- A Journey through Hemetsberger–Knittel, Leimgruber–Batcho and Bartoli Reactions: Access to Several Hydroxy 5- and 6-Azaindoles
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The preparation of various 5- and 6-azaindoles, heterocyclic structures that are frequently part of molecules in clinical development, and their monohydroxy analogues were described. Different strategies, relying on the de novo pyrrole ring formation, were investigated and, thanks to Hemetsberger–Knittel, Bartoli and Leimgruber–Batcho approaches, 4- and 7-monohydroxy 5- and 6-azaindoles were obtained. The crucial introduction of the oxygen atom was carried out from halogen derivatives, using nucleophilic substitution reactions under basic conditions with or without a copper catalyst. Some preliminary oxidation reactions have shown that it was yet not possible to synthesize the azaquinone indole structure from monohydroxy azaindole, using molecular oxygen in the presence of salcomine as a catalyst.
- Radix, Sylvie,Hallé, Fran?ois,Mahiout, Zahia,Teissonnière, Amélie,Bouchez, Grégoire,Auberger, Ludovic,Barret, Roland,Lomberget, Thierry
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- AZAINDOLE CARBOXAMIDE COMPOUNDS FOR THE TREATMENT OF MYCOBACTERIAL INFECTIONS
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Provided herein are compounds of Formula (I) and Formula (II): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of tuberculosis.
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Page/Page column 115
(2021/04/02)
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- 1-(2-hydroxy-2-methyl-3-phenoxypropanoyl)indoline-4-carbonitrile derivatives as potent and tissue selective androgen receptor modulators
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We present a novel series of selective androgen receptor modulators (SARMs) which shows excellent biological activity and physical properties. 1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)-indoline-4-carbonitriles showed potent binding to the androgen receptor (AR) and activated AR-mediated transcription in vitro. Representative compounds demonstrated diminished activity in promoting the intramolecular interaction between the AR carboxyl (C) and amino (N) termini. This N/C-termini interaction is a biomarker assay for the undesired androgenic responses in vivo. In orchidectomized rats, daily administration of a lead compound from this series showed anabolic activity by increasing levator ani muscle weight. Importantly, minimal androgenic effects (increased tissue weights) were observed in the prostate and seminal vesicles, along with minimal repression of circulating luteinizing hormone (LH) levels and no change in the lipid and triglyceride levels. This lead compound completed a two week rat toxicology study, and was well tolerated at doses up to 100 mg/kg/day, the highest dose tested, for 14 consecutive days.
- Chekler, Eugene L. Piatnitski,Unwalla, Rayomond,Khan, Taukeer A.,Tangirala, Raghuram S.,Johnson, Mark,St. Andre, Michael,Anderson, James T.,Kenney, Thomas,Chiparri, Sue,McNally, Chris,Kilbourne, Edward,Thompson, Catherine,Nagpal, Sunil,Weber, Gregory,Schelling, Scott,Owens, Jane,Morris, Carl A.,Powell, Dennis,Verhoest, Patrick R.,Gilbert, Adam M.
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p. 2462 - 2471
(2014/04/17)
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- Azaindolines: Derisking the indoline structural alert
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4-Substitued azaindolines, which are isosteres of indolines, are useful synthetic building blocks that reduce the risk of bioactivation induced idiosyncratic toxicity have been prepared. Multigram routes to 2,3-dihydro-1H-pyrrolo[2,3-c]pyridine-4-triflate 16, 2,3-dihydro-1H-pyrrolo[2,3- b]pyridine-4-carbonitrile 20 and 4-chloro-2,3-dihydro-1H-pyrrolo[2,3-d] pyridazine 30 are outlined.
- Piatnitski Chekler, Eugene L.,Khan, Taukeer A.,Mamidala, Rajanikanth,Anderson, James T.,Tangirala, Raghuram S.,Verhoest, Patrick R.,Gilbert, Adam M.
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p. 377 - 379
(2012/01/31)
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- COMPOUNDS
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The present invention discloses novel compounds having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders.
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Page/Page column 25
(2010/12/31)
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- INDAZOLECARBOXAMIDE DERIVATIVES FOR THE TREATMENT AND PREVENTION OF MALARIA
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The invention relates to methods of treating or preventing malaria which comprises administering to a patient in need thereof, an effective amount of a 1H-indazole-3-carboxamide derivative of general formula (I), in the form of a base or of an addition salt with an acid, or in the form of a hydrate or of a solvate of said base or acid addition salt.
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Page/Page column 12
(2010/11/28)
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- Indazolecarboxamide derivatives, preparation and use thereof as CDK1, CDK2 and CDK4 inhibitors
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Compound corresponding to general formula (I): [image] in which, R1 represents a hydrogen or halogen atom, an NH2, NHR2, NHCOR2, NO2, CN, CH2NH2 and CH2NHR2; or alternatively R1 represents an optionally substituted phenyl or an optionally substituted heteroaromatic group; Ar represents an optionally substituted phenyl group or an optionally substituted heteroaromatic group; n represents 0, 1, 2 or 3; in the form of a base, of an addition salt with an acid, of a hydrate or of a solvate. Application in therapy.
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Page/Page column 24
(2008/06/13)
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- 3,5 Disubstituted indazole compounds with nitrogen-bearing 5-membered heterocycles, pharmaceutical compositions, and methods for mediating or inhibiting cell proliferation
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3,5 disubstituted indazole compounds with substituted nitrogen bearing 5-membered heterocycles in the 3-position that modulate and/or inhibit cell proliferation, such as the activity of protein kinases are described. These compounds and pharmaceutical com
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Page/Page column 82-83
(2010/02/11)
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