- Preparation method of 6-cyano-7-azaindole and derivative thereof
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The invention discloses a preparation method of 6-cyano-7-azaindole and a derivative thereof, which comprises the following steps: dissolving a compound represented by formula (1) in a solvent, and performing a reaction with an organic alkali and a cyaniding reagent under the action of a catalyst to obtain the final product represented by formula (2). According to the process disclosed by the invention, the safe and non-toxic potassium ferrocyanide is used as a cyano source, the reaction operation is simple and convenient, the yield is high, the influence on the environment is relatively small, and the process is suitable for preparing the 6-cyano-7-azaindole and the derivative 1-benzoyl-6-cyano-7-azaindole thereof on a large scale.
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Paragraph 0025-0029
(2020/09/30)
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- INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7)
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The present invention provides, inter alia, compounds having the structures of formulas described herein; pharmaceutically acceptable salts, solvates, hydrates, tautomers, and isotopic forms thereof; and compositions (e.g., pharmaceutical compositions and kits) containing one or more of the foregoing. Also provided are methods of administering and uses involving the compounds and/or pharmaceutical compositions for treating or preventing disease. The disease can be a proliferative disease, such as a cancer (e.g., a blood cancer (e.g., a leukemia or lymphoma), a brain cancer, a breast cancer, melanoma, multiple myeloma, or an ovarian cancer) a benign neoplasm, pathologic angiogenesis, or a fibrotic disease. While no aspect of the invention is limited by the biological events that may transpire, administering a compound or other composition described herein may selectively inhibit the aberrant expression or activity of cyclin-dependent kinase 7 (CDK7) and, thereby, induce cellular apoptosis and/or inhibit the transcription of disease-related genes in the patient (or in a biological sample).
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Paragraph 317
(2019/08/08)
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- INHIBITORS OF CYCLIN DEPENDNT KINASE 7 (CDK7)
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The present invention provides novel compounds of Formula (I) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of cyclin-dependent kinase 7 (CDK7), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.
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Paragraph 481
(2018/02/28)
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- An orally available, brain-penetrant CAMKK2 inhibitor reduces food intake in rodent model
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Hypothalamic CAMKK2 represents a potential mechanism for chemically affecting satiety and promoting weight loss in clinically obese patients. Single-digit nanomolar inhibitors of CAMKK2 were identified in three related ATP-competitive series. Limited optimization of kinase selectivity, solubility, and pharmacokinetic properties were undertaken on all three series, as SAR was often transferrable. Ultimately, a 2,4-diaryl 7-azaindole was optimized to afford a tool molecule that potently inhibits AMPK phosphorylation in a hypothalamus-derived cell line, is orally bioavailable, and crosses the blood–brain barrier. When dosed orally in rodents, compound 4 t limited ghrelin-induced food intake.
- Price, Daniel J.,Drewry, David H.,Schaller, Lee T.,Thompson, Brian D.,Reid, Paul R.,Maloney, Patrick R.,Liang, Xi,Banker, Periette,Buckholz, Richard G.,Selley, Paula K.,McDonald, Octerloney B.,Smith, Jeffery L.,Shearer, Todd W.,Cox, Richard F.,Williams, Shawn P.,Reid, Robert A.,Tacconi, Stefano,Faggioni, Federico,Piubelli, Chiara,Sartori, Ilaria,Tessari, Michela,Wang, Tony Y.
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p. 1958 - 1963
(2018/04/20)
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- ARYLOXYACETYLINDOLES AND ANALOGS AS ANTIBIOTIC TOLERANCE INHIBITORS
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The disclosure provides compounds and pharmaceutical compositions of aryloxyacetylindoles compounds and analogs useful for treating chronic and acute bacterial infections. Certain of the compounds are compounds of general Formula (I) (I) or a pharmaceutically acceptable salt or prodrug thereof. Certain compounds of this disclosure are MvfR inhibitors. MvfR inhibitors reduce the formation of antibiotic tolerant bacterial strains and are useful for treating Gram-negative bacterial infections and reducing the virulence of Pseudomonas aeruginosa. Methods of treating bacterial infections in a subject, including Pseudomonas aeruginosa infections, are also provided by the disclosure.
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- RING-FUSED COMPOUND
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The present invention relates to a compound that has URAT1 inhibitory action, and a URAT1 inhibitor, a blood uric acid level-reducing agent and a pharmaceutical composition comprising the compound. More specifically, the present invention relates to a compound represented by Formula (I) below. [in the formula, R1 is -Q1-A1 and the like; ---- is a double bond or a single bond; when ---- is a double bond, W1 is a nitrogen atom or a group represented by the general formula: =C(Ra)-, and W2 is a nitrogen atom or a group represented by the general formula: =C(Rb) -; when ---- is a single bond, W1 is a group represented by the general formula: -C(Raa)(Rab)- or a group represented by the general formula: -(C=O) -, and W2 is a group represented by the general formula: C(Rba)(Rbb)-, a group represented by the general formula: - (C=O) - or a group represented by the general formula: -N(Rbc)-; W3, W4 and W5 are each independently a nitrogen atom or a methine group and the like that may have a substituent; X is a single bond, an oxygen atom and the like; Y is a single bond or (CRYiRYi')n; and Z is a hydroxyl group or COOR2 and the like.
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- OXAZINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF NEUROLOGICAL DISORDERS
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The invention relates to novel heterocyclic compounds of the formula (I), in which all of the variables are as defined in the specification, in free form or in pharmaceutically acceptable salt form, to their preparation, to their medical use and to medicaments comprising them.
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Page/Page column 80
(2012/07/28)
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- FUNCTIONALLY SELECTIVE AZANITRILE ALPHA2C ADRENORECEPTOR AGONISTS
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In its many embodiments, the present invention provides a novel class of azanitrile compounds as inhibitors of α2C adrenergic receptor agonists, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, method
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Page/Page column 74-75
(2010/04/25)
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- Synthesis of 4-, 5- and 6-benzoylated 7-azaindoles
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Efficient syntheses of 4-, 5- and 6-benzoyl-7-azaindoles are described. Two strategies were developed: i) formation of 4-lithio and 5-lithio-7-azaindole and reaction with aldehydes and ii) organomagnesium addition to 6-cyano-7-azaindole. Both methods shou
- Pillard, Christelle,Bassene, Carine Ekambome,Suzenet, Franck,Guillaumet, Gerald
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experimental part
p. 2049 - 2054
(2009/04/03)
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- The first practical and efficient one-pot synthesis of 6-substituted 7-azaindoles via a Reissert-Henze reaction
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A variety of 6-substituted 7-azaindoles (30 examples) were obtained via selective O-methylation of 7-azaindole-N-oxide m-chlorobenzoic acid salt and subsequent, base-catalyzed one-pot reaction with a range of N-, O-, S-nucleophiles or cyanide. Georg Thieme Verlag Stuttgart.
- Storz, Thomas,Bartberger, Michael D.,Sukits, Steven,Wilde, Chris,Soukup, Troy
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p. 201 - 214
(2008/12/21)
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- Synthesis of new substituted 2-(trimethylstannyl)indoles
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Synthesis of the previously unreported 2-(trimethylstannyl)indole derivatives, 5-bromo-1-(tert-butoxycarbonyl)-2-(trimethylstannyl)-1H-indole, 6-bromo-1-(tert-butoxycarbonyl)-2-(trimethylstannyl)-1H-indole, 1-(tert-butoxycarbonyl)-2-(trimethylstannyl)-1H-indole-5-carbonitrile, 1-(tert-butoxycarbonyl)-2-(trimethylstannyl)-1H-indole-6-carbonitrile and 1-(tert-butoxycarbonyl)-2-(trimethylstannyl)-1H-pyrrolo[2,3-b] pyridine-6-carbonitrile, is described. Georg Thieme Verlag Stuttgart.
- Kumar, Arvind,Say, Martial,Boykin, David W.
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p. 707 - 710
(2008/09/21)
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- COMPOUNDS AND METHODS OF USE
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Selected compounds are effective for prophylaxis and treatment of diseases, such as angiogenesis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
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Page/Page column 128
(2010/11/27)
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- Synthesis and Biological Activity of 1H-Pyrrolo[2,3-b]pyridine Derivatives: Correlation between Inhibitory Activity against the Fungus Causing Rice Blast and Ionization Potential
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Synthesis and biological activity of a variety of 3- and 6-substituted 1H-pyrrolo[2,3-6]pyridine (7-azaindole) derivatives are described. Many of the synthesized 7-azaindoles exhibited considerable fungicidal activity toward Pyricularia oryzae, a fungus which causes rice blast, in vivo. When quantum parameters of the tested 7-azaindoles were evaluated by semiempirical molecular orbital calculations, a relationship was observed between the activity and the calculated ionization potentials of the 7-azaindole derivatives.
- Minakata, Satoshi,Hamada, Takayuki,Komatsu, Mitsuo,Tsuboi, Hiroyuki,Kikuta, Hiroshige,Ohshiro, Yoshiki
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p. 2345 - 2348
(2007/10/03)
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