- Discovery of a Potent (4 R,5 S)-4-Fluoro-5-methylproline Sulfonamide Transient Receptor Potential Ankyrin 1 Antagonist and Its Methylene Phosphate Prodrug Guided by Molecular Modeling
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Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel expressed in sensory neurons where it functions as an irritant sensor for a plethora of electrophilic compounds and is implicated in pain, itch, and respiratory disease. To s
- Chen, Huifen,Volgraf, Matthew,Do, Steven,Kolesnikov, Aleksandr,Shore, Daniel G.,Verma, Vishal A.,Villemure, Elisia,Wang, Lan,Chen, Yong,Hu, Baihua,Lu, Ai-Jun,Wu, Guosheng,Xu, Xiaofeng,Yuen, Po-Wai,Zhang, Yamin,Erickson, Shawn D.,Dahl, Martin,Brotherton-Pleiss, Christine,Tay, Suzanne,Ly, Justin Q.,Murray, Lesley J.,Chen, Jun,Amm, Desiree,Lange, Wienke,Hackos, David H.,Reese, Rebecca M.,Shields, Shannon D.,Lyssikatos, Joseph P.,Safina, Brian S.,Estrada, Anthony A.
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p. 3641 - 3659
(2018/05/01)
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- SUBSTITUTED HETEROCYCLIC SULFONAMIDE COMPOUNDS USEFUL AS TRPA1 MODULATORS
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The invention is concerned with the compounds of formula I or II: and salts thereof. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I or II as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.
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Paragraph 0666; 0667
(2015/04/28)
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- HEPATITIS C VIRUS INHIBITORS
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This disclosure concerns novel compounds of Formula (I) as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds
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Page/Page column 144-145
(2012/04/10)
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- VLA-4 inhibitor compounds
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Compounds that selectively inhibit the binding of ligands to alpha4beta1 integrin (VLA-4) and methods for their preparation are disclosed. In one embodiment, compounds of the invention are represented by Formula I: As selective inhibitors of VLA-4 mediated cell adhesion, compounds of the present invention are useful in the treatment of conditions associated with such adhesion, including, but not limited to, such conditions as inflammatory and autoimmune responses, diabetes, asthma, psoriasis, inflammatory bowel disease, transplantation rejection, and tumor metastasis. Also disclosed are pharmaceutical compositions, methods of inhibiting VLA-4 mediated cell adhesion and methods of treating conditions associated with LA-4 mediated cell adhesion, which involve compounds of Formula I.
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- SYNTHESIS OF TRANS-5-METHYLPROLINE AND ITS INFLUENCE ON CIS-TRANS ISOMERISM IN &β-CASOMORPHIN-5
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Starting from L-proline, trans-5-methylproline has been prepared using electrochemical oxidation followed by methylcopper substitution.After incorporation of this amino acid into β-casomorphin-5 at the two and four position, an NMR study revealed only limited influence on the cis/trans ratio of the peptide bond.The opioid receptor affinities did not allow to confirm the requirement for a cis Tyr-Pro peptide bond for biological activity.
- Tourwe, D.,Betsbrugge, J. Van,Verheyden, P.,Hootele, C.
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p. 201 - 206
(2007/10/02)
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