- Pyrimidine derivative and application thereof in medicines
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The invention discloses a pyrimidine derivative and application thereof in medicines, and particularly relates to a novel pyrimidine derivative and a pharmaceutical composition containing the compound. The invention also relates to a method for preparing the compound and the pharmaceutical composition, and application of the compound and the pharmaceutical composition in preparation of drugs for treating KRAS G12C-mediated diseases and/or symptoms, especially in preparation of drugs for treating cancers.
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Paragraph 0319-0322
(2021/07/21)
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- Ni-Catalyzed Arylboration of Unactivated Alkenes: Scope and Mechanistic Studies
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A method for the Ni-catalyzed arylboration of unactivated monosubstituted, 1,1-disubstituted, and trisubstituted alkenes is disclosed. The reaction is notable in that it converts highly substituted alkenes, aryl bromides, and diboron reagents to products that contain a quaternary carbon and a synthetically versatile carbon-boron bond with control of stereoselectivity and regioselectivity. In addition, the method is demonstrated to be useful for the synthesis of saturated nitrogen heterocycles, which are important motifs in pharmaceutical compounds. Finally, due to the unusual reactivity demonstrated, the mechanistic details of the reaction were studied with both computational and experimental techniques.
- Sardini, Stephen R.,Lambright, Alison L.,Trammel, Grace L.,Omer, Humair M.,Liu, Peng,Brown, M. Kevin
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supporting information
p. 9391 - 9400
(2019/06/17)
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- Amino 6-membered ring derivative and pharmaceutical applications thereof including the use for manufacturing dipeptidyl peptidase-4(IDPP-IV) inhibitor
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The present invention relates to an amino 6-membered ring derivative and pharmaceutical applications thereof, which specifically relates to the amino 6-membered ring derivative represented by the general formula (I) or stereoisomers thereof, pharmaceutically acceptable salts thereof, a prodrug, a pharmaceutical composition comprising the derivative, and the pharmaceutical use for manufacturing dipeptidyl peptidase-4(IDPP-IV) inhibitor, wherein the definition of each substituent in the general formula (I) is the same as described in the specification.
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- HUMAN PLASMA KALLIKREIN INHIBITORS
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Disclosed are compounds of formula I, and pharmaceutically acceptable salts thereof. The compounds are inhibitors of plasma kallikrein. Also provided are pharmaceutical compositions comprising at least one compound of the invention, and methods involving use of the compounds and compositions of the invention in the treatment and prevention of diseases and conditions characterized by unwanted plasma kallikrein activity.
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Page/Page column 167
(2017/05/10)
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- PHENOXYETHYL CYCLIC AMINE DERIVATIVES AND THEIR ACTIVITY AS EP4 RECEPTOR MODULATORS
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The present invention provides a compound of the Formula (I): wherein X, R, R1,R2,R3, R4,R5,R6, R7, R8, and R9 are as defined herein, or a pharmaceutically acceptable salt thereof.
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Page/Page column 20; 21
(2015/07/07)
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- DIHYDROPYRROLIDINO-PYRIMIDINES AS KINASE INHIBITORS
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The present invention provides compounds of Formula (I) and pharmaceutically acceptable salts thereof; as further described herein. The present invention further provides pharmaceutical compositions comprising these compounds, and combinations comprising these compounds combined with or used with a therapeutic co-agent, as well as therapeutic uses of these compounds and compositions. These are useful in the treatment of diseases such as cancer that are associated with activation of ERKl and/or ERK2, and especially for MAPK pathway dependent cancers showing resistance to Raf and/or MEK inhibitory cancer therapeutics
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Page/Page column 69
(2014/04/04)
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- PYRROLOPYRIDAZINE JAK3 INHIBITORS AND THEIR USE FOR THE TREATMENT OF INFLAMMATORY AND AUTOIMMUNE DISEASES
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Disclosed are compounds of formula (I) and pharmaceutically acceptable salts thereof. The compounds of formula (I) inhibit tyrosine kinase activity of JAK3, thereby making them useful for the treatment of inflammatory and autoimmune diseases.
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Page/Page column 74-75
(2012/10/07)
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- PYRROLOPYRIDAZINE JAK3 INHIBITORS AND THEIR USE FOR THE TREATMENT OF INFLAMMATORY AND AUTOIMMUNE DISEASES
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Disclosed are compounds of Formula (I), and pharmaceutically acceptable salts thereof. The compounds of formula (I) inhibit tyrosine kinase activity of JAK3, thereby making them useful for the treatment of inflammatory and autoimmune diseases.
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Page/Page column 85
(2012/10/07)
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- OXADIAZOLE COMPOUNDS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF
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The invention provides novel beta-secretase inhibitors and methods for their including methods of treating Alzheimer's disease.
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Page/Page column 95
(2012/05/05)
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- METABOTROPIC GLUTAMATE RECEPTORS 5 MODULATORS AND METHODS OF USE THEREOF
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Compounds that modulate GluR5 activity and methods of using the same are disclosed.
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Page/Page column 149-150
(2012/12/13)
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- COMPOUNDS CONTAINING FUSED RINGS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF
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The invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating Alzheimer's disease.
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Page/Page column 87-88
(2011/11/01)
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- Part 3: Design and synthesis of proline-derived α2δ ligands
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A potent series of substituted (2S,4S)-benzylproline α 2δ ligands have been designed from the readily available starting material (2S,4R)-hydroxy-l-proline. The ligands have improved pharmacokinetic profile over the (4S)-phenoxyproline derivati
- Rawson, David J.,Brugier, Delphine,Harrison, Anthony,Hough, Jo,Newman, Julie,Otterburn, Joe,Maw, Graham N.,Price, Jenny,Thompson, Lisa R.,Turnpenny, Paul,Warren, Andrew N.
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p. 3771 - 3773
(2011/08/06)
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- Daucus carota mediated-reduction of cyclic 3-oxo-amines
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Carrots (Daucus carota) were used to reduce cyclic amino-ketones in high yields and enantiomeric excesses. This cheap, eco-compatible, and efficient reducing reagent allows the easy access to precursors of biologically active products.
- Lacheretz, Romain,Pardo, Domingo Gomez,Cossy, Janine
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supporting information; experimental part
p. 1245 - 1248
(2009/08/08)
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- N-HYDROXYAMIDE DERIVATIVES POSSESSING ANTIBACTERIAL ACTIVITY
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Novel N-hydroxyamide derivatives are disclosed. These N-hydroxyamide derivatives inhibit UPD-3O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase, an enzyme present in gram negative bacteria and are therefore useful as antimicrobials and antibiotics. Methods of synthesis and of use of the compounds are also disclosed.
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- CARBONYL COMPOUNDS
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The invention relates to the novel compounds of formula (I), wherein D, E, G, W, X, Y, T, R and R are defined as in claim 1. The inventive compounds inhibit coagulation factor Xa and can be used in the prophylaxis and/or therapy of thrombo-embolic diseases and for treating tumors.
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Page/Page column 71
(2008/06/13)
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- Design, synthesis, and biological evaluation of matrix metalloproteinase inhibitors derived from a modified proline scaffold
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The synthesis and structure-activity relationship (SAR) studies of a series of proline-based matrix metalloproteinase inhibitors are described. The data reveal a remarkable potency enhancement in those compounds that contain an sp2 center at the C-4 carbon of the ring relative to similar, saturated compounds. This effect was noted in compounds that contained a functionalized oxime moiety or an exomethylene at C-4, and the potencies were typically 3 hybridization and the effect was typically an order of magnitude loss in potency. A comparison of compounds 14 and 34 exemplifies this observation. An X-ray structure was obtained for a stromelysin-inhibitor complex which provided insights into the SAR and selectivity trends observed within the series. In vitro intestinal permeability data for many compounds was also accumulated.
- Cheng, Menyan,De, Biswanath,Almstead, Neil G.,Pikul, Stanislaw,Dowty, Martin E.,Dietsch, Charles R.,Dunaway, C. Michelle,Gu, Fei,Hsieh, Lily C.,Janusz, Michael J.,Taiwo, Yetunde O.,Natchus, Michael G.,Hudlicky, Tomas,Mandel, Martin
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p. 5426 - 5436
(2007/10/03)
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