- TETRAHYDROPYRAZOLO [1,5-A] PYRIMIDINE AS ANTI-TUBERCULOSIS COMPOUNDS
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A compound of Formula (I) or a pharmaceutically acceptable salt thereof: wherein: R1 represents a group selected from: i) phenyl optionally substituted with one or two substituents independently selected from Me, OMe, CF3, F, Cl and NMe2;furanyl, thiophenyl, pyrrolyl, pyridyl, cyclohexyl or naphthyl, each of which is optionally substituted with one or two substituents independently selected from Me, OMe, CF3, F, Cl and NMe2; andiii) benzo[1,3]dioxo5-yl or 2,3-dihydrobenzo[1,4]dioxin-6-yl; R2 represents CF3, C1-4alkyl, or CHF2; when R1 represents optionally substituted furanyl, thiophenyl, pyrrolyl, pyridyl or naphthyl, R3 represents Et; when R1 represents optionally substituted cyclohexyl, R3 represents Et or Me; otherwise R3 represents Et, Me, Br or OMe, compositions containing them, their use in therapy, for example in the treatment of tuberculosis, and methods for the preparation of such compounds, are provided, together with certain novel compounds.
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Paragraph 0246; 0249
(2014/02/16)
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- Discovery of tetrahydropyrazolopyrimidine carboxamide derivatives as potent and orally active antitubercular agents
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Tetrahydropyrazolo[1,5-a]pyrimidine scaffold was identified as a hit series from a Mycobacterium tuberculosis (Mtb) whole cell high through-put screening (HTS) campaign. A series of derivatives of this class were synthesized to evaluate their structure-activity relationship (SAR) and structure-property relationship (SPR). Compound 9 had a promising in vivo DMPK profile in mouse and exhibited potent in vivo activity in a mouse efficacy model, achieving a reduction of 3.5 log CFU of Mtb after oral administration to infected mice once a day at 100 mg/kg for 28 days. Thus, compound 9 is a potential candidate for inclusion in combination therapies for both drug-sensitive and drug-resistant TB.
- Yokokawa, Fumiaki,Wang, Gang,Chan, Wai Ling,Ang, Shi Hua,Wong, Josephine,Ma, Ida,Rao, Srinivasa P. S.,Manjunatha, Ujjini,Lakshminarayana, Suresh B.,Herve, Maxime,Kounde, Cyrille,Tan, Bee Huat,Thayalan, Pamela,Ng, Seow Hwee,Nanjundappa, Mahesh,Ravindran, Sindhu,Gee, Peck,Tan, Maria,Wei, Liu,Goh, Anne,Chen, Pei-Yu,Lee, Kok Sin,Zhong, Chen,Wagner, Trixie,Dix, Ina,Chatterjee, Arnab K.,Pethe, Kevin,Kuhen, Kelli,Glynne, Richard,Smith, Paul,Bifani, Pablo,Jiricek, Jan
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p. 451 - 455
(2013/07/11)
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- TETRAHYDROPYRAZOLO [1,5 -A] PYRIMIDINE AS ANTI -TUBERCULOSIS COMPOUNDS
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A compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 represents a group selected from: i) phenyl optionally substituted with one or two substituents independently selected from Me, OMe, CF3, F, CI and NMe2; ii) furanyl, thiophenyl, pyrrolyl, pyridyl, cyclohexyl or naphthyl, each of which is optionally substituted with one or two substituents independently selected from Me, OMe, CF3, F, CI and NMe2; and iii) benzo[1,3]dioxo5-yl or 2,3-dihydrobenzo[1,4]dioxin-6-yl; R2 represents CF3, C1-4alkyl, or CHF2; When R1 represents optionally substituted furanyl, thiophenyl, pyrrolyl, pyridyl or naphthyl, R3 represents Et; When R1 represents optionally substituted cyclohexyl, R3 represents Et or Me; Otherwise R3 represents Et, Me, Br or OMe, compositions containing them, their use in therapy, for example in the treatment of tuberculosis, and methods for the preparation of such compounds, are provided, together with certain novel compounds
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Page/Page column 26
(2012/11/07)
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