- 4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable stearoyl-CoA desaturase-1 (SCD1) inhibitors: Part 2. Pyridazine-based analogs
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Design, synthesis, and biological evaluation of pyridazine-based, 4-bicyclic heteroaryl-piperidine derivatives as potent stearoyl-CoA desaturase-1 (SCD1) inhibitors are described. In a chronic study of selected analog (3e) in Zucker fa/fa (ZF) rat, dose-dependent decrease of body weight gain and plasma fatty acid desaturation index (DI) in both C16 and C18 are also demonstrated. The results indicate that the plasma fatty acid DI may serve as an indicator for direct target engagement and biomarker for SCD1 inhibition.
- Yang, Shyh-Ming,Tang, Yuting,Rano, Thomas,Lu, Huajun,Kuo, Gee-Hong,Gaul, Michael D.,Li, Yaxin,Ho, George,Lang, Wensheng,Conway, James G.,Liang, Yin,Lenhard, James M.,Demarest, Keith T.,Murray, William V.
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supporting information
p. 1437 - 1441
(2014/03/21)
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- 4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable Stearoyl-CoA desaturase-1 (SCD1) inhibitors. Part 1: Urea-based analogs
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A new series of urea-based, 4-bicyclic heteroaryl-piperidine derivatives as potent SCD1 inhibitors is described. The structure-activity relationships focused on bicyclic heteroarenes and aminothiazole-urea portions are discussed. A trend of dose-dependent decrease in body weight gain in diet-induced obese (DIO) mice is also demonstrated.
- Yang, Shyh-Ming,Tang, Yuting,Zhang, Rui,Lu, Huajun,Kuo, Gee-Hong,Gaul, Michael D.,Li, Yaxin,Ho, George,Conway, James G.,Liang, Yin,Lenhard, James M.,Demarest, Keith T.,Murray, William V.
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supporting information
p. 6773 - 6776
(2014/01/06)
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- Synthesis and Neuroleptic Activity of 3-(1-Substituted-4-piperidinyl)-1,2-benzisoxazoles
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The synthesis of a series of 3-(1-substituted-4-piperidinyl)-1,2-benzisoxazoles is described.The neuroleptic activity of the series was evaluated by utilizing the climbing mice assay and inhibition of spiroperidol binding.Structure-activity relationships were studied by variation of the substituent on the benzisoxazole ring with concomitant variation of four different 1-piperidinyl substituents.Maximum neuroleptic activity was realized when there was a 6-fluoro substituent on the benzisoxazole ring.The 1-piperidinyl substituent appeared less significant, although in most cases, the (1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)propyl group imparted maximum potency.The most potent compound in both assays was 6-fluoro-3--4-piperidinyl>-1,2-benzisoxazole (11b).
- Strupczewski, Joseph T.,Allen, Richard C.,Gardner, Beth Ann,Schmid, Blaine L.,Stache, Ulrich,et al.
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p. 761 - 769
(2007/10/02)
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