91477-84-8Relevant articles and documents
HEDGEHOG ACYLTRANSFERASE INHIBITORS AND USES THEREOF
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, (2018/02/24)
Hedgehog acyltransferase (Hhat), a membrane-bound O-acyl transferase (MBOAT) protein, is responsible for the palmitoylation of Shh and is crucial to proper Shh signaling. Hhat inhibitors that are capable of preventing Shh palmitoylation and mitigating Shh
Modulation of Amide Bond Rotamers in 5-Acyl-6,7-dihydrothieno[3,2-c]pyridines
Lanyon-Hogg, Thomas,Ritzefeld, Markus,Masumoto, Naoko,Magee, Anthony I.,Rzepa, Henry S.,Tate, Edward W.
, p. 4370 - 4377 (2015/05/13)
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).
Fused piperidines as a novel class of potent and orally available transient receptor potential melastatin type 8 (TRPM8) antagonists
Tamayo, Nuria A.,Bo, Yunxin,Gore, Vijay,Ma, Vu,Nishimura, Nobuko,Tang, Phi,Deng, Hong,Klionsky, Lana,Lehto, Sonya G.,Wang, Weiya,Youngblood, Brad,Chen, Jiyun,Correll, Tiffany L.,Bartberger, Michael D.,Gavva, Narender R.,Norman, Mark H.
experimental part, p. 1593 - 1611 (2012/04/17)
The transient receptor potential melastatin type 8 (TRPM8) is a nonselective cation channel primarily expressed in a subpopulation of sensory neurons that can be activated by a wide range of stimuli, including menthol, icilin, and cold temperatures (25 °C). Antagonism of TRPM8 is currently under investigation as a new approach for the treatment of pain. As a result of our screening efforts, we identified tetrahydrothienopyridine 4 as an inhibitor of icilin-induced calcium influx in CHO cells expressing recombinant rat TRPM8. Exploration of the structure-activity relationships of 4 led to the identification of a potent and orally bioavailable TRPM8 antagonist, tetrahydroisoquinoline 87. Compound 87 demonstrated target coverage in vivo after oral administration in a rat pharmacodynamic model measuring the prevention of icilin-induced wet-dog shakes (WDS).
An efficient and convenient synthesis of 4,5,6,7-tetrahydrothieno[3,2-c] pyridines by a modified Pictet-Spengler reaction via a formyliminium ion intermediate
Kitabatake, Michikazu,Hashimoto, Aki,Saitoh, Toshiaki,Sano, Takehiro,Mohri, Kunihiko,Horiguchi, Yoshie
, p. 1903 - 1921 (2011/04/12)
A synthesis of N-formyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridines (5) was achieved in a highly efficient manner via trifluoroacetic acid catalyzed cyclization of formyliminium ion (4), which was produced by imination of 2-(2-thienyl)ethylamine (1) and a carbonyl compound (2) using titanium(IV) tetraisopropoxide followed by formylation with acetic-formic anhydride in a one-pot procedure. This modified Pictet-Spengler reaction provides a convenient method for preparing 4,5,6,7-tetahydrothieno[3,2-c]pyridines (6) possessing various substituents at C-4. The Japan Institute of Heterocyclic Chemistry.
SUBSTITUTED SULFONAMIDE DERIVATIVES
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Page/Page column 111, (2009/11/29)
The invention relates to substituted sulfonamide derivatives, processes for the preparation thereof, medicaments containing these compounds and the use of substituted sulfonamide derivatives for the preparation of medicaments.
4,5,6,7-tetrahydro-thieno[3, 2-C]pyridine derivatives, their preparation and use
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, (2008/06/13)
The present invention relates to pharmaceutical compositions comprising a pharmaceutically acceptable carrier or diluent and a compound of formula I wherein A together with the double bond of formula I is benzene or thiophene; R1is optionally s
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
Madsen, Peter,Lundbeck, Jane M.,Jakobsen, Palle,Varming, Annemarie R.,Westergaard, Niels
, p. 2277 - 2289 (2007/10/03)
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.
Synthesis of Thienooxazonine and Thienooxazecine Derivatives by Cyanogen-Bromide-Induced Ring Expansion
Bremner, John B.,Browne, Elaine J.,Chohan, Veronica,Yates, Brian F.
, p. 1043 - 1047 (2007/10/02)
4-Phenyl-4,6,7,8,9,10-hexahydrothienooxazonine-8-carbonitrile (5a) and the analogous 4-phenyl-6,7,8,9,10,11-hexahydro-4H-thienooxazecine-9-carbonitrile (5b) were prepared in moderate yields by cyanogen bromide-induced ring expansio
