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1. 发明授权

EP0525057B1 ANTIMICROBIAL QUINOLONYL LACTAMS 失效转让
标题翻译： ANTIMIKROBIELLE CHINOLONYL内酰胺
公开(公告)号：EP0525057B1
公开(公告)日：2000-06-14
申请号：EP91908230.5
申请日：1991-04-12
申请人： Procter & Gamble Pharmaceuticals, Inc.
发明人： DEMUTH, Thomas, Prosser, Jr. , WHITE, Ronald, Eugene
IPC分类号： C07D501/28 , C07D501/30 , C07D501/34
CPC分类号： C07D477/14 , C07D477/20 , C07D499/00 , C07D499/88 , C07D501/00

2. 发明授权

EP0599968B1 OXAZOLIDINONE DERIVATIVES USEFUL AS ANTIARRHYTHMIC AND ANTIFIBRILLATORY AGENTS 失效转让
标题翻译：抗心律失常及效果抗纤维性颤动恶唑烷酮衍生物
公开(公告)号：EP0599968B1
公开(公告)日：2000-01-12
申请号：EP92918216.0
申请日：1992-08-10
申请人： PROCTER & GAMBLE PHARMACEUTICALS, INC.
发明人： PELOSI, Stanford, Salvatore, Jr. , YU, Chia-Nien
IPC分类号： C07D413/12 , A61K31/42 , C07D413/14 , A61K31/34 , A61K31/41
CPC分类号： C07D413/10 , C07D413/12 , C07D413/14
摘要： The novel cyclic urethanes, and their pharmaceutically-acceptable salts and esters, described herein which are useful as antiarrhythmic and antifibrillatory agents and have general structure (I), wherein (a) X is a saturated or unsaturated, 5-, 6-, or 7-membered heterocycle or carbocycle; (b) R is selected from the group consisting of covalent bond, nil, heteroatom, carbonyl, heterocyclic ring, carbocyclic ring, alkyl, alkenyl, alkoxy, alkylamino, arylalkyl, aryloxy, acyl, acyloxy, and acylamino; (c) Y is a substituted or unsubstituted, saturated or unsaturated, 5-, 6-, or 7-membered heterocyclic ring or carbocyclic ring, or is nil; and wherein when R is nil, X and Y are fused ring systems; and when R is a covalent bond, X and Y are ring systems linked through a covalent bond; and when Y is nil, R is a covalent bond, and X is a carbocycle bound to L through R; (d) R1, R2, and R3 are independently selected from the group consisting of nil, Cl, F, Br, NH2, CF3, OH, SO3H, CH3SO2NH, COOH, alkoxy, alkyl, alkoxycarbonyl, hydroxyalkyl, carboxyalkyl, aminoalkyl, acylamino, and acyloxy; (e) L is selected from the group consisting of alkylamino, alkenylamino, alkylimino, alkenylimino and acylamino; wherein the nitrogen atom thereof is bound to the nitrogen atom at the 3-position of the cyclic urethane ring moiety; (f) R4 is selected from the group consisting of alkyl, alkenyl, alkynyl, alkylacyl, and heteroalkyl; (g) A is a substituted or unsubstituted, saturated or unsaturated, straight-chain or branched, C1-C8 heteroalkyl; or a substituted or unsubstituted, saturated or unsaturated heterocycle having 6- or 7-members which may not have an oxygen atom; and A has one nitrogen atom which is adjacent to R4; and (h) R5 is a substituted or unsubstituted C1 or C2 alkyl; and the pharmaceutically-acceptable salts and esters thereof.

3. 发明授权

EP0643716B1 QUATERNARY NITROGEN-CONTAINING PHOSPHONATE COMPOUNDS FOR TREATING ABNORMAL CALCIUM AND PHOSPHATE METABOLISM 失效
标题翻译：季氮，含含膦酸盐化合物用于治疗不正常的钙，磷代谢
公开(公告)号：EP0643716B1
公开(公告)日：1999-12-08
申请号：EP93914198.2
申请日：1993-05-27
申请人： THE PROCTER & GAMBLE PHARMACEUTICALS, INC.
发明人： EBETINO, Frank, H. , KAAS, Susan, M. , FRANCIS, Marion, David
IPC分类号： C07F9/576 , A61K31/66 , C07F9/38 , C07F9/6561 , C07F9/572 , C07F9/60
CPC分类号： C07F9/3873 , C07F9/5726 , C07F9/5765 , C07F9/60 , C07F9/6561
摘要： The present invention relates to a quaternary nitrogen-containing, saturated or unsaturated monocyclic and bicyclic ring containing phosphonate and the pharmaceutically-acceptable salts and esters thereof, having structure (I). The present invention further relates to pharmaceutical compositions containing a safe and effective amount of a compound of the present invention, and pharmaceutically-acceptable excipients. Finally, the present invention relates to methods for treating or preventing pathological conditions characterized by abnormal calcium and phosphate metabolism in humans or other mammals. This method comprises administering to a human or other mammal in need of such treatment of a safe and effective amount of a compound or composition of the present invention.

4. 发明授权

EP0646119B1 QUATERNARY NITROGEN-CONTAINING PHOSPHONATE COMPOUNDS FOR TREATING ABNORMAL CALCIUM AND PHOSPHATE METABOLISM AS WELL AS DENTAL CALCULUS AND PLAQUE 失效
标题翻译：季氮，含含膦酸盐化合物用于治疗不正常的钙，磷代谢和牙垢的形成
公开(公告)号：EP0646119B1
公开(公告)日：1998-07-15
申请号：EP93914197.4
申请日：1993-05-27
申请人： PROCTER & GAMBLE PHARMACEUTICALS, INC.
发明人： EBETINO, Frank, Hallock , DANSEREAU, Susan Mary , FRANCIS, Marion, David , NELSON, Dennis, George, Anthony , JANUSZ, John, Michael
IPC分类号： C07F9/38 , A61K31/66 , C07F9/58 , C07F9/59 , C07F9/576 , C07F9/6506
CPC分类号： C07F9/582 , C07F9/3873 , C07F9/5722 , C07F9/5765 , C07F9/592 , C07F9/65062
摘要： The present invention relates to quaternary nitrogen-containing phosphonate compounds, and the pharmaceutically-acceptable salts and esters thereof and having general structure (I). The present invention further relates to pharmaceutical compositions containing a safe and effective amount of a compound of the present invention, and pharmaceutically-acceptable excipients. Finally, the present invention relates to methods for treating or preventing pathological conditions characterized by abnormal calcium and phosphate metabolism such as osteoporosis, rheumatoid arthritis, and osteoarthritis in humans or other mammals and to methods for treating or preventing dental calculus, plaque and gingivitis. This method comprises administering to a human or other mammal in need of such treatment a safe and effective amount of a compound or composition of the present invention.

5. 发明公开

EP0650361A1 COMPOSITIONS FOR THE TREATMENT OF ARTHRITIS CONTAINING PHOSPHONATES AND NSAIDS 失效
标题翻译：药物治疗关节炎包括膦酸盐和NSAIDS。
公开(公告)号：EP0650361A1
公开(公告)日：1995-05-03
申请号：EP93914470.0
申请日：1993-06-14
申请人： PROCTER & GAMBLE PHARMACEUTICALS, INC.
发明人： HOVANCIK, Kristine , FRANCIS, Marion David , UNDERWOOD, Richard Allen
IPC分类号： A61K31 , A61K45 , A61P3 , A61P19 , A61P43
CPC分类号： A61K31/675 , A61K31/54 , A61K31/52 , A61K31/19 , A61K31/405 , A61K2300/00
摘要： The present invention provides methods of treating a human or other animal subject afflicted with arthritis, including rheumatoid, arthritis and osteoarthritis, comprising a sixty (60)-day treatment period, comprised of an optional NSAID administration regimen and a phosphonate administration regimen, wherein (a) said optional NSAID administration regimen which comprises the administration to said subject of NSAIDs at a level of from 20% to 80%, preferably 20% to 70%, most preferably 20% to 50% of the conventionally prescribed daily dose on each day that said NSAID is administered; provided that said NSAID is administered in sufficient quantities and on a sufficient number of days to alleviate symptoms of inflammation, and wherein (b) said phosphonate administration regimen comprises the administration to said subject of a phosphonate at a dose equivalent to a systemic level of from about 0.0005 mgP/kg to about 1.0 mgP/kg per day that said phosphonate is administered; provided that said phosphonate is administered at least 1 day of every said sixty (60)-day treatment period.

6. 发明公开

EP0613373A1 RISEDRONATE DELAYED-RELEASE COMPOSITIONS 有权转让
标题翻译：利塞膦含药缓释。
公开(公告)号：EP0613373A1
公开(公告)日：1994-09-07
申请号：EP92924208.0
申请日：1992-11-02
申请人： THE PROCTER & GAMBLE PHARMACEUTICALS, INC.
发明人： DANSEREAU, Richard, John , MOSHER, Russell, Youker , AXELROD, Douglas, Wayne , SIETSEMA, William, Kendall
IPC分类号： A61K9 , A61K31 , A61K47 , A61P3 , A61P5 , A61P19 , A61P21 , A61P29 , A61P35 , A61P43
CPC分类号： A61K31/675 , A61K9/2846 , A61K9/2866 , A61K9/5026 , A61K9/5078
摘要： Nouvelle forme pharmaceutique entérosoluble administrable par voie orale d'un ingrédient actif au risédronate. Elle est constituée d'une quantité inoffensive et efficace d'une composition pharmaceutique composée d'un ingrédient actif au risédronate et d'excipients pharmaceutiquement acceptables. Ces formes pharmaceutiques empêchent l'exposition de l'ingrédient actif au risédronate aux tissus épithéliaux et muqueux de la cavité buccale, du pharynx, de l'oesophage et de l'estomac, et peuvent donc protéger ces tissus de l'érosion, de l'ulcération ou d'une irritation semblable. Par conséquent, lesdites formes pharmaceutiques assurent la libération dans l'intestin inférieur de l'homme ou d'un autre mammifère d'une quantité inoffensive et efficace d'un ingrédient actif au risédronate, ainsi qu'un soulagement sensible de l'oesophagite ou de l'irritation oesophagienne qui sont parfois associées à l'administration par voie orale des ingrédients actifs au risédronate.

7. 发明公开

EP0997466A1 Novel antimicrobial lactam-quinolones 失效
标题翻译：新型抗菌内酰胺 - 喹诺酮类
公开(公告)号：EP0997466A1
公开(公告)日：2000-05-03
申请号：EP99204491.7
申请日：1989-10-18
申请人： PROCTER & GAMBLE PHARMACEUTICALS, INC.
发明人： White, Ronald Eugene , Demuth Jr, Thomas Prosser
IPC分类号： C07D501/20 , C07D499/00 , C07D499/88 , C07D401/12 , C07D463/16 , C07D477/14 , C07D477/20 , C07D503/00 , C07D505/00 , C07D513/04 , C07D498/04 , C07D487/04 , A61K31/546 , A61K31/431 , A61P31/04
CPC分类号： C07D401/04 , C07D215/56 , C07D401/12 , C07D401/14 , C07D417/14 , C07D455/04 , C07D463/18 , C07D463/22 , C07D471/04 , C07D477/10 , C07D487/04 , C07D499/00 , C07D501/00 , C07D503/00 , C07D505/00 , C07D513/04
摘要： Antimicrobial lactam-quinolone compounds comprising a lactam-containing moiety linked to a quinolone moiety, of the formula:
wherein

(1) A 1 , A 2 , A 3 , R 1 , R 4 and R 6 generally form any of a variety of quinolone, naphthyridine or related cyclic moieties known in the art to have antimicrobial activity; and
(2) R 1 or R 3 contain a linking moiety, linking the quinolone moiety to a lactam-containing moiety having the formula:
wherein
(3) R 10 , R 11 , R 12 , R 13 , and R 14 , together with bonds "a" and "b" form any of a variety of lactam-containing moieties known in the art to have antimicrobial activity; and
(4) the linking moiety includes (for example) carbamate, dithiocarbamate, urea, thiourea, isouronium, isothiouronium, guanidine, carbonate, trithiocarbonate, reversed carbamate, xanthate, reversed isouronium, reversed dithiocarbamate, reversed isothiouronium, amine, imine, ammonium, heteroarylium, ether, thioether, phosphono, phosphoramide, phosphate, sulfonamide, ester, thioester, amide, and hydrazide groups.
摘要翻译：包含与喹诺酮部分连接的含内酰胺部分的抗微生物内酰胺 - 喹诺酮化合物，其具有下式：其中（1）A1，A2，A3，R1，R4和R6通常形成多种喹诺酮，萘啶或相关环状部分中的任一种本领域已知具有抗微生物活性; （2）R 1或R 3含有连接部分，将喹诺酮部分连接至具有下式的含内酰胺部分：其中（3）R 10，R 11，R 12，R 13和R 14连同键“a”和“b “形成本领域已知的具有抗微生物活性的各种含内酰胺部分中的任何一种; （4）连接部分包括氨基甲酸酯，二硫代氨基甲酸酯，脲，硫脲，异脲鎓，异硫脲鎓，胍，碳酸酯，三硫代碳酸酯，反向氨基甲酸酯，黄原酸酯，反异脲鎓，反二硫代氨基甲酸酯，反异硫脲，胺，亚胺，杂芳基醚，醚，硫醚，膦酰基，磷酰胺，磷酸酯，磺酰胺，酯，硫酯，酰胺和酰肼基团。

8. 发明授权

EP0650361B1 COMPOSITIONS FOR THE TREATMENT OF ARTHRITIS CONTAINING PHOSPHONATES AND NSAIDS 失效
标题翻译：治疗关节炎的膦酸盐药物NSAIDS CONTAIN
公开(公告)号：EP0650361B1
公开(公告)日：1999-04-28
申请号：EP93914470.5
申请日：1993-06-14
申请人： PROCTER & GAMBLE PHARMACEUTICALS, INC.
发明人： HOVANCIK, Kristine , FRANCIS, Marion David , UNDERWOOD, Richard Allen
IPC分类号： A61K31/675
CPC分类号： A61K31/675 , A61K31/54 , A61K31/52 , A61K31/19 , A61K31/405 , A61K2300/00

9. 发明授权

EP0606336B1 PROCESS FOR MAKING ANTIMICROBIAL QUINOLONYL LACTAMS 失效转让
标题翻译：用于生产抗菌喹诺酮内酰胺
公开(公告)号：EP0606336B1
公开(公告)日：1997-03-19
申请号：EP92920743.9
申请日：1992-09-28
申请人： PROCTER & GAMBLE PHARMACEUTICALS, INC.
发明人： WHITE, Ronald, Eugene , DEMUTH, Thomas, Prosser, Jr.
IPC分类号： C07D499/883 , C07D477/14 , C07D463/22 , C07D505/24 , C07D519/06
CPC分类号： C07D505/00 , C07D477/02 , C07D499/88 , Y02P20/55
摘要： The present invention provides methods of making compounds of the structure [Q - L1] - L - [L2 - B], wherein Q is a quinolone moiety; B is a beta-lactam moiety; L, L?1, and L2¿ together comprise a carbamate-containing linking moiety, comprising the steps of: 1) reacting a lactam compound of the formula B-L4-H with phosgene to form an intermediate compound of the formula B-L4-C(=O)-Cl, where L4 is oxygen; and 2) coupling said intermediate compound with a quinolone compound of the formula Q-l3-R44, wherein L3 is nitrogen; R44 is hydrogen, Si(R45)3, or Sn(R45)3; and R45 is lower alkyl. Preferably, the process additionally comprises steps prior to the reacting and coupling steps where esters of the lactam and quinolone compounds are made. Also preferably, the coupling step comprises adding a solution containing the quinolone compound to a solution containing the intermediate compound. The process steps are also preferably performed at a temperature of from about -80 °C to about 0 °C. Preferred antimicrobial compounds made by these processes are those where the beta-lactam moiety is a penem.

10. 发明公开

EP0648120A1 USE OF PHOSPHONATES FOR THE TREATMENT OF OSTEOPOROSIS 有权转让
标题翻译：膦酸盐骨质疏松症的治疗。
公开(公告)号：EP0648120A1
公开(公告)日：1995-04-19
申请号：EP93914339.0
申请日：1993-06-04
申请人： PROCTER & GAMBLE PHARMACEUTICALS, INC.
发明人： FRANCIS, Marion, David , BOYCE, Rogely, Waite
IPC分类号： A61K31 , A61P3 , A61P19 , A61P43 , C07F9
CPC分类号： A61K31/675 , A61K31/66 , C07F9/582 , C07F9/592
摘要： A method of increasing bone mass in a human or other mammal subject afflicted with osteoporosis, comprising a thirty (30) day treatment period, comprised of a high potency phosphonate compound administration regimen wherein a) said high potency phosphonate administration regimen comprises the systemic administration to said subject of a high potency phosphonate compound at a level of from 0.00001 mgP/kg to 0.1 mgP/kg per day that said high potency phosphonate compound is administered, provided that said high potency phosphonate compound is administered at least one day of every said thirty (30) day treatment period; and wherein b) said thirty (30) day treatment period may be followed by a rest period of at least one day.

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