Blood glucose lowering sulfonamides with asymmetric carbon atoms. 2

Biere, H.; Rufer, C.; Ahrens, H.; Loge, O; Schroeder, E.

doi:10.1021/jm00253a011

Cited by 18 publications

(16 citation statements)

References 5 publications

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“…Structure-activity studies on this second generation of compounds delimited two functionally important parts of these molecules and led to the idea, over thirty years ago, that there were two overlapping "binding" or "interaction" sites for these compounds within a larger binding pocket in the sulfonamide or sulfonylurea "receptor" [139][140][141][142]. Using glibenclamide (6) as an example, site A was proposed originally to interact with the sulfonylurea group, while site B associated with the amide group.…”

Section: Structure Activity Relations Of 2 Nd Gene-ration Hypoglycemimentioning

confidence: 99%

“…3 summarizes a qualitative pharmacophore model for compounds that bind to sulfonylurea receptors and affect their ability to activate the K IR pore. This model is based largely on the early ideas developed in Gutsche et al [139], Rufer et al [140] and Biere et al [141] and more recent studies by Grell et al [149], Meyer et al [150], and Hastedt and Panten [156]. There are three lipophilic or hydrophobic centers (positions i, ii, and iii) separated by an amide and an anionic linker, respectively.…”

Section: Structure Activity Relations Of 2 Nd Gene-ration Hypoglycemimentioning

confidence: 99%

“…This region of SUR2 is different, less able to accommodate these side-chains. The importance of an anionic group has been pointed out repeatedly [140][141][142][148][149][150]] and a recent report shows that introduction of a phosphate in place of -COO -in meglitinide increases the affinity of binding to SUR1 ( [156], compare compounds 9, 10, and 11 with 12). The SUR residue(s) which interact with the anionic group appear to be part of the overlap between the A and B-sites, possibly conserved basic residues able to form strong hydrogen bonds.…”

Section: Structure Activity Relations Of 2 Nd Gene-ration Hypoglycemimentioning

confidence: 99%

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Insulin Secretagogues, Sulfonylurea Receptors and KATP Channels

Bryan¹,

Crane²,

Vila-Carriles³

et al. 2005

CPD

119

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ATP-sensitive K+ channels, termed K(ATP) channels, provide a link between cellular metabolism and membrane electrical activity in a variety of tissues. Channel isoforms have been identified and are targets for compounds that both stimulate and inhibit their activity resulting in membrane hyperpolarization and depolarization, respectively. Examples include relaxation of vascular smooth muscle and stimulation of insulin secretion. This article reviews the cloning, molecular biology, and structure of K(ATP) channels, with particular focus on the SUR1/K(IR)6.2 neuroendocrine channels that are important for the regulation of insulin secretion. We integrate the extensive pharmacologic structure-activity-relationship data on these channels, which defines a bipartite drug binding pocket in the SUR (sulfonylurea receptor), with recent structure-function studies that identify domains of SUR and K(IR)6.2, the channel pore, which are critical for channel assembly, for gating, and for the ligand-receptor interactions that modulate channel activity. The atomic structure of a sulfonylurea in a protein pocket is used to develop insight into the recognition of these compounds. A homology model of K(ATP) channels, based on VC-MsbA, another member of the ABC protein family, is described and used to position amino acids important for the action of channel openers and blockers within the core of SUR. The model has a central chamber which could serve as a multifaceted binding pocket.

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Section: Structure Activity Relations Of 2 Nd Gene-ration Hypoglycemimentioning

confidence: 99%

Section: Structure Activity Relations Of 2 Nd Gene-ration Hypoglycemimentioning

confidence: 99%

Section: Structure Activity Relations Of 2 Nd Gene-ration Hypoglycemimentioning

confidence: 99%

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Insulin Secretagogues, Sulfonylurea Receptors and KATP Channels

Bryan¹,

Crane²,

Vila-Carriles³

et al. 2005

CPD

119

View full text Add to dashboard Cite

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“…The mass spectra were determined using a Varian MAT CH-5 spectrometer (70 eV). 5-(1H-Indol-3-yl)-1-phenyl-1H-pyrazole-3-carbohydrazide 1 18) ; 2-(1-(1H-indol-3-yl)ethylidene)hydrazinecarbothioamide 9 19) and hydrazonoyl chlorides 7 23) were prepared according to the reported procedures. 25) Yield 76%; IR (KBr) nЈϭ3380-3028 (3NH), 1653 (CϭO) cm Ϫ1 .…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Antiviral Activity of New Indole-Based Heterocycles

Abdel‐Gawad

Mohamed

Dawood

et al. 2010

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…The IR spectra (KBr) were recorded on a Shimadzu CVT-04 spectrophotometer. The 17,18) ; ethyl 1-phenyl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxylate 7, 24) hydrazonoyl chlorides 36) were prepared according to the procedures reported in the literature. 6-(3-Hydroxy-1H-inden-2-yl)-3-thioxo-3,4-dihydro-1,2,4 …”

Section: Methodsmentioning

confidence: 99%