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1. 发明授权

US06441207B1 Method for making hydroxy-25-ene-vitamin D compounds 有权
标题翻译：制备羟基-25-烯 - 维生素D化合物的方法
公开(公告)号：US06441207B1
公开(公告)日：2002-08-27
申请号：US09716316
申请日：2000-11-20
申请人： Hans Wynberg , Ton Vries , Kees Pouwer
发明人： Hans Wynberg , Ton Vries , Kees Pouwer
IPC分类号： C07C40100
CPC分类号： C07C401/00 , C07C29/147 , C07C67/333 , C07C67/343 , C07C303/28 , C07C315/00 , C12P7/22 , C07C33/025 , C07C69/533 , C07C317/14 , C07C309/66
摘要： The present invention provides a method for preparing a novel class of vitamin D compounds in which the C-25 or equivalent position has a double bond. In addition, the side chain is optionally extended by one or two methylene or methyne groups. The compounds prepared by the method of the present invention are of value as prodrugs for active 1&agr;, 24-dihydroxylated vitamin D compounds.
摘要翻译：本发明提供一种制备其中C-25或等同位置具有双键的新一类维生素D化合物的方法。此外，侧链任选地被一个或两个亚甲基或甲炔基延伸。通过本发明的方法制备的化合物作为活性1α，24-二羟基化维生素D化合物的前药具有价值。

2. 发明授权

US4885375A Resolution of 3-(4-methoxyphenyl)glycidic acid with in situ conversion to alkyl esters 失效
标题翻译：原位转化为烷基酯的3-（4-甲氧基苯基）缩水甘油的拆分
公开(公告)号：US4885375A
公开(公告)日：1989-12-05
申请号：US195749
申请日：1988-05-18
申请人： Hans Wynberg , Wolter ten Hoeve
发明人： Hans Wynberg , Wolter ten Hoeve
IPC分类号： C07B57/00 , C07D303/48
CPC分类号： C07D303/48
摘要： Optically active 3-(4-methoxyphenyl)glycidic acid alkyl esters of high enantiomeric purity can be prepared through optical resolution of a racemic or optically enriched sample of a 3-(4-methoxyphenyl) glycidic acid. The alkali metal salt of the acid, generated in situ by hydrolysis of the corresponding alkyl ester with an alkali metal hydroxide is contacted with a suitable resolving agent such as an optically pure amine to form the corresponding diastereomeric salts. The desired diastereomeric salt is separated from the mixture and transformed to an alkali metal salt, which optionally without isolation is converted into the desired alkyl ester of high enantiomeric purity.

3. 发明授权

US4975380A Chemiluminescent labeled organic reagents and their use in analysis of organic compounds 失效
标题翻译：化学发光标记的有机试剂及其在有机化合物分析中的应用
公开(公告)号：US4975380A
公开(公告)日：1990-12-04
申请号：US445147
申请日：1989-11-30
申请人： Jan C. Hummelen , Hans Wynberg
发明人： Jan C. Hummelen , Hans Wynberg
IPC分类号： G01N33/52 , C07C41/00 , C07C43/196 , C07C67/00 , C07C209/00 , C07C231/00 , C07C231/14 , C07C233/06 , C07D207/00 , C07D207/46 , C07D321/00 , C07D405/00 , C07D407/12 , C07K14/00 , C07K14/76 , C07K16/00 , C09K11/06 , G01N33/533 , G01N33/536 , G01N33/58
CPC分类号： C07D407/12 , C07D207/46 , C07D321/00 , G01N33/533 , Y10S436/80
摘要： Thermochemically induced luminescence is generated in a fluorescent labeled organic compound containing a covalently bonded fluorescent label which is a polycyclic aromatic radical having at least three linearly fused benzene rings and capable of being excited to a fluorescent electronic excited state by energy transfer from an energy donor molecule or radical having an electronic excited state, by a process comprising generating an energy donor radical or molecule by a thermochemical reaction in the presence of the fluorescent label. The energy donor radical may be generated by a chemical reaction in the presence of the fluorescent labeled organic compound or the fluorescent labeled compound itself may be additionally labeled with a radical capable of being excited to an electronic excited state by a thermochemical reaction, i.e., by a process initiated by adsorption of thermal energy.
摘要翻译：在含有共价键合的荧光标记的荧光标记的有机化合物中产生热化学发光，所述荧光标记是具有至少三个线性稠合的苯环并且能够通过从能量供体分子的能量转移而被激发成荧光电子激发态的多环芳族基团或具有电子激发态的基团，通过包括在荧光标记物的存在下通过热化学反应产生能量供体基团或分子的方法。能量供体基团可以在荧光标记的有机化合物存在下通过化学反应产生，或者荧光标记的化合物本身可以另外用能够通过热化学反应被激发成电子激发态的基团，即，通过一个由吸热热能引发的过程。

4. 发明授权

US5677432A Immunological detection of organophosphates 失效
标题翻译：有机磷的免疫检测
公开(公告)号：US5677432A
公开(公告)日：1997-10-14
申请号：US290841
申请日：1994-08-19
申请人： William Thomas Jones , Hans Wynberg , Wolter Ten Hoeve
发明人： William Thomas Jones , Hans Wynberg , Wolter Ten Hoeve
IPC分类号： A61K47/48 , A62D3/00 , A62D3/02 , C07C69/67 , C07D319/06 , C07F9/6571 , C07F9/6574 , C07K16/00 , C07K16/18 , C07K16/44 , C07K19/00 , C12N5/10 , C12N5/20 , C12N15/02 , C12N15/13 , C12P21/08 , C12R1/91 , E01H4/02 , G01N33/53 , G01N33/563 , G01N33/577 , G01N33/68 , C07K17/00
CPC分类号： A62D3/02 , A61K47/48284 , C07D319/06 , C07F9/657118 , C07F9/657154 , C07F9/65742 , C07K16/44 , G01N33/5308 , G01N33/6857 , A62D2101/02 , A62D2101/26 , Y10S436/815 , Y10S530/807
摘要： A compound useful for forming immunoconjugates used in the detection of organophosphate pesticides is provided. The compound has the formula ##STR1## wherein X is selected from the group consisting of R--O--, R--S-- and R--NH--, where R is an optionally substituted aromatic or heterocyclic group, or an optionally substituted alkyl or alkenyl group; Y is O or S; R.sup.1 is H or alkyl; and R.sup.2 is a group of the formula --(CH.sub.2).sub.n -- wherein n is an integer of from 1 to 10, or branched chain alkylene, or a group of the formula R.sup.3 --O--R.sup.4 wherein R.sup.3 and R.sup.4 are both or straight or branched chain alkylene; or a salt or ester thereof.
摘要翻译： PCT No.PCT / NZ93 / 00010 Sec。 371日期：1994年8月19日 102（e）日期1994年8月19日PCT提交1993年2月26日PCT公布。出版物WO93 / 17030 日期1993年9月2日提供了用于形成用于检测有机磷农药的免疫缀合物的化合物。该化合物具有式（I），其中X选自R-O-，R-S-和R-NH-，其中R是任选取代的芳族或杂环基团，或任选取代的烷基或链烯基; Y为O或S; R1是H或烷基; 并且R 2是式 - （CH 2）n - 其中n是1至10的整数，或支链亚烷基，或式R3-O-R4的基团，其中R3和R4都是直链或支链亚烷基或其盐或酯。

5. 发明授权

US4973756A Hydroxylated ene ketones, acetylenic grignards and hydroxylated yne ketones therefrom 失效
标题翻译：羟基化烯酮，炔属格子酮和羟基化酮
公开(公告)号：US4973756A
公开(公告)日：1990-11-27
申请号：US395933
申请日：1989-08-21
申请人： Hans Wynberg , Wolter T. Hoeve , Gerrit A. Barf , Johannes N. Koek , David R. Borcherding
发明人： Hans Wynberg , Wolter T. Hoeve , Gerrit A. Barf , Johannes N. Koek , David R. Borcherding
IPC分类号： C07B37/04 , C07C45/51 , C07C49/252 , C07C221/00 , C07C225/14 , C07C225/16
CPC分类号： C07C225/16 , C07C221/00 , C07C45/513 , C07C49/252 , C07C2101/04
摘要： An alpha-hydroxyl-alpha,alpha-di(inert-substituted)-gamma',delta'-yne ketone can be prepared by a procedure comprising contacting an acetylenic Grignard reagent with an alpha-hydroxyl-alpha,alpha-di(inert substituted)-alpha',beta'-ene ketone, and the alpha-hydroxyl-alpha,alpha-di(inert-substituted)-alpha',beta'-ene ketone can be prepared by a procedure comprising steps of contacting, first, an alkoxy allene with a lithium donating organic agent, second, product of the first step with a di(inert-substituted)ketone, and third, product of the second step with an acidic substance. For example, 1-cyclobutyl-7-(N,N-dimethylamino)-1-hydroxy-1-phenylhept-5-yn-2-one, hydrochloride salt (ML-1012), can be prepared by the reaction of 1-cyclobutyl-1-hydroxy-1-phenylbut-3-en-2-one and 1-(N,N-dimethylamino)-2-propyn-3-magnesium chloride, followed by salt formation with hydrogen chloride gas, and the 1-cyclobutyl-1-hydroxy-1-phenylbut-3-en-2-one can be prepared by the serial reactions of (1) 1-methoxy allene with n-butyllithium, (2) product of this first step with cyclobutylphenyl ketone, and (3) product of this second step with sulfuric acid.

6. 发明授权

US4935407A Thermochemiluminescent cyclodextrin complexes 失效
标题翻译：热化学发光环糊精复合物
公开(公告)号：US4935407A
公开(公告)日：1990-06-19
申请号：US99865
申请日：1987-09-22
申请人： Theo M. Luider , Jan C. Hummelen , Johannes N. Koek , Hans Wynberg
发明人： Theo M. Luider , Jan C. Hummelen , Johannes N. Koek , Hans Wynberg
IPC分类号： G01N33/532 , C07D321/00 , C07D405/12 , C08B37/16 , C09K11/07 , G01N21/76 , G01N33/533 , G01N33/543 , G01N33/544 , G01N33/58
CPC分类号： G01N33/533 , G01N33/586
摘要： Thermochemiluminescent complexes of an adamanthylideneadamantane 1,2-dioxetane and a cyclodextrin are non-volatile at the temperatures used to excite the thermochemiluminescence. The complexes can be encapsulated in immunosensitized microcapsules, e.g., liposomes, to provide a labeled immunoreagent useful in immunoassay using thermochemiluminescent labeled immunoreagents.
摘要翻译：金刚烷基金刚烷1,2-二氧环乙烷和环糊精的热化学发光配合物在用于激发热化学发光的温度下是不挥发的。复合物可以包封在免疫敏化微胶囊例如脂质体中，以提供可用于使用热化学发光标记的免疫试剂的免疫测定中的标记的免疫反应物。

7. 发明授权

US5463050A Method of preparing aryl(homo)piperazines 失效
标题翻译：制备芳基（同）哌嗪的方法
公开(公告)号：US5463050A
公开(公告)日：1995-10-31
申请号：US17497
申请日：1993-02-12
申请人： Wolter Ten Hoeve , Jantje R. G. Thiecke , Hans Wynberg , Chris G. Kruse
发明人： Wolter Ten Hoeve , Jantje R. G. Thiecke , Hans Wynberg , Chris G. Kruse
IPC分类号： C07D213/74 , C07D243/06 , C07D243/08 , C07D245/02 , C07D295/02 , C07D295/08 , C07D295/12 , C07D319/18 , C07D333/36
CPC分类号： C07D213/74 , C07D243/08 , C07D319/18 , C07D333/36
摘要： The present invention is concerned with a method for the preparation of a compound of the general formula 2 ##STR1## by reaction of a compound of the formula 3Ar--Y (3)with a compound of the general formula 4 ##STR2## wherein Ar means a (hetero)aryl group, preferably selected from phenyl, naphtyl, furyl, thienyl, pyridyl, bicylic heteroaryl and tricyclic heteroaryl, which (hetero)aryl group is optionally sustituted with one to five non-strongly-electron-withdrawing substituents;M is a metal from the groups I or II of the periodic table;R.sub.12 is an electronegative group; andis 0 or 1.The invention also relates to compounds prepared according to this method and to new substituted aryl(homo)piperazines.
摘要翻译：本发明涉及通过式3 Ar-Y（3）的化合物与通式4化合物（IMA）的反应制备通式2的化合物（2）的方法（4）其中Ar表示优选选自苯基，萘基，呋喃基，噻吩基，吡啶基，双环杂芳基和三环杂芳基的（杂）芳基，该（杂）芳基任选地被一至五个非 - 吸电子取代基; M是周期表第I或II族的金属; R12是电负性基团; 并且为0或1.本发明还涉及根据该方法制备的化合物和新的取代的芳基（同）哌嗪。

8. 发明授权

US5252191A Method for the photochemical isomerization of organic compounds under the influence of a photosensitizer 失效
标题翻译：在光敏剂影响下有机化合物光化学异构化的方法
公开(公告)号：US5252191A
公开(公告)日：1993-10-12
申请号：US690684
申请日：1991-04-24
申请人： Louis F. Pauli , Alphons Dufourny , Robert B. Koolstra , Hans Wynberg , Wolter Ten Hoeve
发明人： Louis F. Pauli , Alphons Dufourny , Robert B. Koolstra , Hans Wynberg , Wolter Ten Hoeve
IPC分类号： C07B37/08 , C07C401/00 , C07D333/18 , C07D333/20 , C07D333/36 , C07D409/04 , C07D409/06 , C07D409/14 , C07J7/00 , C07G13/00
CPC分类号： C07D409/04 , C07C401/00 , C07D333/20 , C07D333/36 , C07D409/14
摘要： The invention relates to a method for the photochemical isomerization of organic compounds, in particular for the photochemical conversion of tachysterol compounds into previtamin D compounds and of trans-vitamin D compounds into cis-vitamin D compounds, under the influence of radiation, by exposing a solution of the organic compound to be converted in the presence of a non-polymeric photosensitizer to light with approx. 300-1,000 nm wavelength, and by then isolating the resulting product, wherein a substituted thiophene derivative having a substantial absorption in said wavelength region is used as the photosensitizer. The invention also relates to a new photosensitizer to be used for said isomerization reaction.

9. 发明授权

US4705847A Polycycloalkylidene-polycycloalkanes, epidioxy derivatives thereof and method of preparation 失效
标题翻译：聚环亚烷基 - 多环烷烃，其表
面衍生物及其制备方法
公开(公告)号：US4705847A
公开(公告)日：1987-11-10
申请号：US568224
申请日：1983-12-07
申请人： Jan C. Hummelen , Egbert W. Meijer , Hans Wynberg
发明人： Jan C. Hummelen , Egbert W. Meijer , Hans Wynberg
IPC分类号： C07C43/18 , C07B39/00 , C07C17/00 , C07C17/10 , C07C17/20 , C07C17/361 , C07C23/20 , C07C29/58 , C07C45/00 , C07C49/653 , C07C67/00 , C07C69/013 , C07C69/708 , C07C231/00 , C07C231/06 , C07C231/08 , C07C231/10 , C07C231/12 , C07C233/06 , C07C233/08 , C07C233/09 , C07C235/14 , C07C239/00 , C07C241/00 , C07C271/24 , C07D207/00 , C07D207/44 , C07D207/448 , C07D321/00 , C07D405/00 , C07D405/04 , C07J1/00 , C07J9/00 , C07J17/00 , C07C23/38
CPC分类号： C07D207/448 , C07B39/00 , C07C17/10 , C07C17/208 , C07C17/361 , C07C29/58 , C07C49/653 , C07D321/00 , C07D405/04 , C07J1/0029 , C07J17/00 , C07J9/005 , C07B2200/09 , C07C2103/74
摘要： The invention relates to a process for preparing substituted polycyclo-alkylidene polycyclo-alkanes, such as substituted adamantylidene adamantanes, and the corresponding epidioxy compounds, in which polycyclo-alkylidene polycyclo-alkanes are halogenated with an N-halosuccinimide, tert.-butylhypohalite or sodium hypohalite/CH.sub.3 COOH, the halogenation product is optionally subjected to a substitution reaction, and the substituted polycycloalkylidene polycyclo-alkanes are converted to the corresponding epidioxy compounds in a way known per se.Further, the invention relates to compounds of formula 44 ##STR1## in which A and B represent alkylene radicals, which alkylene radicals may be attached to each other via an alkylene radical C, and R.sub.1 represents a substituent, which, in case of 4-eq.-R.sub.1 -2,2'-adamantylidene adamantane cannot be chloro, hydroxy, oxo, D or a group of formula 1: ##STR2## as well as to compounds of formula 45: ##STR3## in which A, B and C are as defined above, and R.sub.2 is a substituent which, in case of 4-eq.-R.sub.2 -2,2'-epidioxy-2,2'-adamantyl adamantane cannot be chloro or hydroxy.Compounds of formula 45 are useful as thermochemiluminescent labels and probes in the study of biological processes and in immuno-assays.
摘要翻译： PCT No.PCT / NL83 / 00014 Sec。 371日期：1983年12月7日 102（e）1983年12月7日，PCT提交1983年4月7日PCT公布。公开号WO83 / 03604 日本公开1983年10月27日。本发明涉及一种制备取代的多环亚烷基多环烷烃如取代的金刚烷基金刚烷的方法，以及相应的表卤代化合物，其中多环亚烷基多环烷烃与N-卤代琥珀酰亚胺，叔丁基次卤酸盐或次卤酸钠/ CH 3 COOH，卤代产物任选进行取代反应，取代的聚环亚烷基多环烷烃以本身已知的方式转化为相应的表二氢化合物。此外，本发明涉及式44的化合物，其中A和B表示亚烷基，该亚烷基可以通过亚烷基C彼此连接，并且R 1表示取代基，其在4- 方程式-R1-2,2'-金刚烷金刚烷不能是氯，羟基，氧代，D或式1的基团：以及式45化合物：其中A，B和C R 4是取代基，在4当量-R 2 -2,2'-表氢氧-2,2'-金刚烷基金刚烷的情况下不能是氯或羟基。在研究生物过程和免疫测定中，式45的化合物可用作热化学发光标记和探针。

10. 发明授权

US4778767A Solid phase immunoassay using immunoreagents immobilized on inert synthetic resin surfaces 失效
标题翻译：使用固定在惰性合成树脂表面上的免疫试剂进行固相免疫测定
公开(公告)号：US4778767A
公开(公告)日：1988-10-18
申请号：US682373
申请日：1984-12-17
申请人： Jan C. Hummelen , Theo Luider , Hans Wynberg
发明人： Jan C. Hummelen , Theo Luider , Hans Wynberg
IPC分类号： G01N33/53 , G01N20060101 , G01N33/545 , G01N33/546
CPC分类号： G01N33/545 , Y10S436/823 , Y10S436/824
摘要： A solid phase immunoassay comprises the steps of(a) immobilizing an immunoreagent on the surface of a carrier comprised of an inert synthetic resin selected from the group consisting of polyimides and polyfluorinated synthetic resins,(b) contacting the immunoreagent with a complementary immunoreagent whereby an immunocomplex immobilized on said carrier is formed,(c) quantitating the immobilized immunocomplex.An element useful in conducting this solid phase immunoassay is prepared by a process of treating the surface of an article comprised of a synthetic polymer selected from the group consisting of polyimides and polyfluorinated synthetic resins to make it adsorptive of an immunoreagent which comprises the steps of(a) thoroughly rinsing the surface with a water-miscible organic solvent,(b) thoroughly rinsing the surface with water.
摘要翻译：固相免疫测定法包括以下步骤：（a）将免疫反应物固定在由选自聚酰亚胺和多氟化合成树脂的惰性合成树脂构成的载体的表面上，（b）使免疫反应物与互补免疫试剂接触，由此使形成固定在所述载体上的免疫复合物，（c）定量固定的免疫复合物。可用于进行该固相免疫测定的元件是通过处理由选自聚酰亚胺和多氟化合成树脂的合成聚合物构成的制品的表面的方法制备的，以使其吸附免疫反应物的方法，该方法包括以下步骤： a）用水混溶性有机溶剂彻底冲洗表面，（b）用水彻底冲洗表面。

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