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US 12,195,432 B2Granted
2-arylbenzimidazoles as Ppargc1a activators for treating neurodegenerative diseases
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsSamuel D. Banister, Edgar Engleman, Khoa D. Nguyen, Mark Smith
Life of this patent
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Abstract
A genus of compounds encompassed by formula (III) and their use is disclosed: The compounds activate Ppargc1a and, as a consequence, are useful for treating a variety of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, Huntington's disease, frontotemporal degeneration, dementia with Lewy bodies, motor neuron diseases, and a demyelinating disease.
Claims12
A compound of formula (I):
- wherein:
- W2 is C—R2;
- W3 is N or C—R3;
- W4 is N or C—R4;
- W5 is N or C—R5;
- W6 is CH;
- W7 is N or C—R7;
- W8 is C—R8;
- wherein:
- R1 is —CH2OC(═O)R30;
- wherein:
- R30 is chosen from
- (a) (C1-C6)alkyl,
- (b) phenyl substituted with (Ci-C4)alkylamino,
- (c) the descarboxy residue of a natural amino acid,
- (d) (Ci-C3)hydrocarbyl substituted with carboxyl,
- (e) (Ci-C5)oxaalkyl, and
- (f) pyridyl;
- R2, R3, R4 and R5 are chosen independently from hydrogen, halogen, and perfluoro(C1-C4)alkyl;
- R10 is hydrogen;
- R7 is H or (C3-C4)alkyl;
- R9 is hydrogen;
- and
- R8 is chosen from (C1-C4)alkyl, (C1-C4)alkoxy, and NH2.
21 more elements
A compound of formula (II):
- wherein
- Ar is
- W1 is N—R1;
- W2 is N or C—R2;
- W3 is N or C—R3;
- W4 is N or C—R4;
- W5 is N or C—R5;
- W9 is C;
- wherein:
- R1 is chosen from H, —CH2OC(═O)R30, —CH2OP(═O)OR40OR41, —C(═O)OR42, and —C(═O)R43;
- wherein:
- R30 is chosen from (C1-C10)hydrocarbyl, (C1-C10)hydrocarbyl substituted with amino, (C1-C10)hydrocarbyl substituted with (C1-C4)alkoxycarbonyl, (C1-C10)hydrocarbyl substituted with carboxyl, carboxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkoxycarbonylamino, methylthio, heterocyclyl, (C1-C10)oxaalkyl, CHR44NHR45, and guanidino;
- wherein:
- R44 is chosen from any naturally occurring amino acid sidechain;
- and
- R45 is chosen from H, methyl, and (C1-C4)alkoxycarbonyl;
- and
- R40 and R41 are chosen independently from hydrogen and (C1-C6)hydrocarbyl;
- R42 is (C1-C5)alkyl;
- and
- R43 is (C1-C3)alkyl;
- and
- R2, R3, R4 and R5 are chosen independently from hydrogen, deuterium, halogen, perfluoro(C1-C4)alkyl, (C1-C4)alkyl, (C1-C4)alkoxy, perfluoro(C1-C4)alkoxy, (C1-C4)acyl, (C1-C4)alkoxy(C1-C4)alkyl, hydroxy(C1-C4)alkyl, hydroxy, carboxy, (C1-C4)alkoxycarbonylamino [—HNC(═O)O-alkyl], carboxamido [—C(═O)NH2], (C1-C4)alkylaminocarbonyl [—C(═O)NH-alkyl], cyano, acetoxy, nitro, amino, (C1-C4)alkylamino, di(C1-C4)alkylamino, mercapto, (C1-C4)alkylthio, aminosulfonyl, (C1-C4)alkylsulfonyl, and (C1-C4)acylamino;
- with the provision that Ar includes
- only when:
- R1 is not H.
23 more elements
The compound of formula:
Dependencies are inferred from the claim text.