- Design, synthesis, biological screening, and molecular docking studies of piperazine-derived constrained inhibitors of DPP-IV for the treatment of type 2 diabetes
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Novel piperazine-derived conformationally constrained compounds were designed, synthesized, and evaluated for in vitro Dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. From a library of compounds synthesized, 1-(2-(4-(7-Chloro-4-quinolyl)piperazin-1-yl)acetyl)pyrrolidine (2g) was identified as a potential DPP-IV inhibitor exhibiting better inhibitory activity than P32/98, reference inhibitor. The in vivo studies carried out in STZ and db/db mice models indicated that the compound 2g showed moderate antihyperglycemic activity as compared to the marketed drug Sitagliptin. A two-week repeated dose study in db/db mice revealed that compound 2g significantly declined blood glucose levels with no evidence of hypoglycemia risk. Furthermore, it showed improvement in insulin resistance reversal and antidyslipidemic properties. Molecular docking studies established good binding affinity of compound 2g at the DPP-IV active site and are in favor of the observed biological data. These data collectively suggest that compound 2g is a good lead molecule for further optimization studies.
- Kushwaha, Ram N.,Srivastava, Rohit,Mishra, Akansha,Rawat, Arun K.,Srivastava, Arvind K.,Haq, Wahajul,Katti, Seturam B.
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p. 439 - 446
(2015/03/18)
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- NOVEL 5-SUBSTITUTED INDOLE DERIVATIVES AS DIPEPTIDYL PEPTIDASE IV (DPP-IV) INHIBITORS
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The present invention relates to 5-substituted indole derivatives of formula (I): having inhibitory potential of dipeptidyl peptidase IV (DPP IV) enzyme where x and R1 are defined as defined in the specification
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Page/Page column 64
(2008/06/13)
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- Preparation of amino acid amides
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A process for making amino acid amides, comprising reacting an amino acid, or acid salt of an amino acid, with a halogenating agent, or with a substance that reacts with carboxylic acids to form a leaving group, to form an intermediate, then reacting the intermediate with ammonia. When the amino acid or acid salt is enantiomerically pure, the amide will be a stereoisomer. An amide made by the process can be used to form levetiracetam.
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Page/Page column 2
(2008/06/13)
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- Synthesis of α-amino dithioesters and endothiodipeptides
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The α-amino ester hydrochlorides (1) are converted into N-protected α-amino amides (3), α-amino thioamides (4) and α-amino dithiomethylesters (5). Condensation of 5 with the alkali salts of α-amino acids gives rise to the endothiodipeptide alkali salts (7). Johann Ambrosius Barth 1996.
- Hartke, Klaus,Barrmeyer, Stephan
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p. 251 - 256
(2007/10/03)
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- First successful synthesis of acryloyl-L-prolylamide derivatives
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Acryloyl-L-prolylamide (1b) and its two simple derivatives, acryloyl-L- propyl-N',N'-dimethylamide (1a) and acryloyl-L-prolyl-N'-methylamide (1c), were synthesized for the first time.
- Yonezawa,Jingu,Katakai
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p. 1239 - 1246
(2007/10/02)
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