COMPOSTOS DE 1,2,4-OXADIAZOL COMO INIBIDORES DE VIAS DE SINALIZAÇÃO CD47, COMPOSIÇÃO FARMACÊUTICA E USOS DOS COMPOSTOS PARA MODULAR A ATIVIDADE FAGOCÍTICA DE MACRÓFAGOS EM DIREÇÃO A UMA CÉLULA CANCERÍGENA OU TUMORAL E PARA TRATAR OU RETARDAR A PROGRESSÃO DE ATEROSCLEROSE, ESCLEROSE MÚLTIPLA OU DOENÇAS OU DISTÚRBIOS MEDIADOS POR CD47

Description

1 / 88 “1,2,4-OXADIAZOLE COMPOUNDS AS INHIBITORS OF PATHWAYS OF CD47 Signaling, Pharmaceutical Composition and Uses of the Compounds to Modulate the Phagocytic Activity of Macrophages Toward a Cancerous or Tumor Cell and to Treat or Delay the Progression of Atherosclerosis, Sclerosis Multiple CD47-mediated diseases or disorders

[001] Divided from BR 11 2020 014202 6, filed on 11 / 01 / 2019.RELATED PATENT APPLICATION

[002] This application claims the benefit of Indian provisional application number 201841001438, filed on January 12, 2018; the content of which is incorporated herein by reference in its entirety. TECHNICAL FIELD

[003] The present invention relates to therapeutically useful 1,2,4-oxadiazole compounds of formula (I) as inhibitors of the CD47 signaling pathway. The invention also relates to pharmaceutical compositions comprising said compounds or a pharmaceutically acceptable salt or an amide or an ester, or a stereoisomer thereof. FUNDAMENTALS

[004] Antagonist antibodies targeting CTLA-4, PD-1, and PD-L1 impact the adaptive immune system, predominantly T cells, and have shown impressive clinical efficacy in a wide range of cancers. Despite the success of these T-cell-based checkpoint inhibitors in a subset of patients, most patients still do not show an adequate clinical response. Checkpoint proteins on cells of the innate immune system are also known to regulate the immune response. Among the innate immune checkpoint proteins, CD47 is upregulated in a wide range of malignancies that downregulate the Petition 870260028627, dated 03 / 26 / 2026, page 10 / 130 2 / 88 Macrophage-mediated phagocytosis. CD47-mediated phagocytosis is primarily through interactions with SIRP1a expressed on macrophages. Blocking SIRP1a / CD47 has been shown to dramatically improve phagocytosis of tumor cells and dendritic cell maturation for better antigen presentation, leading to substantially improved antitumor responses in preclinical cancer models (MP Chao et al., Curr Opin Immunol. 2012 (2): 225-232). CD-47 as a target for eliminating tumor cells.

[005] CD47, also known as integrin-associated protein (IAP), ovarian cancer antigen OA3, Rh-related antigen, and MER6, is a transmembrane protein that, in humans, is encoded by the CD47 gene. CD47 belongs to the immunoglobulin superfamily and partners with integrin and also binds to the ligands thrombospondin-1 (TSP-1) and signal-regulatory protein alpha (SIRPa). CD47 is best known for its central role in preventing the phagocytic removal of healthy cells by binding to signal-regulatory protein alpha expressed on phagocytes (SIRPa). SIRPa, an inhibitory protein expressed on macrophages, once activated, suppresses the phagocytosis of cells expressing CD47. This CD47 / SIRPa axis is an important homeostatic mechanism that prevents the removal of normal healthy cells expressing CD47. Conversely, the downregulation of CD47 in damaged, aged, and superfluous cells ensures their timely removal.

[006] CD47 is expressed in virtually all non-malignant cells, and blocking CD47, loss of CD47 expression, or alterations in membrane distribution can serve as markers of aged or damaged cells, particularly in red blood cells (RBCs). Alternatively, SIRPa blockade also allows phagocytosis of targets that are not normally phagocytosed, for those cells where pre-phagocytic signals are also present. CD47 is a widely expressed transmembrane glycoprotein with Petition 870260028627, dated 03 / 26 / 2026, page 11 / 130 3 / 88 a single Ig-like domain and five membrane-spanning regions, which functions as a cellular ligand for SIRPα with binding mediated through the V-like domain of the NH2-terminal of SIRPα. SIRPα is primarily expressed on myeloid cells, including macrophages, granulocytes, myeloid dendritic cells (DCs), mast cells, and their precursors, including hematopoietic stem cells.

[007] CD47 is also constitutively upregulated in several types of cancer, such as non-Hodgkin lymphoma (NHL), acute myeloid leukemia (AML), breast, colon, glioblastoma, glioma, ovarian, bladder, and prostate cancer. Overexpression of CD47 by tumor cells, which effectively helps them escape the immune system and death by innate immune cells.

[008] CD47 has been shown to be a potential target for the treatment of atherosclerosis. This is because the process of atherogenesis, i.e., the formation of atheroma in the arterial wall, is associated with the upregulation of CD47, which makes malignant cells resistant to programmed cell removal, or “efferocytosis.” This efferocytosis effect is reversed by administering CD47-blocking antibodies, which normalizes the clearance of diseased vascular tissue and improves atherosclerosis in several mouse models (Kojima Y, et al., Nature. August 4, 2016; 536 (7614): 86-90). Additionally, it has been reported that blocking CD47 with the CD47-Fc fusion protein is effective in regulating experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), pathology and provides a potential therapeutic target in the prevention and treatment of MS (Gao Q et al., J. Autoimmun. 2016 May; 69: 74-85).

[009] Various publications such as US20160304609, WO2016188449, US20170081407, WO2017194627 and WO2017194634 disclosing compounds (i.e., antibodies and peptides) that modulate CD47 have been published.

[010] Despite several recent advances, there is still an unmet need for effective CD47 inhibitors that block the signaling pathway of Petition 870260028627, dated 03 / 26 / 2026, p. 12 / 130 4 / 88 SIRP1a-CD47 for the treatment of cancers that are mediated by high levels of CD47 expression. SUMMARY OF THE INVENTION

[011] The present invention provides pharmaceutically acceptable compounds and their salts. These compounds are capable of suppressing and / or inhibiting the CD47 signaling pathway.

[012] In one aspect, the present invention provides compounds of Formula (I): or a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof; wherein, Ra is hydrogen or acyl; and Ri represents hydrogen, -(CH2)2CONH2, (CH2)2COOH, -CH2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, CH(CH3)-CH2-CH3, -CH2-aryl or -CH2-heteroaryl; wherein the said aryl and heteroaryl are unsubstituted; or Ra and R1, together with the atoms to which they are attached, form a pyrrolidine ring optionally substituted by an oxo group; R2 represents hydrogen, -CH2-OH, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, (CH2)2COOH, -CH2-aryl or -CH2-heteroaryl; wherein the said aryl and heteroaryl are unsubstituted; Rb is hydrogen; and R3 represents hydrogen, -CH2-aryl, -(CH2)3NHC(=NH)NH2, -CH2COOH, -CH(CH3)-CH2-CH3, -CH2-CH(CH3)2, -(CH2)2CONH2, -(CH2)2COOH, (CH2)4NH2 or -CH2-heteroaryl; wherein the said aryl and heteroaryl are unsubstituted; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[013] In another aspect, the present invention relates to compositions Petition 870260028627, dated 03 / 26 / 2026, p. 13 / 130 5 / 88 pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt or amide or ester, or a stereoisomer thereof, and processes for the preparation of such compositions.

[014] Yet another aspect of the present invention provides a method of treating CD47-mediated diseases or disorders comprising administering a compound of formula (I) or a pharmaceutically acceptable salt or an amide or an ester, or a stereoisomer thereof. DETAILED DESCRIPTION OF THE INVENTION

[015] The present invention provides 1,2,4-oxadiazole compounds and their derivatives as useful therapeutic agents for the treatment of CD-47-mediated disorders.

[016] Each embodiment is provided by way of explanation of the invention and not by way of limitation of the invention. In fact, it will be evident to those skilled in the art that various modifications and variations can be made to the compounds, compositions and methods described herein without departing from the scope or essence of the invention. For example, the features illustrated or described as part of one embodiment can be applied to another embodiment to produce yet another embodiment. Thus, it is intended that the present invention includes such modifications and variations and their equivalents. Other objects, features and aspects of the present invention are disclosed or are evident from the detailed description that follows. It should be understood by those common to the art that the present discussion is only a description of exemplary embodiments and should not be interpreted as limiting the broader aspects of the present invention.

[017] In certain embodiments, the present invention provides a compound of formula (I): Petition 870260028627, dated 03 / 26 / 2026, p. 14 / 130 6 / 88 or a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof; wherein, Ra is hydrogen or acyl; and Ri represents hydrogen, -(CH2)2CONH2, (CH2)2COOH, -CH2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, CH(CH3)-CH2-CH3, -CH2-aryl, or -CH2-heteroaryl; wherein said aryl and heteroaryl are unsubstituted; or Ra and R1, together with the atoms to which they are attached, form a pyrrolidine ring optionally substituted with the oxo group; R2 represents hydrogen, -CH2-OH, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, (CH2)2COOH, -CH2-aryl, or -CH2-heteroaryl; wherein said aryl and heteroaryl are not substituted; Rb is hydrogen; and R3 represents hydrogen, -CH2-aryl, -(CH2)3NHC(=NH)NH2, -CH2COOH, -CH(CH3)-CH2-CH3, -CH2-CH(CH3)2, -(CH2)2CONH2, -(CH2)2COOH, (CH2)4NH2 or -CH2-heteroaryl; wherein said aryl and heteroaryl are unsubstituted; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[018] In certain embodiments, the present invention provides a compound of formula (I): in which, Ra is hydrogen; and R1 represents hydrogen, -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, -CH2-aryl, or -CH2-heteroaryl; or Ra and R1, together with the atoms to which they are attached, form a pyrrolidine ring; R2 represents hydrogen, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, (CH2)2COOH, -CH2-aryl, or -CH2-heteroaryl; Rb is hydrogen; and R3 represents hydrogen, -CH2-aryl, -(CH2)3NHC(=NH)NH2, Petition 870260028627, dated 03 / 26 / 2026, page 15 / 130 7 / 88 -(CH2)2CONH2, -(CH2)2COOH, -(CH2)4NH2 or -CH2-heteroaryl; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring. In certain embodiments, the present invention provides a compound of formula (I): wherein, Ra is hydrogen or acyl; and Ri represents hydrogen, -CH2COOH, (CH2)3NH(C=NH)NH2, -CH2CONH2, -CH(CH3)-CH2-CH3, or -CH2-heteroaryl; wherein said aryl and heteroaryl are not substituted; or Ra and R1, together with the atoms to which they are attached, form a pyrrolidine ring optionally substituted by the oxo group; R2 represents hydrogen, -CH2-OH or -CH2-heteroaryl; wherein the said heteroaryl group is not substituted; Rb is hydrogen; and R3 represents -CH2-aryl, -CH(CH3)2, -CH2COOH, -CH(CH3)CH2-CH3, -CH2-CH(CH3)2, -(CH2)2COOH, or -(CH2)4NH2; wherein the said aryl group is not substituted;

[019] In certain embodiments, the present invention provides a compound of formula (I): in which, Ra is hydrogen or acyl; and R1 represents -(CH2)2CONH2, -(CH2)4NH2, (CH2)3NH(C=NH)NH2 or -CH2-heteroaryl; wherein the said heteroaryl is not substituted; R2 represents; -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, or CH2-aryl; wherein the said aryl group is not substituted; Rb is hydrogen; and R3 represents hydrogen, -(CH2)2CONH2, or -CH2heteroaryl; wherein said heteroaryl is not substituted; or Rb and R3, together with the atoms to which they are attached, form the pyrrolidine ring.

[020] In certain embodiments, Ri represents hydrogen, -(CH2AONH2, (CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, CH(CH3)-CH2-CH3, Petition 870260028627, dated 03 / 26 / 2026, page 16 / 130 8 / 88 CH2-aryl, or -CH2-heteroaryl; wherein the said heteroaryl group is not substituted;

[021] These models, which represent the hydrogen, -(CH2)2CONH2, (CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, CH(CH3)-CH2-CH3, CH2-fenil, -CH2-indolil, or -CH2-imidazolil.

[022] These models, which represent the hydrogen, -(CH2)2CONH2, (CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, -CH2-fenil, or -CH2imidazolil.

[023] Em certas modalidades, Ri representa -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, -CH2-fenil, ou -CH2-imidazolil.

[024] Em certas modalidades, Representa -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, -(CH2)4NH2, ou -CH2-imidazolil.

[025] Em certas modalidades, Ri representa -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, ou -CH2-fenil.

[026] Em certas modalidades, Ri representa -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, ou -(CH2)4NH2.

[027] Em certas modalidades, Ri representa -(CH2)3NH(C=NH)NH2, (CH2)2CONH2, ou -(CH2)2COOH.

[028] In certain embodiments, Ri stands for -(CH2)2COOH, -CH2COOH, CH2CONH2, -CH(CH3)-CH2-CH3 or -CH2-aryl; wherein the said aryl is not substituted.

[029] In certain embodiments, Ri stands for -(CH2)2CONH2, or (CH2)2COOH.

[030] In certain embodiments, Ra is hydrogen. In certain embodiments, Ra is acyl. In certain embodiments, Ra is acetyl.

[031] In other embodiments, in formula (I), Ra and Ri, together with the atoms to which they are attached, form a pyrrolidine ring optionally substituted by the oxo group.

[032] In certain embodiments, R2 represents hydrogen, -CH2-OH, Petition 870260028627, dated 03 / 26 / 2026, page 17 / 130 9 / 88 (CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, -CH2-phenyl, -CH2-indolyl, or -CH2imidazolyl.

[033] In certain embodiments, R2 represents hydrogen, (CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, -CH2-phenyl, or -CH2-imidazolyl.

[034] In certain embodiments, R2 represents hydrogen, (CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, or -CH2-phenyl.

[035] In certain embodiments, R2 represents hydrogen, (CH2)3NHC(=NH)NH2, -(CH2)2COOH, or -CH2-phenyl.

[036] In certain embodiments, R2 represents hydrogen, (CH2)3NHC(=NH)NH2, -(CH2)2CONH2, or -(CH2)2COOH.

[037] In certain embodiments, R2 represents hydrogen, (CH2)3NHC(=NH)NH2, -(CH2)2CONH2, or -(CH2)2COOH.

[038] In certain embodiments, R2 represents hydrogen, (CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, or -CH2-phenyl.

[039] In some cases, R2 represents hydrogen or -(CH2)3NHC(=NH)NH2.

[040] In certain embodiments, R3 represents hydrogen, (CH2)3NHC(=NH)NH2, -CH2COOH, -CH(CH3)-CH2-CH3, -CH2-CH(CH3)2,(CH2)2CONH2, -(CH2)2COOH, -(CH2)4NH2, -CH2-phenyl, -CH2-indolyl, or -CH2-imidazolyl.

[041] In certain embodiments, R3 represents hydrogen, -CH2-phenyl, (CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, -CH(CH3)-CH2-CH3, -CH2CH(CH3)2, -(CH2)4NH2 or -CH2-imidazolyl.

[042] In certain embodiments, R3 represents hydrogen, -CH2-phenyl, (CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, -CH(CH3)-CH2-CH3, -CH2CH(CH3)2, -(CH2)4NH2 or -CH2-imidazolyl.

[043] In certain embodiments, R3 represents hydrogen, -CH2-phenyl, (CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, -(CH2)4NH2 or -CH2-heteroaryl; wherein said heteroaryl is unsubstituted; Petition 870260028627, dated 03 / 26 / 2026, page 18 / 130 10 / 88

[044] In certain embodiments, R3 represents hydrogen, -CH2-phenyl, (CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, -(CH2)4NH2 or -CH2-imidazolyl.

[045] In certain embodiments, R3 represents hydrogen, -CH2-phenyl, (CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, or -(CH2)4NH2.

[046] In certain embodiments, R3 represents hydrogen, -CH2-phenyl, (CH2)3NHC(=NH)NH2, -(CH2)2CONH2, or -(CH2)2COOH.

[047] In certain embodiments, R3 represents hydrogen, -CH(CH3)-CH2-CH3, -CH2-CH(CH3)2, CH3COOH or -CH2-heteroaryl; wherein said heteroaryl is not substituted.

[048] In certain embodiments, R3 represents -CH2-phenyl, (CH2)3NHC(=NH)NH2, -(CH2)2COOH or -(CH2)4NH2;

[049] In certain embodiments, Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[050] In other embodiments, the present invention provides a compound of formula (I): in which; Ra is hydrogen or acyl; and Ri represents hydrogen, -(CH2)2CONH2, (CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, -CH(CH3)-CH2-CH3, CH2-phenyl, -CH2-indolyl, or -CH2-imidazolyl; wherein said phenyl, indolyl, and imidazolyl are not substituted; or Ra and R1, together with the atoms to which they are attached, form a pyrrolidine ring optionally substituted by the oxo group. R2 represents hydrogen, CH2-OH, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, (CH2)2COOH, -CH2-phenyl, -CH2-indolyl, or -CH2-imidazolyl; wherein the said imidazolyl is not substituted. Rb represents hydrogen; and R3 represents hydrogen, -CH2-phenyl, (CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -CH2COOH, -CH2-CH(CH3)2, -(CH2)2CONH2, (CH2)2COOH, -(CH2)4NH2, -CH2-indolyl, or -CH2-imidazolyl; wherein said phenyl, Petition 870260028627, dated 03 / 26 / 2026, page 19 / 130 11 / 88 indolyl and imidazolyl are not substituted; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[051] In certain embodiments, the present invention provides a compound of formula (I): wherein Rae represents hydrogen; R1 represents hydrogen, -(ChbjzCONhb, -(ChbjzCOOH, (CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, -CH2-phenyl, or -CH2-imidazolyl; or Rae R1, together with the atoms to which they are attached, form a pyrrolidine ring; R2 represents hydrogen, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, (CH2)2COOH, -CH2-phenyl, or -CH2-imidazolyl; Rb is hydrogen; R3 represents hydrogen, -CH2-phenyl, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, -(CH2)4NH2 or -CH2-imidazolyl; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[052] In certain forms, the compound is not one of

[053] In certain embodiments, the present invention provides a compound (IA) or a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof; wherein R1, R2 and R2 are as defined in the compound Petition 870260028627, dated 03 / 26 / 2026, page 20 / 130 12 / 88 of formula (I).

[054] In certain embodiments, Ri stands for hydrogen, -CH2-COOH, -CH2CONH2, -CH(CH3)-CH2-CH3, -(CH2)2CONH2, -(CH2)2COOH, -(CH2)3NH(C=NH)NH2, (CH2)4NH2, -CH2-phenyl, -CH2-indolyl or -CH2-imidazolyl.

[055] In certain embodiments, Ri stands for hydrogen, -(CH2)2CONH2, (CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2-phenyl, or -CH2-imidazolyl.

[056] In certain embodiments, Ri represents -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C = NH)NH2, or -(CH2)4NH2.

[057] In certain embodiments, Ri stands for -(CH2)2CONH2, or (CH2)2COOH.

[058] In certain embodiments, R2 represents hydrogen, -CH2-OH (CH2)2CONH2, -(CH2)3NHC(=NH)NH2, -(CH2)2COOH or -CH2-phenyl.

[059] In certain embodiments, R2 represents hydrogen, (CH2)3NHC(=NH)NH2, or -(CH2)2COOH.

[060] In certain embodiments, R2 represents hydrogen, -(CH2)2CONH2, or (CH2)2COOH.

[061] In other embodiments, the present invention provides a compound of formula (IA): wherein Ra is hydrogen; and Ri represents hydrogen, -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2-phenyl, or -CH2-imidazolyl; R2 represents hydrogen, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, (CH2)2COOH, -CH2-phenyl or -CH2-imidazolyl.

[062] In certain embodiments, the present invention provides a compound of formula (IA): in which; Ra is hydrogen; and Ri represents hydrogen, -CH2-COOH, -CH2-CONH2, CH(CH3)-CH2-CH3, -(CH2)2CONH2, -(CH2)2COOH, -(CH2)3NH(C=NH)NH2, Petition 870260028627, dated 03 / 26 / 2026, page 21 / 130 13 / 88 (CH2)4NH2, -CH2-phenyl, -CH2-indolyl or -CH2-imidazolyl; wherein said phenyl, indolyl and imidazolyl are not substituted; R2 represents hydrogen, -CH2-OH -(CH2)2CONH2, -(CH2)3NHC(=NH)NH2, (CH2)2COOH or -CH2-phenyl; wherein the said phenyl is not substituted;

[063] In other embodiments, the present invention provides a compound of formula (IA): in which; Ra is hydrogen; and Ri represents hydrogen, -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, -CH2COOH, -CH2CONH2, -(CH2)4NH2, -CH(CH3)-CH2-CH3, CH2-phenyl, -CH2-indolyl or -CH2-imidazolyl; R2 represents hydrogen, -CH2-OH, -(CH2)3NHC(=NH)NH2, -(CH2)2COOH, CH2-phenyl, or -CH2-imidazolyl.

[064] In other embodiments, the present invention provides a compound of formula (IA): in which; Ra is hydrogen; and Ri represents hydrogen, -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH(CH3)-CH2-CH3, -CH2-phenyl, or -CH2-imidazolyl; R2 represents hydrogen, -CH2-OH, -(CH2)3NHC(=NH)NH2, -(CH2)2COOH, CH2-phenyl, or -CH2-imidazolyl.

[065] In other embodiments, the present invention provides a compound of formula (IA): wherein Ra stands for hydrogen; and Ri represents -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, or -(CH2)4NH2. R2 represents hydrogen, -(CH2)3NHC(=NH)NH2, -(CH2)2COOH, -CH2-phenyl, or -CH2-imidazolyl.

[066] In certain embodiments, compounds of formula (IA) are selected from, Petition 870260028627, dated 03 / 26 / 2026, page 22 / 130 14 / 88 Petition 870260028627, dated 03 / 26 / 2026, p. 23 / 130 15 / 88 Petition 870260028627, dated 03 / 26 / 2026, p. 24 / 130 16 / 88 or a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof;

[067] In certain embodiments, compounds of formula (I) selected from, OH ; or either a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof; Petition 870260028627, dated 03 / 26 / 2026, p. 25 / 130 17 / 88

[068] In certain embodiments of the present invention, the compound of formula (IA) may also be written showing its absolute stereochemistry, as

[069] In certain embodiments, the present invention provides a compound of formula (IB): (IS> or a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof; wherein Ri, Ra, Rb and R3 are as defined in the compound of formula (I).

[070] In other embodiments, the present invention provides a compound of formula (IA): in which, R1 represents hydrogen, -CH2-COOH, -CH2-CONH2, -CH(CH3)-CH2-CH3, (CH2)2CONH2, -(CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CHz-indolyl, -CH2imidazolyl or -CH2-phenyl. Rb is hydrogen; R3 represents hydrogen, -CH2-COOH, -CH(CH3)-CH2-CH3, CH2-CH(CH3)2, -(CH2)4NH2, -(CH2)2CONH2, -(CH2)2COOH, -CH2-phenyl, CH2-imidazolyl or CH2-imidazolyl; or Rb is hydrogen. In certain embodiments, in formula (IB), Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring. Petition 870260028627, dated 03 / 26 / 2026, page 26 / 130 18 / 88

[071] In certain embodiments, Ri represents hydrogen, -CH2-COOH, -CH2CONH2, -CH(CH3)-CH2-CH3, -(CH2)2CONH2, -(CH2)2COOH, -(CH2)3NH(C=NH)NH2, (CH2)4NH2, -CH2-indolyl, -CH2-imidazolyl or -CH2-phenyl.

[072] In certain embodiments, Ri stands for hydrogen, -(CH2)2CONH2, (CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, or -CH2-phenyl.

[073] In certain embodiments, Ri stands for -(CH2)2CONH2, or (CH2)2COOH.

[074] In certain embodiments, R3 represents hydrogen, -CH2-phenyl, (CH2)2CONH2, or -(CH2)2COOH.

[075] In certain embodiments, Rb is hydrogen; R3 represents hydrogen, CH2-COOH, -CH2-CH(CH3)2, -CH(CH3)-CH2-CH3, -(CH2)4NH2, -(CH2)2CONH2, (CH2)2COOH, -CH2-phenyl, CH2-imidazolyl or CH2-imidazolyl; or Rb is hydrogen. In certain embodiments, in formula (IB), Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[076] In certain embodiments, R3 represents hydrogen, or -CH2-phenyl.

[077] In certain embodiments, in formula (IB), Rb is hydrogen. In certain embodiments, in formula (IB), Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[078] In certain embodiments, the present invention provides a compound of formula (IB): wherein Ri represents -(CH2)2CONH2, or -(CH2)2COOH; Rb is hydrogen; and R3 represents hydrogen, or -CH2-phenyl; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[079] In certain embodiments, compounds of formula (I) selected from, Petition 870260028627, dated 03 / 26 / 2026, p. 27 / 130 19 / 88 or a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof;

[080] In certain embodiments, the present invention provides a compound of formula (IC): or a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof; wherein Ri, Ra, R3 and Rb are as defined in the compound of formula (I).

[081] In certain embodiments, Ri represents -(CH2)2COOH, -(CH2)2CONH2, (CH2)3NH(C = NH)NH2, Or -(CH2)4NH2.

[082] In certain embodiments, Ri represents -(CH2)2CONH2, (CH2)3NH(C=NH)NH2, or -(CH2)4NH2.

[083] In certain embodiments, Ri represents -(CH2)2CONH2, or (CH2)3NH(C=NH)NH2.

[084] In certain embodiments, in formula (IC), Ra is hydrogen. In certain Petition 870260028627, dated 03 / 26 / 2026, page 28 / 130 20 / 88 forms, in formula (IC), Ra and Ri, together with the atoms to which they are attached, form a pyrrolidine ring.

[085] In certain embodiments, R3 represents hydrogen, -CH2-phenyl, (CH2)3NHC(=NH)NH2, -CH2-imidazolyl or Rb and R3, together with the atoms to which they are attached, form the pyrrolidine ring.

[086] In certain embodiments, R3 represents hydrogen, -CH2-phenyl, (CH2)3NHC(=NH)NH2, or -CH2-imidazolyl.

[087] In certain embodiments, in formula (IC), Rb is hydrogen. In certain embodiments, in formula (IC), Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[088] In other embodiments, the present invention provides a compound of formula (IC): wherein Ri represents -(CH2)2COOH, -(CH2)2CONH2, -(CH2)3NH(C=NH)NH2, or (CH2)4NH2; and R3 represents hydrogen, -CH2-phenyl, -(CH2)2CONH2, or -(CH2)2COOH.

[089] In other embodiments, the present invention provides a compound of formula (IC): wherein Ra is hydrogen; and Ri represents -(CH2)2CONH2, -(CH2)3NH(C=NH)NH2, or (CH2)4NH2; or Ra and Ri, together with the atoms to which they are attached, form a pyrrolidine ring; and Rb is hydrogen; and R3 represents -CH2-phenyl, -(CH2)3NHC(=NH)NH2, or -CH2imidazolyl; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[090] In other embodiments, the present invention provides a compound of formula (IC): wherein Ra is hydrogen; and Ri represents -(CH2)2CONH2, or -(CH2)3NH(C=NH)NH2; or Ra and Ri, together with the atoms to which they are bonded, form a ring of Petition 870260028627, dated 03 / 26 / 2026, p. 29 / 130 21 / 88 pyrrolidine; and Rb is hydrogen; and R3 represents hydrogen, -CH2-phenyl, (CH2)3NHC(=NH)NH2, or -CH2-imidazolyl; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[091] In certain embodiments, compounds of formula (I) selected from, or a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof.

[092] In certain embodiments, the present invention provides a compound of the formula (ID): Petition 870260028627, dated 03 / 26 / 2026, p. 30 / 130 22 / 88 or a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof; wherein, Ri, Ra, R3 and Rb are as defined in the compound of formula (I).

[093] In certain embodiments, Ri represents -(CH2)3NH(C=NH)NH2, (CH2)4NH2, or -CH2CONH2.

[094] In certain embodiments, R3 represents hydrogen, (CH2)3NHC( = NH)NH2, Or -(CH2)4NH2.

[095] In certain embodiments, in formula (ID), Rb is hydrogen. In certain embodiments, in formula (ID), Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[096] In certain embodiments, where Rb is hydrogen; R3 represents hydrogen, -(CH2)3NHC(=NH)NH2, or -(CH2)4NH2; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[097] In other embodiments, the present invention provides a compound of the formula (ID): wherein Ri represents -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, or -CH2CONH2; Rb is hydrogen; R3 represents hydrogen, -(CH2)3NHC(=NH)NH2, or (CH2)4NH2; or Rb and R3, together with the atoms to which they are bonded, form the pyrrolidine ring.

[098] In other embodiments, the present invention provides a compound of the formula (ID): wherein Ri represents -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, or -CH2CONH2; Rb is hydrogen; and R3 represents hydrogen, -(CH2)3NHC(=NH)NH2, or Petition 870260028627, dated 03 / 26 / 2026, page 31 / 130 23 / 88 (CH2)4NH2; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[099] In certain embodiments, compounds of formula (I) selected from, ; or OH OH n-YOHHO the NH2 or a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof.

[0100] In certain embodiments, the present invention provides a compound of formula (i.e.): NN COOHH1½Kb R3 is a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof; where R2, R3 and Rb are as defined in the compound. Petition 870260028627, dated 03 / 26 / 2026, p. 32 / 130 24 / 88 of formula (I).

[0101] In certain embodiments, R2 represents hydrogen, -CH2-OH, (CH2)2COOH, -(CH2)3NHC(=NH)NH2, -CH2-phenyl or -CH2-indolyl.

[0102] In certain embodiments, R2 represents hydrogen, or (CH2)3NHC(=NH)NH2.

[0103] In other embodiments, the present invention provides a compound of the formula (ID): wherein wherein; R2 represents hydrogen, -CH2-OH, -(CH2)2COOH, -(CH2)3NHC(=NH)NH2, CH2-phenyl or -CH2-indole; R3 represents hydrogen, -CH2-COOH, -(CH2)2COOH, -CH2-CH(CH3)2, CH(CH3)-CH2-CH3, -(CH2)4NH2, -CH2-phenyl, -CH2-indolyl, or -CH2-imidazolyl or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring;

[0104] In certain embodiments, in formula (IE), Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[0105] In certain embodiments, R2 represents hydrogen, (CH2)3NHC(=NH)NH2, -CH2-OH -(CH2)2COOH, -CH2-phenyl or -CH2-indolyl.

[0106] In other embodiments, the present invention provides a compound of formula (IE): wherein, R2 represents hydrogen, or -(CH2)3NHC(=NH)NH2; Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[0107] In certain embodiments, R3 represents hydrogen, -CH2-COOH, (CH2)2COOH, -CH2-CH(CH3)2, -CH(CH3)-CH2-CH3, -(CH2)4NH2, -CH2-phenyl, -CH2indolyl, or -CH2-imidazolyl or Rb and R3, together with the atoms to which they are attached, form the pyrrolidine ring;

[0108] In certain embodiments, the present invention provides a compound of formula (IF): Petition 870260028627, dated 03 / 26 / 2026, page 33 / 130 25 / 88 or a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof; wherein, R2, R3 and Rb are as defined in the compound of formula (I).

[0109] In certain embodiments, R2 represents hydrogen, -CH2-phenyl, (CH2)3NHC(=NH)NH2, or -(CH2)2COOH.

[0110] In certain embodiments, R3 represents -CH2-phenyl, -(CH2)2CONH2, (CH2)2COOH, or -(CH2)4NH2.

[0111] In certain embodiments, R3 represents -CH2-phenyl, -(CH2)2CONH2, or (CH2)2COOH.

[0112] In certain embodiments, in formula (IF), Rb is hydrogen. In certain embodiments, in formula (IF), Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[0113] In certain embodiments, the present invention provides a compound of formula (IF): wherein R2 represents hydrogen, -CH2-phenyl, -(CH2)3NHC(=NH)NH2, or (CH2)2COOH; R3 stands for -CH2-phenyl, -(CH2)2CONH2, -(CH2)2COOH, or -(CH2)4NH2.

[0114] In certain embodiments, the present invention provides a compound of formula (IF): wherein R2 represents hydrogen, -CH2-phenyl, -(CH2)3NHC(=NH)NH2, or (CH2)2COOH; Rb is hydrogen; and R3 represents -CH2-phenyl, -(CH2)2CONH2, or -(CH2)2COOH; or Rb and R3, together with the atoms to which they are bonded, form a ring of Petition 870260028627, dated 03 / 26 / 2026, page 34 / 130 26 / 88 pyrrolidine.

[0115] In certain embodiments, compounds of formula (I) selected from, OH J or or a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof.

[0116] In certain embodiments, Ra is hydrogen; and Ri represents hydrogen, (CH2)2CONH2, -(CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, -CH2aryl, or -CH2-heteroaryl; or Ra and R1, together with the atoms to which they are attached, form a pyrrolidine ring; Petition 870260028627, dated 03 / 26 / 2026, page 35 / 130 27 / 88 R2 represents hydrogen, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, (CH2)2COOH, -CH2-aryl, or -CH2-heteroaryl; Rb is hydrogen; and R3 represents hydrogen, -CH2-aryl, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, -(CH2)4NH2 or -CH2-heteroaryl; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[0117] In certain embodiments, Ra is hydrogen; and Ri represents hydrogen, (CH2)2CONH2, -(CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, -CH2phenyl, or -CH2-imidazolyl; or Ra and R1, together with the atoms to which they are attached, form a pyrrolidine ring; R2 represents hydrogen, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, (CH2)2COOH, -CH2-phenyl, or -CH2-imidazolyl; Rb is hydrogen; and R3 represents hydrogen, -CH2-phenyl, (CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, -(CH2)4NH2 or -CH2-imidazolyl; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[0118] In certain embodiments, the present invention provides a compound selected from:___________________________________________________ Compound Structure 1 / ~z” __ / XZ !----' ro Z^\ 1 ,° XZ r?o <N ( T / \ Z / ----f ~Z· \ / <N 2H 1 T Petition 870260028627, dated 03 / 26 / 2026, p. 36 / 130 28 / 88 Compound Structure 3 z. T o ZI t AM x 5 r< \— ~Z· f / CM O x 4 ZN> / ' z / —' -z. \__ / I ) N> z<=\ 1 zou . V, IZ 1? >° o I 5 ι ,o Z / —\ 1 / z °\ri IZ o T 6 =1= P K5 / / Z / --\ / T zA MY IZ Cx^f° o I 7 HN^Nl·^ HN CK / OH Ί Ύ Cl A Vo η2νΛΥνΥ^νΛνΛΥ0Η MHHSJ 8 HN^NH; O;>,.OH HN. O_ AO \ c^c^AmAí-A / Oh / HH π H N-0 HH o J Petition 870260028627, dated 03 / 26 / 2026, p. 37 / 130 29 / 88 Compound Structure 9 HN^NH2 CkWN ΙΝΠ2 ] | oX S. 0 x h2nAYnV^nAnJVoh n-ó HH o · J 10 I o N> / / Z / —\ T? “^A °1 X 1 IZ IZ ο=Αλ σε \__ / 11 X o X ZI οι ZI I saw oz 1 'pZ CM ( T / \ Z / —' z. Fe 1 X 12 X ox \' ZI oo=( ZI 1-na / / 'Vo ·,<N O I 13 I zto Xo ZT I / ZT VVo o z 1 VsZ -r / Z- T / csl -z.— / T 14 X N> z A | z TO z. A……A -JZZ. xz °=( ο V 7 X \ / Petition 870260028627, dated 3 / 26 / 2026, p. 38 / 130 30 / 88 Compound Structure 15 I or ZT °CT / ZT vi oz 1 VsZ -r / --- Z. J_ / Oxl z—'f T 16 I or 0^0 °=( ΖΞΕ Q z<N T 17 T O m / / Z > --V ' ob IZ o I 18 z / —z __ / TZ !----' N> Zs=\ Ί.-Ζ. o T 19 TN> \ Z / -- A IZ o 20 TON> / / / ---\ □:z >° o I 21 T o ó^0? °C t / ZT VU oz 1 CN T / z / —Ç )>—' Z. / / CN ο I Petition 870260028627, dated 3 / 26 / 2026, p. 39 / 130 31 / 88 Compound Structure 22 °Y0H HN^ 1 J. NI ° Η2ΝχΝγ^Ν^Νχ°Η &-JHHSJ 23 T oo^O ZI AL I Γ T. OA z \\ CM oi 24 z Oc zy— z \ □= ΐ Z o ΞΕ 25 ___ / ΞΕ Z >----' k> T zlo ΞΕ 26 ΗΝγΝΗ2<ZX L O nX S o y-oH h2nAvnXxnAnÁ n-o H Yy J 27 X SA ro / \ 2 7-- / Z \ V j N> Az z— yx i TZ o ΖΕ Petition 870260028627, de 26 / 03 / 2026, pág. 40 / 130 32 / 88 Compound Structure 28 TV 7 N> \ / z T.-Z. >O o I 29 ΞΕ ro Z >--- f ,2 z—ç ΞΖ oz 30 hn^nh2 HN^ HC xl lo í VX > o yon h2n'^nY^n^nA N-0 HXJ 31 ΗΝγΝΗn-Xn-Xn-Xn H2 H2 X o / °yo Yx J 32 I o O^~Çj °=< ΞΓ VL o Z 1 XsZ ΞΕ / ° \ ^ / / <N O 33 ΟγγΟΗ X Ca ? θ Q\ H2N J / VoH Ν'Ο H Petição 870260028627, de 26 / 03 / 2026, pág. 41 / 130 33 / 88 Composto Estrutura 34 z P K> / / Z / --V ' O / T z=\ \>X^O 1 OI 35 z P z ,--VX—7 o / I z=\ ΞΕΖ Λζ^° OI 36 ΗΝγΝΗ2 OH HN. N Ύ k Jp 1 = í? ( H Η2ΛΛγΝ<ΑΝΛΛΛγΗ MHH Ã J 37 ΗΝγΗΗ2 ΟγΟΗ HN η2νΛΥΥνννννΛοοH JN M20H^ â Ο Ο<γΟΗ / ^Ν / γΝγ'Ν^Ν'Λ H LJ HJ 39 TON> / / Z / —X \ / / -----' IZ / O Petition 870260028627, dated 3 / 26 / 2026, p. 42 / 130 34 / 88 Compound Structure 40 Q o^O ZI Cl / ----( Vi 1 ° H \' Z. / / CM Ο I 41 CM T ΞΕ Ζ,—χ ° '--\ \=O ZI ZI CM AZ T / Z y—< \' Z. / / Cxl O x 42 Ο γ γ γ γ γ 12 Η f hAVnVA '' fi—ii—i II N-0 π n OJ 43 CM TT ° \—\}=o zx CM ZI VXo o ZI VsZ CM » ( / \ z \\ CM OX 44 hn^nh2 O^OHHN I ί S ° H2nYí'N^An^N^N^H N^H 43 H HN^NH2 ^H2 O^OHHN A ! - 0 1 u MA / N^xMAhlA / 0H H2N γ y NN NO H Η H Petition 870260028627, of 26 / 03 / 2026, p. 43 / 130 35 / 88 Compound Structure 46 ΗΝγΝΗ2 CK / OH HN. VJ LLL nh 1 - 0 hAV / nV MHHSJ 47 ΗΝγΝΗ2 °γ0Η A oh 7 S. ο Λ hAnãaAoh Γ4 HH â J 48 ΗΝγΝΗ2 CK^OH HN. 1 - 0 h2n\nÁnAnVH Λ-ο HH â J 49 ZI M ZT y? oi AT / \— ~Z- / / <N O I 50 I I o o v° O Y—\ ZT CM T / )> — 'Z- / / CXI OI 51 HNx,NH2 O^OHHN O <yOH ! ° i H2N yNY / XNz^N γΟΗ N-0 H Η H . Petition 870260028627, of 26 / 03 / 2026, p. 44 / 130 36 / 88 stereoisomers of the same.

[0119] In certain embodiments, the present invention provides a compound selected from: Compound Structure 2 N> / \ Z / ----' ~Z- \ J □: 2 N> Z^A 1 z O _γ ) 1 | / O IZ o I 3 hn^nh2 CK^OH HN k S o °yoH η2ν'^ΝΥ^ν^νΑ N-0 H IV J Petition 870260028627, dated 03 / 26 / 2026, p. 45 / 130 37 / 88 5 τ PZ / —\ 1 / z °A í} · « 11 ' K) IZ >° o T 6 TO / 'C; ZI <N T / Z / —< \— Z / / <n O T 7 =\ ά / > ° \ / ^° ZI MT / ZT ) / Δρ oz 1 VsZ OJ T / Z / —f ~z. \ / <n pi - x 8 t o )="o" cm ( \ z --' zt. °="(" zi v u o 2 1 vsz γ 10 hn^nhs gk,nh2hn, -ív ύ ί jlj>LO H2NÁVNyANANÁYOH NO HHO · J 12 =1= PZ y-- °Λ Y s >•'11' N> TZ )=oo TZ ,-- z O=( 1? o T Petition 870260028627, dated 03 / 26 / 2026, p. 46 / 130 38 / 88 14 N-—, _ <;ã n H 1 0 Ϊ NO N 0 J 16 X o A ZI QZ CN <Z0 °Ã T / ZT VÃ O z 1 CN X / \—' / / CM o I 41 nh2 CA / NH2 J i 0 ! A. A .OH h2n Y y n n Y N-o H H o J 42 O<Y / NH2 o^nh2 ! 0 I Η2ΝΥ^ΝΑΝγθΗ M H H â J Petition 870260028627, dated 03 / 26 / 2026, p. 47 / 130 39 / 88 43 nh2 NH °YNH2 k Nrl2 ] Γ crY \ ο T zY M Ί IZ >° IZ oo=( '— oo or a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof.

[0120] In a certain embodiment, the present invention provides a pharmaceutical composition comprising the compound as disclosed herein, optionally mixed with a pharmaceutically acceptable carrier or diluent.

[0121] The present invention also provides methods for formulating the disclosed compounds for pharmaceutical administration.

[0122] The compositions and methods of the present invention can be used to treat an individual in need thereof. In certain embodiments, the individual is a mammal, such as a human or non-human mammal. When administered to an animal, such as a human, the composition or compound is preferably administered as a pharmaceutical composition comprising, for example, a compound of the invention and a pharmaceutically acceptable carrier. In a preferred embodiment, when these pharmaceutical compositions are for human administration, particularly for invasive routes of administration (i.e., routes such as injection or implantation, which bypass transport or diffusion across an epithelial barrier), the aqueous solution Petition 870260028627, dated 03 / 26 / 2026, page 48 / 130 40 / 88 is pyrogen-free, or substantially pyrogen-free. Excipients may be chosen, for example, to effect delayed release of an agent or to selectively target one or more cells, tissues or organs. The pharmaceutical composition may be in the form of dosage units such as tablets, capsules (including spray capsules and gelatin capsules), granules, lyophilized powder for reconstitution, powder, solution, syrup, suppository, injection or similar. The composition may also be present in a transdermal delivery system, for example, a skin patch. The composition may also be present in a solution suitable for topical administration, such as eye drops.

[0123] A pharmaceutically acceptable carrier may contain physiologically acceptable agents that act, for example, to stabilize, increase the solubility, or increase the absorption of a compound, such as the compounds of the present invention. These physiologically acceptable agents include, for example, carbohydrates such as glucose, sucrose, or dextrans, antioxidants such as ascorbic acid or glutathione, chelating agents, low molecular weight proteins, or other stabilizers or excipients. The choice of a pharmaceutically acceptable carrier, including a physiologically acceptable agent, depends, for example, on the route of administration of the composition. The preparation of the pharmaceutical composition may be a self-emulsifying drug delivery system or a self-microemulsifying drug delivery system.The pharmaceutical composition (preparation) may also be a liposome or other polymeric matrix, which may incorporate, for example, a compound of the invention. Liposomes, for example, comprising phospholipids or other lipids, are physiologically acceptable and metabolizable non-toxic carriers that are relatively simple to manufacture and administer.

[0124] The expression "pharmaceutically acceptable" is used in this document to refer to these compounds, materials, compositions and / or forms of Petition 870260028627, dated 03 / 26 / 2026, page 49 / 130 41 / 88 dosages that are, within the scope of medical judgment, suitable for use in contact with the tissues of humans and animals without excessive toxicity, irritation, allergic response, or other problem or complication, assessed according to a reasonable risk / benefit ratio.

[0125] The phrase "pharmaceutically acceptable carrier," as used in this document, means a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulation material. Each carrier must be acceptable in the sense of being compatible with the other ingredients in the formulation and not harmful to the patient. Some examples of materials that may serve as pharmaceutically acceptable vehicles include: (1) sugars, such as glucose, lactose, and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose and its derivatives, such as sodium carboxymethylcellulose, ethylcellulose, and cellulose acetate; (4) tragacanth powder; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, sunflower oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil;(10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) phosphate buffer solutions; and (21) other compatible non-toxic substances used in pharmaceutical formulations.

[0126] A pharmaceutical composition (preparation) may be administered to a subject by any number of routes of administration including, for example, orally (e.g., liquid remedies such as in aqueous or non-aqueous solutions or suspensions, tablets, capsules (including spray capsules and gelatin capsules), boluses, powders, granules, pastes for application to the tongue); absorption through Petition 870260028627, dated 03 / 26 / 2026, page 50 / 130 42 / 88 of the buccal mucosa (e.g., sublingual); anal, rectal, or vaginal (e.g., as a pessary, cream, or foam); parenteral (including intramuscular, intravenous, subcutaneous, or intrathecal, such as a sterile solution or suspension); nasal; intraperitoneal; subcutaneous; transdermal (e.g., as a patch applied to the skin); and topical (e.g., as a cream, ointment, or spray applied to the skin, or as eye drops). The compound may also be formulated for inhalation. In certain embodiments, a compound may simply be dissolved or suspended in sterile water.

[0127] Formulations may conveniently be presented in unit dosage form and may be prepared according to any of the methods known in the field of pharmaceutical art. The amount of active ingredient that can be combined with the carrier material to produce a single dosage form will vary depending on the host treated and the specific mode of administration. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will generally be that amount of the compound that produces a therapeutic effect. Generally, from one hundred percent, this amount will vary from about 1 percent to about ninety-nine percent of active ingredient, preferably from about 5 percent to about 70 percent, more preferably from about 10 percent to about 30 percent.

[0128] The methods for preparing these formulations or compositions include the step of combining an active compound, such as a compound of the present invention, with the carrier and, optionally, one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately combining a compound of the present invention with liquid carriers or finely divided solid carriers or both and then, if necessary, molding the product. Petition 870260028627, dated 03 / 26 / 2026, page 51 / 130 43 / 88

[0129] The formulations of the invention suitable for oral administration may be in the form of capsules (including spray capsules and gelatin capsules), wafers, pills, tablets, pellets (using a flavored base, typically sucrose and acacia or tragacanth), lyophilized powder, granules, or as a solution or suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion, or as an elixir or syrup, or as lozenges (using an inert base, such as gelatin and glycerin, or sucrose and acacia) and / or as mouthwashes and the like, each containing a predetermined amount of a compound of the present invention as the active ingredient. The compositions or compounds may also be administered as a bolus, electuary, or paste.

[0130] To prepare solid dosage forms for oral administration (capsules (including spray capsules and gelatin capsules), tablets, pills, dragees, powders, granules and the like), the active ingredient is mixed with one or more pharmaceutically acceptable carriers, such as sodium citrate or dicalcium phosphate, and / or any of the following: (1) fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol and / or silicic acid; (2) binders, such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and / or acacia; (3) humectants, such as glycerol; (4) disintegrating agents, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates and sodium carbonate; (5) solution retarders, such as paraffin; (6) absorption accelerators, such as quaternary ammonium compounds;(7) wetting agents, such as, for example, cetyl alcohol and glycerol monostearate; (8) absorbents, such as kaolin and bentonite clay; (9) lubricants, such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate and mixtures thereof; (10) complexing agents, such as modified and unmodified cyclodextrins; and (11) agents; Petition 870260028627, dated 03 / 26 / 2026, page 52 / 130 44 / 88 colorants. In the case of capsules (including spray capsules and gelatin capsules), tablets and pills, the pharmaceutical compositions may also comprise buffering agents. Solid compositions of a similar type may also be used as fillers in soft and hard gelatin-filled capsules using excipients such as lactose or milk sugars, as well as high molecular weight polyethylene glycols and the like.

[0131] A tablet can be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets can be prepared using a binder (e.g., gelatin or hydroxypropyl methylcellulose), lubricant, inert diluent, preservative, disintegrant (e.g., sodium starch glycolate or cross-linked sodium carboxymethylcellulose), surfactant or dispersant. Molded tablets can be made by molding, in a suitable machine, a mixture of the moistened powder compound with an inert diluent liquid.

[0132] Tablets and other solid dosage forms of pharmaceutical compositions, such as coated tablets, capsules (including spray capsules and gelatin capsules), pills and granules, may optionally be scored or prepared with coatings and shells, such as enteric coatings and other coatings known in the pharmaceutical formulation art. They may also be formulated to provide slow or controlled release of the active ingredient, using, for example, hydroxypropylmethylcellulose in varying proportions to provide the desired release profile, other polymeric matrices, liposomes and / or microspheres. They may be sterilized, for example, by filtration through a bacteria-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions that may be dissolved in sterile water or some other sterile injectable medium immediately before use.These compositions may also optionally contain opacifying agents and may be of a composition that releases the active ingredient(s) only, or... Petition 870260028627, dated 03 / 26 / 2026, page 53 / 130 45 / 88 preferably, in a certain portion of the intestinal tract, optionally in a delayed manner. Examples of incorporation compositions that may be used include waxes and polymeric substances. The active ingredient may also be in microencapsulated form, if appropriate, with one or more of the excipients described above.

[0133] Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, lyophilized powders for reconstitution, microemulsions, solutions, suspensions, syrups, and elixirs. In addition to the active ingredient, liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, cyclodextrins and derivatives thereof, solubilizing and emulsifying agents such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils (in particular, cottonseed, peanut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofuryl alcohol, polyethylene glycols, and sorbitan fatty acid esters and mixtures thereof.

[0134] In addition to inert diluents, oral compositions may also include adjuvants such as humectants, emulsifiers and suspending agents, sweeteners, flavorings, colorings, fragrances and preservatives.

[0135] Suspensions, in addition to the active compounds, may contain suspending agents such as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum meta-hydroxide, bentonite, agar-agar and tragacanth and mixtures thereof.

[0136] Formulations of pharmaceutical compositions for rectal, vaginal or urethral administration may be presented as a suppository, which may be prepared by mixing one or more active compounds with one or more suitable non-irritating excipients or carriers comprising, for example, cocoa butter, polyethylene glycol, a suppository wax or a salicylate and which are Petition 870260028627, dated 03 / 26 / 2026, page 54 / 130 46 / 88 are solid at room temperature, but liquid at body temperature and will therefore melt in the rectum or vaginal cavity and release the active compound.

[0137] Pharmaceutical formulations for oral administration may be presented as a mouthwash, an oral spray, or an oral ointment.

[0138] Alternatively or additionally, the compositions may be formulated for delivery via a catheter, stent, wire, or other intraluminal device. Administration via these devices may be especially useful for delivery to the bladder, urethra, ureter, rectum, or bowel.

[0139] Formulations that are suitable for vaginal administration also include pessaries, tampons, creams, gels, pastes, foams or spray formulations that contain such carriers as are known in the art to be appropriate.

[0140] Dosage forms for topical or transdermal administration include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches, and inhalants. The active compound may be mixed under sterile conditions with a pharmaceutically acceptable carrier and with any preservatives, buffers, or propellants that may be required.

[0141] Ointments, pastes, creams and gels may contain, in addition to an active compound, excipients such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof.

[0142] Powders and sprays may contain, in addition to an active compound, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays may additionally contain common propellants such as chlorofluorohydrocarbons and substituted volatile hydrocarbons such as butane and propane. Petition 870260028627, dated 03 / 26 / 2026, page 55 / 130 47 / 88

[0143] Transdermal patches have the added advantage of providing controlled delivery of a compound of the present invention to the body. Such dosage forms can be made by dissolving or dispersing the compound in the appropriate medium. Absorption enhancers can also be used to increase the flux of the compound through the skin. The rate of such flux can be controlled by providing a membrane control rate or by dispersing the compound in a polymer or gel matrix.

[0144] The phrases parenteral administration and administered parenterally, as used in this document, mean modes of administration other than enteric and topical administration, typically by injection, and include, without limitation, intravenous, intramuscular, intra-arterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intra-articular, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion.

[0145] Pharmaceutical compositions suitable for parenteral administration comprise one or more active compounds in combination with one or more pharmaceutically acceptable sterile isotonic aqueous or non-aqueous solutions, dispersions, suspensions or emulsions or sterile powders that can be reconstituted into sterile injectable solutions or dispersions immediately prior to use, which may contain antioxidants, buffers, bacteriostatics, solutes that make the formulation isotonic with the blood of the intended recipient or with the suspension or thickening agents.

[0146] Examples of suitable aqueous and non-aqueous carriers that can be employed in the pharmaceutical compositions of the invention include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like) and suitable mixtures thereof, vegetable oils such as olive oil and injectable organic esters such as ethyl oleate. Appropriate fluidity can be maintained by Petition 870260028627, dated 03 / 26 / 2026, page 56 / 130 48 / 88 for example, by using coating materials such as lecithin, by maintaining the necessary particle size in the case of dispersions, and by using surfactants.

[0147] These compositions may also contain adjuvants such as preservatives, humectants, emulsifying agents and dispersing agents. Prevention of microorganism action can be ensured by the inclusion of various antibacterial and antifungal agents, for example, parabens, chlorobutanol, sorbic acid, phenol and the like. It may also be desirable to include isotonic agents such as, for example, sugars, sodium chloride and the like in the compositions. In addition, prolonged absorption of the injectable pharmaceutical form can be achieved by the inclusion of absorption-retardant agents, such as aluminum monostearate and gelatin.

[0148] In some cases, in order to prolong the effect of a drug, it is desirable to slow down the absorption of the drug from subcutaneous or intramuscular injection. This can be achieved by using a liquid suspension of crystalline or amorphous material with low solubility in water. The rate of drug absorption then depends on its dissolution rate, which in turn may depend on the crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered pharmacological form is achieved by dissolving or suspending the drug in an oily vehicle.

[0149] Injectable depot formulations are made by forming microencapsulated matrices of the compounds in question in biodegradable polymers, such as polylactide-polyglycolide. Depending on the drug-to-polymer ratio and the nature of the particular polymer employed, the drug release rate can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Injectable depot formulations are also prepared by trapping the drug in liposomes or microemulsions that are compatible with body tissue. Petition 870260028627, dated 03 / 26 / 2026, page 57 / 130 49 / 88

[0150] For use in the methods of the present invention, the active compounds may be given per se or as a pharmaceutical composition containing, for example, 0.1 to 99.5% (more preferably, 0.5 to 90%) of active ingredient in combination with a pharmaceutically acceptable carrier.

[0151] Delivery methods can also be provided by rechargeable or biodegradable devices. Several slow-release polymeric devices have been developed and tested in vivo in recent years for the controlled delivery of drugs, including proteinaceous biopharmaceuticals. A variety of biocompatible polymers (including hydrogels), including both biodegradable and non-degradable polymers, can be used to form an implant for the sustained release of a compound to a specific target site.

[0152] Actual dosage levels of the active ingredients in pharmaceutical compositions may be varied in order to obtain an amount of the active ingredient that is effective in achieving the desired therapeutic response for a particular patient, composition and route of administration, without being toxic to the patient.

[0153] The dosage level selected will depend on a variety of factors, including the activity of the particular compound or combination of compounds employed, or the ester, or salt, or starch thereof, the route of administration, the time of administration, the excretion rate of the particular compound being employed, the duration of treatment, other drugs, compounds and / or materials used in combination with the specific compounds employed, the age, gender, weight, condition, general health and previous medical history of the patient to be treated and similar factors well known in medical techniques.

[0154] In general, an adequate daily dose of an active compound used in the compositions and methods of the invention will be the amount of the compound that is the lowest effective dose to produce a therapeutic effect. This effective dose will generally depend on the factors described above. Petition 870260028627, dated 03 / 26 / 2026, page 58 / 130 50 / 88

[0155] If desired, the effective daily dose of the active compound may be administered as one, two, three, four, five, six or more sub-doses administered separately at appropriate intervals throughout the day, optionally in unit dosage forms. In certain embodiments of the present invention, the active compound may be administered two or three times a day. In preferred embodiments, the active compound will be administered once a day.

[0156] The patient receiving this treatment is any animal in need, including primates, particularly humans, and other mammals such as horses, cattle, pigs and sheep; and birds and pets in general.

[0157] Humectants, emulsifiers and lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweeteners, flavorings and fragrances, preservatives and antioxidants may also be present in the compositions.

[0158] Examples of pharmaceutically acceptable antioxidants include: (1) water-soluble antioxidants, such as ascorbic acid, cysteine ​​hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite and the like; (2) oil-soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, alpha-tocopherol and the like; and (3) metal chelating agents, such as citric acid, ethylenediaminetetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid and the like.

[0159] In certain embodiments, the compounds described in this document enhance the phagocytic activity of macrophages towards a cancerous cell, for example, an AML cell. In other embodiments, phagocytic activity is enhanced, for example, by 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80% or 90%, relative to a macrophage in the absence of the compounds described in this document. Petition 870260028627, dated 03 / 26 / 2026, page 59 / 130 51 / 88

[0160] In certain embodiments, the present invention provides uses of compounds of the present invention for the preparation of a medicament.

[0161] In certain embodiments, the present invention provides uses of compounds of the present invention for the preparation of a medicament, for example, for the treatment of cancer.

[0162] In certain embodiments, the present invention provides methods for the treatment of cancer, wherein the method comprises administering compounds of the present invention, for example, in a therapeutically effective amount, to the subject in need.

[0163] In certain embodiments, the present invention provides methods for inhibiting the growth of tumor cells and / or metastases by administering a compound of the present invention, for example, in a therapeutically effective amount, to the subject in need.

[0164] In certain embodiments, the present invention provides the compound of formula (I), or a pharmaceutically acceptable salt or an amide or an ester, or a stereoisomer thereof, for the treatment of cancer, wherein, Ra is hydrogen; and Ri represents hydrogen, -(CH2)2CONH2, -(CH2)2COOH, CH2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, -CH(CH3)-CH2-CH3, CH2-aryl, or -CH2-heteroaryl; wherein said aryl and heteroaryl are not substituted; or Ra and R1, together with the atoms to which they are attached, form a pyrrolidine ring optionally substituted with the oxo group; R2 represents hydrogen, -CH2-OH, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, (CH2)2COOH, -CH2-aryl, or -CH2-heteroaryl; wherein said aryl and heteroaryl are not substituted; Rb is hydrogen; and R3 represents hydrogen, -CH2-aryl, -(CH2)3NHC(=NH)NH2, -CH2COOH, -CH(CH3)-CH2-CH3, -CH2-CH(CH3)2, -(CH2)2CONH2, -(CH2)2COOH, (CH2)4NH2 or -CH2-heteroaryl; wherein said aryl and heteroaryl are not substituted; Petition 870260028627, dated 03 / 26 / 2026, page 60 / 130 52 / 88 or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

[0165] Representative tumor cells include cancer cells such as, but not limited to, melanoma, renal cancer, prostate cancer, breast cancer, colon cancer and lung cancer, bone cancer, pancreatic cancer, skin cancer, head or neck cancer, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, anal region cancer, stomach cancer, testicular cancer, fallopian tube carcinoma, endometrial carcinoma, cervical carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, non-Hodgkin's lymphoma, esophageal cancer, small bowel cancer, endocrine system cancer, thyroid gland cancer, parathyroid gland cancer, adrenal gland cancer, soft tissue sarcoma, urethral cancer, penile cancer, chronic or acute leukemias, including acute myeloid leukemia, chronic myeloid leukemia, leukemia acute lymphoblastic leukemia, chronic lymphocytic leukemia, solid tumors of childhood,Lymphocytic lymphoma, bladder cancer, kidney or ureter cancer, renal pelvis carcinoma, central nervous system (CNS) neoplasm, non-small cell lung cancer (NSCLC), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brainstem glioma, pituitary adenoma, Kaposi's sarcoma, squamous cell carcinoma, squamous cell carcinoma, T-cell lymphoma, B-cell lymphomas, environmentally induced cancers, including those induced by asbestos (e.g., mesothelioma), and combinations of these cancers.

[0166] In certain embodiments, the present invention provides uses of compounds of the present invention for the preparation of a medicament for the treatment of bacterial, viral and fungal infections, as well as methods of administering compounds of the present invention, for example, in a therapeutically effective amount, for the treatment of a bacterial, viral or fungal infection. Petition 870260028627, dated 03 / 26 / 2026, page 61 / 130 53 / 88 fungal.

[0167] Still other embodiments of the present invention provide methods of treating infection by blocking the CD-47 pathway, comprising administering a compound of the present invention to the subject in need thereof, for example, in a therapeutically effective amount.

[0168] In certain embodiments, the invention provides uses of compounds of the present invention in inhibiting the CD-47 pathway.

[0169] In certain embodiments, the present invention provides methods for treating infectious diseases in a subject comprising administering a compound of the present invention, for example, in a therapeutically effective amount, for the treatment of the infectious disease.

[0170] Representative infectious diseases include but are not limited to HIV, influenza, herpes, Giardia, malaria, Leishmania, pathogenic infection by Hepatitis viruses (A, B and C), herpes viruses (e.g., VZV, HSV-I, HAV-6, HSV-II and CMV, Epstein-Barr virus), adenovirus, influenza virus, flavivirus, echovirus, rhinovirus, coxsackievirus, respiratory syncytial virus, mumps virus, rotavirus, measles virus, rubella virus, parvovirus, vaccine virus, HTLV virus, dengue virus, papillomavirus, molluscum contagiosum virus, poliovirus, rabies virus, JC virus and arboviral encephalitis virus, pathogenic infection by Chlamydia bacteria, rickettsial bacteria, mycobacteria, staphylococci, streptococci, pneumococci, meningococci and conococoss, klebsiella, proteus, serratia, pseudomonas, E.E. coli, Legionella, diphtheria, Salmonella, bacilli, cholera, tetanus, botulism, anthrax, plague, leptospirosis, and Lyme disease bacteria; pathogenic infection by the fungi Candida (albicans, krusei, glabrata, tropicalis, etc.), Cryptococcus neoformans, Aspergillus (fumigatus, niger, etc.), Genus Mucorales (mucor, absidia, rhizophus), Sporothrix schenkii, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Coccidioides immitis, and Histoplasma capsulatum; and pathogenic infection by the parasites Entamoeba. Petition 870260028627, dated 03 / 26 / 2026, page 62 / 130 54 / 88 histolytica, Balantidium coli, Naegleriafowleri, Acanthamoeba sp., Giardia lambia, Cryptosporidium sp., Pneumocystis carinii, Plasmodium vivax, Babesia microti, Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondi or Nippostrongylus brasiliensis.

[0171] In certain embodiments, the present invention provides a method for treating or delaying the progression of CD47-mediated atherosclerosis and multiple sclerosis in an individual, wherein the method comprises administering to said individual an effective amount of a compound of formula (I).

[0172] In certain embodiments, the present invention provides methods for the treatment of atherosclerosis and multiple sclerosis in a subject comprising administering a therapeutically effective amount of compound of formula (I).

[0173] The compounds may be used alone, or preferably in a pharmaceutical composition in which the compound is mixed with one or more pharmaceutically acceptable materials.

[0174] The term treatment includes prophylactic and / or therapeutic treatments. The term prophylactic or therapeutic treatment is recognized in the art and includes the administration to the host of one or more of the compositions in question. If administered before the clinical manifestation of the undesirable condition (e.g., disease or other undesirable state of the host animal), then the treatment is prophylactic (i.e., it protects the host against the development of the undesirable condition), whereas if the composition in question is administered after the manifestation of the undesirable condition, the treatment is therapeutic (i.e., it is intended to reduce, improve or stabilize the existing undesirable condition or its side effects).

[0175] As used in this document, the term "compound(s)" includes compounds with formula (I), (IA), (IB), (IC), (ID), (IE), (IF) and their salts or Petition 870260028627, dated 03 / 26 / 2026, page 63 / 130 55 / 88 pharmaceutically acceptable stereoisomers thereof.

[0176] The term aryl, as used in this document, includes single-ring aromatic groups, substituted or unsubstituted, in which each ring atom is carbon. Preferably, the ring is a 5- to 7-membered ring, more preferably a 6-membered ring. The term aryl also includes polycyclic ring systems having two or more cyclic rings, in which two or more carbons are common to the two adjacent rings, wherein at least one of the rings is aromatic, for example, the other cyclic rings may be cycloalkyls, cycloalkenes, cycloalkynes, aries, heteroaryls, or heterocyclides. Aryl groups include benzene, naphthalene, phenanthrene, phenol, aniline, and the like. Preferably, the term "aryl" includes phenyl.

[0177] The term heteroaryl includes, unless otherwise specified, single-ring aromatic substituted or unsubstituted rings, preferably rings with 5 to 7 members, more preferably rings with 5 to 6 members, whose ring structures include at least one heteroatom, preferably one to four heteroatoms, more preferably two heteroatoms. The term heteroaryl and heteroaryl also include polycyclic ring systems having two or more cyclic rings, in which two or more carbons are common to the two adjacent rings, wherein at least one of the rings is heteroaromatic, for example, the other cyclic rings may be cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, and / or heterocyclyl. Heteroaryl groups include, for example, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine, indole, 1,2,4-oxadiazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole, benzimidazole, pyrimidine, and the like.A heteroaryl group may be substituted in one or more positions, as permitted by valence, with any optional substituents described in this document. Preferably, the term "heteroaryl" includes imidazolyl and indolyl.

[0178] The term acyl is recognized in the art and refers to a group represented by the general formula alkyl-C(O)—. Examples of the "acyl" group are, but Petition 870260028627, dated 03 / 26 / 2026, p. 64 / 130 56 / 88 not limited to, acetyl, propionyl and butyryl.

[0179] As used in this document, a therapeutic that prevents a disorder or condition refers to a compound that, in a statistical sample, reduces the occurrence of the disorder or condition in the treated sample relative to an untreated control sample or delays the onset or reduces the severity of one or more symptoms of the disorder or condition relative to the untreated control sample.

[0180] The term treatment includes prophylactic and / or therapeutic treatments. The term prophylactic or therapeutic treatment is recognized in the art and includes the administration to the host of one or more of the compositions in question. If administered before the clinical manifestation of the undesirable condition (e.g., disease or other undesirable state of the host animal), then the treatment is prophylactic (i.e., it protects the host against the development of the undesirable condition), whereas if the composition in question is administered after the manifestation of the undesirable condition, the treatment is therapeutic (i.e., it is intended to reduce, improve or stabilize the existing undesirable condition or its side effects).

[0181] As used herein, the phrase delaying progression refers to procedures or applications that aim to delay the development of a disease or symptoms of a disease (including delaying the appearance or occurrence of at least one symptom in a particular individual).

[0182] The term prodrug is intended to encompass compounds that, under physiological conditions, are converted into the therapeutically active agents of the present disclosure (for example, a compound of formula (I)). A common method of producing a prodrug is to include one or more selected fractions that are hydrolyzed under physiological conditions to reveal the desired molecule. In other embodiments, the prodrug is converted by an enzymatic activity of the animal. Petition 870260028627, dated 03 / 26 / 2026, page 65 / 130 57 / 88 host. For example, esters or carbonates (e.g., esters or carbonates of alcohols or carboxylic acids) are preferred prodrugs of the present invention. In certain embodiments, some or all of the compounds of formula (I) in a formulation represented above may be replaced by the corresponding suitable prodrug, for example, wherein a hydroxyl group in the precursor compound is presented as an ester or a carbonate or carboxylic acid present in the precursor compound is presented as an ester.

[0183] As used here, the term includes or comprising is generally used in the sense of including, that is, allowing the presence of one or more (unspecified) additional resources or components.

[0184] As used in this document, the term including, as well as other forms such as include, includes and included, is not limiting.

[0185] As used in this document, the term disease or disorder refers to a pathological condition in an organism resulting from a cause or condition including, but not limited to, infections, acquired conditions, genetic conditions and characterized by identifiable symptoms. Diseases and disorders also include those caused by the absence of a compound, such as TIGIT modulators.

[0186] As used in this document, patient or subject or individual to be treated includes human beings and / or non-human animals, including mammals. Mammals include primates, such as humans, chimpanzees, gorillas and monkeys; domesticated animals, such as dogs, horses, cats, pigs, goats, cows; and rodents such as rats, mice, hamsters and gerbils.

[0187] This invention includes the use of pharmaceutically acceptable salts of compounds of the invention in the compositions and methods of the present invention. In certain embodiments, the salts contemplated in the invention include, but are not limited to, alkyl, dialkyl, trialkyl, or tetraalkyl ammonium salts. In certain embodiments, the salts contemplated in the invention include, but are not limited to, Petition 870260028627, dated 03 / 26 / 2026, page 66 / 130 58 / 88 L-arginine, berentamine, benzathine, betaine, calcium hydroxide, choline, deanol, diethanolamine, diethylamine, 2-(diethylamino)ethanol, ethanolamine, ethylenediamine, N-methylglucamine, hydrabamine, 1H-imidazole, lithium, L-lysine, magnesium, 4-(2-hydroxyethyl)morpholine, piperazine, potassium, 1-(2-hydroxyethyl)pyrrolidine, sodium, triethanolamine, tromethamine, and zinc salts. In certain embodiments, the salts contemplated in the invention include, but are not limited to, Na, Ca, K, Mg, Zn, or other metallic salts.

[0188] Pharmaceutically acceptable acid addition salts may also exist as various solvates, such as water, methanol, ethanol, dimethylformamide and the like. Mixtures of such solvates may also be prepared. The source of this solvate may be the crystallization solvent, inherent in the preparation or crystallization solvent, or incidental to that solvent.

[0189] As used in this document, the term pharmaceutically acceptable salt is intended to include all salts known and used in the pharmaceutical art. Pharmaceutically acceptable salts include, but are not limited to, amine salts, such as, but not limited to, chloroprocaine, choline, N,N'-dibenzylethylenediamine, ammonia, diethanolamine and other hydroxyalkylamines, ethylenediamine, N-methylglucamine, procaine, N-benzylphenethylamine, 1-para-chlorobenzyl-2-pyrrolidin-1'-ylmethylbenzimidazole, diethylamine and other alkylamines, piperazine and tris(hydroxymethyl)aminomethane; alkali metal salts, such as, without limitation, lithium, potassium and sodium; alkaline earth metal salts, such as, without limitation, barium, calcium and magnesium; transition metal salts, such as, but not limited to, zinc; and other metallic salts, such as, without limitation, sodium hydrogen phosphate and disodium phosphate;and also including, without limitation, salts of mineral acids, such as, without limitation, hydrochlorides and sulfates; and salts of organic acids, such as, without limitation, acetates, lactates, malates, tartrates, citrates, ascorbates, succinates, butyrates, valerates and fumarates. Examples of pharmaceutically acceptable salts include; Petition 870260028627, dated 03 / 26 / 2026, page 67 / 130 59 / 88 acetate, lactobionate, benzenesulfonate, laurate, benzoate, malate, bicarbonate, maleate, bisulfate, mandelate, bitartrate, mesylate, borate, methyl bromide, methyl nitrate, calcium edetate, methyl sulfate, camsylate, mucate, carbonate, natochloride, nitrate, clavulanate, N-methylglucamine, citrate, ammonium salt, dihydrochloride, oleate, edetate, oxalate, edisilate, pamoate (embonate), estolate, palmitate, esilate, pantothenate, fumarate, phosphate / diphosphate, gluceptate, polygalactonate, polygalactonate salicylate, glutamate, stearate, glycolylarsanilate, sulfate, hexylresorcinate, subacetate, hydrabamine, succinate, hydrobromide, tannate, hydrochloride, tartrate, sodium hydroxynaphtate, theoaclate, iodide, tosylate, triethiodide as dosage form and lactate, background, hydrochloride, iodide, tosylate, triethiodide, theoaclate, iodide, tosylate, triethiodide,It can be used as a way to modify solubility or hydrolysis characteristics, or it can be used in sustained-release or prodrug formulations. The preparation of the pharmaceutically acceptable salts described above and other typical pharmaceutically acceptable salts is more fully described by Berg et al., Pharmaceutical Salts, J. Pharm. Sci. 66: 1-19 (1977).

[0190] In certain preferred embodiments, the invention includes pharmaceutically acceptable salts of compounds of the invention and their use in the methods and compositions of the present invention. In certain embodiments, the salts contemplated in the invention include, but are not limited to, alkyl, dialkyl, trialkyl, or tetraalkyl ammonium salts. In certain embodiments, the salts contemplated in the invention include, but are not limited to, L-arginine, benentamine, benzathine, betaine, calcium hydroxide, choline, deanol, diethanolamine, diethylamine, 2-(diethylamino)ethanol, ethanolamine, ethylenediamine, N-methylglucamine, hydrabamine, 1H-imidazole, lithium, L-lysine, magnesium, 4-(2-hydroxyethyl)morpholine, piperazine, potassium, 1-(2-hydroxyethyl)pyrrolidine, sodium, triethanolamine, tromethamine, and zinc salts. In certain embodiments, the salts contemplated in the invention include, but are not limited to, Na, Ca, K, Mg, Zn, or other metallic salts. Petition 870260028627, dated 03 / 26 / 2026, page 68 / 130 60 / 88

[0191] Pharmaceutically acceptable acid addition salts may also exist as various solvates, such as water, methanol, ethanol, dimethylformamide and the like. Mixtures of such solvates may also be prepared. The source of this solvate may be the crystallization solvent, inherent in the preparation or crystallization solvent, or incidental to that solvent.

[0192] The term stereoisomers refers to any enantiomers, diastereomers, or geometric isomers, such as the compounds of the invention. When the compounds of the disclosure are chiral, they may exist in racemic form or in optically active form. Since the pharmaceutical activity of the racemates or stereoisomers of the compounds according to the invention may differ, it may be desirable to use compounds that are enriched in one of the enantiomers. In these cases, the final product or even the intermediates may be separated into enantiomeric compounds by chemical or physical measures known to those skilled in the art or even employed as such in the synthesis. In the case of racemic amines, diastereomers are formed from the mixture by reaction with an optically active resolving agent.Examples of suitable resolving agents are optically active acids such as the R and S forms of tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid, suitable N-protected amino acids (e.g., N-benzoylproline or N-benzenesulfonylproline), or the various optically active camphorsulfonic acids. Resolution of the chromatographic enantiomer with the aid of an optically active resolving agent (e.g., dinitrobenzoylphenylglycine, cellulose triacetate, or other carbohydrate derivatives or chirally immobilized methacrylate polymers on silica gel) is also advantageous.

[0193] The term ester, as used in this document, refers to a -C(O)ORii group where R11 represents a hydrocarbyl group. Petition 870260028627, dated 03 / 26 / 2026, page 69 / 130 61 / 88

[0194] The term amide, as used in this document, refers to a -C(O)NH2 group.

[0195] In certain embodiments, the compounds of the invention may be racemic. In certain embodiments, the compounds of the invention may be enriched in one enantiomer. For example, a compound of the invention may have more than 30% ee, 40% ee, 50% ee, 60% ee, 70% ee, 80% ee, 90% ee, or even 95% or more ee. In certain embodiments, the compounds of the invention may have more than one stereocenter. In certain such embodiments, the compounds of the invention may be enriched in one or more diastereomers. For example, a compound of the invention may contain more than 30% of, 40% of, 50% of, 60% of, 70% of, 80% of, 90% of, or even 95% or more of.

[0196] The subject term includes mammals (especially humans) and other animals, such as domestic animals (e.g., pets, including cats and dogs) and non-domestic animals (such as wild animals).

[0197] The abbreviations used throughout the descriptive report can be summarized below in this document with their specific meanings.

[0198] oC (degrees Celsius); % (percentage); ACN (Acetonitrile), brine (NaCl solution); CH2Cl2 / DCM (Dichloromethane); Boc (Tert-butyloxycarbonyl); DIC: N,N'-Diisopropylcarbodiimide; DMF (Dimethylformamide); EtOH (Ethanol); Et2NH (Diethylamine); ECF (Ethyl chloroformate), Fmoc (9-Fluorenylmethyloxycarbonyl); g or gr (gram); h or hr (hours); HPLC (High-performance liquid chromatography); K2CO3 (Potassium carbonate); LCMS (Liquid chromatography-mass spectrometry); mmol (Millimoles); M (Molar); μl (Microliter); mL (Milliliter); mg (Milligram); min (Minutes); NaHCO3 (Sodium bicarbonate); NMM (N-Methylmorpholine); Na2SO4 (Sodium sulfate); NH3 (Ammonia), NH2OH.HCl (Hydroxylamine chloride), prep-HPLC / HOBt preparative (Hydroxybenzotriazole); HPLC (High-performance liquid chromatography) Petition 870260028627, dated 03 / 26 / 2026, pp. 70 / 130 62 / 88 preparative); TEA / Et3N (Triethylamine); THF (Tetrahydrofuran); TFA (Trifluoroacetic acid); TFAA (Trifluoroacetic acid anhydrous), TIPS (Triisopropylsilane); tR (Retention time); EXPERIMENTAL

[0199] The present invention provides methods for preparing compounds of formula (I) according to the procedures of the following examples, using appropriate materials. One skilled in the art will readily understand that known variations of the conditions and processes of the following preparative procedures can be used to prepare these compounds. Furthermore, using the procedures described in detail, a person skilled in the art can prepare additional compounds of the present invention.

[0200] The intermediates or starting materials required for the synthesis are commercially available (commercial sources such as Sigma-Aldrich, USA or Germany; Chem-Impex USA; GL Biochem, China and Spectrochem, India) or, alternatively, these intermediates or starting materials can be prepared using methods known from the literature. The invention is described in greater detail by means of specific examples. Analytical methods for HPLC: Method 1: Column: ZIC-HILLIC (Sequant), C18 (4.6 X 250 mm, 5 pm) 200A° Flow rate: 1.0 mL / min; Column temperature: 25.0 °C Mobile phase: A = 5 mM ammonium acetate PH-4.0 (acetic acid), IACN Gradient (Tim / % B): 0 / 85, 2 / 85, 20 / 40, 20.1 / 85, 30 / 85. Method 2 Column: Phenomenex Aeris C18 (2) 100A peptide (250 x 4.6 mm, 3.6 μm) Flow rate: 1.0 mL / min; Column temperature: 25.0 °C Mobile phase: A = 0.1% TFA (Aq), B = ACN Petition 870260028627, dated 03 / 26 / 2026, p. 71 / 130 63 / 88 Gradient (Time / %B): 0 / 2, 2 / 2, 15 / 70, 20 / 95, 25 / 100, 30 / 100, 32 / 2, 42 / 2 HPLC preparatory method:

[0201] Preparative HPLC was performed on a Phenomenex Luna 5μ 100A° column (250 mm χ 21.2 mm, 5 μm), flow rate: 15.0 mL / min. The elution conditions used were: Buffer A: 0.1% formic acid in water, Buffer B: acetonitrile, Equilibrium of the column with 0% buffer B and elution by a gradient from 0% to 10% buffer B for 30 min.

[0202] LCMS was performed on the AP1 2000 LC / MS / MS triple quadrupole spectrometer with Agilent 1100 series HPLC with G1315 B DAD, using the Mercury MS column or using the Agilent LC / MSD VL single quadrupole with Agilent 1100 series HPLC with G1315 B DAD, using the Mercury MS column or using the Shimadzu LCMS 2020 single quadrupole with Prominence UFLC system with SPD20 A DAD.

[0203] LCMS was performed on the triple quadrupole AP1 2000 LC / MS / MS (Applied biosystems) with Agilent 1100 series HPLC with G1315 B DAD, using the Mercury MS column or using the single quadrupole Agilent LC / MSD VL with Agilent 1100 series HPLC with G1315 B DAD, using the Mercury MS column or using the single quadrupole Shimadzu LCMS 2020 with Prominence UFLC system with SPD20 A DAD.

[0204] One embodiment of the present invention provides for the preparation of compounds of formula (I) according to the procedures of the following examples, using appropriate materials. One skilled in the art will readily understand that known variations of the conditions and processes of the following preparative procedures can be used to prepare these compounds. Furthermore, using the procedures described in detail, a person skilled in the art can prepare additional compounds of the present invention.

[0205] Starting materials are generally available from sources Petition 870260028627, dated 03 / 26 / 2026, page 72 / 130 64 / 88 commercial companies, such as Sigma-Aldrich, India or Germany; Combi-Blocks USA, Ark Pharm USA, Chem-Impex USA; GL Biochem, China and Spectrochem, India. Example 1: (((S)-4-amino- 1-(3-((S)-1,5-diaminopentyl)-1,2,4-oxadiazol-5-yl)-4oxobutyl)carbamoyl)-Proline-L (Compound 1) Synthesis of compound 1b NHBoc THE

[0206] Ethyl chloroformate (2.47 mL, 25.9 mmol) and NMM (2.9 mL, 25.9 mmol) were added to a solution of compound 1a (6.0 g, 17.3 mmol) in THF (60 mL) and stirred at -20°C for 20 min. After 20 minutes, 25% aqueous ammonia (24 mL) was added to the resulting active mixed anhydride, and the reaction mass was stirred at 5°C for 30 min. The completeness of the reaction was confirmed by TLC analysis. The volatiles were evaporated under reduced pressure and partitioned between water and ethyl acetate. The organic layer was washed with NaHCOa solution followed by citric acid solution and brine solution. The separated organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure to yield 5.6 g of compound 1b. LCMS: 346.4 [M+H]+. Synthesis of compound 1c Petition 870260028627, dated 03 / 26 / 2026, page 73 / 130 65 / 88

[0207] Trifluoroacetic anhydride (6.85 mL, 48.6 mmol) was added to a solution of compound 1b (5.6 g, 16.2 mmol), pyridine (7.84 mL, 97.2 mmol) in DCM (60 mL) at 0 °C and stirred at room temperature for one hour. The completion of the reaction was confirmed by TLC analysis. The volatiles were evaporated under reduced pressure and partitioned between water and CH2Cl2. The organic layer was washed with NaHCO3 solution followed by citric acid solution and brine. The separated organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure to yield 5.42 g of compound 1c, which was used directly in the next step. Synthesis of compound 1d lc ld

[0208] Hydroxylamine hydrochloride (3.43 g, 49.5 mmol), water (10 mL), and K2CO3 (4.54 g, 32.9 mmol) were added to a solution of compound 1c (5.4 g, 16.5 mmol) in EtOH (60 mL) and stirred at room temperature overnight. Completion of the reaction was confirmed by TLC analysis. After completion of the reaction, the compound was extracted from the water using CH2Cl2 followed by washing the organic layer with water, brine, and concentration under reduced pressure to yield 5.8 g of compound 1d. LCMS: 361.3 [M+H]+. Synthesis of compound 1f Petition 870260028627, dated 03 / 26 / 2026, page 74 / 130 66 / 88 ID

[0209] HOBt (3.24 g, 24.0 mmol) and DIC (3.36 mL, 24.0 mmol) were added to a solution of Fmoc-Gln(Trt)-OH (compound 1e) (9.83 g, 16.1 mmol) in DMF (100 mL) at 0 °C and stirred for 15 min. Compound 1d (5.8 g, 16.1 mmol) was added to the reaction mass at the same temperature and the resulting mixture was stirred for one hour at the same temperature, followed by stirring at room temperature for a further 2 h. Completion of the reaction was confirmed by TLC analysis. The reaction mixture was quenched with ice-cold water; the white precipitated solid was filtered; washed with water (150 mL) and dried under reduced high pressure to yield 8.62 g of compound 1f. LCMS: 953.7 [M+H]+. Synthesis of compound 1g

[0210] Acetic acid (5 mL) was added to a solution of compound 1f (5.0 g, 5.0 mmol) in acetonitrile (50 mL) at room temperature, and the reaction mass was refluxed at 85°C for 12 h. The completion of the reaction was confirmed by TLC analysis. The volatiles were evaporated under reduced pressure to obtain a crude semi-solid which was diluted with water and ethyl acetate. The organic layer was washed with NaHCO3 solution followed by citric acid solution and brine. The organic layer was dried over filtered Na2SO4 and evaporated under reduced pressure to obtain the solid. Petition 870260028627, dated 03 / 26 / 2026, page 75 / 130 67 / 88 crude. The compound was purified using column chromatography to give 4.3 g of the title compound. LCMS: 935.6 [M+H]+. Synthesis of compound 1h ig lh

[0211] Compound 1 g (4.3 g, 4.5 mmol) was added to a 20% piperidine solution in DMF (20 mL) at 0°C and the reaction mass was stirred at the same temperature for one hour. The completion of the reaction was confirmed by TLC analysis. After completion, the reaction mixture was quenched with ice-cold water and the resulting white precipitate was filtered and dried under vacuum. The crude product obtained was diluted with hexane, stirred, and filtered to yield 3.0 g of compound 1 h. LCMS: 713.4 [M+H]+ Synthesis of compound 1i

[0212] Pyridine (0.33 mL, 4.2 mmol) was added to a solution of compound 1h (1.5 g, 2.1 mmol) in CH2Cl2 (15 mL) and the resulting solution was stirred at room temperature for 10 min. 4-Nitrophenyl chloroformate (0.84 g, 4.2 mmol) in CH2Cl2 (15 mL) was added to the above mixture and the resulting mixture was stirred at room temperature for one hour. After completion of the reaction (confirmed by TLC), it was diluted with CH2Cl (50 mL) and washed with water (100 mL x 2), 1N HCl (100 mL x 2), water followed by saline solution (100 mL x 2). The organic layer was dried over Na2SO4; filtered and evaporated under reduced pressure to yield 0.72 g of Petition 870260028627, dated 03 / 26 / 2026, page 76 / 130 68 / 88 compound 1i, which was taken to the next step without any further purification. LCMS: 878.9 [M-100]. Synthesis of compound 1j ij

[0213] TEA (0.34 mL, 2.46 mm) was added to a solution of H-ProOtBu.HCl (0.21 g, 1.23 mmol) and compound 1i (0.72 g, 0.82 mmol) in THF (10 mL) at room temperature and stirred for 12 h. The volatiles were evaporated and partitioned between ethyl acetate and water. The reaction mixture was diluted with cold water and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude compound obtained was purified by column chromatography and compound 1i eluted in 50% ethyl acetate in hexane. Yield: 0.5 g of compound 1j. LCMS: 910.6 [M+H]+. Synthesis of Compound 1

[0214] Compound 1j (0.5 g, 0.55 mmol) was added to a cocktail mixture (10 mL) of TFA:TIPS:H2O (95:2.5:2.5) and stirred at room temperature for 3 h. The resulting reaction mixture was evaporated under reduced pressure, diluted with diethyl ether, and filtered to yield 0.2 g of crude compound 1. The crude solid material was purified by the preparative HPLC method described under experimental conditions. LCMS: 412.2 [M+H]+HPLC tR(min): 9.6. Petition 870260028627, dated 03 / 26 / 2026, page 77 / 130 69 / 88

[0215] The compounds below were prepared by a procedure similar to that described in Example 1 (compound 1) with appropriate variations in reagents, amounts of reagents, solvents, and reaction conditions. The characterization data for the compounds are summarized below the table. Compound Structure Observed mass [M+H]+ 2. hn^nh2 HN O^OH XX Ο ΟγθΗ h2nXnyXnX and H 441.4 3. hn^nh2 CU / OH HN Y X_ o 0y0H H2N YNY^N ^NXN—OHO4. CK,NH2 YYO °yOH A. Jk Á H2N Yf -γ N ΝΛ N-0 H Lj 440.3 5. T 0 ZI Y í IU \—' 2 / / <N O I 440,5 6. cy,nh2 X 0 °yoH h2n^yny^n^nX n-o H Yy 341,4 Example 2: acid (S)-4-(3-((S)-1-amino-4-guanidinobutyl)-1,2,4-oxadiazolePetition 870260028627, dated 03 / 26 / 2026, pp. 78 / 130 70 / 88 5-yl)-4-(3-((S)-1)-carboxy-2-phenylethyl)ureide)butanoic (Compound 7) Synthesis of compound 2b 2a 2b

[0216] Ethyl chloroformate (1.75 mL, 18.23 mmol) and NMM (2.0 mL, 18.23 mmol) were added to a solution of compound 2a (8.0 g, 15.18 mmol) in THF (45 mL), and the resulting mixture was stirred at -20°C for 20 min. After 20 minutes, 25% aqueous ammonia (25 mL) was added to the generated active mixed anhydride and stirred at 0-5°C for 30 min. The completeness of the reaction was confirmed by TLC analysis. The volatiles were evaporated under reduced pressure and partitioned between water and ethyl acetate. The organic layer was washed with NaHCOa solution followed by citric acid solution and brine solution. The separated organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure to yield 7.1 g of compound 2b. LCMS: 526.3 [M+H]+. Synthesis of compound 2c HN^NHPbf HN.^NHPbf

[0217] Trifluoroacetic anhydride (TFAA) (2.83 mL, 20.26 mmol) was added to Petition 870260028627, dated 03 / 26 / 2026, page 79 / 130 71 / 88 a solution of compound 2b (7.1 g, 13.51 mmol) in pyridine (7.08 g, 87.80 mmol) and the resulting mixture was stirred at room temperature for 2 h. The completion of the reaction was confirmed by TLC analysis. The volatiles were evaporated under reduced pressure and partitioned between water and ethyl acetate. The organic layer was washed with citric acid and brine solution. The separated organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure. The crude solid was purified by column chromatography (60-120 silica gel) to yield 5.8 g of compound 2c. LCMS: 508.3 [M+H]+. Synthesis of compound 2d HN^NHPbf HN^,NHPbfI HN NH2OH.HC1Ί S K2CO3,EtOHBochN\'NH2BocHN'XYNN OH 2c2d

[0218] Hydroxylamine hydrochloride (1.56 g, 22.50 mmol), water (30 mL), and potassium carbonate (3.11 g, 11.25 mmol) were added to a solution of compound 2c (5.8 g, 11.25 mmol) in EtOH (60 mL) and stirred at 90°C for 3 h. The completion of the reaction was confirmed by TLC analysis. The volatiles were evaporated under reduced pressure and partitioned between water and ethyl acetate. The organic layer was washed with brine solution, dried over Na2SO4, then filtered and evaporated under reduced pressure; the resulting solid was washed with 20% ethyl acetate to yield 6.1 g of compound 2d. LCMS: 541.3 [M+H]+. Synthesis of compound 1e Petition 870260028627, dated 03 / 26 / 2026, pp. 80 / 130 72 / 88

[0219] HOBt (2.28 g, 16.9 mmol) and DIC (2.62 mL, 16.9 mmol) were added to a solution of Fmoc-Glu(OtBu)-OH (compound 2e) (4.0 g, 9.02 mmol) in DMF (60 mL) at 0 °C and the resulting mixture was stirred for 15 min. Then, compound 2d (6.1 g, 11.28 mmol) was added to the above mixture at the same temperature and the reaction mixture was stirred for one hour and then at room temperature for 2 h. The completion of the reaction was confirmed by TLC analysis. The reaction mixture was quenched with ice water, the white precipitated solid was filtered, washed with water (150 mL) and dried under high pressure under reduced pressure. The solid was taken in 10% MeOH in DCM and the organic layer was washed with 10% NaHCO3, water, and brine solution. The organic layer was dried over Na2SO4 and concentrated under reduced pressure to yield 8.0 g of compound 2f. LCMS: 948.7 [M+H]+ Synthesis of compound 2g HNx. ,NHPbf

[0220] Acetic acid (7 mL) was added to a solution of compound 2f (7.0 g, 7.38 mmol) in THF (70 mL) at room temperature, and the resulting mixture was refluxed at 70°C for 12 h. The completion of the reaction was confirmed by TLC analysis. The volatiles were evaporated under reduced pressure to obtain crude semisolid, which was diluted with water and ethyl acetate. The organic layer was washed with Petition 870260028627, dated 03 / 26 / 2026, page 81 / 130 73 / 88 solution of NaHCO3 followed by brine. The organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure to obtain the crude solid. The compound was purified by column chromatography (60-120 silica gel) to yield 5.4 g of the compound. LCMS: 930.5 [M + H]+ Synthesis of compound 2h 50% piperidine in DMF 2g 2h

[0221] Compound 2g (5.4 g, 5.80 mmol) was added to a 50% piperidine solution in DMF (20 mL) at 0°C and stirred at the same temperature for 2 h. Completion of the reaction was confirmed by TLC analysis. The reaction mass was quenched with water (100 mL), and the resulting precipitate was filtered. The obtained solid was dissolved in ethyl acetate and the organic layer was washed with 10% NaHCO3, water, and brine. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude product obtained was diluted with hexane, and the resulting precipitate was filtered followed by washing with hexane to obtain 3.0 g of compound 2h. LCMS 708.6 [M+H]+ Synthesis of compound 2i 4-NO2Ph-OCOCl A / OtBu3 CIHH2NY pyridine / CH2Cl2 THE 2i H-Phe-OtBu.HCl

[0222] Pyridine (0.75 mL, 9.3 mmol) was added to a solution of H-PheOtBu.HCl (2.0 g, 7.75 mmol) in CH2Cl (20 mL). Pyridine was added and the resulting solution was stirred at room temperature for 10 min. This reaction mixture was Petition 870260028627, dated 03 / 26 / 2026, page 82 / 130 74 / 88 a solution of 4-nitrophenyl chloroformate (1.87 g, 9.30 mmol) in CH2Cl2 (20 mL) was added and the resulting mixture was stirred at room temperature for 3 h. After the reaction was complete (confirmed by TLC), it was diluted with CH2Cl (50 mL) and washed with water (100 mL χ2), 10% citric acid (100 mL χ2), water (100 mL), followed by saline solution (100 mL). The organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure to yield 1.7 g of compound 2i, which was carried to the next step without any further purification. Synthesis of compound 2j

[0223] TEA (0.29 mL, 2.1 mmol) was added to a solution of compound 2h (1.0 g, 1.41 mmol) and compound 2i (0.54 g, 1.41 mmol) in THF (10 mL) at room temperature and stirred for 3 h. The volatiles were evaporated and divided between EtOAc and water. The reaction mixture was diluted with ice-cold water and extracted with EtOAc followed by washing with 10% K2CO3 (100 mL x 4), water, and brine solution. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude product obtained was diluted with hexane, and the resulting precipitate was filtered followed by washing with hexane, yielding 0.98 g of compound 2j. LCMS: 955.6 [M+H]+. Synthesis of Compound 7 Petition 870260028627, dated 03 / 26 / 2026, p. 83 / 130 75 / 88 2k

[0224] Compound 2j (0.5 g, 5.2 mmol) was added to the cocktail mixture (5 mL) of trifluoroacetic: TIPS: water (95:2.5:2.5). The cleavage solution was stirred at room temperature for 3 h. The resulting reaction mixture was evaporated under reduced pressure, diluted with diethyl ether, and filtered to yield 0.34 g of crude compound 2. The crude solid material was purified by the preparative HPLC method as described under experimental conditions. LCMS: 491.1 [M+H]+ HPLC tR: (min): 11.1

[0225] The compounds below were prepared by a procedure similar to that described in Example 2 (Compound 7) with appropriate variations in reagents, amounts of reagents, solvents, and reaction conditions. The characterization data for the compounds are summarized below the table. Compound Structure Observed mass [M+H]+ 8. hn^nh2 O^OH HN _ y 0 i / Η Η Π Η Ν-0 Η Η Ο 441.25 9. ην^νη2 Ο^ΝΗ^Ν Ι\Ι Γί2 j Ί - 0 I Η2ΝΛνΝγΛΝΛΝΛγ°Η Ν—θ' Η Η ΰ 457.2 Petition 870260028627, dated 03 / 26 / 2026, p. 84 / 130 76 / 88 Compound Structure Observed mass [M+H]+ 10. HN^NH2 Ογ^ΝΗ2ΗΝ Ύ Ί £j 1 "° hAYhAhVh N-0 HH 0 490.6 11. ΗΝγ^ΝΗ2 HN Ογ,ΝΗ2 I "° hAívAv™ N-ó HH i 400.3 12. HN^NHs CK.NH2HN O^NH2 I = 0 1 Η / / '<,'':γΝΑΙί'Υ°Η N-0 HHS 471.7 13. ZIO ^== / \=o ZI MI / 21 Ví oz 1 y^z -r / --- ZT / <M z—> T 453.8 14. / =\ 1 ó ύ o \ / ^° ZI ZI r=( Vo rz CM T 400.2 15. T or° ZT I / 2T ví. oz 1 VsZ -r / ---- 'Z- T / CM z— / T 373.0

[0226] The compounds below were also prepared by a procedure similar to that described in Example 1 (compound 1) with appropriate variations in Petition 870260028627, dated 03 / 26 / 2026, p. 85 / 130 77 / 88 reagents, reagent quantities, solvents, and reaction conditions. The characterization data for the compounds are summarized below the table. Compound Structure Observed Mass 16 o °y°H H2N0'Ny^0N'\ N-0 H '— / 360.1 (M+1) 17 z PZ / —\ y-* oz=A b IZ o I 342.3 (M+1) 19 AA <ZX Ll o nA A / A 0 AoH η 1 Ji T h2n'YNY^n'^nA n-o H Ly 439,9 (M+1) 20 z P z / —\ A IZ o T 431,0 (M+1) 21 O^NH2 o^oh 1| > 0 °yOH H2N1 NN Ί No HA / 413.1 (M+1) 22 P ΙΌ / / Z >--VV— / o Zí=\ b' IZ >° TZ 1 z-^ 382.0 (M+1). Petition 870260028627, of 26 / 03 / 2026, p. 86 / 130 78 / 88 Compound Observed Mass Structure 23 hn^nh2 OH HN> X o X^OH H2n\NXnÃnA n—o H a / 427.0 (M+1) 24 ΗΝγΝΗ2 nh2hn> (r\ X 0 0 <y-OH N-0 H '— / 473,4 (M+1) 25 X o A~0 ΖΞΕ 04 / 1 l · < vX H X X A X / <N Z—' ΞΕ 440,5 (M+1) 27 ΗΝγΝΗ2ΗΝγΝΗ2 HN HN x Xo °yoH h2nxX'nY^n^nA n-o H Ay 468,5 (M+1) 28 X V 7 N> \ / z 5= / T z z-( °\rlo X 459.5 (M+1) 29 X ro Z / --- T zz— xz o X 425.4 (M+1) Petition 870260028627, of 26 / 03 / 2026, p. 87 / 130 79 / 88 Compound Observed Mass Structure 30 ΗΝγΝΗ2 HN^ XX Ί 0 í V 0uyOH η2ν\Ν¥^ΛνΑ no H IV 498.4 (M+1) 31 ΗΝγ NoγΗ2 HN vo °yoH H2N^ N^N'^ N'A 369.4 (M+1) 32 X o ó^OXVV o XI yx X / o / \ \' ~z. / / OJ O 3= 414.3 (M+1) 33 Oe^ / OH TQ z\ . NOA\ h2n VV VOH N—o H 432,3 (M+1) 35 XO Vv\ zV °v / ZI IJo \ 1 X / \— ~Z- / / OI OI 372,0 (M+1) 36 ΗΝγΝΗ2 O^OH HN NII v> V Vo fV V HH HΛ— 480.8 (M+1) Petition 870260028627, of 26 / 03 / 2026, p. 88 / 130 80 / 88 Compound Structure Observed Mass 37 HNγNH2 CK.OH HN. hAvAV N-0 HH 0 457.4 (M+1) 38 HN^NHH2 CK^OH HI\L ο Λ 1 0 °V0H JL JL n A JL 1 NX 'VN NΛ H N-0 HU> 483.4 (M+1) 39 XON> / / z / —¥ 4 * \ / X / ------' 1x0 IZ O 469.3 (M+1) 40 O ó^0 ZI x 5 rC \— ~Z- / / CM ß I 455.3 (M+1)

[0227] Similar to the reagents, the characterization of the compounds below was also prepared by the procedure described in Example 2 (Compound 7) with appropriate variations in reagent ages, solvents, and reaction conditions. The data for the compounds are summarized below the table. Compound Structure Observed Mass 41 nh2 0<^nh2 J ! 0 1 Η?γΥ·ΝΑΝΛ|Τ0Η N-ó HH ΰ 372.3 (M+1) Petition 870260028627, dated 03 / 26 / 2026, p. 89 / 130 81 / 88 Compound Structure Mass Observed 42 O^NH2 o^nh2 i 0 f hAvAVh N—0 HH Ã 372.3 (M+1) 43 nh2NH oynh2 JA o A u μΛΛχ / σΛιΑΧΠ H2N v NN yr '' ' Η Η II N-0 π n 0 429.3 (M+1) 44 HN^NH2 ΓγΟΗΝ I 1 - 0 1 HoN NN rí N—OHH o 457.3 (M+1) 45 hn^nh2 nh2 ΓγΟΗΝ AIA 0 I II μΑζΝ, / Χ.Α ,,X\ / OH H2N 1 TNNYN—OHH o 472.3 (M+1) 46 HI\K / NH2 1 / 7 Oe- / OH HN. VA LL NH I - o Λ—AHH fl 530.3 (M+1) 47 hn^nh2 °γ0Η H% oh \ XO ¢^0 Η2ΝΛγΝγΛΝΛΝΛγ0Η Ai HH i 459.1 (M+1) Petition 870260028627, de 26 / 03 / 2026, pág. 90 / 130 82 / 88 Compound Structure Observed Mass 48 401.0 (M+1) 49 I o N> / / Z / --\ z / T zC ” C IZ IZ X \_ / 491.3 (M+1) 50 O^NH2 CK / OH I 0 I η2νΛΥΝ^νΛνΛΥοη N—OHHO 373.2 (M+1) 51 HNγ,ΝΗ2 O^OHHN ° <y0h ! - 0 i u μανα'κα,, α οη h2n jí 'η n ri n—o h o 473,4 (m+1) 52 (m+1)Example 3: Percentage rescue of phagocytosis Reagents

[0228] DPBS (Gibco), RPMI 1640 WITH HEPES E L-GLN-500 ML (Lonza), Recombinant human MCSF (R&D systems), CD47 monoclonal antibody (B6H12), functional grade antibody (Ebioscience), Mouse IgG1 kappa isotype control, Functional grade (Ebioscience), Vacutainer (multiple sample luer adapter) (BD), Vacutainer (sodium heparin (NH), 158 USP units, Blood collection tubes (BD), Histopaque (density - 1.077 g / ml) (SIGMA 1077), Solution Petition 870260028627, dated 03 / 26 / 2026, pp. 91 / 130 83 / 88 Trypan Blue (SIGMA-T8154), Hematometer (Bright-line-SIGMA Z359629), Scalp Vein Infusion Set (JMS), Cell Dissociation Buffer (Gibco), Sterile 48-Well Flat-Bottom Plates (Corning), Luciferase-Expressing Raji Cell Luminometer (internally generated by transfection of the luciferase gene into Raji cells), Hygromycin B (Invitrogen), Bright Glo Luciferase Assay System (Promega), 96-Well Plate, Polystyrene, High Band, White Flat-Bottom Wells (Sigma CLS3912), Anti-Mouse / Human CD11b Antibody APC (Biolegend), H929 Cells, CFSE (Ebioscience), Fetal Bovine Serum (Gibco Cat #: 10437028), Round-Bottom FAC Tubes (BD), BD FACS Verse versitometer, 96-well plates, ultra-low fixation (Corning). Protocol -1: Luciferase-based phagocytosis assay

[0229] An in vitro phagocytosis assay was performed to evaluate the ability of the test item to enhance the phagocytic activity of macrophages. Monocytes were isolated from healthy donor blood and cultured for 6–8 days using 10% RPMI (Roswell Park Memorial Institute) medium and recombinant human M-CSF to differentiate into macrophages. The media was changed every other day. After differentiation, adherent macrophages were collected by gentle scraping and cultured in 10% RPMI overnight at a density of 0.1 million per well in a 48-well tissue culture plate. Simultaneously, Raji cells expressing luciferase were cultured in 10% RPMI medium with 100 μg / mL hygromycin B in a tissue culture flask. On the day of phagocytosis, macrophages were subjected to serum deprivation for 2 hours.0.4 million Raji cells expressing luciferase per well were incubated with purified CD47 anti-human B6H12 antibody or IgG1 K control isotype, or various concentrations of the test item in serum-free medium for 30 minutes at 37°C and added to the respective well of a 48-well plate seeded with macrophages. After 2 hours, the cells were washed twice with PBS and 100 μL of serum-free RPMI was added. Petition 870260028627, dated 03 / 26 / 2026, page 92 / 130 84 / 88 each well. In addition, 50 μL of Bright Glow reagent were added to each well, followed by cell mixing and incubation for 5 min in the dark. Luminescence readings were performed using a plate reader after transferring the contents of each well to a white plate. The intensity of luminescence indicated the extent of phagocytosis. Each experimental condition was performed in duplicate. The results for the selected compound of the invention are presented in the table below._________ Compound % of normalized phagocytosis (at 10 μM) 1 39 3 42 6 66 7 58 8 20 9 38 12 44 13 49 14 47 Protocol 2: FACS-based phagocytosis assay

[0230] Monocytes were isolated from healthy donor blood and cultured for 6-8 days using 10% RPMI (Roswell Park Memorial Institute) medium and recombinant human M-CSF to differentiate into macrophages. The media was changed every other day. Simultaneously, H929 cells were cultured in 10% RPMI medium with 50 μg / mL betamercaptoethanol in a tissue culture flask. On the day of phagocytosis, adherent macrophages were serum-inactivated for 2 hours in RPMI medium. Simultaneously, H929 cells were stained with 0.3 μM CFSE dye. After washing, 0.2 million CFSE-stained H929 cells were incubated with anti-human CD47 antibody or IgG1 K control isotype or various concentrations of test item in serum-free medium for 30 minutes at 37 °C. Petition 870260028627, dated 03 / 26 / 2026, page 93 / 130 85 / 88 After 2 hours of serum starvation, macrophages were dissociated with cell dissociation buffer and collected by gentle scraping and added at a concentration of 0.05 million per well to the respective wells of the 96-well ultra-low insertion plate seeded with H929 cells. Phagocytosis was allowed for 2 hours. After 2 hours, the cells were washed with PBS and stained with 1 μL of anti-CD11 β-APC human antibody prepared in 100 μL of PBS for 30 min at 4 °C in the dark. The cells were further washed and fixed in 100 μL of fixation buffer until they were acquired by flow cytometry. The extent of phagocytosis of H929 cells by human macrophages was measured by acquiring the samples by flow cytometry. Samples acquired by flow cytometry were analyzed using FlowJo software. Each experimental condition was performed in duplicate. FITC-positive (CFSE) and CD11b-APC positive cells were considered phagocytosed macrophages.Raw phagocytosis percentages by macrophages were obtained in the form of a FlowJo Excel spreadsheet. The phagocytosis percentage of the isotype control (background phagocytosis) was subtracted from the phagocytosis percentage of macrophages treated with the compound, as well as other controls, to obtain the corrected phagocytosis values. The corrected phagocytosis values ​​of the compound-treated samples were normalized to the positive control phagocytosis (B6H12) using the formula.

[0231] Normalized phagocytosis percentage = [(corrected phagocytosis percentage of the compound) / (corrected phagocytosis percentage of B6H12) *100]___________________________________ Compound % of normalized phagocytosis (at 10 μM) 1 45 2 37 3 73 5 56 6 74 7 38 Petition 870260028627, dated 03 / 26 / 2026, pp. 94 / 130 86 / 88 Compound % of normalized phagocytosis (at 10 μM) 8 40 10 28 12 20 13 29 14 26 15 62 16 27 17 33 19 52 21 13 22 33 23 60 24 37 29 26 30 23 31 58 32 46 33 31 35 35 37 17 39 23 40 27 41 31 43 43 44 20 46 30 47 18 48 29 Petition 870260028627, dated 03 / 26 / 2026, pp. 95 / 130 87 / 88 Compound % of normalized phagocytosis (at 10 μM) 49 35 50 26 51 24 52 77 Example 4: Efficacy of compound 6 in the A20 syngeneic lymphoma model

[0232] Female Balb / c (BALB / cAnNTac) mice (6-8 weeks old) bred in-house were used in this efficacy study in the A20 syngeneic lymphoma model. Animals were individually tagged with tail tags and kept in cages identified by a cage card showing the study code, experiment date, sex, and number of animals. During the experiment, animals were weighed daily. The A20 cell line (B-cell lymphoma line derived from a spontaneous reticulum cell neoplasm found in an old BALB / cAnN mouse) was acquired from ATCC. When mean tumor volumes reached approximately 75 mm3, animals were randomized based on tumor volumes into four groups of twelve animals each. After randomization into multiple treatment groups, administration of the vehicle and Compound 6 was initiated.All treatments were administered orally at a twice-daily dosing frequency, using doses of 3 mg / kg, 10 mg / kg, and 30 mg / kg. Treatment was continued for a period of 21 days, after which overall efficacy and tolerability were assessed based on changes in tumor volume and body weight observed during the treatment period. On day 21 of treatment, animals from all treatment groups were sacrificed sequentially 1 hour after the last dose administration.

[0233] The individual body weights of the animals were recorded daily before administration of the test item throughout the period. Petition 870260028627, dated 03 / 26 / 2026, pp. 96 / 130 88 / 88 experimental. Animals were observed for mortality / morbidity once daily throughout the experimental period and also for clinical signs once daily throughout the experimental period. Tumor volumes were measured in all treatment group animals three times a week (once every 2-3 days) using a Vernier digital caliper. From an ethical standpoint, any treatment / control group with an average tumor weight greater than 10% of the animal's body weight was humanely sacrificed. As a measure of efficacy, the % T (treatment) / C (control) and % TGI (% inhibition of tumor growth) values ​​were calculated. Graphs and statistical analyses were performed in GraphPad Prism®, version 7.0. For tumor volume data analysis, statistical comparison was performed on day 21 for all groups using one-way ANOVA with Dunnett's multiple comparison test.All analyses and comparisons were evaluated at the 5% level (p < 0.05). A p-value less than 0.05 was considered significant.

[0234] Compound 6 was well tolerated without any signs of body weight loss and / or clinical signs of toxicity. In terms of antitumor efficacy, compound 6 demonstrated statistically significant inhibition of tumor growth (TGI) at all dose levels tested. Treatment with compound 6 resulted in tumor growth inhibition values ​​of 53%, 64%, and 67% at doses of 3 mg / kg, 10 mg / kg, and 30 mg / kg, respectively. Tumor growth inhibition by Compound 6 in the A200 model. Group Compound Dose TGI (%) 1 Vehicle control 0 mg / kg (bid) 2 Compound 6 3 mg / kg (bid) 53* 3 Compound 6 10 mg / kg (bid) 64** 4 Compound 6 30 mg / kg (bid) 67** Statistics: One-way ANOVA, Dunnett's multiple comparison test: *-p < 0.05; **-p < 0.01 Petition 870260028627, dated 03 / 26 / 2026, pp. 97 / 130 < / n>

Claims

1 / 16 CLAIMS 1. Compound CHARACTERIZED in that it is of formula (I): either a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof; wherein, Ra is hydrogen or acyl; and Ri represents hydrogen, -(CH2)2CONH2, (CH2)2COOH, -CH2COOH, -(CH2)3NHC(=NH)NH2, -(CH2)4NH2, -CH2CONH2, CH(CH3)-CH2-CH3, -CH2-aryl or -CH2-heteroaryl; wherein said aryl and heteroaryl are unsubstituted; or Ra and R1, together with the atoms to which they are attached, form a pyrrolidine ring optionally substituted by an oxo group; R2 represents hydrogen, -CH2-OH, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, (CH2)2COOH, -CH2-aryl or -CH2-heteroaryl; wherein the said aryl and heteroaryl are unsubstituted; Rb is hydrogen; and R3 represents hydrogen, -CH2-aryl, -(CH2)3NHC(=NH)NH2, -CH2COOH, -CH(CH3)-CH2-CH3, -CH2-CH(CH3)2, -(CH2)2CONH2, -(CH2)2COOH, (CH2)4NH2 or -CH2-heteroaryl; wherein the said aryl and heteroaryl are unsubstituted;or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

2. Compound according to claim 1, CHARACTERIZED in that R1 represents hydrogen, -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NHC(=NH)NH2, -(CH2)4NH2, -CH2CONH2, -CH(CH3)-CH2-CH3, -CH2-phenyl, -CH2indolyl or -CH2-imidazolyl.

3. Compound, according to claim 1 or 2, CHARACTERIZED in that R2 represents hydrogen, -CH2-OH, -(CH2)3NHC(=NH)NH2, - Petition 870260028627, dated 03 / 26 / 2026, page 98 / 130 2 / 16 (CH2)2CONH2, -(CH2)2COOH, -CH2-phenyl, -CH2-indolyl or -CH2-imidazolyl.

4. Compound, according to any one of claims 1 to 3, CHARACTERIZED in that R3 represents hydrogen, -(CH2)3NHC(=NH)NH2, -CH2COOH, -CH(CH3)-CH2-CH3, -CH2-CH(CH3)2, -(CH2)2CONH2, -(CH2)2COOH, (CH2)4NH2, -CH2-phenyl, -CH2-indolyl or -CH2-imidazolyl.

5. Compound according to claim 1, CHARACTERIZED in that it is represented by the compound of formula (IA): either a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof.

6. Compound according to claim 5, CHARACTERIZED in that Ri represents hydrogen, -CH2-COOH, -CH2-CONH2, -CH(CH3)-CH2-CH3, (CH2)2CONH2, -(CH2)2COOH, -(CH2)3NHC(=NH)NH2, -(CH2)4NH2, -CH2-phenyl, -CH2indolyl or -CH2-imidazolyl.

7. Compound according to claim 5 or 6, CHARACTERIZED in that R2 represents hydrogen, -CH2-OH, -(CH2)3NHC(=NH)NH2, (CH2)2CONH2, -(CH2)2COOH, -CH2-phenyl or -CH2-imidazolyl.

8. Compound according to any one of claims 5 to 7, CHARACTERIZED in that Ra is hydrogen; and Ri represents hydrogen, -CH2-COOH, -CH2-CONH2, CH(CH3)-CH2-CH3, -(CH2)2CONH2, -(CH2)2COOH, -(CH2)3NHC(=NH)NH2, (CH2)4NH2, -CH2-phenyl, -CH2-indolyl or -CH2-imidazolyl; and R2 represents hydrogen, -CH2-OH -(CH2)2CONH2, -(CH2)3NHC(=NH)NH2, (CH2)2COOH or -CH2-phenyl. Petition 870260028627, dated 03 / 26 / 2026, page 99 / 130 3 / 16 9. Compound according to claim 1, CHARACTERIZED in that it is represented by the compound of formula (IB): either a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof.

10. Compound according to claim 9, CHARACTERIZED in that: Ri represents hydrogen, -CH2-COOH, -CH2-CONH2, -CH(CH3)-CH2-CH3, (CH2)2CONH2, -(CH2)2COOH, -(CH2)3NHC(=NH)NH2, -(CH2)4NH2, -CH2-indolyl, -CH2imidazolyl or -CH2-phenyl; and Rb is hydrogen; R3 represents hydrogen, -CH2-COOH, -CH2-CH(CH3)2, CH(CH3)-CH2-CH3, -(CH2)4NH2, -(CH2)2CONH2, -(CH2)2COOH, -CH2-phenyl, CH2imidazolyl or CH2-imidazolyl; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

11. Compound according to claim 1, CHARACTERIZED in that it is represented by the compound of formula (IC), (ID), (IE) or (IF): (ic) Petition 870260028627, dated 03 / 26 / 2026, page 100 / 130 4 / 16 or a salt or an amide or a pharmaceutically acceptable ester, or a stereoisomer thereof.

12. Compound CHARACTERIZED hair fact that it is selected from: Compound Structure 1 nh2 L CA-NH2 A Ao °yoH \^z CXI I / \ Z / —' Z. \ / <N I Petição 870260028627, de 26 / 03 / 2026, pág. 101 / 130 5 / 16 Composto Estrutura 3 z O N> / / Z / —\ °A -} '1 1 1' N· IZ >° o I 4 Z o M OJ ZT vAo o Z 1 ysZ<N *—( T / \ Z / — / z \ / OJ - Z 5 i P ro / / Z / --\ °Λ 5 2 η ' ro IZ > ° or I -X 6 T o ó^O ZI I / Z )>— / / <N O I 7 hn^nh2 HN, Ο^,ΟΗ x-, Ί Ύ £ ] I “° N-0 H H â · J 8 ZZ J 1 / z P °-\Λ. Σ.-Ζ. ± z > ° ,M ZZ ,---' -Z. \_ / z 1 N> °=( oz -X Petition 870260028627, dated 26 / 03 / 2026, p. 102 / 130 6 / 16 Compound Structure 9 T or CM I / \ Z ,--' \\CM-Z z CM O z 10 HI\yNH2 Ύ L Xj Y XO N-0 HHSJ 11 X ΙΌ / \ Z / —' z \ / I n> 1 z O °\r\ TZ 1 °4 o I 12 X p Z y--<( Tf °Λ A ízz )= 11 o I> ^^ZTO 4° ZT T / HT VVo oz | γζ <N ,—' z. T / CM Z.—! T 14 / =\ z: Ά # ° y° ZI A ZT X ^4° Z^zZTZ 1 A' z.OJ T 15 -IO 7 ZT V'Vo O z | y=z -r / --- T / cm z—f T. Petição 870260028627, de 26 / 03 / 2026, pág. 103 / 130 7 / 16 Composto Estrutura 16 ΞΕ N> z ZA / / λ x iz o ΞΕ 17 I o M / / Z / --\ / I zA IZ o I 18 I / ~2 __ / IZ !----' N> ζ=Λ IZ o ΞΕ 19<ZX Là o 0 y-OH h2nà / Xx^AnÁ N-0 H J 20 x P Z / —\ TZ > =° at 21 O <ss / NH2 O<ss / OH L L O %-0H H2nÃznyxí''nx^nà n—o H L_ / J 22 i P Z / --¥ yx o / I zr\ IZ > ° IZ oc \ I xz^ Petição 870260028627, de 26 / 03 / 2026, pág. 104 / 130 8 / 16 Composto Estrutura 23 i QM \\ Z VO \ j / I} I 1 1 ' N> IZ >° o I 24 hn^nh2 nh2hn> \ 0 °yOH h2n-\n^AA N-0 H YV . J 25 __ / IZ / ---' M / W ΞΕ T'z z-^ °AXE 2 1 1 ' N> zz o ΞΕ 26 ΞΕ O 0^0 M ZI <N , 1 I ! ( T / \ Z\ / Y-o / Γ^ \ 1 ΞΕ / ~z. \ . <n 27 i ? z z—r ιό x —' ~z. \_ ; ιό °5„ y i o 28 5=" / " t ΐ>°Λ XE 2 1 1 1 1 ' N3 IZ o I Petition 870260028627, of 26 / 03 / 2026, p. 105 / 130 9 / 16 Compound Structure 29 HN^ / NH2 HN VY o °yoH η2ν\ν<·<·ν^νΑ N-0 H / ' J 30 hn^nh2 HN^ A Al lo í ¥\ > ο γοΗ Η2ΝχγΝ<γΝ'^Ν'\ N-0 HA / ; J 31 HN^NH2 HN. A o °yoH H2N 'ΎN N Ν Ά. WH ; J 32 Ο.ΌΗ 0.ΌΗ Y ao °y0H h / aVAA N-0 H / ; J 33 Ογ-OH xL MO 9x H^YY--J / VoH N-0 H ; 34 IP -Z. >----Y ' o / I z=\ Ó^Z TZ VvA Y°çO \>Ύ 1 o I -X Petition 870260028627, of 26 / 03 / 2026, p. 106 / 130 10 / 16 Compound Structure 35 TO °γζ ZI °zc \=ZT / / / <N Ο I 36 ΗΝγΝΗ2 CK / OH HN N Ύ k ) o f N H2N η v N N π II 1 Η H 11 N---O O J 37 hn^,nh2 O^OH HN i - 0 T Η2ΝΛγΝγΛΝΛΝΛγ°Η M H H S J 38 HN^NH2 Ο^,ΟΗ HN. o k ]° °Y0H n''kr N Yk'k k H n-ο H - / J 39 ην<5^νη2 °^.°x HN i 1 0 °Y°X H2NkNk^n N-ο N / J 40 hn^nh2 O^OH HN Ίι° °Y°A Jl n k. JL a H2N Y -γ N NA N-0 H kV J Petição 870260028627, de 26 / 03 / 2026, pág. 107 / 130 11 / 16 Composto Estrutura 41 CM T T ° '—\ Vo ΖΞ ΖΞ cm T / Z / —Ύ ' Z. / / CM o T 42 CA / NH2 ck,nh2 1 0 I h2n\nY'nAnVh N—OHH | ; J 43 CM TT ° '—\ )=° ZI °A <3 ZI Aí» oz | Az CM < ΕΖ \ zY z \\ CM OI 44 hn^nh2 On^OHN^ h2n\-nÃnXnA0H N-0 HHS ; ; 45 hn^nh2 nh2 OcADHHN AI - 0 I i_i / OH H2N γ YNN [f N-0 HH 0 ; 46 hn^nh2 Ox / OH HN LL nh A Ao f^7 n2nAnY^nLnAoi MHHS ? J Petition 870260028627, de 26 / 03 / 2026, pág. 108 / 130 12 / 16 Compound Structure 47 ΗΝγΝΗ2 °γ0ΗΝ> ​​oh ] Z o M μΔN. <ακλνδ0η η2ν τι ν υ ii 1 η 11 ν---ο ο 48 ην^νη2 ο^οη ην. i - 0 αγλγ μ s j 49 ξε ν· ζ —\ x ζ4 vo ιζ °υα \__ 50 ογ νη2 ο^,οη η2ν γ ν ]< '' ' ν-0 51 ο^ οηην, θ<γ-θη u ,ά.ά οη h2n η n-ο π 52 0^.0 ηην, αυ ! ° jf τρ ν-o 53 ογ-οη η2ν'^^νυχχχ'ν^'να ν-ο υρ e petição 870260028627, de 26 03 2026, pág. 109 130 13 16 composto estrutura 54 hn ύνη2 o a iz z="\" o ou um sal uma amida éster farmaceuticamente aceitável, estereoisômero do mesmo.

13. Pharmaceutical composition CHARACTERIZED in that it comprises a compound of formula (I), as defined in any one of claims 1 to 12, and a pharmaceutically acceptable carrier.

14. A compound, according to any one of claims 1 to 12, CHARACTERIZED in that it is for use as a medicament.

15. Use of a compound, as defined in any one of claims 1 to 12, CHARACTERIZED in that it is used in the manufacture of a medicament to modulate the phagocytic activity of macrophages towards a cancerous cell or tumor cell.

16. Use, according to claim 15, CHARACTERIZED in that the cancer cell is a cancer cell selected from melanoma, renal cancer, prostate cancer, breast cancer, colon cancer and lung cancer, bone cancer, pancreatic cancer, skin cancer, head or neck cancer, malignant cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, anal region cancer, stomach cancer, testicular cancer, fallopian tube carcinoma, endometrial carcinoma, cervical carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, non-Hodgkin's lymphoma, esophageal cancer, small bowel cancer, endocrine system cancer, thyroid gland cancer, parathyroid gland cancer, adrenal gland cancer, soft tissue sarcoma, urethral cancer, penile cancer, chronic leukemias or Petition 870260028627, dated 03 / 26 / 2026, page.110 / 130 14 / 16 acute including acute myeloid leukemia (AML), chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, childhood solid tumors, lymphocytic lymphoma, bladder cancer, kidney or ureter cancer, renal pelvis carcinoma, central nervous system (CNS) neoplasm, non-small cell lung cancer (NSCLC), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brainstem glioma, pituitary adenoma, Kaposi's sarcoma, squamous cell carcinoma, T-cell lymphoma, B-cell lymphomas, environmentally induced cancers, including those induced by asbestos (e.g., mesothelioma) and combinations of the aforementioned cancers.

17. Use of a compound, as defined in any one of claims 1 to 12, CHARACTERIZED in that it is in the manufacture of a medicament for treating or delaying the progression of CD47-mediated diseases or disorders.

18. Use according to claim 17, CHARACTERIZED in that the disease or disorder mediated by CD47 is: (i) cancer that is selected from melanoma, renal cancer, prostate cancer, breast cancer, colon cancer and lung cancer, bone cancer, pancreatic cancer, skin cancer, head or neck cancer, malignant cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, anal region cancer, stomach cancer, testicular cancer, fallopian tube carcinoma, endometrial carcinoma, cervical carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, non-Hodgkin's lymphoma, esophageal cancer, small bowel cancer, endocrine system cancer, thyroid gland cancer, parathyroid gland cancer, adrenal gland cancer, soft tissue sarcoma, urethral cancer, penile cancer, chronic or acute leukemias including acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia,Chronic lymphocytic leukemia, solid tumors of childhood, lymphocytic lymphoma, bladder cancer, kidney or ureter cancer, renal pelvis carcinoma, central nervous system (CNS) neoplasm, non-small cell lung cancer (NSCLC), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brainstem glioma, pituitary adenoma, Kaposi's sarcoma, squamous cell carcinoma, T-cell lymphoma, B-cell lymphomas, environmentally induced cancers, including those induced by asbestos (e.g., mesothelioma) and combinations of said cancers; or (ii) bacterial, viral and fungal infectious diseases that are selected from among HIV, influenza, herpes, giardia, malaria, leishmania, pathogenic infection by Hepatitis virus (A, B and C), herpes virus (e.g., VZV, HSV-I, HAV-6, HSV-II and CMV, Epstein-Barr virus), adenovirus, influenza virus, flavivirus, echovirus,rhinovirus, coxsackievirus, coronavirus, respiratory syncytial virus, mumps virus, rotavirus, measles virus, rubella virus, parvovirus, vaccinia virus, HTLV virus, dengue virus, papillomavirus, molluscum contagiosum virus, poliovirus, rabies virus, JC virus and arboviral encephalitis virus, pathogenic infection by chlamydia bacteria, rickettsial bacteria, mycobacteria, staphylococci, streptococci, pneumococci, meningococci and conococci, klebsiella, proteus, serratia, pseudomonas, E. coli, legionella, diphtheria, salmonella, bacilli, cholera, tetanus, botulism, anthrax, plague, leptospirosis, and Lyme disease bacteria, pathogenic infection by Candida fungi (albicans, krusei, glabrata, tropicalis, etc.), Cryptococcus neoformans, Aspergillus (fumigatus, niger, etc.), Genus Mucorales (mucor, absidia, rhizophus), Sporothrix schenkii, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Coccidioides immitis and Histoplasma capsulatum,and pathogenic infection by the parasites Entamoeba histolytica, Balantidium coli, Naegleria fowleri, Acanthamoeba sp., Giardia lamblia, Cryptosporidium sp., Pneumocystis carinii, Plasmodium vivax, Babesia microti, Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii and Nippostrongylus brasiliensis. Petition 870260028627, dated 03 / 26 / 2026, pp. 112 / 130 16 / 16, 19. Use of a compound, as defined in any one of claims 1 to 12, CHARACTERIZED by the fact that it is used in the manufacture of a medicament to treat or delay the progression of atherosclerosis and CD47-mediated multiple sclerosis. Petition 870260028627, dated 03 / 26 / 2026, pp. 113 / 130 < / n>