123018-23-5

Upstream product

• 10533-22-9 1-(1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-ethanone 
• 613-73-0 1,2-phenylenediacetonitrile 
• 35760-18-0 3-acetyl-7-chlorosulfonyl-2,3,4,5-tetrahydro-1H-3-benzazepine 
• 4424-20-8 2,3,4,5-tetrahydro-1H-3-benzazepine 
• 123462-52-2 3-acetyl-7-methylsulfonyl-2,3,4,5-tetrahydro-1H-3-benzazepine 

Downstream Products

• 264264-45-1 trans-3-(2-(4-aminocyclohexyl)ethyl)-7-methylsulfonyl-2,3,4,5-tetrahydro-1H-3-benzazepine 
• 264264-44-0 trans-3-(2-(4-(N-tert-butoxycarbonylamino)cyclohexyl)ethyl)-7-methylsulfonyl-2,3,4,5-tetrahydro-1H-3-benzazepine 

Relevant academic research and scientific papers

NOVEL COMPOUNDS OF AMINO SULFONYL DERIVATIVES

The present invention relates to compounds with formula (I) or a pharmaceutically acceptable salt thereof: (I);wherein; T is a (4 to 10)-membered heterocyclyl and wherein R1, R2 and R3 are as defined in the specification. The invention also relates to pharmaceutical compositions comprising the compounds of formula (I) and methods of treating a condition that is mediated by the modulation of the 11-β-hsd-1 enzyme.

M3 MUSCARINIC ACETYLCHOLINE RECEPTOR ANTAGONISTS

Muscarinic Acetylcholine receptor antagonists and methods of using them are provided.

Tetrahydrobenzazepine derivatives useful as modulators of dopamine d3 receptors (antipsychotic agents)

The invention provides compounds of formula (I): wherein: R2 and R3 independently represent various substituents; R1 and R4 independently represent H, F, Cl, Br, Cl1-2alkyl, C1alkoxy, OH, CN, or NO2; B represents a sulfur atom or a —CH2-group; t represents 3 or 4; and A represents an optionally substituted 5- or 6-membered aromatic heterocyclic ring, or an optionally substituted bicyclic heterocyclic ring system in which at least the ring bound to the group B in Formula (I) is aromatic; or a salt thereof. Preferably, A is selected from one of the groups (i), (ii) or (iii): wherein X1 and X2 are independently N or CR8, and X3 is NR8, O or S; Y1 and Y3 are independently N or CR9, and Y2 is NR9, O or S; Z1 is NR10, O or S, and Z2 and Z3 are independently N or CR10; R8, R9, and R10 are as herein defined, and R7 is H, a halogen atom, OH, cyano, nitro, C1-4alkyl, C1-4alkoxy, C1-4alkylenedioxy, C1-4alkanoyl, or C1-4alkylsulfonyl, an optionally substituted 3-, 4-, 5- or 6-membered cycloalkyl ring, or a group of the formula (a), (b), (c) or (d) as defined by the formulas (a), (b), (c) or (d). The compounds are modulators of dopamine D3 receptors and have potential in the treatment of psychotic conditions (e.g. schizophrenia) or substance abuse.

Design and Synthesis of trans-3-(2-(4-((3-(3-(5-Methyl-1,2,4-oxadiazolyl))-phenyl)carboxamido) cyclohexyl)ethyl)-7-methylsulfonyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SB-414796): A Potent and Selective Dopamine D3 Receptor Antagonist

At their clinical doses, current antipsychotic agents share the property of both dopamine D2 and D3 receptor blockade. However, a major disadvantage of many current medications are the observed extrapyramidal side-effects (EPS), postulated to arise from D2 receptor antagonism. Consequently, a selective dopamine D3 receptor antagonist could offer an attractive antipsychotic therapy, devoid of the unwanted EPS. Using SAR information gained in two previously reported series of potent and selective D3 receptor antagonists, as exemplified by the 2,3,4,5-tetrahydro-1H-3-benzazepine 10 and the 2,3-dihydro-1H-isoindoline 11, a range of 7-sulfonyloxy- and 7-sulfonylbenzazepines has been prepared. Compounds of this type combined a high level of D3 affinity and selectivity vs D2 with an excellent pharmacokinetic profile in the rat. Subsequent optimization of this series to improve selectivity over a range of receptors and reduce cytochrome P450 inhibitory potential gave trans-3-(2-(4-((3-(3-(5-methyl-1,2,4-oxidiazolyl))phenyl)carboxamido)cyclohexyl) ethyl)-7-methylsulfonyl-2,3,4,5-tetrahydro-1H-3-benzazepine (58, SB-414796). This compound is a potent and selective dopamine D3 receptor antagonist with high oral bioavailability and is CNS penetrant in the rat. Subsequent evaluation in the rat has shown that 58 preferentially reduces firing of dopaminergic cells in the ventral tegmental area (A10) compared to the substantia nigra (A9), an observation consistent with a prediction for atypical antipsychotic efficacy. In a separate study, 58 has been shown to block expression of the conditioned place preference (CPP) response to cocaine in male rats, suggesting that it may also have a role in the treatment of cue-induced relapse in drug-free cocaine addicts.

Sulfinyl and sulfonyl substituted 2,3,4,5 tetrahydro-1H-3-benzazepines and their use in treating gastrointestinal motility disorders

Sulfinyl and sulfonyl substituted 3-benzazepine compounds are useful in treating gastrointestinal motility disorders and emesis. A particular compound of this invention is 7-methylsulfonyl-2,3,4,5-tetrahydro-1H-3-benzazepine.