292644-33-8Relevant articles and documents
Synthesis and structure-activity relationship of non-peptidic antagonists of neuropilin-1 receptor
Liu, Wang-Qing,Megale, Valentino,Borriello, Lucia,Leforban, Bertrand,Montes, Matthieu,Goldwaser, Elodie,Gresh, Nohad,Piquemal, Jean-Philip,Hadj-Slimane, Reda,Hermine, Olivier,Garbay, Christiane,Raynaud, Francoise,Lepelletier, Yves,Demange, Luc
, p. 4254 - 4259 (2014/09/29)
Neuropilins (NRPs) are VEGF-A165 co-receptors over-expressed in tumor cells, and considered as targets in angiogenic-related pathologies. We previously identified compound 1, the first non-peptidic antagonist of the VEGF-A165/NRP binding, which exhibits in vivo anti-angiogenic and anti-tumor activities. We report here the synthesis and biological evaluations of new antagonists structurally-related to compound 1. Among these molecules, 4a, 4c and 4d show cytotoxic effects on HUVEC and MDA-MB-31 cells, and antagonize VEGF-A165/NRP-1 binding. This study confirmed our key structure-activity relationships hypothesis and paved the way to compound 1 'hit to lead' optimization.
PHARMACEUTICAL COMPOSITIONS COMPRISING NEUROPILIN INHIBITORS, AND THEIR USE FOR THE PREVENTION AND/OR TREATMENT OF ANGIOGENIC DISORDERS AND CANCERS
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Page/Page column 30-31, (2012/12/13)
The present invention relates to a compound of general formula (I), wherein Z1 is S or O, preferably S; -Z2- is -NRa-, wherein Ra is H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, preferably Ra is H; -N=; O; S; -CRb=, wherein Rb is H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, C1, Br, I, F, preferably H; -CHRC- wherein Rc is H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, C1, Br, I, F, or -CH2-; preferably -Z2- is -NH- or -N=; each of R1 and R2 independently is H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, C1, Br, I, F; preferably R1 and R2 together and with N and Z2 form an heterocycle eventually substituted, provided that said heterocycle is not an indole; R5 is H, OH, C1-4 alkyl, C1-4 alkoxy, C1-4 alkenyl, C1-4 alkynyl, amine, preferably R5 is NH2, NO2, C1, F, Br, I; more preferably R5 is H or CH3; even more preferably R5 is CH3; each of R8 and R9 independently is, H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, C1, Br, I, F; preferably R8 and R9 together form a cycle comprising 5 or 6 atoms, preferably an heterocycle comprising 5 or 6 atoms, more preferably a 1,3- dioxacyclopentene or a 1,4-dioxane; and - each of R3, R4, R6, R7, R10 and R11 independently is, H, OH, C1-4 alkyl, C1-4 alkoxy, C1-4 alkenyl, C1-4 alkynyl, amine, NO2, F, C1, Br, I; preferably H, CH3, OCH3, OH, NH2, NO2, C1, F, Br, I; more preferably is H or CH3; even more preferably is H; and to a pharmaceutical composition comprising a compound of general formula (I) or esters or salts thereof, in association with at least one pharmaceutically acceptable vehicle; and to the use thereof for inhibiting the Neuropilin pathways in the treatment of cancer and of angiogenic diseases.
Pharmaceutical compositions comprising Neuropilin inhibitors, and their use for the prevention and/or treatment of angiogenic disorders and cancers
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, (2012/12/13)
The present invention relates to a pharmaceutical composition comprising a compound of general formula (I), wherein - Z1 is S or O, preferably S; - -Z2- is -NRa-, wherein Ra is H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, preferably Ra is H; -N=; O; S; -CRb=, wherein Rb is H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, Cl, Br, I, F, preferably H; -CHRc-, wherein Rc is H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, Cl, Br, I, F, or -CH2-; preferably -Z2- is -NH- or -N=; - each of R1 and R2 is independently H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, Cl, Br, I, F; preferably R1 and R2 together and with N and Z2 form an heterocycle eventually substituted, more preferably a substituted azocine, 3H-indole, indazole, 2-imidazoline, 2-pyrazoline, benzthiazole, purine, pyrimidine, pyridine, pyridazine, pyrazine, pyrazole, thiazole, isothiazole, oxazole, isoxazole, quinoline, isoquinoline, quinoxaline, quinazoline, 1-8-naphthyridine, perimidine, [1,10]-phenantroline, phthalazine, pteridine, triazole, triazine, furazan, 6H-1,2,5-thiadiazine, 1,3,4-thiadiazole, tetrazole, or a substituted imidazole and even more preferably a benzimidazole; - R5 is H, OH, C1-4 alkyl, C1-4 alkoxy, C1-4 alkenyl, C1-4 alkynyl, amine, preferably R5 is NH2, NO2, Cl, F, Br, I; more preferably R5 is H or CH3; even more preferably R5 is CH3; - each of R8 and R9 is independently, H, OH, alkyl, alkoxy, aryle, alkenyl, alkynyl, amine, NO2, Cl, Br, I, F; preferably R8 and R9 together form a cycle comprising 5 or 6 atoms, preferably an heterocycle comprising 5 or 6 atoms, more preferably a 1,3-dioxacyclopentene or a 1,4-dioxane; and - each of R3, R4, R6, R7, R10 and R11 is independently, H, OH, C1-4 alkyl, C1-4 alkoxy, C1-4 alkenyl, C1-4 alkynyl, amine, NO2, F, Cl, Br, I; preferably H, CH3, OCH3, OH, NH2, NO2, Cl, F, Br, I; more preferably is H or CH3; even more preferably is H, or esters or salts thereof; in association with at least one pharmaceutically acceptable vehicle; and to the use thereof for inhibiting the Neuropilin pathways in the treatment of cancer and of angiogenic diseases.
HETEROCYCLIC AMIDES USEFUL FOR THE TREATMENT OF CANCER AND PSORIASIS
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Page/Page column 60-61, (2009/04/25)
The present disclosure relates to heterocyclic amide compounds, which are useful for inhibiting the Hedgehog pathway, and their use in treating a disease or medical condition mediated alone or in part by Hedgehog pathway inhibition. Also disclosed are methods for manufacture of these compounds, pharmaceutical compositions including these compounds, and use of these compounds in the manufacture of medicaments for treating such diseases and medical conditions in a subject. Formula (IA) with the provisio that either R2or R3 is (Z).
