869936-88-9

Upstream product

• 6928-85-4 N-amino-N'-methylpiperazine 
• 78755-94-9 5-fluoro-2H-benzo[d][1,3]-oxazine-2,4(1H)-dione 
• 434-76-4 2-amino-6-fluorobenzoic acid 

Relevant academic research and scientific papers

6-Fluorophenylbenzohydrazides inhibit Mycobacterium tuberculosis growth through alteration of tryptophan biosynthesis

A major constraint in reducing tuberculosis epidemic is the emergence of strains resistant to one or more of clinically approved antibiotics, which emphasizes the need of novel drugs with novel targets. Genetic knockout strains of Mycobacterium tuberculosis (Mtb) have established that tryptophan (Trp) biosynthesis is essential for the bacterium to survive in vivo and cause disease in animal models. An anthranilate-like compound, 6-FABA, was previously shown to synergize with the host immune response to Mtb infection in vivo. Herein, we present a class of anthranilate-like compounds endowed with good antimycobacterial activity and low cytotoxicity. We show how replacing the carboxylic moiety with a hydrazide led to a significant improvement in both activity and cytotoxicity relative to the parent compound 6-FABA. Several new benzohydrazides (compounds 20–31, 33, 34, 36, 38 and 39) showed good activities against Mtb (0.625 ≤ MIC≤6.25 μM) and demonstrated no detectable cytotoxicity against Vero cell assay (CC50 ≥ 1360 μM). The target preliminary studies confirmed the hypothesis that this new class of compounds inhibits Trp biosynthesis. Taken together, these findings indicate that fluorophenylbenzohydrazides represent good candidates to be assessed for drug discovery.

2-Arylaminopyrimidine derivatives as PLK inhibitors

Anilino-pyrimidine and 1,2,4-triazine compounds (1) are new. Anilino-pyrimidine and 1,2,4-triazine compounds of formula (1), their tautomers, racemates, enantiomers and/or diastereomers and acid-addition salts are new. X : NR 1a>, O or S; Y : CH or N; Z : hydrogen, halo, (halo)1-3C alkyl, 2-3C alkenyl, 2-3C alkynyl, formyl, 1-3C (halo)alkylcarbonyl, 2-3C alkenyl-, 2-3C alkynyl-carbonyl or pseudohalo; A : (hetero)aryl group (i) or (ii); R a> - R f>e.g. hydrogen, halo or nitro; R 1> and R 1a>hydrogen or methyl; R 2>e.g. Cl, Br, I, OR 6>; R 3>e.g. -CONR 1>-L-Q 3-Q 4-R 9>, -NR 1>-CO-L-Q 3-Q 4-R 9>; R 4>e.g. OR 6>, COR 6>, CONR 6>R 7>, NR 6>R 7>, NR 6>COR 7>, NR 6>SO 2R 7>, N=CR 6>R 7>, SR 6>, SOR 6>, SO 2R 6>, SO 2NR 6>R 7> or pseudohalogen, or any of 1-8C alkyl, 2-10C alkenyl or alkynyl, 3-8C cycloalkyl, (hetero)aryl or heterocyclyl; R 5>hydrogen, halo, trifluoromethyl, 1-3C alkyl or OR 6>; R 6>, R 7>e.g. hydrogen or any of 1-5C alkyl, 2-5C alkenyl or alkynyl, 3-10C cycloalkyl, (hetero)aryl or heterocyclyl; L : e.g. bond or residue of 1-16C alkyl, 2-16C alkenyl or alkynyl, 3-10C cycloalkyl, (hetero)aryl or heterocyclyl; Q 3 and Q 4bond or a mono- or bi-cyclic heterocyclyl, optionally substituted by one or more of Me, Et, halo, amino, hydroxy or pseudohalo; R 9>as L but not a bond; and T : N, O or S. Full definitions are given in the DEFINITIONS (Full Definitions) field. [Image] [Image] ACTIVITY : Cytostatic; Antiinflammatory; Immunosuppressive; Virucide; Anti-HIV; Dermatological; Nootropic; Neuroprotective; Nephrotropic; Vulnerary; Antibacterial; Fungicide; Antiparasitic; Antipsoriatic; Osteopathic; Cardiovascular-Gen; Vasotropic; Gastrointestinal-Gen. MECHANISM OF ACTION : Kinase inhibitor; Polo-like kinase (PLK) inhibitor. In a trial, (1) was found to have EC 50 against recombinant human PLK1 of below 5, generally 1 mu M. No results for specific compounds were given.