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Your search keyword '"B.E. Abboa-Offei"' showing total 2 results
Start Over Author "B.E. Abboa-Offei" Journal bioorganic & medicinal chemistry letters
2 results on '"B.E. Abboa-Offei"'

1. Arylpropanolamines: Selective β3 agonists arising from strategies to mitigate phase I metabolic transformations

Author

A A Seymour, William N. Washburn, Dorothy Slusarchyk, P.J. McCann, B.E. Abboa-Offei, Minsheng Zhang, G.T. Allen, Ravindar N. Girotra, B.H. Frohlich, Michael Cap, Jollie D. Godfrey, Peter T. W. Cheng, R.J. George, C. Shao, Anita D. Russell, S. Skwish, Philip M. Sher, Jon J. Hangeland, A.V. Gavai, T.L. Waldron, Belay Tesfamariam, Yolanda Caringal, T.W. Harper, Tamara Dejneka, Kenneth E.J. Dickinson, Ginger Wu, Syed Z. Ahmed, Amarendra B. Mikkilineni, and Hongwei Zhang

Subjects
Agonist, β3 adrenergic receptor, Alkylation, medicine.drug_class, Chemistry, Organic Chemistry, Clinical Biochemistry, Pharmaceutical Science, Adrenergic beta-3 Receptor Agonists, Oxidative phosphorylation, Adrenergic beta-Agonists, Pharmacology, Biochemistry, Propanolamines, Structure-Activity Relationship, Drug Discovery, medicine, Molecular Medicine, Adrenergic agonist, β adrenergic receptor, Oxidation-Reduction, Molecular Biology, Drug metabolism
Abstract

Utilization of N-substituted-4-hydroxy-3-methylsulfonanilidoethanolamines 1 as selective beta(3) agonists is complicated by their propensity to undergo metabolic oxidative N-dealkylation, generating 0.01-2% of a very potent alpha(1) adrenergic agonist 2. A summary of the SAR for this hepatic microsomal conversion precedes presentation of strategies to maintain the advantages of chemotype 1 while mitigating the consequences of N-dealkylation. This effort led to the identification of 4-hydroxy-3-methylsulfonanilidopropanolamines 15 for which the SAR for the unique stereochemical requirements for binding to the beta adrenergic receptors culminated in the identification of the potent, selective beta(3) agonist 15f.

Published
2007

2. BMS-196085: A potent and selective full agonist of the human β3 adrenergic receptor

Author

Liesl G. Fisher, P.J. McCann, D.A. Young, C.M. Arbeeny, S. Skwish, Amarendra B. Mikkilineni, Poss Kathleen M, G.T. Allen, Chongqing Sun, Michael Cap, R.J. George, Dorothy Slusarchyk, B.E. Abboa-Offei, Ravindar N. Girotra, William N. Washburn, Carl P. Ciosek, A.V. Gavai, Belay Tesfamariam, T.W. Harper, Ginger Wu, B.H. Frohlich, D.E. Hillyer, Tammy C. Wang, A A Seymour, Mark S. Bednarz, Philip M. Sher, Kenneth E.J. Dickinson, T.L. Waldron, and Arvind Mathur

Subjects
Blood Glucose, Agonist, medicine.medical_specialty, Adrenergic receptor, medicine.drug_class, Clinical Biochemistry, Drug Evaluation, Preclinical, Administration, Oral, Mice, Obese, Pharmaceutical Science, Adrenergic, Adrenergic beta-3 Receptor Agonists, Biochemistry, Partial agonist, Mice, Structure-Activity Relationship, Internal medicine, Chlorocebus aethiops, Drug Discovery, medicine, Animals, Humans, Inverse agonist, Anilides, Receptor, Molecular Biology, Chemistry, Fatty Acids, Organic Chemistry, Adrenergic Agonists, Endocrinology, Adrenergic beta-1 Receptor Agonists, Receptors, Adrenergic, beta-3, Molecular Medicine, Receptors, Adrenergic, beta-1, Endogenous agonist
Abstract

A series of 4-hydroxy-3-methylsulfonanilido-1,2-diarylethylamines were prepared and evaluated for their human beta(3) adrenergic receptor agonist activity. SAR studies led to the identification of BMS-196085 (25), a potent beta(3) full agonist (K(i)=21 nM, 95% activation) with partial agonist (45%) activity at the beta(1) receptor. Based on its desirable in vitro and in vivo properties, BMS-196085 was chosen for clinical evaluation.

Published
2001

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