- Ruthenium(II)-Catalyzed Highly Chemo- And Regioselective Oxidative C6 Alkenylation of Indole-7-carboxamides
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We disclosed the first efficient method for highly chemo- and regioselective C6 alkenylation of indole-7-carboxamides using inexpensive Ru(II) catalyst through chelation assisted C-H bond activation. Electronically diverse indole-7-carboxamides and alkenes react efficiently to produce a wide range of C6 alkenyl indole derivatives. Further the C6 alkenyl indole-7-carboxamides modified to their derivatives through simple chemical transformations. The observed regioselectivity and kinetics has been evidenced by deuterium incorporation and intermolecular competitive studies. In addition, for mechanistic insights, the intermediates were analyzed by HRMS.
- Jadhav, Pankaj P.,Kahar, Nilesh M.,Dawande, Sudam G.
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supporting information
p. 8673 - 8677
(2021/11/20)
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- METHODS FOR HAIR FOLLICLE STEM CELL PROLIFERATION
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The present invention relates to compositions of minoxidil and Sonic Hedgehog (Shh) pathway activators and optionally, Wnt agonists and methods of using them to induce self-renewal of hair follicle stem cells, including inducing the hair follicle stem cells to proliferate while maintaining, in the daughter cells, the capacity to differentiate into hair follicle epithelial cells.
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Paragraph 0431-0433
(2020/05/06)
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- 1,2-DIHYDRO-3H-PYRAZOL-3-ONE COMPOUNDS AND METHODS OF USING SAME
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The present disclosure relates to 1,2-dihydro-3H-pyrazol-3-one compounds and methods of using them to induce self-renewal of stem/progenitor supporting cells, including inducing the stem/progenitor cells to proliferate while maintaining, in the daughter c
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Paragraph 0341; 0342
(2020/11/27)
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- 1,2-DIHYDRO-3H-PYRAZOL-3-ONE COMPOUNDS AND METHODS OF USING SAME
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The present disclosure relates to l,2-dihydro-3H-pyrazol-3-one compounds and methods of using them to induce self-renewal of stem/progenitor supporting cells (e.g. cochlear cells), including inducing the stem/progenitor cells to proliferate while maintain
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Paragraph 0292
(2019/07/13)
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- 1,5-DIHYDRO-2H-PYRROL-2-ONE COMPOUNDS AND METHODS OF USING SAME
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The present invention relates to 1,5-dihydro-2H-pyrrol-2-one compounds and methods of using them to induce self-renewal of stem/progenitor supporting cells, including inducing the stem/progenitor cells to proliferate while maintaining, in the daughter cells, the capacity to differentiate into tissue cells.
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Paragraph 0333-0335
(2018/08/20)
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- 1H-PYRROLE-2,5-DIONE COMPOUNDS AND METHODS OF USING THEM TO INDUCE SELF-RENEWAL OF STEM/PROGENITOR SUPPORTING CELLS
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The present invention relates to 1H-pyrrole-2,5-dione compounds and methods of using them to induce self-renewal of stem/progenitor supporting cells, including inducing the stem/progenitor cells to proliferate while maintaining, in the daughter cells, the capacity to differentiate into tissue cells.
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Paragraph 0288; 0289
(2018/07/29)
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- METHODS FOR HAIR FOLLICLE STEM CELL PROLIFERATION
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The present invention relates to compositions of Sonic Hedgehog (Shh) pathway activators and Wnt agonists and methods of using them to induce self-renewal of hair follicle stem cells, including inducing the hair follicle stem cells to proliferate while maintaining, in the daughter cells, the capacity to differentiate into hair follicle epithelial cells.
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Paragraph 0284; 0334; 0335
(2018/11/10)
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- POTENTIATION OF CANCER CHEMOTHERAPY
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An improved method for treating gastric cancer, ovarian cancer, non-small cell lung cancer, or colorectal cancer in a patient is described, as well as pharmaceutical compositions useful for the method and a process for preparing said compositions.
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Paragraph 0040
(2015/12/19)
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- HEMATOPOIETIC NEOPLASM CHEMOTHERAPY
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A method and medicament for treating mixed lineage leukemia; translocated mixed lineage leukemia; translocated mixed lineage leukemia based acute myelogenous leukemia; translocated mixed lineage leukemia based acute lymphoid leukemia; a non-MLL based chronic myeloproliferative disorder, or non-MLL based acute lymphoid leukemia is provided.
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- Discovery of the dual orexin receptor antagonist [(7 R)-4-(5-chloro-1,3- benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl][5-methyl-2-(2 H -1,2,3-triazol-2-yl)phenyl]methanone (MK-4305) for the treatment of insomnia
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Despite increased understanding of the biological basis for sleep control in the brain, few novel mechanisms for the treatment of insomnia have been identified in recent years. One notable exception is inhibition of the excitatory neuropeptides orexins A and B by design of orexin receptor antagonists. Herein, we describe how efforts to understand the origin of poor oral pharmacokinetics in a leading HTS-derived diazepane orexin receptor antagonist led to the identification of compound 10 with a 7-methyl substitution on the diazepane core. Though 10 displayed good potency, improved pharmacokinetics, and excellent in vivo efficacy, it formed reactive metabolites in microsomal incubations. A mechanistic hypothesis coupled with an in vitro assay to assess bioactivation led to replacement of the fluoroquinazoline ring of 10 with a chlorobenzoxazole to provide 3 (MK-4305), a potent dual orexin receptor antagonist that is currently being tested in phase III clinical trials for the treatment of primary insomnia.
- Cox, Christopher D.,Breslin, Michael J.,Whitman, David B.,Schreier, John D.,McGaughey, Georgia B.,Bogusky, Michael J.,Roecker, Anthony J.,Mercer, Swati P.,Bednar, Rodney A.,Lemaire, Wei,Bruno, Joseph G.,Reiss, Duane R.,Harrell, C. Meacham,Murphy, Kathy L.,Garson, Susan L.,Doran, Scott M.,Prueksaritanont, Thomayant,Anderson, Wayne B.,Tang, Cuyue,Roller, Shane,Cabalu, Tamara D.,Cui, Donghui,Hartman, George D.,Young, Steven D.,Koblan, Ken S.,Winrow, Christopher J.,Renger, John J.,Coleman, Paul J.
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supporting information; experimental part
p. 5320 - 5332
(2010/10/20)
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- SUBSTITUTED DIAZEPAN OREXIN RECEPTOR ANTAGONISTS
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The present invention is directed to diazepan compounds which are antagonists of orexin receptors, and which are useful in the treatment of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which orexin receptors are involved.
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Page/Page column 35-36
(2009/06/27)
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- Substituted diazepan orexin receptor antagonists
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The present invention is directed to substituted diazepan compounds which are antagonists of orexin receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
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Page/Page column 13
(2008/12/05)
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- BENZAZEPIN-2(1H)-ONE DERIVATIVES
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Compounds of formula (I) and pharmaceutically acceptable salts thereof are agonists at the beta-2 adrenoceptor. They are useful as feed additives for livestock animals.
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Page/Page column 47
(2008/06/13)
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- OXO BRIDGED DIAZEPAN OREXIN RECEPTOR ANTAGONISTS
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The present invention is directed to oxo bridged diazepan compounds which are antagonists of orexin receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
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Page/Page column 29
(2009/01/20)
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- Substituted 3-imidazo[1,2-a]pyridin-3-yl-4-(1,2,3,4-tetrahydro-[1,4] diazepino-[6,7,1-hi]indol-7-yl)pyrrole-2,5-diones as highly selective and potent inhibitors of glycogen synthase kinase-3
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Glycogen synthase kinase-3 (GSK3) is involved in signaling from the insulin receptor. Inhibitors of GSK3 are expected to effect lowering of plasma glucose similar to insulin, making GSK3 an attractive target for the treatment of type 2 diabetes. Herein we report the discovery of a series of potent and selective GSK3 inhibitors. Compounds 7-12 show oral activity in an in vivo model of type II diabetes, and 9 and 12 have desirable PK properties.
- Engler, Thomas A.,Henry, James R.,Malhotra, Sushant,Cunningham, Brian,Furness, Kelly,Brozinick, Joseph,Burkholder, Timothy P.,Clay, Michael P.,Clayton, Joshua,Diefenbacher, Clive,Hawkins, Eric,Iversen, Philip W.,Li, Yihong,Lindstrom, Terry D.,Marquart, Angela L.,McLean, Johnathan,Mendel, David,Misener, Elizabeth,Briere, Daniel,O'Toole, John C.,Porter, Warren J.,Queener, Steven,Reel, Jon K.,Owens, Rebecca A.,Brier, Richard A.,Eessalu, Thomas E.,Wagner, Jill R.,Campbell, Robert M.,Vaughn, Renee
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p. 3934 - 3937
(2007/10/03)
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- PURINE DERIVATIVES AS KINASE INHIBITORS
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The present invention provides kinase inhibitors of Formula I.
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Page/Page column 65-66
(2008/06/13)
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