- Discovery of novel 4-azaaryl-N-phenylpyrimidin-2-amine derivatives as potent and selective FLT3 inhibitors for acute myeloid leukaemia with FLT3 mutations
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Feline McDonough sarcoma (FMS)-like tyrosine kinase 3 (FLT3) is one of the most pursued targets in the treatment of acute myeloid leukaemia (AML) as its gene amplification and mutations, particularly internal tandem duplication (ITD), contribute to the pa
- Long, Yi,Yu, Mingfeng,Ochnik, Aleksandra M.,Karanjia, Jasmine D.,Basnet, Sunita KC.,Kebede, Alemwork A.,Kou, Lianmeng,Wang, Shudong
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- Indazole compounds and preparation method and application thereof
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The invention provides indazole compounds and a preparation method and application thereof. A series of completely new small molecule PI3Kdelta inhibitors are designed and synthesized by using indazole as a structural mother nucleus, the PI3Kdelta kinase inhibitory activity test and MV-4-11 cell activity test of the compounds are carried out, and the indazole compounds exhibit better kinase subtype selectivity, and exhibit better in vitro proliferation inhibitory activity against tumor cell lines. The compounds can be used in the preparation of antitumor drugs and in the preparation of activedrugs for inhibiting PI3Kdelta kinase, and a new way is provided for the antitumor drug research. The raw materials are cheap and easy to obtain, the preparation method is simple, and the large-scaleproduction is suitable. The structural formula is as shown in the specification.
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- METHODS OF USING INDAZOLE-3-CARBOXAMIDES AND THEIR USE AS WNT/B-CATENIN SIGNALING PATHWAY INHIBITORS
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This disclosure features the use of one or more indazole-3-carboxamide compounds or salts or analogs thereof, in the treatment of one or more diseases or conditions independently selected from the group consisting of a tendinopathy, dermatitis, psoriasis, morphea, ichthyosis, Raynaud's syndrome, and Darier's disease; and/or for promoting wound healing. The methods include administering to a subject (e.g., a subject in need thereof) a therapeutically effective amount of one or more indazole-3-carboxamide compounds or salts or analogs thereof as described anywhere herein.
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Paragraph 0366; 0367
(2018/05/16)
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- THERAPEUTIC INHIBITORY COMPOUNDS
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Provided herein are heterocyclic derivative compounds and pharmaceutical compositions comprising said compounds. Said heterocyclic derivative compounds are complement factor D inhibitors. Such compounds are useful for treating complement related disorders including, but are not limited to, autoimmune, inflammatory, and neurodegenerative diseases.
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Paragraph 00236
(2018/02/22)
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- P2X3 AND/OR P2X2/3 COMPOUNDS AND METHODS
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The present disclosure provides novel compounds and methods for preparing and using these compounds. In one embodiment, the compounds are of the structure of formula (I), wherein R1-R7 are defined herein. In a further embodiment, these compounds are useful in method for regulating one or both of the P2X3 or P2X2/3 receptors. In another embodiment, these compounds are useful for treating pain in patients by administering one or more of the compounds to a patient. In another embodiment, these compounds are useful for treating respiratory dysfunction in patients by administering one or more of the compounds to a patient.
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Paragraph 0271-0274
(2018/04/17)
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- BICYCLIC HETEROARYL INDOLE ANALOGUES USEFUL AS ROR GAMMA MODULATORS
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The present disclosure is directed to compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein X, X1, M, R2, R3, R4, R5, m, n, and p are as defined herein, which are active as modulators of retinoid-related orphan receptor gamma t (RORγt). These compounds prevent, inhibit, or suppress the action of RORγt and are therefore useful in the treatment of RORγt mediated diseases, disorders, syndromes or conditions such as, e.g., pain, inflammation, COPD, asthma, rheumatoid arthritis, colitis, multiple sclerosis, neurodegenerative diseases and cancer.
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- INDAZOLE INHIBITORS OF THE WNT SIGNAL PATHWAY AND THERAPEUTIC USES THEREOF
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Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases due to mutations in Wnt signaling components. Also provided are methods for treating Wnt-related disease states.
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Paragraph 0082; 0083
(2015/11/16)
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- INDAZOLE-3-CARBOXAMIDES AND THEIR USE AS WNT/B-CATENIN SIGNALING PATHWAY INHIBITORS
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lndazole-3-carboxamide compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an indazole-3- carboxamide compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.
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Paragraph 00334
(2013/03/28)
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- INDAZOLE INHIBITORS OF THE WNT SIGNAL PATHWAY AND THERAPEUTIC USES THEREOF
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Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt path
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Paragraph 0409
(2013/10/22)
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- Synthesis and biological evaluation of imidazo[4,5-b]pyridine and 4-heteroaryl-pyrimidine derivatives as anti-cancer agents
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A series of N-phenyl-imidazo[4,5-b]pyridin-2-amines, 4-indazolyl-N- phenylpyrimidin-2-amines and N-phenyl-4-pyrazolo[3,4-b]pyridin-pyrimidin-2- amines have been synthesized. Their anti-proliferative activities were tested in HCT-116 human colon carcinoma and MCF-7 breast carcinoma cell lines. Many exhibited potent anti-proliferative and CDK9 inhibitory activities. A lead compound 18b demonstrated the ability to reduce the level of Mcl-1 anti-apoptotic protein, to activate caspase 3/7 and induce cancer cell apoptosis.
- Lukasik, Pawel M.,Elabar, Sherifa,Lam, Frankie,Shao, Hao,Liu, Xiangrui,Abbas, Abdullah Y.,Wang, Shudong
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p. 311 - 322
(2013/01/15)
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- INDAZOLES AS WNT/B-CATENIN SIGNALING PATHWAY INHIBITORS AND THERAPEUTIC USES THEREOF
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Described herein are methods of treating a disorder or disease in which aberrant Wnt signaling is implicated, with a variety of compounds, including Wnt inhibitor compounds. More particularly, it concerns the use of an indazole compound or analogs thereof
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- Synthesis and SAR optimization of diketo acid pharmacophore for HCV NS5B polymerase inhibition
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Hepatitis C virus (HCV) NS5B polymerase is a key target for anti-HCV therapeutics development. Here we report the synthesis and biological evaluation of a new series of α,γ-diketo acids (DKAs) as NS5B polymerase inhibitors. We initiated structure-activity
- Bhatt, Aaditya,Gurukumar,Basu, Amartya,Patel, Maulik R.,Kaushik-Basu, Neerja,Talele, Tanaji T.
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p. 5138 - 5145
(2011/11/28)
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- POLYSUBSTITUTED DERIVATIVES OF 6-HETEROARYLIMIDAZO[1,2-a]PYRIDINES, AND PREPARATION AND THERAPEUTIC USE THEREOF
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Compounds of formula (I): wherein R1, R2, R3, R4, Het and X are as defined in the disclosure, or an acid addition salt thereof, and the therapeutic use and process of synthesis thereof.
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Page/Page column 17
(2011/04/18)
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- Design and synthesis of a new indazole library: direct conversion of?N-methoxy-N-methylamides (Weinreb amides) to 3-keto and 3-formylindazoles
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Nucleophilic addition of Grignard or lithiated reagents on the new Weinreb amides 3 and 4 afforded efficiently the corresponding ketones and allowed the design and synthesis of a new indazole library. These 3-ketoindazoles were obtained by a direct and or
- Crestey, Fran?ois,Stiebing, Silvia,Legay, Rémi,Collot, Valérie,Rault, Sylvain
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p. 419 - 428
(2007/10/03)
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- New practical access to 2-azatryptophans and dehydro derivatives via the Wittig-Horner reaction
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The Wittig-Horner reaction of protected 3-formylindazoles 1 with (±)-N-(benzyloxycarbonyl)-α-phosphonoglycine trimethyl ester 2 has been developed as a new practical synthesis of dehydro 2-azatryptophans and amino acid derivatives. The preparation of 5-br
- Crestey, Fran?ois,Collot, Valérie,Stiebing, Silvia,Lohier, Jean-Fran?ois,Santos, Jana Sopkova-de Oliveira,Rault, Sylvain
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p. 2457 - 2460
(2007/10/03)
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- [(1H-INDAZOL-3-YL)METHYL]PHENOLS AND (HYDROXYPHENYL)(1H-INDAZOL-3-YL)METHANONES
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This invention provides anti-inflammatory agents of formula (I), having the structure: formula (I), formula (II), wherein A and R1-R10 are as defined in the specification, or a N-oxide thereof or a pharmaceutically acceptable salt th
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Page/Page column 63
(2008/06/13)
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