- Investigation of the N-substituent conformation governing potency and μ receptor subtype-selectivity in (+)-(3R,4R)-dimethyl-4-(3- hydroxyphenyl)piperidine opioid antagonists
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A study of the binding site requirements associated with the N- substituent of (+)-(3R,4R)dimethyl-4-(3-hydroxyphenyl)piperidine (4) derivatives was undertaken using a set of rigid vs flexible N-substituents. The study showed that compounds 7-9 bearing th
- Thomas, James B.,Wayne Mascarella,Rothman, Richard B.,Partilla, John S.,Xu, Heng,McCullough, Karen B.,Dersch, Christina M.,Cantrell, Buddy E.,Zimmerman, Dennis M.,Carroll, F. Ivy
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- Diastereo- and Enantioselective Cross-Couplings of Secondary Alkylcopper Reagents with 3-Halogeno-Unsaturated Carbonyl Derivatives
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Chiral secondary alkylcopper reagents were prepared from the corresponding alkyl iodides with retention of configuration by an I/Li-exchange using tBuLi (?100 °C, 1 min) followed by a transmetalation with CuBr?P(OEt)3 (?100 °C, 20 s). These ste
- Kremsmair, Alexander,Skotnitzki, Juri,Knochel, Paul
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- TARGETED COVALENT PROBES AND INHIBITORS OF PROTEINS CONTAINING REDOX-SENSITIVE CYSTEINES
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Covalent, irreversible small-molecule inhibitors that modify the sulfenyl form (i.e., sulfenic acid, RSOH and sulfenamide, RSNR'2) of therapeutically important proteins (particularly kinases and phosphatases) are disclosed, where the compositions include a compound having a substituted aryl or heterocyclic core structure that promotes binding interactions with a specific protein, and a nucleophilic reaction center (carbon, nitrogen, sulfur, or phosphorous) that is capable of forming a covalent bond with a sulfenic acid- or sulfenamide-modified cysteine residue in the protein. Methods for synthesizing these compounds are also disclosed, as well as methods of using them for determining the bioactivity of a chemical composition comprising an active compound toward a specific protein and for determining the potency of an inhibitor against a specific protein.
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