Design, synthesis, and biological evaluation of novel diarylalkyl amides as TRPV1 antagonists.
We have developed a new class of diarylalkyl amides as novel TRPV1 antagonists. They exhibited potent (45)Ca(2+) uptake inhibitions in rat DRG neuron. In particular, the amide 59 was identified as a potent antagonist with IC(50) of 57 nM. The synthesis and structure-activity relationship of the diarylalkyl amides are also described.
Li
Fu-Nan
FN
College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
Kim
Nam-Jung
NJ
Paek
Seung-Mann
SM
Kwon
Do-Yeon
DY
Min
Kyung Hoon
KH
Jeong
Yeon-Su
YS
Kim
Sun-Young
SY
Park
Young-Ho
YH
Kim
Hee-Doo
HD
Park
Hyeung-Geun
HG
Suh
Young-Ger
YG
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015195:Drug Design; D020128:Inhibitory Concentration 50; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000577:Amides; C541658:N-(3-cyano-5-fluoro-4-(methylsulfonamido)benzyl)-3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)propanamide; D013449:Sulfonamides; D050916:TRPV Cation Channels; D013764:Tetrahydronaphthalenes; C493922:Trpv1 protein, rat; D002118:Calcium