- Development of indole sulfonamides as cannabinoid receptor negative allosteric modulators
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Existing CB1 negative allosteric modulators (NAMs) fall into a limited range of structural classes. In spite of the theoretical potential of CB1 NAMs, published in vivo studies have generally not been able to demonstrate the expected therapeutically-relevant CB1-mediated effects. Thus, a greater range of molecular tools are required to allow definitive elucidation of the effects of CB1 allosteric modulation. In this study, we show a novel series of indole sulfonamides. Compounds 5e and 6c (ABD1075) had potencies of 4 and 3?nM respectively, and showed good oral exposure and CNS penetration, making them highly versatile tools for investigating the therapeutic potential of allosteric modulation of the cannabinoid system.
- Greig, Iain R.,Baillie, Gemma L.,Abdelrahman, Mostafa,Trembleau, Laurent,Ross, Ruth A.
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supporting information
p. 4403 - 4407
(2016/08/25)
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- Electrophilicity of pyridazine-3-carbonitrile, pyrimidine-2-carbonitrile, and pyridine-carbonitrile derivatives: A chemical model to describe the formation of thiazoline derivatives in human liver microsomes
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(Chemical Equation Presented) Certain aromatic nitriles are well-known inhibitors of cysteine proteases. The mode of action of these compounds involves the formation of a reversible or irreversible covalent bond between the nitrile and a thiol group in th
- Sinha, Sarmistha,Ahire, Deepak,Wagh, Santosh,Mullick, Dibakar,Sistla, Ramesh,Selvakumar, Kumaravel,Cortes, Janet Caceres,Putlur, Siva Prasad,Mandlekar, Sandhya,Johnson, Benjamin M.
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p. 2052 - 2061
(2015/02/19)
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- N- (ARYLALKYL) - 1H- INDOLE- 2 - SULFONIC ACID AMIDE COMPOUNDS AND THEIR THERAPEUTIC USE AS CANNABINOID ALLOSTERIC MODULATORS
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The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain /V-(arylalkyl)-1 H-indole- 2-sulfonic acid amide compounds that, inter alia, inhibit cannabinoid receptor signalling. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit cannabinoid receptor signalling; to treat disorders that are ameliorated by the inhibition of cannabinoid receptor signalling; to treat metabolic syndrome, type-2 diabetes, dyslipidaemia, obesity, eating disorders, cardiovascular diseases and disorders, and other conditions as described herein.
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Page/Page column 145
(2012/09/21)
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