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    • 2. 发明申请
    • NEW COMPOUNDS
    • 新化合物
    • WO2008107365A1
    • 2008-09-12
    • PCT/EP2008/052416
    • 2008-02-28
    • MEDIVIR ABBELDA, OscarSUND, ChristianIVANOV, VladimirWIKTELIUS, DanielSAHLBERG, ChristerSAMUELSSON, BertilROSENQUIST, ÅsaWÅNGSELL, FredrikKVARNSTRÖM, Ingemar
    • BELDA, OscarSUND, ChristianIVANOV, VladimirWIKTELIUS, DanielSAHLBERG, ChristerSAMUELSSON, BertilROSENQUIST, ÅsaWÅNGSELL, FredrikKVARNSTRÖM, Ingemar
    • A61K31/44C07D213/40C07C237/12C07D213/38
    • C07D307/33C07C237/22C07C255/60C07D213/38C07D213/40
    • The invention provides compounds of the formula I wherein Q is aryl or heterocyclyl any of which is optionally substituted; Z is O, S, NRa or S(=O) p ; Y is NH, NHNH, CH 2 NH, O, S or S(=O) p ; n is 0, 1, 2 or 3; m is 0, 1 or 2; p is 1 or 2; Ra is H or C 1 -C 4 alkyl; R 1 is hydrogen, C 1 -C 6 alkyl, C 0 -C 3 alkanediylC 3 -C 7 cycloalkyl, C 0 -C 3 alkanediylaryl or C 0 - C3alkanediylheterocyclyl; R 2 is hydrogen or C 1 -C 6 alkyl; X' is hydrogen, fluoro, hydroxy, amino or C 1 -C 6 alkoxy; X" is hydrogen, or when X' is fluoro, then X" may also be fluoro; R 3 is C 1 -C 6 alkyl; R 4' is C 1 -C 6 alkyl; R 4" is H or C 1 -C 6 alkyl; or R 4' and R 4" together with the carbon atom to which they are attached define a C 3 -C 6 cycloalkyl; W is C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, aryl or heterocyclyl any of which is optionally substituted; or a pharmaceutically acceptable salt, hydrate or N-oxide thereof. The compounds of the invention are inhibitors of aspartyl proteases such as renin and are among other things useful for the treatment of conditions associated with activities of the RAS, such as hypertension, heart failure and renal insufficiency.
    • 本发明提供式I化合物,其中Q是任选被取代的芳基或杂环基; Z是O,S,NR a或S(= O)p。 Y是NH,NHNH,CH 2 NH,O,S或S(= O)p; n为0,1,2或3; m为0,1或2; p为1或2; R a是H或C 1 -C 4烷基; R 1是氢,C 1 -C 6烷基,C 0 -C 3 - 烷二基C 3 -C 7环烷基,C 0 -C 3烷二基芳基或C 0 < / C3-烷二基杂环基; R 2是氢或C 1 -C 6烷基; R 2是氢或C 1 -C 6烷基; X'是氢,氟,羟基,氨基或C 1 -C 6烷氧基; X“是氢,或者当X'是氟时,X”也可以是氟; R 3是C 1 -C 6烷基; R 3是C 1 -C 6烷基; R 4是C 1 -C 6烷基; R 4是C 1 -C 6烷基; R 4是H或C 1 -C 6烷基;或R 4'和R“ 4“与它们所连接的碳原子一起定义为C 3 -C 6环烷基; W是C 1 -C 6烷基,C 3 -C 7环烷基,芳基或杂环基,其中任何一个 任选地被取代; 或其药学上可接受的盐,水合物或N-氧化物。 本发明的化合物是天冬氨酰蛋白酶如肾素的抑制剂,并且其它可用于治疗与RAS活性有关的病症,例如高血压,心力衰竭和肾功能不全。
    • 5. 发明申请
    • PROTEASE INHIBITORS
    • PROTEASE抑制剂
    • WO2010034789A1
    • 2010-04-01
    • PCT/EP2009/062407
    • 2009-09-24
    • Medivir ABIVANOV, VladimirSAMUELSSON, BertilJOHANSSON, Per-OlaKAHNBERG, PiaWÄHLING, Horst
    • IVANOV, VladimirSAMUELSSON, BertilJOHANSSON, Per-OlaKAHNBERG, PiaWÄHLING, Horst
    • C07D491/048A61K31/496A61P19/00
    • C07D491/048
    • Compounds of the formula II, wherein R 3 is C 1 -C 3 alkyl or C 3 -C 6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R 3 is C 3 -C 6 cycloalkyl it may alternatively be gem substituted with fluoro; R 4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A 1 is CH or N, A 2 is CR 6 R 7 or NR 6 , provided at least one of A 1 and A 2 comprises N; n is 0 or 1 such that the ring containing A 1 and A 2 is a saturated, nitrogen-containing ring of 5 or 6 ring atoms; R 6 is H, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 3 alkyl-O-C 1 -C 3 alkyl, or when A 2 is C, R 6 can also be C 1 -C 4 alkoxy or F; R 7 is H, C 1 -C 4 alkyl or F; or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.
    • 其中R 3为C 1 -C 3烷基或C 3 -C 6环烷基,其中R 3为C 3 -C 6环烷基时,任选被一个或两个甲基和/或氟,三氟甲基或甲氧基取代, 被氟取代; R4是甲基或氟; m为0,1或2; E是任选被甲基或氟取代的键或噻唑基; A1是CH或N,A2是CR6R7或NR6,条件是A1和A2中的至少一个包括N; n为0或1,使得含有A 1和A 2的环是5或6个环原子的饱和的含氮环; R6是H,C1-C4烷基,C1-C4卤代烷基,C1-C3烷基-O-C1-C3烷基,或当A2是C时,R6也可以是C1-C4烷氧基或F; R 7为H,C 1 -C 4烷基或F; 或其药学上可接受的盐,N-氧化物或其水合物,可用于治疗组织蛋白酶K不适当表达或活化的疾病,例如骨质疏松症,骨关节炎,类风湿性关节炎或骨转移。
    • 6. 发明申请
    • RADIATION SOURCE
    • 辐射源
    • WO2013029906A1
    • 2013-03-07
    • PCT/EP2012/065037
    • 2012-08-01
    • ASML NETHERLANDS B.V.YAKUNIN, AndreiIVANOV, VladimirVAN SCHOOT, JanKRIVTSUN, VladimirSWINKELS, GerardusMEDVEDEV, Viacheslav
    • YAKUNIN, AndreiIVANOV, VladimirVAN SCHOOT, JanKRIVTSUN, VladimirSWINKELS, GerardusMEDVEDEV, Viacheslav
    • H05G2/00G03F7/20
    • G03F7/70033H05G2/005H05G2/006H05G2/008
    • A radiation source (60) suitable for providing a beam of radiation to an illuminator of a lithographic apparatus. The radiation source comprises a nozzle configured to direct a stream of fuel droplets (62) along a trajectory (64) towards a plasma formation location (66). The radiation source is configured to receive a first amount of radiation (68) such that the first amount of radiation is incident on a fuel droplet (62a) at the plasma formation location, and such that the first amount of radiation transfers energy into the fuel droplet to generate a modified fuel distribution (70), the modified fuel distribution having a surface. The radiation source is also configured to receive a second amount of radiation (72) such that the second amount of radiation is incident on a portion of the surface (70a) of the modified fuel distribution, the second amount of radiation having a p-polarized component with respect to the portion of the surface; and such that the second amount of radiation transfers energy to the modified fuel distribution to generate a radiation generating plasma, the radiation generating plasma emitting a third amount of radiation (74). The radiation source further comprises a collector (CO) configured to collect and direct at least a portion of the third amount of radiation. The radiation source is configured such that the second amount of radiation propagates in a first direction, the first direction being non-parallel to a normal to the portion of the surface of the modified fuel distribution.
    • 适于向光刻设备的照明器提供辐射束的辐射源(60)。 辐射源包括被配置为沿着轨迹(64)将燃料液滴(62)流引向等离子体形成位置(66)的喷嘴。 辐射源被配置为接收第一量的辐射(68),使得第一量的辐射入射在等离子体形成位置处的燃料液滴(62a)上,并且使得第一量的辐射将能量转移到燃料 液滴以产生改进的燃料分配(70),所述改进的燃料分布具有表面。 辐射源还被配置为接收第二数量的辐射(72),使得第二量的辐射入射在改性燃料分布的表面(70a)的一部分上,第二量的辐射具有p偏振 相对于表面的部分; 并且使得第二量的辐射将能量传递到经修改的燃料分布以产生辐射产生等离子体,该辐射产生等离子体发射第三量的辐射(74)。 辐射源还包括收集器(CO),其被配置成收集并引导第三量的辐射的至少一部分。 辐射源被配置成使得第二数量的辐射在第一方向上传播,第一方向不平行于改性燃料分布的表面部分的法线。