- General methods for the synthesis and late-stage diversification of 2,4-substituted 7-azaindoles
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As part of a medicinal chemistry program, we adapted known synthetic methods for the late-stage diversification of 2,4-substituted 7-azaindoles. The strengths and weaknesses of these strategies are discussed. In the course of this work, three optimized co
- Varnes, Jeffrey G.,McGuire, Thomas,Meadows, Rebecca E.,Barlaam, Bernard,Clark, Jemma,Cook, Calum R.,Davison, Gemma,Dishington, Allan,De Savi, Chris,Donald, Craig,Grebe, Tyler,Hande, Sudhir,Hawkins, Janet,Hird, Alexander W.,Holmes, Jane,Lister, Andrew,Lucas, Simon,Moore, Jane,Moore, Esther,Patel, Anil,Pike, Kurt G.,Roberts, Bryan,Stark, Andrew,Stead, Darren,Thakur, Kumar,Turner, Paul,Vasbinder, Melissa,Yang, Bin
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Read Online
- Pyrimidine derivative, and preparation method and application thereof
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The invention discloses a compound represented by general formula (I) capable of being used as an ATR protein kinase inhibitor, and an isomer or pharmaceutically acceptable salt thereof. The compound, and the isomer or the pharmaceutically acceptable salt thereof can be used for preparing medicines for treating and/or preventing hyperproliferative diseases.
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Paragraph 0108-0111
(2021/06/12)
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- CDK9 Kinase inhibitors
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The present application relates to CDK9 kinase inhibitors which provide a compound of formula (I) or a stereoisomer thereof. A solvate, a metabolite, a pharmaceutically acceptable salt or prodrug, and a pharmaceutical composition comprising the same. Also provided are the use of compounds and pharmaceutical compositions in the manufacture of a medicament for the treatment of cancer.
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Paragraph 0234-0236; 0240
(2021/11/21)
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- Development of Potent PfCLK3 Inhibitors Based on TCMDC-135051 as a New Class of Antimalarials
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The protein kinase PfCLK3 plays a critical role in the regulation of malarial parasite RNA splicing and is essential for the survival of blood stage Plasmodium falciparum. We recently validated PfCLK3 as a drug target in malaria that offers prophylactic,
- Mahindra, Amit,Janha, Omar,Mapesa, Kopano,Sanchez-Azqueta, Ana,Alam, Mahmood M.,Amambua-Ngwa, Alfred,Nwakanma, Davis C.,Tobin, Andrew B.,Jamieson, Andrew G.
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supporting information
p. 9300 - 9315
(2020/10/19)
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- Synthesis of Differentially Protected Azatryptophan Analogs via Pd2(dba)3/XPhos Catalyzed Negishi Coupling of N-Ts Azaindole Halides with Zinc Derivative from Fmoc-Protected tert-Butyl (R)-2-Amino-3-iodopropanoate
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Unnatural amino acids play an important role in peptide based drug discovery. Herein, we report a class of differentially protected azatryptophan derivatives synthesized from N-tosyl-3-haloazaindoles 1 and Fmoc-protected tert-butyl iodoalanine 2 via a Neg
- Nimje, Roshan Y.,Vytla, Devaiah,Kuppusamy, Prakasam,Velayuthaperumal, Rajeswari,Jarugu, Lokesh Babu,Reddy, China Anki,Chikkananjaiah, Nanjundaswamy Kanikahalli,Rampulla, Richard A.,Cavallaro, Cullen L.,Li, Jianqing,Mathur, Arvind,Gupta, Anuradha,Roy, Amrita
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p. 11519 - 11530
(2020/10/12)
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- TYROSINE AMIDE DERIVATIVES AS RHO- KINASE INHIBITORS
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The invention relates to compounds of formula I inhibiting Rho Kinase that are bicyclic dihydropyrimidine-carboxamide derivatives, methods of preparing such compounds, pharmaceutical compositions containing them and therapeutic use thereof Particularly the compounds of the invention may be useful in the treatment of many disorders associated with ROCK enzymes mechanisms, such as pulmonary diseases including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH).
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Page/Page column 70
(2020/02/14)
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- ATR INHIBITOR AND APPLICATION THEREOF
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Disclosed are a compound as an ATR inhibitor and an application in preparing a drug as an ATR inhibitor. In particular, disclosed is a compound represented by formula (I) or an isomer or pharmaceutically acceptable salt thereof.
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Paragraph 0105; 0106
(2020/12/29)
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- TYROSINE ANALOGUES DERIVATIVES AS RHO- KINASE INHIBITORS
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The invention relates to compounds of formula (I) inhibiting Rho Kinase that are tyrosine analogues derivatives, methods of preparing such compounds, pharmaceutical compositions containing them and therapeutic use thereof. Particularly the compounds of the invention may be useful in the treatment of many disorders associated with ROCK enzymes mechanisms, such as pulmonary diseases including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH).
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Page/Page column 70
(2019/04/09)
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- Development and Scale-up of a Route to ATR Inhibitor AZD6738
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AZD6738 is currently being tested in multiple phase I/II trials for the treatment of cancer. Its structure, comprising a pyrimidine core decorated with a chiral morpholine, a cyclopropyl sulfoximine, and an azaindole, make it a challenging molecule to syn
- Goundry, William R. F.,Dai, Kuangchu,Gonzalez, Miguel,Legg, Daniel,O'Kearney-Mcmullan, Anne,Morrison, James,Stark, Andrew,Siedlecki, Paul,Tomlin, Paula,Yang, Jianbo
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p. 1333 - 1342
(2019/08/12)
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- DIHYDROISOQUINOLINE-2(1H)-CARBOXAMIDE AND RELATED COMPOUNDS AND THEIR USE IN TREATING MEDICAL CONDITIONS
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The invention provides dihydroisoquinoline-2(1H)-carboxamide and related compounds, pharmaceutical compositions, and their use in the treatment of medical conditions, such as cancer, and in inhibiting HPK1 activity.
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Paragraph 000551
(2019/11/04)
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- HETEROCYCLIC INHIBITORS OF ATR KINASE
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The present invention relates to heterocyclic compounds and methods which may be useful as inhibitors of ATR kinase for the treatment or prevention of cancer.
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Paragraph 0701-0703
(2019/02/28)
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- Synthesis of novel 7-azaindole derivatives containing pyridin-3-ylmethyl dithiocarbamate moiety as potent PKM2 activators and PKM2 nucleus translocation inhibitors
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Multiple lines of evidence have indicated that pyruvate kinase M2 (PKM2) is upregulated in most cancer cells and it is increasingly recognized as a potential therapeutic target in oncology. In a continuation of our discovery of lead compound 5 and SAR study, the 7-azaindole moiety in compound 5 was systematically optimized. The results showed that compound 6f, which has a difluoroethyl substitution on the 7-azaindole ring, exhibited high PKM2 activation potency and anti-proliferation activities on A375 cell lines. In a xenograft mouse model, oral administration of compound 6f led to significant tumor regression without obvious toxicity. Further mechanistic studies revealed that 6f could influence the translocation of PKM2 into nucleus, as well as induction of apoptosis and autophagy of A375 cells. More importantly, compound 6f significantly inhibited migration of A375 cells in a concentration-dependent manner. Collectively, 6f may serve as a lead compound in the development of potent PKM2 activators for cancer therapy.
- Liu, Bin,Yuan, Xia,Xu, Bo,Zhang, Han,Li, Ridong,Wang, Xin,Ge, Zemei,Li, Runtao
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- AZAINDOLE DERIVATIVES AS RHO- KINASE INHIBITORS
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The invention relates to compounds of formula (I) inhibiting Rho Kinase that are azaindole derivatives, methods of preparing such compounds, pharmaceutical compositions containing them and therapeutic use thereof Particularly the compounds of the inventio
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Page/Page column 40; 41
(2020/01/08)
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- TYROSINE AMIDE DERIVATIVES AS RHO- KINASE INHIBITORS
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Bicyclic dihydropyrimidine-carboxamide compounds of formula I described herein inhibit Rho Kinase and may be used for the treatment of many disorders associated with ROCK enzymes mechanisms, such as pulmonary diseases including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH).
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Paragraph 0467-0468
(2018/08/20)
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- Azaquinazoline Inhibitors Of Atypical Protein Kinase C
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The present application provides a compound of formula (I) and/or a salt thereof, wherein R1, G, and X are as defined herein. A compound of formula (I) and/or its salts have aPKC inhibitory activity, and may be used to treat proliferative disor
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Paragraph 0202
(2015/12/24)
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- TETRACYCLIC CDK9 KINASE INHIBITORS
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Disclosed are compounds of Formula (Ia), and pharmaceutically acceptable salts thereof, wherein X, Y, R1, R2, R3A, R3B, and R4 are as described herein. The compounds may be used as agents in the treatment of diseases, including cancer. Also disclosed are pharmaceutical compositions comprising one or more compounds of Formula (Ia).
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Paragraph 1138
(2015/09/22)
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- PYRROLO[2,3-B]PYRIDINE CDK9 KINASE INHIBITORS
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Disclosed are compounds of Formula (IIa), wherein R1, R2, R3A, R3B, R3C, R3D, R3E, and R4 are as defined in the specification, and pharmaceutically acceptable salts thereof. The compounds may be used as agents in the treatment of diseases, including cancer. Also provided are pharmaceutical compositions comprising one or more compounds of Formula (IIa)
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Page/Page column 454; 455
(2014/09/29)
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- CDK9 KINASE INHIBITORS
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Disclosed are compound of Formula (Ia), wherein R1A, R1, R2, R10, J, L, T, X, Y, and Z are as defined in the specification, and pharmaceutically acceptable salts thereof. The compounds may be used as agents in the treatment of diseases, including cancer. Also provided are pharmaceutical compositions, comprising one or more compounds of Formula (Ia).
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Paragraph 0616
(2014/09/30)
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- NOVEL COMPOUNDS
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The present invention relates to novel NADPH oxidase II inhibitors and their use in the treatment of diseases mediated by the NADPH oxidase enzymes.
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Page/Page column 40
(2013/02/27)
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- CHEMICAL COMPOUNDS
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There is provided pyrimidinyl compounds of Formula (I), wherein: R2 is or pharmaceutically acceptable salts thereof, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.
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- PYRROLOPYRIDINE AND PYRROLOPYRIMIDINE INHIBITORS OF KINASES
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The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein A, B, R1, R2, R3, R4a, R5, and Z 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 aurora.
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Page/Page column 32
(2011/11/30)
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- Pyrrolo [2,3,B] Pyridine Derivatives Useful As RAF Kinase Inhibitors
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The present invention provides pyrrolo pyridine compounds, compositions containing the same, as well as processes for the preparation and their use as pharmaceutical agents.
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Page/Page column 14
(2009/01/24)
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- NOVEL COMPOUNDS
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The invention is directed to certain novel compounds. Specifically, the invention is directed to compounds according to formula (I) and salts thereof. The compounds of the invention are inhibitors of kinase activity, in particular IKK2 activity.
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Page/Page column 42; 89
(2009/01/20)
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- Knowledge-based design of 7-azaindoles as selective B-Raf inhibitors
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The synthesis of a 7-azaindole series of novel, potent B-Raf kinase inhibitors using knowledge-based design was carried out. Compound 6h exhibits not only excellent potency in both the enzyme assay (IC50 = 2.5 nM) and the cellular assay (ICsub
- Tang, Jun,Hamajima, Toshihiro,Nakano, Masato,Sato, Hideyuki,Dickerson, Scott H.,Lackey, Karen E.
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scheme or table
p. 4610 - 4614
(2009/04/08)
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- COMPOUNDS
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Invented are novel azaindole compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.
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Page/Page column 34-35
(2008/06/13)
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- PYRROLOPYRIDINES USEFUL AS INHIBITORS OF PROTEIN KINASE
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The present invention relates to compounds of formula (I) wherein Q, Z, R1 , R2 , and R3 are as described in claim 1 useful as inhibitors of protein kinases, particularly of JAK family and ROCK family kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.
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Page/Page column 85
(2010/11/25)
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