- Structure-activity relationships for analogs of the tuberculosis drug bedaquiline with the naphthalene unit replaced by bicyclic heterocycles
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Replacing the naphthalene C-unit of the anti-tuberculosis drug bedaquiline with a range of bicyclic heterocycles of widely differing lipophilicity gave analogs with a 4.5-fold range in clogP values. The biological results for these compounds indicate on average a lower clogP limit of about 5.0 in this series for retention of potent inhibitory activity (MIC90s) against M.tb in culture. Some of the compounds also showed a significant reduction in inhibition of hERG channel potassium current compared with bedaquiline, but there was no common structural feature that distinguished these.
- Sutherland, Hamish S.,Tong, Amy S.T.,Choi, Peter J.,Conole, Daniel,Blaser, Adrian,Franzblau, Scott G.,Cooper, Christopher B.,Upton, Anna M.,Lotlikar, Manisha U.,Denny, William A.,Palmer, Brian D.
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- ANTIBACTERIAL COMPOUNDS AND USES THEREOF
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The present invention relates to compounds of formula (I) including any stereochemically isomeric form thereof, or pharmaceutically acceptable salts thereof, for the treatment of tuberculosis.
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- COMPOUNDS AND METHODS FOR MODULATING FXR
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Compounds of formula. wherein variables are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating dyslipidemia and related diseases.
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Page/Page column 21
(2008/06/13)
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- TRIAZOLOPYRAZINE COMPOUNDS USEFUL FOR THE TREATMENT OF DEGENERATIVE & INFLAMMATORY DISEASES
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Novel [1.2.4]triazolo[1,5-a]pyrazine compounds are disclosed that have a formula represented by the following (formula I). The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, arthritis, inflammation, and others.
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(2008/06/13)
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- Synthesis and biological activity of various derivatives of a novel class of potent, selective, and orally active prostaglandin D2 receptor antagonists. 2. 6,6-dimethylbicyclo[3.1.1]heptane derivatives
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In an earlier paper, we reported that novel prostaglandin D2 (PGD2) receptor antagonists having the bicyclo[2.2.1]heptane ring system as a prostaglandin skeleton were a potent new class of antiallergic agents and suppressed various allergic inflammatory responses such as those observed in conjunctivitis and asthma models. In the present study, we synthesized PGD2 receptor antagonists having the 6,6-dimethylbicyclo [3.1.1]heptane ring system. These derivatives have the amide moiety, in contrast to those with the bicyclo[2.2.1]heptane ring system, which have the sulfonamide group. The derivatives having the 6,6-dimethylbicyclo[3.1.1]heptane ring also exhibited strong activity in PGD2 receptor binding and cAMP formation assays. In in vivo assays such as allergic rhinitis, conjunctivitis, and asthma models, these series of derivatives showed excellent pharmacological profiles. In particular, compound 45 also effectively suppressed eosinophil infiltration in allergic rhinitis and asthma models. This compound (45, S-5751) is now being developed as a promising alternative antiallergic drug candidate.
- Mitsumori, Susumu,Tsuri, Tatsuo,Honma, Tsunetoshi,Hiramatsu, Yoshiharu,Okada, Toshihiko,Hashizume, Hiroshi,Inagaki, Masanao,Arimura, Akinori,Yasui, Kiyoshi,Asanuma, Fujio,Kishino, Junji,Ohtani, Mitsuaki
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p. 2446 - 2455
(2007/10/03)
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