Novel N-Benzylamide Substituted Derivatives of 2-(Acylamido)acetic Acid and 2-(Acylamido)propionic Acids: Potent Neurological Agents

A compound of Formula Ia:

• wherein:
• R is R2 or CH2X′R5, where X′ is O, S, or N—R6, and R6a is hydrogen, alkyl, or cycloalkyl;
• R1 is alkyl or cycloalkyl, each of which can be unsubstituted or substituted with from one to four independently selected electron-donating or electron-withdrawing groups;
• R2 is alkyl, cycloalkyl, aryl, five- or six-membered cyclic heterocyclic or heteroaromatic groups, or —X—Y—Z, where X and Y═O, S, N—R6, and Z═R6, and where R6 is hydrogen, alkyl, or cycloalkyl, each of which is unsubstituted or substituted with from one to four electron withdrawing or electron donating groups;
• R5 is alkyl, alkenyl, alkynyl, or arylalkyl, each of which is unsubstituted or substituted with from one to four electron donating or electron withdrawing groups;
• R3a R3b, and R4 are each independently hydrogen, an electron donating or electron-withdrawing group, or alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heterocyclo, heteroaryl, arylalkyl, heteroarylalkyl, heterocycloalkyl, arylalkyloxy, arylalkylamino, arylalkylthio, heteroarylalkyloxy, heteroarylalkylamino, heteroarylalkylthio, heterocycloalkyloxy, heterocycloalkylamino, heterocycloalkylthio, arylaminooxy, heteroarylaminooxy, heterocycloaminooxy, aryloxyamino, heteroaryloxyamino, heterocyclooxyamino, arylalkyl, heteroarylalkyl, heterocycloalkyl, arylalkenyl, heteroarylalkenyl, heterocycloalkenyl, aryl alkynyl, heteroarylalkynyl, heterocycloalkynyl, arylhydrazino, heteroarylhydrazino, heterocyclohydrazino, aryl azo, heteroarylazo, heterocycloazo, arylalkylaminoalkyl, heteroarylalkylaminoalkyl, heterocycloalkylaminoalkyl, arylalkyloxyalkyl, heteroarylalkyloxyalkyl, heterocycloalkyloxyalkyl, each of which can be unsubstituted or substituted with from one to four independently selected electron-donating or electron-withdrawing groups;
• wherein at least one of R3a and R4 is not H;
• and wherein at least one, or both, of R3a and R4 is a primary substituent selected from the group consisting of electron donating groups, electron-withdrawing groups, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heterocyclo, heteroaryl, arylalkyl, heteroarylalkyl, heterocycloalkyl, arylalkyloxy, arylalkylamino, arylalkylthio, heteroarylalkyloxy, heteroaryalkylamino, heteroarylalkylthio, heterocycloalkyloxy, heterocycloalkylamino, heterocycloalkylthio, arylaminooxy, heteroarylaminooxy, heterocycloaminooxy, aryloxyamino, heteroaryloxyamino, heterocyclooxyamino, arylalkyl, hetero aryl alkyl, heterocycloalkyl, aryl alkenyl, heteroarylalkenyl, heterocycloalkenyl, arylalkynyl, heteroarylalkynyl, heterocycloalkynyl, arylhydrazino, heteroarylhydrazino, heterocyclohydrazino, arylazo, heteroarylazo, heterocycloazo, arylalkylaminoalkyl, heteroarylalkylaminoalkyl, heterocycloalkylaminoalkyl, arylalkyloxyalkyl, heteroarylalkyloxyalkyl, heterocycloalkyloxyalkyl;
• and which primary substituent is in turn optionally but preferably substituted with from one to four secondary substituents independently selected from the group consisting of electron-donating groups and electron-withdrawing groups;
• or a pharmaceutically acceptable salt or prodrug thereof.