A5056693530- Chemical Synthesis and Analysis
- Neuroscience and Neuropharmacology Research
- Synthesis and biological activity
- Synthesis and Characterization of Heterocyclic Compounds
- Carbohydrate Chemistry and Synthesis
- Phenothiazines and Benzothiazines Synthesis and Activities
- Synthetic Organic Chemistry Methods
- Chemical Synthesis and Reactions
- Cytokine Signaling Pathways and Interactions
- Estrogen and related hormone effects
- Quinazolinone synthesis and applications
- Receptor Mechanisms and Signaling
- Protein Kinase Regulation and GTPase Signaling
- Catalytic C–H Functionalization Methods
- Organic and Inorganic Chemical Reactions
- Sulfur-Based Synthesis Techniques
- Metabolism and Genetic Disorders
- Cell Adhesion Molecules Research
- Molecular spectroscopy and chirality
- Chronic Myeloid Leukemia Treatments
- Catalytic Cross-Coupling Reactions
- Click Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- Bioactive Compounds and Antitumor Agents
- Pharmacological Receptor Mechanisms and Effects
Janssen (United States)
2014-2024
Springhouse
2016-2018
Johnson & Johnson (United States)
2004-2011
Freeport-McMoRan (United States)
1991-1993
Nova Medical (United States)
1990-1993
The Ohio State University
1984-1986
Estrogen-related receptor α (ERRα) is an orphan nuclear that has been functionally implicated in the regulation of energy homeostasis. Herein described development diaryl ether based thiazolidenediones, which function as selective ligands against this receptor. Series optimization provided several potent analogues inhibit recruitment a coactivator peptide fragment vitro biochemical assays (IC(50) < 150 nM) and cellular two-hybrid reporter ligand binding domain = 1-5 μM). A cocrystal...
[reaction: see text] An efficient and versatile method for stereoselective synthesis of (E)-3,3-(diarylmethylene)indolinones by a palladium-catalyzed tandem Heck-carbocyclization/Suzuki-coupling sequence is presented. Factors influencing yield selectivity, namely catalyst, coordinating ligand, solvent, are detailed.
The cFMS proto-oncogene encodes for the colony-stimulating factor-1 receptor, a receptor-tyrosine kinase responsible differentiation and maturation of certain macrophages. Upon binding its ligand autophosphorylates, dimerizes, induces phosphorylation downstream targets. We report novel crystal structure unphosphorylated in complex with two members different classes drug-like protein inhibitors. exhibits typical bi-lobal fold, activation loop DFG motif are found to be canonical inactive...
The interleukin (IL)-23 pathway is a pathogenic driver in psoriasis, psoriatic arthritis, and inflammatory bowel disease. Currently, no oral therapeutics selectively target this pathway. JNJ-77242113 peptide targeting the IL-23 receptor with high affinity (KD: 7.1 pM). In human cells, potently inhibited proximal signaling (IC50: 5.6 pM) without impacting IL-12 signaling. IL-23-induced interferon (IFN)γ production NK blood from healthy donors psoriasis patients 18.4, 11 9 pM, respectively)....
2-Hydroxy-4,6-diamino-[1,3,5]triazines are described which a novel class of potent inhibitors the VEGF-R2 (flk-1/KDR) tyrosine kinase. 4-(Benzothiazol-6-ylamino)-6-(benzyl-isopropyl-amino)-[1,3,5]triazin-2-ol (14d) exhibited low nanomolar potency in vitro enzyme inhibition assay (IC50 = 18 nM) and submicromolar inhibitory activity KDR-induced MAP kinase autophosphorylation HUVEC cells 280 nM), also demonstrated good selectivity against panel growth factor receptor kinases. Further, 14d...
A single-step process for the preparation of 2-amino-7-chlorothiazolo[5,4-d]pyrimidines, 2, was achieved by reaction commercially available 4,6-dichloro-5-aminopyrimidine 1 with isothiocyanates. This mild accommodates a variety functionalized isothiocyanates and proceeds in good to excellent yields. The utility such intermediates is exemplified subsequent alkyl or arylamine nucleophiles afford novel, differentially 2,7-diaminothiazolo[5,4-d]pyrimidines, 3.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAsymmetric synthesis of a potent and selective competitive NMDA antagonistGregory S. Hamilton, Zhiwen Huang, Xiao Jing Yang, Raymond J. Patch, B. A. Narayanan, John W. FerkanyCite this: Org. Chem. 1993, 58, 25, 7263–7270Publication Date (Print):December 1, 1993Publication History Published online1 May 2002Published inissue 1 December 1993https://pubs.acs.org/doi/10.1021/jo00077a058https://doi.org/10.1021/jo00077a058research-articleACS...
2R,4R,5S-(2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid) (NPC 17742), the most potent isomer of mixture 2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid 12626), was evaluated for activity in tests associated with receptors excitatory amino acids. In receptor binding assays, NPC 17742 selective N-methyl-D-aspartate (NMDA) a potency comparable to that D(-, -3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid. Like (+/-)cis-4-phosphono-methyl-2-piperidine carboxylic (CGS 19755)...
The development of a reproducible process for multihundred gram production (Z)-5-((1-(4-chloro-2-(trifluoromethyl)benzyl)-1H-indazol-5-yl)methylene)-3-((3R,4R)-3-fluoro-1-methylpiperidin-4-yl)thiazolidine-2,4-dione (26), potent and selective inhibitor estrogen-related receptor 1 (ERR1), is described. This synthesis was achieved via magnesium perchlorate-catalyzed regioselective epoxide ring-opening tert-butyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (9) with thiazolidine-2,4-dione (6,...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT(Aminoalkoxy)chromones. Selective .sigma. receptor ligandsRonald H. Erickson, Kenneth J. Natalie Jr., William Bock, Zhijian Lu, Farzaneh Farzin, Ronald G. Sherrill, David Meloni, Raymond Patch, Waclaw Rzesotarski, and Cite this: Med. Chem. 1992, 35, 9, 1526–1535Publication Date (Print):May 1, 1992Publication History Published online1 May 2002Published inissue 1...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEpimeric cis-decahydroquinoline-5-carboxylic acids: effects on .gamma.-aminobutyric acid uptake and receptor binding in vitroDonald T. Witiak, Kuniyuki Tomita, Raymond J. Patch, S. EnnaCite this: Med. Chem. 1981, 24, 7, 788–794Publication Date (Print):July 1, 1981Publication History Published online1 May 2002Published inissue 1 July 1981https://doi.org/10.1021/jm00139a005Request reuse permissionsArticle Views704Altmetric-Citations22LEARN ABOUT...
The long circulating half-life and inherently bivalent architecture of IgGs provide an ideal vehicle for presenting otherwise short-lived G-protein-coupled receptor agonists in a format that enables avidity-driven enhancement potency. Here, we describe the site-specific conjugation dual agonist peptide (an oxyntomodulin variant engineered potency vivo stability) to complementarity-determining regions (CDRs) immunologically silent IgG4. A cysteine-containing heavy chain CDR3 was identified...
ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTMultivalent Templated Saccharides: Convenient Syntheses of Spacer-Linked 1,1'-Bis -and 1,1',1''-Tris-β-glycosides by the Glycal Epoxide Glycosidation MethodRaymond J. Patch, Hang Chen, and Chennagiri R. PanditView Author Information Department Rational Drug Design, Procept, Inc., 840 Memorial Drive, Cambridge, Massachusetts 02139 Cite this: Org. Chem. 1997, 62, 5, 1543–1546Publication Date (Web):March 7, 1997Publication History Received24 September...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereoselective syntheses of the trans-decahydroquinoline-5-carboxylic acid epimers. Diastereomeric zwitterionic probes .gamma.-aminobutyric acid-related biological properties in vitro and vivoDonald T. Witiak, Raymond J. Patch, S. Enna, Yiu K. FungCite this: Med. Chem. 1986, 29, 1, 1–8Publication Date (Print):January 1986Publication History Published online1 May 2002Published inissue 1 January...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSubstituted 2-(aminomethyl)piperidines: a novel class of selective protein kinase C inhibitorsBarry G. Shearer, James P. Sullivan, J. Paul Carter, Rose M. Mathew, Phillip Waid, Jane R. Connor, Raymond Patch, and Ronald BurchCite this: Med. Chem. 1991, 34, 9, 2928–2931Publication Date (Print):September 1, 1991Publication History Published online1 May 2002Published inissue 1 September 1991https://doi.org/10.1021/jm00113a038Request reuse...