BISPECIFIC ANTAGONISTS OF RETINOL-BINDING PROTEIN 4 THAT STABILIZE TRANSTHYRETIN TETRAMERS, THEIR PREPARATION, AND USE IN THE TREATMENT OF COMMON AGE-RELATED COMORBIDITIES

The present invention provides a compound having the structure:whereinX is CR6 or N;R1, R2, R3, R4, and R6 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), —O-(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)R8 or —NHC(S) R8,wherein R7 is, H, -(alkyl), —OH, —O(alkyl), —NH2, —NH(alkyl) or —N(alkyl)2, andwherein R8 is, -(alkyl), —O-(alkyl), —NH2, —NH(alkyl) or —N(alkyl)2;Y is O, S, N, NH, or a bond;Z is O, S, N, NH, (CH2)o, or a bond;R5 is H, OH, halogen, alkyl, or R5 is (CH2)p and is bound to Y when Y is N to form a ring together with Z;o and p are independently 0, 1, 2, or 3;m and n are independently 0, 1, 2, 3, or 4;A, C, and D are each independently N or CR9;R9 is H, halogen, —OH, alkyl, cycloalkyl, cycloalkylalkyl, —O-(alkyl), —S-(alkyl), —NH2, —NH(alkyl), —NH(alkyl)2, —CO2H, —CO(O-alkyl);B and E are N, CR9, or CFG wherein at least one of B or E is CFG;F is absent or present, and when present isG is H, substituted or unsubstituted monocycle, bicycle, heteromonocycle, heterobicycle, aryl, heteroaryl, alkyl, cycloalkyl, cycloalkylalkyl, CO2H, COOR10, OH, OR10, NH2, NHR10, NR10R11, SO2(alkyl), SO2(cycloalkyl), SO2(cycloalkylalkyl), CH2NHR10, CH2NR10R11, or CH2COOR10,wherein each R10 and R11 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), —N(alkyl)2,or a pharmaceutically acceptable salt thereof..

Medienart:	Patent

Erscheinungsjahr:	2023
Erschienen:	2023

Enthalten in:	Europäisches Patentamt - (2023) vom: 02. Nov. Zur Gesamtaufnahme - year:2023

Sprache:	Englisch

Beteiligte Personen:	PETRUKHIN KONSTANTIN [VerfasserIn] RACZ BOGLARKA [VerfasserIn] VARADI ANDRAS [VerfasserIn] MUTHURAMAN PARTHASARATHY [VerfasserIn] RAJA ARUN [VerfasserIn] CIOFFI CHRISTOPHER L [VerfasserIn]

Links:	Volltext [kostenfrei]

Themen:	Sonstige Themen: 615 A61P: Specific therapeutic activity of chemical compounds (...) C07D: Heterocyclic compounds (macromolecular compounds c0 (...) che

Anmerkungen:	Source: www.epo.org (no modifications made), First posted: 2023-11-02, Last update posted on www.tib.eu: 2023-11-30, Last updated: 2023-12-08

Patentnummer:	US2023348415

Förderinstitution / Projekttitel:

PPN (Katalog-ID):	EPA018538312