Aza-bridged-bicyclic amino acid derivatives as alpha4 integrin antagonists
OwnerAlexey Dyatkin, Yong Gong +2inventors
InventorsAlexey Dyatkin, Yong Gong, Wei He, Tamara Miskowski
Life of this patent
Estimating the term…
Abstract
The invention is directed to aza-bridged-bicyclic compounds having Formula (I): and pharmaceutically acceptable salts thereof. The compounds are useful α4 integrin receptor antagonists and, in particular, α4β1 and α4β7 integrin receptor antagonists. The invention is further directed to methods for use of the instant compounds for treating integrin mediated disorders including, but not limited to, inflammatory disorders, autoimmune disorders and cell-proliferative disorders, methods for preparing the compounds and methods for preparing the intermediates, derivatives and pharmaceutical compositions thereof.
Claims28
A compound of Formula (I):
- wherein
- Y is selected from the group consisting of a bond, —C(O)—, —C(O)O— and —C(O)NH—;
- R1 is selected from the group consisting of R3 and R4;
- R2 is selected from the group consisting of hydrogen and C1-4alkyl;
- wherein C1-4alkyl is optionally substituted with one to three substituents independently selected from amino, N—(C1-4alkyl)amino, N,N—(C1-4dialkyl)amino, hydroxy, C1-4alkoxy, —CF3 and —OCF3;
- R3 and R5 are independently selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl optionally substituted with one to five substituents independently selected from the group consisting of halogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkylcarbonyl, C1-8alkoxycarbonyl, carboxyl, aryl, heteroaryl, arylcarbonyl, heteroarylcarbonyl, arylsulfonyl, amino, N—(C1-6alkyl)amino, N,N—(C1-6dialkyl)amino, —CF3 and —OCF3;
- and, wherein the heterocycl, aryl and heteroaryl substituents and the aryl portion of the arylcarbonyl substituent are optionally substituted with one to five substituents independently selected from the group consisting of halogen, C1-8alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, carboxyl, amino, N—(C1-6alkyl)amino, N,N—(C1-6dialkyl)amino, —CF3 and —OCF3;
- R4, is independently selected from the group consisting of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and (halo)1-3(C1-6)alkyl;
- wherein C1-6alkyl, C2-6alkenyl and C2-6alkynyl are optionally substituted on a terminal carbon with one to three substituents independently selected from R5;
- provided that when Y is C(O)NH and R4 is a C1-6alkyl substituted with R5 and;
- provided that when Y is a bond then R1 is R4 and R4 is C1-6alkyl optionally substituted with R5, and R5 is selected from the group consisting of heterocyclyl and aryl optionally substituted with halo, C1-4alkyl, C1-4alkoxy, N—(C1-4alkyl)amino, N,N—(C1-4dialkyl)amino, —CF3 and —OCF3
- and pharmaceutically acceptable salts, racemic mixtures, diastereomers and enantiomers thereof.
Dependencies are inferred from the claim text.