公开(公告)号：US6093734A

公开(公告)日：2000-07-25

申请号：US131481

申请日：1998-08-10

申请人： Michael E. Garst ,  George Sachs ,  Jai Moo Shin

发明人： Michael E. Garst ,  George Sachs ,  Jai Moo Shin

IPC分类号： C07D235/28 ,  C07D401/12 ,  C07D401/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  C07F9/6558 ,  A61K31/4439 ,  A61K31/445 ,  C07D413/12

CPC分类号： C07D401/12 ,  C07D235/28 ,  C07D401/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  C07F9/65583

摘要： Prodrugs of the pyridyl methyl sulfinyl benzimidazole type proton pump inhibitor drugs have a hydrolyzable sulfinyl or arylsulfonyl group attached to the benzimidazole nitrogen, or include a group that forms a Mannich base with the benzimidazole nitrogen. The prodrugs of the invention hydrolyze under physiological conditions to provide the proton pump inhibitors with a half life measurable in hours, and are capable of providing sustained plasma concentrations of the proton pump inhibitor drugs for longer time than presently used drugs. The generation of the proton pump inhibitor drugs from the prodrugs of the invention under physiological conditions allows for more effective treatment of several diseases and conditions caused by gastric acid secretion.

摘要翻译： 吡啶基甲基亚磺酰基苯并咪唑型质子泵抑制剂药物的前药具有与苯并咪唑氮连接的可水解亚磺酰基或芳基磺酰基，或包括与苯并咪唑氮形成曼尼希碱的基团。 本发明的前药在生理条件下水解以提供质子泵抑制剂，其半衰期可在几小时内测量，并且能够提供质子泵抑制剂药物的持续血浆浓度比目前使用的药物更长时间。 在生理条件下从本发明前药产生的质子泵抑制剂药物可以更有效地治疗由胃酸分泌引起的几种疾病和病症。

公开(公告)号：US20100317689A1

公开(公告)日：2010-12-16

申请号：US12310867

申请日：2007-09-15

申请人： Michael E. Garst ,  George Sachs ,  Jai Moo Shin

发明人： Michael E. Garst ,  George Sachs ,  Jai Moo Shin

IPC分类号： A61K31/437 ,  C07D471/02 ,  A61P1/00 ,  A61P1/04

CPC分类号： C07D471/04

摘要： The compounds of formulas (I), (II), (III) and (IV), where the symbols are as defined in the specification are prodrugs of proton pump inhibitors. The R4 group includes at least one acidic group or its pharmaceutically acceptable salt, and the compound having the R4 group have improved aqueous solubility, stability in plasma and improved bioavailability.

摘要翻译： 符号如本说明书中所定义的式（I），（II），（III）和（IV）的化合物是质子泵抑制剂的前药。 R4基团包括至少一个酸性基团或其药学上可接受的盐，并且具有R4基团的化合物具有改善的水溶性，血浆中的稳定性和改善的生物利用度。

公开(公告)号：US20100113524A1

公开(公告)日：2010-05-06

申请号：US12310868

申请日：2007-09-15

申请人： Michael E. Garst ,  George Sachs ,  Jai Moo Shin

发明人： Michael E. Garst ,  George Sachs ,  Jai Moo Shin

IPC分类号： A61K31/4439 ,  C07D401/14 ,  A61P1/04

CPC分类号： C07D401/14

摘要： The compounds of the formulas (I), (II), (III) and (IV), where the symbols are as defined in the specification are prodrugs of proton pump inhibitors. The R4 group includes at least one acidic group or its pharmaceutically acceptable salt, and the compound having the R4 group have improved aqueous solubility, stability in plasma and improved bioavailability.

摘要翻译： 符号如本说明书中所定义的式（I），（II），（III）和（IV）的化合物是质子泵抑制剂的前药。 R4基团包括至少一个酸性基团或其药学上可接受的盐，并且具有R4基团的化合物具有改善的水溶性，血浆中的稳定性和改善的生物利用度。

公开(公告)号：US06559167B1

公开(公告)日：2003-05-06

申请号：US09783807

申请日：2001-02-14

申请人： Michael E. Garst ,  George Sachs ,  Jai Moo Shin

发明人： Michael E. Garst ,  George Sachs ,  Jai Moo Shin

IPC分类号： A61K31445

CPC分类号： C07D401/12 ,  C07D235/28 ,  C07D401/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  C07F9/65583

摘要： Prodrugs of the pyridyl methyl sulfinyl benzimidazole type proton pump inhibitor drugs have a hydrolyzable arylsulfonyl or heteroarylsulfonyl group attached to the benzimidazole nitrogen. The prodrugs of the invention hydrolyze under physiological conditions to provide the proton pump inhibitors with a half life measurable in hours, and are capable of providing sustained plasma concentrations of the proton pump inhibitor drugs for longer time than presently used drugs. The generation of the proton pump inhibitor drugs from the prodrugs of the invention under physiological conditions allows for more effective treatment of several diseases and conditions caused by gastric acid secretion.

摘要翻译： 吡啶基甲基亚磺酰基苯并咪唑型质子泵抑制剂药物的前药具有连接到苯并咪唑氮的可水解的芳基磺酰基或杂芳基磺酰基。 本发明的前药在生理条件下水解以提供质子泵抑制剂，其半衰期可在几小时内测量，并且能够提供质子泵抑制剂药物的持续血浆浓度比目前使用的药物更长时间。 在生理条件下从本发明前药产生的质子泵抑制剂药物可以更有效地治疗由胃酸分泌引起的几种疾病和病症。

公开(公告)号：US5183906A

公开(公告)日：1993-02-02

申请号：US693204

申请日：1991-04-30

申请人： Gary C. M. Lee ,  Michael E. Garst ,  George Sachs

发明人： Gary C. M. Lee ,  Michael E. Garst ,  George Sachs

IPC分类号： A61K31/34 ,  A61K31/341 ,  A61P29/00 ,  C07D307/60 ,  C07F7/08 ,  C07F9/655

CPC分类号： C07D307/60 ,  C07F7/0814 ,  C07F9/65515

摘要： Novel anti-inflammatory furanone compounds have the following formula ##STR1## where R.sub.1 independently is H, phenyl, C.sub.1 -C.sub.6 alkyl substituted phenyl, halogen substituted phenyl, or alkyl of 1 to 6 carbons and n is an integer having the values of 1 or 2, and where when n is 1 the R.sub.1 group is attached either to the 3 or to the 5 position of the 2-furanone, when n is 2 then R.sub.1 is attached to both the 3 and 5 positions, with the proviso that when n is 1 then R.sub.1 is not H; Y.sub.1 is H, alkyl of 1 to 20 carbons, phenyl C.sub.1 -C.sub.20 alkyl, C.sub.1 -C.sub.20 alkenyl containing one or more olephinic bonds, PO(OH).sub.2, PO(OH)OR.sub.2, PO(OH)R.sub.2, PO(OR.sub.2).sub.2, where R.sub.2 is independently alkyl of 1 to 20 carbons, phenyl, or halogen substituted phenyl or C.sub.1 -C.sub.6 alkyl substituted phenyl, further Y.sub.1 is CO--R.sub.3, CO--OR.sub.3, CONHR.sub.3, SO.sub.2 R.sub.3, SO.sub.2 NHR.sub.3, (CH.sub.2).sub.p --O--R.sub.3, or (CH.sub.2).sub.p --O--(CH.sub.2).sub.m --O--R.sub.3, where p, and m, are integers and are independently 1 to 20 and R.sub.3 is H, C.sub.1 -C.sub.20 alkyl, C.sub.1 -C.sub.20 alkenyl containing one or more olephinic bonds, phenyl, halogen substituted phenyl or C.sub.1 -C.sub.6 alkyl substituted phenyl, with the proviso that when Y.sub.1 is CO--R.sub.3, CO--OR.sub.3, and CONHR.sub.3 then R.sub.3 is not hydrogen; Y.sub.2 is H, an alkyl group of 1 to 25 carbons, phenyl, naphthyl, phenyl (C.sub.1 -C.sub.20)alkyl-, naphthyl (C.sub.1 -C.sub.20)alkyl-, halogen substituted phenyl, C.sub.1 -C.sub.6 alkyl substituted phenyl, halogen substituted naphthyl, C.sub.1 -C.sub.6 substituted naphthyl; Y.sub.3 is H, alkyl of 1 to 20 carbons, CO--R.sub.4, CO--O--R.sub.4, CO--NH--R.sub.4, PO(OR.sub.4).sub.2 or PO(OR.sub.4)R.sub.4, where R.sub.4 independently is H, alkyl of 1 to 20 carbons, phenyl, or halogen substituted phenyl or C.sub.1 -C.sub.6 alkyl substituted phenyl.

摘要翻译： 新型抗炎呋喃酮化合物具有下式：其中R 1独立地为H，苯基，C 1 -C 6烷基取代的苯基，卤素取代的苯基或1至6个碳的烷基，n是具有1或 2，当n为1时，R1基团连接到2-呋喃酮的3位或5位，当n为2时，则R1连接在3和5位上，条件是当n 是1，那么R1不是H; Y 1是H，1至20个碳的烷基，含有一个或多个烯基键的C 1 -C 20烷基，C 1 -C 20链烯基，PO（OH）2，PO（OH）OR 2，PO（OH）R 2，PO（OR 2） 2，其中R2独立地为1至20个碳的烷基，苯基或卤素取代的苯基或C1-C6烷基取代的苯基，另外Y1为CO-R3，CO-OR3，CONHR3，SO2R3，SO2NHR3，（CH2）p -O -R3或（CH2）pO-（CH2）mO-R3，其中p和m是整数，并且独立地是1-20，R3是H，C1-C20烷基，含有一个或多个烯基键的C1-C20链烯基 ，苯基，卤素取代的苯基或C 1 -C 6烷基取代的苯基，条件是当Y 1是CO-R 3，CO-OR 3和CONHR 3时，R 3不是氢; Y2是H，1至25个碳的烷基，苯基，萘基，苯基（C1-C20）烷基 - ，萘基（C1-C20）烷基 - ，卤素取代的苯基，C1-C6烷基取代的苯基，卤素取代的萘基， C1-C6取代的萘基; Y 3为H，碳数1〜20的烷基，CO-R 4，CO-O-R 4，CO-NH-R 4，PO（OR 4）2或PO（OR 4）R 4，其中，R 4独立地为H， 碳，苯基或卤素取代的苯基或C 1 -C 6烷基取代的苯基。

公开(公告)号：US5418234A

公开(公告)日：1995-05-23

申请号：US298494

申请日：1994-08-30

申请人： Charles Gluchowski ,  Michael E. Garst ,  James A. Burke ,  Larry A. Wheeler ,  Michael E. Garst

发明人： Charles Gluchowski ,  Michael E. Garst ,  James A. Burke ,  Larry A. Wheeler ,  Michael E. Garst

IPC分类号： A61K31/495 ,  C07D403/12 ,  A61K31/50

CPC分类号： C07D403/12 ,  A61K31/495 ,  Y10S514/816 ,  Y10S514/854 ,  Y10S514/93

摘要： A method of treating a mammal comprises administering to a mammal an effective amount to provide a desired therapeutic effect in the mammal of a compound selected from the group consisting of those having the formula: ##STR1## pharmaceutically acceptable acid addition salts thereof and mixtures thereof, wherein R.sub.1 and R.sub.4 are independently selected from the group consisting of H and alkyl radicals having 1 to 4 carbon atoms; the R.sub.2 s are independently selected from H or alkyl radicals having 1 to 4 carbon atoms or are, together, oxo; the R.sub.3 s are independently selected from H or alkyl radicals having 1 to 4 carbon atoms or are, together, oxo; the 2-imidazolin-2-ylamino group may be in any of the 5-, 6, 7- or 8-positions of the quinoxaline nucleus; and R.sub.5, R.sub.6 and R.sub.7 each is located in one of the remaining 5-, 6-, 7- or 8-positions of the quinoxaline nucleus and is independently selected from the group consisting of Cl, Br, H and alkyl radicals having 1 to 3 carbon atoms. Such compounds, when administered to a mammal, provide desired therapeutic effects, such as reduction in peripheral pain and reduction in or prevention of at least one effect of ischemia.

摘要翻译： 治疗哺乳动物的方法包括向哺乳动物施用有效量以在哺乳动物中提供所需治疗效果，所述化合物选自下列化合物：具有下式的那些化合物：其药学上可接受的酸加成盐及其混合物， 其中R 1和R 4独立地选自H和具有1至4个碳原子的烷基; R 2独立地选自H或具有1至4个碳原子的烷基，或者一起是氧代; R 3独立地选自H或具有1至4个碳原子的烷基，或者一起是氧代; 2-咪唑啉-2-基氨基可以在喹喔啉核的5-，6-或7-位中的任一个中; 并且R5，R6和R7各自位于喹喔啉核的剩余的5-，6-，7-或8-位中的一个，并且独立地选自Cl，Br，H和具有1至 3个碳原子。 当向哺乳动物施用时，这些化合物提供期望的治疗效果，例如减少外周疼痛和减少或预防至少一种局部缺血的作用。

公开(公告)号：US08865766B2

公开(公告)日：2014-10-21

申请号：US13371851

申请日：2012-02-13

申请人： David F. Woodward ,  Jenny W. Wang ,  Neil J. Poloso ,  Todd Gac ,  Robert M. Burk ,  Michael E. Garst

发明人： David F. Woodward ,  Jenny W. Wang ,  Neil J. Poloso ,  Todd Gac ,  Robert M. Burk ,  Michael E. Garst

IPC分类号： A61K8/42 ,  A61Q7/00 ,  C07C405/00

CPC分类号： C07C235/34 ,  A61K8/42 ,  A61Q7/00 ,  C07C405/00 ,  C07C405/0041 ,  C07C2601/08

摘要： Provided herein, inter alia, are prodrugs of bimatoprost, methods of using the same and compositions including the same.

摘要翻译： 本文提供的是比马前列素的前药，其使用方法和包含其的组合物。

公开(公告)号：US08716238B2

公开(公告)日：2014-05-06

申请号：US12499911

申请日：2009-07-09

申请人： Michael E. Garst

发明人： Michael E. Garst

IPC分类号： A61K38/13

CPC分类号： A61K38/13 ,  A61K9/0014 ,  A61K9/0048 ,  A61K38/00 ,  C07K7/645

摘要： The present invention provides a method for the treatment of ocular or dermal diseases and/or conditions, e.g. an aqueous deficient dry eye state, uveitis or phacoanaphylactic endophthalmitis in an eye, or balanitis, psoriasis, or atopic dermatitis of the skin, said method comprising administering, topically to the eye or the skin, a therapeutically effective amount of a novel cyclosporin A derivative selected from the group consisting of compounds represented by the formula: wherein R1 is S-Alk-R wherein Alk is an alkylene linkage, preferably a methylene or poly methylene linkage, e.g. a C2 to C6 polymethylene linkage, or a polyalkenylene linkage, e.g. a C3 to C6 alkenylenyl linkage, R is R is —N═C(NR3R4)(NR5R6) or —NR7[(NR3R4)C═NR5], i.e. guanidines or —N═C(R8)(NR9R10), i.e. amidines wherein R3-R10 is H, Alk, Ar or (CH2)nAr wherein Ar is an aryl group and n is an integer of from 1 to 13 or R3 and R4 or R4 and R5 or R5 and R7 or R3 and R7, or R9 and R10, together may be —CH2—CH2— or —CH2—CH2—CH2— and R2 is selected from the group consisting of hydroxyl, lower alkyl and hydroxyl-substituted lower alkyl and R2 is selected from the group consisting of hydroxy and lower alkyl.

摘要翻译： 本发明提供了用于治疗眼部或皮肤疾病和/或病症的方法，例如， 所述方法包括向眼睛或皮肤局部施用治疗有效量的新型环孢菌素A衍生物，所述方法包括向所述眼睛或皮肤局部施用治疗有效量的新的环孢菌素A衍生物 选自由下式表示的化合物：其中R 1是S-Alk-R，其中Alk是亚烷基键，优选亚甲基或聚亚甲基键，例如 C2-C6聚亚甲基连接，或聚亚烯基键，例如。 C 3 -C 6亚烯基键，R 3是-N = C（NR 3 R 4）（NR 5 R 6）或-NR 7 [（NR 3 R 4）C≡NR5]，即胍或-N = C（R 8）（NR 9 R 10） R 10是H，Alk，Ar或（CH 2）n Ar，其中Ar是芳基，n是1至13的整数，或者R 3和R 4或R 4和R 5或R 5和R 7或R 3和R 7或R 9和R 10， 一起可以是-CH 2 -CH 2 - 或-CH 2 -CH 2 -CH 2 - ，并且R 2选自羟基，低级烷基和羟基取代的低级烷基，R 2选自羟基和低级烷基。

公开(公告)号：US20130274230A1

公开(公告)日：2013-10-17

申请号：US13863934

申请日：2013-04-16

申请人： Richard L. Beard ,  Tien Duong ,  John E. Donello ,  Veena Viswanath ,  Michael E. Garst

发明人： Richard L. Beard ,  Tien Duong ,  John E. Donello ,  Veena Viswanath ,  Michael E. Garst

IPC分类号： C07C309/15 ,  C07D257/04 ,  C07D261/12 ,  C07F9/40

CPC分类号： C07C309/15 ,  C07D257/04 ,  C07D261/12 ,  C07F9/3808 ,  C07F9/4006 ,  C07F9/4021

摘要： The present invention relates to (2-ureidoacetamido)alkyl derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of the N-formyl peptide receptor 2.

摘要翻译： 本发明涉及（2-脲基乙酰胺基）烷基衍生物，其制备方法，含有它们的药物组合物及其作为药物用作N-甲酰基肽受体2的调节剂的用途。

公开(公告)号：US08524671B2

公开(公告)日：2013-09-03

申请号：US12785133

申请日：2010-05-21

申请人： Michael E. Garst ,  Michael E. Stern

发明人： Michael E. Garst ,  Michael E. Stern

IPC分类号： A61K38/13

CPC分类号： C07K7/645 ,  A61K38/13

摘要： The present invention provides a method for the treatment of inflammatory diseases and/or conditions, e.g. allergic conjunctivitis, uveitis or phacoanaphylactic endophthalmitis in an eye of a mammal, said method comprising administering to said mammal in need of treatment a therapeutically effective amount of a novel cyclosporin A derivative selected from the group consisting of compounds represented by the formula: wherein R1 is S-Alk-R wherein Alk is an alkylene linkage, preferably a methylene or poly methylene linkage, or a polyalkenylene linkage, e.g. a C3 to C6 alkenylenyl linkage and R is a hydrogen or a unsubstituted or substituted hydrocarbyl group.

摘要翻译： 本发明提供了治疗炎性疾病和/或病症的方法，例如， 过敏性结膜炎，葡萄膜炎或哺乳动物眼中的眼内炎眼内炎，所述方法包括向需要治疗的所述哺乳动物施用治疗有效量的新型环孢菌素A衍生物，其选自由下式表示的化合物：其中R1为 S-Alk-R其中Alk是亚烷基键，优选亚甲基或聚亚甲基键，或聚亚烯基键，例如 C3至C6链烯基，R为氢或未取代或取代的烃基。