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1. 发明申请

WO2009018065A2 NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME 审中-公开
标题翻译：新型葡糖激酶激活剂及其使用方法
公开(公告)号：WO2009018065A2
公开(公告)日：2009-02-05
申请号：PCT/US2008070962
申请日：2008-07-24
申请人： SQUIBB BRISTOL MYERS CO , SHI YAN , CHENG PETER T W , WANG YING , RYONO DENIS E
发明人： SHI YAN , CHENG PETER T W , WANG YING , RYONO DENIS E
IPC分类号： C07D213/81 , A61K31/4164 , A61K31/4196 , A61K31/426 , A61P3/00 , C07C237/22 , C07D231/14 , C07D233/90 , C07D241/24 , C07D249/10 , C07D277/56 , C07D277/68 , C07D471/04 , C07D513/04
CPC分类号： C07D277/56 , C07C317/22 , C07D213/81 , C07D231/14 , C07D233/90 , C07D241/24 , C07D249/10 , C07D277/68 , C07D471/04 , C07D513/04
摘要： Compounds are provided which are activators of the enzyme glucokinase and thus are useful in treating diabetes and related diseases, which compounds have the structure Formula: (I); where Q is Formula: (II); or Formula: (III); and R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.
摘要翻译：提供了作为酶葡糖激酶活化剂的化合物，因此可用于治疗糖尿病和相关疾病，所述化合物具有结构式：（I）; 其中Q是式（II）; 或式（III）; 且R 1，R 2，R 3，R 4，R 5，R 6，R 7和R 8如本文所定义或其药学上可接受的盐。还提供了使用上述化合物治疗糖尿病和相关疾病的方法。

2. 发明申请

WO0194293A2 BENZAMIDE LIGANDS FOR THE THYROID RECEPTOR 审中-公开
标题翻译：苄基受体的苯扎林配体
公开(公告)号：WO0194293A2
公开(公告)日：2001-12-13
申请号：PCT/US0117742
申请日：2001-06-01
申请人： SQUIBB BRISTOL MYERS CO , RYONO DENIS E
发明人： RYONO DENIS E
IPC分类号： A61K45/00 , A61K31/07 , A61K31/166 , A61K31/195 , A61K31/22 , A61K31/351 , A61K31/40 , A61K31/404 , A61K31/4418 , A61K31/455 , A61K31/592 , A61K38/28 , A61P3/00 , A61P3/04 , A61P3/06 , A61P5/14 , A61P5/16 , A61P9/04 , A61P9/06 , A61P9/10 , A61P17/00 , A61P17/02 , A61P17/10 , A61P17/16 , A61P19/10 , A61P25/24 , A61P27/06 , A61P35/00 , C07C235/52 , C07C235/00
CPC分类号： A61K31/166 , C07C235/52 , C07C2601/02
摘要： New thyroid receptor ligands are provided which have the general formula (I) in which: X is -0-, -S-, -CH2-, -CO-, or -NH-; R1 is halogen, trifluoromethyl, or alkyl of 1 to 6 carbons or cycloalkyl of 3 to 7 carbons; R2 and R3 are the same or different and are hydrogen, halogen, alkyl of 1 to 4 carbons or cycloalkyl of 3 to 6 carbons, at least one of R2 and R3 being other than hydrogen; R4 is methyl, ethyl, n-propyl or trifluoromethyl; R5 is hydrogen or lower alkyl; R6 is carboxylic acid, or esters or prodrugs; R7 is hydrogen or an alkanoyl or an aroyl. In addition, a method is provided for preventing, inhibiting or treating a disease associated with metabolism dysfunction or which is dependent upon the expression of a T3 regulated gene, wherein a compound as described above is administered in a therapeutically effective amount. Examples of such diseases associated with metabolism dysfunction or are dependent upon the expression of a T3 regulated gene include obesity, hypercholesterolemia, atherosclerosis, cardiac arrhythmias, depression, osteoporosis, hypothyroidism, goiter, thyroid cancer as well as glaucoma, congestive heart failure and skin disorders.
摘要翻译：提供了具有通式（I）的新甲状腺受体配体，其中：X是-O - ， - S - ， - CH 2 - ， - CO-或-NH-; R1是卤素，三氟甲基或1-6个碳的烷基或3-7个碳的环烷基; R2和R3相同或不同，为氢，卤素，1至4个碳的烷基或3至6个碳的环烷基，R2和R3中的至少一个不是氢; R4是甲基，乙基，正丙基或三氟甲基; R5是氢或低级烷基; R6是羧酸，或酯或前药; R7是氢或烷酰基或芳酰基。此外，提供了用于预防，抑制或治疗与代谢功能障碍相关的疾病或依赖于T3调节基因的表达的方法，其中以治疗有效量施用如上所述的化合物。与代谢功能障碍相关或依赖于T3调节基因的表达的这种疾病的实例包括肥胖症，高胆固醇血症，动脉粥样硬化，心律失常，抑郁症，骨质疏松症，甲状腺功能减退，甲状腺癌，青光眼，充血性心力衰竭和皮肤病。

3. 发明申请

WO2004067482A3 SUBSTITUTED ANILIDE LIGANDS FOR THE THYROID RECEPTOR 审中-公开
标题翻译：用于甲状腺受体的取代的苯胺配体
公开(公告)号：WO2004067482A3
公开(公告)日：2004-10-21
申请号：PCT/US2004001985
申请日：2004-01-23
申请人： SQUIBB BRISTOL MYERS CO , KAROBIO AB , WASHBURN WILLIAM N , MENG WEI , RYONO DENIS E , ELLSWORTH BRUCE A , ERICSSON THOMAS , RAHIMI-GHADIM MAHMOUD , GARG NEERAJ , MALM JOHAN
发明人： WASHBURN WILLIAM N , MENG WEI , RYONO DENIS E , ELLSWORTH BRUCE A , ERICSSON THOMAS , RAHIMI-GHADIM MAHMOUD , GARG NEERAJ , MALM JOHAN
IPC分类号： A61K31/195 , A61K31/24 , A61K31/277 , A61K31/44 , C07C20060101 , C07C229/08 , C07C229/22 , C07C233/25 , C07D213/57
CPC分类号： A61K45/06 , A61K31/195 , A61K31/277 , A61K31/44 , C07C233/25 , A61K2300/00
摘要： Novel thyroid receptor ligands are provided having the general formula I wherein X, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12. and R13 are as defined herein. In addition, a method is provided for preventing, inhibiting or treating diseases or disorders associated with metabolic dysfunction or which are dependent upon the expression of a T3 regulated gene, wherein a compound as described above is administered in a therapeutically effective amount.
摘要翻译：提供具有通式I的新的甲状腺受体配体，其中X，R1，R2，R3，R4，R5，R6，R7，R8，R9，R10，R11，R12。和R13如本文所定义。此外，提供了用于预防，抑制或治疗与代谢功能障碍相关的疾病或病症或依赖于T3调节基因表达的方法，其中如上所述的化合物以治疗有效量施用。

4. 发明专利

CA2096460A1 DUAL ACTION INHIBITORS 未知
公开(公告)号：CA2096460A1
公开(公告)日：1993-11-19
申请号：CA2096460
申请日：1993-05-18
申请人： KARANEWSKY DONALD S , BARRISH JOEL C , PETRILLO EDWARD W , ROBL JEFFREY A , RYONO DENIS E
发明人： KARANEWSKY DONALD S , BARRISH JOEL C , PETRILLO EDWARD W JR , ROBL JEFFREY A , RYONO DENIS E
IPC分类号： C07D223/24 , A61K31/395 , A61K31/4353 , A61K31/54 , A61K31/55 , A61K31/551 , A61K31/553 , A61K31/554 , A61K38/00 , A61K38/55 , A61P1/16 , A61P9/04 , A61P9/12 , A61P13/12 , A61P43/00 , C07D211/76 , C07D223/10 , C07D223/12 , C07D223/16 , C07D225/02 , C07D225/06 , C07D233/16 , C07D243/02 , C07D243/08 , C07D267/08 , C07D267/14 , C07D279/00 , C07D279/06 , C07D281/00 , C07D281/02 , C07D281/04 , C07D281/06 , C07D281/10 , C07D281/18 , C07D283/00 , C07D283/02 , C07D285/36 , C07D313/04 , C07D313/08 , C07D403/12 , C07D455/02 , C07D471/04 , C07D487/02 , C07D487/04 , C07D498/04 , C07D513/02 , C07D513/04 , C07K1/113 , C07K5/06 , C07K5/078 , C07K14/81 , C07D267/00 , C07D405/12 , C07D413/12
摘要： Compounds of the formula are disclosed as possessing inhibotory activity against angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) and thus being useful as cardiovascular agents. Processes for preparing these compounds are also disclosed.

5. 发明专利

CA2096460C DUAL ACTION INHIBITORS 未知
公开(公告)号：CA2096460C
公开(公告)日：2004-03-16
申请号：CA2096460
申请日：1993-05-18
申请人： KARANEWSKY DONALD S , BARRISH JOEL C , PETRILLO EDWARD W JR , ROBL JEFFREY A , RYONO DENIS E
发明人： KARANEWSKY DONALD S , BARRISH JOEL C , PETRILLO EDWARD W JR , ROBL JEFFREY A , RYONO DENIS E
IPC分类号： C07D223/24 , A61K31/395 , A61K31/4353 , A61K31/54 , A61K31/55 , A61K31/551 , A61K31/553 , A61K31/554 , A61K38/00 , A61K38/55 , A61P1/16 , A61P9/04 , A61P9/12 , A61P13/12 , A61P43/00 , C07D211/76 , C07D223/10 , C07D223/12 , C07D223/16 , C07D225/02 , C07D225/06 , C07D233/16 , C07D243/02 , C07D243/08 , C07D267/08 , C07D267/14 , C07D279/00 , C07D279/06 , C07D281/00 , C07D281/02 , C07D281/04 , C07D281/06 , C07D281/10 , C07D281/18 , C07D283/00 , C07D283/02 , C07D285/36 , C07D313/04 , C07D313/08 , C07D403/12 , C07D455/02 , C07D471/04 , C07D487/02 , C07D487/04 , C07D498/04 , C07D513/02 , C07D513/04 , C07K1/113 , C07K5/06 , C07K5/078 , C07K14/81 , C07D267/00 , C07D405/12 , C07D413/12
摘要： Compounds of the formula (see formula I) are disclosed as possessing inhibotory activity against angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) and thus being useful as cardiovascular agents. Processes for preparing these compounds are also disclosed.

6. 发明专利

CA2178355A1 DIAZEPINE CONTAINING DUAL ACTION INHIBITORS 未知
公开(公告)号：CA2178355A1
公开(公告)日：1996-12-08
申请号：CA2178355
申请日：1996-06-06
申请人： RYONO DENIS E , SUN CHONG QING
发明人： RYONO DENIS E , SUN CHONG-QING
IPC分类号： C07D243/02 , A61K31/50 , A61K31/55 , A61K31/675 , A61K38/00 , A61P9/00 , A61P9/10 , A61P9/12 , A61P13/02 , A61P15/00 , A61P27/02 , A61P43/00 , C07D237/04 , C07D471/04 , C07D487/04 , C07F9/645 , C07F9/6509 , C07K5/02 , C07K5/06 , C07K5/078 , C07D243/10 , C07D401/12 , C07D403/12 , C07D405/12 , C07D409/12 , C07D417/12 , C07F9/6561
摘要： Compounds of the formula wherein: A is or are dual inhibitors of NEP and ACE. Compounds wherein A is or are selective ACE inhibitors.

7. 发明专利

CA2089185A1 BIPHENYL-SUBSTITUTED QUINOLINE DERIVATIVES 未知
公开(公告)号：CA2089185A1
公开(公告)日：1993-08-15
申请号：CA2089185
申请日：1993-02-10
申请人： RYONO DENIS E , LLOYD JOHN
发明人： RYONO DENIS E , LLOYD JOHN
IPC分类号： A61K31/435 , A61K31/4375 , A61K31/47 , A61K31/675 , A61P9/00 , A61P9/12 , C07D215/20 , C07D215/36 , C07D215/38 , C07D215/50 , C07D215/60 , C07D401/10 , C07D401/12 , C07D471/04 , C07D401/02 , C07D405/14 , C07F9/60
摘要： HA603a BIPHENYL-SUBSTITUTED OUINOLINE DERIVATIVES Compounds of the formula I wherein X, R1, R2, R3, R4, R5, R6, A, B, D and E are as defined herein. These compounds inhibit the action of angiotensin II and are useful, therefore, for example, as antihypertensive agents.

8. 发明公开

EP1601641A4 SUBSTITUTED ANILIDE LIGANDS FOR THE THYROID RECEPTOR 审中-公开
标题翻译：替补ANILIDBINDER甲状腺
公开(公告)号：EP1601641A4
公开(公告)日：2007-03-21
申请号：EP04704944
申请日：2004-01-23
申请人： SQUIBB BRISTOL MYERS CO , KAROBIO AB
发明人： WASHBURN WILLIAM N , MENG WEI , RYONO DENIS E , ELLSWORTH BRUCE A , ERICSSON THOMAS , RAHIMI-GHADIM MAHMOUD , GARG NEERAJ , MALM JOHAN
IPC分类号： C07C233/25 , A61K31/195 , A61K31/24 , A61K31/277 , A61K31/44 , C07C20060101 , C07C229/08 , C07C229/22 , C07D213/57
CPC分类号： A61K45/06 , A61K31/195 , A61K31/277 , A61K31/44 , C07C233/25 , A61K2300/00

9. 发明专利

ES2291325T3 LIGANDOS DE BENZAMIDA PARA EL RECEPTOR TIROIDEO. 未知
公开(公告)号：ES2291325T3
公开(公告)日：2008-03-01
申请号：ES01946036
申请日：2001-06-01
申请人： SQUIBB BRISTOL MYERS CO
发明人： RYONO DENIS E
IPC分类号： A61K45/00 , C07C235/52 , A61K31/07 , A61K31/166 , A61K31/195 , A61K31/22 , A61K31/351 , A61K31/40 , A61K31/404 , A61K31/4418 , A61K31/455 , A61K31/592 , A61K38/28 , A61P3/00 , A61P3/04 , A61P3/06 , A61P5/14 , A61P5/16 , A61P9/04 , A61P9/06 , A61P9/10 , A61P17/00 , A61P17/02 , A61P17/10 , A61P17/16 , A61P19/10 , A61P25/24 , A61P27/06 , A61P35/00
摘要： Un compuesto de fórmula en la que: X es oxígeno (-O-); R1 es halógeno, trifluorometilo, o alquilo de 1 a 6 átomos de carbono o cicloalquilo de 3 a 7 átomos de carbono; R2 y R3 son el mismo o diferente y son hidrógeno, halógeno, alquilo de 1 a 4 átomos de carbono o cicloalquilo de 3 a 6 átomos de carbono, siendo al menos uno de R2 y R3 distinto de hidrógeno; R4 es metilo, etilo, n-propilo o trifluorometilo; R5 es hidrógeno o alquilo inferior; R6 es un ácido carboxílico, o un éster del mismo, o un profármaco del mismo; R7 es hidrógeno o un grupo alcanoilo o aroilo u otro grupo capaz de bioconversión para generar la estructura libre de fenol (en la que R7 = H); incluyéndose todos los estereoisómeros del mismo, un profármaco del mismo, y una sal farmacéuticamente aceptable del mismo.

10. 发明专利

PE20050324A1 DERIVADOS DE ANILIDA SUBSTITUIDA COMO LIGANDOS DEL RECEPTOR DE TIROIDES 未知
公开(公告)号：PE20050324A1
公开(公告)日：2005-05-12
申请号：PE2004000094
申请日：2004-01-26
申请人： KAROBIO AB , SQUIBB BRISTOL MYERS CO
发明人： WASHBURN WILLIAM N , MENG WEI , RYONO DENIS E , ERICSSON THOMAS , GARG NEERAJ , RAHIMI-GHADIM MAHMOUD , ELLSWORTH BRUCE A , MALM JOHAN
IPC分类号： A61K31/195 , A61K31/24 , A61K31/277 , A61K31/44 , C07C20060101 , C07C211/46 , C07C229/08 , C07C229/22 , C07C233/25 , C07D213/57
摘要： SE REFIERE A COMPUESTOS DERIVADOS DE ANILIDA SUBSTITUIDA DE FORMULA I EN DONDE, X ES O, Se, S, SULFONILO, ENTRE OTROS; R1 ES H, HALOGENO, CF3, ALQUILO C1-C6; R2 ES HALOGENO, CF3, ALQUILO C1-C6, ALQUENILO C2-C6, ENTRE OTROS; R3 ES H, ALQUILO, BENCILO, AROILO o ALCANOILO; R4 ES HALOGENO o ALQUILO; R5 ES H, HALOGENO o ALQUILO; R6 Y R7 SON H, HALOGENO, CIANO, ALQUILO C1-C4 o CICLOALQUILO C3-C6, DONDE AL MENOS UNO DE R6 Y R7 NO ES H; R8 Y R9 SON H, HALOGENO, ALCOXI, HIDROXI, CIANO, ENTRE OTROS; CON TAL QUE NO MAS QUE UNO DE R6, R7, R8 Y R9 ES H; R10 ES H o ALQUILO; R11 ES CO2R14; R12 Y R13 SON H, HALOGENO o ALQUILO; R14 ES H, ALQUILO, CICLOALQUILO, ARILO, ENTRE OTROS. SON COMPUESTOS PREFERIDOS: ACIDO 3-[N-[3,5-DIBROMO-4-[4-HIDROXI-3-(1-METILETIL-5-METIL)-FENOXI]-2-METILFENIL]AMINO]-3-OXOPROPANOICO; ACIDO 3-[N-[2,3,5-TRICLORO-4-[4-HIDROXI-3-(1-METILETIL-5-METIL)-FENOXI]FENIL]AMINO]-3-OXOPROPANOICO; ACIDO 3-[N-[3,5-DICLORO-4-[4-HIDROXI-3-(1-METILETIL-5-METIL)-FENOXI]-2-METILFENIL]AMINO]-3-OXOPROPANOICO; ENTRE OTROS. TAMBIEN SE REFIERE A UNA FORMULACION FARMACEUTICA. ESTOS COMPUESTOS SON LIGANDOS DEL RECEPTOR DE LA HORMONA DE TIROIDES Y SON UTILES PARA PREVENIR, INHIBIR O TRATAR ENFERMEDADES O TRASTORNOS ASOCIADOS CON LA DISFUNCION METABOLICA, O LOS CUALES DEPENDEN DE LA EXPRESION DE UN GEN REGULADO POR (3,5,3'-TRIYODO-L-TIRONINA (T3)

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