- THIENODIAZEPINE DERIVATIVES AND APPLICATION THEREOF
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The present invention relates to a class of thienodiazepine derivatives and an application thereof in the preparation of a drug for the treatment of diseases associated with bromodomain and extra-terminal (BET) Bromodomain inhibitors. Specifically, the present invention relates to compounds represented by formulas (I) and (II), as well as pharmaceutically acceptable salts thereof.
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- FLUOROALLYLAMINE DERIVATIVE AND USE THEREOF
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The present invention relates to a fluoroallylamine derivative and use thereof. In particular, the present invention relates to a compound as shown in Formula I, a prodrug, an isomer, an isotope-labeled compound, a solvate or a pharmaceutically acceptable salt thereof, which has VAP-1/SSAO inhibitory activity, and can be used for treating a disease associated with VAP-1/SSAO overactivity.
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Paragraph 0179
(2020/03/17)
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- IDO/TDO Inhibitor
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A compound of formula (I) given below or a pharmaceutically acceptable salt of the compound is useful as an IDO/TDO inhibitor. Thus, the compound of formula (I) or the pharmaceutically acceptable salt of the compound can be used as, for example, a therapeutic agent for a disease or a disorder selected from tumor, infectious disease, neurodegenerative disorder, cataract, organ transplant rejection, autoimmune disease, postoperative cognitive impairment, and disease related to women's reproductive health [in the following formula (I), ring A represents an aromatic ring, an aliphatic ring, a heterocyclic ring, or a condensed ring of two or more rings selected from an aromatic ring, an aliphatic ring and a heterocyclic ring; X, R1 and R2 represent a substituent on a ring atom constituting ring A; m represents an integer of 0 to 6; X represents, for example, a halogen atom; and R1 and R2 are the same or different and are selected from, for example, the group consisting of groups of formula (a) or formula (b); and in the following formula (a) and formula (b), Y is selected from the group consisting of O, S, and Se, Z is selected from the group consisting of O, S, and Se, n represents an integer of 1 to 8, r represents an integer of 1 to 8, s represents an integer of 1 to 8, R4 represents, for example, —C(═NH)—HN2, and R6 represents, for example, a substituted or unsubstituted aryl group].
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Paragraph 0334; 0337; 0338; 0370; 0371
(2020/08/19)
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- HETEROARYL COMPOUNDS AND METHODS OF USE THEREOF
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Provided herein are thiophene 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 neurological disorders, including but not limited to, psychosis and schizophrenia.
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Page/Page column 73
(2013/08/28)
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- PHARMACEUTICAL COMPOUNDS
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The invention provides a compound for use in medicine, the compound being a compound of the formula (VI0) or a salt, solvate, tautomer or N-oxide thereof: wherein the bicyclic group: is selected from the structures C1, C5 and C6: wherein n is 0, 1, 2 or 3; R1 is hydrogen, hydroxy, or O—Rz; R2a is hydroxy, methoxy or O—Rz; provided that at least one of R1 and R2a is O—Rz; Rz is Lp-Rp1; SO3H; a glucuronide residue; a mono-, di- or tripeptide residue; or Lp is a bond, C═O, (C═O)O, (C═O)NRp1 or S(O)xNRp1; x is 1 or 2; Rp1 is hydrogen or a an optionally substituted C1-25 hydrocarbyl group containing 0, 1 or 2 carbocyclic rings and 0, 1, 2, 3, 4, 5 or 6 carbon-carbon multiple bonds, provided that Rp1 is not hydrogen when Lp is a bond, C═O or (C═O)O; and provided also that O—Rz does not contain an O—O moiety; and excluding compounds wherein R1 is hydroxy and R2a is methoxy; Rp2 and Rp3 are the same or different and each is a group Rp1; and R3, R4a, R8 and R10 are defined in the claims. The compounds of formula (VI0) are pro-drugs of parent compounds wherein R1 and/or R2a are hydroxy, wherein the parent compounds have Hsp90 inhibiting activity.
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Page/Page column 73
(2010/06/22)
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- Discovery of (2,4-Dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1- ylmethyl)-1,3-dihydroisoindol-2-yl]methanone (AT13387), a novel inhibitor of the molecular chaperone Hsp90 by fragment based drug design
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Inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) are currently generating significant interest in clinical development as potential treatments for cancer. In a preceding publication (DOI: 10.1021/jm100059d) we describe Astex's approach to screening fragments against Hsp90 and the subsequent optimization of two hits into leads with inhibitory activities in the low nanomolar range. This paper describes the structure guided optimization of the 2,4-dihydroxybenzamide lead molecule 1 and details some of the drug discovery strategies employed in the identification of AT13387 (35), which has progressed through preclinical development and is currently being tested in man.
- Woodhead, Andrew J.,Angove, Hayley,Carr, Maria G.,Chessari, Gianni,Congreve, Miles,Coyle, Joseph E.,Cosme, Jose,Graham, Brent,Day, Philip J.,Downham, Robert,Fazal, Lynsey,Feltell, Ruth,Figueroa, Eva,Frederickson, Martyn,Lewis, Jonathan,McMenamin, Rachel,Murray, Christopher W.,O'Brien, M. Alistair,Parra, Lina,Patel, Sahil,Phillips, Theresa,Rees, David C.,Rich, Sharna,Smith, Donna-Michelle,Trewartha, Gary,Vinkovic, Mladen,Williams, Brian,Woolford, Alison J.-A.
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supporting information; experimental part
p. 5956 - 5969
(2010/11/04)
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- Design, synthesis and discovery of 1-(2-(6-chloro-3-methylsulfonyl)- naphthyl)-1H-pyrazole-5-carboxylamides as highly potent factor Xa inhibitors
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Based upon the biphenyl 1-(2-naphthyl)-1H-pyrazole-5-carboxylamides reported in our previous communications, we designed and discovered 2-(6-chloro-3-methylsulfonyl)-naphthyl as an optimal factor Xa S1 binding element. Employing a key Diels-Alder reaction of 1,4-dihydro-2,3-benzoxathiin-3- oxide with maleic anhydride and a key Cu(I)-mediated methylsulfonylation, we prepared two biphenyl 1-(2-(6-chloro-3-methylsulfonyl)-naphthyl)-1H-pyrazole-5- carboxylamides as highly potent factor Xa inhibitors with Ki values of 0.065 nM and 0.045 nM respectively, and demonstrated the synergistically enhanced binding interaction in the factor Xa S1 site.
- Jia, Zhaozhong Jon,Scarborough, Robert Murry,Zhang, Penglie,Halfon, Sherin,Arfsten, Ann Elizabeth,Sinha, Uma,Zhu, Bing-Yan
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scheme or table
p. 1004 - 1007
(2010/03/31)
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- SUBSTITUTED BENZOYLAMINO-INDAN-2-CARBOXYLIC ACIDS AND RELATED COMPOUNDS
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The present invention relates to A compound of the formula Ia wherein in any of its stereoisomers forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, wherein the substituents are as described herein. The inventive compounds have CXCR5 inhibitory activity are particularly useful in treating or preventing various inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis, lupus, Crohn's Disease, associated with the modulation of the human CXCR5 receptor.
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- PHARMACEUTICAL COMBINATIONS
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The invention provides combinations comprising (or consisting essentially of) one or more ancillary compound(s) and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1- 5 hydrocarbyloxy; R4 is selected from hydrogen; a group -(O)n-R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl-amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The combinations have activity as Hsp90 inhibitors.
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Page/Page column 205
(2008/06/13)
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- PHARMACEUTICAL COMBINATIONS
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The invention provides combinations comprising (or consisting essentially of) one or more ancillary compound(s) and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1-5 hydrocarbyloxy; R4 is selected from hydrogen; a group -(O)n-R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl-amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The combinations have activity as Hsp90 and/or glycogen synthase kinase-3 and/or cyclin dependent kinase inhibitors.
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Page/Page column 226-227
(2008/06/13)
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- PHARMACEUTICAL COMBINATIONS
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The invention provides combinations comprising (or consisting essentially of) one or more ancillary compound(s) and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1-5 hydrocarbyloxy; R4 is selected from hydrogen; a group -(O)n-R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl-amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The combinations have activity as Hsp90 and/or glycogen synthase kinase-3 and/or cyclin dependent kinase and/or aurora kinase inhibitors.
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Page/Page column 279
(2008/06/13)
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- PHARMACEUTICAL COMPOUNDS
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The invention provides the use of a compound for the manufacture of a medicament for the treatment of pain, wherein the compound is a compound of the formula (Vl): or a salt, solvate, tautomer or N-oxide thereof; wherein the bicydic group: is selected from the structures C1, C5 and C6: wherein n, R1, R2a, R3, R4a, R8 and R10 are as defined in the claims. The invention also provides the use of a compound of the formula (Vl) for the manufacture of a medicament for the prophylaxis or treatment of a fungal, protozoal, viral or parasitic disease state or condition (other than a disease state or condition due to Plasmodium falciparum) or for use in the prophylaxis or treatment of Ewing's sarcoma, atherosclerosis or lupus erythematosus
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Page/Page column 123
(2008/06/13)
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- NOVEL SULFONYL DERIVATIVES
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Sulfonyl derivatives represented by the following general formula (I): Q1-Q2-T1-Q3-SO2-QA and drugs containing the same (wherein Q1 is an optionally substituted, saturated or unsaturated, five- or six-membered cyclic hydrocarbon group, a five- or six-membered heterocyclic group, or the like; Q2 is a single band, oxygen, sulfur, C1-C6 alkylene or the like; QA is optionally substituted arylalkenyl, heteroarylalkenyl or the like; and T1 is carbonyl or the like). These compounds have potent FXa-inhibitory effects and promptly exert satisfactory and persistent antithrombotic effects through oral administration, thus being useful as anticoagulant agents little accompanied with side effects.
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- Antiviral agent containing benzodithiin derivative as active ingredient
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Antiviral agents comprising, as an active ingredient, a 1,4-dihydro-2,3-benzodithiin derivative of the formula STR1 wherein each symbol is as defined in the Specification, or a pharmacologically acceptable salt thereof. The antiviral agents of the present invention have superior antiviral activity and are effective for the preventive and therapeutic treatment of viral diseases caused typically by RS virus.
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- 2-[2H-(1,3-dihydroisoindole)alkylene]-4,5-dihydroimidazoles and pharmaceutical compositions thereof
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A compound of formula (I): STR1 or a pharmaceutically acceptable salt, ester or amide thereof, wherein: Z represents a residue of a substituted or unsubstituted aryl group, X represents O or NRo wherein Ro represents a hydrogen atom,
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- Carboxylic acid ester and an insecticidal and/or acaricidal composition containing the same
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This invention relates to a novel carboxylic acid ester represented by the following general formula (I) and an insecticidal and/or acaricidal composition containing the same as an active ingredient: STR1 wherein X is represented by the formula, STR2 and further also relates to a carboxylic acid or a reactive derivative thereof represented by the general formula, STR3 wherein R16 is hydroxy group, chlorine or bromine atom, or a C1-2 alkoxy group, W is oxygen atom or --CH2 -- group, k is an integer of 0 or 1, E is hydrogen, chlorine, fluorine or bromine atom, and n is an integer of 1 to 4.
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