Novel 2-phenylpiperazine derivatives
AssigneeNippon Zoki Pharmaceutical Co., Ltd.
InventorsTakashi Ogino, Yukari Konishi, Kunihiko Higashiura, Kazuhito Furukawa
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Abstract
Excellent tachykinin receptor antagonistic activity is provided by 2-phenylpiperazine derivatives. The piperazine derivatives exhibit a strong inhibitory action against a tachykinin-induced increase of vascular permeability in in vivo tests. Moreover, the derivatives show a preferred transfer into blood, a long half-life in blood in pharmacokinetic tests of oral administration to rats or guinea pigs, and are very stable in blood plasma of various animals. Consequently, a piperazine derivative of the present invention is very useful as a tachykinin antagonist.
Claims23
A 2-phenylpiperazine derivative represented by the following formula (I) or a pharmaceutically acceptable salt, hydrate, or complex thereof, said 2-phenylpiperazine derivative being represented by the formula (I):
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- wherein each of X1 and X3 is oxygen or two hydrogen atoms, X2 is O, NH, NCH3, or CH2, n is an integer of 0 or 1, R1 is hydrogen or lower alkyl and R2 is hydrogen, cyano, tetrazolyl, aminotriazolyl, mesyl, t-butoxycarbonyl, or lower alkyl, wherein when R2 is lower alkyl, the lower alkyl may be optionally substituted with a substituent selected from the following substituents (a) to (j) and/or oxo,
- (a) triazolonyl,
- (b) tetrazolyl,
- (c) dimethylaminomethyltriazolyl;
- (d) phosphotriazolonyl,
- (e) pyridyl,
- (f) dimethylamino,
- (g) cyano,
- (h) pyrrolidino,
- (i) amino,
- (j) phenyl,
- R3 is hydrogen, halogen, lower alkyl or lower alkoxy, each of R4 and R5 is hydrogen, lower alkoxy or trifluoromethyl, and a broken line indicates a single or double bond.
(5S,6S)-6-(3,5-Bis(trifluoromethyl)benzyloxymethyl)-1-methyl-4-(5-oxo-4,5-dihydro-1H-(1,2,4)triazol-3-ylmethyl)-5-phenylpiperazin-2-one.
Dependencies are inferred from the claim text.