1,2,4-OXADIAZOLE COMPOUNDS AS INHIBITORS OF CD47 SIGNALING PATHWAYS

Abstract

The present invention relates to compounds of formula (I), compositions, methods, and uses involving formula (I) that inhibit the CD47 signaling pathway. The present invention also relates to methods for preparing such compounds and their uses for the treatment of CD47-mediated disorders.

Description

1,2,4-OXADIAZOLE COMPOUNDS AS INHIBITORS OF CD47 SIGNALING PATHWAYS RELATED REQUEST This application claims the benefit of Indian Provisional Application No. 201841001438, filed on January 12, 2018, the contents of which are incorporated herein in their entirety by this reference. TECHNICAL FIELD 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, amide, ester, or stereoisomer thereof. BACKGROUND Antagonistic antibodies targeting CTLA-4, PD-1, and PD-L1 affect the adaptive immune system, predominantly T cells, and have demonstrated impressive clinical efficacy across a wide range of cancers. Despite the success of these T cell-based checkpoint inhibitors in a subset of patients, the majority still fail to show an adequate clinical response. Checkpoint proteins on cells of the innate immune system are also known to regulate the immune response. Among innate immune checkpoint proteins, CD47 is upregulated in a wide range of malignancies, negatively regulating macrophage-mediated phagocytosis. CD47-mediated phagocytosis primarily occurs through interactions with SIRPIa expressed on macrophages.Blockade of SIRP1a / CD47 has been shown to dramatically enhance tumor cell phagocytosis and dendritic cell maturation for improved antigen presentation leading to substantially enhanced antitumor responses in preclinical cancer models (MP Chao et al. Curr Opin Immunol. 2012 (2): 225-232). CD-47 as a target to eliminate tumor cells 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 associates with membrane integrins and also binds to the ligands thrombospondin-1 (TSP-1) and signal regulatory protein alpha (SIRPa). CD47 is known for its pivotal role in preventing phagocytic clearance of healthy cells by binding to phagocyte-expressed signal regulatory protein alpha (SIRPa). SIRPa, an inhibitory protein expressed on macrophages, once activated, suppresses phagocytosis of CD47-expressing cells. This CD47 / SIRPa axis is an important homeostatic mechanism that prevents the elimination of healthy normal cells that express CD47.Conversely, downregulation of CD47 on damaged, aged, and superfluous cells ensures their timely removal. CD47 is expressed on virtually all non-malignant cells, and CD47 blockade, loss of CD47 expression, or changes in membrane distribution can serve as markers of aged or damaged cells, particularly red blood cells (RBCs). Alternatively, blocking SIRPα also allows the uptake of targets not normally phagocytosed, for those cells where prephagocytic signals are also present. CD47 is a broadly expressed transmembrane glycoprotein with a single Ig-like domain and five membrane-spanning regions, which functions as a cellular ligand for SIRPα with binding mediated through the NH2-terminal type V domain 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. CD47 is also constitutively upregulated in several cancers, including non-Hodgkin lymphoma (NHL), acute myeloid leukemia (AML), breast cancer, colon cancer, glioblastoma, glioma, ovarian cancer, bladder cancer, and prostate cancer. Overexpression of CD47 by tumor cells effectively helps them escape immune surveillance and killing by cells of the innate immune system. CD47 has been shown to be a potential target for the treatment of atherosclerosis. Because the process of atherogenesis, i.e., the formation of atheromas in the arterial wall, is associated with the upregulation of CD47, which renders malignant cells resistant to programmed cell elimination, or “efferocytosis.” This effect of efferocytosis is reversed by the administration of CD47-blocking antibodies, which normalizes the clearance of diseased vascular tissue and improves atherosclerosis in multiple mouse models (Kojima Y, et al., Nature. 2016 August 4;536(7614):86-90). Furthermore, CD47 blockade with CD47-Fc fusion protein has been reported to be effective in regulating the pathology of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), and provides a potential therapeutic target in the prevention and treatment of MS (Gao Q et al., J Autoimmun. May 2016; 69: 74-85). Several publications have been published such as US20160304609, WO2016188449, US20170081407, WO2017194627 and WO2017194634 describing compounds (i.e., antibodies and peptides) that modulate CD47. pori ηη / ηζηζ / Β / γι Despite several recent advances, there is still an unmet need for effective CD47 inhibitors that block the SIRP1a-CD47 signaling pathway for the treatment of cancers mediated by elevated levels of CD47 expression. COMPENDIUM OF THE INVENTION The present invention provides compounds and their pharmaceutically acceptable salts. These compounds are capable of suppressing and / or inhibiting the CD47 signaling pathway. In one aspect, the present invention provides the compounds of formula (I): pQf / nn / nznz / B / Yi or a pharmaceutically acceptable salt, amide, ester or stereoisomer thereof; where: R is hydrogen or acyl; and R represents hydrogen, -(CH2)2CONH2, -(CH2)2COOH, CH2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, -CH(CH3)-CH2-CH3, -CH2-ahlo or CH2-heteroaryl; wherein aryl and heteroaryl are unsubstituted; or R1 together with the atoms to which they are attached form a pyrrolidine ring optionally substituted with an oxo group; R2 represents hydrogen, -CH2-OH, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, CH2-aryl or -CH 2-heteroaryl; wherein aryl and heteroaryl are unsubstituted; Rb represents 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 aryl and heteroaryl are unsubstituted; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring. In another aspect, the present invention relates to pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt, an amide, an ester or a stereoisomer thereof, and processes for preparing said compositions. 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, amide, ester or stereoisomer thereof. DETAILED DESCRIPTION OF THE INVENTION The present invention provides 1,2,4-oxadiazole compounds and their derivatives as therapeutic agents useful for the treatment of CD-47 mediated disorders. Each embodiment is provided merely to explain the invention and not to limit it. Indeed, it will be apparent to those skilled in the art that various modifications and variations may be made to the compounds, compositions, and methods described herein without departing from the scope or spirit of the invention. For example, features illustrated or described as part of one embodiment may be applied to another embodiment to provide yet another embodiment. Therefore, the present invention is intended to include such modifications and variations and their equivalents. Other objects, features, and aspects of the present invention are described in the following detailed description or will be apparent therefrom. One skilled in the art will understand that the present discussion is merely a description of exemplary embodiments and should not be construed as limiting broader aspects of the present invention. In certain embodiments, the present invention provides a compound of formula pQf / nn / nznz / B / Yi or a pharmaceutically acceptable salt, amide, ester or stereoisomer thereof; where, R is hydrogen or acyl; and R represents hydrogen, -(CH2)2CONH2, -(CH2)2COOH, CH2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, -CH(CH3)-CH2-CH3, -CH2-ahlo or CH2-heteroaryl; wherein aryl and heteroaryl are unsubstituted; or R1 together with the atoms to which they are attached form a pyrrolidine ring optionally substituted with an oxo group; R2 represents hydrogen, -CH2-OH, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, CH2-ahlo or -CH2-heteroaryl; wherein the aryl and heteroaryl are unsubstituted; Rb represents 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 aryl and heteroaryl are unsubstituted; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring. In certain other embodiments, the present invention provides a compound of formula (I): where, R1 is hydrogen; and R1 represents hydrogen, -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, -CH2-aryl or -CH2-heteroaryl; or R1, together with the atoms to which they are bonded, form a pyrrolidine ring; R2 represents hydrogen, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, -CH2-ahlo or CH2-heteroahlo; 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. In certain embodiments, the present invention provides a compound of formula (I): where, Ra is hydrogen or acyl; and Ri represents hydrogen, -CH2COOH, -(CH2)3NH(C=NH)NH2, CH2CONH2, -CH(CH3)-CH2-CH3, or -CH2-heteroaryl; wherein the aryl and heteroaryl are unsubstituted; or Ray Ri, together with the atoms to which they are attached, form a pyrrolidine ring optionally substituted with an oxo group; R2 represents hydrogen, -CH2-OH or -CH2-heteroaryl; where the heteroaryl is unsubstituted; 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 aryl is unsubstituted; In certain embodiments, the present invention provides a compound of formula (I): where, Ra is hydrogen or acyl; and Ri represents -(CH2)2CONH2, -(CH2)4NH2, -(CH2)3NH(C=NH)NH2, or -CH2-heteroaryl; wherein the heteroaryl is unsubstituted; R2 represents; -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH or -CH2-aryl; wherein the aryl is unsubstituted; Rb is hydrogen; and R3 represents hydrogen, -(CH2)2CONH2, or -CH2-heteroaryl; where the heteroaryl is unsubstituted; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring. In certain embodiments, Ri represents hydrogen, -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, CH(CH3)-CH2-CH3, -CH2-aryl, or -CH2-heteroaryl; wherein the heteroaryl is unsubstituted; <h2 style=";text-align:left;direction:ltr">En determinadas modalidades, Ri representa hidrógeno, -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, CH(CH3)-CH2-CH3, -CH2-fenilo, -CH2-indolilo o CH2-imidazol¡lo.<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> In specified quantities, Ri represents hydrogen, -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, -(CH2)4NH2i-CH2CONH2, -CH2-phenyl or -CH2-imidazolidinyl.<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> In specified quantities, Ri represents -(CH2)2CONH2, -(CH2)2COOH, pQf / nn / nznz / B / Yi (CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, -CH2-phenyl or -CH2-imidazole.<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> En determinadas modalidades, Ri representa -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, -(CH2)4NH2, o -CH2-imidazol¡lo.<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> In specified quantities, Ri represents -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2o -CH2-phenyl.<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> In specified quantities, Ri represents -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2o -(CH2)4NH2.<h2 style=";text-align:left;direction:ltr"> In certain embodiments, Ri represents -(CH2)3NH(C=NH)NH2, -(CH2)2CONH2or (CH2)2COOH. In certain embodiments, Ri represents -(CH2)2COOH, -CH2COOH, -CH2CONH2, pQf / nn / nznz / B / Yi CH(CH3)-CH2-CH3o -CH2-aryl; where the aryl is unsubstituted. In certain embodiments, Ri represents -(CH2)2CONH2or -(CH2)2COOH. In certain embodiments, Ra is hydrogen. In certain embodiments, Ra is acyl. In certain embodiments, Ra is acetyl. In other embodiments, in formula (I), Ray Ri, together with the atoms to which they are attached, form a pyrrolidine ring optionally substituted with an oxo group. In certain embodiments, R2 represents hydrogen, -CH2-OH, -(CH2)3NHC(=NH)NH2, (CH2)2CONH2, -(CH2)2COOH, -CH2-phenyl, -CH2-indolyl or -CH2-imidazolyl. In certain embodiments, R2 represents hydrogen, (CH2)2CONH2, -(CH2)2COOH, -CH2-phenyl or -CH2-imidazolyl. -(CH2)3NHC(=NH)NH2, In certain embodiments, R2(CH2)2CONH2, -(CH2)2COOH or -CH2-phenyl. represents hydrogen, -(CH2)3NHC(=NH)NH2, In certain embodiments, (CH2)2COOH or -CH2-phenyl. In certain embodiments, (CH2)2CONH2, or-(CH2)2COOH. In certain embodiments, (CH2)2CONH2, or-(CH2)2COOH. In certain modalities, r2r2r2 R2 represents represents represents represents hydrogen, hydrogen, hydrogen, hydrogen, -(CH2)3NHC(=NH)NH2, -(CH2)3NHC(=NH)NH2, -(CH2)3NHC(=NH)NH2, -(CH2)3NHC(=NH)NH2, (CH2)2CONH2, -(CH2)2COOH or -CH2-phenyl. In certain embodiments, R2 represents hydrogen or -(CH2)3NHC(=NH)NH2. 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, -CH2indolyl or -CH2-imidazolyl. In certain embodiments, R3 represents hydrogen, -CH2-phenyl, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, -CH(CH3)-CH2-CH3, -CH2-CH(CH3)2, -(CH2)4NH2, or -CH2-imidazolyl. In certain embodiments, R3 represents hydrogen, -CH2-phenyl, -(CH2)3NHC(=NH)NH2, (CH2)2CONH2, -(CH2)2COOH, -CH(CH3)-CH2-CH3, -CH2-CH(CH3)2, -(CH2)4NH2, or -CH2-imidazolyl. In certain embodiments, R3 represents hydrogen, -CH2-phenyl, -(CH2)3NHC(=NH)NH2, (CH2)2CONH2, -(CH2)2COOH, -(CH2)4NH2, or -CH2-heteroaryl; wherein the heteroaryl is unsubstituted; In certain embodiments, R3 represents hydrogen, -CH2-phenyl, -(CH2)3NHC(=NH)NH2, (CH2)2CONH2, -(CH2)2COOH, -(CH2)4NH2, or -CH2-imidazolyl. In certain embodiments, R3 represents hydrogen, -CH2-phenyl, -(CH2)3NHC(=NH)NH2, (CH2)2CONH2, -(CH2)2COOH or -(CH2)4NH2. In certain embodiments, R3 represents hydrogen, -CH2-phenyl, -(CH2)3NHC(=NH)NH2, (CH2)2CONH2 or -(CH2)2COOH. In certain embodiments, R3 represents hydrogen, -CH(CH3)-CH2-CH3, -CH2-CH(CH3)2, CH3COOH, or -CH2-heteroaryl; wherein the heteroaryl is unsubstituted. In certain embodiments, R3 represents -CH2-phenyl, -(CH2)3NHC(=NH)NH2, (CH2)2COOH or -(CH2)4NH2; In certain embodiments, Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring. In other embodiments, the present invention provides a compound of formula (I): where; 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 phenyl, indolyl and imidazolyl are unsubstituted; or Ray Ri, together with the atoms to which they are attached, form a pyrrolidine ring optionally substituted with an oxo group; R2 represents hydrogen, -CH2-OH, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, CH2-phenyl, -CH2-indolyl or -CH2-imidazolyl; wherein the imidazolyl is unsubstituted. Rb is hydrogen; and R3 represents hydrogen, -CH2-phenyl, -(CH2)3NHC(=NH)NH2, (CH2)2CONH2, -CH2COOH, -CH2-CH(CH3)2, -(CH2)2CONH2, -(CH2)2COOH, -(CH2)4NH2, -ch2indolyl or -CH2-imidazolyl; wherein phenyl, indolyl and imidazolyl are unsubstituted; 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 Raes hydrogen; Ri represents hydrogen, -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, -CH2-phenyl or -CH2-imidazolyl; o Ray Ri, together with ρορ / ηη / ηζηζ / Β / γι 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. In certain embodiments, the compound is not one of pQf / nn / nznz / B / Yi In certain embodiments, the present invention provides a compound of formula (IA): or a pharmaceutically acceptable salt, amide, ester or stereoisomer thereof; wherein, Ri, Ray and R2 are as defined in the compound of formula (I). In certain embodiments, Ri represents hydrogen, -CH2-COOH, -CH2-CONH2, CH(CH3)-CH2-CH3%CH2)2CONH2, -(CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2-phenyl, CH2-indolyl or -CH2-imidazolyl. In certain embodiments, Ri represents hydrogen, -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2-phenyl or -CH2-imidazolyl. In certain embodiments, Ri represents -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2or -(CH2)4NH2. In certain embodiments, Ri represents -(CH2)2CONH2or -(CH2)2COOH. In certain embodiments, R2 represents hydrogen, -CH2-OH -(CH2)2CONH2, (CH2)3NHC(=NH)NH2, -(CH2)2COOH or -CH2-phenyl. In certain embodiments, R2 represents hydrogen, -(CH2)3NHC(=NH)NH2 or (CH2)2COOH. In certain embodiments, R2 represents hydrogen, -(CH2)2CONH2 or -(CH2)2COOH. In other embodiments, the present invention provides a compound of formula (IA): wherein Ra is hydrogen; and R1 represents hydrogen, -(CH2)2CONH2, -(CH2)2COOH, (OΗ2)3NH(O=NH)NH2, -(CH2)4NH2, -CH2-phenyl or -CH2-midazolyl; R2 represents hydrogen, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, -CH2-phenyl or -CH2-midazolyl. In certain embodiments, the present invention provides a compound of formula (IA): wherein; R1 is hydrogen; and R1 represents hydrogen, -CH2-COOH, -CH2-CONH2, -CH(CH3)-CH2CH3, -(CH2)2CONH2, -(CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2-phenyl, -CH2-indolyl or -CH2-imidazolyl; wherein phenyl, indolyl and imidazolyl are unsubstituted; R2 represents hydrogen, -CH2-OH -(CH2)2CONH2, -(CH2)3NHC(=NH)NH2, -(CH2)2COOH or CH2-phenyl; where phenyl is unsubstituted; In other embodiments, the present invention provides a compound of formula (IA): wherein; Ra is hydrogen; and R1 represents hydrogen, -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, -CH2COOH, -CH2CONH2, -(CH2)4NH2, -CH(CH3)-CH2-CH3,-CH2-phenyl, -CH2indolyl or -CH2-midazolyl; R2 represents hydrogen, -CH2-OH, -(CH2)3NHC(=NH)NH2, -(CH2)2COOH, -CH2-phenyl or CH2-imidazolyl. In other embodiments, the present invention provides a compound of formula (IA): wherein; Ra is hydrogen; and R1 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-midazolyl. In other embodiments, the present invention provides a compound of formula (IA): wherein Ra is hydrogen; and R1 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 -CH2pQf / nn / nznz / B / Yi imidazolyl. In certain embodiments, the compounds of formula (IA) are selected from pQf / nn / nznz / B / Yi pqc i ηη / ηζηζ / Ε / γίΛΐ or a pharmaceutically acceptable salt, amide, ester or stereoisomer thereof; In certain embodiments of the present invention, the compound of formula (IA) can also be written showing the absolute stereochemistry thereof, as pQf / nn / nznz / B / Yi OH In certain embodiments, the present invention provides a compound of formula (IB): A 9xA A. AA ΊΤ VN COOH H and / or । NOT A (B) or a pharmaceutically acceptable salt, amide, ester or stereoisomer thereof; wherein, Ri, Ra, Rb and R3 are as defined in the compound of formula (I). In certain embodiments, the present invention provides a compound of formula (IA): where, Ri represents hydrogen, -CH2-COOH, -CH2-CONH2, -CH(CH3)-CH2-CH3, -(CH2)2CONH2, (CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2-indolyl, -CH2-imidazolyl 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 Rbs hydrogen. In certain embodiments, in formula (IB), Rby R3, together with the atoms to which they are attached, form a pyrrolidine ring. In certain embodiments, R1 represents hydrogen, -CH2-COOH, -CH2-CONH2, CH(CH3)-CH2-CH3, -(CH2)2CONH2, -(CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2-indolyl, -CH2-imidazolyl, or -CH2-phenyl. In certain embodiments, R1 represents hydrogen, -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, -(CH2)4NH2, or -CH2-phenyl. In certain embodiments, R1 represents -(CH2)2CONH2, or -(CH2)2COOH. In certain embodiments, R3 represents hydrogen, -CH2-phenyl, -(CH2)2CONH2 or (CH2)2COOH. 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, CH2imidazolyl, 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. In certain embodiments, R3 represents hydrogen or -CH2-phenyl. 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. In certain embodiments, the present invention provides a compound of formula (IB), wherein R1 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. In certain embodiments, the compounds of formula (I) are selected from pQf / nn / nznz / B / Yi or a pharmaceutically acceptable salt, amide, ester or stereoisomer thereof; In certain embodiments, the present invention provides a compound of formula (IC): or a pharmaceutically acceptable salt, amide, ester or stereoisomer thereof; wherein Ri, Ra, Rj and Rb are as defined in the compound of formula (I). In certain embodiments, Ri represents -(CH2)2COOH, -(CH2)2CONH2, (CH2)3NH(C=NH)NH2 or -(CH2)4NH2. In certain embodiments, Ri represents -(CH2)2CONH2, -(CH2)3NH(C=NH)NH2or (CH2)4NH2. In certain embodiments, Ri represents -(CH2)2CONH2 or -(CH2)3NH(C=NH)NH2. In certain embodiments, in formula (IC), Ra is hydrogen. In certain embodiments, in formula (IC), Ray Ri, together with the atoms to which they are attached, form a pyrrolidine ring. 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 a pyrrolidine ring. In certain embodiments, R3 represents hydrogen, -CH2-phenyl, -(CH2)3NHC(=NH)NH2 or -CH2-imidazolyl. 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. In other embodiments, the present invention provides a compound of formula (IC): wherein R1 represents -(CH2)2COOH, -(CH2)2CONH2, -(CH2)3NH(C=NH)NH2or -(CH2)4NH2; and R3 represents hydrogen, -CH2-phenyl, -(CH2)2CONH2 or -(CH2)2COOH. In other embodiments, the present invention provides a compound of formula (IC): wherein Ra is hydrogen; and R1 represents -(CH2)2CONH2, -(CH2)3NH(C=NH)NH2, or -(CH2)4NH2; or Ray R1, together with the atoms to which they are bonded, form a pyrrolidine ring; and Rb is hydrogen; and R3 represents -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. 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 Ray Ri, together with the atoms to which they are bonded, form a pyrrolidine ring; and Rb is hydrogen; and R3 represents hydrogen, -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. In certain embodiments, the compounds of formula (I) are selected from pQf / nn / nznz / B / Yi or a pharmaceutically acceptable salt, amide, ester or stereoisomer thereof. In certain embodiments, the present invention provides a compound of formula or a pharmaceutically acceptable salt, amide, ester or stereoisomer thereof; where, Ri, Ra, R3 and Rb are as defined in the compound of formula (I). In certain embodiments, R1 represents -(CH2)3NH(C=NH)NH2, -(CH2)4NH2 or CH2CONH2. In certain embodiments, R3 represents hydrogen, -(CH2)3NHC(=NH)NH2, or (CH2)4NH2. 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. In certain embodiments, where Rb is hydrogen; R3 represents hydrogen, (CH2)3NHC(=NH)NH2 or -(CH2)4NH2;O Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring. In other embodiments, the present invention provides a compound of formula (ID): wherein R1 represents -(CH2)3NH(C=NH)NH2, -(CH2)4NH2o -CH2CONH2; Rb is hydrogen; R3 represents hydrogen, -(CH2)3NHC(=NH)NH2 or -(Ch^NhU or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring; In other embodiments, the present invention provides a compound of formula (ID): wherein R1 represents -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, or -CH2CONH2; R is hydrogen; and R represents hydrogen, -(CH)NHC(=NH)NH or -(CH)NH; or R by R, and R, together with the atoms to which they are attached, form a pyrrolidine ring. In certain embodiments, the compounds of formula (I) are selected from ηη / ηζηζ / Β / γι or a pharmaceutically acceptable salt, amide, ester or stereoisomer thereof. In certain embodiments, the present invention provides a compound of formula (IE): (IE) or a pharmaceutically acceptable salt, amide, ester or stereoisomer thereof; wherein, R2, R3 and Rb are as defined in the compound of formula (I). In certain embodiments, R2 represents hydrogen, -CH2-OH, -(CH2)2COOH, (CH2)3NHC(=NH)NH2, -CH2-phenyl, or -CH2-indolyl. In certain embodiments, R2 represents hydrogen or -(CH2)3NHC(=NH)NH2. In other embodiments, the present invention provides a compound of formula (ID): wherein; R2represents hydrogen, -CH2-OH, -(CH2)2COOH, -(CH2)3NHC(=NH)NH2, -CH2-phenyl or -CH2indole; 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; In certain embodiments, in formula (IE), Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring. In certain embodiments, R2 represents hydrogen, -(CH2)3NHC(=NH)NH2, -CH2-OH (CH2)2COOH, -CH2-phenyl, or -CH2-indolyl. 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. In certain embodiments, R3 represents hydrogen, -CH2-COOH, -(CH2)2COOH, -CH219 CH(CH3)2, -CH(CH3)-CH2-CH3.-(CH2)4NH2, -CH2-phenyl, -CH2-indolyl or -CH2- imidazolyl or Rby 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 (IF): pQf / nn / nznz / B / Yi r3b COOH or a pharmaceutically acceptable salt, amide, ester or stereoisomer thereof; wherein, R2, R3 and Rb are as defined in the compound of formula (I). In certain embodiments, R2 represents hydrogen, -CH2-phenyl, -(CH2)3NHC(=NH)NH2 or -(CH2)2COOH. In certain embodiments, R3 represents -CH2-phenyl, -(CH2)2CONH2, -(CH2)2COOH or (CH2)4NH2. In certain embodiments, R3 represents -CH2-phenyl, -(CH2)2CONH2 or -(CH2)2COOH. 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. 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 represents -CH2-phenyl, -(CH2)2CONH2, -(CH2)2COOH or -(CH2)4NH2. 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; R is hydrogen; and R represents -CH-phenyl, -(CH)CONH, or -(CH)COOH; or Rb and R, together with the atoms to which they are attached, form a pyrrolidine ring. In certain embodiments, the compounds of formula (I) are selected from or a pharmaceutically acceptable salt, amide, ester or stereoisomer thereof. In certain embodiments, Ra is hydrogen; and Ri represents hydrogen, -(CH2)2CONH2, (CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, -CH2-aryl, or -CH2-heteroaryl; or Ray 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, (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, R is hydrogen; and R represents hydrogen, -(CH)CONH, (CH)COOH, -(CH)NH(C=NH)NH, -(CH)NH, -CHCONH, -CH-phenyl, or -CH-imidazolyl; or R, 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. In certain embodiments, the present invention provides a compound selected from: ρορ / ηη / ηζηζ / Β / γι Compound Structure 1 nh2 L o^nh2 S So QyoH h2n ^Sr NN Á N—0 HL— / ; 2 HN^NHz HN. 0^,0 HSS 0 °^ΟΗ H2N te te N Nte, N—O “ O ; 3 X 0 ZI CN ,1 1 I > < I / \ 1 ° H \---' ~Z- / / CN OX 4 hn^nh2 HN. O^.NH2 S So °2 / XNχ— Η 5 i ON) / / E - \ ? \ / 1 2 1 I / N> TZ >° o 6 O^NHs O °^ΟΗ 1 N / re JL A H2N XVNN^XN—OH '-- / ; / 8 hn^nh2 O^OH HN.,Α^ΟΗ 7 NN π H N-ο HH 0 ; 9 ην^νη2 NH o^nh2hn y 0 ) Pre / OH N2^ Ure. ·==' ZT T / '\ Li Vi 1 i Λ 2 / / <xi O T pqp / ηη / ηζηζ / Ε / γίΛΐ Compuesto Estructura 11 ην^νη2 HN O-.NH2 I - 0 hAvAV N—0 H H ÍJ ; 12 hn^nh2 ο^νη2ην. o^nh2 I 0 1 N—0 H H i ; 13 nh2 k O^OH N k Ύ X > A H2N XNNYN—0 HH 0 ; 14 N-—, n H 1 0 JL A. .OH H2N X -VNNXN—0 HH Í ; 15 == r-'z- m __ / 1 Z y---' wf ZO °\Λ 1 >° °4 0 T 16 ΞΕ z >° 0 I cor i ηη / ηζηζ / Ε / γίΛΐ Compuesto Estructura 17 ip M / / Z z--V ' oy IZ >° o X 18 XO °Ά ZI y^z I / OI 19 N-—, «A la o 0 yOH H^XífAA^AA N—0 H LJ ; 20 A AA 0 ogoH h2n\NV^AnA N—0 H '-- / ; 21 0^nh2 o^oh AA 0 °yOH h2n\NA O n—o H Gy · 22 °yOH HN^ 1 j. NI ° N—OHH i ; 23 T o ó^A? °A ZT CN Z 1 < < T / \ / A vi X f oK z \\ CM OI pop / nn / iz / B / yi Compuesto Estructura 24 IO 0=® í te LI / ΕΕ / \ Z—AZ \\<N O X 25 ΞΕ O °^o í m I j -A / — I / CM 26 ΗΝγΝΗ2 HN> O \ o \ 0 V0H HI ? VT η2νΧτνυΧΧΑ n—o H ; 27 ΗΝγΝΗ2Ν^ΝΗ2 HN HN So °yoH η2νΧτν·υχΧα N-0 H < / ; 28 T O o^~Qi °%x CM / 1 । ' · ( ζμ -. Π ρορ / ηη / ηζηζ / Β / γι Compuesto Estructura 29 □z ro Z ,--- l zz > =° o ZT 30 TO <+0 °At f Λ yi I Γ n=\ / \ CN 31 ΗΝγΗΗ2 HN S o °yoH h^V'AÁ N—0 H If ? 32 ΕΕ O ó^OO / \ ​​# ' 4^0 ° Z\- 1 ΕΕ / ° Z\ / >---' z / / cxi OX 33 YH o H2N^^Ny--C OH N—O7 34 IPZ y--V / -7 O ¿Y pz \>x^o 1 o I Compuesto 27 Estructura 35 I O -Z.-J Ογ Í'C z / T / o / λ \— Z. / / OI O X 36 hn^nh2 O^OH HN N x k jy Λ > 0 f N Λ-i H H S ; 37 ΗΝγΝΗ2 O^OH HN. 1 - o γ h^V^A^oh i-i H H S ; 38 hn^nh2 O^OH HN. o^| \ o °y°H A M N-0 M L-V ; 39 o7 o^O <N / / ZH vi - / X / )—' 2 / / CN O X 40 oz o^Qi ZI ZH vi - s ' z / / CN O X ρορ / ηη / ηζηζ / Β / γι Compuesto Estructura 41 <N X X Z^ O '---\ ZI ZI x / Z >—< \--' / / CN O I 42 I P K> / / Z >--¥ ' Z / X z% '2 XZ xz V—o o=\ '— o z X X K> 43 nh2 NH o^nh2 ) ΝΠ2 ] Γ 0^ A 0 Λ ha^vv1 ft-ó H H S ; 44 hn^nh2 O^OHHN. । i - ° H2N jf Ίμ LJ^^lT N—0 H H o 45 hn^nh2 nh2 0^0 HHN. < 1 - 0 I u , / OH \ ® 0 f^0 . / Af'A'V Λ—A H H S ; 48 ΗΝγΝΗ2 O^OH HN 1 - o M H H S ; 49 ZI ¿A ΞΕ / Z y—< \ / / <n o n: 50 x ιό z y--y ' t ζ·="\" iz>° IZ < oo=\ '— oo I z 51 hnvnh2 O^OHHN Ο·^| / ΟΗ I = 0 I HzN jf NN—0 HH q 52 HN^NH2 O^OHHN. I - ° u .oh H2N qf n N—0 HH 0 53 0 °^-OH '' / 1—1 1 ✓ N—O ' / ; water cor i ηη / ηζηζ / Ε / γίΛΐ or a pharmaceutically acceptable salt, an amide, an ester or a stereoisomer thereof. pQf / nn / nznz / B / Yi In certain modalities, the present invention provides a compound selected from: 6 i O 0^0 and ζτ h <N X / \ / / CN o I 7 ην^νη2 HN. O^OH L l ÍJ te te 0 Η2ΝΛγΝγΛΝΛΝΛΥ°Η N—0 H H ü ; 8 IZ 1 zte 1 B 9 IZ ± z > ° IZ / --' z \ _ / I IXJ o=\ o T 10 / =\ I / 7 ° tete Zx tel — ~z. / / CN OI 12 I 9 Z / —\ -Z.^\ MT 1 / z o5„„te 1 IZ 0O O IZ ,--1 / zo=¿ »? o I 14 N-, Xj η Ξ 0 η2ν^<ν0'ν7'ν0'ΟΗ N—0 HH ΰ ; pqp i ηη / ηζηζ / Ε / γίΛΐ 16 x γό ζ ΧΖ >° or χ 17 Ο^ΟΗ Λ 0 θ^^ΟΗ Ν—0 Η te / . 18 41 <Ν XI ζ^ Ο '—\ ζχ C. νζ ΝΗ2 1 l· 0 ( H2r'*^~'VN'< Ν—0 Η Η 5 ; pqc / ηη / ηζηζ / Ε / γίΛΐ nh2 l· ll 49 h2n' V / N-0 0 Η H Ix. U ^OH 0 ;y CK „nh2 CteOH 50 h2n V 7 N-0 0 ^N^N' Η HA^OH 0 ; cor i ηη / ηζηζ / Ε / γίΛΐ o una sal faracéuticamente aceptable, una amida, un éster o un estereoisómero de este. In certain ways, the present invention provides a pharmaceutical composition that includes compounds as described herein, optionally mixed with a pharmaceutically acceptable carrier or diluent. The present invention also provides methods for formulating the described components for pharmaceutical administration. 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 a 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 such pharmaceutical compositions are intended for human administration, particularly for invasive routes of administration (i.e., routes, such as injection or implant, that circumvent transport or diffusion across an epithelial barrier), the aqueous solution 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 unit dosage form, such as a tablet, capsule (including dispersible capsule and gelatin capsule), granule, lyophilized powder, solution, syrup, suppository, injection, or the like. 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 an eye drop. 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 of the present invention. Such 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, which includes 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, for example, have a compound of the invention incorporated therein. Liposomes, for example, which comprise phospholipids or other lipids, are nontoxic, physiologically acceptable, and metabolizable carriers that are relatively simple to manufacture and administer. The term "pharmaceutically acceptable" is used herein to refer to those compounds, materials, compositions and / or dosage forms that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and animals without undue toxicity, irritation, allergic response or other problems or complications, in a manner commensurate with a reasonable risk / benefit ratio. The term “pharmaceutically acceptable carrier” as used herein refers to a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material. Each carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not deleterious to the patient. Some examples of materials that can function as pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose, 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) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository waxes;(9) oils, such as peanut oil, cottonseed 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 buffers; and (21) other compatible nontoxic substances employed in pharmaceutical formulations. A pharmaceutical composition (preparation) may be administered to a subject by any number of routes of administration including, for example, oral (e.g., oral solutions such as in aqueous or non-aqueous solutions or suspensions, tablets, capsules (including dispersible capsules and gelatin capsules), boluses, powders, granules, pastes for application to the tongue); absorption through the oral mucosa (e.g., sublingually); anal, rectal, or vaginal (e.g., as a paste, cream, or foam); parenteral (including intramuscular, intravenous, subcutaneous, or intrathecal such as, for example, 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 an eye drop). The compound may also be formulated for inhalation.In certain embodiments, the compound may simply be dissolved or suspended in sterile water. The formulations may conveniently be presented in unit dosage form and may be prepared by any of the methods known in the art of pharmacy. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will vary depending on the host being treated and the particular 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, of one hundred percent, this amount will range from about 1 percent to about ninety-nine percent of the active ingredient, preferably from about 5 percent to about 70 percent, more preferably from about 10 percent to about 30 percent. Methods for preparing these formulations or compositions include the step of bringing into association an active compound, such as a compound of the present invention, with the carrier and, optionally, one or more auxiliary ingredients. In general, the formulations are prepared by uniformly and intimately bringing into association a compound of the present invention with liquid carriers or finely divided solid carriers, or both, and then, if necessary, shaping the product. Formulations of the invention suitable for oral administration may be in the form of capsules (including dispersible capsules and gelatin capsules), cachets, pills, caplets, dragees (using a flavored base, typically sucrose and acacia or tragacanth), lyophilize, powders, 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 an active ingredient. The compositions or compounds may also be administered as a bolus, electuary, or paste. In order to prepare solid dosage forms for oral administration (capsules (including dispersible 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, polyvinylpyrrolidinone, 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 retarding agents 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) coloring agents. In the case of capsules (including dispersible capsules and gelatin capsules), tablets, and pills, the pharmaceutical compositions may also comprise buffering agents. It is also possible to employ solid compositions of a similar type as fillers in soft or hard gelatin capsules by using excipients such as lactose or milk sugars, as well as high molecular weight polyethylene glycols and the like. A tablet may be manufactured by compression or molding, optionally with one or more auxiliary ingredients. Tablets may 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), surface active agent, or dispersing agent. Molded tablets may be manufactured by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. Tablets and other solid dosage forms of pharmaceutical compositions, such as dragees, capsules (including dispersible capsules and gelatin capsules), pills, and granules, may optionally be qualified 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 therein using, for example, hydroxypropyl methylcellulose 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 the incorporation of sterilizing agents in the form of sterile solid compositions that can be dissolved in water under sterile conditions or some other sterile injectable medium immediately before use. These compositions may also optionally contain opacifying agents and may be of a composition such that they release the active ingredient(s) only or preferentially in a particular part of the gastrointestinal tract, optionally in a delayed manner. Examples of inclusion compositions that may be employed include waxes and polymeric substances. The active ingredients may also be in microencapsulated form, if appropriate, with one or more of the aforementioned excipients. Liquid dosage forms useful for oral administration include emulsions, lyophiles for reconstitution, microemulsions, pharmaceutically acceptable solutions, suspensions, syrups and elixirs. In addition to the active ingredient, the 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 (particularly cottonseed, peanut, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofuryl alcohol, polyethylene glycols and sorbitan fatty acid esters and mixtures thereof. In addition to inert diluents, oral compositions may also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening agents, flavoring agents, coloring agents, perfuming agents, and preservatives. 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 metahydroxide, bentonite, agar-agar and tragacanth and mixtures thereof. 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 is solid at room temperature but liquid at body temperature and will therefore melt in the rectum or vaginal cavity and release the active compound. Formulations of pharmaceutical compositions for oral administration may be presented as a mouthwash, an oral spray, or an oral ointment. Alternatively or additionally, the compositions may be formulated for administration via a catheter, stent, wire, or other intraluminal device. Administration via such devices may be especially useful for administration to the bladder, urethra, ureter, rectum, or intestine. Formulations that are suitable for vaginal administration also include ρoρ / ηη / ηζηζ / Β / γι pessaries, tampons, creams, gels, pastes, foams or spray formulations containing such carriers as are considered suitable in the art. Dosage forms for topical or transdermal administration include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches, and inhalers. The active compound can be mixed under sterile conditions with a pharmaceutically acceptable carrier and any necessary preservatives, buffers, or propellants. 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 of these. Powders and aerosols may contain, in addition to an active ingredient, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates, and polyamide powder, or mixtures of these substances. Aerosols may also contain conventional propellants, such as chlorofluorohydrocarbons and unsubstituted volatile hydrocarbons, such as butane and propane. Transdermal patches have the additional 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 active 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 either by providing a rate-controlling membrane or by dispersing the compound in a polymeric gel or matrix. The phrases "parenteral administration" and "administered parenterally" as used herein mean modes of administration other than enteral and topical administration, often by injection, and include, but are not limited to, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal, and intrasternal injection and infusion. Pharmaceutical compositions suitable for parenteral administration comprise one or more active compounds in combination with one or more sterile, pharmaceutically acceptable, isotonic aqueous or non-aqueous solutions, dispersions, suspensions or emulsions or sterile powders which can be reconstituted into sterile injectable solutions or dispersions just prior to use, which may contain antioxidants, buffers, bacteriostats, solutes which render the formulation isotonic with the blood of the recipient or desired suspending or thickening agents. Examples of suitable aqueous and non-aqueous carriers which may 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. Adequate fluidity may be maintained, for example, by the use of coating materials such as lecithin, by maintaining the necessary particle size in the case of dispersions and by the use of surfactants. These compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents, and dispersing agents. Prevention of the action of microorganisms may be ensured by the inclusion of various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, and the like. It may also be desirable to include isotonic agents, such as sugars, sodium chloride, and the like, in the compositions. Furthermore, prolonged absorption of the injectable pharmaceutical form may be achieved by the inclusion of agents that delay absorption, such as aluminum monostearate and gelatin. In some cases, to prolong the effect of a drug, it is desirable to slow the absorption of the agent from subcutaneous or intramuscular injection. This can be achieved by using a liquid suspension of crystalline or amorphous material with low water solubility. 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 drug form is achieved by dissolving or suspending the drug in an oily vehicle. Injectable depot forms are produced by forming microencapsulated matrices of the present compounds in biodegradable polymers such as polylactide-polyglycolide. Depending on the ratio of drug to polymer and the nature of the particular polymer used, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Injectable depot formulations are also prepared by entrapping the drug in liposomes or microemulsions that are compatible with body tissues. For use in the methods of the present invention, the active compounds may be administered alone 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. Delivery methods can also be provided by refillable 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-biodegradable polymers, can be used to form an implant for sustained release of a compound at a particular target site. Actual dosage levels of the active ingredients in the pharmaceutical compositions may vary 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 mode of administration, without being toxic to the patient. The dosage level selected will depend upon a variety of factors including the activity of the particular compound or combination of compounds employed or the ester, salt or amide thereof, the route of administration, the time of administration, the rate of excretion of the particular compounds employed, the duration of treatment, other drugs, compounds and / or materials used in combination with the particular compounds employed, the age, sex, weight, condition, general health and previous medical history of the patient being treated and similar factors known in the medical art. In general, a suitable daily dose of an active compound used in the compositions and methods of the invention will be that amount of the compound that represents the minimum effective dose to produce a therapeutic effect. Such effective dose will generally depend on the factors described above. If desired, the effective daily dose of the active compound may be administered as one, two, three, four, five, six, or more subdoses 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 daily. In preferred embodiments, the active compound will be administered once daily. The patient who receives this treatment is any animal that needs it, which includes primates, particularly humans, and other mammals such as horses, cattle, pigs, and sheep; as well as poultry and pets in general. Wetting, emulsifying and lubricating agents, such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants, may also be present in the compositions. 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, ethylenediamine tetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, and the like. In certain embodiments, the compounds described herein enhance the phagocytic activity of macrophages toward a cancer cell, e.g., an AML cell. In other embodiments, phagocytic activity is enhanced, e.g., by 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90%, relative to a macrophage in the absence of the compounds described herein. In certain embodiments, the present invention provides uses of compounds of the present invention for the preparation of a medicament. 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. In certain embodiments, the present invention provides methods for treating cancer, wherein the method comprises administering compounds of the present invention, for example, in a therapeutically effective amount, to the subject in need thereof. In certain embodiments, the present invention provides methods for inhibiting tumor cell growth and / or metastasis by administering a compound of the present invention, for example, in a therapeutically effective amount, to the subject in need thereof. In certain embodiments, the present invention provides a compound of formula (I), or a pharmaceutically acceptable salt, amide, ester or 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 the aryl and heteroaryl are unsubstituted; or RayRi, together with the atoms to which they are attached, form a pyrrolidine ring optionally substituted with an oxo group; R2 represents hydrogen, -CH2-OH, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, CH2-aryl or -CH 2-heteroaryl; wherein 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 aryl and heteroaryl are unsubstituted; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring. Representative tumor cells include cells from a cancer 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 infraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's disease, non-Hodgkin's lymphoma, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, soft tissue sarcoma, cancer of the urethra, penile cancer, chronic or acute leukemias including acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia,Chronic lymphocytic leukemia, childhood solid tumors, lymphocytic lymphoma, bladder cancer, cancer of the kidney or ureter, carcinoma of the renal pelvis, central nervous system (CNS) malignancy, non-small cell lung cancer (NSCLC), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brainstem glioma, pituitary adenoma, Kaposi's sarcoma, squamous cell cancer, squamous cell cancer, T-cell lymphoma, B-cell lymphomas, environmentally induced cancers including those induced by asbestos (e.g., mesothelioma), and combinations of such cancers. In certain embodiments, the present invention provides uses of compounds of the present invention for the preparation of a medicament for the treatment of a bacterial, viral or fungal infection, as well as methods of administering a compound of the present invention, for example, in a therapeutically effective amount, for the treatment of a bacterial, viral or fungal infection. Still other embodiments of the present invention provide methods for treating an 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. In certain embodiments, the invention provides uses of compounds of the present invention for inhibiting the CD-47 pathway. In certain embodiments, the present invention provides methods for treating an infectious disease 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. Representative infectious diseases include, but are not limited to, HIV, Influenza, Herpes, Giardiasis, Malaria, Leishmaniasis, pathogenic Hepatitis virus infection (A, B, and C), Herpes viruses (e.g., VZV, HSV-I, HAV-6, HSV-II, and CMV, Epstein-Barr virus), Adenovirus, Influenza virus, Flaviviridae, Echovirus, Rhinovirus, Coxsackievirus, Respiratory syncytial virus, Mumps virus, Rotavirus, Measles virus, Rubella virus, PQF / NN / NZNZ / B / YI parvovirus, Vaccinia virus, HTLV virus, Dengue virus, Papillomavirus, Molluscum virus, Poliovirus, Rabies virus, JC virus, and Arboviral encephalitis virus, pathogenic Chlamydia bacteria infection, Rickettsial bacteria, Mycobacteria, Staphylococci, streptococci, pneumococci, meningococci and conococci, Klebsiella bacteria, Proteus, Serratia, Pseudomonas, E.coli, legionella, diphtheria, salmonella, bacilli, cholera, tetanus, botulism, anthrax, plague, leptospirosis and Lyme disease, pathogenic infection by 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 parasites Entamoeba histolytica, Balantidium coli, Naegleriafowleri, Acanthamoeba sp., Giardia lambía, Cryptosporidium sp., Pneumocystis carinii, Plasmodium vivax, Babesia microti, Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondi, Nippostrongylus brasiliensis. 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, the method comprising administering to the individual an effective amount of a compound of formula (I). In certain embodiments, the present invention provides methods for treating atherosclerosis and multiple sclerosis in a subject comprising administering a therapeutically effective amount of a compound of formula (I). 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. The term “treating” includes prophylactic and / or therapeutic treatments. The term “prophylactic or therapeutic” treatment is art recognized and includes administering to the host one or more of the compositions herein. If administered prior to the clinical manifestation of the unwanted condition (e.g., disease or other unwanted condition of the host animal), the treatment is prophylactic (i.e., it protects the host from developing the unwanted condition), whereas if administered after the manifestation of the unwanted condition, the treatment is therapeutic (i.e., it is intended to lessen, alleviate, or stabilize the existing unwanted condition, or the side effects thereof). As used herein, the term “compound(s)” encompasses the compounds of formula (I), (IA), (IB), (IC), (ID), (IE), (IF) and their pharmaceutically acceptable salts or stereoisomers thereof. The term "aryl" as used herein includes, unless otherwise specified, substituted or unsubstituted single ring aromatic groups in which each ring atom is carbon. Preferably, the ring is a 5- to 7-membered ring, more preferably, a 6-membered ring. The term "aryl" also includes polycyclic ring systems having two or more cyclic rings where two or more carbons are common to two adjacent rings, wherein at least one of the rings is aromatic, e.g., the other cyclic rings may be cycloalkyls, cycloalkenyls, cycloalkynyls, aryls, heteroaryls, and / or heterocyclyls. Suitable aryl groups include benzene, naphthalene, phenanthrene, and the like. Preferably, the term "aryl" includes phenyl. The term "heteroaryl" includes, unless otherwise specified, substituted or unsubstituted aromatic single ring structures, preferably 5- to 7-membered rings, more preferably 5- to 6-membered rings, which ring structures include at least one heteroatom, preferably one to four heteroatoms, more preferably one or two heteroatoms. The terms "heteroaryl" and "hetaryl" also include polycyclic ring systems having two or more cyclic rings where two or more carbons are common to two adjacent rings, wherein at least one of the rings is heteroaromatic, e.g., 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 at one or more positions, as valency permits, with any optional substituents described herein. Preferably, the term “heteroaryl” includes imidazolyl and indolyl. The term "acyl" is art-recognized and refers to a group represented by the general formula alkyl-C(O)—. Examples of the "acyl" group include, but are not limited to, acetyl, propionyl, and butyryl. As used herein, a therapeutic agent 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. The term “treating” includes prophylactic and / or therapeutic treatments. The term “prophylactic or therapeutic” treatment is art recognized and includes administering to the host one or more of the compositions herein. If administered prior to the clinical manifestation of the unwanted condition (e.g., disease or other unwanted state of the host animal), the treatment is prophylactic (i.e., it protects the host against the development of the unwanted condition), whereas, if administered after the manifestation of the unwanted condition, the treatment is therapeutic (i.e., it is intended to thereby lessen, palliate, or stabilize the existing unwanted condition, or the side effects thereof). As used herein, the phrase "delay the progression" refers to procedures or applications that are intended to delay the development of a disease or symptoms of a disease (including delaying the onset of at least one symptom of the particular disease). The term “prodrug” is intended to encompass compounds that, under physiological conditions, are converted to the therapeutically active agents of the present invention (e.g., a compound of formula (I)). A common method for making a prodrug is to include one or more selected moieties that hydrolyze under physiological conditions to reveal the desired molecule. In other embodiments, the prodrug is converted by the enzymatic activity of the host animal. 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 depicted above may be replaced with the corresponding appropriate prodrug, for example, where a hydroxyl in the parent compound is present as an ester or a carbonate or carboxylic acid present in the parent compound is present as an ester. As used herein, the term "comprises" or "comprising" is generally used to mean including, that is, allowing for the presence of one or more additional (unspecified) features or components. As used herein, the term "including" as well as other forms such as "includes" and "included" are not exhaustive. As used herein, the term "disease" or "disorder" refers to a pathological condition in an organism that results from a cause or condition, including, but not limited to, infections, acquired conditions, genetic conditions, and is characterized by identifiable symptoms. Diseases and disorders also include those caused by the absence of a compound, such as TIGIT modulators. As used herein, “patient,” “subject,” or “individual” to be treated includes humans 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 mice, rats, hamsters, and gerbils. The present invention includes pharmaceutically acceptable salts of compounds of the invention and their use in the compositions and methods of the present invention. In certain embodiments, contemplated salts of the invention include, but are not limited to, alkyl, dialkyl, trialkyl, or tetraalkyl ammonium salts. In certain embodiments, salts contemplated by 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, salts contemplated by the invention include, but are not limited to, Na, Ca, K, Mg, Zn, or other metal salts. Pharmaceutically acceptable acid addition salts can also exist as various solvates, such as with water, methanol, ethanol, dimethylformamide, and the like. Mixtures of such solvates can also be prepared. The source of the solvates can be from the crystallization solvent, inherent in the preparation or crystallization solvent, or adventitious to said solvent. As used herein, the phrase "pharmaceutically acceptable salt" is intended to include all salts known and used in the art of pharmaceuticals. Pharmaceutically acceptable salts include, but are not limited to, amine salts such as, but are not limited to, chloroprocaine, choline, N,N'-dibenzyl-ethylenediamine, ammonia, diethanolamine and other hydroxyalkylamines, ethylenediamine, N-methylglucamine, procaine, N-benzyl-phenethylamine, 1-para-chlorobenzyl-2-pyrrolidin-1'-ylmethyl-benzimidazole, diethylamine and other alkylamines, piperazine, and tris(hydroxymethyl)aminomethane; alkali metal salts such as, but are not limited to, lithium, potassium, and sodium; alkaline earth metal salts such as, but are not limited to, barium, calcium, and magnesium; transition metal salts such as, but are not limited to, zinc; and other metal salts such as, but not limited to, sodium hydrogen phosphate and disodium phosphate; and also include, but are not limited to,salts of mineral acids such as, but not limited to, hydrochlorides and sulfates; and salts of organic acids such as, but not limited to, acetates, lactates, malates, tartrates, citrates, ascorbates, succinates, butyrates, valerates, and fumarates. Illustrative pharmaceutically acceptable salts include acetate, lactobionate, benzenesulfonate, laurate, benzoate, malate, bicarbonate, maleate, bisulfate, mandelate, bitartrate, mesylate, borate, methyl bromide, methyl nitrate, calcium edetate, methyl sulfate, camsylate, mucate, carbonate, napsylate, bromide, chloride, nitrate, clavulanate, N-methylIglucamine, citrate, ammonium salt, dihydrochloride, oleate, edetate, oxalate, edisylate, pamoate (embonate), estolate, palmitate, esylate, pantothenate, fumarate, phosphate / diphosphate, glucceptate, polygalacturonate, gluconate, salicylate, glutamate, stearate, glycolylarsanilate, sulfate, hexylresorcinate, subacetate, hydrabamine, succinate, hydrobromide, tannate, hydrochloride,tartrate, hydroxynaphthoate, theoclate, iodide, tosylate, triethiodide, lactate, panoate, and valerate, which may be used as dosage forms to modify solubility or hydrolysis characteristics or may be used as prodrug or sustained-release formulations. The preparation of the above-described pharmaceutically acceptable salts and other typical pharmaceutically acceptable salts is described in greater detail in Berg et al., “Pharmaceutical Salts,” J. Pharm. Sci. 66: 1-19 (1977). In certain preferred embodiments, the invention includes pharmaceutically acceptable salts of compounds of the invention and their use in the compositions and methods of the present invention. In certain embodiments, contemplated salts of the invention include, but are not limited to, alkyl, dialkyl, trialkyl, or tetraalkyl ammonium salts. In certain embodiments, contemplated salts of 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 contemplated salts of the invention include, but are not limited to, Na, Ca, K, Mg, Zn or other metal salts. Pharmaceutically acceptable acid addition salts can also exist as various solvates, such as with water, methanol, ethanol, dimethylformamide, and the like. Mixtures of such solvates can also be prepared. The source of the solvates can be from the crystallization solvent, inherent in the preparation or crystallization solvent, or adventitious to said solvent. The term “stereoisomers” refers to any enantiomer, diastereomer or geometrical isomer, such as the compounds of the invention. When the compounds of the invention are chiral, they may exist in racemic or optically active form. Since the pharmaceutical activity of the racemates or stereoisomers of the compounds according to the invention may differ, it may be convenient to use compounds that are enriched in one of the enantiomers. In these cases, the final product or even the intermediates can 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, the 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, diacetyl tartaric acid, dibenzoyl tartaric 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. Chromatographic resolution of enantiomers with the aid of an optically active resolving agent (e.g. dinitrobenzoylphenylglycine, cellulose triacetate or other carbohydrate derivatives or chirally derived methacrylate polymers immobilized on silica gel) is also convenient. The term "ester" as used herein refers to a -C(O)ORn group in pQf / nn / nznz / B / Yi where Rn represents a hydrocarbyl group. The term "amide" as used herein refers to a -C(O)NH2 group. 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 greater 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 such certain embodiments, the compounds of the invention may be enriched in one or more diastereomers. For example, a compound of the invention may have greater than 30%, 40%, 50%, 60%, 70%, 80%, 90%, or even 95% or more. The term “subject” includes mammals (especially humans) and other animals, such as domestic animals (for example, household pets including dogs and cats) and non-domestic animals (such as wild animals). The abbreviations used throughout the specification can be summarized below with their particular meaning. °C (degrees Celsius); % (percentage); ACN (Acetonitrile), brine (NaCl solution); CH2Cl2 / DCM (Dichloromethane); Boc (Tertiary-butyloxycarbonyl); DIC: N,N'-Diisopropylcarbodiimide; DMF (Dimethyl formamide); EtOH (Ethanol); Et2NH (Diethylamine); ECF (Ethylchloroformate), Fmoc (Fluorenylmethyloxycarbonyl); g or gr (gram); h or hr (Hours); HPLC (high performance liquid chromatography); K2CO3 (potassium carbonate); LCMS (liquid chromatography with mass spectroscopy); mmol (Millimoles); M (Molar); pl (Microliter); mL (Milliliter); mg (Milligram); min (Minutes); NaHCO3 (sodium bicarbonate); NMM (N-Methylmorpholine); Na2SO4 (sodium sulfate); NH3 (ammonia), NH2OH.HCl (hydroxylamine hydrochloride), preparative prep-HPLC / HOBt (Hydroxybenzotriazole); HPLC (preparative high performance liquid chromatography); TEA / Et3N (Triethylamine); THF (Tetrahydrofuran); TFA (Trifluoroacetic acid); TFAA (trifluoroacetic acid anhydrous), TIPS (Triisopropylsilane); tR (retention time); EXPERIMENTAL PRACTICE The present invention provides methods for preparing compounds of formula (I) according to the procedures of the following examples with suitable materials. Those skilled in the art will understand that known variations of the conditions and processes of the following preparative procedures can be used to prepare these compounds. In addition, by using the procedures described in detail, one skilled in the art can prepare additional compounds of the present invention. The intermediates or starting materials required for the synthesis are commercially available (commercial sources such as Sigma-Aldrich, USA or Germany; Chem-lmpex USA). pQf / nn / nznz / B / Yi USA; GL Biochem, China; and Spectrochem, India) or, alternatively, these intermediates or starting materials can be prepared using known literature methods. The invention is described in more detail by means of specific examples. HPLC analytical methods: Method 1: Column: ZIC-HILLIC (Sequant), C18 (4.6 X 250mm, 5pm) 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 (Time / % B): 0 / 85, 2 / 85, 20 / 40, 20.1 / 85, 30 / 85. Method 2: Column: Phenomenex Peptide Aeris C18 (2) 100A (250 x 4.6mm, 3.6μ) Flow rate: 1.0 ml / min; Column temperature: 25.0 °C Mobile phase: A= 0.1% TFA (Ac) B=ACN Gradient (Time / % B): 0 / 2, 2 / 2, 15 / 70, 20 / 95, 25 / 100, 30 / 100, 32 / 2, 42 / 2 Preparative HPLC method: 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 are: Buffer A: 0.1% formic acid in water, Buffer B: acetonitrile, column equilibration with 0% buffer B and elution by a gradient of 0% to 10% buffer B over 30 min. LCMS was carried out as triple quadrupole AP1 2000 LC / MS / MS on Agilent 1100 series HPLC with G1315 B DAD using a Mercury MS column or single quadrupole Agilent VL LC / MSD on Agilent 1100 series HPLC with G1315 B DAD using a Mercury MS column or single quadrupole Shimadzu 2020 LCMS on Prominence UFLC system with SPD-20 A DAD. LCMS was carried out as triple quadrupole LC / MS / MS AP1 2000 (Applied Biosystems) with Agilent 1100 series HPLC with G1315 B DAD, using a Mercury MS column or Agüen single quadrupole VL LC / MSD with Agilent 1100 series HPLC with G1315 B DAD, using a Mercury MS column or Shimadzu single quadrupole 2020 LCMS with Prominence UFLC system with SPD-20 A DAD. 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. Those skilled in the art will understand that known variations of the conditions and processes of the following preparative procedures can be used to prepare these compounds. Furthermore, by using the procedures described in detail, one skilled in the art can prepare additional compounds of the present invention. pori ηη / ηζηζ / Β / γι Starting materials are generally available from commercial sources such as Sigma-Aldrich, India or Germany; Combi-Blocks USA, Ark Pharm USA, Chem-lmpex USA; GL Biochem, China and Spectrochem, India. pQf / nn / nznz / B / Yi Example 1: (((S)-4-amino-1-(3-((S)-1,5-diaminopentyl)-1,2,4-oxadiazol-5-yl)-4-oxobutyl)carbamoyl)-L-proline (Compound 1) Synthesis of compound 1b the Ib 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 min, 25% aqueous ammonia (24 mL) was added to the resulting active anhydride mixture and the reaction mass was stirred at 0-5 °C for 30 min. The completion of the reaction was confirmed by TLC analysis. The volatile components were evaporated under reduced pressure and partitioned between water and ethyl acetate. The organic layer was washed with NaHCO3 solution, followed by citric acid solution and brine solution. The separated organic layer was dried over Na2SO4, filtered and evaporated under reduced pressure to obtain 5.6 g of compound 1b. LCMS: 346.4 [M+H]+. Synthesis of compound 1c 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 1 h. 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 solution. The separated organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure to give 5.42 g of compound 1c, which was used directly in the next step. Synthesis of compound 1d NHBoc por1 ηη / ηζηζ / Β / γι NHBoc NH2OH.HC1 1 K2CO3, EtOH 1 nh2 BocHN Y 2 BocHN^' II n'oh íc Id 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. The reaction was confirmed to be complete by TLC analysis. After the reaction was completed, the compound was extracted from water using CH2Cl2 followed by washing the organic layer with water, brine, and concentrated under reduced pressure to yield 5.8 g of compound 1d. LCMS: 361.3 [M+H]+. Synthesis of compound 1f HOBt (3.24 g, 24.0 mmol) and DIC (3.36 mL, 24.0 mmol) were added to a solution of Fmoc-GIn(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 1 h at the same temperature, followed by stirring at room temperature for an additional 2 h. The completion of the reaction was confirmed by TLC analysis. The reaction mixture was quenched with ice-water, and the precipitated white solid was filtered; washed with water (150 mL), and dried under reduced high pressure to obtain 8.62 g of compound 1f. LCMS: 953.7 [M+H]+. Synthesis of compound 1g pQf / nn / nznz / B / Yi 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. Volatiles were evaporated under reduced pressure to give 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 solution. The organic layer was dried over NaSO, filtered, and evaporated under reduced pressure to give a crude solid. 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 NHBoc Compound 1g (4.3 g, 4.5 mmol) was added to a 20% solution of piperidine in DMF (20 mL) at 0 °C, and the reaction mass was stirred at the same temperature for 1 hour. The completion of the reaction was confirmed by TLC analysis. After completion, the reaction mixture was quenched with ice-water, and the resulting white precipitate was filtered and dried in vacuo. The obtained crude product was diluted with hexane, stirred, and filtered to obtain 3.0 g of compound 1h. LCMS: 713.4 [M+H]+. Synthesis of compound 1 i Ih por1 ηη / ηζηζ / Β / γι 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 CH2Cl2 (50 mL) and washed with water (100 mL χ 2), 1 N HCl (100 mL χ 2), water followed by brine solution (100 mL χ 2). The organic layer was dried over Na2SO4; It was filtered and evaporated under reduced pressure to obtain 0.72 g of compound 1i, which was used in the next step without further purification. LCMS: 878.9 [M-100], Synthesis of compound 1j TEA (0.34 mL, 2.46 mm) was added to a solution of H-Pro-O'Bu.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. Volatiles were evaporated and partitioned between ethyl acetate and water. The reaction mixture was diluted with ice-water and extracted with EtOAc. The organic layer was separated and dried over Na2SO4 and concentrated under reduced pressure. The crude compound obtained was purified by column chromatography and the compound eluted in 50% ethyl acetate in hexane. Yield: 0.5 g of compound 1j. LCMS: 910.6 [M+H]+. Synthesis of compound 1 lj Compound 1 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 obtain 0.2 g of crude compound 1. The crude solid material was purified by the preparative HPLC method described under the experimental conditions. LCMS: 412.2 [M+H]+. HPLC ir (min): 9.6. The compounds below were prepared by a procedure similar to that described in Example 1 (Compound 1) with appropriate variations in reactants, reagent amounts, solvents, and reaction conditions. The characterization data for the compounds are summarized herein in the table below. pqpi ηη / ηζηζ / Β / γι Compound Structure Observed Mass [M+H]+ 2. HN^NH2 HN O^OH A So °y-0H h^AN^^AnA n—o HL~y 441.4 3. hn^nh2 O^OH HN AA 0 °y-OH ^νΑ^ΛΑ N—OH '— / 441.2 4. hn^nh2 HN. O^-NH; AAO AOH A ,na A H2N XXNN^\ n-ο H Ly 440.3 5. ην^νη2 o^nh2hn \| yo Aoh H2N Af NA N-θ' HO 440.5 Compound Structure Observed mass [M+H]+ 6. TO <x~Qi ZI s T / Z y— / \ / / CN O 341.4 Example 2: (S)-4-(3-((S)-1-amino-4-guanidinobutyl)-1,2,4-oxadiazol-5-i )-4-(3-((S)-1carboxy-2-phenylethyl)ureido)butanoic acid (Compound 7) ρορ / ηη / ηζηζ / Β / γι Synthesis of compound 2b 2a 2b 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 min, 25% aqueous ammonia (25 mL) was added to the generated active mixed anhydride and stirred at 0-5 °C for 30 min. The completion of the reaction was confirmed by TLC analysis. The volatile components were evaporated under reduced pressure and partitioned between water and ethyl acetate. The organic layer was washed with NaHCO3 solution, followed by citric acid solution and brine solution. The separated organic layer was dried over Na2SO4, filtered and evaporated under reduced pressure to give 7.1 g of compound 2b. LCMS: 526.3 [M+H]+. Synthesis of compound 2c pQC / nn / nznz / E / Yii Trifluoroacetic anhydride (TFAA) (2.83 mL, 20.26 mmol) was added to 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. Completion of the reaction was confirmed by TLC analysis. 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 give 5.8 g of compound 2c. LCMS: 508.3 [M+H]+. Synthesis of compound 2d HN^NHPbf HN^NHPbf1 IHN HN NH2OH.HC1Ί S K2CO3,EtOHBocHNYNH2BocHN^C^NN OH 2c2d 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 volatile components 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 obtained solid was washed with 20% ethyl acetate to obtain 6.1 g of compound 2d. LCMS: 541.3 [M+H]+. Synthesis of compound 1e pQf / nn / nznz / B / Yi HOBt (2.28 g, 16.9 mmol) and DIC (2.62 mL, 16.9 mmol) were added to a solution of Fmoc-Glu^Buj-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 continued to be stirred for 1 h 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, and the precipitated white solid was filtered, washed with water (150 mL), and dried under reduced pressure. The solid was taken up in 10% MeOH / DCM, and the organic layer was washed with 10% NaHCO3 solution, water, and brine. The organic layer was dried over Na2SO4 and concentrated under reduced pressure to give 8.0 g of compound 2f. LCMS: 948.7 [M+H]+. Synthesis of compound 2g 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. Volatiles were evaporated under reduced pressure to give a crude semi-solid, which was diluted with water and ethyl acetate. The organic layer was washed with NaHCO3 solution, followed by brine solution. The separated organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure to give a crude solid. The compound was purified by column chromatography (60-120 silica gel) to give 5.4 g of compound 2g. LCMS: 930.5 [M+H]+. Synthesis of compound 2h 2g 2h Compound 2g (5.4 g, 5.80 mmol) was added to a 50% solution of piperidine in DMF (20 mL) at 0 °C and stirred at the same temperature for 2 h. The 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 obtained crude product 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 H-Phe-OfBu.HCI Pyridine (0.75 mL, 9.3 mmol) was added to a solution of H-Phe-O^u.HCl (2.0 g, 7.75 mmol) in CH2Cl2 (20 mL), pyridine was added and the resulting solution was stirred at room temperature for 10 min. A solution of 4-nitrophenyl chloroformate (1.87 g, 9.30 mmol) in CH2Cl2 (20 mL) was added to the above reaction mixture and the resulting mixture was stirred at room temperature for 3 h. After completion of the reaction (confirmed by TLC), it was diluted with CH2Cl2 (50 mL) and washed with water (100 mL x 2), 10% citric acid (100 mL x 2), water (100 mL), followed by brine solution (100 mL). The organic layer was washed with Na2SO4, filtered and evaporated under reduced pressure to obtain 1.7 g of compound 2i, which was used in the next step without further purification. Synthesis of compound 2j by1 ηη / ηζηζ / Β / γι TEA (0.29 mL, 2.1 mmol) was added to a solution of compound 2h (1.0 g, 1.41 mmol) and compound 2¡ (0.54 g, 1.41 mmol) in THF (10 mL) at room temperature and stirred for 3 h. Volatiles were evaporated and partitioned between EtOAc and water. The reaction mixture was diluted with ice-water and extracted with EtOAc followed by washing with 10% K2CO3 (100 mL x 4), water, and brine solution. The separated 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 0.98 g of compound 2j. LCMS: 955.6 [M+H]+. Synthesis of compound 7 Compound 2j (0.5 g, 5.2 mmol) was added to a cocktail mixture (5 mL) of trifluoroacetic acid: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 obtain 0.34 g of crude compound 2. The crude solid material was purified by preparative HPLC as described in the experimental conditions. LCMS: 491.1 [M+H]+. HPLCtR: (min): 11.1 The compounds below were prepared by a procedure similar to that described in Example 2 (Compound 7) with appropriate variations in reactants, amounts of reagents, solvents, and reaction conditions. The characterization data for the compounds are summarized herein in the table below. Compound Structure Observed mass [M+H]+ 8. IZ J 1 / 2 PV, . IZ 7 z >° IZ ,--' Z \ / TN) O=\ O 441.25 9. ην^νη2 nh2 °γΝΗ2ΗΝ> Cr\ S. 0 | N—0 HH i 457.2 10. IOM / / Z y--¥ Z^P í 1 / z ZA °Λ y 111' m TZ >° IZ °^Ά T \_ / 490.6 11. ην^νη2 HN. O^NH2 I - 0 N-0 HH 0 400.3 12. ην^νη2 o^nh2hn ο^νη2 I ” 0 i hAVnÁnVH N-0 HH (J 471.7 13. ? ZTO ZT °b te Vo ° Λ । tez y >—' -z. I / CN z^ I 453.8 ρορ / ηη / ηζηζ / Β / γι Compound Structure Observed Mass [M+H]+ 14. X N3 A . IZ IZ ° \ V-\ ovyx \_ / 400.2 15. X oh zi I / ZT o 2 I y=z te / — X / CN z—7 T 373.0 pQC / nn / nznz / B / Yi The compounds below were also prepared by a procedure similar to that described in Example 1 (Compound 1) with appropriate variations in reactants, amounts of reagents, solvents, and reaction conditions. The characterization data for the compounds are summarized herein in the table below. Compound Structure Observed mass 16 0 OyOH η2ν / ΥΝΑΖχΛνΑ no HA / 360.1 (M+1) 17 x OM / / Z y--¥ V- / oq xz o X 342.3 (M+1) 19 XM \___ / Z / -- IZ o X 439.9 (M+1) . Compound Structure Observed mass 20 A 0 %-ΟΗ Λ n / < JL A h2n^V y^n νΎ n—o H <y . 431.0 (M+1) 21 X O o^O M T / ZI Wú ° z. l o, VZ r / Z y*— / \— Z / / CN O I 413.1 (M+1) 22 f / ) °\ zx zx V?z X / o λ— Z / / OJ O i 382.0 (M+1) 23 I o o^O zx CN / I 1 i < I / \ z\ / Yo ZH vi T Γ O—A Z Ά <N O I 427.0 (M+1) 24 ΗΝγΝΗ2 NH2 h% A. 0 ΟςγΟΗ η2ν0ΤΝ%^0νΑ>N-0 HY / 473.4 (M+1) 25 XO 0^0 ΖΞΕ CN / 11 < Vi X Γ --- / z X / <N z^ X 440.5 (M+1) pqpi ηη / ηζηζ / Β / γι Compound Structure Observed mass 27 ΗΝγΝΗ2ΗΝγΝΗ2 HN HN fe ugly °y-0H n-ο H Ay 468.5 (M+1) 28 ΗΝγΝΗ2 HN fe o °yoH n—o H Ay X9 h-fe ( 2 11' in TZ or X 425.4 (M+1) 30 ΗΝγΝΗ2 HN—. .fe 1 L o í Arfe fe o -yon ÍnAvAnA n—o H Ay 498.4(M+1) 31 ΗΝγΝΗ2 HN fe o °yoH ^Nfef^N^NÁ ν-o H Ay 369.4 (M+1) 32 / Ν . >----Y fe—' of fe o O® _á' Y.., / o xz 1 o X 414.3 (M+1) pqpi ηη / ηζηζ / Β / γι Compound 64 Structure Observed mass 33 YH or H2N^YNyX J °VoH N—O 432.3 (M+1) 35 XO z— / ZX o7 Z VO z / \=z I / O / r\ / / CN OI 372.0 (M+1) H^6 N^ε ΗΗ2 0 í^N AskkAA Λ-i HHS 480.8 (M+1) 37 ΗΝγΝΗ2 CteOH HN. 3 v- te Htete»Atete Λ-i HHS 457.4 (M+1) 38 ^>=oo xz ,—v ° iz \ / z---' w IZ o X 483.4 (M+1) 39 o7 cYD °=< ZT C4 t--—-ς( te Yo\ / 2 <N O X 469.3 (M+1) ροο / ηη / ηζηζ / Β / γι Compuesto Estructura Masa observada 40 zr O ΙΌ Λ \ / I z----* M IZ > ° to 455.3 (M+1) pQC / nn / nznz / E / Yi The compounds below were also prepared by a procedure similar to that described in Example 2 (Compound 7) with appropriate variations in reactants, amounts of reagents, solvents, and reaction conditions. The characterization data for the compounds are summarized herein in the table below. Compound Structure Observed Mass 41 nh2 CVNH2 JI 0 I Rd HHS 372.3 (M+1) 42 0 <x^NH2 ovnh2 i 0 ! ¿AíVA® R-d H H S 372.3 (M+1) 43 T ΞΕ ° '-\ A° ZI °A ZI Vio O Z 1 UZ CXJ ^·· ( T / X Z—Λ Z V ÍN O T 429.3 (M+1) 44 hn^nh2 O^OHHN. i ! = 0 h2n Vf N<V n n vr°H N—0 H H o 457.3 (M+1) Compuesto Estructura Masa observada 45 hn^nh2 nh2 O^OHHN < I - 0 I ii hAn.® .A. / OH h2n YY n A γ N—0 HH 0 472.3 (M+1) 46 HN^NH2 O^OH HN. \=\ 1 l J. NH A LO hYYA°H Λ—AHHA 530.3 (M+1) 47 ΗΝγΝΗ2 °γ0Η HfS oh Λ Λ—¿ hh S 401.0 (M+1) 49 ΞΕ OM / / 2 / --\ * 2 / 2 2=\ >° IZ 11 \__ / 491.3 (M+1) 50 II oo \\ Ao OA— ZT °=( ZI IN I / z / ^\ \' zi / cxi OX 373.2 (M+1) ρορ / ηη / ηζηζ / Β / γι Compuesto structura masa observed 51 hn^nh2 O^OHHN Ο <γοη s ° f h2n γνυ^νζ^ν'γοη n—o h o 473.4 (m+1) 52 hn^nh2 o^ohhn. 1 h2n^f n^f 473.4(m+1)pori ηη / ηζηζ / Β / γι Example 3: Phagocytosis rescue percentage Reagents DPBS (Gibco), RPMI 1640 WITH HEPES AND L-GLN-500 ML (Lonza), Recombinant human M-CSF (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 units USP), blood collection tubes (BD), Histopaque (density-1.077 gm / ml) (SIGMA 1077), Trypan Blue Solution (SIGMA-T8154), Hemacytometer (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 (generated in-house 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. No. 10437028), FAC round-bottom tubes (BD), BD FACS Verse flow cytometer, 96-well plates, ultra-low binding (Corning). Protocol -1: Luciferase-based phagocytosis assay An in vitro phagocytosis assay was performed to evaluate the ability of the test element to enhance the phagocytic activity of macrophages. Monocytes were isolated from the blood of a healthy donor and cultured for 6–8 days using 10% RPMI (Roswell Park Memorial Institute) media and recombinant human M-CSF to differentiate into macrophages. The media was changed daily. 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, luciferase-expressing Raji cells were cultured in 10% RPMI medium with 100 pg / mL hygromycin B in a tissue culture flask. On the day of phagocytosis, macrophages were serum-starved for 2 hours. 0 were incubated.4 million luciferase-expressing Raji cells per well were plated with purified anti-human CD47 antibody B6H12 or mouse IgG1 K isotype control antibody or various concentrations of the test element in serum-free medium for 30 min at 37 °C and added to the respective well of the macrophage-cultured 48-well plate. After 2 hours, the cells were washed twice with PBS and 100 μL of serum-free RPMI was added to each well. Further, 50 μL of Bright Glow reagent was added to each well followed by cell mixture and incubated for 5 min in the dark. Luminescence reading was taken using a plate reader after transferring the contents of each well to the white plate. The intensity of luminescence indicated the degree of phagocytosis. Each experimental condition was carried out in duplicate. The results of the selected compound of the invention are given in the table below. pQf / nn / nznz / B / Yi Compound % normalized phagocytosis (at 10 pM) 1 39 3 42 6 66 7 58 8 20 9 38 12 44 13 49 14 47 Protocol - 2: FACS-based phagocytosis assay Monocytes were isolated from the blood of a healthy donor and cultured for 6–8 days using 10% RPMI (Roswell Park Memorial Institute) media and recombinant human M-CSF to differentiate into macrophages. The media was changed daily. Simultaneously, H929 cells were cultured in 10% RPMI medium with 50 pg / mL beta-mercaptoethanol in tissue culture flasks. On the day of phagocytosis, adherent macrophages were serum starved for 2 hours in RPMI medium. H929 cells were simultaneously stained with 0.3 μM CFSE dye. After washing, 0.2 million CFSE-stained H929 cells were incubated with human anti-CD47 or mouse IgG1 K isotype control antibody or various concentrations of the test element in serum-free media for 30 min at 37°C. After 2 h of serum consumption, macrophages were dissociated with cell dissociation buffer and collected by gentle scraping and added at a concentration of 0.05 million per well in respective wells of ultra-low attachment 96-well plate with H929 cell culture. Phagocytosis was allowed for 2 hours. After 2 hours, cells were washed with PBS and stained with 1 pL of anti-human CD11b-APC antibody prepared in 100 pL of PBS for 30 min at 4 °C in the dark. Cells were further washed and fixed in 100 pL of fixation buffer until acquired by flow cytometry. The degree of phagocytosis of H929 cells by human macrophages was measured by acquiring the samples by flow cytometry. Samples acquired by flow cytometry were analyzed with the use of FlowJo software. Each experimental condition was carried out in duplicate. FITC-positive cells (CFSE) and CD11b-APC were considered phagocytosed macrophages. Raw data on the % phagocytosis per macrophage were obtained as an Excel spreadsheet from FlowJo.% phagocytosis of the isotype control (background phagocytosis) was subtracted from the % phagocytosis of compound-treated macrophages as well as other controls to obtain corrected phagocytosis values. Corrected phagocytosis values ​​of compound-treated samples were normalized to phagocytosis of the positive control (B6H12) using the formula % normalized phagocytosis = [(% compound corrected phagocytosis) / (B6H12 corrected phagocytosis) * 100] pQC / nn / nznz / B / Yi. Compound % normalized phagocytosis (at 10 pM) 1 45 2 37 3 73 5 56 6 74 7 38 Compound % normalized phagocytosis (at 10 pM) 8 40 10 28 12 20 13 29 14 26 15 62 Composite % normalized phagocytosis (at 10 μM) 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 Composite % normalized phagocytosis (at 10 μM) 37 17 39 23 40 27 41 31 43 43 44 20 46 30 47 18 48 29 49 35 50 26 51 24 52 77 ρορ / ηη / ηζηζ / Β / γι Example 4: Efficacy of Compound 6 in the A20 syngeneic lymphoma model In this efficacy study, female Balb / c (BALB / cAnNTac) mice (6 to 8 weeks old) bred in-house in the A20 syngeneic lymphoma model were used. Animals were individually tail-tagged and maintained in cages identified by a cage card bearing the study code, date of experimentation, sex, and number of animals. Animals were weighed daily throughout the experiment. The A20 cell line (a B-cell lymphoma line derived from a spontaneous reticular cell neoplasm found in an aged BALB / cAnN mouse) was obtained from ATCC. When mean tumor volumes reached approximately 75 mm3, animals were randomized based on tumor volumes into four groups of twelve animals in each group. After randomization into multiple treatment groups, dosing with vehicle and Compound 6 was initiated.All treatments were administered orally at a dosing frequency of twice daily with doses of 3 mg / kg, 10 mg / kg, and 30 mg / kg. Treatment continued for 21 days, after which overall efficacy and tolerability were assessed based on tumor volume and body weight changes observed during the treatment period. On day 21 of treatment, animals in all treatment groups were sacrificed in sequential order 1 hour after the last dose. Individual animal body weights were recorded daily prior to administration of the test item throughout the experimental period. Animals were observed for mortality / morbidity once daily throughout the experimental period and for clinical signs once daily throughout the experimental period. Tumor volumes were measured in all animals in the treatment group three times weekly (once every 2–3 days) using a digital Vernier caliper. From an ethical standpoint, any treatment / control group with a mean tumor weight exceeding 10% of the animal's body weight was humanely euthanized. As a measure of efficacy, %T (treatment) / C (control) and %TGI (% tumor growth inhibition) values ​​were calculated. Graphs and statistical analysis were performed using GraphPad Prism®, Version 7.0.For tumor volume analysis, statistical comparisons were 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. Compound 6 was well tolerated with no signs of body weight loss or clinical signs of toxicity. In terms of antitumor efficacy, compound 6 demonstrated statistically significant tumor growth inhibition (TGI) at all dose levels tested. Treatment with compound 6 produced tumor growth inhibition values ​​of 53%, 64%, and 67% at doses of 3 mg / kg, 10 mg / kg, and 30 mg / kg, respectively. Inhibition of tumor growth by Compound 6 in the A20 pQf / nn / nznz / B / Yi model Compound Group TGI Dose (%) 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 < / n>

Claims

CLAIMS by1 ηη / ηζηζ / B / γι or a pharmaceutically acceptable salt, an amide, an 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-ahlo or CH2-heteroaryl; wherein the 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 an oxo group; R2 represents hydrogen, -CH2-OH, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, CH2-aryl or -CH2-heteroyl; wherein the aryl and heteroaryl groups 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-heteroyl; wherein the aryl and heteroaryl groups are unsubstituted; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

2. The compound of claim 1, wherein Ra is hydrogen; and R1 represents hydrogen, -(CH2)2CONH2, -(CH2)2COOH, (CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, -CH2-ahlo or -CH2-heteroahlo; wherein the aryl and heteroaryl groups are unsubstituted; 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; wherein the aryl and heteroaryl groups are unsubstituted; Rb is hydrogen; and R3 represents hydrogen, -CH2-aryl, -(CH2)3NHC(=NH)NH2, (CH2)2CONH2, -(CH2)2COOH, -(CH2)4NH2 or -CH2-heteroaryl; wherein the aryl and heteroaryl are unsubstituted; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

3. The compound of claim 1, wherein 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.

4. The compound of claim 1, wherein R1 represents hydrogen, -(CH2)2CONH2, (CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, -CH2-phenyl or -CH2-imidazolyl.

5. The compound of claim 1, wherein Ri represents -(CH2)2CONH2, -(CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2CONH2, -CH2-phenyl or -CH2-imidazolyl.

6. The compound of any of claims 1 to 5, wherein R2 represents hydrogen, -CH2-OH, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, -CH2-phenyl, -CH2indolyl or -CH2-imidazolyl.

7. The compound of any of claims 1 to 5, wherein R2 represents hydrogen, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, -CH2-phenyl or -CH2-imidazolyl.

8. The compound of any of claims 1 to 5, wherein R2 represents hydrogen, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH or -CH2-phenyl.

9. The compound of any of claims 1 to 8, wherein 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.

10. The compound of any of claims 1 to 8, wherein R3 represents hydrogen, -CH2-phenyl, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, -CH(CH3)-CH2-CH3, CH2-CH(CH3)2, -(CH2)4NH2 or -CH2-imidazolyl.

11. The compound of any of claims 1 to 8, wherein R3 represents hydrogen, -CH2-phenyl, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, -(CH2)4NH2 or -CH2imidazolyl.

12. The compound of claim 1, wherein Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

13. The compound of claim 1, represented by the 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; or Ra and R1, together with the atoms to which they are attached, form a pyrrolidine ring optionally substituted with an oxo group; R2 represents hydrogen, -CH2-OH or -CH2-heteroaryl; Rb is hydrogen; and R3 represents -CH2-ahlo, -CH2COOH, -CH(CH3)-CH2-CH3, -CH2-CH(CH3)2, -(CH2)2COOH or -(CH2)4NH2.

14. The compound of claim 1, represented by the compound of formula (I), wherein Ra is hydrogen; and R1 represents -(CH2)2CONH2, -(CH2)4NH2, -(CH2)3NH(C=NH)NH2 or CH2-heteroaryl; R2 represents -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH or -CH2-aryl; Rb is hydrogen; and R3 represents hydrogen, -(CH2)2CONH2 or -CH2-heteroaryl; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring. pQf / nn / nznz / B / Yi 15. The compound of claim 1, represented by the compound of formula (IA): (IA) pqp1 ηη / ηζηζ / Β / γι or a pharmaceutically acceptable salt, an amide, an ester or a stereoisomer thereof; wherein, Ri, Ra and R2 are as defined in claim 1.

16. The compound of claim 15, wherein Ri represents hydrogen, -CH2-COOH, CH2-CONH2, -CH(CH3)-CH2-CH3, -(CH2)2CONH2, -(CH2)2COOH, -(CH2)3NH(C=NH)NH2, (CH2)4NH2, -CH2-phenyl, -CH2-indolyl or -CH2-imidazolyl.

17. The compound of claim 15, wherein R1 represents -(CH2)2CONH2 or (CH2)2COOH.

18. The compound of claim 15, wherein R2 represents hydrogen, -CH2-OH, (CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, -CH2-phenyl or -CH2-imidazolyl.

19. The compound of claim 15, wherein Ra is hydrogen; and R1 represents hydrogen, -CH2-COOH, -CH2-CONH2, -CH(CH3)-CH2CH3, -(CH2)2CONH2, -(CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2-phenyl, -CH2-indolyl or -CH2-imidazolyl; R2 represents hydrogen, -CH2-OH, -(CH2)2CONH2, -(CH2)3NHC(=NH)NH2, -(CH2)2COOH or CH2-phenyl.

20. The compound of claim 1, represented by the compound of formula (IB): \ O R3 A. n. AA A. AA Ά H (®) or a pharmaceutically acceptable salt, an amide, an ester or a stereoisomer thereof; wherein, R1, Ra, Rb and R3 are as defined in claim 1.

21. The compound of claim 20, wherein R1 represents hydrogen, -CH2-COOH, CH2-CONH2, -CH(CH3)-CH2-CH3, -(CH2)2CONH2, -(CH2)2COOH, -(CH2)3NH(C=NH)NH2, (CH2)4NH2, -CH2-indolyl, -CH2-imidazolyl or -CH2-phenyl.

22. The compound of claim 20, wherein Ri represents hydrogen, -(CH2)2CONH2, (CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2 or -CH2-phenyl.

23. The compound of claim 20, wherein Rb is hydrogen; R3 represents hydrogen, CH2-COOH, -CH2-CH(CH3)2, -CH(CH3)-CH2-CH3, -(CH2)4NH2, -(CH2)2CONH2, -(CH2)2COOH, -CH2phenyl, CH2-indolyl or CH2-imidazolyl; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

24. The compound of claim 20, wherein; R1 represents hydrogen, -CH2-COOH, -CH2-CONH2, -CH(CH3)-CH2-CH3, -(CH2)2CONH2, (CH2)2COOH, -(CH2)3NH(C=NH)NH2, -(CH2)4NH2, -CH2-indolyl, -CH2-imidazolyl or -CH2-phenyl; 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 and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

25. The compound of claim 1, represented by the compound of formula (IC): pQf / nn / nznz / B / Yi or a pharmaceutically acceptable salt, amide, ester or stereoisomer thereof; wherein, R1, Ra, R3 and Rb are as defined in claim 1.

26. The compound of claim 25, wherein Ra is hydrogen; R1 represents (CH2)2COOH, -(CH2)2CONH2, -(CH2)3NH(C=NH)NH2 or -(CH2)4NH2; or Ra and R1, together with the atoms to which they are attached, form a pyrrolidine ring.

27. The compound of claim 25, wherein Rb is hydrogen; R3 represents hydrogen, CH2-phenyl, -(ChkhCONhh or -(CH2)2COOH; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

28. The compound of claim 25, wherein; Ra is hydrogen; R1 represents -(OH2)2OOOH, -(CH2)2CONH2, -(CH2)3NH(C=NH)NH2, or (CH2)4NH2; or Ra and R1, together with the atoms to which they are attached, form a pyrrolidine ring; Rb is hydrogen; R3 represents hydrogen, -CH2-phenyl, -(CH2)2CONH2 or -(CH2)2COOH; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

29. The compound of claim 1, represented by the compound of formula (ID): (ID) or a pharmaceutically acceptable salt, an amide, an ester or a stereoisomer thereof; wherein, Ri, Ra, R3 and Rb are as defined in claim 1.

30. The compound of claim 29, wherein Ri represents -(CH2)3NH(C=NH)NH2, (CH2)4NH2 or -CH2CONH2.

31. The compound of claim 29, wherein 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.

32. The compound of claim 29, wherein; R1 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 attached, form a pyrrolidine ring.

33. The compound of claim 1, represented by the compound of formula (IE): or a pharmaceutically acceptable salt, an amide, an ester or a stereoisomer thereof; wherein, R2, R3 and Rb are as defined in claim 1.

34. The compound of claim 33, wherein R2 represents hydrogen, -CH2-OH, (CH2)2COOH, -(CH2)3NHC(=NH)NH2, -CH2-phenyl or -CH2-indolyl.

35. The compound of claim 33, wherein, R3 represents hydrogen, -CH2-COOH, (CH2)2COOH, -CH2-CH(CH3)2, -CH(CH3)-CH2-CH3, -(CH2)4NH2, -CH2-phenyl, -CH2-indolyl or -CH2imidazolyl or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.

36. The compound of claim 33, wherein; R2 represents hydrogen, -CH2-OH, -(CH2)2COOH, -(CH2)3NHC(=NH)NH2, -CH2-phenyl or CH2-indolyl; 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.

37. The compound of claim 1, represented by the compound of formula (IF): o^nh2 R2 O R3 1 NXAA H2N qf NN COOH m A H 1 N—O Rb (IF) or a pharmaceutically acceptable salt, an amide, an ester or a stereoisomer thereof; wherein, R2, R3 and Rb are as defined in claim 1.

38. The compound of claim 37, wherein R2 represents hydrogen, -CH2-phenyl, (CH2)3NHC(=NH)NH2 or -(CH2)2COOH.

39. The compound of claim 37, wherein R3 represents -CH2-phenyl, -(CH2)2CONH2, pQf / nn / nznz / B / Yi (CH2)2COOH or -(CH2)4NH2.

40. The compound of claim 37, wherein, R2 represents hydrogen, -CH2-phenyl, -(CH2)3NHC(=NH)NH2 or -(CH2)2COOH; R3 represents -CH2-phenyl, -(CH2)2CONH2, -(CH2)2COOH or -(CH2)4NH2.

41. A compound is selected from Compound Structure 4 hn^nh2 HN O^.NH2 for tea or °y0H Jl n for tea. h2n^XVN not H '— / ; 5 TO 0^0 M ZI CXI / < te M x * r\ / / (NO τ 6 T o °^O ZI I / z \— ~Z1 / (XI OX 7 hn^nh2 HN. O^OH L Ύ JO te te 0 H^tete Otetete N—0 NOH^A Hn'0 ; 8 h Η Η Π Η N-0 HH 0 ; 9 TO CSI . hn^nh2 O^NH2HN TTO η LO N—0 HHS ; 1 tez Y / -- T / CN Z.— / X 14 Nn r^íi <ZX L Ϊ woMAV N-¿ » H & - 15 I / ~z __ / X Z y---' Ni T Z O °\Λ T IZ o I 16 X o 0^0 te ZI o z CN X cor / ηη / ηζηζ / Ε / γίΛΐ Compuesto Estructura 17 O^OH te o °y-oH I n te H2N^tef V b b ó N—0 H y / · 18 ” __ / i Z ¡----' K> 7 IZ >° 0zP o I 19 I ro \____ / z )— Cp IZ >° Ox° o I 20 IO 0 Z / — / \— ~z. r / cm OX 21 I op~0 I / ZT ozl CN VZ I / Z y—< )>— ~z. / / (XI OT 22 °0OH HNte I í N te o f''7 H2N^qfN'0*^N^N^te|x°HN—OHH (ü ; ηη / ηζηζ / Ε / γίΛΐ Compound Structure 24 i o NJ \\ zy— z \ / T y ho ΐ zz^ 1 >° o I 25 w __ / ΞΓ Z / ---' (M ,mh ote )2 Z6 'Z '^ 1. N—η HNX <x l o \ y-oh η2νχτνα^χνα n-0 h te ; 27 hn^nhzhn^n^ hn. k °yoh 28 i v 7 z =7 t z^ a 5>•11' NJ IZ >° or I 29 hn^nh2 HN. Y te 0 °V-0H JLn^ a T h2n^tef te ü > N—0 H te / ; pores ηη / ηζηζ / Β / γι Compuesto Estructura 30 hn^nh2 HN-—. H\ xl lo A \ o y-οκ N-0 HA / ; 31 hn^nh2 HN A o °yoH hxyv'A A N-0 HA / ; 32 ΞΕ O ó^Q °x vi O HV 1 tez X / o Z\ \' z / / CU OI 33 ηη / ηζηζ / Ε / γίΛΐ pqpi ηη / ηζηζ / Β / γι Compuesto Estructura 42 O^NH2 o^nh2 1 0 1 N—0 HH ü ; 43 nh2 NH O^NH2 ) IN Π 2 Γ 0^^ S. 0 < «AyAVh Kd HHS ; 44 hn^nh2 O^OHHN^^ AybV? N—0 HH or 45 ΗΝγΝΗ2 Nh2 Oí^HHN^ N—0 HH or 46 HN. .NH2 l Í7 O^OΗ HN. VA LL NH VAO η2νΛΥνΑνΛνΛΥ0Η r!|—i HHS ; 47 HN^NH2 °y0H HN> OH AA or lÜ—i HHS ; pqp / ηη / ηζηζ / Ε / γίΛΐ pqpi ηη / ηζηζ / Β / γι 42. A pharmaceutical composition that includes a compound of formula (I) of indications with indications 1-41, and a pharmaceutically acceptable carrier.

43. A compound of any of claims 1-41 for use as a medicament.

44. A method for modulating the phagocytic activity of macrophages towards a cancer cell or tumor cell in an individual comprising administering to the individual an effective amount of a compound of formula (I) according to any of claims 1-41.

45. The method of claim 44, wherein 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, cancer of the head or neck, malignant cutaneous or infraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's disease, non-Hodgkin's lymphoma, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, soft tissue sarcoma, cancer of the urethra, penile cancer, chronic or acute leukemias 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, malignant neoplasm of the central nervous system (CNS), non-small cell lung cancer (NSCLC), primary CNS lymphoma, tumor angiogenesis, spinal cord tumor, brainstem glioma, pituitary adenoma, Kaposi's sarcoma, squamous cell carcinoma, squamous cell carcinoma, T-cell lymphoma, B-cell lymphomas, environmentally induced cancers including asbestos-induced cancers (e.g., mesothelioma), and combinations of such cancers.

46. ​​The method of claim 44, wherein the cancer cell is an AML cell.

47. A method for treating or delaying the progression of CD47-mediated diseases or disorders in an individual, the method comprising administering to the individual an effective amount of a compound of formula (I) according to any of claims 1-41.

48. The method of claim 47, wherein the CD47-mediated disease or disorder is cancer.

49. The method of claim 48, wherein the cancer is selected from melanoma, renal cancer, prostate cancer, breast cancer, colon cancer, lung cancer, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, malignant cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's disease, non-Hodgkin's lymphoma, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, soft tissue sarcoma, cancer of the urethra, penile cancer, chronic leukemias or acute, including acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia,chronic lymphocytic leukemia, childhood solid tumors, lymphocytic lymphoma, bladder cancer, kidney or ureter cancer, renal pelvis carcinoma, malignant neoplasm of the central nervous system (CNS), non-small cell lung cancer (NSCLC), primary CNS lymphoma, tumor angiogenesis, spinal cord tumor, brainstem glioma, pituitary adenoma, Kaposi's sarcoma, squamous cell carcinoma, squamous cell carcinoma, T-cell lymphoma, B-cell lymphomas, environmentally induced cancers including asbestos-induced cancers (e.g., mesothelioma), and combinations of such cancers.

50. The method of claim 47, wherein the CD47-mediated disease or disorder is a bacterial, viral, and fungal infection.

51. The method of claim 50, wherein the infectious disease is HIV, influenza, herpes, giardiasis, malaria, leishmaniasis, 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, human 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 coccococci, klebsiella bacteria, proteus, serratia, pseudomonas, E.coli, legionella, diphtheria, salmonella, bacilli, cholera, tetanus, botulism, anthrax, plague, leptospirosis and Lyme disease, pathogenic infection by the fungi Candida (albicans, krusei, glabrata, tropicalis, etc.), Cryptococcus neoformans, Aspergillus (fumigatus, niger, etc.), Genus Mucorales (mucor, absidia, rhizophus), Sporothrix schenckii, 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 gondi or Nippostrongylus brasiliensis.

52. A method for treating or delaying the progression of CD47-mediated atherosclerosis and multiple sclerosis in an individual, the method comprising administering to the individual an effective amount of a compound of formula (I) according to any one of claims 1-41.

53. The compound of formula (I) according to any one of claims 1 to 41, consisting of COOH or a pharmaceutically acceptable salt, an amide, an ester, or a stereoisomer thereof, for the treatment of cancer, 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-ahlo, or CH2-heteroahlo; wherein the aryl and heteroaryl groups are unsubstituted; or Ra and R1, together with the atoms to which they are attached, form a pyrrolidine ring optionally substituted with an oxo group; R2 represents hydrogen, -CH2-OH, -(CH2)3NHC(=NH)NH2, -(CH2)2CONH2, -(CH2)2COOH, CH2-aryl or -CH2-heteroyl; wherein the aryl and heteroaryl groups 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-heteroyl;where the aryl and heteroaryl groups are not substituted; or Rb and R3, together with the atoms to which they are attached, form a pyrrolidine ring.< / x>