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1. 发明授权

US5382580A N9 morpholino derivatives of 7,8-disubstituted guanines 失效
标题翻译： 7,8二取代鸟嘌呤的N9吗啉衍生物
公开(公告)号：US5382580A
公开(公告)日：1995-01-17
申请号：US250484
申请日：1994-05-27
申请人： Robert Chen , Michael G. Goodman , Allen Reitz
发明人： Robert Chen , Michael G. Goodman , Allen Reitz
IPC分类号： C07D473/18 , A61K31/535
CPC分类号： C07D473/18
摘要： Immunostimulating 7,8-disubstituted guanine derivatives that also contain a morpholinyl group as a position-9 substituent are disclosed whose structures are represented by formula I ##STR1## wherein X is O or S; R.sup.1 is a hydrocarbyl or substituted hydrocarbyl group having a length of about one to about seven carbon atoms; R.sup.2 is a hydrogen or C.sub.1 -C.sub.8 acyl; R.sup.3 is hydrogen, a C.sub.1 -C.sub.5 aliphatic hydrocarbyl, aralkyl or substituted aralkyl group; and the pharmaceutically acceptable base addition salts thereof. Also disclosed are compositions containing an immunostimulating substituted guanine derivative and processes for using the same.
摘要翻译：公开了其还含有吗啉基作为位置-9取代基的7,8-二取代的鸟嘌呤衍生物，其结构由式I其中X是O或S表示; R1是长度为约1至约7个碳原子的烃基或取代的烃基; R2是氢或C1-C8酰基; R3是氢，C1-C5脂族烃基，芳烷基或取代的芳烷基; 及其药学上可接受的碱加成盐。还公开了含有免疫刺激性取代的鸟嘌呤衍生物的组合物及其使用方法。

2. 发明授权

US4849411A Modulation of animal cellular responses with compositions containing 8-substituted guanine derivatives 失效
标题翻译：用含8-取代鸟嘌呤衍生物的组合物调节动物细胞反应
公开(公告)号：US4849411A
公开(公告)日：1989-07-18
申请号：US14618
申请日：1987-02-13
申请人： Michael G. Goodman , William O. Weigle
发明人： Michael G. Goodman , William O. Weigle
IPC分类号： C07H19/16
CPC分类号： C07H19/16 , Y10S514/885
摘要： Compositions and methods for their use in modulating animal cellular responses are disclosed. The compositions include as an active agent an effective amount of an 8-substituted guanine derivative bonded 9-1' to an aldose having 5 or 6 carbon atoms in the aldose chain. The composition includes a diluent amount of a physiologically tolerable carrier. The guanine derivative is free of electrically charged functionality, while the 8-substituent has an electron withdrawing inductive effect greater than that of hydrogen and contains fewer than about 15 atoms. Animal cellular responses are modulated by contacting the cells with a composition of this invention.
摘要翻译：公开了其用于调节动物细胞反应的组合物和方法。组合物包含作为活性剂的有效量的8-取代的鸟嘌呤衍生物与醛糖链中具有5或6个碳原子的醛糖结合9-1'。组合物包括稀释剂量的生理上可耐受的载体。鸟嘌呤衍生物没有带电的官能团，而8-取代基的吸电子效应大于氢并且含有少于约15个原子。通过使细胞与本发明的组合物接触来调节动物细胞反应。

3. 发明授权

US4643992A Modulation of animal cellular responses with compositions containing 8-substituted guanine derivatives 失效
标题翻译：用含8-取代鸟嘌呤衍生物的组合物调节动物细胞反应
公开(公告)号：US4643992A
公开(公告)日：1987-02-17
申请号：US546679
申请日：1983-11-01
申请人： Michael G. Goodman , William O. Weigle
发明人： Michael G. Goodman , William O. Weigle
IPC分类号： C07H19/16 , A61K31/70 , C12N5/00
CPC分类号： C07H19/16
摘要： Compositions and methods for their use in modulating animal cellular responses are disclosed. The compositions include as an active agent an effective amount of an 8-substituted guanine derivative bonded 9-1' to an aldose having 5 or 6 carbon atoms in the aldose chain. The composition includes a diluent amount of a physiologically tolerable carrier. The guanine derivative is free of electrically charged functionality, while the 8-substituent has an electron withdrawing inductive effect greater than that of hydrogen and contains fewer than about 15 atoms. Animal cellular responses are modulated by contacting the cells with a composition of this invention.
摘要翻译：公开了其用于调节动物细胞反应的组合物和方法。组合物包含作为活性剂的有效量的8-取代的鸟嘌呤衍生物与醛糖链中具有5或6个碳原子的醛糖结合9-1'。组合物包括稀释剂量的生理上可耐受的载体。鸟嘌呤衍生物没有带电的官能团，而8-取代基的吸电子效应大于氢并且含有少于约15个原子。通过使细胞与本发明的组合物接触来调节动物细胞反应。

4. 发明授权

US5093318A Immunostimulating guanosine derivatives and their pharmaceutical compositions 失效
标题翻译：免疫刺激鸟苷衍生物及其药物组合物
公开(公告)号：US5093318A
公开(公告)日：1992-03-03
申请号：US190694
申请日：1988-05-05
申请人： Michael G. Goodman , Robert Chen
发明人： Michael G. Goodman , Robert Chen
IPC分类号： C07D473/18 , A61K31/52 , A61K31/522 , A61K31/70 , A61K31/7042 , A61K31/7052 , A61K31/7076 , A61K31/708 , A61K39/39 , A61P9/04 , A61P37/04 , C07H19/16
CPC分类号： C07H19/16 , A61K39/39 , A61K2039/55511
摘要： 7,8-Disubstituted guanosine nucleoside derivatives are found to be potent immune response enhancing agents in human and animal cells. 7-Substituents are heteroatom-substituted-hydrocarbyl radicals having a length greater than ethyl and less than about decyl. 8-Substituents are .dbd.O, .dbd.S, .dbd.Se and .dbd.NCN. Compositions and methods of use are also disclosed.
摘要翻译：发现7,8-二取代鸟苷核苷衍生物在人和动物细胞中是有效的免疫应答增强剂。 7-取代基是长度大于乙基且小于约癸基的杂原子取代的烃基。 8-取代基是= O，= S，= Se和= NCN。还公开了组合物和使用方法。

5. 发明授权

US5786359A N.sup.9 alkyl or aralkyl derivatives of 7, 8-disubstituted guanines 失效
标题翻译： 7,8-二取代的guanines的N9烷基或芳烷基衍生物
公开(公告)号：US5786359A
公开(公告)日：1998-07-28
申请号：US703578
申请日：1996-08-27
申请人： Allen Reitz , Michael G. Goodman , Robert Chen , Bruce E. Maryanoff
发明人： Allen Reitz , Michael G. Goodman , Robert Chen , Bruce E. Maryanoff
IPC分类号： C07D473/18 , A61K31/52
CPC分类号： C07D473/18
摘要： Immunostimulating 7,8-disubstituted guanine derivatives that also contain a 9-alkyl, 9-alkoxy or 9-aralkyl substituent are disclosed whose structures are represented by Formula I ##STR1## wherein X is O or S; R.sup.1 is a hydrocarbyl or substituted hydrocarbyl group having a length of about one to about seven carbon atoms; R.sup.2 is a hydrocarbyl or hydroxyl- or ether-substituted hydrocarbyl group having a length of about four to about ten carbon atoms; and the pharmaceutically acceptable base addition salts thereof. Also disclosed are compositions containing an immunostimulating guanine derivative and processes for using the same.
摘要翻译：公开了也含有9-烷基，9-烷氧基或9-芳烷基取代基的7,8-二取代鸟嘌呤衍生物的免疫刺激，其结构由式I其中X是O或S表示; R1是长度为约1至约7个碳原子的烃基或取代的烃基; R2是长度为约4至约10个碳原子的烃基或羟基或醚取代的烃基; 及其药学上可接受的碱加成盐。还公开了含有免疫刺激性鸟嘌呤衍生物的组合物及其使用方法。

6. 发明授权

US5476659A Cancerous B cell treatment using substituted nucleoside derivatives 失效
标题翻译：使用取代的核苷衍生物进行癌细胞B细胞治疗
公开(公告)号：US5476659A
公开(公告)日：1995-12-19
申请号：US151142
申请日：1993-11-12
申请人： Michael G. Goodman , Lawrence D. Piro
发明人： Michael G. Goodman , Lawrence D. Piro
IPC分类号： A61K35/74 , A61K47/48 , C07H19/16 , A61K39/39 , A61K31/70 , C12N5/06 , C12N5/08
CPC分类号： A61K31/70 , A61K47/48276 , C07H19/16 , C12N5/0093 , C12N2501/06 , C12N2501/999 , Y10S514/908
摘要： Processes for the killing of cancerous B cells, and particularly chronic lymphocytic leukemia (CLL) cells are disclosed. In one process, cancerous B cells that do not proliferate when contacted with an immune response-enhancing agent are contacted with an amount of such an agent sufficient to cause peripheral CLL cells to undergo blast transformation and proliferation. The contacted cells are then maintained for a time period sufficient for them to die from that contact. Further contacting of those cells with a cytotoxic amount of an anti-cancer drug or cytotoxic conjugate enhances the death of those cancer cells. In another process, peripheral CLL cells that proliferate on contact with an immune response-enhancing-agent are contacted with a proliferation-inducing amount of such an agent. The contacted cells are maintained for a time period sufficient to undergo blast transformation and proliferation, and the blasts are then contacted with a cytotoxic amount of an anti-cancer drug or cytotoxic conjugate and maintained.
摘要翻译：公开了杀死癌性B细胞，特别是慢性淋巴细胞性白血病（CLL）细胞的方法。在一个过程中，当与免疫应答增强剂接触时不增殖的癌性B细胞与足以引起外周CLL细胞经历blast转化和增殖的量的这种试剂接触。然后将接触的细胞保持足以使它们从该接触死亡的时间段。这些细胞与细胞毒性量的抗癌药物或细胞毒性缀合物的进一步接触增强了那些癌细胞的死亡。在另一个方法中，与免疫应答增强剂接触时增殖的外周CLL细胞与增殖诱导量的这种试剂接触。将接触的细胞保持足以进行细胞转化和增殖的时间段，然后将母细胞与细胞毒性量的抗癌药物或细胞毒性缀合物接触并保持。

7. 发明授权

US5439907A Use of N9 morpholino derivatives of 7,8-disubstituted guanines 失效
标题翻译：使用7,8-二取代鸟嘌呤的N9吗啉代衍生物
公开(公告)号：US5439907A
公开(公告)日：1995-08-08
申请号：US373374
申请日：1995-01-17
申请人： Robert Chen , Michael G. Goodman , Allen Reitz
发明人： Robert Chen , Michael G. Goodman , Allen Reitz
IPC分类号： C07D473/18 , A61K31/535
CPC分类号： C07D473/18
摘要： Immunostimulating 7,8-disubstituted guanine derivatives that also contain a morpholinyl group as a position-9 substituent are disclosed whose structures are represented by formula I ##STR1## wherein X is O or S; R.sup.1 is a hydrocarbyl or substituted hydrocarbyl group having a length of about one to about seven carbon atoms; R.sup.2 is a hydrogen or C.sub.1 -C.sub.8 acyl; R.sup.3 is hydrogen, a C.sub.1 -C.sub.5 aliphatic hydrocarbyl, aralkyl or substituted aralkyl group; and the pharmaceutically acceptable base addition salts thereof. Also disclosed are compositions containing an immunostimulating substituted guanine derivative and processes for using the same.
摘要翻译：公开了其还含有吗啉基作为位置-9取代基的7,8-二取代的鸟嘌呤衍生物，其结构由式I其中X是O或S表示; R1是长度为约1至约7个碳原子的烃基或取代的烃基; R2是氢或C1-C8酰基; R3是氢，C1-C5脂族烃基，芳烷基或取代的芳烷基; 及其药学上可接受的碱加成盐。还公开了含有免疫刺激性取代的鸟嘌呤衍生物的组合物及其使用方法。

8. 发明授权

US5317013A Modulation of animal cellular responses with compositions containing 8-substituted guanine derivatives 失效
标题翻译：用含8-取代鸟嘌呤衍生物的组合物调节动物细胞反应
公开(公告)号：US5317013A
公开(公告)日：1994-05-31
申请号：US945215
申请日：1992-09-15
申请人： Michael G. Goodman , William O. Weigle
发明人： Michael G. Goodman , William O. Weigle
IPC分类号： C07H19/16 , A61K31/70 , A61K45/05 , C07K13/00
CPC分类号： C07H19/16 , Y10S514/885
摘要： Compositions and methods for their use in modulating animal cellular responses are disclosed. The compositions include as an active agent an effective amount of an 8-substituted guanine derivative bonded 9-1' to an aldose having 5 or 6 carbon atoms in the aldose chain. The composition includes a diluent amount of a physiologically tolerable carrier. The guanine derivative is free of electrically charged functionality, while the 8-substituent has an electron withdrawing inductive effect greater than that of hydrogen and contains fewer than about 15 atoms. Animal cellular responses are modulated by contacting the cells with a composition of this invention.
摘要翻译：公开了其用于调节动物细胞反应的组合物和方法。组合物包含作为活性剂的有效量的8-取代的鸟嘌呤衍生物与醛糖链中具有5或6个碳原子的醛糖结合9-1'。组合物包括稀释剂量的生理上可耐受的载体。鸟嘌呤衍生物没有带电的官能团，而8-取代基的吸电子效应大于氢并且含有少于约15个原子。通过使细胞与本发明的组合物接触来调节动物细胞反应。

9. 发明授权

US5166141A Immunostimulating 7-deaza-7-oxa- and 7-deaza-7-oxo-analogs of 8-substituted-guanine-9-(1'-beta-D-aldoglycosidyl) derivatives and methods of treating test animals 失效
标题翻译：免疫刺激8-取代鸟嘌呤-9-（1'-β-D-缬氨酰糖基）衍生物的7-脱氮-7-氧杂和7-脱氮-7-氧代 - 类似物和治疗试验动物的方法
公开(公告)号：US5166141A
公开(公告)日：1992-11-24
申请号：US198141
申请日：1988-05-24
申请人： Michael G. Goodman , Edward P. Gamson
发明人： Michael G. Goodman , Edward P. Gamson
IPC分类号： A61K31/435 , A61K31/70 , A61K31/7042 , A61K31/7052 , A61P37/00 , C07D498/04 , C07D513/04 , C07H19/16 , C07H19/24
CPC分类号： C07H19/16 , C07H19/24
摘要： An immune response-enhancing guanosine analog derivative having a structure that conforms to the formula ##STR1## wherein Z is oxygen (O) or sulfur (S); X is oxygen (O), sulfur (S) selenium (Se) or cyanimino (NCN); and R.sub.1 is an aldoglycoside is disclosed. Also disclosed are a composition containing the guanosine analog derivative as active ingredient and a method of using the composition for immunostimulation.
摘要翻译：具有符合其中Z为氧（O）或硫（S）的结构式的其他结构的免疫应答增强鸟苷类似物衍生物; X是氧（O），硫（S）硒（Se）或氰氨基（NCN）; 并公开了R1是醛糖苷。还公开了含有鸟苷类似物衍生物作为活性成分的组合物和使用该组合物进行免疫刺激的方法。

10. 发明授权

US5147636A Modulation of animal cellular responses with compositions containing 8-substituted guanine derivatives and interferons 失效
标题翻译：用含8-取代鸟嘌呤衍生物和干扰素的组合物调节动物细胞反应
公开(公告)号：US5147636A
公开(公告)日：1992-09-15
申请号：US562101
申请日：1990-08-02
申请人： Michael G. Goodman , William O. Weigle
发明人： Michael G. Goodman , William O. Weigle
IPC分类号： C07H19/16
CPC分类号： C07H19/16
摘要： Compositions and methods for their use in modulating animal cellular responses are disclosed. The compositions include as an active agent an effective amount of an 8-substitued guanine derivative bonded 9-1' to an aldose having 5 or 6 carbon atoms in the aldose chain. The composition includes a diluent amount of a physiologically tolerable carrier. The guanine derivative is free of electrically charged functioinality, while the 8-substituent has an electron withdrawing inductive effect greater than that of hydrogen and contains fewer than about 15 atoms. Animal cellular responses are modulated by contacting the cells with a composition of this invention.
摘要翻译：公开了其用于调节动物细胞反应的组合物和方法。组合物包含作为活性剂的有效量的8-取代的鸟嘌呤衍生物与醛糖链中具有5或6个碳原子的醛糖结合9-1'。组合物包括稀释剂量的生理上可耐受的载体。鸟嘌呤衍生物不具有带电功能，而8-取代基具有大于氢的吸电子诱导效应，并且含有少于约15个原子。通过使细胞与本发明的组合物接触来调节动物细胞反应。

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