- PIPERIDIN-1- YL-N-PYRYDI NE-3-YL-2-OXOACET AM IDE DERIVATIVES USEFUL FOR THE TREATMENT OF MTAP-DEFICIENT AND/OR MT A-ACCUMULATING CANCERS
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Compounds are provided according to Formula (I) and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R1, R2, R3, R4, R6, R7, R8 and n are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.
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Paragraph 0980
(2022/02/09)
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- SYNTHESIS, CRYSTAL STRUCTURE, AND A DFT STUDY OF TERT-BUTYL-5-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-YL)-1H-INDAZOLE-1-CARBOXYLATE
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Abstract: Tert-butyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole-1-carboxylate is a significant intermediate of 1H-indazole derivatives. In this paper, the title compound is acquired through two substitution reactions. The structure is corroborated by FTIR, 1H and 13C NMR spectroscopy, and MS. In the meantime, the single crystal is detected by means of X-ray diffraction, calculated by exerting density functional theory (DFT), and subjected to the crystallographic and conformational analysis. The results of comparing the DFT calculated value with the X-ray diffraction value display that the optimized molecular structure does cohere with the single crystal structure ascertained via the experiment. The 98.28% stable conformer and 1.72% unstable conformers are found in the DFT calculations. Furthermore, to reveal the physicochemical features of the title compound, the molecular electrostatic potential and frontier molecular orbitals are investigated through DFT.
- Chen, D.-M.,Chen, Y.-M.,Liao, T.-H.,Wu, Q.-M.,Yang, D.-Z.,Ye, W.-J.,Zhou, Z.-X.
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p. 1357 - 1364
(2021/11/04)
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- Bioisosteric replacements of the indole moiety for the development of a potent and selective PI3Kδ inhibitor: Design, synthesis and biological evaluation
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Based on indole scaffold, a potent and selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, namely FD223, was developed by the bioisosteric replacement drug discovery approach and studied for the treatment of acute myeloid leukemia (AML). In vitro
- Yang, Chengbin,Xu, Chenyue,Li, Zhipeng,Chen, Yi,Wu, Tianze,Hong, Hui,Lu, Mingzhu,Jia, Yu,Yang, Yongtai,Liu, Xiaofeng,Deng, Mingli,Chen, Zhenxia,Li, Qingquan,Ling, Yun,Zhou, Yaming
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supporting information
(2021/07/10)
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- METHODS AND COMPOUNDS FOR RESTORING MUTANT p53 FUNCTION
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Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods that restore DNA binding affinity of p53 mutants. The compounds of the present disclosure can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.
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Paragraph 0264
(2022/01/06)
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- GDF-8 INHIBITORS
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Disclosed are 2,2'-bipyridyl compounds, as well as pharmaceutical compositions and methods of use thereof. One embodiment is a compound having the structure and pharmaceutically acceptable salts, prodrugs and N-oxides thereof (and solvates and hydrates thereof), wherein R1, Z and n are as described herein. In certain embodiments, a compound disclosed herein inhibits GDF8, and can be used to treat disease by blocking GDF8 signaling.
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Paragraph 0164; 0165
(2016/09/15)
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- 2,3-DISUBSTITUTED PYRIDINE COMPOUNDS AS TGF-BETA INHIBITORS AND METHODS OF USE
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The invention described herein comprises compounds of formula (IV) and a method of treating cancer comprising administering to a subject having cancer one of the compounds in conjunction with another therapeutic treatment of cancer. The compounds (IV) inhibit signaling by a member of the TGF-β superfamily such as Nodal or Activin.
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Paragraph 0149
(2015/11/27)
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- FATTY ACID SYNTHASE INHIBITORS
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This invention relates to carboxamides and reverse carboxamides according to Formula (I) and the use of carboxamides and reverse carboxamides for the modulation, notably the inhibition of the activity or function of fatty acid synthase (FAS). Suitably, the present invention relates to the use of carboxamides and reverse carboxamides in the treatment of cancer.
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Page/Page column 55
(2013/03/26)
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- FATTY ACID SYNTHASE INHIBITORS
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This invention relates to the use of imidazole, triazole, and tetrazole derivatives for the modulation, notably the inhibition of the activity or function of fatty acid synthase (FAS). Suitably, the present invention relates to the use of imidazoles, triazoles, and tetrazoles in the treatment of cancer.
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Page/Page column 53
(2012/04/04)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Page/Page column 106
(2012/09/21)
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- Scaffold oriented synthesis. Part 3: Design, synthesis and biological evaluation of novel 5-substituted indazoles as potent and selective kinase inhibitors employing [2+3] cycloadditions
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We report the synthesis and biological evaluation of 5-substituted indazoles and amino indazoles as kinase inhibitors. The compounds were synthesized in a parallel synthesis fashion from readily available starting materials employing [2+3] cycloaddition r
- Akritopoulou-Zanze, Irini,Wakefield, Brian D.,Gasiecki, Alan,Kalvin, Douglas,Johnson, Eric F.,Kovar, Peter,Djuric, Stevan W.
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scheme or table
p. 1476 - 1479
(2011/04/16)
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- Scaffold oriented synthesis. Part 4: Design, synthesis and biological evaluation of novel 5-substituted indazoles as potent and selective kinase inhibitors employing heterocycle forming and multicomponent reactions
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We report the synthesis and biological evaluation of 5-substituted indazoles as kinase inhibitors. The compounds were synthesized in a parallel synthesis fashion from readily available starting materials employing heterocycle forming and multicomponent reactions and were evaluated against a panel of kinase assays. Potent inhibitors were identified for Gsk3β, Rock2, and Egfr.
- Akritopoulou-Zanze, Irini,Wakefield, Brian D.,Gasiecki, Alan,Kalvin, Douglas,Johnson, Eric F.,Kovar, Peter,Djuric, Stevan W.
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scheme or table
p. 1480 - 1483
(2011/04/23)
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- BENZIMIDAZOLES AS FATTY ACID SYNTHASE INHIBITORS
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This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of fatty acid synthase (FAS). Suitably, the present invention relates to the use of benzimidazoles in the treatment of cancer.
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Page/Page column 53
(2011/06/11)
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- FLUORINATION OF ORGANIC COMPOUNDS
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Methods for fluorinating organic compounds are described herein.
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Page/Page column 83
(2010/07/10)
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- NOVEL COMPOUNDS AS ANTAGONISTS OR INVERSE AGONISTS FOR OPIOID RECEPTORS
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This invention relates to novel compounds which are antagonists or inverse agonists at one or more of the opioid receptors, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy.
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Page/Page column 91
(2010/09/07)
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- 3-INDAZOLYL-4-PYRIDYLISOTHIAZOLES
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The present invention provides 3-indazoyl-4-pyridylisothiazoles or a pharmaceutically acceptable salt thereof, pharmaceutical compositions thereof, and methods of using the same, as well as processes for preparing the same, and intermediates thereof.
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Page/Page column 6
(2009/10/18)
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- Fluorination of boronic acids mediated by silver(I) Triflate
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A regiospecific Ag-mediated fluorination reaction of aryl- and alkenylboronic acids and esters Is reported. The fluorination reaction uses commercially available reagents, does not require the addition of exogenous ligands, and can be performed on a multigram scale. This report discloses the first practical reaction sequence from arylboronic acid to aryl fluorides.
- Furuya, Takeru,Ritter, Toblas
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supporting information; experimental part
p. 2860 - 2863
(2009/12/05)
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- Indazoles: Regioselective protection and subsequent amine coupling reactions
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(Chemical Equation Presented) Indazoles are unselectively protected under strongly basic conditions to give a mixture at N-1 and N-2. Under mildly acidic conditions, regioselective protection at N-2 takes place. Thermodynamic conditions lead to regioselective protection at N-1. This trend applies to various substituted indazoles. Protected 5-bromoindazoles participate in Buchwald reactions with a range of amines to generate novel derivatives.
- Slade, David J.,Pelz, Nicholas F.,Bodnar, Wanda,Lampe, John W.,Watson, Paul S.
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supporting information; experimental part
p. 6331 - 6334
(2009/12/26)
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- 6-AMINOIMIDAZO[1,2-b]PYRIDAZINE ANALOGS AS RHO KINASE INHIBITORS FOR THE TREATMENT OF RHO KINASE-MEDIATED DISEASES AND CONDITIONS
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Methods for using 6-aminoimidazo[1,2-b]pyridazine analogs are disclosed herein to treat rho kinase-mediated diseases or rho kinase-mediated conditions, including controlling intraocular pressure and treating glaucoma, are disclosed. Ophthalmic pharmaceutical compositions useful in the treatment of eye diseases such as glaucoma, and additionally useful for controlling intraocular pressure, the compositions comprising an effective amount of 6-aminoimidazo[1,2-b]pyridazine analogs, are disclosed herein.
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Page/Page column 21
(2008/12/06)
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- COMBINATION OF A HYPNOTIC AGENT AND SUBSTITUTED BIS ARYL AND HETEROARYL COMPOUND AND THERAPEUTIC APPLICATION THEREOF
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The invention concerns the combination of a short-acting hypnotic agent and a compound of formula (I): Wherein X, Y, Z, A, B, D, Ar, R1 and R2 are as defined herein. The combination of this invention is useful in treating a varie
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Page/Page column 21
(2008/12/06)
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- 5-HETEROARYL SUBSTITUTED INDAZOLES AS KINASE INHIBITORS
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The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein A, R1, R2, R3 and m, are defined in the description. The present invention relates also to methods of making said compounds, and compositions containing said compounds which are useful for inhibiting kinases such as Glycogen Synthase kinase 3 (GSK-3), Rho kinase (ROCK), Janus Kinases (JAK), AKT, PAK4, PLK, CK2, KDR, MK2, JNK1, aurora, pim 1 and nek 2.
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Page/Page column 70
(2009/01/24)
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- SUBSTITUTED BIS ARYL AND HETEROARYL COMPOUNDS AS SELECTIVE 5HT2A ANTAGONISTS
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The present invention relates to a series of substituted bis aryl and heteroaryl compounds of formula (I): Wherein X, Y, Z, A, B, D, Ar, R 1 and R2 are as defined herein. The compounds of this invention are selective 5HT2A antagonists, and are therefore, useful in treating a variety of diseases including but not limited to a wide variety of sleep disorders as disclosed and claimed herein.
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Page/Page column 59
(2008/06/13)
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- FUSED HETEROARYL DERIVATIVES FOR USE AS P38 KINASE INHIBITORS IN THE TREATMENT OF I.A. RHEUMATOID ARTHRITIS
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Compounds of formula: (I) are inhibitors of p38 kinase and are useful in the treatment of conditions or disease states mediated by p38 kinase activity or mediated by cytokines produced by the activity of p38.
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Page/Page column 30
(2010/02/13)
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- FUSED HETEROARYL DERIVATIVES FOR USE AS P38 KINASE INHIBITORS IN THE TREATMENT OF I.A. RHEUMATOID ARTHRISTIS
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Compounds of formula (I): wherein A is a 5-membered heteroaryl ring are inhibitors of p38 kinase and are useful in the treatment of conditions or disease states mediated by p38 kinase activity or mediated by cytokines produced by the activity of p38, such as rheumatoid arthritis.
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Page/Page column 26-27
(2010/11/30)
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