V1A receptor agonists

摘要

Compounds of formula (I), salts thereof, and compositions and uses thereof are described. The compounds are useful as V1a vasopressin agonists, for the treatment of, e.g., complications of cirrhosis, including bacterial peritonitis, HRS2 and refractory ascites.;

主权项

1. A compound according to formula (I): or a salt thereof, wherein: R1 is selected from (C1-C10)alkyl, (C1-C10)alkoxy, (C1-C10)alkylNH, Ar1-L1- and unsubstituted or substituted cycloalkyl; Ar1-L1- is selected from Ar1-, Ar1-CH2CH2—, Ar1-O—, Ar1-CH2O—, Ar1-NH— and Ar1-CH2NH—; Ar1 is unsubstituted aryl or substituted aryl; R2 is selected from hydrogen, (C1-C6)alkyl, hydroxy, (C1-C6)alkoxy and halogen; R3 is selected from (C1-C6)alkyl, unsubstituted or substituted cycloalkyl and Cy3-CH2—; Cy3- is unsubstituted or substituted aryl or unsubstituted or substituted cycloalkyl; R4 is selected from (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, —((C1-C6)alkylene)-OR4a, —((C1-C6)alkylene)-NR4a2, —((C1-C6)alkylene)-S(C1-C6)alkyl, —((C1-C6)alkylene)-C(═O)OR4a2, —((C1-C6)alkylene)-C(═O)NR4a2, —((C1-C6)alkylene)-C(═NR4a)NR4a2, —((C1-C6)alkylene)-OC(═O)R4a, —((C1-C6)alkylene)-OC(═O)OR4a, —((C1-C6)alkylene)-OC(═O)NR4a2, —((C1-C6)alkylene)-NR4aC(═O)R4a, —((C1-C6)alkylene)-NR4aC(═O)OR4a, —((C1-C6)alkylene)-NR4aC(═O)NR4a2, —((C1-C6)alkylene)-NR4aC(═NR4a)NR4a2, Ar4 and —((C1-C6)alkylene)-Ar4; each R4a is independently selected from hydrogen and (C1-C6)alkyl; Ar4 is selected from unsubstituted or substituted aryl and unsubstituted or substituted heteroaryl; R5 is selected from —((C1-C6)alkylene)-NR5a2 and —((C1-C6)alkylene)-NR5aC(═NR5a)NR5a2; each R5a is independently selected from hydrogen and (C1-C6)alkyl; Q is selected from the groups Q1, Q2, Q3 and Q4: a and b denote the bonds attaching Q to the remainder of the molecule; R6 is selected from hydrogen, (C1-C6)alkyl and —C(═NR6a)NR6a2; each R6a is hydrogen or (C1-C6)alkyl; R7 is selected from (C1-C6)alkyl, Ar7-, Ar7-((C1-C4)alkylene)-, Cy7-, and Cy7-((C1-C4)alkylene)-, Ar7 is unsubstituted or substituted aryl or unsubstituted or substituted heteroaryl; Cy7 is unsubstituted or substituted cycloalkyl; R8 is selected from NH2 and hydroxyl; R9 is selected from hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, —((C1-C6)alkylene)-OR9a, —((C1-C6)alkylene)-NR9a2, —((C1-C6)alkylene)-SR9a, —((C1-C6)alkylene)-C(═O)OR9a2, —((C1-C6)alkylene)-C(═O)NR9a2, —((C1-C6)alkylene)-C(═NR9a)NR9a2, —((C1-C6)alkylene)-OC(═O)R9a, —((C1-C6)alkylene)-OC(═O)OR9a, —((C1-C6)alkylene)-OC(═O)NR9a2, —((C1-C6)alkylene)-NR9aC(═O)R9b, —((C1-C6)alkylene)-NR9aC(═O)OR9a, —((C1-C6)alkylene)-NR9aC(═O)NR9a2, —((C1-C6)alkylene)-NR9aC(═NR9a)NR9a2, Ar9 and —((C1-C6)alkylene)-Ar9; each R9a is independently selected from hydrogen and (C1-C6)alkyl; each R9b is independently selected from hydrogen and (C1-C10)alkyl; Ar9 is selected from unsubstituted aryl, substituted aryl, unsubstituted heteroaryl substituted heteroaryl; R10 is selected from —((C1-C6)alkylene)-OR10a, —((C1-C6)alkylene)-C(═O)NR10a2 and Ar10-CH2—; A10 is unsubstituted heteroaryl or substituted heteroaryl; each R10a is selected from hydrogen and (C1-C6)alkyl; Ar is aryl or substituted aryl; each X is NH and each Y is C═O; or each X is C═O and each Y is NH; m is 0, 1, 2, 3, 4 or 5; n is 0, 1, 2, 3 or 4; o is 1 or 2; p is 1, 2 or 3; and r is 0, 1, 2, 3, 4, 5 or 6; provided that R9 is hydrogen if r is greater than one.