308287-68-5

Upstream product

• 30433-91-1 [2-(2-thyenyl)ethyl]amine 
• 2719-27-9 cyclohexanylcarbonyl chloride 
• 98-89-5 Cyclohexanecarboxylic acid 

Downstream Products

• 308287-66-3 4-cyclohexyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine 
• 308287-69-6 4-cyclohexyl-6,7-dihydrothieno[3,2-c]pyridine 

Relevant academic research and scientific papers

Modulation of Amide Bond Rotamers in 5-Acyl-6,7-dihydrothieno[3,2-c]pyridines

2-Substituted N-acyl-piperidine is a widespread and important structural motif, found in approximately 500 currently available structures, and present in nearly 30 pharmaceutically active compounds. Restricted rotation of the acyl substituent in such molecules can give rise to two distinct chemical environments. Here we demonstrate, using NMR studies and density functional theory modeling of the lowest energy structures of 5-acyl-6,7-dihydrothieno[3,2-c]pyridine derivatives, that the amide E:Z equilibrium is affected by non-covalent interactions between the amide oxygen and adjacent aromatic protons. Structural predictions were used to design molecules that promote either the E- or Z-amide conformation, enabling preparation of compounds with a tailored conformational ratio, as proven by NMR studies. Analysis of the available X-ray data of a variety of published N-acyl-piperidine-containing compounds further indicates that these molecules are also clustered in the two observed conformations. This finding emphasizes that directed conformational isomerism has significant implications for the design of both small molecules and larger amide-containing molecular architectures. (Figure Presented).

11-BETA-HYDROXYSTEROID DEHYDROGENASE INHIBITORS

There is provided a compound having Formula (I ) R1-Z-R2 wherein R1 is a group selected from optionally substituted fused polycyclic groups, substituted alkyl groups, branched alkyl groups, and optionally substituted cycioalkyl groups Z is a linker which is or comprises a carbonyl group or a isostere of a carbonyl group R2 is selected from optionally substituted aromatic rings and optionally substituted heterocyclic rings wherein (a) R2 is a 2-substituted thiophene group, and/or (b) Z is a group of the formula -C(=O)-CR3R4-X-(CR5R6)n-, wherein X is selected from NR7, S, O, S=O, and S(=O)2, wherein n is 0 or 1 and/or (c) R1 is an adamantyl group and Z is or comprises an amide group, and/or (d) R1 is an adamantyl group and Z is or comprises a group of the formula -(CR8R9)p- NR10-S(=O)2-(CR11R12)q-, wherein p is 0 or 1 and q is 0 or 1 and/or (e) R1 is an adamantyl group and Z is or comprises a group of the formula -(CR13R14)V-Y- (CR15R16)W- where Y is a heteroaryl group in which a bond in the heteroaryl ring is a isostere of a carbonyl group, wherein v is o or 1 and w is 0 or 1 ; wherein each of R3, R4, R5, R6, R8, R9, R11, R12, R13, R14, R15 and R16, are independently selected from H, hydrocarbyl and halogen, wherein each of R7 and R10 are independently selected from H and hydrocarbyl.

Glucose-6-phosphatase catalytic enzyme inhibitors: Synthesis and in vitro evaluation of novel 4,5,6,7-tetrahydrothieno[3,2-c]- and -[2,3-c]pyridines

The discovery of the first class of potent glucose-6-phosphatase catalytic site inhibitors, substituted 4,5,6,7-tetrahydrothieno[3,2-c]- and -[2,3-c]pyridines, is described. Optimisation of this series involved solution phase combinatorial synthesis and very potent compounds were prepared with IC50 values down to 140 nM. The structure-activity relationship (SAR) of these compounds indicates that: a tetrahydrothieno[3,2-c]pyridine core ring system and the isomeric [2,3-c] system are equipotent and much better than the corresponding benzo analogue, 1,2,3,4-tetrahydro-isoquinoline. The 4-substituent of the tetrahydrothieno[3,2-c]pyridine ring has to be a phenyl group, optionally substituted with a lipophilic 4-substituent, such as trifluoromethoxy or chloro. The 5-substituent of the tetrahydrothieno[3,2-c]pyridine ring has to be a substituted benzoyl; anisoyl and (E)-3-furan-3-ylacryloyl are the best of the investigated groups. Substitution in the benzoyl ortho position seems to be forbidden, whereas substitution in the meta position is tolerated only if a methoxy para substituent is present. These SAR findings were parallel to those obtained in the 4,5,6,7-tetrahydrothieno[2,3-c]pyridine system. Enantioselectivity in enzyme recognition was observed and the activity resided in all cases only in one of the enantiomers. Copyright (C) 2000 Elsevier Science Ltd.