- Compound JK-03M having higher protein kinase G inhibitory activity or pharmaceutically acceptable salt thereof and preparation method thereof
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The invention discloses a compound which has higher protein kinase G inhibitory activity and is shown in a formula I or pharmaceutically acceptable salt thereof and a preparation method thereof. The compound JK-03M having the higher protein kinase G inhibitory activity comprises a pharmaceutical composition of a new compound and application of the new compound in treatment of pain, in particular to chronic pain. The formula (1) is shown in the description.
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- Compounds with higher PKG (protein kinase G) inhibitory activity and preparation method of compounds
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The invention discloses compounds which have higher PKG (protein kinase G) inhibitory activity and are represented as a formula I, pharmaceutically acceptable salts, pharmaceutical composition containing the novel compounds, as well as an application of the novel compounds in treatment of pain, especially chronic pain. The invention further discloses a preparation method of the compounds and new intermediates. R1 and R2 are the same or different and are selected from a group comprising halogen (such as F or Cl), C1-C6 alkoxy, C1-C6 alkyl, C2-C6 alkenyl and C2-C6 alkynyl; R3 is a terminal group and is selected from a group comprising H, halogen, alkyl, naphthenic base, alkenyl, alkynyl, aryl and heteroaryl; n is the number of repetitive units and is an integer in a range from 1 to 15.
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- COMPOUND HAVING HIGHER INHIBITION OF PROTEIN KINASE G ACTIVITY AND PREPARATION METHOD THEREFOR
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Disclosed are a compound of Formula I having higher inhibition of protein kinase G (PKG) activity and pharmaceutically acceptable salts thereof. In Formula I, R1 and R2 are the same or different, each being independently chosen from the halogens, the C1-C6 alkoxyl group, the C1-C6 alkyl group, the C2-C6 alkenyl group, and the C2-C6 alkynyl group; R3 is chosen from H, the halogens, the substituted or unsubstituted C1-C6 alkyl group, C3-C6 cycloalkyl group, C2-C6 alkenyl group, and C2-C6 alkynyl group, aryl group, and heteroaryl group; and n is an integer between 0 and 15. Also disclosed is a pharmaceutical composition comprising said compound, the use of the compound in treating pains, in particular chronic pain, a preparation method for the compound, and a new intermediate.
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- The Importance of Being Me: Magic Methyls, Methyltransferase Inhibitors, and the Discovery of Tazemetostat
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Posttranslational methylation of histones plays a critical role in gene regulation. Misregulation of histone methylation can lead to oncogenic transformation. Enhancer of Zeste homologue 2 (EZH2) methylates histone 3 at lysine 27 (H3K27) and abnormal methylation of this site is found in many cancers. Tazemetostat, an EHZ2 inhibitor in clinical development, has shown activity in both preclinical models of cancer as well as in patients with lymphoma or INI1-deficient solid tumors. Herein we report the structure-activity relationships from identification of an initial hit in a high-throughput screen through selection of tazemetostat for clinical development. The importance of several methyl groups to the potency of the inhibitors is highlighted as well as the importance of balancing pharmacokinetic properties with potency.
- Kuntz, Kevin W.,Campbell, John E.,Keilhack, Heike,Pollock, Roy M.,Knutson, Sarah K.,Porter-Scott, Margaret,Richon, Victoria M.,Sneeringer, Chris J.,Wigle, Tim J.,Allain, Christina J.,Majer, Christina R.,Moyer, Mikel P.,Copeland, Robert A.,Chesworth, Richard
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supporting information
p. 1556 - 1564
(2016/03/05)
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- 3-CYCLOHEXENYL AND CYCLOHEXYL SUBSTITUTED INDOLE AND INDAZOLE COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF
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The present invention relates to compounds according to Formula I and pharmaceutically acceptable salts or solvates thereof. Such compounds can be used in the treatment of RORgammaT-mediated diseases or conditions.
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Paragraph 0301
(2015/07/15)
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- One-pot synthesis of novel 3,5-disubstituted-1,2,4-oxadiazoles from indazole carboxylic acid esters and amidoximes
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An efficient and high-yielding one-pot synthesis of 3,5-disubstituted-1,2, 4-oxadiazoles from indazole carboxylic acid methyl esters and amidoximes is described. In this study a series of novel 3,5-disubstituted-1,2,4-oxadiazoles (3a-d), (4a-d), (5a-d), (6a-d), (7a-d) were synthesized using amidoximes 2a-d and indazole carboxylic acid esters (3-6).
- Swamy, Udutha Kumara,Mohan, H. Rama,Prasad, U. Viplava,Suresh,Kumar, T. Laxmi
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p. 1921 - 1930
(2014/06/09)
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- Synthesis of substituted 4-(1H-indol-6-yl)-1H-indazoles as potential PDK1 inhibitors
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The development of a preparative route to a series of novel 4-(1H-indol-6-yl)-1H-indazole compounds as potential PDK1 inhibitors is described. The synthetic strategy centres on the late-stage Suzuki cross-coupling of N-unprotected indazole and indole frag
- Brzozowski, Martin,O'Brien, Nathan J.,Wilson, David J.D.,Abbott, Belinda M.
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p. 318 - 326
(2014/01/06)
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- 3-CYCLOHEXENYL SUBSTITUTED INDOLE AND INDAZOLE COMPOUNDS AS RORGAMMAT INHIBITORS AND USES THEREOF
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Disclosed are compounds of Formula (I) or a pharmaceutically acceptable salt or solvate thereof. Such compounds can be used in the treatment of RORgammaT-mediated diseases or conditions.
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Page/Page column 39-40
(2014/03/22)
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- 3-CYCLOHEXENYL AND CYCLOHEXYL SUBSTITUTED INDOLE AND INDAZOLE COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF
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The present invention relates to compounds according to Formula I and pharmaceutically acceptable salts or solvates thereof. Such compounds can be used in the treatment of RORgammaT-mediated diseases or conditions.
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Page/Page column 56
(2014/03/22)
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- 4-HETEROARYL SUBSTITUTED BENZOIC ACID COMPOUNDS AS RORGAMMAT INHIBITORS AND USES THEREOF
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Provided are compounds according to Formula I or a pharmaceutically acceptable salt or solvate thereof. Such compounds can be used in the treatment of RORgammaT-mediated diseases or conditions.
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Page/Page column 59
(2014/03/22)
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- 3-AMINOCYCLOALKYL COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF
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The present invention relates to compounds according to Formula I and pharmaceutically acceptable salts or solvates thereof. Such compounds can be used in the treatment of RORgammaT-mediated diseases or conditions.
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Page/Page column 50; 51
(2014/03/22)
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- 4-HETEROARYL SUBSTITUTED BENZOIC ACID COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF
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The present invention relates to compounds according to Formula I (Formula I), and pharmaceutically acceptable salts or solvates thereof. Such compounds can be used in the treatment of RORgammaT-mediated diseases or conditions.
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Page/Page column 61; 62
(2014/03/22)
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- COMPOUNDS ACTING AT MULTIPLE PROSTAGLANDIN RECEPTORS GIVING A GENERAL ANTI-INFLAMMATORY RESPONSE
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The present invention provides a compound, that is a 1-({halo-2-[(2-hydrocarbyl or substituted hydrocarbyl)oxy]phenyl}methyl)-(fused bicyclic nitrogen heteroaryl) carboxylic acid or an ester or sulfonamide thereof. The compound may be represented by the f
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Page/Page column 36
(2013/07/05)
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- N1/N2-Lactam Acetyl-CoA carboxylase inhibitors
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The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof; wherein G is R1, R2 and R3 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl-CoA carboxylase enzyme(s) in an animal
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Page/Page column 31-32
(2012/05/07)
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- SUBSTITUTED ACETYL-COA CARBOXYLASE INHIBITORS
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The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof; wherein G is R1, R2 and R3 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl-CoA carboxylase enzyme(s) in an animal.
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Page/Page column 22
(2012/11/07)
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- RORGAMMAT INHIBITORS
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The present invention relates to compounds according to Formula (I) or a pharmaceutically acceptable salt or solvate thereof. Such compounds can be used in the treatment of RORgammaT-mediated diseases or condition.
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Page/Page column 99
(2012/08/28)
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- ARYL SUBSTITUTED OLEFINIC COMPOUNDS AS PDE10A INHIBITORS
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The present invention provides aryl substituted olefinic compounds as Phosphodiesterase 1 0A (PDE 1 0A) inhibitors. In particular, compounds described herein are useful for treating or preventing diseases, conditions and/or disorders by inhibiting Phospho
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Page/Page column 54
(2011/11/30)
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- 2-(HETEROARYL) ALKYL INDAZOLE 6-PHENYL AND THIENYL METHYL AMIDE AS THROMBIN INHIBITORS
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The invention relates to substituted indazoles and methods for production thereof and use thereof for the production of medicinal products for the treatment and/or prophylaxis of diseases, especially of cardiovascular diseases, preferably of thromboemboli
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Page/Page column 17
(2010/05/13)
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- TRICYCLIC INDOLE DERIVATIVES AND METHODS OF USE THEREOF
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The present invention relates to Tricyclic Indole Derivatives, compositions comprising at least one Tricyclic Indole Derivatives, and methods of using the Tricyclic Indole Derivatives for treating or preventing a viral infection or a virus-related disorder in a patient
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Page/Page column 81; 82
(2010/01/07)
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- 2,3-SUBSTITUTED AZAINDOLE DERIVATIVES FOR TREATING VIRAL INFECTIONS
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The present invention relates to 2,3-Substituted Azaindole Derivatives, compositions comprising at least one 2,3-Substituted Azaindole Derivatives, and methods of using the 2,3-Substituted Azaindole Derivatives for treating or preventing a viral infection or a virus-related disorder in a patient.
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Page/Page column 112-113
(2009/04/25)
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- SUBSTITUTED INDOLE DERIVATIVES AND METHODS OF USE THEREOF
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The present invention relates to Substituted Indole Derivatives, compositions comprising at least one Substituted Indole Derivative, and methods of using these Substituted Indole Derivatives for treating or preventing a viral infection or a virus-related disorder in a patient.
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Page/Page column 187
(2009/04/25)
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- a-AMINO ACID DERIVATIVE AND PHARMACEUTICAL COMPRISING THE SAME AS ACTIVE INGREDIENT
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The present invention provides novel α-amino acid derivatives of formula (1): (wherein, R1, R2, R3, R4, X and Y are as defined in the claims) or pharmaceutically acceptable salts, prodrugs or solvates thereof. T
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Page/Page column 48-49
(2009/04/23)
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- INDAZOLE DERIVATIVES USEFUL AS MELANIN CONCENTRATING RECEPTOR LIGANDS
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The present invention relates to novel compounds, in particular, novel indazole that may be used as melanin concentrating hormone receptor ligands, methods of preparing such compounds, compositions containing such compounds, and methods of using such compounds to treat MCH related disorders.
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Page/Page column 29-30
(2008/12/05)
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- Substituted 1-alkylamino-1H-indazoles for the treatment of glaucoma
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Substituted 1-alkylamino-1H-indazoles for lowering intraocular pressure and treating glaucoma are disclosed.
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Page/Page column 7
(2010/11/30)
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- IDENTIFICATION OF COMPOUNDS SUITABLE FOR TREATING AD
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The invention provides a method of screening for compounds which inhibit the hyperphosphorylation of tau, and hence are suitable for treating AD and related conditions.
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Page/Page column 17
(2008/06/13)
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- MODULATORS OF CELLULAR ADHESION
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The present invention provides compounds having formula (I): and pharmaceutically acceptable derivatives thereof, wherein R1-R4, n, p, A, B, D, E, L and AR1 are as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof for the treatment of disorders mediated by the CD11/CD18 family of cellular adhesion molecules (e.g., LFA-1).
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Page/Page column 118-119
(2010/02/11)
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- Indazole derivatives and their use as inhibitors of phosphodiesterase (PDE) type IV and the production of tumor necrosis factor (TNF)
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The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R, R1, and R2, are as defined herein. The invention further relates to pharmaceutical compositions containing, and methods of using, the compounds of formula (I), or acceptable salts thereof, for the inhibition of phosphodiesterase (PDE) type IV or the production of tumor necrosis factor (TNF) in a mammal. The invention also relates to intermediates that are useful in the preparation of the compounds of formula (I).
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- Integrin antagonists
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This invention relates to novel heterocycles which are useful as antagonists of the αvβ3 integrin, the α2bβ3 integrin, and related cell surface adhesive protein receptors, to pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of cell adhesion, the treatment of angiogenic disorders, inflammation, bone degradation, cancer metastasis, diabetic retinopathy, thrombosis, restenosis, macular degeneration, and other conditions mediated by cell adhesion and/or cell migration and/or angiogenesis.
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- Disubstituted indazoles as potent antagonists of the integrin α(v)β3
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A new series of indazole-containing α(v)β3 integrin antagonists is described. Starting with lead compound 18a, variations in a number of structural features were explored with respect to inhibition of the binding of β3-transfected 29
- Batt, Douglas G.,Harlow, Patricia P.,Barbera, Frank A.,Spitz, Susan M.,Wexler, Ruth R.,Jadhav, Prabhakar K.,Petraitis, Joseph J.,Houghton, Gregory C.,Modi, Dilip P.,Cain, Gary A.,Corjay, Martha H.,Mousa, Shaker A.,Bouchard, Peter J.,Forsythe, Mark S.
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- Integrin receptor antagonists
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This invention relates to novel heterocycles including 3-?1-?3-(imidazolin-2-ylamino)propyl!indazol-5-ylcarbonylamino!-2-(benzyloxycarbonylamino)propionic acid, which are useful as antagonists of the αv β3 integrin and related cell surface adhesive protein receptors, to pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of cell adhesion, the treatment of angiogenic disorders, inflammation, bone degradation, cancer metastasis, diabetic retinopathy, thrombosis, restenosis, macular degeneration, and other conditions mediated by cell adhesion and/or cell migration and/or angiogenesis.
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- Substituted 6,11-ethano-6,11-dihydrobenzo[b] quinolizinium salts and compositions and methods of use thereof
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Substituted 6,11-ethano-6,11-dihydrobenzo[b]quinolizinium salts, pharmaceutical compositions containing them, and methods for the treatment of neurodegenerative disorders or neurotoxic injuries utilizing them, wherein the substituted 6,11-ethano-6,11-dihydrobenzo[b]quinolizinium salts have the formula: STR1 wherein: R1, R2, R3, R4, R5, R6, R7, X and p are as defined in the specification.
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