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Your search keyword '"Morytko, Michael"' showing total 6 results
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6 results on '"Morytko, Michael"'

1. Structure activity optimization of 6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazines as Jak1 kinase inhibitors

Author

Anwar Murtaza, Edit Tarcsa, Ana L. Aguirre, Neil Wishart, Gagandeep Somal, Lu Wang, Kent D. Stewart, Stacy Van Epps, Kristine E. Frank, Heather Davis, Michael Friedman, Bin Li, Jeffrey W. Voss, Maria A. Argiriadi, Jonathan George, Morytko Michael J, Jeremy J. Edmunds, Dawn M. George, Deborah Hyland, Kevin R. Woller, Eric R. Goedken, and Bryan A. Fiamengo

Subjects
Male, Models, Molecular, Pyrazine, Stereochemistry, Clinical Biochemistry, Pharmaceutical Science, Biochemistry, Rats sprague dawley, Cell Line, Rats, Sprague-Dawley, Structure-Activity Relationship, chemistry.chemical_compound, Jak1 Kinase, Drug Discovery, Animals, Humans, Structure–activity relationship, Protein Kinase Inhibitors, Molecular Biology, chemistry.chemical_classification, Dose-Response Relationship, Drug, Molecular Structure, Janus kinase 1, Chemistry, Kinase, Organic Chemistry, Janus Kinase 1, Triazoles, Combinatorial chemistry, Rats, Pyrazines, Molecular Medicine, Selectivity, Tricyclic
Abstract

Previous work investigating tricyclic pyrrolopyrazines as kinase cores led to the discovery that 1-cyclohexyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (12) had Jak inhibitory activity. Herein we describe our initial efforts to develop orally bioavailable analogs of 12 with improved selectivity of Jak1 over Jak2.

Published
2015

2. Thienopyrrole acetic acids as antagonists of the CRTH2 receptor

Author

Mcpherson Michael J, Morytko Michael J, Grier A. Wallace, Tegest Kebede, Ayome Abibi, Dominique Bonafoux, Christopher M. Harris, Brian M. Bettencourt, Andrew Burchat, Anna M. Ericsson, and Xiaoyun Wu

Subjects
Stereochemistry, Carboxylic acid, Clinical Biochemistry, Receptors, Prostaglandin, Pharmaceutical Science, Biological Availability, Acetates, Biochemistry, Chemical synthesis, Mice, Pharmacokinetics, Drug Discovery, Animals, Pyrroles, Receptors, Immunologic, Molecular Biology, ADME, chemistry.chemical_classification, Indole test, Organic Chemistry, Antagonist, Biological activity, Bioavailability, Rats, chemistry, Microsomes, Liver, Molecular Medicine
Abstract

The bioisosteric replacement of the indole core of CRTH2 antagonists using thienopyrroles was investigated, resulting in potent antagonists with good selectivity over DP1. Early ADME/PK assessment of this chemotype demonstrated bioavailability in mice.

Published
2010

3. Synthesis and activity of N-cyanoguanidine-piperazine P2X7 antagonists

Author

Nathan S. Josephsohn, John W. Maull, Moore Nigel St John, Brian Bettencourt, Morytko Michael J, Lu Wang, Edit Tarcsa, Jonathan George, Biqin Li, Paul Rafferty, Diana L. Donnelly-Roberts, Marian T. Namovic, Patrick Betschmann, Michael Friedman, Jose-Andres Salmeron-Garcia, Gavin C. Hirst, Donald Konopacki, and Woller Kevin R

Subjects
Chemistry, Pharmaceutical, Clinical Biochemistry, Interleukin-1beta, Pharmaceutical Science, Pharmacology, Biochemistry, Chemical synthesis, Guanidines, Piperazines, chemistry.chemical_compound, Inhibitory Concentration 50, Structure-Activity Relationship, In vivo, Drug Discovery, Purinergic P2 Receptor Antagonists, Structure–activity relationship, Animals, Humans, Receptor, Molecular Biology, Piperazine, Whole blood, Molecular Structure, Chemistry, Receptors, Purinergic P2, Organic Chemistry, Biological activity, In vitro, Rats, Models, Chemical, Drug Design, Molecular Medicine, Receptors, Purinergic P2X7
Abstract

A novel series of cyanoguanidine-piperazine P2X(7) antagonists were identified and structure-activity relationship (SAR) studies described. Compounds were assayed for activity at human and rat P2X(7) receptors in addition to their ability to inhibit IL-1 beta release from stimulated human whole blood cultures. Compound 27 possesses potent activity (0.12 microM) in this latter assay and demonstrates moderate clearance in-vivo.

Published
2008

4. Synthesis and in vitro activity of N'-cyano-4-(2-phenylacetyl)-N-o-tolylpiperazine-1-carboximidamide P2X7 antagonists

Author

Haipeng Chen, Morytko Michael J, Anna M. Ericsson, Patrick Betschmann, Diana L. Donnelly-Roberts, Michael F. Jarvis, Marian T. Namovic, William A. Carroll, Paul Rafferty, and Woller Kevin R

Subjects
Nitrile, Stereochemistry, Clinical Biochemistry, Pharmaceutical Science, In Vitro Techniques, Biochemistry, Chemical synthesis, Piperazines, chemistry.chemical_compound, Structure-Activity Relationship, Drug Discovery, Purinergic P2 Receptor Antagonists, Structure–activity relationship, Moiety, Animals, Humans, Receptor, Molecular Biology, Molecular Structure, Chemistry, Receptors, Purinergic P2, Organic Chemistry, Antagonist, In vitro, Recombinant Proteins, Rats, Piperazine, Molecular Medicine, Receptors, Purinergic P2X7
Abstract

A novel series of cyanoguanidine-piperazine P2X(7) antagonists was designed based upon the structure of A-740003. Structure-activity relationship (SAR) studies focused on the piperazine moiety and the right hand side substitution. Compounds were assayed for activity at human and rat P2X(7) receptors and compound 29 was found to possess potent activity (IC(50)=30-60 nM) at both species.

Published
2007

5. Discovery of thienopyridines as Src-family selective Lck inhibitors

Author

Lily Abbott, Kelly D. Mullen, David J. Calderwood, Morytko Michael J, Heather Davis, Bryant Yang, Gavin C. Hirst, Andrew Burchat, Peter Hrnciar, Patrick Betschmann, and Biqin Li

Subjects
Pyridines, Clinical Biochemistry, Pharmaceutical Science, chemical and pharmacologic phenomena, Computational biology, Biochemistry, Inhibitory Concentration 50, Structure-Activity Relationship, Drug Discovery, Thienopyridines, Structure–activity relationship, Inhibitory concentration 50, Humans, Binding site, Molecular Biology, Src family, Binding Sites, Chemistry, Organic Chemistry, hemic and immune systems, src-Family Kinases, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Drug Design, Molecular Medicine, Hinge region
Abstract

We describe the identification, SAR, and in vivo pharmacology of a new series of Src-family selective Lck inhibitors. These thienopyridines were designed based on a desire to access the unique residues in the extended hinge region of Lck.

Published
2006

6. Novel cytokine release inhibitors. Part II: Steroids

Author

Fu-Chih Huang, Wei He, Navin Jariwala, Kin-Tak Yu, and Morytko Michael J

Subjects
medicine.medical_treatment, Clinical Biochemistry, Anti-Inflammatory Agents, Pharmaceutical Science, Alcohol, Biochemistry, Chemical synthesis, Monocytes, Steroid, chemistry.chemical_compound, Inhibitory Concentration 50, Structure-Activity Relationship, Drug Discovery, medicine, Humans, Phenols, Molecular Biology, Cells, Cultured, Monocyte, Organic Chemistry, In vitro, Interleukin 1β, Cytokine, medicine.anatomical_structure, chemistry, Molecular Medicine, Steroids, Interleukin-1
Abstract

Steroidal derivatives as IL-1 beta release inhibitors are discussed.

Published
1999

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