公开(公告)号：US5484937A

公开(公告)日：1996-01-16

申请号：US117269

申请日：1993-09-07

申请人： Philippe R. Bovy ,  David B. Reitz ,  Robert E. Manning

发明人： Philippe R. Bovy ,  David B. Reitz ,  Robert E. Manning

IPC分类号： C07D521/00 ,  C07D403/10 ,  A61K31/41

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D249/08

摘要： A class of N-substituted N-(.alpha.-triazolyltoluyl)pyrrole compounds described for use in treatment of circulatory disorders. Compounds of particular interest are angiotensin II antagonists of the formula ##STR1## wherein m is one; wherein R.sup.1 is selected from alkyl; and wherein R.sup.2 is selected from alkyl; and wherein each of R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9 and R.sup.10 is independently selected from hydrido, halo, nitro, trifluoromethyl, hydroxy, alkoxy, cyano, carboxyl and methoxycarbonyl; with the proviso that at least one of R.sup.5 and R.sup.8 must be selected from COOH, SH, PO.sub.3 H.sub.2, SO.sub.3 H, CONHNH.sub.2, CONHNHSO.sub.2 CF.sub.3, OH, ##STR2## wherein each of R.sup.42 and R.sup.43 is independently selected from chloro, cyano, nitro, trifluoromethyl, methoxycarbonyl and trifluoromethylsulfonyl; or a tautomer thereof or a pharmaceutically-acceptable salt thereof. These compounds are particularly useful in treatment or control of hypertension and congestive heart failure.

摘要翻译： 描述用于治疗循环系统疾病的一类N-取代的N-（α-三唑基甲苯磺酰基）吡咯化合物。 特别感兴趣的化合物是式IMAMA的血管紧张素II拮抗剂，其中m是1; 其中R1选自烷基; 并且其中R 2选自烷基; R 3，R 4，R 5，R 6，R 7，R 8，R 9和R 10各自独立地选自氢，卤素，硝基，三氟甲基，羟基，烷氧基，氰基，羧基和甲氧基羰基; 条件是R 5和R 8中的至少一个必须选自COOH，SH，PO3H2，SO3H，CONHNH2，CONHNHSO2CF3，OH，其中R42和R43各自独立地选自氯，氰基，硝基，三氟甲基， 甲氧基羰基和三氟甲基磺酰基; 或其互变异构体或其药学上可接受的盐。 这些化合物特别可用于治疗或控制高血压和充血性心力衰竭。

公开(公告)号：US5175180A

公开(公告)日：1992-12-29

申请号：US630714

申请日：1990-12-20

申请人： Philippe R. Bovy ,  David B. Reitz ,  Robert E. Manning

发明人： Philippe R. Bovy ,  David B. Reitz ,  Robert E. Manning

IPC分类号： C07D403/10 ,  C07D403/14

CPC分类号： C07D403/10 ,  C07D403/14

摘要： A class of N-substituted N-(.alpha.-triazolyltoluyl)pyrrole compounds described for use in treatment of circulatory disorders. Compounds of particular interest are angiotensin II antagonists of the formula ##STR1## wherein m is one; wherein R.sup.1 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, 4-methylbutyl, n-pentyl, neopentyl, phenyl, benzyl, phenethyl, cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexanoyl, 1-oxo-2-cyclohexylethyl, benzoyl, 1-oxo-2-phenethyl, 1-oxopropyl, 1-oxobutyl, 1-oxopentyl and 2-hydroxybutyl; wherein R.sup.2 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclohexyl, cyclohexylmethyl, propylthio, butylthio, and hydroxyalkyl; wherein each of R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9 and R.sup.10 is independently selected from hydrido, halo, nitro, trifluoromethyl, hydroxy, alkoxy, cyano, carboxyl and methoxycarbonyl; with the proviso that at least one of R.sup.5 and R.sup.8 must be selected from COOH, SH, PO.sub.3 H.sub.2, SO.sub.3 H, CONHNH.sub.2, CONHNHSO.sub.2 CF.sub.3, OH, ##STR2## wherein each of R.sup.42 and R.sup.43 is independently selected from chloro, cyano, nitro, trifluoromethyl, methoxycarbonyl and trifluoromethylsulfonyl; or a tautomer thereof or a pharmaceutically-acceptable salt thereof. These compounds are particularly useful in treatment or control of hypertension and congestive heart failure.

摘要翻译： 描述用于治疗循环系统疾病的一类N-取代的N-（α-三唑基甲苯磺酰基）吡咯化合物。 特别感兴趣的化合物是式IMAMA的血管紧张素II拮抗剂，其中m是1; 其中R1选自甲基，乙基，正丙基，异丙基，正丁基，仲丁基，异丁基，叔丁基，4-甲基丁基，正戊基，新戊基，苯基，苄基，苯乙基，环己基，环己基甲基，环己基乙基 ，环己酰基，1-氧代-2-环己基乙基，苯甲酰基，1-氧代-2-苯乙基，1-氧代丙基，1-氧代丁基，1-氧代戊基和2-羟基丁基; 其中R2选自甲基，乙基，正丙基，异丙基，正丁基，仲丁基，异丁基，叔丁基，正戊基，异戊基，新戊基，苯基，苄基，苯乙基，环己基，环己基甲基，丙硫基，丁硫基 ，和羟烷基; 其中R 3，R 4，R 5，R 6，R 7，R 8，R 9和R 10各自独立地选自氢，卤素，硝基，三氟甲基，羟基，烷氧基，氰基，羧基和甲氧基羰基; 条件是R 5和R 8中的至少一个必须选自COOH，SH，PO3H2，SO3H，CONHNH2，CONHNHSO2CF3，OH，其中R42和R43各自独立地选自氯，氰基，硝基，三氟甲基， 甲氧基羰基和三氟甲基磺酰基; 或其互变异构体或其药学上可接受的盐。 这些化合物特别可用于治疗或控制高血压和充血性心力衰竭。

公开(公告)号：US06492397B1

公开(公告)日：2002-12-10

申请号：US09616639

申请日：2000-07-26

申请人： David B. Reitz ,  Robert E. Manning

发明人： David B. Reitz ,  Robert E. Manning

IPC分类号： A01N4330

CPC分类号： C07D401/06 ,  C07D401/10 ,  C07D401/14

摘要： A class of N-arylheteroarylalkyl imidazol-2-one compounds is described for use in treatment of arteriosclerosis. Compounds of particular interest are angiotensin II antagonists of Formula I: wherein Ar is selected from wherein m is one; wherein R1 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, 4-methylbutyl, 2-ethylbutyl, n-pentyl, neopentyl, phenyl, methylphenyl, difluorophenyl, benzyl, phenethyl, cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexanoyl, 1-oxo-2-cyclohexylethyl, benzoyl, 1-oxo-2-phenethyl, 1-oxopropyl, 1-oxobutyl, 1-oxopentyl and 2-hydroxybutyl; wherein R0 is hydrido; wherein R2 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclohexyl, cyclohexylmethyl, propylthio, butylthio, and hydroxyalkyl; wherein each of R3, R4, R6, R7, R8, R9, R10 and R11 is hydrido and R5 may be selected from COOH and tetrazolyl; or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

摘要翻译： 描述了一类用于治疗动脉硬化的N-芳基杂芳基烷基咪唑-2-酮化合物。 特别感兴趣的化合物是式I的血管紧张素II拮抗剂：其中Ar选自其中m是1;其中R 1选自甲基，乙基，正丙基，异丙基，正丁基，仲丁基，异丁基，叔丁基， 4-甲基丁基，2-乙基丁基，正戊基，新戊基，苯基，甲基苯基，二氟苯基，苄基，苯乙基，环己基，环己基甲基，环己基乙基，环己酰基，1-氧代-2-环己基乙基，苯甲酰基，1-氧代-2-苯乙基， 1-氧代丙基，1-氧代丁基，1-氧代戊基和2-羟基丁基; 其中R 0是氢的; 其中R2选自甲基，乙基，正丙基，异丙基，正丁基，仲丁基，异丁基，叔丁基，正戊基，异戊基，新戊基，苯基，苄基，苯乙基，环己基，环己基甲基，丙硫基，丁硫基 ，和羟烷基; 其中R 3，R 4，R 6，R 7，R 8，R 9，R 10和R 11各自为氢，R 5可以选自COOH和四唑基; 或其互变异构体或其药学上可接受的盐。

公开(公告)号：US5441970A

公开(公告)日：1995-08-15

申请号：US107742

申请日：1993-08-19

申请人： David B. Reitz ,  Robert E. Manning

发明人： David B. Reitz ,  Robert E. Manning

IPC分类号： A61K31/4439 ,  C07D401/06 ,  C07D401/10 ,  C07D401/14 ,  A61K31/44

CPC分类号： C07D401/06 ,  A61K31/4439 ,  C07D401/10 ,  C07D401/14

摘要： ##STR1## A class of N-arylheteroarylalkyl imidazol-2-one compounds is described for use in treatment of circulatory disorders such as hypertension and congestive heart failure. Compounds of particular interest are angiotensin II antagonists of formula (I) wherein A is selected from (a), (b), (c), (d), (e) and (f), wherein m is one; R
1 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, 4-methylbutyl, 2-ethylbutyl, n-pentyl, neopentyl, phenyl, methylphenyl, difluorophenyl, benzyl, phenetyl, cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexanoyl, 1-oxo-2-cyclohexylethyl, benzoyl, 1-oxo-2-phenethyl, 1-oxopropyl, 1-oxobutyl, 1-oxopentyl and 2-hydroxybutyl; wherein R
0 is hydrido; wherein R
2 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclohexyl, cyclohexylmethyl, propylthio, butylthio, and hydroxyalkyl; wherein each of R
3 , R
4 , R
6 , R
7 , R
8 , R
9 , R
10 and R
11 is hydrido and R
5 must be seleted from COOH, SH, PO
3 H
2 , SO
3 H, CONHNH
2 , CONHNHSO
2 CF
3 , OH, (g), (h) and (i) wherein each of R
42 and R
43 is independently selected from chloro, cyano, nitro, trifluoromethyl, methoxycarbonyl and trifluoromethylsulfonyl; or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

摘要翻译： PCT No.PCT / US92 / 02439 Sec。 371日期：1993年8月19日 102（e）日期1993年8月19日PCT提交1992年4月1日PCT公布。 第WO92 / 17469号公报 （i）（g）（h）（i）（a）（b）（c）< （f）（f）描述了一类N-芳基杂芳基烷基咪唑-2-酮化合物用于治疗循环系统疾病如高血压和充血性心力衰竭。 特别感兴趣的化合物是式（I）的血管紧张素II拮抗剂，其中A选自（a），（b），（c），（d），（e）和（f） R1选自甲基，乙基，正丙基，异丙基，正丁基，仲丁基，异丁基，叔丁基，4-甲基丁基，2-乙基丁基，正戊基，新戊基，苯基，甲基苯基，二氟苯基， 苯乙酰基，环己基，环己基甲基，环己基乙基，环己酰基，1-氧代-2-环己基乙基，苯甲酰基，1-氧代-2-苯乙基，1-氧代丙基，1-氧代丁基，1-氧代戊基和2-羟基丁基; 其中R 0是氢的; 其中R2选自甲基，乙基，正丙基，异丙基，正丁基，仲丁基，异丁基，叔丁基，正戊基，异戊基，新戊基，苯基，苄基，苯乙基，环己基，环己基甲基，丙基

公开(公告)号：US06858636B2

公开(公告)日：2005-02-22

申请号：US10649210

申请日：2003-08-27

申请人： David B. Reitz ,  Robert E. Manning

发明人： David B. Reitz ,  Robert E. Manning

IPC分类号： A61K31/415 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  A61P9/14 ,  A61P27/02 ,  A61P27/06 ,  C07D233/70 ,  C07D403/10 ,  A61K31/4166 ,  A61K31/4178

CPC分类号： C07D403/10 ,  C07D233/70

摘要： A class of 1-phenyl imidazol-2-one biphenylmethyl compounds is described for use in treatment of circulatory disorders. Compounds of particular interest are angiotensin II antagonists of the formula wherein each of R1, R2 and R3 is independently selected from hydrido, alkyl, alkoxy, cyano, halo, hydroxy, carboxyl, alkoxycarbonyl, formyl and acetyl; alkylcarbonyl and haloalkylcarbonyl; with the proviso that at least one of R1, R2 and R3 must be a substituent other than hydrido, and with the further proviso that when each of R1 and R3 is hydrido, then R2 cannot be chloro; wherein R4 is hydrido; wherein R5 is alkyl; and wherein R6 is tetrazolyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof. These compounds are particularly useful in treatment or control of hypertension and congestive heart failure.

摘要翻译： 描述了一类用于治疗循环障碍的1-苯基咪唑-2-酮联苯甲基化合物。 R 1，R 2和R 3各自独立地选自氢，烷基，烷氧基，氰基，卤素，羟基，羧基，烷氧基羰基，甲酰基和乙酰基。 ; 烷基羰基和卤代烷基羰基; 条件是R 1，R 2和R 3中的至少一个必须是除氢环以外的取代基，另外条件是当R 1和R 3各自为氢时 那么R 2不能是氯; 其中R 4是氢的; 其中R 5是烷基; 并且其中R 6是四唑基; 或其立体异构体或其互变异构体或其药学上可接受的盐。 这些化合物特别可用于治疗或控制高血压和充血性心力衰竭。

公开(公告)号：US5861420A

公开(公告)日：1999-01-19

申请号：US784223

申请日：1997-01-16

申请人： David B. Reitz ,  Robert E. Manning

发明人： David B. Reitz ,  Robert E. Manning

IPC分类号： C07D401/06 ,  C07D401/10 ,  C07D401/14 ,  A01N43/40 ,  C07D401/00 ,  C07D413/00 ,  C07D417/04

CPC分类号： C07D401/06 ,  C07D401/10 ,  C07D401/14

摘要： A class of N-arylheteroarylalkyl imidazol-2-one compounds is described for use in treatment of circulatory disorders such as hypertension and congestive heart failure. Compounds of particular interest are angiotensin II antagonists of the formula ##STR1## wherein A is selected from ##STR2## wherein m is one; wherein R.sup.1 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, 4-methylbutyl, 2-ethylbutyl, n-pentyl, neopentyl, phenyl, methylphenyl, difluorophenyl, benzyl, phenethyl, cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexanoyl, 1-oxo-2-cyclohexylethyl, benzoyl, 1-oxo-2-phenethyl, 1-oxopropyl, 1-oxobutyl, 1-oxopentyl and 2-hydroxybutyl; wherein R.sup.0 is hydrido; wherein R.sup.2 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclohexyl, cyclohexylmethyl, propylthio, butylthio, and hydroxyalkyl; wherein each of R.sup.3, R.sup.4, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 and R.sup.11 is hydrido and R.sup.5 must be selected from COOH, SH, P0.sub.3 H.sub.2, SO.sub.3 H, CONHNH.sub.2, CONHNHSO.sub.2 CF.sub.3, OH, ##STR3## wherein each of R.sup.42 and R.sup.43 is independently selected from chloro, cyano, nitro, trifluoromethyl, methoxycarbonyl and trifluoromethylsulfonyl; or a tautomer thereof or a pharmaceutically-aceptable salt thereof.

摘要翻译： 描述了一类N-芳基杂芳基烷基咪唑-2-酮化合物用于治疗循环系统疾病如高血压和充血性心力衰竭。 特别感兴趣的化合物是下式的血管紧张素II拮抗剂：其中A选自 和，其中m是1; 其中R 1选自甲基，乙基，正丙基，异丙基，正丁基，仲丁基，异丁基，叔丁基，4-甲基丁基，2-乙基丁基，正戊基，新戊基，苯基，甲基苯基，二氟苯基， 苯乙基，环己基甲基，环己基乙基，环己酰基，1-氧代-2-环己基乙基，苯甲酰基，1-氧代-2-苯乙基，1-氧代丙基，1-氧代丁基，1-氧代戊基和2-羟基丁基; 其中R 0是氢的; 其中R2选自甲基，乙基，正丙基，异丙基，正丁基，仲丁基，异丁基，叔丁基，正戊基，异戊基，新戊基，苯基，苄基，苯乙基，环己基，环己基甲基，丙硫基，丁硫基 ，和羟烷基; 其中R 3，R 4，R 6，R 7，R 8，R 9，R 10和R 11各自为氢，R 5必须选自COOH，SH，PO 3 H 2，SO 3 H，CONHNH 2，CONHNHSO 2 CF 3，OH，

公开(公告)号：US5393790A

公开(公告)日：1995-02-28

申请号：US194762

申请日：1994-02-10

申请人： David B. Reitz ,  Robert E. Manning ,  Horng-Chi Huang ,  Jinglin Li

发明人： David B. Reitz ,  Robert E. Manning ,  Horng-Chi Huang ,  Jinglin Li

IPC分类号： C07C311/16 ,  C07C311/29 ,  C07C317/14 ,  C07C317/22 ,  C07C323/65 ,  C07D213/34 ,  C07D213/61 ,  C07D213/70 ,  C07D317/56 ,  C07C309/32 ,  A61K31/18 ,  C07D211/54

CPC分类号： C07D213/70 ,  C07C311/16 ,  C07C311/29 ,  C07C317/14 ,  C07C317/22 ,  C07C323/65 ,  C07D213/34 ,  C07D213/61 ,  C07D317/56 ,  C07C2102/50 ,  Y10S514/883 ,  Y10S514/886

摘要： A class of substituted spiro compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula III: ##STR1## wherein n is a number selected from 0, 1 and 2; wherein R.sup.3 is methylsulfonyl or sulfamyl; and wherein R.sup.8 is selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, isobutyl, methoxy, ethoxy, propoxy, butoxy, hydroxyl, mercapto, methylthio, ethylthio, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, trifluoromethoxy, hydroxymethyl, methoxymethyl and ethoxymethyl; or a pharmaceutically-acceptable salt thereof.

摘要翻译： 描述了一类取代的螺环化合物用于治疗炎症和炎症相关疾病。 特别感兴趣的化合物由式III定义：其中n是选自0,1和2的数; 其中R 3是甲基磺酰基或亚磺酰基; 甲基，乙基，正丙基，异丙基，丁基，叔丁基，异丁基，甲氧基，乙氧基，丙氧基，丁氧基，羟基，巯基，甲硫基，乙硫基， 氰基，氟甲基，二氟甲基，三氟甲基，氯甲基，二氯甲基，三氯甲基，五氟乙基，七氟丙基，二氟氯甲基，二氯氟甲基，二氟乙基，二氟丙基，二氯乙基，二氯丙基，三氟甲氧基，羟甲基，甲氧基甲基和乙氧基甲基; 或其药学上可接受的盐。

公开(公告)号：US5164403A

公开(公告)日：1992-11-17

申请号：US681011

申请日：1991-04-05

申请人： David B. Reitz ,  Robert E. Manning

发明人： David B. Reitz ,  Robert E. Manning

IPC分类号： A61K31/4439 ,  C07D401/06 ,  C07D401/10 ,  C07D401/14

CPC分类号： C07D401/06 ,  A61K31/4439 ,  C07D401/10 ,  C07D401/14

摘要： A class of N-arylheteroarylalkyl imidazol-2-one compounds is described for use in treatment of circulatory disorders such as hypertension and congestive heart failure. Compounds of particular interest are angiotensin II antagonists of the formula ##STR1## wherein A is selected from ##STR2## wherein m is one; wherein R.sup.1 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, 4-methylbutyl, n-pentyl, neopentyl, phenyl, benzyl, phenethyl, cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexanoyl, 1-oxo-2-cyclohexylethyl, benzoyl, 1-oxo-2-phenethyl, 1-oxopropyl, 1-oxobutyl, 1-oxopentyl and 2-hydroxybutyl; wherein R.sup.0 is selected from hydrido, methyl, fluoro, chloro, monofluoromethyl, difluoromethyl, trifluoromethyl, formyl, carboxyl and dimethoxymethyl; wherein R.sup.2 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclohexyl, cyclohexylmethyl, propylthio, butylthio, and hydroxyalkyl; wherein each of R.sup.3, R.sup.4, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 and R.sup.11 is hydrido and R.sup.5 must be selected from COOH, SH, PO.sub.3 H.sub.2, SO.sub.3 H, CONHNH.sub.2, CONHNHSO.sub.2 CF.sub.3, OH, ##STR3## wherein each of R.sup.42 and R.sup.43 is independently selected from chloro, cyano, nitro, trifluoromethyl, methoxycarbonyl and trifluoromethylsulfonyl; or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

摘要翻译： 描述了一类N-芳基杂芳基烷基咪唑-2-酮化合物用于治疗循环系统疾病如高血压和充血性心力衰竭。 特别感兴趣的化合物是下式的血管紧张素II拮抗剂：其中A选自 其中m为1; 其中R1选自甲基，乙基，正丙基，异丙基，正丁基，仲丁基，异丁基，叔丁基，4-甲基丁基，正戊基，新戊基，苯基，苄基，苯乙基，环己基，环己基甲基，环己基乙基 ，环己酰基，1-氧代-2-环己基乙基，苯甲酰基，1-氧代-2-苯乙基，1-氧代丙基，1-氧代丁基，1-氧代戊基和2-羟基丁基; 其中R 0选自氢，甲基，氟，氯，单氟甲基，二氟甲基，三氟甲基，甲酰基，羧基和二甲氧基甲基; 其中R2选自甲基，乙基，正丙基，异丙基，正丁基，仲丁基，异丁基，叔丁基，正戊基，异戊基，新戊基，苯基，苄基，苯乙基，环己基，环己基甲基，丙硫基，丁硫基 ，和羟烷基; 其中R 3，R 4，R 6，R 7，R 8，R 9，R 10和R 11各自为氢，R 5必须选自COOH，SH，PO 3 H 2，SO 3 H，CONHNH 2，CONHNHSO 2 CF 3，OH，NNNHR 42和+ RE 其中R 42和R 43各自独立地选自氯，氰基，硝基，三氟甲基，甲氧基羰基和三氟甲基磺酰基; 或其互变异构体或其药学上可接受的盐。

公开(公告)号：US5302610A

公开(公告)日：1994-04-12

申请号：US810321

申请日：1991-12-19

申请人： Robert E. Manning ,  David B. Reitz

发明人： Robert E. Manning ,  David B. Reitz

IPC分类号： A61K47/48 ,  C07D233/68 ,  C07D403/10 ,  A61K31/415 ,  A61K31/495 ,  C07D233/54 ,  C07D241/04 ,  C07D257/04 ,  C07D265/30

CPC分类号： C07D403/10 ,  A61K47/48023 ,  A61K47/48061 ,  C07D233/68

摘要： Renal-selective compounds are described which, in one embodiment, are prodrugs preferentially converted in the kidney to compounds capable of blocking angiotensin II (AII) receptors. These prodrugs are conjugates formed from two components, namely, a first component provided by an AII antagonist compound and a second component which is capable of being cleaved from the first component when both components are chemically linked within the conjugate. The two components are chemically linked by a bond which is cleaved selectively in the kidney, for example, by an enzyme. The liberated AII antagonist compound is then available to block AII receptors within the kidney. Conjugates of particular interest are glutamyl derivatives of biphenylmethyl 1H-substituted imidazole compounds, of which N-acetyl-L-glutamic acid, 5-[[4'-[2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-ylmethyl][1,1'-biphenyl]-2-yl]carbonyl]hydrazide (shown below) is an example: ##STR1##

摘要翻译： 描述了肾选择性化合物，其在一个实施方案中是优先在肾中转化为能够阻断血管紧张素II（AII）受体的化合物的前药。 这些前药是由两种组分形成的缀合物，即由AII拮抗剂化合物提供的第一组分和当两种组分在缀合物内化学连接时能够从第一组分切割的第二组分。 两种组分通过在肾脏中有选择性地切割的键化学连接，例如通过酶。 然后释放的AII拮抗剂化合物可用于阻断肾脏内的AII受体。 特别感兴趣的缀合物是联苯甲基1H-取代的咪唑化合物的谷氨酰基衍生物，其中N-乙酰基-L-谷氨酸5 - （（4' - （2-丁基-4-氯-5-（羟甲基） 咪唑-1-基甲基）（1,1'-联苯）-2-基）羰基）酰肼（如下所示）是一个实例：（*化学结构*）

公开(公告)号：US5087634A

公开(公告)日：1992-02-11

申请号：US606806

申请日：1990-10-31

申请人： David B. Reitz ,  Robert E. Manning

发明人： David B. Reitz ,  Robert E. Manning

IPC分类号： C07D233/70 ,  C07D403/10 ,  C07D409/14

CPC分类号： C07D403/10 ,  C07D233/70 ,  C07D409/14

摘要： A class of N-substituted imidazol-2-one compounds is described for use in treatment of circulatory disorders. Compounds of particular interest are angiotensin II antagonists of the formula ##STR1## wherein m is one; wherein R.sup.1 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, 4-methylbutyl, n-pentyl, neopentyl, phenyl, benzyl, phenethyl, cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexanoyl, 1-oxo-2-cyclohexylethyl, benzoyl, 1-oxo-2-phenethyl, 1-oxopropyl, 1-oxobutyl, 1-oxopentyl and 2-hydroxybutyl; wherein R.sup.0 is selected from hydrido, methyl, fluoro, chloro, monofluoromethyl, difluoromethyl, trifluoromethyl, formyl, carboxyl and dimethoxymethyl; wherein R.sup.2 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclohexyl, cyclohexylmethyl, propylthio, butylthio, and hydroxyalkyl; wherein each of R.sup.3, R.sup.4, R.sup.6, R.sub.7, R.sup.8, R.sup.10 and R.sup.11 is hydrido; with the proviso that at least one of R.sup.5 and R.sup.9 must be selected from COOH, SH, PO.sub.3 H.sub.2, SO.sub.3 H, CONHNH.sub.2, CONHNHSO.sub.2 CF.sub.3, OH, ##STR2## wherein each of R.sup.42 and R.sup.43 is independently selected from chloro, cyano, nitro, trifluoromethyl, methoxycarbonyl and trifluoromethylsulfonyl; or a tautomer thereof or a pharmaceutically-acceptable salt thereof. These compounds are particularly useful in treatment or control of hypertension and congestive heart failure.

摘要翻译： 描述了一类用于治疗循环障碍的N-取代咪唑-2-酮化合物。 特别感兴趣的化合物是式IMAMA的血管紧张素II拮抗剂，其中m是1; 其中R1选自甲基，乙基，正丙基，异丙基，正丁基，仲丁基，异丁基，叔丁基，4-甲基丁基，正戊基，新戊基，苯基，苄基，苯乙基，环己基，环己基甲基，环己基乙基 ，环己酰基，1-氧代-2-环己基乙基，苯甲酰基，1-氧代-2-苯乙基，1-氧代丙基，1-氧代丁基，1-氧代戊基和2-羟基丁基; 其中R 0选自氢，甲基，氟，氯，单氟甲基，二氟甲基，三氟甲基，甲酰基，羧基和二甲氧基甲基; 其中R2选自甲基，乙基，正丙基，异丙基，正丁基，仲丁基，异丁基，叔丁基，正戊基，异戊基，新戊基，苯基，苄基，苯乙基，环己基，环己基甲基，丙硫基，丁硫基 ，和羟烷基; 其中R3，R4，R6，R7，R8，R10和R11各自为氢; 条件是R 5和R 9中的至少一个必须选自COOH，SH，PO 3 H 2，SO 3 H，CONHNH 2，CONHNHSO 2 CF 3，OH，其中R 42和R 43各自独立地选自氯， 氰基，硝基，三氟甲基，甲氧基羰基和三氟甲基磺酰基; 或其互变异构体或其药学上可接受的盐。 这些化合物特别可用于治疗或控制高血压和充血性心力衰竭。