15644-88-9Relevant articles and documents
Synthesis of (E)-2-(4,7-dichloroquinolin-2-yl)-3-dimethylamino-2-propene-1-al and its use as a synthetic intermediate
De, Dibyendu,Mague, Joel T.,Byers, Larry D.,Krogstad, Donald J.
, p. 205 - 208 (1995)
A novel synthesis is described for (E)-2-(4,7-dichloroquinolin-2-yl)-3-dimethylamino-2-propene-1-al (4), which reacts with nucleophiles to yield heterocycle-substituted 4,7-dichloroquinolines (5-7).
Novel, potent, orally bioavailable and selective mycobacterial ATP synthase inhibitors that demonstrated activity against both replicating and non-replicating M. tuberculosis
Singh, Supriya,Roy, Kuldeep K.,Khan, Shaheb R.,Kashyap, Vivek Kr.,Sharma, Abhisheak,Jaiswal, Swati,Sharma, Sandeep K.,Krishnan, Manju Yasoda,Chaturvedi, Vineeta,Lal, Jawahar,Sinha, Sudhir,Gupta, Arnab D.,Srivastava, Ranjana,Saxena, Anil K.
supporting information, p. 742 - 752 (2015/02/19)
The mycobacterial F0F1-ATP synthase (ATPase) is a validated target for the development of tuberculosis (TB) therapeutics. Therefore, a series of eighteen novel compounds has been designed, synthesized and evaluated against Mycobacterium smegmatis ATPase. The observed ATPase inhibitory activities (IC50) of these compounds range between 0.36 and 5.45 μM. The lead compound 9d [N-(7-chloro-2-methylquinolin-4-yl)-N-(3-((diethylamino)methyl)-4-hydroxyphenyl)-2,3-dichlorobenzenesulfonamide] with null cytotoxicity (CC50 >300 μg/mL) and excellent anti-mycobacterial activity and selectivity (mycobacterium ATPase IC50 = 0.51 μM, mammalian ATPase IC50 >100 μM, and selectivity >200) exhibited a complete growth inhibition of replicating Mycobacterium tuberculosis H37Rv at 3.12 μg/mL. In addition, it also exhibited bactericidal effect (approximately 2.4 log10 reductions in CFU) in the hypoxic culture of non-replicating M. tuberculosis at 100 μg/mL (32-fold of its MIC) as compared to positive control isoniazid [approximately 0.2 log10 reduction in CFU at 5 μg/mL (50-fold of its MIC)]. The pharmacokinetics of 9d after p.o. and IV administration in male Sprague-Dawley rats indicated its quick absorption, distribution and slow elimination. It exhibited a high volume of distribution (Vss, 0.41 L/kg), moderate clearance (0.06 L/h/kg), long half-life (4.2 h) and low absolute bioavailability (1.72%). In the murine model system of chronic TB, 9d showed 2.12 log10 reductions in CFU in both lung and spleen at 173 μmol/kg dose as compared to the growth of untreated control group of Balb/C male mice infected with replicating M. tuberculosis H37Rv. The in vivo efficacy of 9d is at least double of the control drug ethambutol. These results suggest 9d as a promising candidate molecule for further preclinical evaluation against resistant TB strains.
N-(3-((DIETHYLAMINO) METHYL)-4-HYDROXYPHENYL)-N-(QUINOLIN-4-YL) SULFONAMIDES FOR THE TREATMENT OF TUBERCULOSIS AND PROCESS OF PREPARATION THEREOF
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Page/Page column 12-13, (2013/07/19)
The present invention relates to novel N-(3-((diethylamino)methyl)-4-hydroxyphenyl)-N-(quinolin-4- yl)sulfonamide derivatives, their preparation, to pharmaceutical compositions comprising them, and to their use as therapeutic agents, particularly in the prevention or treatment of tuberculosis. The present invention particularly relates to compounds of formula A[Formula I]: wherein: R = methyl, (or) R = a group of the structure [Formula II] wherein, R1, R2, and R3 may be same or different present at any position(s) and are groups selected from the group consisting of hydrogen, halogen, alkyl (C1-C3), nitro, cyano, trifluoromethyl, (or) R is a group of the structure [Formula III] wherein X may be CH or N, and the attachment point of sulfonyl may be at the position 1 or 2, (or) R is a group of the structure [Formula IV] Where R1 is hydrogen or halogen, (or) R is a group of the structure. [Formula V]