- Copper-catalyzed selective oxygenation of methyl and benzyl substituents in pyridine with O2
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A selective oxygenation of picolines and their derivatives has been achieved by usingasimple copper salt as a catalyst and molecular oxygen as an oxidant, where the α-position of the alkyl substituent is selectively oxidized to give the corresponding aldehydes or ketones. Addition of a catalytic amount of water enhances the catalytic activity, which could be attributed to the role of the proton donor to activate the substrates.
- Abe, Tsukasa,Tanaka, Shinji,Ogawa, Atsuko,Tamura, Masanori,Sato, Kazuhiko,Itoh, Shinobu
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supporting information
p. 348 - 350
(2017/02/23)
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- AMINOPYRIMIDINE HETEROCYCLIC COMPOUND WITH ADENOSINE RECEPTOR ANTAGONISTIC ACTIVITY
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Disclosed hereinis an aminopyrimidine heterocyclic compound with adenosine receptor antagonistic activity, comprising a compound of the general formula (I), or a pharmaceutically acceptable salt thereof. The aminopyrimidine heterocyclic compound with adenosine receptor antagonistic activitydisclosed herein can be used as an effective adenosine receptor antagonist, and can be used for the treatment or prevention of disorders caused by abnormal level of adenosine.
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Paragraph 000119; 000120; 000121
(2017/06/23)
-
- Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure
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A novel class of therapeutic drug candidates for heart failure, highly potent and selective GRK2 inhibitors, exhibit potentiation of β-adrenergic signaling in vitro studies. Hydrazone derivative 5 and 1,2,4-triazole derivative 24a were identified as hit compounds by HTS. New scaffold generation and SAR studies of all parts resulted in a 4-methyl-1,2,4-triazole derivative with an N-benzylcarboxamide moiety with highly potent activity toward GRK2 and selectivity over other kinases. In terms of subtype selectivity, these compounds showed enough selectivity against GRK1, 5, 6, and 7 with almost equipotent inhibition to GRK3. Our medicinal chemistry efforts led to the discovery of 115h (GRK2 IC50 = 18 nM), which was obtained the cocrystal structure with human GRK2 and an inhibitor of GRK2 that potentiates β-adrenergic receptor (βAR)-mediated cAMP accumulation and prevents internalization of βARs in β2AR-expressing HEK293 cells treated with isoproterenol. Therefore, 115h appears to be a novel class of therapeutic for heart failure treatment.
- Okawa, Tomohiro,Aramaki, Yoshio,Yamamoto, Mitsuo,Kobayashi, Toshitake,Fukumoto, Shoji,Toyoda, Yukio,Henta, Tsutomu,Hata, Akito,Ikeda, Shota,Kaneko, Manami,Hoffman, Isaac D.,Sang, Bi-Ching,Zou, Hua,Kawamoto, Tetsuji
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p. 6942 - 6990
(2017/09/07)
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- Anti-inflammatory agents
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Disclosed are novel compounds that are useful in regulating the expression of interleukin-6 (IL-6) and/or vascular cell adhesion molecule-1 (VCAM-1), and their use in the treatment and/or prevention of cardiovascular and inflammatory diseases and related disease states, such as, for example, atherosclerosis, asthma, arthritis, cancer, multiple sclerosis, psoriasis, and inflammatory bowel diseases, and autoimmune disease(s). Also, disclosed are compositions comprising the novel compounds, as well as methods for their preparation.
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Page/Page column 145
(2016/02/05)
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- FUSED MORPHOLINOPYRIMIDINES AND METHODS OF USE THEREOF
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The present disclosure relates to Fused Morpholinopyrimidines, pharmaceutical compositions comprising an effective amount of a Fused Morpholinopyrimidine and methods for using a Fused Morpholinopyrimidine in the treatment of a neurodegenerative disease, comprising administering to a subject in need thereof an effective amount of a Fused Morpholinopyrimidine.
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Paragraph 0320
(2015/10/05)
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- P2X4 RECEPTOR MODULATING COMPOUNDS AND METHODS OF USE THEREOF
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Provided herein are P2X4 receptor modulating compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, including but not limited to, chronic pain, neuropathy, inflammatory diseases and central nervous system disorders.
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Paragraph 00217
(2015/06/25)
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- P2X4 RECEPTOR MODULATING COMPOUNDS
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Provided herein are P2X4 receptor modulating compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, including but not limited to, chronic pain, neuropathy, inflammatory diseases and central nervous system disorders.
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Paragraph 00243
(2015/06/25)
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- COMPOUNDS AND METHODS FOR INHIBITION OF RENIN, AND INDICATIONS THEREFOR
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Compounds active as inhibitors of renin are described, as well as methods of using such compounds to treat diseases and conditions associated with the renin-angiotensin system. Formula (I)
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Page/Page column 64
(2010/11/18)
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- BENZIMIDAZOLES AND RELATED ANALOGS AS SIRTUIN MODULATORS
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Provided herein are sirtuin-modulating compounds of formula (II) The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
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Page/Page column 131-132
(2010/04/03)
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- IMIDAZOPYRIDINE AND RELATED ANALOGS AS SIRTUIN MODULATORS
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Provided herein are novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
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Page/Page column 98-99
(2009/12/27)
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- HETEROARYL SULFONAMIDES AND CCR2
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Compounds are provided that act as potent antagonists of the CCR2 receptor. Animal testing demonstrates that these compounds are useful for treating inflammation, a hallmark disease for CCR2. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR2-mediated diseases, and as controls in assays for the identification of CCR2 antagonists.
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Page/Page column 111
(2008/06/13)
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- 1,3-BENZOTHIAZINONE DERIVATIVES AND USE THEREOF
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This invention provides a compound represented by the formula (I) :wherein R1 is a hydrogen atom, a halogen atom, hydroxy, nitro, optionally halogenated alkyl, alkoxy optionally having substituents, acyl or amino optionally having substituents;R2 is pyridyl, furyl, thienyl, pyrrolyl, quinolyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, tetrahydroquinolyl or thiazolyl, each of which may have substituents;n is 1 or 2; or a salt. And this invention provides a safe pharmaceutical comprising the compound of the formula (I) , which has an excellent apoptosis inhibitory effect and MIF binding effect, for preventing and/or treating heart disease, nervous degenerative disease, cerebrovascular disease, central nervous infectious disease, traumatorathy, demyelinating disease, bone and articular disease, kidney disease, liver disease, osteomyelodysplasia, AIDS, cancer, and the like.
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- N-aryl(thio)anthranilic acid amide derivatives, their preparation and their use as VEGF receptor tyrosine kinase inhibitors
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Described are compounds of formula (I), wherein W is O or S; X is NR8; Y is CR9R10-(CH2)n wherein R9 and R10 are independently of each other hydrogen or lower alkyl, and n is an integer of
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- Regioselective hydroxylation of 2,4-lutidine: A practical synthesis of 4-hydroxymethyl-2-methylpyridine
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A practical synthesis of 4-hydroxymethyl-2-methylpyridine has been developed which makes use of Evans' regioselective lithiation of readily available 2,4-lutidine and trapping with dimethylformamide.
- Ragan, John A.,Jones, Brian P.,Meltz, Clifford N.,Teixeira Jr., John J.
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p. 483 - 486
(2007/10/03)
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- Isonitrile intermediates for the preparation of tri-substituted imidazole compounds with multiple therapeutic properties
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The invention relates to a novel group of isonitrile compounds and a process for their preparation, useful in the preparation of tri-substituted imadazoles having multiple therapeutic properties.
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- Imine intermediates for the preparation of trisubstituted imidazole compounds with multiple therapeutic properties
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The invention relates to a novel group of iminc compounds and a process for their preparation, useful in the preparation of tri-substituted imadazoles having multiple therapeutic properties.
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- Formamide intermediates for the preparation of tri-substituted imidazole compounds with multiple therapeutic properties
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The invention relates to a novel group of formamide compounds and a process for their preparation, useful in the preparation of tri-substituted imadazoles having multiple therapeutic properties.
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- Imidazole compounds, use and process of making
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Novel 1,4,5-substituted imidazole compounds and compositions for use in therapy as cytokine inhibitors.
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- Compounds
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Novel 1,4,5-substituted imidazole compounds and compositions for use in therapy as cytokine inhibitors.
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- Pyridyl imidazole compounds and compositions
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Novel 1, 4, 5-substituted imidazole compounds and compositions for use in therapy as cytokine inhibitors.
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- 1-Substituted 4-aryl-5-pyridinylimidazoles: A new class of cytokine suppressive drugs with low 5-lipoxygenase and cyclooxygenase inhibitory potency
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A series of 1-alkyl- or -aryl-4-aryl-5-pyridinylimidazoles (A) were prepared and tested for their ability to bind to a recently discovered protein kinase termed CSBP and to inhibit lipopolysaccharide (LPS)-stimulated TNF production in mice. The kinase, CS
- Boehm, Jeffrey C.,Smietana, Juanita M.,Sorenson, Margaret E.,Garigipati, Ravi S.,Gallagher, Timothy F.,Sheldrake, Peter L.,Bradbeer, Jeremy,Badger, Alison M.,Laydon, Jeffrey T.,Lee, John C.,Hillegass, Leonard M.,Griswold, Donald E.,Breton, John J.,Chabot-Fletcher, Marie C.,Adams, Jerry L.
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p. 3929 - 3937
(2007/10/03)
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- REACTIVITY OF METHYL DERIVATIVES OF NITROGENOUS HETEROCYCLES IN VAPOR-PHASE CATALYTIC OXIDATION
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A study has been made of the reactivity of methylpyridines, methylpyrazines, and methylquinolines in oxidation in the vapor phase in the presence of β-VO(PO3)2.Relationships have been found between the overall reaction rates of heterocyclic compounds and the charge on the ring nitrogen, and between the partial oxidation rate and the charge on the ring carbon atom adjacent to the methyl group.The partial oxidation rate of methylpyridines is given to a first approximation by the Hammett-type expression lnWa = -3.5 + 4.6 Σ?, with a correlation coefficient of 0.93.
- Leitis, L. Ya.,Skolmeistere, R. A.,Golender, L. O.,Yansone, D. P.,Meksh, P. A.,Shimanskaya, M. V.
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