- Development of a practical synthesis to PI3K α-selective inhibitor GDC-0326
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A practical route to PI3K α-selective inhibitor GDC-0326 is reported. The synthesis leverages an existing scheme to a key tetracyclic benzoxazepine intermediate and optimizes it for robustness and scalability, including removing numerous undesired conditions and reagents, as well as eliminating chromatographic purification steps. The process endgame is streamlined to utilize a single-step, stereocontrolled alkylation of the key phenol with a chiral lactamide mesylate, followed by recrystallization of the lactamide ether product, to deliver the desired enantiomer of the active pharmaceutical ingredient (API) GDC-0326.
- Koenig, Stefan G.,Green, Keena L.,Müller, Barbara,Sowell, C. Gregory,Askin, David,Gosselin, Francis
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- SSAO INHIBITOR
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The present invention provides an SSAO inhibitor and an application thereof in preparing a drug for treating a disease related to SSAO. In particular, the present invention provides a compound shown in formula (IV) and a pharmaceutically acceptable salt thereof.
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Paragraph 0150-0152; 0489; 0490; 0491
(2020/04/02)
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- FUSED HETEROCYCLIC COMPOUND
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The present invention provides a fused heterocyclic compound that has CDK 8 and/or CDK 19 inhibitory activity. The present invention provides a compound represented by formula (I) (wherein the symbols are as defined in the description) or a salt thereof.
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Paragraph 0277
(2017/03/08)
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- The Rational Design of Selective Benzoxazepin Inhibitors of the α-Isoform of Phosphoinositide 3-Kinase Culminating in the Identification of (S)-2-((2-(1-Isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)oxy)propanamide (
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Inhibitors of the class I phosphoinositide 3-kinase (PI3K) isoform PI3Kα have received substantial attention for their potential use in cancer therapy. Despite the particular attraction of targeting PI3Kα, achieving selectivity for the inhibition of this
- Heffron, Timothy P.,Heald, Robert A.,Ndubaku, Chudi,Wei, BinQing,Augistin, Martin,Do, Steven,Edgar, Kyle,Eigenbrot, Charles,Friedman, Lori,Gancia, Emanuela,Jackson, Philip S.,Jones, Graham,Kolesnikov, Aleksander,Lee, Leslie B.,Lesnick, John D.,Lewis, Cristina,McLean, Neville,M?rtl, Mario,Nonomiya, Jim,Pang, Jodie,Price, Steve,Prior, Wei Wei,Salphati, Laurent,Sideris, Steve,Staben, Steven T.,Steinbacher, Stefan,Tsui, Vickie,Wallin, Jeffrey,Sampath, Deepak,Olivero, Alan G.
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p. 985 - 1002
(2016/02/23)
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- SELECTIVELY SUBSTITUTED QUINOLINE COMPOUNDS
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Embodiments of the disclosure relate to selectively substituted quinoline compounds that act as antagonists or inhibitors for Toll-like receptors 7 and/or 8, and their use in pharmaceutical compositions effective for treatment of systemic lupus erythematosus (SLE) and lupus nephritis.
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Paragraph 0174; 0349
(2015/04/21)
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- Compounds as syk kinase inhibitors
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The present invention relates to a compound of formula (I), to the process for preparing such compounds and to their use in the treatment of a pathological condition or disease susceptible to amelioration by inhibition of Syk kinase.
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Paragraph 0138; 0139
(2013/03/26)
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- COMPOSITION FOR AGRICULTURAL USE FOR CONTROLLING OR PREVENTING PLANT DISEASES CAUSED BY PLANT PATHOGENS
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Disclosed is a composition for agricultural use, which is used for controlling or preventing plant diseases caused by plant pathogens. The composition for agricultural use contains a compound represented by formula (1), a salt thereof or a hydrate of the compound or the salt. (1) [In the formula, Z represents an oxygen atom, a sulfur atom or NRz; and E represents a furyl group, a thienyl group, a pyrrolyl group, a tetrazolyl group, a thiazolyl group, a pyrazolyl group, a phenyl group or the like.]
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Page/Page column 225-226
(2010/11/19)
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- Indazoles, benzisoxazoles and benzisothiazoles as estrogenic agents
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The present invention relates to compounds of formula (I): in which R1, R2, R3, X, Y and A are as defined in the specification. The compounds are modulators of the estrogen receptors.
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Page/Page column 15
(2008/06/13)
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- 5-5-MEMBERED FUSED HETEROCYCLIC COMPOUND AND USE THEREOF AS HCV POLYMERASE INHIBITOR
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The present invention relates to a fused ring compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable a salt thereof, and a hepatitis C virus (HCV) polymerase inhibitor and
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Page/Page column 126
(2008/06/13)
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- Compositions and methods using compounds having cytochrome P450RAI inhibitory activity co-administered with vitamin A
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vitamin A, or a derivative of vitamin A having vitamin A like activity is co-administered with inhibitors of the CP450RAI1 and/or of CP450RAI2 enzymes for the purpose of treating diseases and conditions in mammals, including humans, which diseases or conditions are prevented, treated, ameliorated, or the onset of which is delayed by administration of retinoid compounds or by the mammalian organism's naturally occurring retinoic acid.
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- 4-[(8-Ethynyl, 8-vinyl or 8-ethynyl-methyl)-6-chromanoyl]-benzoic and 2-[4-[(8-ethynyl, 8-vinyl or 8-ethynyl-methyl)-6-chromanoyl]-phenyl]-acetic acid, their esters and salts having cytochrome P450RAI inhibitory activity
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Compounds of Formula 1 1 wherein the variables are defined in the specification have cytochrome P450RAI-1 and P450RAI-2 inhibitory activity, and are suitable for treatment of mammals with conditions which are treatable with retinoids, or which are controlled by or responsive to the organism''s native retinoic acid. Formulations containing the compounds of the invention can also be co-administered with retinoids and/or Vitamin A to enhance or prolong the effects of medications containing retinoids, Vitamin A, or of the organism''s native retinoic acid.[From equivalent US6740676] Compounds of Formula 1: STR1wherein the variables are defined in the specification have cytochrome P450RAI-1 and P450RAI-2 inhibitory activity, and are suitable for treatment of mammals with conditions which are treatable with retinoids, or which are controlled by or responsive to the organism''s native retinoic acid. Formulations containing the compounds of the invention can also be co-administered with retinoids and/or Vitamin A to enhance or prolong the effects of medications containing retinoids, Vitamin A, or of the organism''s native retinoic acid.
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Page/Page column 9; 16
(2008/06/13)
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- FLUOROBENZAMIDES
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The present invention is concerned with fluorobenzamide derivatives of the general formula Wherein R1 is hydrogen, (C1-C6)-alkyl or hydroxy-(C1-C6)-alkyl; R2 is (C1-C6/su
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- Fluorobenzamides and uses thereof
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The invention relates to fluorobenzamide derivatives of the formula wherein R1, R2, R3 R4, R5, R6 and R7 are as defined herein. =, The compounds of the invention are selective monoamine oxidase B inhibitors and therefore they are suitable for the treatment of diseases mediated by monoamine oxidase B, such as Alzheimer's disease or senile dementia.
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- PYRANOINDAZOLES AND THEIR USE FOR THE TREATMENT OF GLAUCOMA
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Pyranoindazoles are disclosed. Also disclosed are methods for the lowering and controlling of normal or elevated intraocular pressure as well as a method for the treatment of glaucoma using compositions containing one or more of the compounds of the prese
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Page 42-43; 45
(2010/11/29)
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- 4-[(8-Substituted)-6-chromanoyl]-and 4-[8-substituted)-chroman-6-yl-ethynyl]-benzoic and phenylacetic acids, their esters and salts having cytochrome P450RAI inhibitory activity
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Compounds of the formula 1where the variables are defined in the specification have cytochrome P450RAI-1 and P450RAI-2 inhibitory activity, and are suitable for treatment of mammals with conditions which are treatable with retinoids, or which are controlled by or responsive to the organism's native retinoic acid. Formulations containing the compounds of the invention can also be co-administered with retinoids and/or Vitamin A to enhance or prolong the effects of medications containing retinoids, Vitamin A, or of the organism's native retinoic acid.
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- Benzyl vinylogous amide substituted aryldihydropyridazinones and aryldimethylpyrazolones as potent and selective PDE3B inhibitors
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Aryldihydropyridazinones and aryldimethylpyrazolones with 2-benzyl vinylogous amide substituents have been identified as potent PDE3B subtype selective inhibitors. Dihydropyridazinone 8a (PDE3B IC50=0.19 nM, 3A IC50=1.3 nM) was selec
- Edmondson, Scott D.,Mastracchio, Anthony,He, Jiafang,Chung, Christine C.,Forrest, Michael J.,Hofsess, Scott,MacIntyre, Euan,Metzger, Joseph,O'Connor, Naphtali,Patel, Kajal,Tong, Xinchun,Tota, Michael R.,Van Der Ploeg, Lex H. T.,Varnerin, Jeff P.,Fisher, Michael H.,Wyvratt, Matthew J.,Weber, Ann E.,Parmee, Emma R.
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p. 3983 - 3987
(2007/10/03)
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- Side-chain liquid crystal polymers derived from oxetane monomers containing 2- or 3-fluorophenyl moieties in the core of the mesogen
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Two series of side-chain liquid crystalline polymers were prepared by cationic ring-opening of oxetane substituted mesogens. Each of the terminally appended side chain polymers prepared had a flexible spacer length of six methylene units separating a meso
- Cowling,Toyne,Goodby
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p. 1590 - 1599
(2007/10/03)
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- Oxazolidinone derivatives, their preparation and therapeutical use
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The present invention relates to isoindole derivatives, and more particularly to 5-(hydroxymethyl)oxazolidine-2-one derivatives which are substituted at the 3 position by an indazole, benzisoxazole or benzisothiazole ring system, to a process for their pr
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