142001-87-4

Upstream product

• 124-63-0 methanesulfonyl chloride 
• 135936-08-2 1-Amino-2-(3,4-dichlorophenyl)-4-(tetrahydropyran-2-yloxy)butane 
• 142001-92-1 N-[2-(3,4-Dichlorophenyl)-4-hydroxybutyl]-N-methylbenzamide 
• 159874-12-1 N-[2-(3,4-Dichlorophenyl)-4-(tetrahydropyran-2-yloxy)butyl]-benzamide 
• 176044-74-9 N-[2-(3,4-Dichlorophenyl)-4-(tetrahydropyran-2-yl-oxy)butyl]-N-methylbenzamide 
• 135936-16-2 α-[2-(Tetrahydropyran-2-yloxy)ethyl]-3,4-dichlorophenyl-acetonitrile 
• 152298-51-6 2-(2-Hydroxyethyl)-2-(3,4-dichlorobenzene)ethanamine 
• 152298-54-9 N-[2-(S)-(3,4-dichlorophenyl)-4-hydroxybutyl]-N-methylamine 
• 3218-49-3 3,4-dichloro-benzeneacetonitrile 

Downstream Products

• 142001-63-6 SR 48212A 
• 1230949-78-6 N-methyl-N-(4-(4-(1-(2-(fur-2-ylmethoxy)ethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)-2-(3,4-dichlorophenyl)butyl)benzamide 

Relevant academic research and scientific papers

4-Amino-2-(aryl)-butylbenzamides and their conformationally constrained analogues. Potent antagonists of the human neurokinin-2 (NK2) receptor

A library, evaluating a range of piperazines, piperidines and acyclic amines, as replacements for the 4-hydroxy-4-phenylpiperidine moiety in lead (1b) was prepared. These efforts identified the 4-((N)-benzimidazolone)piperidine analogue (2a) which was further optimised using classical single-compound synthesis to yield the 3-((N)-morpholino)azetidine (2j). Conformationally constrained analogues of (2j), generally offered no potency advantage in this particular series.

Carboxy substituted acylic carboxamide derivatives

The present invention relates to novel carboxy substituted acyclic carboxamide derivatives of formula (1)): STR1and stereoisomers and pharmaceutically acceptable salts thereof and their use as tachykinin receptor antagonists. Such antagonists are useful in the treatment of tachykinin-mediated diseases and conditions disclosed herein including: asthma, cough, and bronchitis.

SUBSTITUTED N-METHYL-N-(4-(4-(1H-BENZIMIDAZOL-2-YL-AMINO) PIPERIDIN-1-YL)-2-(ARLYL) BUTYL) BENZAMIDES USEFUL FOR THE TREATMENT OF ALLERGIC DISEASES

The present invention relates to novel substituted N-methyl-N-(4-(4-(1H-benzimidazol-2-yl-amino)piperidin-1-yl)-2-(aryl)butyl) benzamide derivatives of the formula: STR1 stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonists. Such antagonists are useful in the treatment of allergic rhinitis, including seasonal rhinitis and sinusitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; asthma; bronchitis; and emesis.

SUBSTITUTED N-METHYL-N-(4-(4-(1H-BENZIMIDAZOL-2-YL) {1,4}DIAZEPAN-1-YL)-2-(ARYL)BUTYL) BENZAMIDES USEFUL FOR THE TREATMENT OF ALLERGIC DISEASES

The present invention relates to novel N-methyl-N-(4-(4-(1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)-2-(aryl)butyl)benzamide derivatives of the formula: STR1 stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonists. Such antagonists are useful in the treatment of allergic rhinitis, including seasonal rhinitis and sinusitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; asthma; bronchitis; and emesis.

SUBSTITUTED N-METHYL-N-(4-(PIPERIDIN-1-YL)-2-(ARYL)BUTYL)BENZAMIDES USEFUL FOR THE TREATMENT OF ALLERGIC DISEASES

The present invention relates to novel substituted N-methyl-N-(4-(piperidin-1-yl)-2-(aryl)butyl)benzamide derivatives of the formula STR1 stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonists. Such antagonists are useful in the treatment of allergic rhinitis, including seasonal rhinitis and sinusitis; inflammatory bowel diseases, including Crohn's disease and ulcerative colitis; asthma; bronchitis; and emesis.

Spiro-substituted piperidines as neurokinin receptor antagonists. II. Syntheses and NK2 receptor-antagonistic activities of N-[2-aryl-4-(spiro- substituted piperidin-1'-yl)butyl]carboxamides

In the course of our research on spiro-compounds as neurokinin receptor antagonists, N-[2-aryl-4-spiro-substituted piperidin-1'-yl)butyl]carboxamides were designed, based on YM-35375 (3) as a lead compound, and evaluated for NK2 receptor-antagonistic activities. Some derivatives inhibited the binding of radio-labeled neurokinin A to the NK2 receptor with IC50 values at the level of 10-9. Among these compounds, (±)-1'-[4-(N-benzoyl-N-methylamino)- 3-(3,4-dichlorophenyl)butyl]spiro[benzo[c]thiophene-1(3H), 4'-piperidine] 2- oxide (58, YM-38336) showed 10 times more potent NK2 receptor binding affinity than compound 3 (IC50 values of 8.9 and 84nM, respectively). It showed more potent inhibitory activity (ID50 20μg/kg (i.v.)) against [β- Ala8]-NKA(4 - 10)-induced bronchoconstriction in guinea pigs than compound 3 (ID50 41 μg/kg (i.v.)). This compound was also effective intraduodenally in the same model, exhibiting an ID50 value of 0.41 μg/kg.

Spiro-substituted piperidines as neurokinin receptor antagonists. I. Design and synthesis of (±)-N-[2-(3,4-Dichlorophenyl)-4- (spiro[isobenzofuran-1(3H),4'-piperidin]-1'-yl)butyl]-N-methylbenzamide, YM- 35375, as a new lead compound for novel neurokinin receptor antagonists

Analysis of the structural requirements of compound 1 (SR48968), a potent NK2 receptor antagonist, revealed that the 4-phenyl group of the piperidine is essential for binding with the NK2 receptor and occupies an equatorial position. Energy calculation of a variety of substituted 4-phenyl piperidines revealed that spiro[isobenzofuran-1(3H), 4'-piperidine] possesses a conformationally restricted equatorial phenyl group. Our compound 12 (YM- 35375) possessing this spiro-substituted piperidine bound to the NK2 receptor with an IC50 value of 84nM and to the NK1 receptor with an IC50 value of 710nM. It showed more potent inhibitory activity (ID50 41μg/kg (i.v.)) against [β-Ala8]-NKA(4-10)-induced bronchoconstriction in guinea pigs than (±)-SR48968 (ID50 68μg/kg (i.v.)). YM-35375 may be a new lead compound for novel NK2 receptor antagonists or NK1-NK2 dual antagonists.

PIPERIDINE DERIVATIVES, PROCESS FOR OBTAINING THEM AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

Piperidine derivatives, process for obtaining them and pharmaceutical compositions containing them, of formula STR1 used as neurokinin receptor antagonists, which are, in particular, useful for the treatment of all substance P-and neurokinin-dependent pathologies.

Parallel-compound synthesis: Methodology for accelerating drug discovery

Parallel compound synthesis enables large numbers of individual compounds to be prepared simultaneously using semiautomated techniques. This fast and efficient methodology has an important role to play in accelerating lead optimisation and hence the whole drug discoveIy process. The potential of this strategy to rapidly optimise chemical leads an.d provide structureactivity relationship (SAR) information was demonstrated in two therapeutic areas, antiviral agents (herpes simplex virus), and neurokinin-2 receptor antagonists.