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Thiazepine

About: Thiazepine is a(n) research topic. Over the lifetime, 327 publication(s) have been published within this topic receiving 2591 citation(s). The topic is also known as: thiazepines.

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Journal ArticleDOI
TL;DR: The synthesis and enzyme inhibition data for a series of thiazine- and thiazepine-based matrix metalloproteinase (MMP) inhibitors are described and the most potent series of inhibitors was obtained by modification of the amino acid D-penicillamine.

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Abstract: The synthesis and enzyme inhibition data for a series of thiazine- and thiazepine-based matrix metalloproteinase (MMP) inhibitors are described. The thiazine- and thiazepine-based inhibitors were discovered by optimization of hetererocyclic sulfonamide-based inhibitors. The most potent series of inhibitors was obtained by modification of the amino acid d-penicillamine. This amino acid provides a gem-dimethyl group on the thiazine or thiazepine ring which has a dramatic effect on the in vitro potency of this series. In particular, the sulfide 4a and the sulfone 5a were potent, broad-spectrum inhibitors of the MMPs with IC50's against MMP-1 of 0.8 and 1.9 nM, respectively. The binding mode of this novel thiazepine-based series of MMP inhibitors was established based on X-ray crystallography of the complex of stromelysin and 4a.

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80 citations


Patent
15 Feb 1994-
Abstract: The invention provides a compound of formula (I), wherein n is an integer of from 0 to 2; R is an optional substituent; R1 is hydrogen or C?1-6?alkyl; R?2? is an atom or group selected from hydrogen, C?1-6?alkyl (including cycloalkyl and cycloalkylalkyl), C1-4alkoxy, pyrryl, thienyl, pyridyl, 1,3-benzodioxolo, phenyl and naphthyl, which groups are optionally substituted; R?3? is hydrogen, OH, C?1-6?alkyl, C1-6alkoxy or -OC1-6acyl; R?4? is a group independently selected from C?1-6?alkyl (including cycloalkyl and cycloalkylalkyl), C2-6alkenyl, and C2-6alkynyl which groups are optionally substituted; R?5? is a group independently selected from C?2-6?alkyl (including cycloalkyl and cycloalkylalkyl), C2-6alkenyl and C2-6alkynyl, which groups are optionally substituted; or R?4 and R5?, together with the carbon atom to which they are attached, form a C?3-7?spiro cycloalkyl group which is optionally substituted; R?6 and R7? are independently selected from hydrogen and C?1-6?alkyl; and X is an aromatic or non-aromatic monocyclic or bicyclic ring system having from 5 to 10 carbon atoms (including the two carbon atoms forming part of the thiazepine ring) wherein optionally one or more of the carbon atoms is/are replaced by heteroatom(s) independently selected from nitrogen, oxygen and sulphur; or X is an aromatic or non-aromatic monocyclic or bicyclic ring system having from 5 to 10 carbon atoms (including the two carbon atoms forming part of the thiazepine ring) wherein one or more of the carbon atoms is/are replaced by heteroatom(s) independently selected from nitrogen, oxygen and sulphur; and salts, solvates and physiologically functional derivatives thereof, pharmaceutical formulations comprising such compounds, processes for their preparation and their use in reducing bile acid uptake and hence as hypolipidaemic compounds.

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76 citations


Journal ArticleDOI
Aranapakam M. Venkatesan1, Yansong Gu1, Osvaldo Dos Santos1, T. Abe1  +9 moreInstitutions (1)
TL;DR: The design and synthesis of a series of seven tricyclic 6-methylidene penems as novel class A and C serine beta-lactamase inhibitors is described and the formation of the 1,4- thiazepine ring structures is proposed based on a 7-endo-trig cyclization.

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Abstract: The design and synthesis of a series of seven tricyclic 6-methylidene penems as novel class A and C serine β-lactamase inhibitors is described. These compounds proved to be very potent inhibitors of the TEM-1 and AmpC β-lactamases and less so against the class B metallo-β-lactamase CcrA. In combination with piperacillin, their in vitro activities enhanced susceptibility of all class C resistant strains from various bacteria. Crystallographic structures of a serine-bound reaction intermediate of 17 with the class A SHV-1 and class C GC1 enzymes have been established to resolutions of 2.0 and 1.4 A, respectively, and refined to R-factors equal 0.163 and 0.145. In both β-lactamases, a seven-membered 1,4-thiazepine ring has formed. The stereogenic C7 atom in the ring has the R configuration in the SHV-1 intermediate and has both R and S configurations in the GC1 intermediate. Hydrophobic stacking interactions between the tricyclic C7 substituent and a tyrosine side chain, rather than electrostatic or hydrogen...

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74 citations


Journal ArticleDOI
Jitendra Kumar Mishra1, Gautam Panda1Institutions (1)
TL;DR: This is the first example where the Mitsunobu approach has been utilized for the construction of S-amino acid based seven- and eight-membered ring systems.

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Abstract: The diversity-oriented organic synthesis of enantiomerically pure benzannulated oxazepine, diazepine, thiazepine, oxazocine, and diazocine scaffolds is described from easily accessible naturally occurring S-amino acids as chiral synthons Inter- and intramolecular Mitsunobu reactions for the formation of carbon−nitrogen, carbon−oxygen, and carbon−sulfur bonds have been used as key transformations to construct these biologically important privileged heterocycles This is the first example where the Mitsunobu approach has been utilized for the construction of S-amino acid based seven- and eight-membered ring systems

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67 citations


Journal ArticleDOI
Hidetsura Cho1, Yusuke Iwama, Kenji Sugimoto, Seiji Mori2  +1 moreInstitutions (2)
TL;DR: It was found that the more electron-rich group migrated preferentially to give the corresponding secondary amines in the reductive ring-expansion reaction of cyclic ketoximes fused to aromatic rings with diisobutylaluminum hydride.

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Abstract: A systematic investigation of the reductive ring-expansion reaction of cyclic ketoximes fused to aromatic rings with diisobutylaluminum hydride (DIBALH) is described. This reaction regioselectively afforded a variety of five- to eight-membered bicyclic heterocycles or tricyclic heterocycles containing nitrogen neighboring an aromatic ring, including indoline, 1,2,3,4,5,6-hexahydrobenz[b]azocine, 3,4-dihydro-2H-benzo[b][1,4]oxazine, 2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine, 1,2,3,4,5,6-hexahydroazepino[3,2-b]indole, 2,3,4,5-tetrahydro-1H-benzothieno[2,3-b]azepine, 2,3,4,5-tetrahydro-1H-benzothieno[3,2-b]azepine, 5,6-dihydrophenanthridine, and 5,6,11,12-tetrahydrodibenz[b, f]azocine. The reaction mechanism leading to the rearrangement was investigated on the basis of the restricted Becke three-parameter plus Lee−Yang−Parr (B3LYP) density functional theory (DFT) with the 6-31G (d) basis set. It was found that the reaction proceeds through a three-centered transition state via a stepwise mechanism because th...

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64 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20212
20205
20192
20181
201712
20167

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Topic's top 5 most impactful authors

Mehdi Bakavoli

7 papers, 43 citations

Luana Perioli

6 papers, 49 citations

Giuliano Grandolini

6 papers, 49 citations

Valeria Ambrogi

6 papers, 49 citations

Hossein Eshghi

5 papers, 40 citations