000			03579nam a22005177a 4500
001			sulb-eb0025954
003			BD-SySUS
005			20160413122557.0
007			cr nn 008mamaa
008			131007s2013 ja | s |||| 0|eng d
020			_a9784431544456 _9978-4-431-54445-6
024	7		_a10.1007/978-4-431-54445-6 _2doi
050		4	_aQD415-436
072		7	_aPNN _2bicssc
072		7	_aSCI013040 _2bisacsh
082	0	4	_a547 _223
100	1		_aMizuhara, Tsukasa. _eauthor.
245	1	0	_aDevelopment of Novel Anti-HIV Pyrimidobenzothiazine Derivatives _h[electronic resource] / _cby Tsukasa Mizuhara.
264		1	_aTokyo : _bSpringer Japan : _bImprint: Springer, _c2013.
300			_aXI, 151 p. 98 illus., 3 illus. in color. _bonline resource.
336			_atext _btxt _2rdacontent
337			_acomputer _bc _2rdamedia
338			_aonline resource _bcr _2rdacarrier
347			_atext file _bPDF _2rda
490	1		_aSpringer Theses, Recognizing Outstanding Ph.D. Research, _x2190-5053
505	0		_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.
520			_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.
650		0	_aChemistry.
650		0	_aPharmaceutical technology.
650		0	_aVirology.
650		0	_aOrganic chemistry.
650		0	_aMedicinal chemistry.
650	1	4	_aChemistry.
650	2	4	_aOrganic Chemistry.
650	2	4	_aPharmaceutical Sciences/Technology.
650	2	4	_aMedicinal Chemistry.
650	2	4	_aVirology.
710	2		_aSpringerLink (Online service)
773	0		_tSpringer eBooks
776	0	8	_iPrinted edition: _z9784431544449
830		0	_aSpringer Theses, Recognizing Outstanding Ph.D. Research, _x2190-5053
856	4	0	_uhttp://dx.doi.org/10.1007/978-4-431-54445-6
912			_aZDB-2-CMS
942			_2Dewey Decimal Classification _ceBooks
999			_c48046 _d48046