A method for designing conformationally restricted analogues based on allylic strain: synthesis of a novel class of noncompetitive NMDA receptor antagonists having the acrylamide structure.
A series of conformationally restricted analogues of milnacipran, a weak NMDA receptor antagonist, were designed by a method based on allylic strain. The conformational analysis study showed that the allylic-strain-based conformational restriction indeed occurred and that the affinity for the NMDA receptor was efficiently improved by the conformational restriction.
Ohmori
Yutaka
Y
Institute for Life Science Research, Asahi Kasei Co, Ltd, Ohito-cho, Shizuoka 410-2321, Japan.
Yamashita
Akitake
A
Tsujita
Ryuichi
R
Yamamoto
Tamotsu
T
Taniuchi
Kaku
K
Matsuda
Akira
A
Shuto
Satoshi
S
D000178:Acrylamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000498:Allyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D018360:Crystallography, X-Ray; D066298:In Vitro Techniques; D008958:Models, Molecular; D008968:Molecular Conformation; D011869:Radioligand Assay; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000178:Acrylamides; D000498:Allyl Compounds; D016194:Receptors, N-Methyl-D-Aspartate