1254699-97-2

Upstream product

• 6893-26-1 D-Glutamic acid 
• 38854-94-3 (2R)-1-benzyl-5-oxopyrrolidine-2-carboxylic acid 
• 246856-66-6 (S)-3-amino-(R)-2-hydroxy-4-phenylbutyramide 

Downstream Products

• 1254698-20-8 (2R)-N-(4-amino-3,4-dioxo-1-phenylbutan-2-yl)-1-benzyl-5-oxopyrrolidine-2-carboxamide 

Relevant academic research and scientific papers

Discovery of ABT-957: 1-Benzyl-5-oxopyrrolidine-2-carboxamides as selective calpain inhibitors with enhanced metabolic stability

Aberrant activation of calpain has been observed in various pathophysiological disorders including neurodegenerative diseases such as Alzheimer's Disease. Here we describe our efforts on ketoamide-based 1-benzyl-5-oxopyrrolidine-2-carboxamides as a novel series of highly selective calpain inhibitors mitigating the metabolic liability of carbonyl reduction. The most advanced compound from this new series, namely A-1212805 (ABT-957, Alicapistat) proceeded to clinical phase I studies.

CARBOXAMIDE COMPOUNDS AND THEIR USE AS CALPAIN INHIBITORS

The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. The carboxamide compounds are compounds of the general formula (I) in which R1, R2, R3a, R3b, R4, Q, Y, A and X have the meanings mentioned in the claims and the description, the tautomers thereof and the pharmaceutically suitable salts thereof. In particular, the compounds have the general formula (Ia) and (Ib) in which R1, r, R2b, R3a, R3b, R4, Y and X have the meanings mentioned in the claims, including the tautomers thereof and the pharmaceutically suitable salts thereof. Of these compounds those are preferred wherein Y is a moiety CH2-CH2, CH2-CH2-CH2, N(Ry#)-CH2, N(Ry#)-CH2-CH2 or CH=CH-CH=, each optionally having 1 or 2 H-atoms replaced with identical or different radicals Ry, wherein Ry and Ry# have the meanings mentioned in the claims.