LEADER 04285nam 22006735 450 001 9910437811403321 005 20200706200752.0 010 $a4-431-54445-3 024 7 $a10.1007/978-4-431-54445-6 035 $a(CKB)3710000000024456 035 $a(EBL)1538836 035 $a(SSID)ssj0001049151 035 $a(PQKBManifestationID)11579120 035 $a(PQKBTitleCode)TC0001049151 035 $a(PQKBWorkID)11017236 035 $a(PQKB)10919884 035 $a(DE-He213)978-4-431-54445-6 035 $a(MiAaPQ)EBC1538836 035 $a(PPN)176126120 035 $a(EXLCZ)993710000000024456 100 $a20131007d2013 u| 0 101 0 $aeng 135 $aur|n|---||||| 181 $ctxt 182 $cc 183 $acr 200 10$aDevelopment of Novel Anti-HIV Pyrimidobenzothiazine Derivatives /$fby Tsukasa Mizuhara 205 $a1st ed. 2013. 210 1$aTokyo :$cSpringer Japan :$cImprint: Springer,$d2013. 215 $a1 online resource (157 p.) 225 1 $aSpringer Theses, Recognizing Outstanding Ph.D. Research,$x2190-5053 300 $aDescription based upon print version of record. 311 $a4-431-54444-5 320 $aIncludes bibliographical references. 327 $aIntroduction -- Development of Divergent Synthetic Methods of Pyrimidobenzothiazine and Related Tricyclic Heterocycles -- Structure?Activity Relationship Study of PD 404182 Derivatives for the Highly Potent Anti-HIV Agents.- Design and Synthesis of Photoaffinity Probes and Their Application to Target Identification Study of PD 404182 -- Conclusion. 330 $aThe author successfully developed novel anti-HIV PD 404182 derivatives that exhibited submicromolar inhibitory activity against both HIV-1 and HIV-2. His thesis is in three parts. The first part expounds efficient methods for the synthesis of tricyclic heterocycles related to PD 404182 based on the sp2-carbon?heteroatom bond formations. Starting from arene or haloarene, C-O, C-N, or C-S bonds were formed by simply changing the reactants. These synthetic methods provide powerful approaches for the divergent preparation of pyrimido-benzoxazine, -quinazoline, or -benzothiazine derivatives. The second part explains SAR studies of PD 404182 for the development of anti-HIV agents. Through optimization studies of the central 1,3-thiazin-2-imine core, the benzene and cyclic amidine ring parts, 3-fold more potent inhibitors were obtained compared with the lead compound. The author also reveals by a time-of-drug-addition experiment that PD 404182 derivatives impaired HIV replication at the binding or fusion stage. The third part of the thesis elucidates the development of photoaffinity probes for the target identification of PD 404182. By the photolabeling experiment of HIV-1-infected H9 cells using these probes, the author detected proteins specifically bound to PD 404182. These new anti-HIV agents may be promising agents for anti-HIV therapy because their mechanisms of action differ from those of the currently approved anti-HIV agents. 410 0$aSpringer Theses, Recognizing Outstanding Ph.D. Research,$x2190-5053 606 $aOrganic chemistry 606 $aPharmaceutical technology 606 $aMedicinal chemistry 606 $aVirology 606 $aOrganic Chemistry$3https://scigraph.springernature.com/ontologies/product-market-codes/C19007 606 $aPharmaceutical Sciences/Technology$3https://scigraph.springernature.com/ontologies/product-market-codes/B21010 606 $aMedicinal Chemistry$3https://scigraph.springernature.com/ontologies/product-market-codes/C28000 606 $aVirology$3https://scigraph.springernature.com/ontologies/product-market-codes/B22003 615 0$aOrganic chemistry. 615 0$aPharmaceutical technology. 615 0$aMedicinal chemistry. 615 0$aVirology. 615 14$aOrganic Chemistry. 615 24$aPharmaceutical Sciences/Technology. 615 24$aMedicinal Chemistry. 615 24$aVirology. 676 $a616.9792 700 $aMizuhara$b Tsukasa$4aut$4http://id.loc.gov/vocabulary/relators/aut$01065629 906 $aBOOK 912 $a9910437811403321 996 $aDevelopment of Novel Anti-HIV Pyrimidobenzothiazine Derivatives$92547232 997 $aUNINA