公开(公告)号：US20240150297A1

公开(公告)日：2024-05-09

申请号：US18264994

申请日：2022-02-10

Applicant: The Trustees of Columbia University in the City of New York ,  Albany College of Pharmacy and Health Sciences in the City of Albany ,  PETRUKIN, Konstantin ,  RACZ, Boglarka ,  VARADI, Andras ,  CIOFFI, Christopher, L. ,  MUTHURAMAN, Parthasarathy ,  RAJA, Arun

Inventor： Konstantin Petrukhin ,  Boglarka Racz ,  Andras Varadi ,  Christopher : Cioffi ,  Parthasarathy Muthuraman ,  Arun Raja

IPC: C07D231/38 ,  A61K31/496 ,  A61P27/02 ,  C07D261/14 ,  C07D275/03 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12

CPC classification number: C07D231/38 ,  A61K31/496 ,  A61P27/02 ,  C07D261/14 ,  C07D275/03 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12

Abstract: The present invention provides a compound having the structure:




wherein

X1 is N or CR5,



wherein R5 is H, OH, halogen or alkyl;

X2, X3 and X4 are each independently NH, N, S, O or CR6, wherein each R6 is independently H, OH, halogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, haloalkyl, —O—(alkyl), —S—(alkyl), —NH2, —NH—(alkyl), —N(alkyl)2 or —CO2H;

R1, R2, R3 and R4 are each independently —H, —F, —Cl, —Br, —I, —NO2, —CN, —CF3, —CF2H, —OCF3, -(alkyl), -(haloalkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(cycloalkyl), -(cycloalkylalkyl), -(heteroalkyl), heterocycle, heterocycloalkyl, -(alkylheteroalkyl), -(alkylaryl), —OH, —OAc, —O-(alkyl), —O-(alkenyl), —O-(alkynyl), —O-(aryl), (heteroaryl), —SH, —S-(alkyl), —S-(alkenyl), —S-(alkynyl), —S-(aryl), —S-(heteroaryl), —NH2, —NH-(alkyl), —NH-(alkenyl), —NH-(alkynyl), —NH-(aryl), —NH-(heteroaryl), —C(O)R7, —S(O)R7, —SO2R7, —NHSO2R7, —OC(O)R7, —SC(O)R7, —NHC(O)R7 or —NHC(S)R7,

wherein R7 is, H, —(alkyl), —OH, —O(alkyl), —NH2, —NH(alkyl) or —N(alkyl)2;

B is absent or present, and when present is











wherein R8 is H, OH, halogen, alkyl, cycloalkyl,
cycloalkylalkyl, —O-(alkyl), —S-(alkyl), —NH2, —NH-(alkyl), —N(alkyl)2 or —CO2H; and

C is H, substituted or unsubstituted monocycle, bicycle, heteromonocycle, heterobicycle, aryl, heteroaryl, alkyl, cycloalkyl, cycloalkylalkyl, CO2H, COOR9, OH, OR9, NH2, NHR9, NR9R10, SO2R11, CH2NHR9, CH2NR9R10 or CH2COOR9,

wherein R9 and R10 are each independently H, alkyl, cycloalkyl, —C(O)-alkyl, —C(O)-cycloalkyl, —C(O)OH, —C(O)—O-alkyl, —C(O)—O-cycloalkyl, —C(O)NH2, —C(O)NH(alkyl), —C(O)NH(cycloalkyl), —C(O)N(alkyl)2, —CH2NH(alkyl), —CH2COOH, —SO2CH3, —OH, —O(alkyl), —NH2, —NH(alkyl) or —N(alkyl)
wherein R11 is alkyl, haloalkyl, cycloalkyl, aryl, heteroaryl, NH2, NH(alkyl), NH(cycloalkyl), NH(heterocycle), NH(aryl), NH(heteroaryl) or NHCOR12,

wherein R12 is alkyl, haloalkyl, cycloalkyl, heterocycle, aryl or heteroaryl,

or a pharmaceutically acceptable salt thereof.