Structure-activity study and analgesic efficacy of amino acid derivatives as N-type calcium channel blockers.
The synthesis and structure-activity relationship (SAR) study of a novel series of N-type calcium channel blockers are described. L-Cysteine derivative 2a was found to be a potent and selective N-type calcium channel blocker with IC(50) 0.63 microM on IMR-32 assay. Compound 2a showed analgesic efficacy in the rat formalin-induced pain model by intrathecal and oral administration.
Seko
T
T
Minase Research Institute, Ono Pharmaceutical Co., Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, 618-8585, Osaka, Japan. seko@ono.co.jp
Kato
M
M
Kohno
H
H
Ono
S
S
Hashimura
K
K
Takimizu
H
H
Nakai
K
K
Maegawa
H
H
Katsube
N
N
Toda
M
M
D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D005557:Formaldehyde; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D013329:Structure-Activity Relationship
D000596:Amino Acids; D000700:Analgesics; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D005557:Formaldehyde