[EN] PYRROLIDINE DERIVATIVES AS CB1-RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS DE PYRROLIDINE SERVANT D'ANTAGONISTES DU RÉCEPTEUR CB1
申请人:TANABE SEIYAKU CO
公开号:WO2005115977A1
公开(公告)日:2005-12-08
The present invention relates to a novel pyrrolidine compound, which has a potent antagonistic activity against central cannabinoid (CB1) receptor, having the formula [I]: wherein each of R1 and R2 is (A) optionally substituted aryl (or heteroaryl) group, or (B) both of the groups combine to form a group of the formula: one of R3 and R4 is hydrogen and another is hydrogen, hydroxyl, hydroxyalkyl, etc., or both of R3 and R4 combine to form oxo group, R5 is hydrogen or alkyl, Y is single bond, oxygen atom or a group of the formula: -N(R7)-, R6 is optionally substituted hydrocarbon group or optionally substituted cyclic group, R7 is alkyl or alkyloxycarbonylalkyl, provided that R6 is not 4-amino-5-chloro- 2-methoxyphenyl group when Y is single bond and one of the R3 and R4 is hydrogen and another is hydroxymethyl, or a pharmaceutically acceptable salt thereof.
demonstrated to function as C1 carbonylsynthon in the carbonylations of triarylbismuth and triarylindium nucleophiles under palladium-catalyzed conditions. All the three aryl groups from both bismuth and indium reagents participated in carbonylative couplings to afford the corresponding functionalized ketones in high yields. This study also disclosed a novel utilization of oxalyl chloride as facile
Xanthenyl and thioxanthenyl chlorides (1) were added to 1,1-bis-(p-alkoxyphenyl)-2-substituted-ethylenes (2) to give 1,1-bis-(p-alkoxyphenyl)-2-substituted-2-[xanthen(or thioxanthen)-9-yl]ethylenes (3). The 2-nitroderivatives (3) were converted in boiling methanolic potassium hydroxide into the allenes, 1,1-bis-(p-alkoxyphenyl)-2-[xanthen(or thioxanthen)-9-ylidene]ethylenes (4). The 2-methyl(or chloro)-derivatives (3) reacted with bromine in the presence of hydrogen bromide, to yield xanthylium or thioxanthylium tribromide (5) and the corresponding 2,2-disubstituted-ethylene (6). The tribromides (5) reacted with the ethylene (2, Z=H to give, after spontaneous dehydrobromination, the corresponding 2-bromo-derivatives (3, Z=Br).
Compounds of formula (I): wherein variable groups are as defined within; for use in the inhibition of 11βHSD1 are described.
描述了式(I)的化合物:其中变量基团如定义的那样;用于抑制11βHSD1。
Novel pyrrolidine compound and a process for preparing the same
申请人:Moritani Yasunori
公开号:US20070167440A1
公开(公告)日:2007-07-19
The present invention relates to a novel pyrrolidine compound, which has a potent antagonistic activity against central cannabinoid (CB1) receptor, having the formula [I]: wherein each of R
1
and R
2
is (A) optionally substituted aryl (or heteroaryl) group, or (B) both of the groups combine to form a group of the formula: one of R
3
and R
4
is hydrogen and another is hydrogen, hydroxyl, hydroxyalkyl, etc., or both of R
3
and R
4
combine to form oxo group, R
5
is hydrogen or alkyl, Y is single bond, oxygen atom or a group of the formula: —N(R
7
)—, R
6
is optionally substituted hydrocarbon group or optionally substituted cyclic group, R
7
is alkyl or alkyloxycarbonylalkyl, provided that R
6
is not 4-amino-5-chloro-2-methoxyphenyl group when Y is single bond and one of the R
3
and R
4
is hydrogen and another is hydroxymethyl, or a pharmaceutically acceptable salt thereof.