OPC-67683, a Nitro-Dihydro-Imidazooxazole Derivative with Promising Action against Tuberculosis In Vitro and In Mice 英文参考文献.docVIP

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OPC-67683, a Nitro-Dihydro-Imidazooxazole Derivative with Promising Action against Tuberculosis In Vitro and In Mice 英文参考文献.doc

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OPC-67683, a Nitro-Dihydro-Imidazooxazole Derivative with Promising Action against Tuberculosis In Vitro and In Mice 英文参考文献

o PL SMEDICINE OPC-67683,aNitro-Dihydro-Imidazooxazole DerivativewithPromisingAction againstTuberculosisInVitroandInMice Makoto Matsumoto1*,Hiroyuki Hashizume1,Tatsuo Tomishige1,Masanori Kawasaki1,Hidetsugu Tsubouchi2, Hirofumi Sasaki2,Yoshihiko Shimokawa3,Makoto Komatsu2 1 Microbiological Research Institute, Otsuka Pharmaceutical, Tokushima, Japan, 2 Medicinal Chemistry Research Institute, Otsuka Pharmaceutical, Tokushima, Japan, 3TokushimaResearchInstitute,OtsukaPharmaceutical,Tokushima,Japan Funding:OtsukaPharmaceutical wasthesolefinancialsupporterof thestudies.Thefunderhadnorole instudydesign,datacollectionand analysis,decisiontopublish,or preparationofthemanuscript. ABSTRACT Background Tuberculosis (TB) is still a leading cause of death worldwide. Almost a third of the world’s populationisinfectedwith TBbacilli,andeachyearapproximately8millionpeopledevelop activeTBand2milliondieasaresult.Today’sTBtreatment,whichdatesbacktothe1970s,is long and burdensome, requiring at least 6 mo of multidrug chemotherapy. The situation is further compounded by the emergence of multidrug-resistant TB (MDR-TB) and by the infection’slethalsynergywithHIV/AIDS.Globalhealthandphilanthropicorganizationsarenow pleadingfornewdruginterventionsthatcanaddresstheseunmetneedsinTBtreatment. CompetingInterests:Allofthe authorsareworkingasscientistsfor OtsukaPharmaceutical,the originatorandownerofOPC-67683 andsolefinancialsupporterofthe studies.However,thecompanyis notpubliclytraded,andnoneofthe authorshaveorareexpectedto havestockoptions. AcademicEditor:PhilipHopewell, UniversityofCaliforniaSan Francisco,UnitedStatesofAmerica MethodsandFindings HerewereportOPC-67683,anitro-dihydro-imidazooxazolederivativethatwasscreenedto helpcombattheunmetneedsinTBtreatment.Thecompoundisamycolicacidbiosynthesis inhibitor found to be free of mutagenicity and to possess highly potent activity against TB, includingMDR-TB,asshownbyitsexceptionallylowminimuminhibitoryconcentration(MIC) range of 0.006–0.024 lg/