149914-98-7Relevant articles and documents
A Preclinical Candidate Targeting Mycobacterium tuberculosis KasA
Ahn, Yong-Mo,Alland, David,Awasthi, Divya,Capodagli, Glenn C.,Connell, Nancy,Freundlich, Joel S.,Grady, Courtney,Ho Liang, Hsin Pin,Inoyama, Daigo,Jadhav, Ravindra,Kumar, Pradeep,Li, Liping,Li, Shao-Gang,Mina, Marizel,Neiditch, Matthew B.,Park, Steven,Perlin, David S.,Richmann, Todd,Russo, Riccardo,Shrestha, Riju,Sukheja, Paridhi,Tsotetsi, Kholiswa,Wang, Xin,Zimmerman, Matthew,Dartois, Véronique
, p. 560 - 570 (2020)
Published Mycobacterium tuberculosis β-ketoacyl-ACP synthase KasA inhibitors lack sufficient potency and/or pharmacokinetic properties. A structure-based approach was used to optimize existing KasA inhibitor DG167. This afforded indazole JSF-3285 with a 30-fold increase in mouse plasma exposure. Biochemical, genetic, and X-ray studies confirmed JSF-3285 targets KasA. JSF-3285 offers substantial activity in an acute mouse model of infection and in the corresponding chronic infection model, with efficacious reductions in colony-forming units at doses as low as 5 mg/kg once daily orally and improvement of the efficacy of front-line drugs isoniazid or rifampicin. JSF-3285 is a promising preclinical candidate for tuberculosis. Inoyama et al. disclose the optimization of an indazole antitubercular targeting the β-ketoacyl-ACP synthase KasA. A structure-based approach has overcome significant issues with mouse metabolic stability and pharmacokinetics. A preclinical drug candidate has been delivered with efficacy in a mouse model of chronic M. tuberculosis infection at 5 mg/kg dosing.
A Serendipitous One-Pot Cyanation/Hydrolysis/Enamide Formation: Direct Access to 3-Methyleneisoindolin-1-ones
Banik, Trisha,Kaliappan, Krishna P.
, p. 628 - 633 (2020/12/09)
A direct, one-pot conversion of 2’-haloacetophenones to 3-methyleneisoindolin-1-one scaffolds using CuCN as the sole reagent without the need for moisture-free or anaerobic conditions is reported. This serendipitously discovered transformation with a broa
CHEMICAL COMPOUNDS
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Paragraph 0394-0396, (2021/01/23)
The present disclosure describes novel compounds, or their pharmaceutically acceptable salts, pharmaceutical compositions containing them, and their medical uses. Compounds of the disclosure have activity as dual modulators of Janus kinase (JAK), alone, or in combination with one or more of an additional mechanism, including a tyrosine kinase, such as TrkA or Syk, and PDE4, and are useful in the in the treatment or control of inflammation, auto-immune diseases, cancer, and other disorders and indications where modulation of JAK would be desirable. Also described herein are methods of treating inflammation, auto-immune diseases, cancer, and other conditions susceptible to inhibition of JAK and PDE4 by administering a compound herein described.
THERAPEUTIC INDOLES
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Page/Page column 27, (2019/03/17)
The invention provides compounds of formula I and salts thereof wherein R1-R4 have any of the meanings described in the specification. The compounds are useful for treating bacterial infections (e.g. tuberculosis).
The synthesis of chiral benzothiazine and thiazinoquinoline derivatives
Wang, Long,Priebbenow, Daniel L.,Chen, Xiao Yun,Pan, Fang-Fang,Bolm, Carsten
, p. 3338 - 3343 (2015/05/20)
The syntheses of a series of enantiopure conformationally restricted benzothiazine and thiazinoquinoline derivatives are presented. Key starting materials are 3-aminoacetophenone and (S)-S-methyl-S-phenylsulfoximine. By using a short reaction sequence, th
Electrophilic bromination of meta-substituted anilines with N-bromosuccinimide: Regioselectivity and solvent effect
Bartoli, Sandra,Cipollone, Amalia,Squarcia, Antonella,Madami, Andrea,Fattori, Daniela
experimental part, p. 1305 - 1308 (2009/12/24)
N-Bromosuccinimide-mediated electrophilic aromatic bromination of a series of anilines substituted with an electron-with-drawing group in the meta position was investigated. The regioselectivity of the reaction is markedly dependent on the polarity of the solvent and the bromination reaction can be tuned by appropriate selection of the reaction medium. Georg Thieme Verlag Stuttgart.
