the residue was purified by silica gel column chromatography (eluents: dichloromethane / methanol = 20:1-8:1) to obtain a crude product, and then the crude product was purified by preparative high-performance liquid chromatography (preparative chromatography manufacturer): SHIMADZU, model: LC-20AP, column: Welch Xtimate C18 250 x 50 mm x 10 µm, mobile phase: water (0.225% FA)-ACN, water elution ratio: 12% to 42%) and lyophilized to obtain 2.53 mg of a compound. (S)-4-(3-aminopropyl)-9-ethyl-5-fluoro-9-hydroxy1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13dione (PY-19) (yield: 12%).

[00344] LCMS (ESI): m / z, 473.2 [M+H]+.

[00345] 1H NMR (400 MHz, DMSO-dβ) δ 1H NMR (400 MHz, DMSO-d β) δ 8.39 (s, 1H), 7.75 (d, J = 11.4 Hz, 1H), 7.30 (s, 1H), 6.53 (s, 1H), 5.43 (s, 2H), 5.25 (s, 2H), 3.16 (d, J = 6.5 Hz, 6H), 2.88 (s, 2H), 2.82 (s, 2H), 2.08 (t, J = 6.2 Hz, 2H), 1.87 (p, J = 7.0 Hz, 2H), 1.76 (s, 2H), 0.88 (t, J = 7.3 Hz, 3H);19F NMR (377 MHz, DMSO-d β) δ -113.12. Example of Preparation 27: Preparation of (S)-4-(2-aminoethyl)-9-ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15hexahydro-10H,13H-benzo[depyrano[3',4':6,7]indolizino[1,2b]quinoline-10,13-dione (PY-20) Petition 870260084912, dated 08 / 20 / 2026, p. 283 / 1402 276 / 694 PY-20 PY-10d PY-20a PY-20 Step 1: Preparation of (S)-(2-(9-ethyl-5-fluoro-9-hydroxy-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-4yl)ethyl)benzyl ester of carbamic acid (PY -20a)

[00346] Compound PY-10d (90.91 mg, 66%, 123.63 pmol, 1 eq) was dissolved in dioxane (4 mL) / water (1 mL), and then potassium benzyl N-[2-(trifluoroboranuidyl)ethyl]carbamate (148.91 mg, 494.53 pmol, 4 eq), tri(o-tolyl)phosphine (18.81 mg, 61.82 pmol, 0.5 eq) and potassium phosphate (78.73 mg, 30.71 pL, 370.90 pmol, 3 eq) were added, and the reaction solution was stirred at 90 °C for 12 hours in a nitrogen atmosphere. The reaction solution was concentrated under reduced pressure and filtered, and the residual solution was purified by preparative high-performance liquid chromatography (preparative chromatography manufacturer: Oriendo, model: BRIX-2860 (R1, 4, 5, 6), column: Phenomenex Luna C18 250 x 50 mm x 10 µm, mobile phase: water). Petition 870260084912, dated 08 / 20 / 2026, page 284 / 1402 277 / 694 (0.225% HCOOH)-acetonitrile, water elution ratio: 30% to 60%), to obtain a white solid product PY 20a (10 mg, yield 13.86%).

[00347] LCMS (ESI): m / z, 584.2 [M+H]+. Step 2: Preparation of (S)-4-(2-aminoethyl)-9-ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[depyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13dione (PY-20)

[00348] Compound PY-20a (10 mg, 17.13 pmol, 1 eq) was dissolved in MeCN (0.5 mL), TMSI (56 mg, 40 pL, 279.87 pmol, 16.334 eq) was added to the solution, and the solution was stirred at 25 °C for 12 hours. The reaction solution was purified by preparative high-performance liquid chromatography (preparative chromatography manufacturer: SHIMADZU, model: LC-20AP, column: YMC-Triart Prep C18 250 x 30 mm x 10 μm, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution ratio: 3% to 33%), to obtain a white solid product (5.16 mg, yield: 67%, purity: 97.64%).

[00349] LCMS (ESI): m / z, 450.2 [M+H]+. Example of Preparation 28: Preparation of (S)-4-ethyl-8-fluoro-4,9-dihydroxy-11-propyl-1,12-dihydro-14Hpyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H)-dione (PY-21-A) Petition 870260084912, dated 08 / 20 / 2026, page 285 / 1402 278 / 694 Step 1: Preparation of 1-(2-amino-4-fluoro-5-methoxyphenyl)but-1-one (PY-21-Ab)

[00350] BCla (1 eq, 830.04 mg, 7.08 mmol) was added to 10 mL of anhydrous benzene solvent in an ice water bath, then 3-fluoro-4-methoxyaniline (1 eq, 1 g, 7.08 mmol) was added to a solution of 20 mL of anhydrous benzene solvent and nitrile (2 eq, 979.24 mg, 14.17 mmol, 1.23 mL) and AlCl3 (1.1053 eq, 1.04 g, 1.04 mol) were added sequentially in a nitrogen atmosphere, and the reaction solution was allowed to react at 100 °C for 16 hours. After cooling in an ice water bath, 50 mL of 2M hydrochloric acid were added slowly and then the mixture was stirred at 80 °C for 1 hour. 100 mL of water were used to extinguish the reaction in a bath. Petition 870260084912, dated 08 / 20 / 2026, page 286 / 1402 279 / 694 ice water, then 2 χ 100 mL of ethyl acetate were used to extract the organic phase, the organic phase was washed with saturated brine, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluents: petroleum ether: ethyl acetate = 10:1), to obtain a light yellow solid compound PY-21-Ab (440 mg, yield: 29%).

[00351] LCMS (ESI): m / z, 212.1 [M+H]+. Step 2: Preparation of (S)-4-ethyl-8-fluoro-4-hydroxy-9-methoxy-11-propyl-1,12-dihydro-14Hpyrano[3',4':6,7]indolizino[1,2-b]quinolin-3,14(4H)-dione (PY-21-Ad)

[00352] (S)-4-ethyl-4-hydroxy-7,8-dihydro-1Hpyrano[3,4-f]indolizino-3,6,10(4H)-trione (1 eq, 62.31 mg, 236.70 pmol) and PPTS (1 eq, 59.48 mg, 236.70 pmol, 10 mL) were added separately to a solution of 1-(2-amino4-fluoro-5-methoxyphenyl)but-1-one (PY-21-Ab) (1 eq, 62.31 mg, 236.70 pmol) in 10 mL of toluene, and the reaction solution was stirred at 130 °C for 16 hours under a nitrogen atmosphere. The reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluents: petroleum ether: ethyl acetate = 5:1) to obtain a yellow solid compound PY-21-Ad (80 mg, Petition 870260084912, dated 08 / 20 / 2026, page 287 / 1402 280 / 694 yield: 77%).

[00353] LCMS (ESI): m / z, 439.1 [M+H]+. Step 3: Preparation of (S)-4-ethyl-8-fluoro-4,9-dihydroxy-11-propyl-1,12-dihydro-14Hpyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H)-dione (PY-21-A)

[00354] AlClA (18.25 mg, 136.84 pmol, 6 eq) was added to a solution of the compound PY-21-Ad (10 mg, 22.81 pmol, 1 eq) in 4 mL of DCM. The reaction solution was stirred under a reaction condition of 70 °C for 16 hours. 100 mL of saturated ammonium chloride solution were used to quench the reaction, and then 2 x 100 mL of ethyl acetate were used to extract the organic phase. The organic phase was washed with saturated brine, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure, and the residue was purified by preparative high-performance liquid chromatography (preparative chromatography manufacturer): SHIMADZU, model: LC-20AP, column: YMC-Triart Prep C18 250 30 mm 10 pm, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution ratio: 12% to 42%) and lyophilized to obtain a white solid compound PY-21-A (4.3 mg, yield: 44%).

[00355] LCMS (ESI): m / z, 425.2 [M+H]+.

[00356] 1H NMR (400 MHz, DMSO-d β) δ 10.90 (s, 1H), Petition 870260084912, dated 08 / 20 / 2026, p. 288 / 1402 281 / 694 7.91 (dd, J = 11.9, 2.8 Hz, 1H), 7.64 - 7.57 (m, 1H), 7.26 (s, 1H), 6.49 (s, 1H), 5.43 (s, 2H), 5.27 (d, J = 3.1 Hz, 2H), 3.06 (t, J = 7.9 Hz, 2H), 1.86 (dq, J = 14.1, 7.0 Hz, 2H), 1.73 (p, J = 7.5 Hz, 2H), 1.05 (t, J = 7.3 Hz, 3H), 0.88 (t, J = 7.3 Hz, 3H). Example of Preparation 29: Preparation of (S)-4-(4-aminobutyl)-9-ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15hexahydro-10H,13H-benzo[depyrano[3',4':6,7]indolizino[1,2b]quinoline-10,13-dione (PY-24) PY-24 Step 1: Preparation of (S)-(4-(9-ethyl-5-fluoro-9-hydroxy-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-4yl)but-3-en-1-yl)tert-butyl carbamate (PY-24c)

[00357] 0.1 equivalents of bis(tri-tert-butylphosphine)palladium (21 mg), 0.2 equivalents of tris(omethylphenyl)phosphorus (25 mg), 6 equivalents of DIPEA (410 pL) Petition 870260084912, dated 08 / 20 / 2026, page 289 / 1402 282 / 694 and 2.5 equivalents of tert-butyl but-3-en-1-ylcarbamate (176 mg) were added separately to a solution of the compound (S)-4-bromo-9-ethyl-5-fluoro-9-hydroxy1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13dione (200 mg) in 15 mL of toluene, and the reaction solution was stirred at 120 °C for 16 hours. The reaction solution was concentrated and then purified by silica gel column chromatography (eluents: dichloromethane / methanol = 20:1-10:1) and concentrated under reduced pressure to obtain 129 mg of crude product (yield: 54%), which was used directly for the next reaction.

[00358] LCMS (ESI): m / z, 576.3 [M+1]+. Step 2: Preparation of (S)-(4-(9-ethyl-5-fluoro-9-hydroxy-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-4yl)butyl)tert-butyl carbamate (PY-24d)

[00359] 0.25 equivalents of Pd / C (1.3 mg) and 0.25 equivalents of Pd(OH)2 (1.7 mg) were added separately to a solution of 6.8 mg of the crude product (S)(4-(9-ethyl-5-fluoro-9-hydroxy-10,13-dioxy-2,3,9,10,13,15hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2b]quinoline-4-yl)but-3-en-1-yl)tert-butyl carbamate in 3 mL of methanol. The reaction solution was stirred at 25 °C for Petition 870260084912, dated 08 / 20 / 2026, pp. 290 / 1402 283 / 694 hours in a hydrogen atmosphere and, after filtration, the reaction solution was concentrated under reduced pressure to obtain 19.6 mg of crude product of the compound (S)-(4-(9ethyl-5-fluoro-9-hydroxy-10,13-dioxo-2,3,9,10,13,15hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2b]quinoline-4-yl)butyl)tert-butyl carbamate (PY-24d) (yield: 55%, purity: 63%), which was used directly for the next reaction.

[00360] LCMS (ESI): m / z, 578.2 [M+1]+. Step 3: Preparation of (S)-4-(4-aminobutyl)-9-ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[depyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13dione (PY-24)

[00361] 0.7 mL of TFA were slowly added to a solution of the compound (S)-(4-(9-ethyl-5-fluoro-9-hydroxy-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-4yl)butyl)carbamate tert-butyl (6.8 mg, purity: 63%) in 2.1 mL of dichloromethane under an ice-water bath condition, and the reaction solution was naturally heated to 25 °C and stirred for 16 hours. The reaction solution was purified by preparative high-performance liquid chromatography (preparative chromatography manufacturer: SHIMADZU, model: LC-20AP, stem: Welch Xtimate C18 250 x Petition 870260084912, dated 08 / 20 / 2026, pp. 291 / 1402 284 / 694 mm χ 10 gm, mobile phase: water (0.225% FA)-ACN, water elution ratio: 12% to 42%) and lyophilized, to obtain 0.35 mg of the compound PY-24 (yield: 5.4%).

[00362] LCMS (ESI): m / z, 473.2 [M+H]+.

[00363] 1H NMR (400 MHz, DMSO-d6) δ 1H NMR (400 MHz, DMSO-d6) δ 8.37 (s, 1H), 7.78-7.71 (m, 1H), 7.30 (s, 1H), 6.51 (s, 1H), 5.43 (s, 2H), 5.25 (s, 2H), 3.16 (d, J = 6.0 Hz, 6H), 2.86 (s, 2H), 2.76 (s, 2H), 2.08 (s, 2H), 1.88 (q, J = 7.0 Hz, 2H), 1.59 (s, 2H), 0.88 (t, J = 7.3 Hz, 3H);19F NMR (377 MHz, DMSO-d6) δ -112.93. Example of Preparation 30: Preparation of 2-((9S)-9-ethyl5-fluoro-9-hydroxy-4-methyl-10,13-dioxy-2,3,9,10,13,15hexahydro-1H,12H-benzo[de]pyrano[3',4:6,7]indolizino[1,2b]quinoline-1-yl)acetic acid (PY-25) % co O SAP 0 HO—\ / ° CaÇuQl N ihctCj0 F PY-25 ° Υϊ^θ YY i ? - ArNH υ ” S nh2 0 PY-251 PY-252 O HO^ ) 0 ΟΥτΥγ Yan hY ° F PY-25 Petition 870260084912, dated 08 / 20 / 2026, p. 292 / 1402 285 / 694 Step 1: Preparation of 2-(8-acetamido-6-fluoro-5-methyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-yl)methyl acetate (PY-251)

[00364] N-(3-fluoro-4-methyl-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (2 g, 8.5 mmol) was added to a 100 mL three-necked flask and dissolved with 30 mL of THF in a nitrogen atmosphere. The reaction solution was cooled to -78 °C, LDA (10.6 mL, 2 M THF) was slowly added to the previous reaction solution and, after the addition, the reaction solution reacted at -78 °C for 1 hour. Methyl bromoacetate (1.3 g, 8.5 mmol) was then added to the reaction solution and the reaction solution was heated to room temperature and reacted for 16 hours.150 mL of water were added to the reaction solution, the reaction solution was extracted with ethyl acetate (100 mL χ 3), the organic phase was washed with saturated brine, dried with anhydrous sodium sulfate and filtered, the filtrate was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (80% PE / 20% EA) to obtain 800 mg of the yellowish solid compound 2-(8-acetamido-6-fluoro-5-methyl-1oxo-1,2,3,4-tetrahydronaphthalene-2-yl)methyl acetate (PY251) (yield: 30.6%). Step 2: Preparation of 2-(8-amino-6-fluoro-5-methyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-yl)acetic acid Petition 870260084912, dated 08 / 20 / 2026, page 293 / 1402 286 / 694 (PY-252)

[00365] 2 mL of aqueous NaOH solution (2 mol / mL) were added to a solution of the compound 2-(8-acetamido-6-fluoro-5-methyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2yl)methyl acetate (PY-251) (400 mg, 1.3 mol) in EtOH (8 mL) and the reaction solution reacted at 75 °C for 16 hours. The reaction solution was adjusted with 2N hydrochloric acid to adjust the pH to 7-8, concentrated under reduced pressure and extracted with ethyl acetate (30 mL χ 3), the organic phase was washed with saturated brine, dried with anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure to obtain 200 mg of crude product, which was used directly for the next step. Step 3: Preparation of 2-((9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxy-2,3,9,10,13,15-hexahydro1H,12H-benzo[de]pyrano[3',4:6,7]indolizino[1,2-b]quinoline1-yl)acetic acid (PY-25)

[00366] 2-(8-amino-6-fluoro-5-methyl-1-oxo-1,2,3,4-tetrahydronaphthalene-2-yl)acetic acid (PY-252) (200 mg, 0.796 mmol) and (S)-4-ethyl-4-hydroxy-7,8-dihydro-1Hpyrano[3,4-f]indolizino-3,6,10(4H)-trione (251 mg, 0.954 mmol) were added to a 50 mL three-necked flask, toluene (10 mL, 50 V) was added, and then p-toluenesulfonic acid (27.3 mg, 0.159 mmol) and o-cresol (0.6 Petition 870260084912, dated 08 / 20 / 2026, page 294 / 1402 287 / 694 mL, 3v) were added, and a reaction solution was reacted at 120 °C–125 °C for 16 hours. The reaction solution was concentrated under reduced pressure, and the residue was purified by preparative high-performance liquid chromatography (Oriendo, BRIX-2860; column: Phenomenex Luna C18 250 χ 50 mm χ 10 gm; mobile phase: water (0.225% HCOOH)-acetonitrile, eluted 45% to 85%), to obtain 70 mg of the compound PY-25 as a yellow powder, with a yield of 18.38%.

[00367] 1H NMR (400 MHz, DMSO) δ 12.50 (s, 1H), 7.76 (d, J = 11.1 Hz, 1H), 7.31 (s, 1H), 6.51 (s, 1H), 5.44 (s, 2H), 5.36 (s, 2H), 3.83 - 3.74 (m, 1H), 3.19-3.05 (m, 2H), 2.70-2.64 (m, 1H), 2.58-2.53 (m, 1H), 2.38 (s, 3H), 2.23 (d, J = 13.6 Hz, 1H), 2.06-1.95 (m, 1H), 1.87 (tt, J = 14.1, 7.0 Hz, 2H), 0.87 (t, J = 7.3 Hz, 3H). Example of Preparation 31: Preparation of 2-((1S,9S)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3,4,6,7]indolizino[1,2b]quinoline-1-yl)-N-(2-hydroxyethyl)acetamide and 2-((1R,9S)9-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2b]quinoline-1-yl)N-(2-hydroxyethyl)acetamide (PY-25A and PY-25B) Petition 870260084912, dated 08 / 20 / 2026, p. 295 / 1402 288 / 694 FY-25A and PY-25B Pi-25A and PY-25B

[00368] HATU (17 mg, 45.14 pmol, 1.2 eq), DIEPA (20 mg, 150.5 pmol, 4 eq) and ethanolamine (2.3 mg, 37.62 pmol, 1.0 eq) were added to the solution of the compound 2-((9S)-9-ethyl 5-fluoro-9-hydroxy-4-methyl-10,13-dioxy-2,3,9,10,13,15-hexahydro-1H,12H-benzo[de]pyrano[3',4]:6,7]indolizino[1,2—b]quinoline-1-yl)acetic acid (PY-25) (18 mg, 37.62 pmol, 1.0 eq) in DMF (3 mL) under an ice water bath and, after addition, the reaction solution was warmed to room temperature and stirred for 2 hours. The reaction solution was concentrated under reduced pressure, and the residue was isolated and purified by preparative high-performance liquid chromatography (Oriendo, BRIX-2860; column: Phenomenex Luna C18 250 x 50 mm χ 10 pm; mobile phase: water (0.225% HCOOH)acetonitrile, eluted from 45% to 85%), to obtain compounds PY-25A (4.01 mg, yield: 18%) and PY-25B (6.62 mg, yield: 30%) as white solids. Petition 870260084912, dated 08 / 20 / 2026, page 296 / 1402 289 / 694

[00369] PY-25A (tempo de retenção LCMS: 1.73 min): LCMS (ESI): m / z, 522,3[M+1]+.

[00370] 1H NMR (400 MHz, DMSO-d6) δ 8.07 (t, J = 4.0 Hz, 1H), 7.76 (d, J = 12.0 Hz, 1H), 7.30 (s, 1H), 6.51 (s, 1H), 5.44 (s, 2H), 5.34 (s, 2H), 4.67 (t, J = 4.0 Hz, 1H), 3.78-3.77 (m, 1H), 3.44-3.36 (m, 3H), 3.18-3.14 (m, 4H), 2.45-2.44 (m, 1H), 2.39 (s, 3H), 2.13-2.11 (m, 1H), 1.971.80 (m, 3H), 0.87 (t, J = 8.0 Hz, 3H).

[00371] PY-25B (tempo de retenção LCMS: 1.83 min): LCMS (ESI): m / z, 522,2[M+1]+.

[00372] 1H NMR (400 MHz, DMSO-d6) δ 8.46 (brs, 0.36H, HCOOH), 8.08-8.06 (m, 1H), 7.75 (d, J = 12.0 Hz, 1H), 7.30 (s, 1H), 6.51 (s, 1H), 5.44 (s, 2H), 5.34 (s, 2H), 4.66 (s, 1H), 3.78-3.76 (m, 1H), 3.38-3.36 (m, 2H), 3.15-3.12 (m, , 4H), 2.48 - 2.30 (m, 5H), 2.14 (s, 1H), 1.88-1.85 (m, 3H), 0.87 (t, J = 8.0 Hz, 3H). Example of Preparation 32: Preparation of (S)-N-((9-ethyl5-fluoro-9-hydroxy-10,13-dioxo-2,3,9,10,13,15-hexahydro1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2b]quinoline-4-yl)methyl)-2-hydroxyacetamide (PY-26) PY-26 Petition 870260084912, dated 08 / 20 / 2026, p. 297 / 1402 290 / 694 HATU, DIEA, DMF

[00373] N,N-diisopropylethylamine (26.71 mg, 206.68 pmol, 3 eq) and HATU (31.43 mg, 82.67 pmol, 1.2 eq) were added to a solution of compound PY-16 (30 mg, 68.89 pmol, 1 eq) and 2-hydroxyacetic acid (6.29 mg, 82.67 pmol, 1.2 eq) in N,N-dimethylformamide (3 mL) at 0 °C. After the addition, the reaction solution reacted for 2 hours at 25 °C. The reaction solution was purified by preparative high-performance liquid chromatography (preparative chromatography manufacturer: ISCO, model: ISCO-R1, column: YMC-Triart Prep C18 250 x 50 mm x 7 µm, mobile phase: water (0.225% FA)acetonitrile, acetonitrile elution ratio: 28% to 37%), to obtain a white solid compound PY-26 (4.37 mg, yield = 12.8%).

[00374] LCMS (ESI): m / z, 494.2[M+H]+.

[00375] 1H NMR (400 MHz, DMSO-de) δ 8.06-8.05 (m, 1H), 7.74 (d, J = 12 Hz, 1H), 7.31 (s, 1H), 6.54 (s, 1H), 5.435.42 (m, 3H), 5.25 (s, 2H), 4.56 (d, J = 8.0 Hz, 2H), 3.82 (d, J = 8.0 Hz, 2H), 3.26-3.23 (m, 2H), 3.15-3.15 (m, 2H), 2.08-2.05 (m, 2H), 1.90-1.83 (m, 2H), 0.87 (t, J = 7.2 Hz, 3H).19F NMR (377 MHz, DMSO-d e) δ -112.11. Example of Preparation 33: Preparation of (S)-(9-ethyl-5 Petition 870260084912, dated 08 / 20 / 2026, p. 298 / 1402 291 / 694 fluorine-9-hydroxy-10,13-dioxo-2,3,9,10,13,15-hexahydro1H,12H-benzo[de]pyrano[3',4':6,7]indolizino[1,2b]quinoline-4-yl)methyl(2-hydroxyethyl)carbamate (PY-27) Step 1: Preparation of (S)-(9-ethyl-5-fluoro-9-hydroxy10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-4yl)methyl(4-nitrophenyl)carbonate (PY -27a)

[00376] Compound PY-10 (8.0 mg, 0.018 mmol, 1.0 eq), bis(4-nitrophenyl)carbonate (44.6 mg, 0.147 mmol, 8.0 eq) and N,N-diisopropylethylamine (28.4 mg, 0.220 mmol, 12.0 eq) were added to N,N-dimethylformamide (2 mL) at room temperature and the reaction solution was stirred at 50 °C for 16 hours. The reaction solution was concentrated under reduced pressure and the residue was purified by thin-layer chromatography using a dichloromethane / methanol (15 / 1) developing agent system to obtain a yellow oily compound PY-27a (18 mg).

[00377] LCMS (ESI): m / z, 602.3 [M+H]+. Petition 870260084912, dated 08 / 20 / 2026, pp. 299 / 1402 292 / 694 Step 2: Preparation of (S)-(9-ethyl-5-fluoro-9-hydroxy-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-4yl)methyl(2-hydroxyethyl)carbamate (PY-27)

[00378] Compound PY-27a (18.0 mg, impure), aminoethanol (1.83 mg, 0.030 mmol) and N,N-diisopropylethylamine (11.6 mg, 0.090 mmol) were added to N,N-dimethylformamide (1 mL) at room temperature and the reaction solution was stirred at 25 °C for 0.5 hours. The reaction solution was purified by high-performance liquid chromatography (preparative chromatography manufacturer: Luna, model: Lab311-ISCO-R4, Phenomenex Luna C18 (250x50 mmx10 µm) was used as the chromatographic column, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution rate: 12% to 42%) and lyophilized to obtain a white solid product PY-27 (4.14 mg, 7.56 µmol, two-step yield): 42%).

[00379] LCMS (ESI): m / z, 524.2 [M+H]+.

[00380] 1H NMR (400 MHz, DMSO-de) δ 7.79 (d, J = 11.2 Hz, 1H), 7.32 (s, 1H), 7.19 (t, J = 5.6 Hz, 1H), 6.54 (s, 1H), 5.44 (s, 2H), 5.27 (d, J = 4.4 Hz, 3H), 4.63 (t,J = 5.6 Hz, 1H), 3.30-3.23 (m, 5H), 3.18 (s, 2H), 3.04 (q,J = 6.0 Hz, 2H), 2.08 (s, 2H), 1.86 (dt, J = 15.2, 7.2 Hz, 2H), 0.87 (t, J = 7.2 Hz, 3H). Example of Preparation 34: Preparation of (S)-4-ethyl Petition 870260084912, dated 08 / 20 / 2026, page 300 / 1402 293 / 694 8,10-difluoro-4,9-dihydroxy-11-(4-hydroxybutyl)-1,12-dihydro14H-pyrano[3,,4,:6,7]indolizino[1,2-b]quinolin-3,14(4H)dione (PY-29) and (S)-4-ethyl-8,10-difluoro-4-hydroxy-11-(4 hydroxybutyl)-9-methoxy-1,12-dihydro-14H pyrano[3,,4,:6,7]indolizino[1,2-b]quinoline-3,14(4H)-dione (PY-29B) Step 1: Preparation of 2,4-difluoro-3-methoxybenzaldehyde (PY-29a)

[00381] 1.2 equivalents of n-BuLi (9.3 mL, 2.5M) were added to a solution of 1,3-difluoro-2-methoxybenzene (2.8g) in 20 mL of THF at -78 °C, the reaction solution was stirred at this temperature for half an hour, then Petition 870260084912, dated 08 / 20 / 2026, pp. 301 / 1402 294 / 694, 6 equivalents of DMF (9.15 mL) were added, the reaction solution was stirred for another half hour, the low-temperature reaction bath was removed, and the reaction solution was reacted at 15 °C for 1 hour. The reaction was quenched with 4M HCl (6 mL), the reaction solution was extracted with ethyl acetate (3 x 50 mL), the organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluents: petroleum ether / ethyl acetate = 20:1-10:1) to obtain 1.8 g of the yellow oily compound PY-29a (yield: 53%).

[00382] LCMS (ESI): m / z, 173 [M+1]+.

[00383] 1H NMR (400 MHz, DMSO-dβ) δ 10.96-9.56 (m, 1H), 7.83-7.43 (m, 1H), 7.30 (b, 1H), 4.22-3.90 (m, 3H). Step 2: Preparation of 2,4-difluoro-3-methoxy-6-nitrobenzaldehyde (PY-29b-1)

[00384] 0.96 equivalents of fuming nitric acid (446 pL) were added to a solution of the compound 2,4-difluoro-3-methoxybenzaldehyde (1.78 g) in 20.3 mL of sulfuric acid and the reaction solution reacted at 25 °C for 1 hour. The reaction solution was added to ice water, subjected to suction filtration under pressure, washed with water and dried, to obtain 925 mg of the yellow solid compound 2,4-difluoro-3-methoxy-6-nitrobenzaldehyde (PY-29b-1) (yield: 40%).

[00385] 1H NMR (400 MHz, DMSO-d β) δ 10.14 (s, 1H), Petition 870260084912, dated 08 / 20 / 2026, pp. 302 / 1402 295 / 694 8.21 (dd, J = 11.1, 2.0 Hz, 1H), 4.13 (t, J = 1.9 Hz, 3H). Step 3: Preparation of 6-amino-2,4-difluoro-3-methoxybenzaldehyde (PY-29c)

[00386] Iron powder (5.5 eq, 1.31 g), water (23.12 eq, 1.77 mL) and hydrochloric acid (0.55 eq, 71 pL) were added separately to a solution of the compound 2,4-difluoro-3-methoxy-6-nitrobenzaldehyde (925 mg) in 30 mL of ethanol, and the reaction solution was stirred at 80 °C for 16 hours. LCMS showed that a product was generated, the reaction solution was cooled to room temperature, then filtered under pressure and concentrated to obtain a crude product, and the crude product was purified by silica gel column chromatography (eluents: petroleum ether / ethyl acetate = 10:1-5:1) and dried to obtain 488 mg of green solid 6-amino-2,4-difluoro-3-methoxybenzaldehyde (PY-29d) (yield: 61%).

[00387] LCMS (ESI): m / z, 187.9 [M+H]+.

[00388] 1H NMR (400 MHz, DMSO-d β) δ 10.04 (s, 1H), 7.48 (s, 2H), 6.44 (dd, J = 13.4, 2.0 Hz, 1H), 3.77 (s, 3H). Step 4: Preparation of (S)-4-ethyl-8,10-difluoro-4hydroxy-9-methoxy-1,12-dihydro-14Hpyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H)-dione (PY-29d) Petition 870260084912, dated 08 / 20 / 2026, pp. 303 / 1402 296 / 694

[00389] 0.67 equivalents of PPTS (134.9 mg) and 1.2 equivalents of compound PY-8f (253.2 mg) were added separately to a solution of compound 6-amino-2,4-difluoro-3-methoxybenzaldehyde (PY-29c) (150 mg) in 10 mL of toluene, and the reaction solution was stirred at 130 °C for 16 hours in a nitrogen atmosphere. The reaction solution was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (eluents: petroleum ether / ethyl acetate = 5:1-0:1) to obtain 233 mg of the yellow solid compound PY-29d (yield: 67%; purity: 78%).

[00390] LCMS (ESI): m / z, 415 [M+H]+. Step 5: Preparation of (S)-11-(4-(benzyloxy)butyl)-4ethyl-8,10-difluoro-4-hydroxy-9-methoxy-1,12-dihydro-14Hpyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H)-dione) (PY-29f)

[00391] Compound PY-29d (193 mg, purity: 78%) was dissolved in 14.6 mL of glacial acetic acid solvent, and 3.6 mL of concentrated sulfuric acid were added slowly under an ice-cold water bath. 1.2 equivalents of ferrous sulfate (66.2 mg) and 2.6 mL of deionized water were added to another reaction flask. The ferrous sulfate solution was added to the PY-29d compound solution above at the same temperature. Then, 5 equivalents of 5Petition 870260084912, dated 20 / 08 / 2026, page 304 / 1402 297 / 694 (benzoyloxy)valeraldehyde (PY-29e) (349 mg) and 54.4 µL of hydrogen peroxide were added sequentially, and the reaction solution was stirred for 45 minutes in an ice-cold water bath. The reaction solution was added to the ice-cold water, the organic phase was extracted with ethyl acetate (50 mL χ 3), washed with saturated brine, dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product, and the crude product was purified by silica gel column chromatography (eluents: dichloromethane / methanol = 20:1-4:1) to obtain 230 mg of the compound PY-29f (purity: 64%).

[00392] LCMS (ESI): m / z, 577.3 [M+H]+. Step 6: Preparation of (S)-4-ethyl-8,10-difluoro-4hydroxy-11-(4-hydroxybutyl)-9-methoxy-1,12-dihydro-14Hpyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H)-dione (PY-29B)

[00393] 0.25 equivalents of palladium on carbon (78 mg) and 0.25 equivalents of Pd(OH)2 (51.4 mg) were added separately to a solution of the compound PY-29f (497 mg) in 10 ml of methanol, and the reaction solution was stirred at 30 °C for 16 hours. The reaction solution was filtered and then concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluents: dichloromethane / methanol = 20:1-10:1) to obtain 55 Petition 870260084912, dated 08 / 20 / 2026, pp. 305 / 1402 298 / 694 mg of compound PY-29B (yield: 38%; purity: 78%).

[00394] LCMS (ESI): m / z, 487.1 [M+H]+. Step 7: Preparation of (S)-4-ethyl-8,10-difluoro-4,9-dihydroxy-11-(4-hydroxybutyl)-1,12-dihydro-14Hpyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H)-dione (PY-29)

[00395] 6 equivalents of compound AlCla (79 mg) were added in batches to a solution of compound PY-29B (48 mg, purity: 78%) in 4 mL of DCM at 2-hour intervals at 90 °C, and the reaction solution was purified by preparative high-performance liquid chromatography (preparative chromatography manufacturer: SHIMADZU, model: LC-20AP, column: YMC-Triart Prep C18 250 χ 30 mm χ 10 μm, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution ratio: 12% to 42%) and lyophilized, to obtain 6.77 mg of the white solid compound PY-29 (yield: 14.5%).

[00396] LCMS (ESI): m / z, 473.2 [M+H]+.

[00397] 1H NMR (400 MHz, DMSO-d a) δ 8.35 (d, J = 6.8 Hz, 1H), 7.89 (d, J = 7.5 Hz, 2H), 7.76 (d, J = 9.0 Hz, 1H), 7.71 (d, J = 9.0 Hz, 1H), 7.71 (d, .5 Hz, 2Hz). 7.55 (t, J = 6.2 Hz, 1H), 7.42 (t, J = 7.5 Hz, 2H), 7.33 (t, J = 7.5 Hz, 2H), 4.33 - 4.20 (m, 4H), 4.11 (p, J = 7.0 Hz, 1H), 6.6 d. Hz, 2H), 1.95 (dt, J = 12.6, 6.3 Hz, 1H), 1.38 (d, J = 1.9 Hz, 9H), 1.24 (d, J = 7.2 Hz, 3H), 0.86 (dd, J = 19.2, 6.7 Hz, 19 Hz); Petition 870260084912, of 20 / 08 / 2026, p. 306 / 1402 299 / 694 F NMR (377 MHz, DMSO-d β) δ -125.50 (d, J = 13.5 Hz). Preparation Example 35: Preparation of (S)-4-ethyl8,10-difluoro-4,9-di-hydroxy-1,12-di-hydro-14Hpyran[3',4':6,7]indolizine[1,2-b]quinoline-3,14(4H)-dione (PY-29A) Step 1: Preparation of (S)-4-ethyl-8,10-difluoro-4,9-dihydroxy-1,12-di-hydro-14H-pyran[3′,4′:6,7]indolizine[1,2b]quinoline-3,14(4H)-dione (PY-29A)

[00398] AlClA (22.2 mg, 166.52 pmol, 3 eq) was added to a solution of compound PY-29d (29.5 mg, 55.51 pmol, 1 eq, purity: 78%) in 3 mL of DCM. The reaction solution reacted at 70 °C for 2 hours. The reagent was purified by preparative high-performance liquid chromatography (preparative chromatography manufacturer: SHIMADZU, model: LC-20AP, column: YMC-Triart Prep C18 250 x 30 mm x 10 μm, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution ratio: 12% to 42%) and lyophilized to obtain a Petition 870260084912, dated 08 / 20 / 2026, page 307 / 1402 300 / 694 white solid compound PY-29A (1.46 mg, yield: 4.9%).

[00399] LCMS (ESI): m / z, 401.1 [M+H]+.

[00400] 1H NMR (400 MHz, DMSO-dβ) δ 8.54 (s, 1H), 7.77 (d, J = 11.9 Hz, 1H), 7.25 (s, 1H), 6.52 (s, 1H), 5.42 (s, 2H), 5.23 (s, 2H), 1.86 (p, J = 7.0 Hz, 2H), 0.87 (t, J = 7.3 Hz, 3H). Preparation Example 36: Preparation of (S)-4(aminomethyl) 5-chloro-9-ethyl-9-hydroxy-1,2,3,9,12,15 hexahydro-10h,13h-benzo[de]pyran[3',4' b]quinoline-10,13-dione (PY-36) J, O H2N X|f jT ZN \ PY- 36 HO0 J 0 i J NH2 Acl cPnh ^A%oA cPnh 'li PY-36 * PY-36 * PY-36 O^NH O^NH ----- 1 '1 I ' 1 '1 I αΖχνζνζΑ'0Η Br Br PY-36e PY-36f O X'nA, * Ο 1 R / X) FKX AJ< AA 0 iA Al 0 pB- N ( \ H0 \ k<H MF^ -—--->ΒΓΧΐΗΑθ ------~ BooHnAA Cl HO O PY-3 PY-361 Step 1: Preparation of ( chlorophenyl)acetamide (PY-36b)

[00401] 3-bromo-5-chloro-aniline :-6, 70, NH ° ----------* Xi j? ΑΑ / Aq^bl! ~1A1---► cAnAX0 HOZ O ΗθΆθ 6J PY- 36 of N-(3-bromo-5- (PY-36a) (5.00 g, Petition 870260084912, of 20 / 08 / 2026, p. 308 / 1402 301 / 694 24.2 mmol, 1.0 eq) and triethylamine (4.90 g, 48.4 mmol, 6.74 mL, 2.0 eq) were added to dichloromethane (50.0 mL), the nitrogen was changed three times, acetyl chloride (2.85 g, 36.3 mmol, 2.58 mL, 1.5 eq) was added dropwise at 0 °C and then the reaction solution was stirred at 25 °C for 2 hours in a nitrogen atmosphere. 30.0 mL of water were added dropwise to the reaction solution at 0 °C, the precipitate precipitated and was filtered, and the filtrate was concentrated under reduced pressure to obtain the compound N-(3-bromo-5-chlorophenyl)acetamide (5.90 g, yield: 97%) as a white solid.

[00402] 1H NMR (400 MHz, DMSO-d6) δ 10.26 (s, 1H), 7.77 (d, J = 1.2 Hz, 1H), 7.68 (d, J = 1.2 Hz, 1H), 7.36 (d, J = 2.0 Hz, 1H), 2.05 (s, 3H). Step 2: Preparation of tert-butyl (E)-4-(3-acetamido5-chlorophenyl)but-3-enoate (PY-36c)

[00403] N-(3-bromo-5-chlorophenyl)acetamide (5.00 g, 20.1 mmol, 1.0 eq) was dissolved in N,N-dimethylformamide (30 mL) and tert-butyl 3-butenoate (4.29 g, 30.2 mmol, 4.89 mL, 1.5 eq), tris(o-methylphenyl)phosphorus (306.2 mg, 1.01 mmol, 0.05 eq), triethylamine (4.07 g, 40.2 mmol, 5.60 mL, 2.0 eq), bis(tri-tert-butylphosphine)palladium (103 mg, 201.2 pmol, 0.01 eq) and N-methyldicyclohexylamine (7.86 g, 40.2 mmol, 8.54 mL, 2.0 eq) were added. The reaction solution Petition 870260084912, dated 08 / 20 / 2026, p. 309 / 1402 302 / 694 reacted at 100 °C for 4 hours in a nitrogen atmosphere. The reaction solution was cooled to room temperature, water (50.0 mL) was added, and then the reaction solution was extracted twice with ethyl acetate (25 mL). The organic phase was washed three times with saturated brine (30 mL), then dried with anhydrous sodium sulfate and filtered, and the filtrate was concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography and eluted with petroleum ether / ethyl acetate = 15 / 1 - 3 / 2, to obtain tert-butyl(E)-4-(3-acetamido-5-chlorophenyl)but-3-enoate (5.10 g, 16.5 mmol, yield: 82.09%) as a white solid.

[00404] LCMS: RT = 0.634 min, MS (ESI) m / z = 254.0 [M+H]+. Step 3: Preparation of tert-butyl 4-(3-acetamido-5-chlorophenyl)butyrate (PY-36d)

[00405] tert-butyl(E)-4-(3-acetamido-5-chlorophenyl)but-3-enoate (5.00 g, 16.1 mmol, 1.0 eq) was added to methanol (50.0 mL), tris(triphenylphosphine)chlororhodium(I) (1.49 g, 1.61 mmol, 0.1 eq) was added in an argon atmosphere, and then the reaction solution was reacted at 25 °C under hydrogen conditions (30 psi) for two hours. The reaction solution was filtered and the filtrate was concentrated to obtain the product. Petition 870260084912, dated 08 / 20 / 2026, p. 310 / 1402 303 / 694 crude tert-butyl 4-(3-acetamido-5-chlorophenyl)butyrate (3.60 g, 11.5 mmol, yield: 71.42%) as a white solid.

[00406] 1HNMR (400MHz, CDCla) δ ppm 7.41 (s, 1 H), 7.137.08 (m, 2 H), 6.85 (s, 1 H), 2.52 (t, J = 7.2 Hz, 2 H), 2.15 (t, J = 7.6 Hz, 1 H), 2.10 (s, 1 H), 1.83-1.81 (m, 2 H), 1.38 (s, 9 H). Step 4: Preparation of tert-butyl 4-(5-acetamido-2-bromo-3-chlorophenyl)butyrate (PY-36e)

[00407] tert-butyl 4-(3-acetamido-5-chlorophenyl)butyrate (100 mg, 320.7 gmol, 1.0 eq) was dissolved in N,N-dimethylformamide (5.00 mL), NBS (68.5 mg, 385 gmol, 1.2 eq) was added slowly and the reaction solution was kept at 25 °C for 1 hour. Water (10.0 mL) was added dropwise to the reaction solution, then the reaction solution was extracted twice with ethyl acetate (10.0 mL), the organic phase was washed three times with saturated brine (10.0 mL), then dried with anhydrous sodium sulfate and filtered, and the filtrate was concentrated to obtain the crude product tert-butyl 4-(5-acetamido-2-bromo-3-chlorophenyl)butyrate (120 mg, 96.0%) as a white solid.

[00408] LCMS: RT = 2,885 min, MS (ESI) m / z = 336.1 [M+H]+. Step 5: Preparation of 4-(5-acetamido-2-bromo-3-chlorophenyl)butyric acid (PY-36f) Petition 870260084912, dated 08 / 20 / 2026, p. 311 / 1402 304 / 694

[00409] 4-(5-acetamido-2-bromo-3-chlorophenyl) tert-butyl butyrate (100 mg, 256 μmol, 1.0 eq) was dissolved in dichloromethane (2.00 mL), trifluoroacetic acid (2.00 mL) was added slowly, dropwise, at 0 °C, and the reaction solution reacted at 25 °C for 2 hours. The reaction solution was concentrated directly under reduced pressure to obtain a solid, and then dichloromethane (8.00 mL) was added, stirred and filtered to obtain the crude product. 4-(5-acetamido-2-bromo-3-chlorophenyl)butyric acid (60.0 mg, 70.0%) was added as a white solid.

[00410] 1HNMR (400MHz, CDCla) δ ppm 12.09 (br, 1H), 10.19 (s, 1 H), 7.87 (d, J = 2.4 Hz, 1 H), 7.37 (d, J = 2.4 Hz, 1 H), 2.72 (t, J = 7.6 Hz, 2 H), 2.28 (t, J = 7.2 Hz, 2 H), 2.04 (s, 3 H), 1.78 (t, J = 7.6 Hz, 2 H). Step 6: Preparation of N-(4-bromo-3-chloro-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-36g)

[00411] 4-(5-acetamido-2-bromo-3-chlorophenyl)butyric acid (1.80 g, 5.38 mmol, 1.0 eq) was dissolved in Eaton's reagent (113.6 g, 477.3 mmol, 75.00 mL, 88.73 eq) and the reaction solution reacted at 100 °C for 1 hour in a nitrogen atmosphere. The reaction solution was cooled to room temperature, slowly added to cold water to completely quench the reaction, and filtered to obtain a solid. The solid was dissolved in Petition 870260084912, dated 08 / 20 / 2026, p. 312 / 1402 305 / 694 dichloromethane (10.0 mL), then concentrated, depulped with mixed solvents (petroleum ether / ethyl acetate = 10 / 1) and filtered to obtain N-(4-bromo-3-chloro-8-oxo-5,6,7,8tetrahydronaphthalene-1-yl)acetamide (1.20 g, 3.79 mmol, yield: 70.45%) as a yellow solid.

[00412] LCMS: RT = 0.961 min, MS (ESI) m / z = 317.9 [M+H]+.

[00413] 1HNMR (400MHz, CDCla) δ ppm 12.11 (s, 1H), 8.86 (s, 1 H), 3.03 (t, J = 6.0 Hz, 2 H), 2.61 (t, J = 6.4 Hz, 2 H), 2.16 (s, 3 H), 2.04 (t, J = 6.4Hz, 2H). Step 7: Preparation of 8-amino-5-bromo-6-fluoro-3,4-dihydronaphthalene-1(2H)-1-one (PY-36h)

[00414] N-(4-bromo-3-chloro-8-oxo-5,6,7,8tetrahydronaphthalene-1-yl)acetamide (900 mg, 2.84 mmol, 1.0 eq) was dissolved in ethanol (15 mL), hydrochloric acid solution (5 mL, 6 mol / mL) was added at room temperature, and the reaction solution was stirred at 80 °C for 3 hours. The reaction solution was cooled to room temperature and concentrated. The concentrate was adjusted with saturated sodium bicarbonate solution to adjust the pH to 8-9 and then extracted twice with ethyl acetate (10 mL). The organic phase was washed once with saturated brine, dried with anhydrous sodium sulfate, filtered, and concentrated to obtain the crude product 8-amino-5-bromo-6 Petition 870260084912, dated 08 / 20 / 2026, page 313 / 1402 306 / 694 fluoro-3,4-dihydronaphthalene-1(2H)-1-one (700 mg, 2.55 mmol, yield: 89.8%) as a yellow solid.

[00415] LCMS: RT = 0. 942 min, MS (ESI) m / z = 275.8 [M+H]+. Step 8: Preparation of (S)-4-bromo-5-chloro-9-ethyl-9hydroxy-1,2,3,9,12,15-hexahydro-10h,13hbenzo[de]pyrano[3,,4,:6,7]indolizino[1,2-b]quinoline-10,13dione(PY-36i)

[00416] 8-amino-5-bromo-6-fluoro-3,4-dihydronaphthalene-1(2H)-1-one (574 mg, 2.09 mmol, 1.1 eq) and compound PY-8f (500 mg, 1.90 mmol, 1.0 eq) were dissolved in toluene (10 mL), p-toluenesulfonic acid (36.1 mg, 0.19 mmol, 0.1 eq) was added, and the reaction solution was reacted at 110 °C for 16 hours in a nitrogen atmosphere. The reaction solution was cooled to room temperature, a solid precipitated, filtered, and then dried to obtain the crude product PY-36i as a yellow solid (850 mg, 1.69 mmol, yield: 89.4%).

[00417] LCMS: RT = 2,233 min, MS (ESI) m / z = 503.3 [M+H]+. Step 9: Preparation of (S)-(5-flúor-9-ethyl-9-hidroxi10,13-dioxo-2,3,9,10,13,15-hexahidro-1h,12hbenzo[de]pirano[3',4':6,7]indolizino[1,2-b]quinolin-4Petição 870260084912, dated 08 / 20 / 2026, page 314 / 1402 307 / 694 tert-butyl yl)methyl)carbamate (PY-36j)

[00418] The compounds PY-36i (400 mg, 0.80 mmol, 1.0 eq), potassium (N-Boc-aminomethyl)trifluoroborate (948 mg, 4.00 mmol, 5.0 eq), butylated di-1-adamantyldiphosphine (375 mg, 0.40 mmol, 0.5 eq), potassium carbonate (221 mg, 1.60 mmol, 2.0 eq) and palladium acetate (53.88 mg, 0.24 mmol, 0.3 eq) were dissolved in 1,4-dioxane (10 mL) and water (2 mL) and the reaction solution was stirred at 80 °C for 2 hours in a nitrogen atmosphere.The reaction solution was cooled to room temperature and concentrated, water (10 mL) was added to the concentrate, then the concentrate was extracted twice with ethyl acetate (10 mL), the organic phase was washed once with saturated brine, dried with anhydrous sodium sulfate, filtered and concentrated to obtain a crude product, and the crude product was purified by reversed-phase chromatography (column: Xtimate C18 150 x 40 mm x 10 µm; mobile phase: [water (FA)-ACN]; gradient: 26%-66% B, 36 min), to obtain the compound PY-36j (54.2 mg, 0.095 mmol, yield: 11.87%) as a white solid.

[00419] LCMS: RT = 2,127 min, MS (ESI) m / z = 552.5 [M+H]+. Step 10: Preparation of (S)-4-(aminomethyl) 5-chloro-9-ethyl-9-hydroxy-1,2,3,9,12,15-hexahydro-10h,13hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13 Petition 870260084912, dated 20 / 08 / 2026, page 315 / 1402 308 / 694 dione (PY-36)

[00420] Compound PY-36j (52.4 mg, 0.095 mmol, 1.0 eq) was dissolved in dichloromethane (5 mL), trifluoroacetic acid (2 mL) was added at 0 °C, and the reaction solution was reacted at 25 °C for 2 hours. The reaction solution was concentrated under reduced pressure, and the crude product was purified by reversed-phase chromatography (column: Xtimate C18 150 χ 40 mm χ 10 pm; mobile phase: [water (TFA)ACN]; gradient: 0%-38% B, 30 min) to obtain compound PY-36 (4.55 mg, 0.01 mmol, yield: 10.53%) as a white solid.

[00421] LCMS: RT = 1,566 min, MS (ESI) m / z = 452.2 [M+H]+.

[00422] 1HNMR (400MHz, DMSO-d6) δ ppm 8.23 ​​(s, 1 H), 8.19 (s, 2 H), 7.34 (s, 1 H), 6.55 (s, 1 H), 5.45 (s, 2 H), 5.30 (s, 2 H), 4.41 (s, 2 H), 3.20-3.18 (m, 4 H), 2.12 (t, J = 4.8 Hz, 2 H), 1.90-1.86 (m, 2 H), 0.88 (t, J = 7.2 Hz, 3 H). Example of Preparation 37: Preparation of (S)-5-chloro-9-ethyl-9-hydroxy-4-(hydroxymethyl)-1,2,3,9,12,15-hexahydro10h,13h-benzo[de]pyrano[3',4':6,7]indolizino[1,2b]quinoline-10,13-dione (PY-37) Petition 870260084912, dated 08 / 20 / 2026, page 316 / 1402 309 / 694

[00423] The compound PY-36i (200 mg, 0.40 mmol, 1.0 eq) and (tributylstannyl)methanol (192 mg, 0.60 mmol, 1.5 eq) were dissolved in 1,4-dioxane (5 mL), and the catalyst chloro(2-dicyclohexylphosphino-2,4,6-triisopropyl-1,1-biphenyl)[2-(2-amino-1,1-biphenyl)]palladium (II) (XPhos Pd G2) (31.4 mg, 0.04 mmol, 0.1 eq) and the reaction solution was allowed to react at 90 °C for 4 hours in a nitrogen atmosphere. The reaction solution was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure, diluted with water, and then extracted twice with ethyl acetate (10 mL). The organic phase was washed with saturated brine (10 mL), dried with anhydrous sodium sulfate, filtered, and concentrated to obtain a crude product. The crude product was purified by reversed-phase chromatography (column: Welch Xtimate C18 150 x 30 mm x 5 µm; mobile phase: [water (FA)-ACN]; gradient: 6%-46% B, 25 min) to obtain the compound PY-37 (2.08 mg, 0.005 mmol, yield: 1.25%). Petition 870260084912, dated 08 / 20 / 2026, p. 317 / 1402 310 / 694 a white solid.

[00424] LCMS: RT = 1,475 min, MS (ESI) m / z = 453.3 [M+H]+.

[00425] 1HNMR (400MHz, DMSO-d6) δ ppm 8.10 (s, 1 H), 7.32 (s, 1 H), 6.53 (s, 1 H), 5.44 (s, 2 H), 5.28 (s, 2 H), 5.19 (t, J = 5.2 Hz, 1 H), 4.83 (d, J = 5.2 Hz, 2 H), 3.17 (t, J = 7.6 Hz, 2 H), 2.09 (t, J = 7.6 Hz, 2 H), 1.89-1.84 (m, 2 H), 1.15-1.14 (m, 2 H), 0.88 (t, J = 7.2 Hz, 3 H). Example of Preparation 38: Preparation of (S)-9-ethyl-9hydroxy-4-(hydroxymethyl)-1,2,3,9,12,15-hexahydro-10h,13hbenzo[de]pyrano[3,,4,:6,7]indolizino[1,2-b]quinoline-10,13dione (PY-37A)

[00426] The compound PY-36i (200 mg, 0.40 mmol, 1.0 eq) and (tributylstannyl)methanol (192 mg, 0.60 mmol, 1.5 eq) were dissolved in 1,4-dioxane (5 mL), and the catalyst chloro(2-dicyclohexylphosphino-2,4,6-triisopropyl-1,1-biphenyl)[2-(2-amino-1,1-biphenyl)]palladium (II) (XPhos Pd G2) Petition 870260084912, dated 08 / 20 / 2026, page 318 / 1402 311 / 694 (31.4 mg, 0.04 mmol, 0.1 eq) and the reaction solution was reacted at 90 °C for 4 hours in a nitrogen atmosphere. The reaction solution was cooled to room temperature and filtered, the filtrate was concentrated under reduced pressure, diluted with water and then extracted twice with ethyl acetate (10 mL), the organic phase was washed with saturated brine (10 mL), dried with anhydrous sodium sulfate, filtered and concentrated to obtain a crude product. The crude product was purified by reversed-phase chromatography (column: Welch Xtimate C18 150 x 30 mm x 5 µm; mobile phase: [water (FA)-ACN]; gradient: 6%-46% B, 25 min), to obtain compound PY-37A (2.23 mg, 0.005 mmol, yield: 1.25%) as a white solid.

[00427] LCMS: RT = 1,233 min, MS (ESI) m / z = 419.4 [M+H]+.

[00428] 1HNMR (400MHz, DMSO-d6) δ ppm 7.99 (d, J = 8.8 Hz 1 H), 7.90 (d, J = 8.8 Hz 1 H), 7.32 (s, 1 H), 6.51 (s, 1 H), 5.44 (s, 2 H), 5.33 (t, J = 4.4 Hz , 1 H), 5.27 (s, 2 H), 4.73 (d, J = 5.2 Hz , 2 H), 3.19-3.16 (m, 1 H), 3.103.07 (m, 1 H), 2.08 (t, J = 3.2 Hz , 2 H), 1.90-1.86 (m, 2 H), 1.15-1.13 (m, 2 H), 0.89 (t, J = 7.2 Hz, 3 H). Preparation example 39: Preparation of (S)-5-chloro-9etil-4,9-di-hidroxi-1,2,3,9,12,15-hexahidro-10h,13hbenzo[de]pirano[3',4':6,7]indolizino[1,2-b]quinolina-10,13Petição 870260084912, dated 08 / 20 / 2026, pág. 319 / 1402 312 / 694 diona (PY-38) Step 1: Preparation of (S)-5-cloro-9-ethyl-9-hidroxi-4(4,4,5,5-tetrametil-1,3,2-dioxaborolano-2-il)1,2,3,9,12,15-hexahidro-10h,13hbenzo[de]pirano[3,,4,:6,7]indolizino[1,2-b]quinolina-10,13diona (PY-38a)

[00429] The compounds PY-36i (400 mg, 0.80 mmol, 1.0 eq), bis(pinacolate)diboron (305 mg, 1.20 mmol, 1.5 eq), potassium acetate (235 mg, 2.40 mmol, 3.0 eq) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium (176 mg, 0.24 mmol, 0.3 eq) were dissolved in 1,4-dioxane (10 mL) and the reaction solution was stirred at 90 °C for 5 hours in a nitrogen atmosphere. The reaction solution was cooled to room temperature and concentrated, water (10 mL) was added to the concentrate, then the concentrate was Petition 870260084912, dated 08 / 20 / 2026, pp. 320 / 1402 313 / 694 extracted with ethyl acetate (10 mL) twice, the organic phase was washed once with saturated brine, dried with anhydrous sodium sulfate, filtered and concentrated to obtain a crude product, and the crude product was purified by preparative thin-layer chromatography (PE / EA=1 / 4), to obtain compound PY-38a (70.2 mg, 0.13 mmol, yield: 16.25%) as a yellow solid.

[00430] LCMS: RT = 2,391 min, MS (ESI) m / z = 549.3 [M+H]+. Step 2: Preparation of (S)-5-chloro-9-ethyl-4,9-dihydroxy-1,2,3,9,12,15-hexahydro-10h,13hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13dione (PY-38)

[00431] Compound PY-38a (70.2 mg, 0.13 mmol, 1.0 eq) was dissolved in tetrahydrofuran (0.2 mL) and water (0.2 mL), sodium perborate tetrahydrate (44.15 mg, 0.39 mmol, 3.0 eq) was added at 0 °C, and the reaction solution was allowed to react at 25 °C for 1 hour. The reaction was stopped with a saturated ammonium chloride solution (0.2 mL) and then the reaction solution was purified by reversed-phase chromatography (column: Xtimate C18 150 χ 40 mm χ 10 pm; mobile phase: [water (FA)-ACN]; gradient: 10%-50% B, 36 min) to obtain the compound PY-38 (0.82 mg, 0.002 mmol, yield: 1.53%) as a white solid. Petition 870260084912, dated 08 / 20 / 2026, page 321 / 1402 314 / 694

[00432] LCMS: RT = 1,491 min, MS (ESI) m / z = 439.3 [M+H]+.

[00433] 1HNMR (400MHz, DMSO-d6) δ ppm 8.36 (s, 0.16 H), 8.03 (s, 1 H), 7.23 (s, 1 H), 6.49 (s, 1 H), 5.42 (s, 2 H), 5.21 (s, 2 H), 3.10 -3.07 (m, 2 H), 3.02 (t, J= 5.6 Hz, 2 H), 2.01 (t, J = 6.4 Hz, 2 H), 1.88-1.85 (m, 2 H), 1.24 (s, 1 H), 0.88 (t, J= 7.6 Hz, 3 H). Example of Preparation 40: Preparation of PY-41A and PY41B sNHAc PY-41A and PY-41B Petition 870260084912, dated 08 / 20 / 2026, p. 322 / 1402 315 / 694 PY-Uc Step 1: Preparation of compounds PY-41A-ae and PY-41A-b

[00434] The compound N-(8-amino-5-bromo-6-fluoro-1-oxo-1,2,3,4-tetrahydronaphthalene-2-yl)acetamide (PY-Uc) (for the preparation method, see Preparation Example 44) (140 mg, 444.25 pmol, 1 eq) was dissolved in toluene (10 mL), (S)4-ethyl-4-hydroxy-7,8-dihydro-1H-pyrano[3,4-f]indolizino3,6,10(4H)-trione (PY-8f) (116.95 mg, 444.25 pmol, 1 eq) and PPTS (111.64 mg, 444.25 pmol, 1 eq) were added, and the reaction solution was stirred at 125 °C for 12 hours. The reaction solution was concentrated under reduced pressure, and the residue was purified by high-performance liquid chromatography (preparative chromatography manufacturer: Petition 870260084912, dated 08 / 20 / 2026, page 323 / 1402 316 / 694 SHIMADZU, model: LC-20AP, column: YMC-Triart Prep C18 250 χ 50 mm x 7 μm, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution ratio: 21% to 51%), to obtain two brown isomeric solids, namely, PY-41-a (54 mg, yield: 22.41%) and PY-41-b (54 mg, yield: 22.41%).

[00435] LCMS (ESI): m / z, 542.2 [M+H]+. Step 2: Preparation of the PY-41A compound

[00436] The compound PY-41A-a (15 mg, 27.66 pmol, 1 eq) was dissolved in dioxane (2 mL), hydroxymethyltributylstanne (26.64 mg, 82.97 pmol, 3 eq) and XPhos Pd G2 (4.35 mg, 5.53 pmol, 0.2 eq), the nitrogen in the reaction solution was replaced three times and the reaction solution was stirred at 90 °C for 12 hours in a nitrogen atmosphere. The reaction solution was filtered and concentrated under reduced pressure, and the residue was purified by preparative high-performance liquid chromatography (preparative chromatography manufacturer: Oriendo, model: BRIX-2860 (R1, 4, 5, 6), Phenomenex Luna C18 (250x50 mmx10 pm) was used as the chromatographic column, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution ratio: 14% to 24%), to obtain a white solid PY-41A (1.10 mg, yield: 8.06%).

[00437] LCMS (ESI): m / z, 494.2 [M+H]+. Step 3: Preparation of the PY-41B compound Petition 870260084912, dated 08 / 20 / 2026, page 324 / 1402 317 / 694

[00438] The compound PY-41A-b (15 mg, 27.66 pmol, 1 eq) was dissolved in dioxane (2 mL), hydroxymethyltributylstanane (26.64 mg, 82.97 pmol, 3 eq) and XPhos Pd G2 (4.35 mg, 5.53 pmol, 0.2 eq) were added, nitrogen shifts were performed on the reaction solution three times, and the reaction solution was stirred at 90 °C for 12 hours in a nitrogen atmosphere. The reaction solution was filtered and concentrated under reduced pressure, and the residue was purified by high-performance liquid chromatography (preparative chromatography manufacturer: Oriendo, model: BRIX-2860 (R1, 4, 5, 6), Phenomenex Luna C18 (250x50 mmx10 µm) was used as the chromatographic column, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution ratio: 12% to 42%), to obtain a white solid product PY41B (1.02 mg, yield: 7.47%).

[00439] LCMS (ESI): m / z, 494.1 [M+H]+. Example of Preparation 41: Preparation of ethyl ((9S)-9-ethyl5-fluoro-9-hydroxy-4-(hydroxymethyl)-10,13-dioxo2,3,9,10,13,15-hexahydro-1H,12Hbenzo[d]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-1yl)carbamate (PY-42) Petition 870260084912, dated 08 / 20 / 2026, page 325 / 1402 318 / 694

[00440] The compound PY-UA (for the preparation method, see Preparation Example 44) (10.53 mg, 95%, 22.15 pmol, 1 eq) was dissolved in DCM (5 mL), TEA (4.48 mg, 6.16 pL, 44.30 pmol, 2 eq) was added and ethyl chloroform (4.81 mg, 4.24 pL, 44.30 pmol, 2 eq) was added at 0 °C. The reaction solution was stirred at 0 °C for 8 hours. The reaction solution was diluted with DCM (10 mL) and washed with water (10 mL), the organic phase was dried, then filtered and purified by high-performance liquid chromatography (preparative chromatography manufacturer): Oriendo, model: BRIX-2860 (R1, 4, 5, 6), column: Welch Xtimate C18 250 x 30 mm x 10 µm, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution ratio: 20% to 50%), to obtain a white solid product PY-42 (1.12 mg, yield: 9.66%, purity: 90%).

[00441] LCMS (ESI): m / z, 524.2 [M+H]+. Petition 870260084912, dated 08 / 20 / 2026, page 326 / 1402 319 / 694 Example of Preparation 42: Preparation of N-((9S)-9-ethyl5-fluoro-9-hydroxy-4-(hydroxymethyl)-10,13-dioxo2,3,9,10,13,15-hexahydro-1H,12Hbenzo[d]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-1-yl) 2-hydroxyacetamide (PY-43) DIPEA, DMF Step 1: 2-((tert-butyldimethylsilyl)oxy)-N-((9S)-9ethyl-5-fluoro-9-hydroxy-4-(hydroxymethyl)-10,13-dioxo2,3,9,10,13,15-hexahydro-1H,12Hbenzo[d]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-1 il)acetamide (PY-43-b)

[00442] The compound PY-UA (5 mg, 100%, 11.08 pmol, 1 eq) was dissolved in DMF (1 mL), and DIPEA (2.86 mg, 3.66 pL, 22.15 pmol, 2 eq) and 2,5-dioxopyrrolidine-1-yl-2-((tert-butyldimethylsilyl)oxy)acetate (PY-43-a) (3.82 mg, 13.29 pmol, 1.2 eq) were added. The reaction solution was stirred at 20 °C for 12 hours. The reaction solution was purified by Petition 870260084912, dated 08 / 20 / 2026, page 327 / 1402 320 / 694 High-performance liquid chromatography preparative (preparative chromatography manufacturer: Oriendo, model: BRIX-2860 (R1, 4, 5, 6), column: GS-120-10-C18AP, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution rate: 30% to 60%), to obtain a white solid product (2 mg, yield: 28.95%).

[00443] LCMS (ESI): m / z, 624.2 [M+H]+. Step 2: Preparation of N-((9S)-9-ethyl-5-fluoro-9-hydroxy-4-(hydroxymethyl)-10,13-dioxo-2,3,9,10,13,15hexahydro-1H,12H-benzo[d]pyrano[3',4':6,7]indolizino[1,2b]quinoline-1-yl)-2-hydroxyacetamide (PY-43)

[00444] Compound PY-43-b (2 mg, 3.21 pmol, 1 eq) was dissolved in THF (1 mL) and HCl (116.91 pg, 500 pL, 3.21 pmol, 1 eq) was added. The reaction solution was stirred at 15 °C for 2 hours. The reaction solution was purified by preparative high-performance liquid chromatography (preparative chromatography manufacturer: Oriendo, model: BRIX-2860 (R1, 4, 5, 6), column: Welch Xtimate C18 250 x 30 mm x 10 µm, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution ratio: 12% to 42%), to obtain a yellow solid product PY-43 (1.10 mg, yield: 67.33%, purity: 100%).

[00445] LCMS (ESI): m / z, 510.2 [M+H]+. Example of Preparation 43: Preparation of (S)-4-amino-9 Petition 870260084912, dated 08 / 20 / 2026, p. 328 / 1402 321 / 694 ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13 dione (PY-A) Step 1: Preparation of 6,8-difluoro-5-nitro-1,2,3,4-tetrahydronaphthalene-1-one (PY-Ab)

[00446] 0.96 equivalents of potassium nitrate (546 mg) were added to a solution of 6,8-difluoro-3,4-dihydronaphthalene-1(2H)-one (PY-Aa) (1.0 g) in 6 mL of sulfuric acid, and the reaction solution was stirred in an ice-cold water bath for 2 hours. The reaction solution was added to the ice-cold water, the reaction was quenched with 50 mL of water, and Petition 870260084912, dated 08 / 20 / 2026, p. 329 / 1402 322 / 694 reaction solution was extracted with ethyl acetate (60 mL χ 3), the organic phase was washed with saturated brine, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain 800 mg of a crude product of the compound PY-Ab (purity: 41%).

[00447] 1H NMR (400 MHz, DMSO-dβ) δ 7.20 - 7.07 (m, 1H), 2.96 (q, J = 6.0 Hz, 2H), 2.61 (ddd, J = 27.9, 7.3, 5.8 Hz, 2H), 2.12 - 2.00 (m, 2H). Step 2: Preparation of 6,8-difluoro-5-amino-1,2,3,4-tetrahydronaphthalene-1-one (PY-Ac)

[00448] 8 equivalents of iron powder (894 mg) and 3 equivalents of ammonium chloride (321 mg) were added separately to a mixed solution of 6,8-difluoro-5-nitro-1,2,3,4-tetrahydronaphthalene-1-one (800 mg) in 9 mL of ethanol and water (volume ratio = 8:1), and the reaction solution was stirred at 80 °C for 2 hours. After the iron powder was filtered, the reaction solution was concentrated directly and the residue was purified by silica gel column chromatography (eluents: ethyl acetate / petroleum ether = 1:1) to obtain 176 mg of 6,8-difluoro-5-amino-1,2,3,4-tetrahydronaphthalene-1-one (PY-Ac) (yield: 45%).

[00449] LCMS (ESI): m / z, 198.1 [M+H]+.

[00450] 1H NMR (400 MHz, DMSO-dβ) δ 7.03 (t, J = 11.4 Hz, 1H), 5.02 (s, 2H), 2.70 (t, J = 6.2 Hz, 2H), 2.08 (s, Petition 870260084912, dated 08 / 20 / 2026, pp. 330 / 1402 323 / 694 1H), 2.00 (p, J = 6.4 Hz, 2H). Step 3: Preparation of N-(2,4-difluoro-5-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-Ad)

[00451] 1.2 equivalents of acetic anhydride (343 pL) and 1.2 equivalents of triethylamine (508 pL) were added separately to a solution of 6,8-difluoro-5-amino-1,2,3,4-tetrahydronaphthalene-1-one (600 mg) in 25 mL of dichloromethane, and the reaction solution was stirred at 60 °C for 36 hours. The reaction solution was concentrated and the residue was purified by silica gel column chromatography (eluents: dichloromethane / methanol = 20:1) to obtain 483 mg of N-(2,4-difluoro-5-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-Ad) (yield: 66%, purity: 95%).

[00452] LCMS (ESI): m / z, 240.1 [M+H]+. Step 4: Preparation of N-(4-amino-2-fluoro-5-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-Ae)

[00453] 35 mL of ammonia were added to a solution of N-(2,4-difluoro-5-oxo-5,6,7,8tetrahydronaphthalene-1-yl)acetamide (PY-Ad) (1.43 g) in 30 mL of DMSO in a sealed tube, and the reaction solution was stirred at 100 °C for 16 hours. The reaction was quenched with 50 mL of water, the reaction solution was extracted with ethyl acetate, the organic phase was washed with saturated brine, dried with anhydrous sodium sulfate, filtered, and concentrated under pressure. Petition 870260084912, dated 08 / 20 / 2026, page 331 / 1402 324 / 694 reduced, and the residue was purified by silica gel column chromatography (eluents: dichloromethane / methanol = 20:1) to obtain 1.01 g of N-(4-amino-2-fluoro-5-oxo-5,6,7,8tetrahydronaphthalene-1-yl)acetamide (PY-Ae) (yield: 72%, purity: 94%).

[00454] LCMS (ESI): m / z, 237.2 [M+H]+. Step 5: Preparation of (S)-N-(9-ethyl-5-fluoro-9-hydroxy-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-4yl)acetamide (PY-Ag)

[00455] 1.2 equivalents of the compound PY-8f (1.3 g) and 0.67 equivalents of PPTS (691 mg) were added separately to a solution of N-(4-amino-2-fluoro-5-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (1.01 g) in 50 mL of toluene, and the reaction solution was stirred at 130 °C for 16 hours. The reaction solution was concentrated and the residue was purified by silica gel column chromatography (eluents: dichloromethane / methanol = 10:1) to obtain 584 mg of the compound PY-Ag (yield: 30%; purity: >99%).

[00456] LCMS (ESI): m / z, 464.0 [M+H]+.

[00457] 1H NMR (400 MHz, DMSO-de) δ 9.82 (s, 1H), 7.80 (d, J = 11.0 Hz, 1H), 7.31 (s, 1H), 6.52 (s, 1H), 5.44 (s, 2H), 5.25 (s, 2H), 3.16 (t, J = 6.1 Hz, 2H), 2.98 (t, J = 6.0 Hz, 2H), 2.14 (s, 3H), 2.06 - 1.99 (m, 2H), 1.87 (p, J Petition 870260084912, dated 08 / 20 / 2026, page 332 / 1402 325 / 694 = 7.1 Hz, 2H), 0.88 (t, J = 7.3 Hz, 3H). Step 6: Preparation of (S)-4-amino-9-ethyl-5-fluoro-9-hydroxy-1,2,3,9,12,15-hexahydro-10H,13Hbenzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13dione (PY-A)

[00458] 12N hydrochloric acid (6 mL) was added to a solution of the compound PY-Ag (78 mg) in 6 mL of ethanol, and the reaction solution was stirred at 60 °C for 16 hours. The reaction solution was purified by preparative high-performance liquid chromatography (preparative chromatography manufacturer: SHIMADZU, model: LC-20AP, column: YMC-Triart Prep C18 250 x 30 mm x 10 μm, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution ratio: 21% to 51%) and lyophilized, to obtain 43.9 mg of the compound PY-A (yield: 61%, purity: 98%).

[00459] LCMS (ESI): m / z, 422.1 [M+H]+.

[00460] 1H NMR (400 MHz, DMSO-dβ) δ 7.63 (d, J = 12.5 Hz, 1H), 7.20 (s, 1H), 6.47 (s, 1H), 5.76 (s, 2H), 5.41 (s, 2H), 5.18 (s, 2H), 3.06 (t, J = 6.1 Hz, 2H), 2.84 (t, J = 6.1 Hz, 2H), 2.02 (t, J = 6.2 Hz, 2H), 1.86 (dq, J = 14.4, 7.0 Hz, 2H), 0.87 (t, J = 7.3 Hz, 3H);19F NMR (377 MHz, DMSOd β) δ -125.24. Example of Preparation 44: Preparation of PY-UA and PY-UPetition 870260084912, dated 08 / 20 / 2026, p. 333 / 1402 326 / 694 F'YU-A and PY-UB PY-U-A and PY-UB Basso 1: Preparation of (E)-N-(4-bromo-3-fluoro-7(hydroxyimino)-8-oxo-5,6,7,8-tetrahydronaphthalene-1-yl)acetamide (PY-Ua)

[00461] Potassium tert-butoxide (3.36g, 29.99 mL, 29.99 mmol, 3 eq, IM in THE) and tert-butyl nitrite (3.09 g, 3.60 mL, 29.99 mmol, 3 eq) were added to a solution of N-(4-bromo-3-fluoro-8-oxo-5,6,7,8-tetrahydronaphthalene-1 Petition 870260084912, dated 20 / 08 / 2026, page. 327 / 694 yl)acetamide (PY-8g) (3g, 10 mmol, 1 eq) in anhydrous THF (150 mL) at 0 °C in a nitrogen atmosphere and, after addition, the reaction solution reacted at 0 °C-10 °C for 1.5 hours. 200 mL of water were added to the reaction solution at 0 °C, the reaction solution was then extracted with ethyl acetate (200 mL χ 3), the organic phases were combined and then washed with saturated brine (100 mL), dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain a crude product of the compound PY-Ua (3.20g, crude product, yield: 48.63%, purity: 50%) as a yellow solid.

[00462] LCMS (ESI): m / z, 329.0 [M+1]+. Step 2: Preparation of the compound N,N'-(4-bromo-3-fluoro-8-oxo-5,6,7,8-tetrahydronaphthalene-1,7-diyl)diacetylamide (PY-Ub)

[00463] Zinc powder (4.77 g, 668.47 pL, 72.92 mmol, 15 eq) was added to a solution of compound PY-Ua (3.20 g, 50%, 4.86 mmol, 1 eq) in acetic acid (40 mL) and acetic anhydride (20 mL), and after the addition, the reaction solution reacted at 15 °C–20 °C for 16 hours. The reaction solution was concentrated to remove the acetic acid, the residue was added to a mixed solution of ethyl acetate (50 mL) and water (50 mL), the mixed solution was stirred for 10 minutes and filtered with diatomaceous earth, the filtrate was added to a Petition 870260084912, dated 08 / 20 / 2026, p. 335 / 1402 328 / 694 Separating funnel to separate the liquids. The aqueous phase was extracted twice with ethyl acetate (50 mL χ 2), the organic phases were combined, washed with brine, dried with anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane: methanol = 10:1) to obtain the yellow solid compound PY-Ub (1.15 g, yield: 55.63%, purity: 84%).

[00464] LCMS (ESI): m / z, 357 [M+H]+, 359 [M+H]+. Step 3: Preparation of N-(8-amino-5-bromo-6-fluoro-1-oxo-1,2,3,4-tetrahydronaphthalene-2-yl)acetamide (PY-Uc)

[00465] The compound PY-Ub (1.15 g, 84%, 2.70 mmol, 1 eq) was dissolved in ethanol (15 mL), then HCl (3.28 g, 15 mL, 90 mmol, 33.2776 eq, 6 M) was added and the reaction solution was stirred at 60 °C for 2 hours. The reaction solution was concentrated to remove most of the solvent, neutralized with sodium bicarbonate (30 mL), and then extracted with DCM (20 mL χ2), and the organic phase was dried, filtered, and concentrated under reduced pressure to be used directly in the next step. The resulting product was a brown solid (700 mg, yield: 68.99%).

[00466] LCMS (ESI): m / z, 315.0 [M+H]+. Step 4: Preparation of N-((9S)-4-bromo-9-ethyl-5-fluoro-9-hydroxy-10,13-dioxo-2,3,9,10,13,15-hexahydro-1H,12H (Reference 870260084912, dated 20 / 08 / 2026, page 336 / 1402) 329 / 694 benzo[d]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-1yl)acetamide (PY-Ud)

[00467] The compound PY-Uc (700 mg, 2.22 mmol, 1 eq) was dissolved in toluene (10 mL), (S)-4-ethyl-4-hydroxy-7,8-dihydro-1H-pyrano[3,4-f]indolizino-3,6,10(4H)-trione (PY8f) (877.11 mg, 3.33 mmol, 1.5 eq) and PPTS (558.20 mg, 2.22 pmol, 1 eq) were added to the solution, and the solution was stirred at 125 °C for 12 hours. The reaction solution was concentrated under reduced pressure and the residue was purified by preparative high-performance liquid chromatography to obtain the brown solid product (1 g, yield): 83.01%, purity: 75%).

[00468] LCMS (ESI): m / z, 542.1 [M+H]+. Step 5: Preparation of N-((9S)-9-ethyl-5-fluoro-9hydroxy-4-(hydroxymethyl)-10,13-dioxo-2,3,9,10,13,15hexahydro-1H,12H-benzo[d]pyrano[3',4':6,7]indolizino[1,2b]quinoline-1-yl)-acetamide (PY-Ue)

[00469] The compound PY-Ud (300 mg, 75%, 414.85 pmol, 1 eq) was dissolved in dioxane (10 mL), and (tributylstanyl)methanol (399.62 mg, 1.24 pmol, 3 eq) and XPhos Pd G2 (65.28 mg, 82.97 pmol, 0.2 eq) were added. Nitrogen shift was performed on the reaction solution, and the reaction solution was stirred at 90 °C for 12 hours in a nitrogen atmosphere. The reaction solution was concentrated Petition 870260084912, dated 08 / 20 / 2026, page 337 / 1402 330 / 694 under reduced pressure and the residue was purified by high-performance liquid chromatography to obtain the white solid product (120 mg, yield: 58.6%).

[00470] LCMS (ESI): m / z, 494.1 [M+H]+. Step 6: Preparation of PY-UA and PY-UB compounds

[00471] The compound PY-Ue (50 mg, 101.32 pmol, 1 eq) was dissolved in HCl (6N, 6 mL), DIPEA was added, and the reaction solution was stirred at 85 °C for 6 hours. The reaction solution was purified by preparative high-performance liquid chromatography (preparative chromatography manufacturer: Oriendo, model: R-120g, Phenomenex Luna C18 (250x50 mmx10 pm) was used as the chromatographic column, mobile phase: water (0.225% HCOOH)-acetonitrile, water elution rate: 10% to 20%), to obtain two blank isomeric solids, namely, PY-UA (62 mg, no yield was calculated for the crude product) and PY-UB (16 mg, yield: 34.98%).

[00472] LCMS (ESI): m / z, 452.2 [M+H]+. Example of Preparation 45: Preparation of (S)-7-ethyl-7hydroxy-14-(3-hydroxypropyl)-10,13-dihydro-11H[1,3]dioxolo[4,5-g]pyrano[3',4':6,7]indolizino[1,2b]quinolin-8,11(7H)-dione (PY-Y) Petition 870260084912, dated 08 / 20 / 2026, page 338 / 1402 331 / 694 Step 1: Preparation of 6-aminobenzo[d][1,3]dioxol-5-carbaldehyde (PY-Y2).

[00473] Iron powder (3.94 g, 70.47 mmol, 5.5 eq) and ammonium chloride (3.77 g, 70.47 mmol, 5.5 eq) were added to ethanol (30.0 mL) and water (3.00 mL), followed by 6-nitrobenzo[d][1,3]oxole-5-carbaldehyde (2.50 g, 12.81 mmol, 1 eq), and the reaction solution was reacted at 80 °C for 4 hours. The reaction solution was filtered, the filtrate was concentrated under reduced pressure, the residue was dissolved in water and dichloromethane (100 mL), the organic phase was washed with saturated sodium bicarbonate (30 mL), dried with anhydrous sodium sulfate and concentrated under reduced pressure, and the Petition 870260084912, dated 08 / 20 / 2026, page 339 / 1402 332 / 694 residue was purified by silica gel column chromatography (SiO2, DCM: MeOH = 1:0, Rf(P) = 0.39) to obtain 6-aminobenzo[d][1,3]dioxol-5-carbaldehyde (1.27 g, yield: 59.83%).

[00474] LCMS: RT = 0. 996 min, MS (ESI) m / z = 166.1 [M+H]+. Step 2: Preparation of (S)-7-ethyl-7-hydroxy-10,13dihydro-11h-[1,3]dioxolo[4.5g]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-8,11(7H)dione (PY-Y3)

[00475] Compound PY-8f (2.00 g, 7.60 mmol, 1 eq) and 6-aminobenzo[d][1,3]dioxol-5-carbaldehyde (1.25 g, 7.60 mmol, 1 eq) were dissolved in toluene (160 mL), then p-toluenesulfonic acid monohydrate (144.52 mg, 759.75 pmol, 0.1 eq) was added, the reaction solution was stirred at 125 °C for 16 hours, cooled to 25 °C and filtered, and the filter cake was washed with 10 mL of tetrahydrofuran and dried under reduced pressure to obtain compound PY-Y3 (1.51 g, yield: 50.65%).

[00476] LCMS: RT = 1. 271 min, MS(ESI) m / z = 393.2 [M+H]+. Step 3: Preparation of (S)-7-ethyl-7-hydroxy-14-(3-hydroxypropyl)-10,13-dihydro-11H-[1,3]dioxolo[4,5] Petition 870260084912, dated 20 / 08 / 2026, page 340 / 1402 333 / 694 g]pyran[3',4':6,7]indolizino[1,2-b]quinolin-8,11(7H)-dione (PY-Y)

[00477] The compound PY-Y3 (400 mg, 795.19 μmol, 1 eq) and ferrous sulfate heptahydrate (353.72 mg, 1.27 mmol, 1.6 eq) were dissolved in 10 mL of water, 98% sulfuric acid (4.59 g, 46.83 mmol, 2.50 mL, 58.89 eq) was added under stirring, the reaction solution was stirred thoroughly for 10 minutes, then 4-hydroxybutyraldehyde (343.3 mg, 3.90 mmol, 5 eq) was added dropwise at 0 °C, hydrogen peroxide (1.26 g, 11.10 mmol, 1.07 mL, purity: 30%, 13.96 eq) was added dropwise to 20 mL of aqueous solution, and the reaction solution was Stirred at 0°C-5°C for 1 hour.The reaction solution was added to ice-cold water, adjusted with saturated sodium bicarbonate solution until the pH reached 8.0, extracted with ethyl acetate (50 mL x 5) and concentrated under reduced pressure, and the residue was purified by preparative high-performance liquid chromatography (Xtimate C18 150 x 40 mm x 10 μm; mobile phase: [water (0.1% FA)-acetonitrile]; gradient: 10%-44% acetonitrile, 36 min) to obtain the compound PY-Y (99.5 mg, purity: 99.6%).

[00478] LCMS: RT = 1. 890 min, MS (ESI) m / z = 451.3 [M+H]+.

[00479] 1HNMR (400MHz, DMSO-d6) δ ppm 7.63 (s, 1 H), 7.50 (s, 1 H), 7.24 (s, 1 H), 6.50 (s, 1 H), 6.29 (s, 2 H), Petition 870260084912, dated 08 / 20 / 2026, pp. 341 / 1402 334 / 694 5.42 (s, 2 H), 5.25 (s, 2 3.49 (t, J = 5.6 Hz, 2 H), (t, J = 1.6 Hz, 1 H), 2.33 (m, 2 H), 0.88 (t, J = 7.2 H), 4.68 (t, J = 5.2 Hz, 1 H), 3.15 (t, J = 6.8 Hz, 2 H), 2.53 (t, J = 1.6 Hz, 1 H), 1.81 - 1.88 Hz, 3 H). Example of Preparation 46: Preparation of N2-(6-(2,5dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl)-N6(2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanoyl)-L-lysine (A) RotaHo^ o HOV Step 1: Preparation of N2-(benzyloxy)carbonyl)-N6(2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanoyl)-L-lysine (Ab)

[00480] (3R,4S,5S,6R)-3,4,5-trihydroxy-6(hydroxymethyl)tetrahydro-2H-pyran-2-one (Aa) (1.27 g, 7.13 Petition 870260084912, dated 08 / 20 / 2026, p. 342 / 1402 335 / 694 mmol) and ((benzyloxy)carbonyl)-L-lysine (Ab) (2 g, 7.13 mmol) were dissolved in methanol (30 mL) at room temperature, and then triethylamine (1.44 g, 14.27 mmol) was added. The reaction solution was stirred at 70 °C for 16 hours. The reaction solution was concentrated under reduced pressure. The resulting residue was isolated by high-performance liquid chromatography (Oriendo, BRIX-2860; column: Phenomenex Luna C18 250 x 50 mm x 10 pm; mobile phase: water (0.225% trifluoroacetic acid)-acetonitrile, eluted 45% to 85%), to obtain a white solid compound Ac (2.5 g, yield: 76.43%).

[00481] LCMS: [M+H]+= 459.1. Step 2: Preparation of N6-(2R,3S,4R,5R)-2,3,4,5,6pentahydroxyhexanoyl)-L-lysine (Ad)

[00482] The compound N2-(benzoyloxy)carbonyl)-N6(2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanoyl)-L-lysine (Ab) (2.5 g, 5.45 mmol) was dissolved in methanol (40 mL) at room temperature and 10% wet palladium on charcoal (250 mg) was added to the reaction solution. The reaction solution was stirred for 6 hours at room temperature in a hydrogen atmosphere. The reaction solution was filtered with diatomaceous earth, the filter cake was washed with water, and the filtrate was lyophilized to obtain a white solid compound Ad (1.6 g, yield: 88.96%). Petition 870260084912, dated 08 / 20 / 2026, p. 343 / 1402 336 / 694

[00483] LCMS: [M+H]+= 325.1.

[00484] 1H NMR (400 MHz, DMSO-d6) δ 4.16-4.19 (d, J = 9.4 Hz, 1H), 3.93-3.97 (t, J = 9.4 Hz, 1H), 3.72 - 3.50 (m, 5H), 3.10-3.20 (m, 2H), 1.68-1.79 (m, 2H), 1.40-1.55 (m, 2H), 1.20-1.35 (m, 2H). Step 3: Preparation of N2-(6-(2,5-dioxo-2,5-dihydro-1Hpyrrol-1-yl)hexanoyl)-N6-(2R,3S,4R,5R)-2,3,4,5,6pentahydroxyhexanoyl)-L-lysine (A)

[00485] The compound N6-(2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanoyl)-L-lysine (Ad) (1.6 g, 4.93 mmol) was dissolved in N,N-dimethylformamide (30 mL) at room temperature, and then 2,5-dioxopyrrolidine-1-yl-6-(2,5dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoate (Ae) (1.52 g, 4.93 mmol) and DIEA (1.27 g, 9.87 mmol) were added separately. The reaction solution was stirred at 70 °C for 16 hours in a nitrogen atmosphere. The reaction solution was filtered and isolated by preparative high-performance liquid chromatography (Orendo, BRIX-2860; column: Phenomenex Luna C18 250 χ 50 mm χ 10 pm; mobile phase: water (0.225% trifluoroacetic acid)-acetonitrile, eluted from 45% to 85%), to obtain a white solid ligand A (400 mg, yield: 15.67%).

[00486] LCMS: [M+H]+= 517.9.

[00487] 1H NMR (400 MHz, DMSO-d6) δ 7.93 (d, J = 7.6 Petition 870260084912, dated 08 / 20 / 2026, p. 344 / 1402 337 / 694 Hz, 1H), 7.60 (t, J = 7.6 Hz, 1H), 6.97 (s, 2H), 5.32 (m, 1H), 4.59 - 4.30 (m, 2H), 4.17 - 3.99 (m, 1H), 3.96-3.91 (m, 1H), 3.89-3.81 (m, 1H), 3.57-3.5 (m, 1H), 3.48-3.39 (m, 2H), 3.34 (s, 4H), 3.12 - 2.89 (m, 2H), 2.05 (t, J = 6.4Hz ,2H), 1.82 - 0.95 (m, 13H). Route 2: Aa Ad Step 1: Preparation of N2-(tert-butoxycarbonyl)-N6(2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanoyl)-L-lysine (Ag)

[00488] (tert-butoxycarbonyl)-L-lysine (Af) (5 g, 0.02 mol), (3R,4S,5S,6R)-3,4,5-trihydroxy-6(hydroxymethyl)tetrahydro-2H-pyran-2-one (Aa) (3.6 g, 0.02 mol) were dissolved in MeOH (80 mL), TEA (4.1 g, 0.04 mol) was added and the reaction solution reacted at 70 °C for 16 hours. The reaction solution was concentrated, MTBE (50 mL x 3) was added, the resulting solution was concentrated under reduced pressure and then sprayed with petroleum ether to obtain 8 g of a crude product, i.e., a white foamy crude product (the product was a salt formed by an acidic compound and TEA), where the yield was not calculated.

[00489] LCMS (ESI): m / z, 425, 2[M+H]+, 4 4 7.2[M+Na]+. Petition 870260084912, dated 08 / 20 / 2026, pp. 345 / 1402 338 / 694

[00490] 1H NMR (400 MHz, DMSO) δ 7.50 (brs, 1H), 5.61 (d, J = 4.0 Hz, 1H), 4.27 (s, 1H), 4.13 (s, 1H), 4.10-3.85 (m, 1H), 3.85-3.66 (m, 4H), 3.28-3.15 (m, 2H), 1.80-1.55 (m, 2H),1.55-1.48 (m, 2H), 1.50-1.21 (m, 11H. Step 2: Preparation of N6-(2R,3S,4R,5R)-2,3,4,5,6pentahydroxyhexanoyl)-L-lysine (Ad)

[00491] N2-(tert-butoxycarbonyl)-N6-(2R,3S,4R,5R)2,3,4,5,6-pentahydroxyhexanoyl)-L-lysine (Ag) (7 g) was dissolved in DCM (35 mL), TFA (35 mL) was added and the reaction solution was maintained at 10 °C-15 °C for 16 hours. The reaction solution was concentrated, DCM (50 mL χ 3) was added, the resulting solution was concentrated under reduced pressure, then water was added for complete dissolution and the resulting solution was lyophilized to obtain 8 g of a viscous yellow crude product, with a 100% yield.

[00492] 1H NMR (400 MHz, DMSO) δ 9.26 (s, 1H), 8.26 (d, J = 25.1 Hz, 3H), 7.69 (dd, J = 37.2, 31.4 Hz, 1H), 3.99 (d, J = 3.7 Hz, 1H), 3.94 - 3.84 (m, 2H), 3.58 (dd, J = 13.3, 3.7 Hz, 1H), 3.51 - 3.45 (m, ...

Claims

1. A compound represented by the general formula (A) or a pharmaceutically acceptable salt thereof, L-L2-Li-Dr (A) where: Dr is selected from the following structures: , and Ri is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, -NRdRe, -(CH2)m-OH, -(CH2)m-NRdRe, -OC(=O)NRf(CH2)m-OH, -OC(=O)NRf-(CH2)m-NRdRe, -(CH2)mC(=O)OH, -(CH2UC(=O)-NRdRe, -(CH2)mC(=O)NRf-(CH2)n-OH, -(CH2)mC(=O)NRf(CH2)n-NRdRe, -NRf-(CH2)m-OH, -NRf-(CH2)m-NRdRe, -O-(CH2) m-OH, O-(CH2) m-NRdRe, -NRfC(=O)O-(CH2) m-OH, -NRbC(=O)O-(CH2) m-NRdRe, -(CH2)m-NRfC(=O)O-(CH2)n-OH-, -(CH2)m-NRfC(=O)O-(CH2)n-NRdRe, (CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-OH, Petition 870250095760, of 10 / 20 / 2025, p. 10 / 136 2 / 126 (CH2) m-NRfC(=O)-(CH2) n-NRdRe, -(CH2) m-NRfC(=O) - (CH2) n-OH, and (CH2) m-NRfC(=0)-G-(CH2) n-OH, with the alkyl, alkoxy, alkenyl,Alkynyl and cycloalkyl groups are optionally replaced by one or more groups selected from halogen, deuterium, amino, alkyl, and hydroxyl; the -(CH2)m- group is optionally replaced by one or more deuterium atoms or halogen groups; and G is selected from cycloalkylene, heterocycloalkylene, heteroarylene, and arylene; R2 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl, and alkynyl, with the alkyl, alkoxyl, alkenyl, and alkynyl groups being additionally replaced by one or more groups selected from halogen; R3 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl, alkynyl, CH2=, -NRdRe, -(CH2)m-OH, -(CH2)m-NRdRe, -C(=0)NRf-(CH2)m-OH, C(=0)NRf-(CH2)m-NRdRe, -(CH2)mC(=0)OH, -(CH2)mC(=0)-NRdRe, (CH2)mC(=0)NRf-(CH2)n-OH, -(CH2)mC(=0)NRf-(CH2)n-NRdRe, -NRf(CH2)m-OH, -NRf-(CH2)m-NRdRe, -NRf-C(=0)Rd, -NRf-C(=0)-(CH2)mRd, -NRfC(=0)0-(CH2)m-Rd,-0-(CH2)m-0H, -0-(CH2)m-NRdRe, NRfC(=0)0-(CH2)m-0H, -NRfC(=0)NRd-(CH2)m-0H, -NRfC(=0)NRd(CH2)m-0-(CH2)n-0H, -NRfC(=0)0-(CH2)m-0-(CH2)n-0H, NRfC(=0)NRd-(CH2)m-0-(CH2)n-NRdRe, -NRfC(=0)0-(CH2)m-0-(CH2)nNRdRe, -NRfC(=0)NRd-(CH2)m-NRdRe, -NRfC(=0)0-(CH2)m-NRdRe, Petition 870250095760, dated 10 / 20 / 2025, pg. 11 / 136 3 / 126 (CH2) m-NRfC(=O)O-(CH2) n-OH, -(CH2) m-NRfC(=O)O-(CH2) n-NRdRe, (CH2) m-OC(=O)NRf-(CH2) n-NRdRe, -(CH2) m-OC(=O)NRf-(CH2) n-OH, (CH2) m-NRfC(=O)-(CH2) n-NRdRe, and -(CH2) m-NRfC(=O)-(CH2) n-OH, wherein the alkyl, alkoxyl, alkenyl and alkynyl groups may be further substituted by one or more groups selected from halogen, deuterium, amino, alkyl and hydroxyl; R4 is selected from hydrogen, halogen, hydroxyl, carboxyl, amino, cyano, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, -NRdRe, -(CH2)m-OH, (CH2)m-NRdRe, -OC(=O)NRf-(CH2)m-OH, -OC(=O)NRf-(CH2)m-NRdRe, (CH2)mC(=O)OH, -(CH2)mC(=O)-NRdRe, -(CH2)mC(=O)NRf-(CH2)n-OH,-(CH2)mC(=O)NRf-(CH2)n-NRdRe, -NRf-(CH2)m-OH, -NRf-(CH2)m-NRdRe, -O-(CH2)m-OH, -O-(CH2)m-NRdRe, -NRfC(=O)O-(CH2)m-OH, NRbC(=O)O-(CH2) m-NRdRe, -(CH2) m-NRfC(=O)O-(CH2) n-OH-, -(CH2)mNRfC(=O)O-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)mOC(=O)NRf-(CH2)n-OH, -(CH2)m-NRfC(=O)-(CH2)n-NRdRe, -(CH2)mNRfC(=O)-(CH2)n-OH, and -(CH2)m-NRfC(=O)-G-(CH2)n-OH, wherein the alkyl, alkoxy, alkenyl, alkynyl and cycloalkyl groups may be optionally substituted by one or more groups selected from halogen, deuterium, amino, alkyl and hydroxyl; the -(CH2)m- group may be optionally substituted by one or more deuterium or halogen atoms; and G is selected from cycloalkylene, heterocyclylene, heteroarylene and arylene. Petition 870250095760, dated 10 / 20 / 2025, p. 12 / 136 4 / 126 R5 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl, and alkynyl groups, wherein the alkyl, alkoxyl,Alkenyl and alkynyl groups may be further substituted by one or more halogen groups; R6 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl, and alkynyl, wherein the alkyl, alkoxyl, alkenyl, and alkynyl groups may be further substituted by one or more halogen groups; R7 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl, and alkynyl, wherein the alkyl, alkoxyl, alkenyl, and alkynyl groups may be further substituted by one or more halogen groups; Rd and Re are each independently selected from hydrogen and alkyl; Rf is selected from hydrogen, alkyl, -C(O)Rc, S(O)Rc, and -S(O)2Rc, wherein the alkyl may be further substituted by cycloalkyl; and Rc is selected from hydrogen, hydroxyl, and alkyl; Li is selected from a bond, -(CH2)m-*, -O-*, NRa-*, -(CH2)mO-*,-(CH2) m-NRa-*, -OC(=O)NRb-(CH2)mO-*, OC(=O)NRb-(CH2) m-NRa-*, -(CH2) mC(=O)O-*, -(CH2) mC(=O)NRa-*, -(CH2) mC(=O)NRb- (CH2) nO-*, -(CH2) mC(=O)NRb-(CH2) n-NRa-*, Petition 870250095760, dated 10 / 20 / 2025, page. 13 / 136 5 / 126 NRb-(CH2)mO-*, -NRb-(CH2)m-NRa-*, -O-(CH2) mO-*, -O-(CH2)mNRa-*, -NRbC(=O)O-(CH2) mO-*, -NRbC(=O)O-(CH2) m-NRa-*, -(CH2)mNRbC(=O)O-(CH2) nO-*, -(CH2) m-NRbC(=O)O-(CH2) n-NRa-*, -(CH2)mOC(=O)NRb-(CH2) n-NRa-*, -(CH2) m-OC(=O)NRb-(CH2) nO-*, -(CH2)mNRbC(=O)-(CH2) n-NRa-*, e -(CH2) m-NRbC(=O)-(CH2)nO-*, where * is a linkage site with L2; Ra and Rb are each independently selected from hydrogen, alkyl, -C(O)Rc, -S(O)Rc, and -S(O)2Rc, with alkyl possibly being additionally substituted with cycloalkyl; and Rc is selected from hydrogen, hydroxyl, and alkyl; O * a linkage where * is a linkage site with Li; L is L4 L3 or O Q.pJ l4 J-3 L3 is an amino acid residue formed by two or more amino acids, with L3 optionally beinginclude one or more of the following structures, and Read is selected between one or more of the following structures: Petition 870250095760, of 20 / 10 / 2025, p. 14 / 136 6 / 126 HO. HO ho^voh HOi )— OH HO ho^>^oh HO—( HO )— JV OH )—( O^N'R \ 0H / N OH A ip· dA OH ho,JOY °H fa X mNH I / °V HO—\ OH / —( 0 HN Y HO )— \ HO V Λ v rο HO y o 3 HO OH HO^ OH / -( OH X” HO )—( / \ H / \ >O ho / mas θ Hi / —% °h HO OH HO. ho\oh Η0Λχ0Η OH OH'n, OH OH 1 ^oj 0 i \ HO—\ OH NH H,0AHn H° h= h. Χ^οΥ-ΑΑ naLn2VÍ J ηο / ^°λ < «ΎΗκή ho yu / —( OH HO OH , η θ * \ / f ΓΊ pt?*31 , where R, HO—( y- oh HO—< yoH y0H , H , H , p Rabb A , H ÍnAA η A ° , or Raa, and Rbb are each independently selected between hydrogen and alkyl L4 is a selected bond between -(CH2), p; -(C2H4O)q-, -(CH2)pC(O)NH-, -(CH2)pO-(CH2)pC(O)NH-, -(CH2) pC(O)-Le-NH-, -(CH2)pO-(CH2)pC(O)-L6-NH-, -C(O)NH-, -C-O,-(O)(O) -NH-, -O-,e -OC(O)NH-; m is an integer from 1 to 6; n is an integer from 1 to 6; s is an integer from 1 to 6; t is an integer from 0 to 10; s1, s2, s3, and s4 are each independently an integer from 0 to 10; sã and s6 are each independently an integer from 1 to 6; ti is an integer from 1 to 6; t2 is an integer from 0 to 6; ta is an integer from 1 to 6; t4 is an integer from 0 to 10; t5 is an integer from 0 to 10; p is an integer from 1 to 10; q is an integer from 1 to 10; and Q is a linking unit.

2. The compound represented by the general formula (A) or Petition 870250095760, dated 10 / 20 / 2025, page. 16 / 136 8 / 126 its pharmaceutically acceptable salt, according to claim 1, wherein Dr is selected from the following structures: Li is selected from -O-*, -NRa-*, -(CH2)mO-*, (CH2) m-NRa-*, -OC(=O)NRb-(CH2) mO-*, -OC(=O)NRb-(CH2) m-NRa-*, (CH2) mC(=O)O-*, -(CH2) mC(=O)NRa-*, -NRb-(CH2) mO-*, -NRb(CH2)m-NRa-*, -O-(CH2)mO-*, -O-(CH2)m-NRa-*, -NRbC(=O)O(CH2)mO-*, -NRbC(=O)O-(CH2)m-NRa-*, -(CH2) m-NRbC(=O)-(CH2) nNRa-*, and -(CH2) m-NRbC(=O)-(CH2) nO-*, where * is a linkage site with L2; Ra is selected from hydrogen and C1-Ce alkyl; Rb is selected from hydrogen, alkyl, -C(O)Rc, S(O)Rc, and -S(O)2Rc, wherein the alkyl may be additionally substituted by cycloalkyl; and Rc is selected from hydrogen, hydroxyl, and C1-Ce alkyl. m is an integer from 1 to 6; preferably, an integer from 1 to 4; more preferably, from 1 to 2;n is an integer from 1 to 6; preferably from 1 to 4; most preferably from 1 to 2;R1 is selected from hydrogen, halogen, hydroxyl, Petition 870250095760, dated 10 / 20 / 2025, page. 17 / 136 9 / 126 amino, cyano, Ci-Ce alkyl, Ci-Ce alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, -NRdRe, -(CH2)m-OH, (CH2) m-NRdRe, -OC(=O)NRf-(CH2) m-OH, -OC(=O)NRf-(CH2) m-NRdRe, (CH2) mC(=O)OH, - (CH2) mC(=O) -NRdRe, - (CH2) mC(=O)NRf- (CH2) n-OH, - (CH2) mC(=O)NRf- (CH2) n-NRdRe, -NRf- (CH2) m-OH, -NRf- (CH2) m-NRdRe, -O-(CH2)m-OH, -O-(CH2)m-NRdRe, -NRfC(=O)O-(CH2)m-OH, NRbC(=O)O-(CH2) m-NRdRe, -(CH2) m-NRfC(=O)O-(CH2) n-OH-, -(CH2)mNRfC(=O)O-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)mOC(=O)NRf-(CH2)n-OH, -(CH2)m-NRfC(=O)-(CH2)n-NRdRe, -(CH2)mNRfC(=O)-(CH2)n-OH, and -(CH2)m-NRfC(=O)-G-(CH2)n-OH, with the structures Ci-Ce alkyl, Ci-Ce alkoxy, alkenyl C2-C6, C2-C6 alkynyl and C3-C6 cycloalkyl groups may be further substituted by one or more groups selected from halogen, deuterium, amino, C1-C1 alkyl and hydroxyl groups;with C1-Ce alkyl and C1-Ce alkoxy being the preferred options; the (CH2)m- group may optionally be replaced by one or more deuterium or halogen groups; and G is selected from cycloalkylene, heterocycloalkene, heteroarylene, and arylene. R2 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-Ce alkyl, C1-Ce alkoxy, C2-Ce alkenyl, and C2-Ce alkynyl, with the C1-Ce alkyl, C1-Ce alkoxy, C2-Ce alkenyl, and C2-Ce alkynyl groups being additionally replaced by one or more groups selected from halogen; halogen being the preferred option; and Petition 870250095760, dated 10 / 20 / 2025, p. 18 / 136 10 / 126 Rd, Re, Rf, men are defined as those in claim 1.; 3. The compound represented by the general formula (A) or its pharmaceutically acceptable salt, according to claim 1, wherein Dr is selected from the following structures: Li is selected from a linkage, -(CH2)m-*, -O-*, (CH2)mO-*, -NRa-*, -(CH2)m-NRa-*, -NRb-(CH2)mO-*, -NRb-(CH2)mNRa-*, -O-(CH2)mO-*, -O-(CH2)m-NRa-*, -(CH2)m-OC(=O)NRb(CH2)n-NRa-*, -(CH2)m-OC(=O)NRb-(CH2)nO-*, -(CH2)m-NRbC(=O)(CH2)n-NRa-*, and -(CH2)m-NRbC(=O)-(CH2)nO-*, where * is a linkage site with L2; Ra is selected from hydrogen and C1-Ce alkyl; Rb is selected from hydrogen, alkyl, -C(O)Rc, S(O)Rc, and -S(O)2Rc, wherein the alkyl may be additionally substituted by cycloalkyl; and Rc is selected from hydrogen, hydroxyl, and C1-Ce alkyl. m is an integer from 1 to 6; preferably an integer from 1 to 4; n is an integer from 1 to 6; preferably a Petition 870250095760, dated 10 / 20 / 2025, page.19 / 136 11 / 126 integer from 1 to 4; and R2 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-C6 alkynyl, wherein the C1-Ce alkyl, C1-Ce alkoxyl, C2-C6 alkenyl and C2-C6 alkynyl groups may be further substituted by one or more groups selected from halogen; halogen being the preferred group.

4. The compound represented by the general formula (A) or its pharmaceutically acceptable salt, according to claim 1, wherein Dr is selected from the following structures: ; Li is selected from -O-*, where * is a binding site with L2; R2 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-Ce alkynyl, wherein the C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-Ce alkynyl groups may be further substituted by one or more groups selected from halogen; halogen being the preferred option; R3 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-C1 alkyl, C1-C1 alkoxy, C2-C6 alkenyl and C2-C6 alkynyl, CH2=, -NRdRe, -(CH2)m-OH, -(CH2)m-NRdRe, OC(=O)NRf-(CH2)m-OH, -OC(=O)NRf-(CH2)m-NRdRe, -(CH2)mC(=O)OH, -(CH2)mC(=O)-NRdRe, -(CH2)mC(=O)NRf-(CH2)n-OH, -(CH2)mC(=O)NRf-(CH2)n-NRdRe, -NRf-(CH2)m-OH,-NRf-(CH2) m-NRdRe, -NRfC(=O)Rd, -NRf-C(=O)-(CH2)m-Rd, -NRfC(=O)O-(CH2)m-Rd, -O-(CH2)mOH, -O-(CH2)m-NRdRe, -NRfC(=O)O-(CH2)m-OH, -NRfC(=O)NRd-(CH2)mOH, -NRfC(=O)NRd-(CH2)mO-(CH2)n-OH, -NRfC(=O)O-(CH2)mO(CH2)n-OH, -NRfC(=O)NRd-(CH2)mO-(CH2)n-NRdRe, -NRfC(=O)O(CH2)mO-(CH2)n-NRdRe, -NRfC(=O)NRd-(CH2)m-NRdRe, -NRfC(=O)O(CH2)m-NRdRe, -(CH2)m-NRfC(=O)O-(CH2)n-OH, -(CH2)m-NRfC(=O)O(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf(CH2)n-OH, -(CH2)m-NRfC(=O)-(CH2)n-NRdRe, and -(CH2)m-NRfC(=O)(CH2)n-OH, wherein the C1-C1 alkyl, C1-C1 alkoxy, C2-C6 alkenyl and C2-C6 alkynyl are optionally substituted by one or more groups selected from halogen, deuterium, amino, C1-C1 alkyl and hydroxyl; and hydrogen or hydroxyl are preferred; R4 is selected from hydrogen, halogen, hydroxyl, carboxyl, amino, cyano, C1-C1 alkyl, C1-C1 alkoxy, C2-C1 alkenyl, C2-C1 alkynyl, C3-C1 cycloalkyl, -NRdRe, -(CH2)m-OH, (CH2)m-NRdRe, -OC(=O)NRf-(CH2)m-OH,-OC(=O)NRf-(CH2)m-NRdRe, (CH2)mC(=O)OH, -(CH2)mC(=O)-NRdRe, -(CH2)mC(=O)NRf-(CH2)n-OH, Petition 870250095760, dated 10 / 20 / 2025, page. 21 / 136 13 / 126 - (CH2) mC(=O)NRf- (CH2) n-NRdRe, -NRf- (CH2) m-OH, -NRf- (CH2) m-NRdRe, -O-(CH2) m-OH, -O-(CH2) m-NRdRe, -NRfC(=O)O-(CH2) m-OH, - NRbC(=O)O-(CH2) m-NRdRe, -(CH2) m-NRfC(=O)O-(CH2) n-OH-, -(CH2)mNRfC(=O)O-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)mOC(=O)NRf-(CH2)n-OH, -(CH2)m-NRfC(=O)-(CH2)n-NRdRe, -(CH2)mNRfC(=O)-(CH2)n-OH, and -(CH2)m-NRfC(=O)-G-(CH2)n-OH, wherein the C1-Ce alkyl, C1-Ce alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, and C1-Ce cycloalkyl are optionally substituted by one or more groups selected from halogen, deuterium, amino, C1-Ce alkyl, and hydroxyl; hydroxyl, C1-Ce alkyl, and C1-Ce alkoxy are preferred; the -(CH2)m- is optionally substituted by one or more deuterium or halogen groups; and G is selected from cycloalkylene, heterocycloylene, heteroarylene, and arylene; and Rd, Re, Rf,Men are defined as those in claim 1.

5. The compound represented by the general formula (A) or its pharmaceutically acceptable salt, according to claim 1, wherein Dr is selected from the following structures: ; Li is selected from -(CH2)mO-* and -(CH2)m-NRa-*, in Petition 870250095760, dated 10 / 20 / 2025, p.22 / 136 14 / 126 where * is a connection site with L2; m is an integer from 1 to 6; preferably, an integer from 1 to 4; Ra is selected from hydrogen and C1-C1 alkyl; R5 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-C1 alkyl, C1-C1 alkoxyl, C2-C6 alkenyl and C2-C6 alkynyl, wherein the C1-C1 alkyl, C1-C1 alkoxyl, C2-C6 alkenyl and C2-C6 alkynyl groups may be further substituted by one or more groups selected from halogen; halogen being the preferred option; and R7 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-Ce alkynyl, wherein the C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-Ce alkynyl groups may be further substituted by one or more groups selected from halogen; hydroxyl and amino being the preferred options.

6. The compound represented by the general formula (A) or its pharmaceutically acceptable salt, according to claim 1, wherein Dr is selected from the following structures: Petition 870250095760, 10 / 20 / 2025, p. 23 / 136 15 / 126; Li is selected from -O-*, where * is a linkage site with L2; R5 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-C1 alkyl, C1-C1 alkoxyl, C2-C1 alkenyl and C2-C6 alkynyl, wherein the C1-C1 alkyl, C1-C1 alkoxyl, C2-C1 alkenyl and C2-C1 alkynyl groups may be further substituted by one or more groups selected from halogen; halogen being the preferred option; Re is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-Ce alkynyl, wherein the C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-Ce alkynyl groups may be further substituted by one or more groups selected from halogen;with hydroxyl and amino being the preferred options; and R7 is selected from hydrogen, halogen, hydroxyl, amino, cyano, C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-Ce alkynyl, with the C1-Ce alkyl, C1-Ce alkoxyl, C2-Ce alkenyl and C2-Ce alkynyl groups being able to be additionally replaced by one or more groups selected from halogen; with hydroxyl and amino being the preferred options.

7. The compound represented by the general formula (A) or its pharmaceutically acceptable salt according to any one of claims 1 to 6, wherein Dr is selected from: , and 8. The compound represented by the general formula (A) or its pharmaceutically acceptable salt, according to any one of claims 1 to 7, wherein when Li is selected from -NRa-*, -(CH2) m-NRa-*, OC(=O)NRb-(CH2) m-NRa-*, -(CH2) mC(=O)NRa-*, -(CH2) mC(=O)NRb(CH2) n-NRa-*, -NRb-(CH2) m-NRa-*, -O-(CH2) m-NRa-*, -NRbC(=O)O(CH2) m-NRa-*, -(CH2) m-NRbC(=O)O-(CH2) n-NRa-*, -(CH2)mOC(=O)NRb-(CH2)n-NRa-*, and -(CH2)m-NRbC(=O)-(CH2)n-NRa-*, being * a linking point with L2, Petition 870250095760, 10 / 20 / 2025, p. 25 / 136 17 / 126 Li2 is selected from a link and where * is a linking point with Li; and Ra, Rb, men are defined as those in any of claims 1 to 7.

9. The compound represented by the general formula (A) or its pharmaceutically acceptable salt, according to any one of claims 1 to 7, wherein when Li is selected from a linkage, -O-*, -(CH2)mO-*, -NRa-*, -OC(=O)NRb-(CH2)mO-*, -(CH2)mC(=O)O-*, -(CH2UC(=O)NRb-(CH2)nO-*, -NRb-(CH2)mO-*, -O-(CH2)mO-*, NRbC(=O)O-(CH2)mO-*, -(CH2)m-NRbC(=O)O-(CH2)nO-*, -(CH2)mOC(=O)NRb-(CH2)nO-*, and -(CH2)m-NRbC(=O)-(CH2)nO-*, wherein * is a linkage site with L2, L2 is selected from a linkage, H, where * is a linkage site with Li; and Ra, Rb, men are defined as those in any of claims 1 to 7.

10. The compound represented by general formula (A) or its pharmaceutically acceptable salt, in accordance with any Petition 870250095760, dated 10 / 20 / 2025, page. 26 / 136 18 / 126 one of claims 1 to 9, where L3 is an amino acid residue formed by two or more amino acids selected from phenylalanine, alanine, glycine, valine, leucine, isoleucine, tryptophan, tyrosine, histidine, lysine, citrulline, serine, threonine, cysteine, glutamic acid, glutamine, aspartic acid, asparagine, methionine and arginine, and L3 comprises more than the following structures: HO HO HO—( H% ) >OH 1 OH H0Λ HO— / HO-^X YOH HO OH OH 1 OH H°y HO ) ' \ H0 I rJt X 0 ,N' OH 2*° A* X y A1 VyxH ° , o , n 0 , hoaoh » y HOX> c? Atv w ho «o. Hojy '° HOx / / —( OH / --( O HO OH , HO OH HO. ho\oh Η0Λχ0Η OH OH N Ho-y / y^ , OH OH I \-n / Q HO—\ OH NH >—< ,oh , x 0 A HO r~\ \ U Ύ H / X Λ H0Hn / 4AV HO J \ Xi, Η JI Ss H HO Y υ / —\ °H HO OH optionally, one or OH HO.J HO.J ° °H Aoh \ x~NH ( θτ-2 1__ / 1 x.HN XH 4 , H ) v A â s ai H , nbb 3 -Raa H A , 0 , or Petition 870250095760, of 20 / 10 / 2025, p. 27 / 136 19 / 126 preferably, R^ paa or where R, Raa and Rbb are each independently selected from hydrogen and C1-C6 alkyl; s is an integer from 1 to 6; preferably, an integer from 2 to 6; more preferably, from 2 to 4; sã and se are each independently an integer Petition 870250095760, of 20 / 10 / 2025, p. 28 / 136 20 / 126 from 1 to 6; preferably, from 2 to 6; more preferably, from 2 to 4; t is an integer from 0 to 10; ti is an integer from 1 to 6; preferably from 1 to 4; more preferably from 2 to 4; or even more preferably, 1 or 2; t2 is an integer from 1 to 6; preferably from 1 to 4; more preferably, 0 or 2; ta is an integer from 1 to 6; preferably from 1 to 4; more preferably, 1 or 2; t4 is an integer from 0 to 10; and t5 is an integer from 0 to 10.

11. The compound represented by general formula (A) or its acceptable pharmaceutical salt according to any one of claims 1 to 10, where La is ^Ib , / Llb s' ^L1b / L'1b .s' x1a , or ^1a , * is a linking site with L2, and • is a linking site with carbonyl or methylene; Lib and L'ib are each independently amino acid residues formed from one or more amino acids selected from phenylalanine, alanine, glycine, valine, leucine, isoleucine, tryptophan, tyrosine, histidine, lysine, citrulline, serine, threonine, cysteine, glutamic acid, glutamine, aspartic acid, asparagine, methionine and arginine; Petition 870250095760, 20 / 10 / 2025, p. 29 / 136 21 / 126 Lia is a link or is selected following structures: HO. Ηθ h_A,oh hoA HO [ y—OH HO OH HrrA / °H HoA HO y-7HO T Γ OH )—\ (4vR < ζ-Λ ohu / N OH A (Λ Λη if1 o , 0 , OH HO.J hclJ ° JT0H Aoh \ yNH I PT HO—, OH Ηο'^γΑγ-^ ι OH OH ( ^oj q HO—, OH NH M / 0H , . OA >0 ho yy / \ u 4 η .. λ , H0 Í ^A0^0rX^N'YN'Uy'N4 HO J \ / ti Η H Ss H : HO Z / —( OH HO OH n ° between one or more of the HO HO—( / —OH HO— / \-OH HN / ° ^n-Aa , H 4 , VA Ã s RI , , R\ Raa . iy AAA , H 0 , ou y ; Petition 870250095760, of 20 / 10 / 2025, p. Ci-Ce, and is preferably hydrogen; Raa and Rbb are each selected independently from Ci-Ce alkyl; s is an integer from 1 to 6; preferably, an integer from 2 to 6; 870250095760, of 20 / 10 / 2025, p.31 / 136 23 / 126 t is an integer from 0 to 10; ti is an integer from 1 to 6; preferably from 1 to 4; more preferably from 2 to 4; or even more preferably, 1 or 2; you is an integer from 1 to 6; preferably from 1 to 4; more preferably, 0 or 2; ta is an integer from 1 to 6; preferably from 1 to 4; more preferably, 1 or 2; t4 is an integer from 0 to 10; and t5 is an integer from 0 to 10.

12. The compound represented by the general formula (A) or its pharmaceutically acceptable salt, according to any one of claims 1 to 11, wherein La is selected from: Petition 870250095760, 20 / 10 / 2025, p. 32 / 136 24 / 126 where: Lib and L'ib are each independently amino acid residues formed from one or more amino acids selected Petition 870250095760, 20 / 10 / 2025, p. 33 / 136 25 / 126 among phenylalanine, alanine, glycine, valine, leucine, isoleucine, tryptophan, tyrosine, histidine, lysine, citrulline, serine, threonine, cysteine, glutamic acid, glutamine, aspartic acid, asparagine, methionine and arginine; R is selected from hydrogen and C1-C1 alkyl and preferably is hydrogen; Raa and Rbb are each independently selected from C1-C1 alkyl; s is an integer from 1 to 6; preferably, an integer from 2 to 6; more preferably, from 2 to 4; Ss and se are each independently an integer from 1 to 6;preferably, from 2 to 6; more preferably, from 2 to 4; t is an integer from 0 to 10; ti is an integer from 1 to 6; preferably, an integer from 1 to 4; more preferably, an integer from 2 to 4; even more preferably 1 or 2; t2 is an integer from 1 to 6; preferably, from 1 to 4; more preferably, 0 or 2; ta is an integer from 1 to 6; preferably, from 1 to 4; more preferably, 1 or 2; t4 is an integer from 0 to 10; ts is an integer from 0 to 10; is a connection site with L2; and is a connection site with carbonyl or methylene. Petition 870250095760, dated 10 / 20 / 2025, p. 34 / 136 26 / 126; 13. The compound represented by the general formula (A) or its acceptable pharmaceutical salt according to claim 11 or 12, wherein Lib and L'ib are each independently an amino acid residue formed from one or more amino acids selected from glycine, phenylalanine, citrulline, leucine, isoleucine, alanine, valine, asparagine, glutamine, arginine, glutamic acid and lysine; preferably an amino acid residue formed from two or more amino acids selected from glycine, phenylalanine, citrulline, valine, lysine, glutamine, glutamic acid, aspartic acid, leucine and alanine.

14. The compound represented by general formula (A) or its acceptable pharmaceutical salt according to any one of claims 11 to 13, wherein Lib and L'ib are each independently selected from -Gly-*, -Val-*, -Gly-PheGly-*, -Phe-Gly-*, -Gly-Val-Cit-*, -Val-Cit-*, -Gly-Val-Arg*, -Val-Arg-*, -Gly-Val-Ala-*, -Val-Ala-*, -Gly-Phe-*, -PheGly-*, -Gly-Gly-Gly-*, Gly-Gly-*, -Gly-Val-Gly-*, -Gly-AlaGly-*, -Gly-Phe-Cit-*, -Gly-Phe-Val-*, -Gly-Phe-Ala-*, -GlyPhe-Lys-*, -Phe-Lys-*, -Gly-Val-*, -Gly-Cit-*, -Gly-Ala-*, -Gly-Gly-Lys-*, Gly-Lys'-*, -Ala-Ala-Ala-*, -Gln-Val-Ala-*, -Gln-Val-Cit-*, -Asp-Val-Ala-*, -Asp-Val-Cit-*, -Lys-GlyVal-Ala-*, -Lys-Gly-Val-Cit-*, -Lys-Gly-Gly-Val-Ala-*, Lys-Gly-Gly-Val-Cit-*, Gly-Gly-Phe-Gly-*, -Lys-Gln-Val-Cit*, -Lys-Gln-Val-Ala-*, -Lys-Glu-Val-Cit-*, -Lys-Glu-Val- Petition 870250095760, dated 10 / 20 / 2025, page.35 / 136 27 / 126 ALa-*, -Lys-Asp-Val-Cit-*, -Lys-Asp-Val-Ala-*, Glu-Val-Cit*, Glu-Val-Ala-*, -Lys-Val-Ala-*, -Lys-Val-Cit-*, -Val-LysGly-*, and -Val-Lys-*; preferably, -Gly-Phe-Gly-*, Gly-Val-Cit-*, -Val-Cit-*, -Gly-Val-Ala-*, -Val-Ala-*, -GlyPhe-Gly-*, -Phe-Gly-*, -Gly-Phe-Lys-, -Phe-Lys- *, -Gln-ValAla-*, -Gln-Val-Cit-*, -Asp-Val-Ala-*, -Lys-Gly-Val-Ala-*, -Lys-Gly-Val-Cit-*, -Lys-Gly-Gly-Val-Ala-*, -Lys-Gly-GlyVal-Cit-*, Gly-Gly-Phe-Gly-*, -Lys-Gln-Val-Cit-*, -Lys-GlnVal-Ala-*, -Lys-Glu-Val-Cit-*, -Lys-Glu-Val-ALa-*, -LysAsp-Val-Cit-*, -Lys-Asp-Val-Ala-*, Glu-Val-Cit-*, Glu-ValAla-*, -Lys-Val-Ala-*, -Lys-Val-Cit-*, -Val-Lys-Gly-*, -ValLys-*, and -Asp-Val-Cit-*, where * is a connection point with L2.

15. The compound represented by general formula (A) or its pharmaceutically acceptable salt, according to any one of claims 1 to 14, wherein L3 is selected from: Petition 870250095760, 20 / 10 / 2025, p. 36 / 136 28 / 126 Petition 870250095760, 20 / 10 / 2025, p. 37 / 136 29 / 126 Petition 870250095760, 20 / 10 / 2025, p. 38 / 136 30 / 126 Petition 870250095760, 20 / 10 / 2025, p. 39 / 136 31 / 126 Petition 870250095760, of 10 / 20 / 2025, p. 40 / 136 32 / 126 Raa and Rbb are each selected independently from Petition 870250095760, of 10 / 20 / 2025, p. 41 / 136 33 / 126 alkyl Ci-Ce; is a connecting site with L2; and is a connecting site with carbonyl or methylene.

16. The compound represented by general formula (A) or its acceptable pharmaceutical salt according to any one of claims 1 to 15 wherein Q is preferably selected from, 17. The compound represented by the general formula (A) or its pharmaceutically acceptable salt according to any of claims 1 to 16, wherein Zi is selected from Petition 870250095760, 10 / 20 / 2025, p. 42 / 136 34 / 126 a linkage, -(CH2)p-, -(CH2)pC(O)NH-, -(CH2)pO-(CH2)pC(O)NH-, -(CH2)pC(O)-L6-NH-, -(CH2)pO-(CH2)pC(O)-L6-NH-, -(CH2)pO-(CH2)pC(O)-L6-NH-, C(O)NH-, -C(O)O-, -C(O)-, -OC(O)-, and -OC(O)NH-, where p is an integer from 1 to 10; preferably, an integer from 1 to 6; si, S2, S3, and S4 are each independently an integer from 0 to 10; preferably an integer from 0 to 6; more preferably an integer from 0 to 4; even more preferably an integer from 0 to 2; selected from L6 is s is an integer from 1 to 6; preferably an integer from 2 to 6; more preferably, from 2 to 4; t is an integer from 0 to 10; and L6 preferably Petition 870250095760, of 20 / 10 / 2025, p. 43 / 136 35 / 126 18. The compound represented by the general formula (A) or its pharmaceutically acceptable salt, according to any one of claims 1 to 17, wherein Zi is selected from a linkage, -(CH2)p-, -(CH2)pC(O)NH-, -(CH2)pO-(CH2)pC(O)NH-, -C(O)NH-, -C(O)O-, -C(O)-, -OC(O)-, and -OC(O)NH-; si is an integer from 0 to 6; preferably, an integer from 0 to 1; s2 is an integer from 0 to 6; preferably, an integer from 0 to 1; sa is 0; s4 is 0; ep is an integer from 1 to 10; preferably, an integer from 1 to 6.

19. The compound represented by the general formula (A) or its pharmaceutically acceptable salt, according to any one of claims 1 to 17, wherein Zi is selected from -(CH2)pC(O)NH-, -(CH2)pO-(CH2)pC(O)NH-, and -C(O)NH-; si is an integer from 1 to 6; preferably an integer from 2 to 6; S2 is an integer from 1 to 10; preferably an integer from 2 to 10; S3 is 0; s4 is 0; ep is an integer from 1 to 10; preferably an integer from 1 to 6.

20. The compound represented by the general formula (A) or its acceptable pharmaceutical salt according to any one of claims 1 to 19, where Q-L4- is selected from: 0 ? χ ô WAAX 7 , AnAX H where: Zi is selected from -C(O)NH-, -C(O)O-, -C(O)-, OC(O)-, and -OC(O)NH-, preferably -C(O)NH-; p is an integer from 1 to 10; preferably, an integer from 1 to 6; Petition 870250095760, dated 10 / 20 / 2025, p.45 / 136 37 / 126 si is an integer from 0 to 6; preferably, an integer from 0 to 1; S2 is an integer from 1 to 10; preferably, an integer from 1 to 8; S3 is an integer from 0 to 6; preferably, an integer from 0 to 1; S4 is an integer from 1 to 6; preferably, an integer from 1 to 2; S7 is an integer from 0 to 6; preferably, an integer from 1 to 2; Ss is an integer from 1 to 4; preferably, an integer from 1 to 2; S9 is an integer from 1 to 10; preferably, an integer from 1 to 8; and Sio is an integer from 1 to 4; preferably, an integer from 1 to 2.

21. The compound represented by general formula (A) or its acceptable pharmaceutical salt according to any one of claims 1 to 20, wherein the compound is selected from: OH OH OH OH Ό NH Petition 870250095760, 20 / 10 / 2025, p. 46 / 136 38 / 126 Petition 870250095760, 20 / 10 / 2025, p. 47 / 136 39 / 126 Petition 870250095760, 20 / 10 / 2025, p. 48 / 136 40 / 126 OH Petition 870250095760, 20 / 10 / 2025, p. 49 / 136 41 / 126 LY-18B LY-18C Petition 870250095760, dated 10 / 20 / 2025, p. 50 / 136 42 / 126 Petition 870250095760, dated 10 / 20 / 2025, p. 51 / 136 43 / 126 Petition 870250095760, dated 10 / 20 / 2025, p. 52 / 136 44 / 126 Petition 870250095760, dated 10 / 20 / 2025, p. 53 / 136 45 / 126 LY-22CF, LY-22CG Petition 870250095760, of 10 / 20 / 2025, p. 54 / 136 46 / 126 / _y°' o70 / ... „ 0 , „.o / x? ηΧ'Α'Α ' 0 Xa ? 0 Ί H A. ^x A A. ^N.. χ...Λχ..., ,0.,-χ ΆΆ·Ν' Υ a o -^ a o -^ qa- a oxa- / H 0 c LY-22CDX HO· / HO· / A 0 0 J 4a XI ,χΧ 5^^ω^ο^ω^ο^ω^ο^ω^ο. 0 s N Y Α Ο^-···..Α·Ν'··.^ A 0 A' A 0 A- -A 0 A- -A 0 A- x δ H o LY-22CDC Í»ÍS-OH HO- (W (ίφ'ΌΗ HO-ÓS) PH z-O^7 AWPH A HO HO 0 ZO H <°X J \ <SA θγψθΗ nA _. h XX vN'-XXu Π Its) V A 0 aA 1 F , c W- OH HO · ÓB) W OH HO'Zs.) O^^\ PH ^rT AsrFH A HP HO 0 Ο η <°A J \ ί3^ o^-pH nA η H iiX - °υν-·ΑΧ ° aA \AxAxf , OH Z OH HO rAAYo^_oÂNXxF A A H JI °A )—Aoh X0- / I o , Ή OH OH ?H pH h^hX0” 0 Ax 6 H Ax^N nX 0= / ) AAoh Petição 870250095760, de 20 / 10 / 2025, pág. 55 / 136 47 / 126 Petição 870250095760, de 20 / 10 / 2025, pág. 56 / 136 48 / 126 Petição 870250095760, de 20 / 10 / 2025, pág. 57 / 136 49 / 126 LY-29C Ο LY-33 LY-34 Petição 870250095760, de 20 / 10 / 2025, pág. 58 / 136 50 / 126 Petição 870250095760, de 20 / 10 / 2025, pág. 59 / 136 51 / 126 LY-41 Ο LY-42A Petição 870250095760, de 20 / 10 / 2025, pág. 60 / 136 52 / 126 Petição 870250095760, de 20 / 10 / 2025, pág. 61 / 136 53 / 126 Petição 870250095760, de 20 / 10 / 2025, pág.62 / 136 54 / 126 Petition 870250095760, dated 10 / 20 / 2025, p. 63 / 136 55 / 126 Petition 870250095760, dated 10 / 20 / 2025, p. 64 / 136 56 / 126 Petition 870250095760, dated 10 / 20 / 2025, p. 65 / 136 57 / 126 Petition 870250095760, dated 10 / 20 / 2025, p. 66 / 136 58 / 126.

22. A compound represented by the general formula (I), or a stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereoisomer thereof or a mixture thereof, or a pharmaceutically acceptable salt thereof; Petition 870250095760, dated 10 / 20 / 2025, page 67 / 136 59 / 126 (I) wherein, R8 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl and alkynyl, wherein the alkyl, alkoxyl, alkenyl and alkynyl groups may be further substituted by one or more groups selected from halogen; halogen being the preferred group; R9 is selected from hydrogen, halogen, hydroxyl, carboxyl, cyano, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, -NRdRe, -(CHa)m-OH, -(CH2)m-NRdRe, -OC(=O)NRf(CHa)m-OH, -OC(=O)NRf-(CH2)m-NRdRe, -(CH2)mC(=O)OH, -(CH2UC(=O)-NRdRe, -(CH2)mC(=O)NRf-(CH2)n-OH, -(CH2)mC(=O)NRf(CH2)n-NRdRe, -NRf-(CH2)m-OH, -NRf-(CH2)m-NRdRe, -O-(CH2)m-OH, O-(CH2)m-NRdRe, -NRfC(=O)O-(CH2)m-OH,-NRbC(=O)O-(CH2) m-NRdRe, -(CH2)m-NRfC(=O)O-(CH2)n-OH, -(CH2)m-NRfC(=O)O-(CH2)n-NRdRe, (CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-OH, (CH2)m-NRfC(=O)-(CH2)n-NRdRe, -(CH2)m-NRfC(=O)-(CH2)n-OH, and (CH2)m-NRfC(=O)-G-(CH2)n-OH, wherein the alkyl, alkoxy, alkenyl, alkynyl, and cycloalkyl groups may be additionally Petition 870250095760, of 20 / 10 / 2025, page 68 / 136 60 / 126 replaced by one or more groups selected from deuterium, halogen, amino, alkyl and hydroxyl; Preferred groups include hydroxyl, C1-C1 alkyl, C1-C1 alkoxy, C1-C1 cycloalkyl, -NRdRe, -(CH2U-OH, -(CH2)m-NRdRe, -(CHa)mNRfC(=O)O-(CHa)n-OH, -(CH2)m-OC(=O)NRf-(CH2)n-OH, -(CH2)mNRfC(=O)-(CH2)n-OH, -O-(CH2)m-NRdRe, -O-(CH2)m-OH, and -(CH2UNRfC(=O)-G-(CH2)n-OH; and the fragment -(CH2)m- may optionally be replaced by one or more deuterium or halogen groups; G is selected from cycloalkylene, heterocycloalkylene, heteroarylene, and arylene; R10 is selected from hydrogen, halogen,hydroxyla, cyano, alquila, alcóxi, alquenila, alquinila, CH2=, -NRdRe, -(CH2)m-OH, -(CH2)m-NRdRe, -OC(=O)NRf-(CH2)m-OH, -OC(=O)NRf(CH2)m-NRdRe, -(CH2)mC(=O)OH, -(CH2)mC(=O)-NRdRe, -(CH2)mC(=O)NRf-(CH2)n-OH, -(CH2)mC(=O)NRf-(CH2)n-NRdRe, -NRf-(CH2)mOH, -NRf-(CH2)m-NRdRe, -NRf-C(=O)Rd, -NRf-C(=O)-(CH2)m-Rd, -NRf-(CH2)m-NRdRe, -O-(CH2)m-OH, -O-(CH2)m-NRdRe, -NRfC(=O)O(CH2)m-OH, -NRfC(=O)NRd-(CH2)m-OH, -NRfC(=O)NRd-(CH2)mO(CH2)n-OH, -NRfC(=O)O-(CH2)mO-(CH2)n-OH, -NRfC(=O)NRd-(CH2)mO-(CH2)n-NRdRe, -NRfC(=O)O-(CH2)mO-(CH2)n-NRdRe, -NRfC(=O)NRd(CH2)m-NRdRe, -NRfC(=O)O-(CH2)m-NRdRe, -NRfC(=O)O-(CH2)m-NRdRe, -(CH2)m-NRfC(=O)O-(CH2)nOH, -(CH2)m-NRfC(=O)O-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)nNRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-OH, -(CH2)m-NRfC(=O)-(CH2)nNRdRe, e -(CH2)m-NRfC(=O)-(CH2)n-OH, sento que os grupos Petition 870250095760, of 20 / 10 / 2025, pág. 69 / 136 61 / 126 alquila, alcóxi,Alkenyl and alkynyl groups may optionally be replaced by one or more groups selected from halogens; with hydrogen, hydroxyl, amino groups being preferred, -(CHa)m-OH, -OC(=O)NRf-(CH2)mOH, -(CH2)mC(=O)OH, -(CH2)mC(=O)NRf-(CH2)n-OH, -NRf-(CH2)mOH, -NRf-C(=O)Rd, -NRf-C(=O)-(CH2)m-Rd, -NRfC(=O)O-(CH2)m-Rd, NRfC(=O)O-(CH2)m-OH, -NRfC(=O)NRd-(CH2)m-OH, -NRfC(=O)NRd(CH2)mO-(CH2)n-OH, -NRfC(=O)O-(CH2)mO-(CH2)n-OH, NRfC(=O)NRd-(CH2)mO-(CH2) n-NRdRe, -NRfC(=O)O-(CH2)mO-(CH2)nNRdRe, -NRfC(=O)NRd-(CH2)m-NRdRe, and -NRfC(=O)O-(CH2)m-NRdRe: Rd and Re are each independently selected from hydrogen and C1-Ce alkyl; Rf is selected from hydrogen, C1-Ce alkyl, -C(O)Rc, -S(O)Rc, and -S(O)2Rc, with the C1-Ce alkyl optionally substituted with C3-C6 cycloalkyl; and Rc is selected from hydrogen, hydroxyl, and C1-Ce alkyl; m is an integer from 1 to 6; en is an integer from 1 to 6.

23. The compound represented by general formula (I) or its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or its pharmaceutically acceptable salt according to claim 22, wherein R9 is selected from hydrogen, C1-C1 alkyl, C1-C1 alkoxy, hydroxyl, carboxyl, -NRdRe, -(CH2)m-OH, Petition 870250095760, 10 / 20 / 2025, p. 70 / 136 62 / 126 (CH2) m-NRdRe, -(CH2) m-NRfC(=O)O-(CH2) n-OH, -(CH2) m-OC(=O)NRf(CH2)n-OH, -(CH2) m-NRfC(=O)-(CH2) n-OH, -O-(CH2) m-NRdRe, and -O(CH2)m-OH; Rd and Re are each independently selected from hydrogen and C1-C6 alkyl; Rf is selected from hydrogen and C1-C6 alkyl; m is an integer from 1 to 6; en is an integer from 1 to 4, preferably 1 or 2.

24. The compound represented by the general formula (I) or its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or its pharmaceutically acceptable salt according to claim 22 or 23, wherein R10 is selected from hydrogen, hydroxyl, amino, CH2=, -(CH2)m-OH, -OC(=O)NRf-(CH2)m-OH, -(CH2)mC(=O)OH, -(CH2)mC(=O)NRf-(CH2)n-OH, -NRf-(CH2)m-OH, -NRf-C(=O)Rd, -NRfC(=O)-(CH2)m-Rd, -NRfC(=O)O-(CH2)m-Rd, -NRf-C(=O)-(CH2)m-OH, and -NRfC(=O)O-(CH2)m-OH; Rd and Re are each independently selected from hydrogen and C1-C6 alkyl; Rf is selected from hydrogen, C1-C6 alkyl, -C(O)Rc, -S(O)Rc, and -S(O)2Rc, with the C1-C6 alkyl optionally replaced by C3-C6 cycloalkyl; and Rc is selected from hydrogen, hydroxyl, and C1-C6 alkyl; Petition 870250095760, dated 10 / 20 / 2025, p.71 / 136 63 / 126 m is an integer from 1 to 6; preferably an integer from 1 to 4 or an integer from 4 to 6; en is an integer from 1 to 4, preferably 1 or 2.

25. The compound represented by general formula (I) or its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or its pharmaceutically acceptable salt according to any one of claims 22 to 24, wherein R8 is selected from halogen.

26. The compound represented by general formula (I) or the stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer thereof, or a mixture thereof, or the pharmaceutically acceptable salt thereof, according to any one of claims 22 to 25, which is selected from: Petition 870250095760, dated 10 / 20 / 2025, p. 72 / 136 64 / 126 HO Petition 870250095760, dated 10 / 20 / 2025, p. 73 / 136 65 / 126 Petition 870250095760, dated 10 / 20 / 2025, p. 74 / 136 66 / 126 Petition 870250095760, dated 10 / 20 / 2025, p. 75 / 136 67 / 126 Petition 870250095760, dated 10 / 20 / 2025, p. 76 / 136 68 / 126 Petition 870250095760, dated 10 / 20 / 2025, p. 77 / 136 69 / 126 OH, OH Petition 870250095760, dated 10 / 20 / 2025, p. 78 / 136 70 / 126 27. A compound represented by the general formula (II) or a stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof; (II) wherein R11 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxy, alkenyl and alkynyl, wherein the alkyl, alkoxy, alkenyl and alkynyl groups may be further substituted by one or more groups selected from halogens; halogen and cyano being preferred.R12 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxy, alkenyl, alkynyl, -NRdRe, -(CH2)m-OH, -(CH2)m-NRdRe, -OC(=O)NRf-(CH2)m-OH, -OC(=O)NRf(CH2)m-NRdRe, -(CH2)mC(=O)OH, -(CH2)mC(=O)-NRdRe, -(CH2)mC(=O)NRf-(CH2)n-OH, -(CH2)mC(=O)NRf-(CH2)n-NRdRe, -NRf-(CH2)mOH, -NRf-(CH2)m-NRdRe, -O-(CH2)m-OH, -O-(CH2)m-NRdRe, NRfC(=O)O-(CH2)m-OH, -NRbC(=O)O-(CH2) m-NRa-*, -(CH2UNRbC(=O)O-(CH2) nO-*, -(CH2) m-NRfC(=O)O-(CH2) n-NRdRe, -(CH2)mOC(=O)NRf-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-OH, -(CH2)mPenitence 870250095760, of 20 / 10 / 2025, page 79 / 136 71 / 126 NRfC(=O)-(CH2) n-NRdRe, and -(CH2) m-NRfC(=O)-(CH2) n-OH, wherein the alkyl, alkoxy, alkenyl and alkynyl groups may be additionally substituted by one or more selected groups among halogens; hydroxyl, amino, C1-C1 alkyl, -(CH2A-OH), and -(CH2)m-NRdRe are preferred.R13 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxy, alkenyl, alkynyl, -NRdRe, -(CH2)m-OH, -(CH2)m-NRdRe, -OC(=O)NRf-(CH2)m-OH, -OC(=O)NRf(CH2)m-NRdRe, -(CH2)mC(=O)OH, -(CH2)mC(=O)-NRdRe, -(CH2)mC(=O)NRf-(CH2)n-OH, -(CH2)mC(=O)NRf-(CH2)n-NRdRe, -NRf-(CH2)mOH, -NRf-(CH2)m-NRdRe, -O-(CH2)m-OH, -O-(CH2)m-NRdRe, NRfC(=O)O-(CH2)m-OH, -NRbC(=O)O-(CH2) m-NRa-*, -(CH2UNRbC(=O)O-(CH2) nO-*, -(CH2) m-NRfC(=O)O-(CH2) n-NRdRe, -(CH2)mOC(=O)NRf-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-OH, -(CH2)mNRfC(=O)-(CH2)n-NRdRe, and -(CH2)m-NRfC(=O)-(CH2)n-OH, wherein the alkyl, alkoxy, alkenyl and alkynyl groups may be further substituted by one or more groups selected from halogens; hydroxyl and amino groups are preferred.Rd and Re are each independently selected from hydrogen and C1-C1 alkyl; Rf is selected from hydrogen, C1-C1 alkyl, -C(O)Rc, -S(O)Rc, and -S(O)2Rc, with Rc being selected from hydrogen, hydroxyl, and C1-C1 alkyl; m is an integer from 1 to 6; and n is an integer from 1 to 6.

28. The compound represented by general formula (II) or its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or its pharmaceutically acceptable salt according to claim 27, wherein R11 is selected from between halogen and cyano.

29. The compound represented by general formula (II) or its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or its pharmaceutically acceptable salt according to claim 27, wherein R12 is selected from Ci-Ce alkyl, -(CHo)m-OH, and -(CH2)m-NRdRe; Rd and Re are each selected independently from hydrogen and Ci-Ce alkyl; em is an integer between 1 and 6.

30. The compound represented by general formula (II) or its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or its pharmaceutically acceptable salt according to claim 27, wherein R13 is selected from hydroxyl and C1-Ce alkoxy.

31. The compound represented by general formula (II) or its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or a mixture thereof, or its acceptable pharmaceutical salt according to any one of claims 27 to 30, which is selected from:

32. A ligand-drug conjugate represented by the general formula (B), or a pharmaceutically acceptable salt thereof, Petition 870250095760, dated 20 / 10 / 2025, p. 82 / 136 74 / 126 Pc--L'--L2—1-!—Dr (B) where: Dr is selected from the following structures: R1 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, -NRdRe, -(CHa)m-OH, -(CH2)m-NRdRe, -OC(=O)NRf(CHa)m-OH, -OC(=O)NRf-(CH2)m-NRdRe, -(CH2)mC(=O)OH, -(CH2UC(=O)-NRdRe, -(CH2)mC(=O)NRf-(CH2)n-OH, -(CH2)mC(=O)NRf(CH2)n-NRdRe, -NRf-(CH2)m-OH, -NRf-(CH2)m-NRdRe, -O-(CH2) m-OH, O-(CH2) m-NRdRe, -NRfC(=O)O-(CH2) m-OH, -NRbC(=O)O-(CH2) m-NRdRe, -(CH2)m-NRfC(=O)O-(CH2)n-OH-, -(CH2)m-NRfC(=O)O-(CH2)n-NRdRe, (CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-OH, (CH2)m-NRfC(=O)-(CH2)n-NRdRe, -(CH2)m-NRfC(=O)-(CH2)n-OH, and (CH2)m-NRfC(=O)-G-(CH2)n-OH, with the alkyl groups, Petition 870250095760, of 10 / 20 / 2025, p. 83 / 136 75 / 126 alkoxy, alkenyl,Alkynyl and cycloalkyl groups are optionally replaced by one or more groups selected from halogen, deuterium, amino, alkyl, and hydroxyl; the -(CHg)m- group is optionally replaced by one or more deuterium atoms or halogen groups; and G is selected from cycloalkylene, heterocycloalkylene, heteroarylene, and arylene; R2 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl, and alkynyl, with the alkyl, alkoxyl, alkenyl, and alkynyl groups being additionally replaced by one or more groups selected from halogen; R3 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl, alkynyl, CH2=, -NRdRe, -(CH2)m-OH, -(CH2)m-NRdRe, -OC(=O)NRf-(CH2)m-OH, OC(=O)NRf-(CH2)m-NRdRe, -(CH2)mC(=O)OH, -(CH2)mC(=O)-NRdRe, (CH2)mC(=O)NRf-(CH2)n-OH, -(CH2)mC(=O)NRf-(CH2)n-NRdRe, -NRf(CH2)m-OH, -NRf-(CH2)m-NRdRe, -NRf-C(=O)Rd, -NRf-C(=O)-(CH2)mRd, -NRfC(=O)O-(CH2)m-Rd,-O-(CH2)m-OH, -O-(CH2)m-NRdRe, NRfC(=O)O-(CH2)m-OH, -NRfC(=O)NRd-(CH2)m-OH, -NRfC(=O)NRd(CH2)mO-(CH2)n-OH, -NRfC(=O)O-(CH2)mO-(CH2)n-OH, NRfC(=O)NRd-(CH2)mO-(CH2)n-NRdRe, -NRfC(=O)O-(CH2)mO-(CH2)nNRdRe, -NRfC(=O)NRd-(CH2)m-NRdRe, -NRfC(=O)O-(CH2)m-NRdRe, (CH2)m-NRfC(=O)O-(CH2)n-OH, -(CH2)m-NRfC(=O)O-(CH2)n-NRdRe, (CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-OH, Petition 870250095760, of 10 / 20 / 2025, page 84 / 136 76 / 126 (CH2) m-NRfC(=O)-(CH2) n-NRdRe, and -(CH2) m-NRfC(=O) - (CH2) n-OH, wherein the alkyl, alkoxyl, alkenyl and alkynyl groups may be further substituted by one or more groups selected from halogen, deuterium, amino, alkyl and hydroxyl; R4 is selected from hydrogen, halogen, hydroxyl, carboxyl, amino, cyano, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, -NRdRe, -(CH2)m-OH, (CH2)m-NRdRe, -OC(=O)NRf-(CH2)m-OH, -OC(=O)NRf-(CH2)m-NRdRe, (CH2)mC(=O)OH, -(CH2)mC(=O)-NRdRe, -(CH2)mC(=O)NRf-(CH2)n-OH,-(CH2)mC(=O)NRf-(CH2)n-NRdRe, -NRf-(CH2)m-OH, -NRf-(CH2)m-NRdRe, -O-(CH2)m-OH, -O-(CH2)m-NRdRe, -NRfC(=O)O-(CH2)m-OH, NRbC(=O)O-(CH2) m-NRdRe, -(CH2) m-NRfC(=O)O-(CH2) n-OH-, -(CH2)mNRfC(=O)O-(CH2)n-NRdRe, -(CH2)m-OC(=O)NRf-(CH2)n-NRdRe, -(CH2)mOC(=O)NRf-(CH2)n-OH, -(CH2)m-NRfC(=O)-(CH2)n-NRdRe, -(CH2)mNRfC(=O)-(CH2)n-OH, and -(CH2)m-NRfC(=O)-G-(CH2)n-OH, wherein the alkyl, alkoxy, alkenyl, alkynyl and cycloalkyl groups may optionally be replaced by one or more groups selected from halogen, deuterium, amino, alkyl and hydroxyl; the -(CH2)m- group may optionally be replaced by one or more deuterium or halogen atoms; and G is selected from cycloalkylene, heterocyclylene, heteroarylene and arylene. R5 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl and alkynyl, Petition 870250095760, of 10 / 20 / 2025, p. 85 / 136 77 / 126 wherein the alkyl, alkoxyl groups,Alkenyl and alkynyl groups may be further substituted by one or more halogen groups; R6 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl, and alkynyl, wherein the alkyl, alkoxyl, alkenyl, and alkynyl groups may be further substituted by one or more halogen groups; R7 is selected from hydrogen, halogen, hydroxyl, amino, cyano, alkyl, alkoxyl, alkenyl, and alkynyl, wherein the alkyl, alkoxyl, alkenyl, and alkynyl groups may be further substituted by one or more halogen groups; Rd and Re are each independently selected from hydrogen and alkyl; Rf is selected from hydrogen, alkyl, -C(O)Rc, S(O)Rc, and -S(O)2Rc, wherein the alkyl is optionally substituted by C3-C6 cycloalkyl; and Rc is selected from hydrogen, hydroxyl, and alkyl; Li is selected from a bond, -(CH2)m-*, -O-*, NRa-*, -(CH2)mO-*,-(CH2) m-NRa-*, -OC(=O)NRb-(CH2)mO-*, OC(=O)NRb-(CH2) m-NRa-*, -(CH2) mC(=O)O-*, -(CH2) mC(=O)NRa-*, -(CH2) mC(=O)NRb-(CH2) nO-*, -(CH2) mC(=O)NRb-(CH2) n-NRa-*, NRb-(CH2)mO-*, -NRb-(CH2)m-NRa-*, -O-(CH2)mO-*, -O-(CH2)mNRa-*, -NRbC(=O)O-(CH2)mO-*, -NRbC(=O)O-(CH2)m-NRa-*, -(CH2)mPetition 870250095760, from 20 / 10 / 2025, page 86 / 136 78 / 126 NRbC(=O)O-(CH2) nO-*, -(CH2) m-NRbC(=O)O-(CH2) n-NRa-*, -(CH2)mOC(=O)NRb-(CH2) n-NRa-*, -(CH2) m-OC(=O)NRb-(CH2) nO-*, -(CH2)mNRbC(=O)-(CH2) n-NRa-*, and -(CH2) m-NRbC(=O)-(CH2) nO-*, where * is a binding site with L2; Ra and Rb are each independently selected from hydrogen, alkyl, -C(O)Rc, -S(O)Rc, and -S(O)2Rc, wherein the alkyl may be additionally substituted by cycloalkyl; and Rc is selected from hydrogen, hydroxyl, and alkyl; L2 is selected from a bond and H, where * is a connection site with Li; or Q' is selected from Petition 870250095760, dated 20 / 10 / 2025,p. 87 / 136 79 / 126 where * is a binding site with L4, and I is a binding site with Pc; L3 is an amino acid residue formed by two or more amino acids, and L3 may optionally comprise one or more of the following structures, and Le is selected from one or more of the following structures: or Petition 870250095760, dated 10 / 20 / 2025, p. 88 / 136 80 / 126 where R, Raa, and Rbb are each independently selected from hydrogen and alkyl; L4 is selected from a linkage, -(CH2)p-, -(C2H4O)q-, -(CH2)pC(O)NH-, -(CH2)pO-(CH2)pC(O)NH-, -(CH2)pC(O)-L6-NH-, -(CH2)pO-(CH2)pC(O)-L6-NH-, -C(O)NH-, -C(O)O-, -C(O)-, OC(O)-, -NH-, -O-, and -OC(O)NH-; m is an integer from 1 to 6; n is an integer from 1 to 6; s is an integer from 1 to 6; t is an integer from 0 to 10; s1, s2, s3, and s4 are each independently an integer from 0 to 10; s6 and s7 are each independently,an integer from 1 to 6; ti is an integer from 1 to 6; t2 is an integer from 0 to 6; ta is an integer from 1 to 6; t4 is an integer from 0 to 10; t5 is an integer from 0 to 10; p is an integer from 1 to 10; Petition 870250095760, dated 10 / 20 / 2025, page 89 / 136 81 / 126 q is an integer from 1 to 10; v varies from 1 to 10, being a decimal or integer number; Pc is an antibody or an antigen-binding fragment derived from an antibody, or a modified antibody; the modified antibody has the structure Pc'-((L5) wF) x where: Pc' is an antibody; L5 is a binding unit; w is 0 or 1; F is a clickable probe, a sulfhydryl group or a precursor thereof that can be attached to Q' after a reaction, such as a metal-free click reaction; preferably, F represents an azide group; ex is an integer from 1 to 8.

33. The ligand-drug conjugate represented by general formula (B) or its pharmaceutically acceptable salt according to claim 32, wherein: La is selected from: Petition 870250095760, 20 / 10 / 2025, p. 90 / 136 82 / 126 Petition 870250095760, 20 / 10 / 2025, p. 91 / 136 83 / 126 HO OH R is selected from hydrogen and C1-C1 alkyl and preferably is hydrogen; Raa and Rbb are each independently selected from C1-C1 alkyl; s is an integer from 1 to 6; preferably, an integer from 2 to 6; more preferably, from 2 to 4; sa and se are each independently an integer from 1 to 6; preferably, from 2 to 6; more preferably, from 2 to 4; t is an integer from 0 to 10; Petition 870250095760, dated 10 / 20 / 2025, page 92 / 136 84 / 126 ti is an integer from 1 to 6; preferably, an integer from 1 to 4; more preferably, an integer from 2 to 4; even more preferably 1 or 2; ta is an integer from 1 to 6;preferably, from 1 to 4; more preferably, 0 or 2; ta is an integer from 1 to 6; preferably, from 1 to 4; more preferably, 1 or 2; t4 is an integer from 0 to 10; ta is an integer from 0 to 10; represents the La-binding site; é is a carbonyl or methylene-binding site; Lib and L'ib are each independently amino acid residues formed by one or more amino acids selected from glycine, phenylalanine, citrulline, leucine, isoleucine, alanine, valine, asparagine, glutamine, arginine, glutamic acid, and lysine; preferably, amino acid residues formed by two or more amino acids selected from glycine, phenylalanine, citrulline, valine, lysine, glutamine, glutamic acid, leucine, and alanine;and preferably, Lib and L'ib are each independently selected from -Gly-*, -Val-*, -GlyPhe-Gly-*, -Phe-Gly-*, -Gly-Val-Cit-*, -Val-Cit-*, -Gly-ValArg-*, -Val-Arg-*, -Gly-Val-Ala-*, -Val-Ala-*, -Gly-Phe-*, -Phe-Gly-*, -Gly-Gly-Gly-*, Gly-Gly-*, -Gly-Val-Gly-*, -GlyAla-Gly-*, -Gly-Phe-Cit-*, -Gly-Phe-Val-*, -Gly-Phe-Ala-*, Petition 870250095760, dated 10 / 20 / 2025, p. 93 / 136 85 / 126 -Gly-Phe-Lys-*, -Phe-Lys-*, -Gly-Val-*, -Gly-Cit-*, -GlyAla-*, -Gly-Gly-Lys-*, Gly-Lys'-*, -Ala-Ala-Ala-*, -Gln-ValAla-*, -Gln-Val-Cit-*, -Asp-Val-Ala-*, -Asp-Val-Cit-*, -LysGly-Val-Ala-*, -Lys-Gly-Val-Cit-*, -Lys-Gly-Gly-Val-Ala-*, -Lys-Gly-Gly-Val-Cit-*, Gly-Gly-Phe-Gly-*, -Lys-Gln-ValCit-*, -Lys-Gln-Val-Ala-*, -Lys-Glu-Val-Cit-*, -Lys-GluVal-ALa-*, -Lys-Asp-Val-Cit-*, -Lys-Asp-Val-Ala-*, Glu-ValCit-*, Glu-Val-Ala-*, -Lys-Val-Ala-*, -Lys-Val-Cit-*, -ValLys-Gly-*, and -Val-Lys-*;preferably, -Gly-Phe-Gly*, -Gly-Val-Cit-*, -Val-Cit-*, -Gly-Val-Ala-*, -Val-Ala-*, -Gly-Phe-Gly-*, -Phe-Gly-*, -Gly-Phe-Lys-, -Phe-Lys-*, Gln-Val-Ala-*, -Gln-Val-Cit-*, -Asp-Val-Ala-*, -Lys-GlyVal-Ala-*, -Lys-Gly-Val-Cit-*, -Lys-Gly-Gly-Val-Ala-*, Lys-Gly-Gly-Val-Cit-*, Gly-Gly-Phe-Gly-*, -Lys-Gln-Val-Cit*, -Lys-Gln-Val-Ala-*, -Lys-Glu-Val-Cit-*, -Lys-Glu-ValALa-*, -Lys-Asp-Val-Cit-*, -Lys-Asp-Val-Ala-*, Glu-Val-Cit*, Glu-Val-Ala-*, -Lys-Val-Ala-*, -Lys-Val-Cit-*, -Val-LysGly-*, -Val-Lys-*, and -Asp-Val-Cit-*, where * represents the linkage point with L2.

34. The ligand-drug conjugate represented by the general formula (B) or its pharmaceutically acceptable salt according to claim 32, where: L' Q'x or Petition 870250095760, dated 10 / 20 / 2025, p. 94 / 136 86 / 126 Q' is selected from ° being * a binding site with L4 and is a binding site with Pc; L3 is an amino acid residue formed by two or more amino acids selected from glycine, phenylalanine, citrulline, leucine, isoleucine, alanine, valine, asparagine, glutamine, arginine, glutamic acid and lysine; preferably, an amino acid residue formed by two or more amino acids selected from glycine, phenylalanine, citrulline, valine, lysine, glutamine, glutamic acid, alanine; leucine and L4 is Zi is C(O)NH-, ; selected from a connection, -(CH2)p-, -(CH2)p-(CH2)pO-(CH2)pC(O)NH-, -(CH2)pC(O)-L6-NH-, Petition 870250095760, dated 10 / 20 / 2025, p.95 / 136 87 / 126 (CH2) pO-(CH2) pC(Q)-Le-NH-, -C(O)NH-, -C(O)O-, -C(O)-, OC(O)-, -NH-, -O-, and -OC(O)NH-; si is an integer from 1 to 6; preferably an integer from 2 to 6; S2 is an integer from 1 to 10; preferably an integer from 2 to 10; S3 is 0; s4 is 0; p is an integer from 1 to 10; preferably an integer from 1 to 6; HO^. OH M / 0H ^Vo HO )~< / \ H / , XAtYw HO Χ / —\ °H Le is selected from H0 0H es is an integer from 1 to 6; preferably, an integer from 2 to 6; more preferably, from 2 to 4; t is an integer from 0 to 10; and Le preferably Petition 870250095760, of 10 / 20 / 2025, p. 96 / 136 88 / 126.

35. The ligand-drug conjugate represented by the general formula (B) or its pharmaceutically acceptable salt according to any one of claims 32 to 34, where L5 and Z2 are each independently selected from -C(O)NH-, -C(O)O-, -C(O)-, -OC(O)-, -NH-, -O-, and OC(O)NH-, preferably -C(O)NH-; ri is an integer from 1 to 6; more preferably, r2 is an integer from 1 to 4; more preferably, r3 is an integer from 0 to 4; more preferably, r4 is an integer from 0 to 4; more preferably, r5 is an integer from 1 to 4; more preferably, 36. The conjugate linker 1 to 8; preferably, from 1 to 3; 1 to 6; preferably, from 1 to 2; 0 to 6; preferably, from 0 to 2; 0 to 6; preferably, from 0 to 2; and 1 to 6; preferably, from 1 to 2. drug represented by Petition 870250095760, dated 10 / 20 / 2025, p. 97 / 136 89 / 126 general formula (B) or its pharmaceutically acceptable salt according to any one of claims 32 to 35, wherein when w is 0, F is sulfhydryl; when w is 1, F is a clickable probe that can be linked to Q' after a reaction as a metal-free clickable reaction; and F is preferably an azide group.

37. The ligand-drug conjugate represented by the general formula (B) or its acceptable pharmaceutical salt according to any one of claims 32 to 36, where Pc is a modified antibody and the modified antibody has a structure of: where: Pc' is an antibody; Z2 and Z3 are each independently selected from -C(O)NH-, -C(O)O-, -C(O)-, -OC(O)-, -NH-, -O-, and OC(O)NH-, preferably -C(O)NH-; ri is an integer from 1 to 8; preferably from 1 to 6; more preferably from 1 to 3; r2 is an integer from 1 to 6; preferably from 1 to 4; more preferably from 1 to 2; r3 is an integer from 0 to 6; preferably from 0 to 4; more preferably from 0 to 2; r4 is an integer from 0 to 6; preferably from 0 to 4; more preferably from 0 to 2; and rs is an integer from 1 to 6; preferably from 1 to 4; more preferably from 1 to 2.

38. The ligand-drug conjugate represented by general formula (B) or its acceptable pharmaceutical salt according to any one of claims 32 to 37, where Pc is a modified antibody and Pc-Q' is selected from: Petition 870250095760, 10 / 20 / 2025, p. 99 / 136 91 / 126 Pc and Pc' is an antibody; Z2 and Z3 are each independently selected from -C(O)NH-, -C(O)O-, -C(O)-, -OC(O)-, -NH-, -O-, and OC(O)NH-, preferably -C(O)NH-; ri is an integer from 1 to 8; preferably from 1 to 6; more preferably from 1 to 3; r2 is an integer from 1 to 6; preferably from 1 to 4; most preferably, from 1 to 2; r3 is an integer from 0 to 6; preferably, from 0 to 4; most preferably, from 0 to 2; r4 is an integer from 0 to 6; preferably, from 0 to 4; most preferably, from 0 to 2; and rs is an integer from 1 to 6; preferably, from 1 to 4; most preferably, from 1 to 2.

39. The ligand-drug conjugate represented by Petition 870250095760, dated 10 / 20 / 2025, p. 100 / 136 92 / 126 general formula (B) or its pharmaceutically acceptable salt according to any one of claims 32 to 38 that is selected from: Petition 870250095760, dated 10 / 20 / 2025, p. 101 / 136 93 / 126 Pc Pc H Petition 870250095760, dated 10 / 20 / 2025, p. 102 / 136 94 / 126 LY21C T-LY22 T-LY22HD Pc F I-LY22AF Petition 870250095760, dated 10 / 20 / 2025, p. 103 / 136 95 / 126 Pc' F •LY22CC F Petition 870250095760, dated 10 / 20 / 2025, p. 104 / 136 96 / 126 F OH oh W>-OH HO' W) OH HO T-22CG HO OH Petition 870250095760, dated 10 / 20 / 2025, p. 105 / 136 97 / 126 pc Petition 870250095760, dated 10 / 20 / 2025, p. 106 / 136 98 / 126 Petition 870250095760, dated 10 / 20 / 2025, p. 107 / 136 99 / 126 Petition 870250095760, of 10 / 20 / 2025, p. 108 / 136 100 / 126 Pc' Η T-LY29C Ο Ο * T-LY33 Petition 870250095760, of 10 / 20 / 2025, p. 109 / 136 101 / 126 Pc· The eye. O OH OH OH T-LY34C T juH ho ho Pc HO I LY35 F ho--Aoh h°.Aoh O T-LY37A Petition 870250095760, dated 10 / 20 / 2025, p. 110 / 136 102 / 126 Petition 870250095760, dated 10 / 20 / 2025, p. 111 / 136 103 / 126 Pc HO H# I X..,H Oh oh o Pc HO HO OH „,OH O -LY46D Petition 870250095760, dated 10 / 20 / 2025, p. 112 / 136 104 / 126 HQ Pc OH OH OH N,,. T-LY4oü NHHN Petition 870250095760, dated 10 / 20 / 2025, p. 113 / 136 105 / 126 HO Ν Η T-LY47E Ο Ο Petition 870250095760, dated 10 / 20 / 2025, p. .LY48C Ι·Ι Y4HIJ Petition 870250095760, of 20 / 10 / 2025, p. 115 / 136 107 / 126 Pc T-LY5QA Pc ι-ι where: v varies from 1 to 10, being a decimal or integer number; antibody.

40. The ligand-drug conjugate represented by the general formula (B) or its pharmaceutically acceptable salt Petition 870250095760, of 20 / 10 / 2025, p.116 / 136 108 / 126 according to any one of claims 32 to 39, wherein the antibody is selected from a murine antibody, a chimeric antibody, a humanized antibody and a fully human antibody; and, preferably, the antibody or an antigen-binding fragment thereof is selected from anti-HER2 antibody (ErbB2), anti-EGFR antibody, anti-B7-H3 antibody, anti-c-Met antibody, anti-HER3 antibody (ErbB3), anti-HER4 antibody (ErbB4), anti-ROR1 antibody, anti-CLDN6 antibody, anti-CLDN9 antibody, anti-CLDN18 antibody.2, anti-NaPi-2b antibody, anti-TNF-α antibody, anti-ENPP3 antibody, anti-DLL3 antibody, anti-CD20 antibody, anti-CD22 antibody, anti-CD28 antibody, anti-CD30 antibody, anti-CD33 antibody, anti-CD37 antibody, anti-CD38 antibody, anti-CD44 antibody, anti-CD45 antibody, anti-CD47 antibody, anti-CD48 antibody, anti-CD56 antibody, anti-CD70 antibody, anti-CD73 antibody, anti-CD98 antibody, anti-CD105 antibody, anti-CEA antibody, anti-EphA2 antibody, anti-MUCI antibody, anti-Lewis Y antibody, anti-VEGFR antibody, anti-GPNMB antibody, anti-integrin antibody, anti-PSMA antibody, anti-tenascin-C antibody, anti-SLC44A4, antiCD79 antibody, anti-TROP-2 antibody, anti-CD79B antibody, anti-mesothelin antibody, anti-nectin-4 antibody, antiTPBG antibody or a fragment of the same antigen.

41. The ligand-drug conjugate represented by Petition 870250095760, dated 10 / 20 / 2025, pp. 117 / 136 109 / 126 general formula (B) or its pharmaceutically acceptable salt according to any of claims 32 to 40, wherein the antibody or antigen-binding fragment is selected from Trastuzumab, Cetuximab, Pertuzumab, Nimotuzumab, Enoblituzumab, Emibetuzumab, Inotuzumab, Pinatuzumab, Brentuximab, Gemtuzumab, Bivatuzumab, Lorvotuzumab, or an antigen-binding fragment thereof.

42. The ligand-drug conjugate represented by general formula (B) or its pharmaceutically acceptable salt according to any one of claims 32 to 41, which is selected from: Petition 870250095760, 10 / 20 / 2025, p. 118 / 136 110 / 126 Trastuzumab—ab • % Trastuzumab—ab Petition 870250095760, 10 / 20 / 2025, p. 119 / 136 111 / 126 Trastuzumab OO T-LY21 ν Trastuzumab F T-LY22AD Trastuzumab F T-LY22AF Petition 870250095760, 10 / 20 / 2025, p. 120 / 136 112 / 126 T-LY22CC Trastuzumab l-LYzzCL Petition 870250095760, dated 10 / 20 / 2025, p. 121 / 136 113 / 126 Trastuzumab T-LY22CE Petition 870250095760, dated 10 / 20 / 2025, p. 122 / 136 114 / 126 T-22CJ Petition 870250095760, dated 10 / 20 / 2025, p. 123 / 136 115 / 126 Petition 870250095760, dated 10 / 20 / 2025, p. 124 / 136 116 / 126 Trastuzumab Trastuzumab Trastuzumab— / S^N # T-LY2O3 LY-290 N -LY33 Trastuzumab Trastuzumab Petition 870250095760, dated 10 / 20 / 2025, p. 125 / 136 117 / 126 Petition 870250095760, dated 10 / 20 / 2025, p.126 / 136 118 / 126 Trastuzumab Trastuzumab Trastuzumab Petition 870250095760, of 20 / 10 / 2025, p. 127 / 136 119 / 126 Trastuzumab T-LY43E Trastuzumab Trastuzumab Trastuzumab* Trast'Z'mab Petition 870250095760, of 20 / 10 / 2025, p. 128 / 136 120 / 126 Trastuzumab Trastuzumab HO T-LY46D Trastuzumab OH OH OH OH OH OH OH •LY46E Petition 870250095760, dated 20 / 10 / 2025, p. 129 / 136 121 / 126 Η0 OH H0« ,ΟΗ Trastuzumab HO. OH T-LY46G Trastuzumab I-LY4 / L Ο Ο Petition 870250095760, of 20 / 10 / 2025, p. 130 / 136 122 / 126 Trastuzumab LY48A Trastuzumab Trastuzumab Petition 870250095760, of 20 / 10 / 2025, p. 131 / 136 123 / 126 Trastuzumab Trastuzumab Trastuzumab T-LY48E -LY5OA Trastuzumab HH l-LYNUC Trastuzumab Petition 870250095760, dated 20 / 10 / 2025, p. 132 / 136 124 / 126 Trastuzumab T-LY51A Trastuzumab '0 T-LY51B containing an integer or decimal number from 1 to 10; preferably, an integer or decimal number from 2 to 8.

43. A pharmaceutical composition comprising the drug-ligand conjugate represented by general formula (B) or its pharmaceutically acceptable salt according to any one of claims 32 to 42, and one or more pharmaceutically acceptable carriers or excipients.

44. Use of the compound represented by general formula (A) or its pharmaceutically acceptable salt according to any of claims 1 to 21, or of the compound represented by general formula (I) or of its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or of a mixture thereof, or of its pharmaceutically acceptable salt according to any of claims 22 to 26, or of the compound represented by general formula (II) or of its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or of a mixture thereof, or of its pharmaceutically acceptable salt according to any of claims 27 to 31, in the preparation of a ligand-drug conjugate.

45. Use of the ligand-drug conjugate represented by general formula (B) or of its pharmaceutically acceptable salt according to any of claims 32 to 42, or of the pharmaceutical composition according to claim 43, in the preparation of a medicament for the treatment of tumor or cancer, the cancer preferably being breast cancer, ovarian cancer, soft tissue sarcoma, liposarcoma, lung cancer, non-small cell lung cancer, gastric cancer, melanoma, head and neck cancer, cervical cancer or prostate cancer.

46. ​​Use of the compound represented by general formula (I) or of its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or of a mixture thereof, or of its pharmaceutically acceptable salt according to any of claims 22 to 26, or of the compound represented by general formula (II) or of its stereoisomer, tautomer, mesomer, racemate, enantiomer or diastereomer, or of a mixture thereof, or of its pharmaceutically acceptable salt according to any of claims 27 to 31, in the preparation of a medicament for the treatment of tumor or cancer, the cancer preferably being breast cancer, ovarian cancer, soft tissue sarcoma, liposarcoma, Petition 870250095760, of 10 / 20 / 2025, p. 134 / 136 126 / 126 lung cancer, non-small cell lung cancer, gastric cancer, melanoma, head and neck cancer, cervical cancer or prostate cancer.

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