- HETEROCYCLIC COMPOUNDS AS MUTANT IDH INHIBITORS
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The present disclosure relates generally to compounds useful in treatment of conditions associated with mutant isocitrate dehydrogenase (mt-IDH), particularly mutant IDH1 enzymes. Specifically, the present invention discloses compound of formula (IA), which exhibits inhibitory activity against mutant IDH1 enzymes. Method of treating conditions associated with excessive activity of mutant IDH1 enzymes with such compound is disclosed. Uses thereof, pharmaceutical composition, and kits are also disclosed.
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Paragraph 0503-0504
(2020/07/16)
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- Iridium-Catalyzed Borylation of Primary Benzylic C-H Bonds without a Directing Group: Scope, Mechanism, and Origins of Selectivity
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Primary benzylic boronate esters are useful intermediates in organic synthesis, but these reagents cannot be prepared by hydroboration. The benzylic C-H borylation of methylarenes would be a method to form these products, but such reactions without neat methylarene or a directing group are unknown. We report an approach to divert the borylation of methylarenes from aromatic positions to benzylic positions with a silylborane as reagent and a new iridium catalyst containing an electron-deficient phenanthroline as ligand. This system forms benzylic boronate esters selectively over the corresponding aryl boronate esters. An Ir diboryl monosilyl complex ligated by the phenanthroline was isolated and determined to be the resting state of the catalyst. Mechanistic studies show that this complex is kinetically competent to be an intermediate in the catalytic process. Kinetic studies of benzylic and aryl C-H borylation catalyzed by various Ir complexes show that the rate of aryl C-H borylation decreases with decreasing electron density at the metal center of the Ir catalyst, but that the rate of benzylic C-H borylation is less sensitive to the degree of electron density at the metal center of the Ir catalyst. Kinetic and computational studies suggest that the two borylation reactions respond differently to the degree of electron density at the metal center because they occur with different turnover-limiting steps. The turnover-limiting step in the borylation of aryl C-H bonds is known to be C-H oxidative addition, but the turnover-limiting step of the borylation of benzylic C-H bonds appears to be an isomerization prior to C-B reductive elimination.
- Larsen, Matthew A.,Wilson, Conner V.,Hartwig, John F.
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supporting information
p. 8633 - 8643
(2015/07/15)
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- ANTIVIRAL COMPOUNDS
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Disclosed herein are new antiviral compounds, together with pharmaceutical compositions that include one or more antiviral compounds, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a paramyxovirus viral infection with one or more small molecule compounds. Examples of paramyxovirus infection include an infection caused by human respiratory syncytial virus (RSV).
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Paragraph 1037
(2015/03/13)
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- PRMT5 INHIBITORS AND USES THEREOF
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Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described
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Paragraph 00408
(2014/07/08)
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- PREPARATION OF PHANTASMIDINE AND ANALOGUES THEREOF
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Described are methods of synthesizing phantasmidine and analogues thereof from commercially available starting materials. The compounds are useful as pharmacological probes and potential lead compounds for the development of selective nicotinic receptor therapeutics.
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Page/Page column 28
(2012/06/30)
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- Synthesis of phantasmidine
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Reaction of 6-chloro-2-fluoro-3-pyridineacetamide with 1,2- bis(trimethylsilyloxy)cyclobutene in ether saturated with hydrogen chloride afforded the keto amide in 85% yield. In the key step, treatment of the keto amide with aqueous KOH in t-BuOH resulted in a tandem intramolecular aldol reaction-intramolecular nucleophilic aromatic substitution sequence to give the tetracylic lactam in 46% yield. Reduction of the lactam with BH3 in THF gave phantasmidine in 67% yield.
- Zhou, Quan,Snider, Barry B.
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supporting information; experimental part
p. 526 - 529
(2011/03/23)
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- METHYL SULFANYL PYRMIDMES USEFUL AS ANTIINFLAMMATORIES, ANALGESICS, AND ANTIEPILEPTICS
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The present invention relates to pyrimidine derivatives of Formula (Ia) and (Ib) (including tautomers, isomers, prodrugs, and pharmaceutically acceptable salts thereof). Said compounds are useful in the treatment of pain (such as neuropathic pain), inflammation, and epilepsy (by acting as anticonvulsants). Methods of medical treatment making use of said compounds, as well as additional compounds of Formula (IIa) and (IIb), are also disclosed.
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Page/Page column 118
(2010/12/18)
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- HETEROBICYCLIC COMPOUNDS USEFUL AS P38 KINASE INHIBITING AGENTS
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Compounds described by the chemical formula (I) or pharmaceutically acceptable salts thereof: (I) are inhibitors of p38 and are useful in the treatment of inflammation such as in the treatment of rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, gouty arthritis and other arthritic conditions; inflamed joints, eczema, psoriasis or other inflammatory skin conditions such as sunburn; inflammatory eye conditions including conjunctivitis; pyresis, pain and other conditions associated with inflammation.
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Page/Page column 73
(2008/06/13)
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- Novel 1,4-benzodiazepine-2,5-diones as Hdm2 antagonists with improved cellular activity
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The disruption of the p53-Hdm2 protein-protein interaction induces cell growth arrest and apoptosis. We have identified the 1,4-benzodiazepine-2,5-dione scaffold as a suitable template for inhibiting this interaction by binding to the Hdm2 protein. Several compounds have been made with improved potency, solubility, and cell-based activities.
- Leonard, Kristi,Marugan, Juan Jose,Raboisson, Pierre,Calvo, Raul,Gushue, Joan M.,Koblish, Holly K.,Lattanze, Jennifer,Zhao, Shuyuan,Cummings, Maxwell D.,Player, Mark R.,Maroney, Anna C.,Lu, Tianbao
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p. 3463 - 3468
(2007/10/03)
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- 1-(HETERO)ARYL-3-AMINO-PYROLLIDINE DERIVATIVES FOR USE AS MGLUR3 RECEPTOR ANTAGONISTS
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The present invention relates to compounds of the Formula (I) which are useful for treating conditions associated with mGluR3 receptors, such as depression, schizophrenia and migraine, pharmaceutical compositions thereof, and methods of using the same.
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Page/Page column 62
(2010/11/08)
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- INHIBITORS OF PHOSPHODIESTERASE TYPE-IV
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The present invention relates to isoxazoline derivatives, which can be used as selective inhibitors of phosphodiesterase (PDE) type IV. In particular, compounds disclosed herein can be useful in the treatment of AIDS, asthma, arthritis, bronchitis, chronic obstructive pulmonary disease (COPD), psoriasis, allergic rhinitis, shock, atopic dermatitis, Crohn's disease, adult respiratory distress syndrome (ARDS), eosinophilic granuloma, allergic conjunctivitis, osteoarthritis, ulcerative colitis and other inflammatory diseases in a patient, particularly in humans. The present invention also relates to processes for the preparation of disclosed compounds, as well as pharmaceutical compositions thereof, and their use as phosphodiesterase (PDE) type IV inhibitors.
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Page/Page column 43
(2008/06/13)
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- Fused heterotricyclic compounds as inhibitors of 17beta-hydroxysteroid dehydrogenase 3
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Fused heterotricyclic compounds, methods of using such compounds in the treatment of hormone sensitive diseases such as prostate cancer, and pharmaceutical compositions containing such compounds.
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Page/Page column 25
(2008/06/13)
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- Sulfonamide compounds and uses thereof as medicines
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The present invention relates to a sulfonamide compound of the formula (I): wherein each symbol is as defined in the specification, a salt thereof, and a pharmaceutical composition containing same. This compound can be an effective agent for the prophylaxis and treatment of the diseases curable based on a hypoglycemic action, and the diseases curable based on a cGMP-PDE inhibitory action, a smooth muscle relaxing action, a bronchodilating action, a vasodilating action, a smooth muscle cell inhibitory action and an allergy suppressing action.
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- Process for the manufacture of bromopyridines
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A novel process for the preparation of 2,4-dibromo-, 2,6-dibromo- and 2,4,6-tribromopyridines, and the new bromopyridines to be obtained therewith, are disclosed. The novel process comprises treating 2,4-dichloro-, 2,6-dichloro- and 2,4,6-trichloropyridines, in an anhydrous organic medium, with gaseous HBr at temperatures between 80° and 130°C, said process being both simple and economical.
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