Synthesis and histamine H2 agonistic activity of arpromidine analogues: replacement of the pheniramine-like moiety by non-heterocyclic groups
摘要:
Analogues of the potent histamine H-2 agonist arpromidine, characterized by non-heterocyclic groups (phenyl, cyclo-hexyl, alkyl) instead of the pheniramine-like portion, were prepared and tested for their H-2 agonistic and H-1 antagonistic activity in the isolated guinea pig right atrium and ileum, respectively. In the diphenylpropylguanidine series an increase in H-2 agonistic potency resulted from mono- or difluorination at one or both phenyl rings in the meta and/or para position (pD2 less-than-or-equal-to 7.75 vs pD2 = 7.15 for the unsubstituted parent compound). Compounds chlorinated at both phenyl rings were considerably less potent. Highest combined H-2 agonistic/H-1 antagonistic potency was found in the 4-fluorophenyl series. The arpromidine analogue with cyclohexyl and methyl group instead of phenyl and pyridine ring proved to be 30 times more potent than histamine in the atrium. The H-1 antagonistic potency in cyclohexyl compounds was lower than in the diaryl series. Thus, aromatic rings appear not to be required for high H-2 agonistic potency but are useful for combined H-2 agonistic/H-1 antagonistic activity.
The present invention comprises small molecular weight, non-peptidic inhibitors of formulae I-VII of Protein Tyrosine Phosphatase 1 (PTP1) which are useful for the treatment and/or prevention of Non-Insulin Dependent Diabetes Mellitus (NIDDM).
Silver-Catalyzed Long-Distance Aryl Migration from Carbon Center to Nitrogen Center
作者:Taigang Zhou、Fei-Xian Luo、Ming-Yu Yang、Zhang-Jie Shi
DOI:10.1021/jacs.5b10267
日期:2015.11.25
Selective cleavage of an inert C-C bond followed by C-O/N bond formation through a long-distance aryl migrationfrom a carbon to a nitrogen center via Ag catalysis is reported. The migration products were easily converted into γ-hydroxy amines and tetrahydroquinoline derivatives in quantitative yields. Preliminary mechanistic studies indicated a radical pathway.
据报道,惰性 CC 键的选择性裂解,然后通过银催化从碳到氮中心的长距离芳基迁移形成 CO/N 键。迁移产物很容易转化为定量产率的 γ-羟基胺和四氢喹啉衍生物。初步的机理研究表明了一种激进的途径。
Azasteroid compounds for the treatment of prostatic hypertrophy, their preparation and use
申请人:Sankyo Company Limited
公开号:EP0484094A2
公开(公告)日:1992-05-06
Compounds of formula (I) :
(in which : R1 is a hydrogen atom, an unsubstituted alkyl group, an aryl-substituted alkyl group or a heterocyclic-substituted alkyl group ; R2 is an aryl-substituted alkyl group, a heterocyclic-substituted alkyl group or a diarylamino group ; R3 is a hydrogen atom, an unsubstituted alkyl group, an aryl-substituted alkyl group or an alkenyl group having from 3 to 6 carbon atoms ; and each of the bonds represented by α-β and y-8 is a carbon-carbon single bond or a carbon-carbon double bond ;) and pharmaceutically acceptable salts and esters thereof are useful for the treatment and prophylaxis of prostatic hypertrophy. We also provide processes for their preparation.
Steroid derivatives for the treatment of prostatic hypertrophy, their preparation and uses
申请人:SANKYO COMPANY LIMITED
公开号:EP0567271A2
公开(公告)日:1993-10-27
Compounds of formula (I):
[wherein : R1 is hydrogen, alkyl, aryl-substituted alkyl or aromatic heterocyclic-substituted alkyl ; R2 is: aryl-substituted alkyl, aromatic heterocyclic-substituted alkyl or diarylamino; and R3 is carboxy or a group of formula -CONHS02 R4 wherein R4 is alkyl] ; and pharmaceutically acceptable salts and esters thereof have valuable 5α-reductase inhibitory activity and can thus be used for the treatment and prophylaxis of, inter alia, prostatic hypertrophy as well as other disorders arising from excess levels of 5α-dihydro-testosterone.
Compounds suitable for use as intermediates in the preparation of Androst-3,5-dien-3-carboxy derivatives
申请人:SANKYO COMPANY LIMITED
公开号:EP0725074A2
公开(公告)日:1996-08-07
A compound of formula (IV)
and a process for the preparation of a compound of the following formula:
in which R10 is a hydroxy group, a group -OR5, in which R5 is a carboxy protecting group, a group -NR1R2, in which R1 is hydrogen, alkyl, aryl-substituted alkyl or aromatic heterocyclic-substituted alkyl and R2 is aryl-substituted alkyl, aromatic heterocyclic-substituted alkyl or diarylamino, or a group -NRR', in which R and R' are hydrogen or alkyl.