Igor Goljer

The metabolism and disposition of GSK2140944 in healthy human subjects

Kitaw Negash, Clara Andonian, Clive C. Felgate, Cathy Yi-Hsuan Chen et autres

1. GSK2140944 is a novel bacterial topoisomerase inhibitor in development for the treatment of bacterial infections. The metabolism and disposition in healthy human subjects was investigated. 2. Six male subjects received [(14)C] GSK2140944 orally (2000 mg) and as a single 2-hour i.v. …

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Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of GSK2336805, an Inhibitor of Hepatitis C Virus (HCV) NS5A, in Healthy Subjects and Subjects Chronically Infected with HCV Genotype 1

David A. Wilfret, Jill T. Walker, Kimberly K. Adkison, L. A. Jones et autres

GSK2336805 is an orally bioavailable hepatitis C virus (HCV) inhibitor working through an NS5A-mediated mechanism. This first-time-in-human study was conducted to assess the safety, tolerability, pharmacokinetics, metabolism, and efficacy of GSK2336805 in healthy subjects and subjects infected with HCV genotype 1. We …

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Metabolism, Excretion, and Mass Balance of the HIV-1 Integrase Inhibitor Dolutegravir in Humans

Stephen Castellino, Lee Moss, David S. Wagner, Julie Borland et autres

The pharmacokinetics, metabolism, and excretion of dolutegravir, an unboosted, once-daily human immunodeficiency virus type 1 integrase inhibitor, were studied in healthy male subjects following single oral administration of [(14)C]dolutegravir at a dose of 20 mg (80 μCi). Dolutegravir was well tolerated, and …

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Identification of Phenylsulfone-Substituted Quinoxaline (WYE-672) as a Tissue Selective Liver X-receptor (LXR) Agonist

Baihua Hu, Rayomand J. Unwalla, Igor Goljer, James W. Jetter et autres

A series of phenyl sulfone substituted quinoxaline were prepared and the lead compound 13 (WYE-672) was shown to be a tissue selective LXR Agonist. Compound 13 demonstrated partial agonism for LXRbeta in kidney HEK-293 cells but did not activate Gal4 LXRbeta fusion …

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Metabolism of Intravenous Methylnaltrexone in Mice, Rats, Dogs, and Humans

Appavu Chandrasekaran, Zeen Tong, Hongshan Li, John C. L. Erve et autres

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ChemInform Abstract: Efficient, Regioselective Palladium‐Catalyzed Tandem Heck‐Isomerization Reaction of Aryl Bromides and Non‐Allylic Benzyl Alcohols.

Matthew L. Crawley, Kristin M. Phipps, Igor Goljer, John F. Mehlmann et autres

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article …

3-(Arylamino)-3-phenylpropan-2-olamines as a new series of dual norepinephrine and serotonin reuptake inhibitors

A. T. Vu, Stephen T. Cohn, Eugene Anthony Terefenko, William Moore et autres

Efficient, Regioselective Palladium-Catalyzed Tandem Heck-Isomerization Reaction of Aryl Bromides and Non-Allylic Benzyl Alcohols

Matthew L. Crawley, Kristin M. Phipps, Igor Goljer, John F. Mehlmann et autres

An efficient and mild method to couple aryl bromides and activated non-allylic alcohols in a Heck reaction with tandem isomerization to selectively afford high yields of 1,5-diarylalkan-1-ones has been developed. Mechanistic insight was gained through NMR studies of products derived from deuterium-labeled …

Evaluating Indole-Related Derivatives as Precursors in the Directed Biosynthesis of Diazepinomicin Analogues§

Anokha S. Ratnayake, Jeffrey E. Janso, Xidong Feng, Gerhard Schlingmann et autres

The effectiveness of precursor-directed biosynthesis to generate diazepinomicin (1) analogues with varied ring-A substitutents was investigated by feeding commercially available, potential ring-A precursors such as fluorinated tryptophans, halogenated anthranilates, and various substituted indoles into growing actinomycete culture DPJ15 (genus Micromonospora). Two new …

Modulation of Wnt Signaling Through Inhibition of Secreted Frizzled-Related Protein I (sFRP-1) with N-Substituted Piperidinyl Diphenylsulfonyl Sulfonamides

William Moore, Jeffrey C. Kern, Ramesh A. Bhat, Thomas J. Commons et autres

The diphenylsulfonyl sulfonamide scaffold represented by 1 (WAY-316606) are small molecule inhibitors of the secreted protein sFRP-1, an endogenous antagonist of the secreted glycoprotein Wnt. Modulators of the Wnt pathway have been proposed as anabolic agents for the treatment of osteoporosis or …

Parallel Synthesis of 2-Aryl-4-aminobenzimidazoles and Their Evaluation as Gonadotropin Releasing Hormone Antagonists

Daniel M. Green, Igor Goljer, Diane S. Andraka, Murty Chengalvala et autres

2-Trifluoromethyl-4-aminobenzimidazoles were previously identified by screening to be active antagonists of the gonadotropin releasing hormone receptor (GnRH-R). Structure activity relationships and diversity oriented synthesis are shown here in greater detail. 2-Substituted benzimidazoles were synthesized in parallel by the coupling of carboxylic acids …

Unexpected rearrangement of enantiomerically pure 3‐aminoquinuclidine as a simple way of preparing diastereomeric octahydropyrrolo[2,3‐c]pyridine derivatives

Igor Goljer, Albert J. Molinari, Yanan He, Lisa M. Nogle et autres

Reaction of (S)- or (R)-3-aminoquinuclidine with 2-chloropyrimidine or 2-bromopyrimidine led to an unexpected formation of both cis- and trans-octahydropyrrolo [2,3]pyridine derivatives. A single-step synthesis of two of the four stereoisomers of these octahydropyrrolo[2,3]pyridine derivatives provides a convenient way of generating stereochemically defined …