公开(公告)号：US5420277A

公开(公告)日：1995-05-30

申请号：US157801

申请日：1993-11-29

申请人： William H. Koster ,  Joseph E. Sundeen ,  Henner Straub ,  Peter Ermann ,  Uwe D. Treuner ,  Kent Amsberry ,  Michael Fakes ,  Sailesh A. Varia

发明人： William H. Koster ,  Joseph E. Sundeen ,  Henner Straub ,  Peter Ermann ,  Uwe D. Treuner ,  Kent Amsberry ,  Michael Fakes ,  Sailesh A. Varia

IPC分类号： C07C211/50 ,  A61K31/495 ,  A61K31/498 ,  A61P31/04 ,  C07C217/84 ,  C07C217/86 ,  C07C251/38 ,  C07C271/66 ,  C07D20060101 ,  C07D241/42 ,  C07D241/44 ,  C07D241/52 ,  C07D417/14 ,  C07D491/04 ,  C07D491/056 ,  C07F9/40 ,  C07F9/6509

CPC分类号： C07D241/52 ,  C07C217/86 ,  C07C271/66 ,  C07D241/44 ,  C07D417/14 ,  C07D491/04 ,  C07F9/650994 ,  Y02P20/55

摘要： Antibacterial activity is exhibited by novel compounds having the formula ##STR1## where R.sub.1, R.sub.2, and M are as defined herein and X is --(CH.sub.2).sub.n -- wherein n is 0, 1, 2, 3 or 4 or CR.sub.3 R.sub.4 wherein R.sub.3 and R.sub.4 are the same or different and each is hydrogen, --CH.sub.3 or --C.sub.2 H.sub.5 or R.sub.3 and R.sub.4 taken together with the carbon atom to which they are attached form a 3, 4, 5, 6 or 7-membered cycloalkyl ring. Also described are various intermediates for the preparation of compounds of formula 1.

摘要翻译： 具有式（IMAGE）1的新化合物表现出抗菌活性，其中R 1，R 2和M如本文所定义，X为 - （CH 2）n - ，其中n为0,1,2,3或4或CR 3 R 4，其中R 3 和R 4相同或不同，各自为氢，-CH 3或-C 2 H 5或R 3和R 4与它们所连接的碳原子一起形成3,4,5,6或7元环烷基环。 还描述了制备式1化合物的各种中间体。

公开(公告)号：US20080275009A1

公开(公告)日：2008-11-06

申请号：US12168366

申请日：2008-07-07

申请人： Ramakrishnan Chidambaram ,  George M. Derbin ,  Masaki Endo ,  Julia ZH Gao ,  Tu Lee ,  Rajeshwar Motheram ,  William Lawrence Parker ,  Victor W. Rosso ,  Sailesh A. Varia

发明人： Ramakrishnan Chidambaram ,  George M. Derbin ,  Masaki Endo ,  Julia ZH Gao ,  Tu Lee ,  Rajeshwar Motheram ,  William Lawrence Parker ,  Victor W. Rosso ,  Sailesh A. Varia

IPC分类号： A61K31/60 ,  A61K31/506 ,  A61P35/00 ,  C07D403/14

CPC分类号： C07D417/12 ,  A61K31/506 ,  A61K45/06 ,  A61K2300/00

摘要： Disclosed are a method of treating cancer and/or other proliferative diseases comprising orally administering N-(2-chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)-1-piperazinyl)-2-methyl-4-pyrimidinyl)amino)-1,3-thiazole-5-carboxamide or a salt thereof, and pharmaceutical compositions comprising N-(2-chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)-1-piperazinyl)-2-methyl-4-pyrimidinyl)amino)-1,3-thiazole-5-carboxamide or a salt thereof. Also disclosed are N-(2-chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)-1-piperazinyl)-2-methyl-4-pyrimidinyl)amino)-1,3-thiazole-5-carboxamide salts, as well as crystalline forms thereof.

摘要翻译： 公开了一种治疗癌症和/或其它增殖性疾病的方法，其包括口服给予N-（2-氯-6-甲基苯基）-2 - （（6-（4-（2-羟乙基）-1-哌嗪基）-2- 甲基-4-嘧啶基）氨基）-1,3-噻唑-5-甲酰胺或其盐，以及包含N-（2-氯-6-甲基苯基）-2 - （（6-（4-（2 - 羟基乙基）-1-哌嗪基）-2-甲基-4-嘧啶基）氨基）-1,3-噻唑-5-甲酰胺或其盐。 还公开了N-（2-氯-6-甲基苯基）-2 - （（6-（4-（2-羟乙基）-1-哌嗪基）-2-甲基-4-嘧啶基）氨基） 噻唑-5-甲酰胺盐，以及其结晶形式。

公开(公告)号：US5705645A

公开(公告)日：1998-01-06

申请号：US399793

申请日：1995-03-07

申请人： William H. Koster ,  Joseph E. Sundeen ,  Henner Straub ,  Peter Ermann ,  Uwe D. Treuner ,  Kent Amsberry ,  Michael Fakes ,  Sailesh A. Varia

发明人： William H. Koster ,  Joseph E. Sundeen ,  Henner Straub ,  Peter Ermann ,  Uwe D. Treuner ,  Kent Amsberry ,  Michael Fakes ,  Sailesh A. Varia

IPC分类号： C07C211/50 ,  A61K31/495 ,  A61K31/498 ,  A61P31/04 ,  C07C217/84 ,  C07C217/86 ,  C07C251/38 ,  C07C271/66 ,  C07D20060101 ,  C07D241/42 ,  C07D241/44 ,  C07D241/52 ,  C07D417/14 ,  C07D491/04 ,  C07D491/056 ,  C07F9/40 ,  C07F9/6509 ,  C07D487/04

CPC分类号： C07D241/52 ,  C07C217/86 ,  C07C271/66 ,  C07D241/44 ,  C07D417/14 ,  C07D491/04 ,  C07F9/650994 ,  Y02P20/55

摘要： Antibacterial activity is exhibited by novel compounds having the formula ##STR1## where R.sub.1, R.sub.2, and M are as defined herein and X is --(CH.sub.2).sub.n -- wherein n is 0, 1, 2, 3 or 4 or CR.sub.3 R.sub.4 wherein R.sub.3 and R.sub.4 are the same or different and each is hydrogen, --CH.sub.3 or --C.sub.2 H.sub.5 or R.sub.3 and R.sub.4 taken together with the carbon atom to which they are attached form a 3, 4, 5, 6 or 7-membered cycloalkyl ring.

摘要翻译： 具有式（IMAGE）1的新化合物表现出抗菌活性，其中R 1，R 2和M如本文所定义，X为 - （CH 2）n - ，其中n为0,1,2,3或4或CR 3 R 4，其中R 3 和R 4相同或不同，各自为氢，-CH 3或-C 2 H 5或R 3和R 4与它们所连接的碳原子一起形成3,4,5,6或7元环烷基环。

公开(公告)号：US06218375B1

公开(公告)日：2001-04-17

申请号：US09483840

申请日：2000-01-17

申请人： Krishnaswamy S. Raghavan ,  Timothy M. Malloy ,  Sailesh A. Varia

发明人： Krishnaswamy S. Raghavan ,  Timothy M. Malloy ,  Sailesh A. Varia

IPC分类号： A61K31715

CPC分类号： B82Y5/00 ,  A61K47/6951 ,  Y10S514/97 ,  Y10S514/973

摘要： A ras-farnesyltransferase inhibitor complex formed of ras-farnesyltransferase inhibitor or a pharmaceutically acceptable salt thereof, of the formula I wherein n is 0 or 1; R1 is selected from Cl, Br, phenyl, pyridyl or cyano; R2 is aralkyl; R3 is selected from lower alkyl, aryl or substituted aryl or heterocyclo; Z1 is selected from CO, SO2, CO2, or SO2NR5, R5 is selected from hydrogen, lower alkyl or substituted alkyl; and sulfobutylether-7-&bgr;-cyclodextrin or 2-hydroxypropyl-&bgr;-cyclodextrin is provided. The complex has unexpectedly high aqueous solubility of the ras-farnesyltransferase inhibitor and is useful for its intravenous delivery to humans with cancer. Also provided is a method for forming the complex. The ras-farnesyltransferase inhibitors are useful as anti-tumor agents.

摘要翻译： 由r-法呢基转移酶抑制剂或其药学上可接受的盐形成的具有式I的ras法呢基转移酶抑制剂复合物，其中n为0或1; R 1选自Cl，Br，苯基，吡啶基或氰基; R2是芳烷基; R3选自低级烷基，芳基或取代的芳基或杂环; Z1选自CO，SO2，CO2或SO2NR5，R5选自氢，低级烷基或取代的烷基; 并提供磺基丁醚-7-β-环糊精或2-羟丙基-β-环糊精。 该复合物具有意想不到的拉法伐西转移酶抑制剂的高溶解度，并且可用于其向癌症患者的静脉内递送。 还提供了形成复合物的方法。 拉法尼基转移酶抑制剂可用作抗肿瘤剂。

公开(公告)号：US4868170A

公开(公告)日：1989-09-19

申请号：US120277

申请日：1987-11-13

申请人： Marilia M. Faustino ,  Sailesh A. Varia ,  Abu T. M. Serajuddin

发明人： Marilia M. Faustino ,  Sailesh A. Varia ,  Abu T. M. Serajuddin

IPC分类号： A61K9/00 ,  A61K31/565 ,  A61K47/00 ,  A61K47/10

CPC分类号： A61K9/0014 ,  A61K31/565 ,  A61K47/10

摘要： A steroid lotion formulation which has enhanced physical and chemical stability is formed of (11.beta.,17.alpha.)-17-(ethylthio)-9.alpha.-fluoro-11.beta.-hydroxy-17-(methylthio)androsta-1,4-diene-3-one (tipredane), and a vehicle containing as major ingredients polyethylene glycol, propylene glycol and water together with a potassium citrate buffer or tromethamine buffer, and sodium metabisulfite and butylated hydroxytoluene as antioxidants.

摘要翻译： 具有增强的物理和化学稳定性的类固醇洗剂制剂由（11β，17α）-17-（乙硫基）-9α-氟-11β-羟基-17-（甲硫基）雄甾-1,4-二烯 -3-one（tipredane）和含有柠檬酸钾缓冲液或氨丁三醇缓冲液的主要成分聚乙二醇，丙二醇和水以及偏亚硫酸氢钠和丁基化羟基甲苯作为抗氧化剂的载体。

公开(公告)号：US5290929A

公开(公告)日：1994-03-01

申请号：US941600

申请日：1992-09-08

申请人： William H. Koster ,  Joseph E. Sundeen ,  Henner Straub ,  Peter Ermann ,  Uwe D. Treuner ,  Kent Amsberry ,  Michael Fakes ,  Sailesh A. Varia

发明人： William H. Koster ,  Joseph E. Sundeen ,  Henner Straub ,  Peter Ermann ,  Uwe D. Treuner ,  Kent Amsberry ,  Michael Fakes ,  Sailesh A. Varia

IPC分类号： C07C211/50 ,  A61K31/495 ,  A61K31/498 ,  A61P31/04 ,  C07C217/84 ,  C07C217/86 ,  C07C251/38 ,  C07C271/66 ,  C07D20060101 ,  C07D241/42 ,  C07D241/44 ,  C07D241/52 ,  C07D417/14 ,  C07D491/04 ,  C07D491/056 ,  C07F9/40 ,  C07F9/6509

CPC分类号： C07D241/52 ,  C07C217/86 ,  C07C271/66 ,  C07D241/44 ,  C07D417/14 ,  C07D491/04 ,  C07F9/650994 ,  Y02P20/55

摘要： Antibacterial activity is exhibited by novel compounds having the formula ##STR1## where R.sub.1, R.sub.2, and M are as defined herein and X is --(CH.sub.2).sub.n -- wherein n is 0, 1, 2, 3 or 4 or CR.sub.3 R.sub.4 wherein R.sub.3 and R.sub.4 are the same or different and each is hydrogen, --CH.sub.3 or --C.sub.2 H.sub.5 or R.sub.3 and R.sub.4 taken together with the carbon atom to which they are attached form a 3, 4, 5, 6 or 7-membered cycloalkyl ring.

摘要翻译： 具有式（IMAGE）1的新化合物表现出抗菌活性，其中R 1，R 2和M如本文所定义，X为 - （CH 2）n - ，其中n为0,1,2,3或4或CR 3 R 4，其中R 3 和R 4相同或不同，各自为氢，-CH 3或-C 2 H 5或R 3和R 4与它们所连接的碳原子一起形成3,4,5,6或7元环烷基环。

公开(公告)号：US4868169A

公开(公告)日：1989-09-19

申请号：US120278

申请日：1987-11-13

申请人： Richard L. O'Laughlin ,  Andrea Panaggio ,  Sailesh A. Varia

发明人： Richard L. O'Laughlin ,  Andrea Panaggio ,  Sailesh A. Varia

IPC分类号： A61K9/06 ,  A61K9/00 ,  A61K31/565 ,  A61K47/00 ,  A61K47/14 ,  A61P29/00

CPC分类号： A61K9/0014 ,  A61K31/565

摘要： A steroid cream formulation which has enhanced physical and chemical stability is formed of (11.beta.,17.alpha.)-17-(ethylthio)-9.alpha.-fluoro-11.beta.-hydroxy-17-(methylthio)androsta-1,4-dien-3-one (tipredane), and a vehicle containing as major ingredients glyceryl monostearate having an acid value of greater than 4, propylene glycol and water together with a sodium citrate or potassium citrate buffer, a non-acidic long chain fatty acid wax to impart proper consistency, and sodium metabisulfite as an antioxidant, together with emulsifiers, skin conditioners, emollients, lubricants and other conventional cream formulation ingredients.

公开(公告)号：US4868168A

公开(公告)日：1989-09-19

申请号：US120276

申请日：1987-11-13

申请人： Richard L. O'Laughlin ,  Andrea Panaggio ,  Sailesh A. Varia

发明人： Richard L. O'Laughlin ,  Andrea Panaggio ,  Sailesh A. Varia

IPC分类号： A61K9/06 ,  A61K9/00 ,  A61K31/565 ,  A61K47/00 ,  A61K47/10 ,  A61P29/00

CPC分类号： A61K31/565 ,  A61K9/0014

摘要： A steroid ointment formulation which has enhanced physical and chemical stability is formed of 11.beta.,17.alpha.)-17-(ethylthio)-9.alpha.-fluoro-11.beta.-hydroxy-17-(methylthio)androsta-1,4-dien-3-one (tipredane), and a vehicle containing as major ingredients propylene glycol and water, cetearyl alcohol and ceteareth 20 or other dispersing agent for propylene glycol, together with a sodium or potassium citrate and magnesium hydroxide buffer to impart a neutral or slightly alkaline apparent pH (5 to 9), a non-acidic long chain fatty acid wax to impart proper consistency to the ointment and sodium metabisulfite and butylated hydroxy toluene as antioxidants, together with thickeners, emollients, lubricants and other conventional ointment formulation ingredients.

公开(公告)号：US5536507A

公开(公告)日：1996-07-16

申请号：US265167

申请日：1994-06-24

申请人： Robert Abramowitz ,  Sunanda A. Ranadive ,  Sailesh A. Varia ,  Nemichand B. Jain

发明人： Robert Abramowitz ,  Sunanda A. Ranadive ,  Sailesh A. Varia ,  Nemichand B. Jain

IPC分类号： A61K9/16 ,  A61K9/32 ,  A61K9/36 ,  A61K9/50 ,  A61K9/58 ,  A61K9/62

CPC分类号： A61K9/5073 ,  A61K9/1635

摘要： A three component pharmaceutical formulation of one or more pharmacologically active substances such that greater than 80% of the pharmacologically active substance will be released in the large intestine. The first component comprises the pharmacologically active substance, microcrystalline cellulose, a pH-sensitive polymer, and optionally an osmotic agent. The second component is a delayed release coating, and the third component is an enteric coating.

摘要翻译： 一种或多种药理学活性物质的三组分药物制剂，使得大于80％的药理活性物质将在大肠中释放。 第一组分包括药理活性物质，微晶纤维素，pH敏感聚合物，以及任选的渗透剂。 第二组分是延迟释放涂层，第三组分是肠溶衣。