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21. 发明申请

WO1993023388A1 METHOD FOR MAKING INTERMEDIATES USEFUL IN SYNTHESIS OF RETROVIRAL PROTEASE INHIBITORS 审中-公开
标题翻译：制备中间体的方法，用于合成抗病毒蛋白酶抑制剂
公开(公告)号：WO1993023388A1
公开(公告)日：1993-11-25
申请号：PCT/US1993004804
申请日：1993-05-20
申请人： G.D. SEARLE & CO. , THE MONSANTO COMPANY , NG, John, S. , PRZYBYLA, Claire, A. , MUELLER, Richard, A. , VAZQUEZ, Michael, L. , GETMAN, Daniel, P.
发明人： G.D. SEARLE & CO. , THE MONSANTO COMPANY
IPC分类号： C07D303/36
CPC分类号： C07K5/0207 , C07B2200/07 , C07C213/00 , C07C213/02 , C07C213/08 , C07C275/22 , C07C275/24 , C07C317/44 , C07D215/48 , C07D303/36 , Y02P20/55 , C07C215/08 , C07C215/28
摘要： A synthesis is described for intermediates which are readily amenable to the large scale preparation of hydroxyethylurea-based chiral HIV protease inhibitors. The method includes forming a diastereoselective epoxide compound of formula (I) from a chiral alpha amino aldehyde and halomethyllithium as an organometallic methylene-adding reagent. In formula (I) R is selected from alkyl, aryl, cycloalkyl, cycloalkylalkyl and arylalkyl, which are optionally substituted with a group selected from alkyl, halogen, NO2, OR or SR , where R represents hydrogen or alkyl; and P and P independently are selected from amine protecting groups, including but not limited to, arylalkyl, substituted arylalkyl, cycloalkenylalkyl and substituted cycloalkenylalkyl, allyl, substituted allyl, acyl, alkoxycarbonyl, aralkoxycarbonyl and silyl.
摘要翻译：对于易于大规模制备基于羟基脲的手性HIV蛋白酶抑制剂的中间体描述了合成。该方法包括由手性α氨基醛和卤代甲基锂作为有机金属亚甲基加成试剂形成式（I）的非对映选择性环氧化合物。在式（I）中，R 1选自烷基，芳基，环烷基，环烷基烷基和芳烷基，其任选被选自烷基，卤素，NO 2，OR 9或SR 9取代， 9>表示氢或烷基; 并且P 1和P 2独立地选自胺保护基团，包括但不限于芳基烷基，取代的芳基烷基，环烯基烷基和取代的环烯基烷基，烯丙基，取代的烯丙基，酰基，烷氧基羰基，芳烷氧基羰基和甲硅烷基。

22. 发明申请

WO1992004026A1 USE OF 4-HYDROXYPHENYL-THIOETHERS FOR STIMULATING SUPEROXIDE GENERATION 审中-公开
标题翻译：用于刺激超氧化物生成的4-羟基苯基硫醚的使用
公开(公告)号：WO1992004026A1
公开(公告)日：1992-03-19
申请号：PCT/US1991005298
申请日：1991-07-31
申请人： G.D. SEARLE & CO. , MUELLER, Richard, August , NAKAO, Akira , PARTIS, Richard, Allen
发明人： G.D. SEARLE & CO.
IPC分类号： A61K31/44
CPC分类号： A61K31/165 , A61K31/10 , A61K31/44 , A61K31/495
摘要： The present invention is directed to a method of stimulating superoxide generation using phenolic thioethers which stimulate the generation of superoxide.

23. 发明申请

WO2004064607A3 BREAST NIPPLE DUCT PROTECTIVE DEVICE 审中-公开
标题翻译：乳房NIPPLE DUCT保护装置
公开(公告)号：WO2004064607A3
公开(公告)日：2006-09-28
申请号：PCT/US2004001539
申请日：2004-01-21
申请人： ACUEITY INC , MUELLER RICHARD L JR
发明人： MUELLER RICHARD L JR
IPC分类号： A61M5/00 , A61B10/00
CPC分类号： A61B10/0041 , A61B10/0045
摘要： A breast nipple duct protective device of the present invention comprises a post having a longitudinal axis, a distal end and a proximal end. The post has an anchor at the distal end, and a grip at the proximal end. The post has an outside diameter of no more than about 0.5 millimeters, and the anchor has a transverse dimension at least about 1.25 times the outside diameter of the post. The transverse dimension of the anchor is selected to be small enough to be pushed through the nipple duct orifice without causing damage to the duct, but large enough to hold the device in place in the duct for a prolonged period of days to weeks. The grip is dimensioned to prevent the device from entering the duct any further than the sum of the lengths of the post and the anchor. The anchor can have an articulating form with an adjustable transverse dimension. The device may also be utilized as a decorative breast nipple ornament.
摘要翻译：本发明的乳房乳头管道保护装置包括具有纵向轴线，远端和近端的柱。该柱在远端具有锚固件，并且在近端具有抓握部。该柱具有不大于约0.5毫米的外径，并且锚具有至少约1.25倍柱的外径的横向尺寸。锚固件的横向尺寸被选择为足够小以被推过乳头管孔而不会损坏管道，但是足够大以将装置保持在管道中的适当位置，持续长达数天至数周。该把手的尺寸被设计成防止装置进一步比柱和锚的长度总和进一步。锚固件可以具有可调横向尺寸的铰接形式。该装置还可以用作装饰性乳房乳头装饰品。

24. 发明申请

WO2004089245A2 BONE ANCHOR 审中-公开
标题翻译：骨锚
公开(公告)号：WO2004089245A2
公开(公告)日：2004-10-21
申请号：PCT/US2004/010319
申请日：2004-04-02
申请人： THEKEN SURGICAL, LLC , MUELLER, Richard
发明人： MUELLER, Richard
IPC分类号： A61F
CPC分类号： A61B17/7037 , A61B17/7032
摘要： A spinal rod and bone for anchoring a spinal rod to a bone anchor is provided for use in polyaxial constructs as well as non-polyaxial constructs. In general, a bone anchor is provided having a proximal end for engaging a rod and securing the rod with a coming or threaded locking assembly, and a distal end for engaging the bone. A partially cylindrical body is provided at the proximal end of the apparatus having opposed flanges and a rod-receiving channel therebetween. The locking device comprises an upper wave cap and a lower cap joined by a post with preset timing grooves therein, and having camming surfaces therebetween. The upper cap has an opening for engaging a drive mechanism and the lower cap has a surface for engaging the rod. Alternatively, the locking device comprises external camming configurations or threaded configurations.
摘要翻译：提供用于将脊柱杆锚定到骨锚的脊柱杆和骨用于多轴构造以及非多轴构造。通常，提供骨锚固件，其具有用于接合杆的近端和用落下或螺纹锁定组件固定杆以及用于接合骨的远端。在具有相对的凸缘的设备的近端处设置有部分圆柱形的主体，并且在它们之间具有杆接收通道。锁定装置包括上波帽和下盖，所述上波帽和下盖通过其中预定的定时凹槽的柱连接，并且在其间具有凸轮表面。上盖具有用于接合驱动机构的开口，并且下盖具有用于接合杆的表面。或者，锁定装置包括外部凸轮配置或螺纹配置。

25. 发明申请

WO02071955A2 METHOD AND APPARATUS FOR TREATMENT OF ATRIAL FIBRILLATION 审中-公开
标题翻译：用于治疗椎间孔纤维化的方法和装置
公开(公告)号：WO02071955A2
公开(公告)日：2002-09-19
申请号：PCT/US0207942
申请日：2002-03-14
申请人： MICROHEART INC , CHEE U HIRAM , MUELLER RICHARD M , KERMODE JAMES R , TOM CURTIS P , MURPHY-CHUTORIAN DOUGLAS
发明人： CHEE U HIRAM , MUELLER RICHARD M , KERMODE JAMES R , TOM CURTIS P , MURPHY-CHUTORIAN DOUGLAS
IPC分类号： A61B17/00 , A61B17/22 , A61B17/28 , A61M25/00
CPC分类号： A61B17/32037 , A61B17/282 , A61B2017/00247 , A61B2018/00392 , A61M2025/0089
摘要： Methods and apparatus of embodiments of the invention are adapted to treat tissue inside a patient's body. Aspects of the invention can be used in a wide variety of applications, but certain embodiments provide minimally invasive alternatives for treating atrial fibrillation by delivering a tissue-damaging agent to selected areas of the heart. One exemplary embodiment of the invention provides a method of treating cardiac arrhythmia. This method includes positioning a distal tissue-contacting portion of a body in surface contact with a tissue surface of cardiac tissue; detecting the surface contact between the tissue-contacting portion and the tissue surface; and thereafter, injecting a tissue-ablating agent into the cardiac tissue through the tissue-contacting portion of the body.
摘要翻译：本发明的实施例的方法和装置适于治疗患者体内的组织。本发明的各方面可以用于各种各样的应用中，但是某些实施方案提供了通过将组织损伤剂输送到心脏的选定区域来治疗心房颤动的微创替代方案。本发明的一个示例性实施方案提供了治疗心律失常的方法。该方法包括将身体的远端组织接触部分定位成与心脏组织的组织表面表面接触; 检测组织接触部分和组织表面之间的表面接触; 然后通过身体的组织接触部分将组织消融剂注入心脏组织。

26. 发明申请

WO0108672A3 GLUCAMINE COMPOUNDS FOR TREATING HEPATITIS VIRUS INFECTIONS 审中-公开
标题翻译：用于治疗肝炎病毒感染的葡糖胺化合物
公开(公告)号：WO0108672A3
公开(公告)日：2001-11-15
申请号：PCT/US0003816
申请日：2000-02-14
申请人： SEARLE & CO , MUELLER RICHARD A , BRYANT MARTIN L , PARTIS RICHARD A
发明人： MUELLER RICHARD A , BRYANT MARTIN L , PARTIS RICHARD A
IPC分类号： C07D295/12 , A61K31/047 , A61K31/13 , A61K31/135 , A61K31/137 , A61K31/165 , A61K31/18 , A61K31/382 , A61K31/4406 , A61K31/4409 , A61K31/445 , A61K31/5375 , A61K31/7052 , A61K45/00 , A61K45/06 , A61P31/12 , C07C215/06 , C07C215/10 , C07C217/06 , C07C233/22 , C07C311/09 , C07C311/32 , C07C317/28 , C07C323/12 , C07C323/25 , C07C323/60 , C07C323/65 , C07D211/46 , C07D213/38 , C07D213/68 , C07D335/02 , A61K31/045 , A61K31/12 , A61K31/1357 , A61P31/14
CPC分类号： A61K45/06 , A61K31/047 , A61K31/137 , C07C215/10
摘要： N-Substituted glucamine compounds of Formula (I) are effective in treatment of hepatitis infections, including hepatitis B and hepatitis C. In treating hepatitis infections, the compounds of Formula (I) may be used alone, or in combination with another antiviral agent selected from among nucleosides, nucleotides, immunomodulators, immunostimulants or various combinations of such other agents.
摘要翻译：式（I）的N-取代的葡糖胺化合物有效治疗肝炎感染，包括乙型肝炎和丙型肝炎。在治疗肝炎感染时，式（I）化合物可以单独使用或与选择的另一种抗病毒剂来自核苷，核苷酸，免疫调节剂，免疫刺激剂或这些其他试剂的各种组合。

27. 发明申请

WO1995024392A1 2-CHLORO AND 2-BROMO DERIVATIVES OF 1,5-IMINOSUGARS 审中-公开
标题翻译： 1-IMINOSUGARS的2-CHLORO和2-BROMO衍生物
公开(公告)号：WO1995024392A1
公开(公告)日：1995-09-14
申请号：PCT/US1995002168
申请日：1995-02-28
申请人： G. D. SEARLE & CO. , BARTA, Thomas, E. , MUELLER, Richard, A.
发明人： G. D. SEARLE & CO.
IPC分类号： C07D211/46
CPC分类号： C07D401/12 , C07D207/12 , C07D211/46 , C07D491/04 , C07F7/1804 , C07F7/2224
摘要： Novel 1,5-iminosugars of formula (I) wherein X is Cl or Br; R1 is H or a C1-C12 branched or unbranched alkyl group, alkoxyalkyl, alkenyl, alkynyl, arylalkyl, substituted arylalkyl, arylalkenyl, or substituted arylalkenyl; and R2, R3 and R4 are independently H or COR5 where R5 is C1-C6 branched or unbranched alkyl, or C6-C12 aryl or alkylaryl. Also claimed are compounds of the formulae II-V.
摘要翻译：式（I）的新的1,5-亚氨基二糖，其中X是Cl或Br; R1是H或C1-C12支链或非支链烷基，烷氧基烷基，烯基，炔基，芳基烷基，取代的芳基烷基，芳基烯基或取代的芳基烯基; 且R 2，R 3和R 4独立地为H或COR 5，其中R 5为C 1 -C 6支链或非支链烷基或C 6 -C 12芳基或烷基芳基。还要求的是式II-V的化合物。

28. 发明申请

WO1995006030A1 HYDROXYETHYLAMINO SULPHONAMIDES USEFUL AS RETROVIRAL PROTEASE INHIBITORS 审中-公开
标题翻译：羟丙基氨基磺酸盐作为替代蛋白酶抑制剂有用
公开(公告)号：WO1995006030A1
公开(公告)日：1995-03-02
申请号：PCT/US1994009139
申请日：1994-08-23
申请人： G.D. SEARLE & CO. , THE MONSANTO COMPANY , VAZQUEZ, Michael, L. , MUELLER, Richard, A. , TALLEY, John, J. , GETMAN, Daniel, P. , DECRESCENZO, Gary, A. , FRESKOS, John, N. , BERTENSHAW, Deborah, E. , HEINTZ, Robert, M.
发明人： G.D. SEARLE & CO. , THE MONSANTO COMPANY
IPC分类号： C07C311/29
CPC分类号： C07D213/30 , A61K38/00 , C07C311/05 , C07C311/18 , C07C311/29 , C07C311/41 , C07C317/10 , C07C317/14 , C07C323/67 , C07C2601/08 , C07C2601/14 , C07C2601/18 , C07C2602/10 , C07D213/64 , C07D213/73 , C07D213/81 , C07D213/89 , C07D215/48 , C07D233/64 , C07D239/26 , C07D277/24 , C07D277/82 , C07D307/20 , C07D307/42 , C07D307/79 , C07D317/62 , C07D333/34 , C07D405/12 , C07D417/12 , C07K5/06026 , C07K5/06139
摘要： Hydroxyethylamino sulphonamide compounds of formulae (1) and (2), wherein A, R , R , R , R , x, P and P are as defined in claims 1 and 8 are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.
摘要翻译：式（1）和（2）的羟乙基氨基磺酰胺化合物，其中A，R 2，R 3，R 4，R 6，x，P 1和P 2定义如上在权利要求1和8中作为逆转录病毒蛋白酶抑制剂是有效的，特别是作为HIV蛋白酶的抑制剂。

29. 发明申请

WO1993010087A1 DERIVATIVES OF CYCLIC PHENOLIC THIOETHERS AS INHIBITORS OR STIMULATORS OF SUPEROXIDE GENERATION 审中-公开
标题翻译：作为抑制剂或超氧化物生成刺激剂的循环酚类衍生物的衍生物
公开(公告)号：WO1993010087A1
公开(公告)日：1993-05-27
申请号：PCT/US1992009560
申请日：1992-11-17
申请人： G.D. SEARLE & CO. , MUELLER, Richard, August , PARTIS, Richard, Allen
发明人： G.D. SEARLE & CO.
IPC分类号： C07C323/52
CPC分类号： C07D213/40 , C07C323/17 , C07C323/20 , C07C323/22 , C07C323/52 , C07C323/60 , C07C2601/08 , C07C2601/14 , C07C2601/18 , C07D307/18 , C07D307/20 , C07D493/04
摘要： The present invention relates to compounds of formula (I) and the pharmaceutically acceptable salts thereof wherein R , R and R are the same or different and independently represent alkyl, alkoxy, hydroxy, phenyl, halogen, trifluoromethyl, cyano, or hydrogen; q is 0 or 1; R represents hydrogen, alkyl, alkoxy, or hydroxy; X represents O, S or (CH2)m wherein m is an integer from 0 to 4; A represents O or S(O)n wherein n is 0, 1, or 2; Alk is straight or branched chain alkyl having 1 to 6 carbon atoms; p is 0 or 1; and R represents: (a) alkyl; (b) OH; (c) OR wherein R is alkyl of 1 to 6 carbon atoms; (d) NR R wherein R is hydrogen or alkyl, and R is hydrogen, alkyl, alkoxyalkyl, heterocyclealkyl, substituted heterocyclealkyl, cycloalkyl, substituted cycloalkyl, phenyl, substituted phenyl, phenylalkyl, substituted phenylalkyl, or Alk-NR R wherein Alk is alkyl of 1 to 10 carbon atoms and R and R each independently are hydrogen or alkyl; or NR R together form a heterocyclic ring which may optionally be substituted; or (e) (CH2)tCOOR wherein t is an integer from 1 to 4 and r is hydrogen or alkyl of 1 to 4 carbon atoms. The compounds are inhibitors or stimulators of superoxide generation.
摘要翻译：本发明涉及式（I）化合物及其药学上可接受的盐，其中R 1，R 2和R 10相同或不同并且独立地表示烷基，烷氧基，羟基，苯基，卤素，三氟甲基，氰基或氢; q为0或1; R 3表示氢，烷基，烷氧基或羟基; X表示O，S或（CH 2）m，其中m为0至4的整数; A表示O或S（O）n，其中n为0,1或2; Alk 1是具有1至6个碳原子的直链或支链烷基; p为0或1; 并且R表示：（a）烷基; （b）OH; （c）OR 4其中R 4为1至6个碳原子的烷基; （d）NR 5 R 6其中R 5是氢或烷基，R 6是氢，烷基，烷氧基烷基，杂环烷基，取代的杂环烷基，环烷基，取代的环烷基，苯基，取代的苯基，苯基烷基，取代的苯基烷基或Alk-NR 8 R 9其中Alk是1-10个碳原子的烷基，R 8和R 9各自独立地是氢或烷基; 或NR 5 R 6一起形成可任选被取代的杂环; 或（e）（CH 2）t COOR 7，其中t是1至4的整数，r 7是氢或1至4个碳原子的烷基。这些化合物是超氧化物产生的抑制剂或刺激剂。

30. 发明申请

WO1992019591A1 PROCESS FOR PREPARATION OF ALPHA-ALKOXY ACETIC ACIDS AND THEIR SALTS 审中-公开
标题翻译：制备ALPHA-ALKOXY ACEIC酸及其盐的方法
公开(公告)号：WO1992019591A1
公开(公告)日：1992-11-12
申请号：PCT/US1992003108
申请日：1992-04-22
申请人： G.D. SEARLE & CO. , MUELLER, Richard, August , PARTIS, Richard, Allen
发明人： G.D. SEARLE & CO.
IPC分类号： C07C323/20
CPC分类号： C07C51/367 , C07C319/20 , C07C323/20
摘要： A process for producing α-alkoxy acetic acids and salts thereof which comprises reacting an alcohol of formula (II), wherein R?1, R2 and R3¿ can be hydrogen, alkyl, alkoxy, halo, phenyl, substituted phenyl, or hydroxy; A can be S, O or -CH¿2?-; and Alk is straight or branched chain alkylene, with a base in an aprotic solvent, then reacting the resulting alkoxide with a monohaloacetic acid ester to give an alkoxyacetate followed by reaction of the alkoxyacetate with a hydrogen halide, organic acid or Lewis acid in nitromethane to give the corresponding α-alkoxyacetic acid which then may be recovered or may optionally be converted to the corresponding salt by contacting the α-alkoxy acetic acid with a base.

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