Substituted 1, 2, 3, 4-Tetrahydroquinolin-6-yloxypropanes as beta3-adrenergic receptor agonists: Design, synthesis, biological evaluation and pharmacophore modeling
IR@CDRI: CSIR-Central Drug Research Institute, Lucknow
View Archive Info| Field | Value | |
| Creator |
Shakya, Neeraj
Roy, K K Saxena, A K |
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| Date |
2010-10-07T05:53:35Z
2010-10-07T05:53:35Z 2009 |
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| Identifier |
Bioorg Med Chem. 2009, 17(2), 830-47
http://hdl.handle.net/123456789/620 |
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| Description |
In search of potent beta3-adrenergic receptor agonists, a series of novel substituted 1,2,3,4-tetrahydroquinolin-6-yloxypropanes has been synthesized and evaluated for their beta3-adrenergic receptor agonistic activity (ranging from -17.73% to 90.64% inhibition at 10 micro M) using well established Human SK-N-MC neuroblastoma cells model. Four molecules viz. 11, 15, 22 and 23 showed beta3-AR agonistic IC50 value of 0.55 microM, 0.59 microM, 1.18 microM and 1.76 microM respectively. These four candidates have been identified as possible leads for further development of beta3-adrenergic receptor agonists for obesity and Type-II diabetes pharmacotherapy. The free OH and NH functions are found to be essential for beta3-adrenergic receptor agonistic activity. Among the synthesized beta3-adrenergic receptor agonists having 1,2,3,4-tetrahydroquinoline scaffold, the N-benzyl group is found to be superior over N-arylsulphonyl group. A putative pharmacophore model has been modeled considering the above four active molecules which distinguishes well between the active and inactive molecules.
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500588 bytes
application/pdf |
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| Language |
en
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| Subject |
1,2,3,4-Tetrahydroquinolin-6-yloxypropanes
beta3-adrenergic receptor agonist Obesity Type-II Diabetes Putative Pharmacophore HipHop Catalyst |
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| Title |
Substituted 1, 2, 3, 4-Tetrahydroquinolin-6-yloxypropanes as beta3-adrenergic receptor agonists: Design, synthesis, biological evaluation and pharmacophore modeling
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Article
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