公开(公告)号：EP0230379B1

公开(公告)日：1991-04-03

申请号：EP87300327.1

申请日：1987-01-15

申请人： PFIZER INC.

发明人： Lipinski, Christopher Andrew

IPC分类号： C07D311/22 ,  C07D335/06 ,  C07D311/32 ,  C07D311/96 ,  A61K31/35 ,  A61K31/38

CPC分类号： C07D335/06 ,  C07D311/22 ,  C07D311/32 ,  C07D311/96 ,  Y10S514/866

公开(公告)号：EP0050458A3

公开(公告)日：1982-09-01

申请号：EP81304724

申请日：1981-10-12

申请人： PFIZER INC.

发明人： LaMattina, John Lawrence ,  Lipinski, Christopher Andrew

IPC分类号： C07D417/04 ,  A61K31/425 ,  C07D277/48 ,  C07D277/56 ,  C07D233/64

CPC分类号： C07D233/64 ,  C07C45/70 ,  C07C45/71 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D277/48 ,  C07D277/56 ,  C07D417/04 ,  C07C49/175

摘要： A series of 2-guanidino-4-heteroarylthiazoles of the formula:
and the pharmaceutically acceptable acid addition salts thereof, wherein X is S or NH; Y is CH, C.CH 3 or N; R is hydrogen, hydroxymethyl, alkyl of 1 to 6 carbon atoms, -(CH 2 ) n Ar, -NH 2 , -NHR 1 or -NHCOR 1 , wherein R 1 is alkyl of 1 to 6 carbon atoms or -(CH 2 ) m Ar; n is an integer from 2 to 4; m is zero or an integer from 1 to 4; Ar is phenyl or phenyl monosubstituted with chloro, bromo, fluoro, alkyl of 1 to 3 carbon atoms or alkoxy of 1 to 3 carbon atoms; provided that when Y is N, X is NH and m is other than zero; and when X is S, R is other than hydroxymethyl, alkyl, or -(CH 2 ) n Ar; and pharmaceutical compositions containing them. The compounds are useful in the prevention or treatment of gastric hyperacidit y and peptic ulcers. Also included are certain intermediates useful in the preparation of the thiazoles.

公开(公告)号：EP0050458A2

公开(公告)日：1982-04-28

申请号：EP81304724.8

申请日：1981-10-12

申请人： PFIZER INC.

发明人： LaMattina, John Lawrence ,  Lipinski, Christopher Andrew

IPC分类号： C07D417/04 ,  A61K31/425 ,  C07D277/48 ,  C07D277/56 ,  C07D233/64

CPC分类号： C07D233/64 ,  C07C45/70 ,  C07C45/71 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D277/48 ,  C07D277/56 ,  C07D417/04 ,  C07C49/175

摘要： A series of 2-guanidino-4-heteroarylthiazoles of the formula:
and the pharmaceutically acceptable acid addition salts thereof,
wherein X is S or NH; Y is CH, C.CH 3 or N; R is hydrogen, hydroxymethyl, alkyl of 1 to 6 carbon atoms, -(CH 2 ) n Ar, -NH 2 , -NHR 1 or -NHCOR 1 , wherein R 1 is alkyl of 1 to 6 carbon atoms or -(CH 2 ) m Ar; n is an integer from 2 to 4; m is zero or an integer from 1 to 4; Ar is phenyl or phenyl monosubstituted with chloro, bromo, fluoro, alkyl of 1 to 3 carbon atoms or alkoxy of 1 to 3 carbon atoms; provided that when Y is N, X is NH and m is other than zero; and when X is S, R is other than hydroxymethyl, alkyl, or -(CH 2 ) n Ar; and pharmaceutical compositions containing them. The compounds are useful in the prevention or treatment of gastric hyperacidit y and peptic ulcers. Also included are certain intermediates useful in the preparation of the thiazoles.

公开(公告)号：EP0171213B1

公开(公告)日：1988-09-21

申请号：EP85305115.9

申请日：1985-07-18

申请人： PFIZER INC.

发明人： Lipinski, Christopher Andrew

IPC分类号： C07D495/10 ,  C07D491/10 ,  A61K31/415

CPC分类号： C07D409/04 ,  C07D333/24 ,  C07D491/10 ,  C07D495/10

公开(公告)号：EP0159143B1

公开(公告)日：1987-12-16

申请号：EP85301809.1

申请日：1985-03-15

申请人： PFIZER INC.

发明人： Lipinski, Christopher Andrew

IPC分类号： C07D235/02 ,  C07D263/52 ,  C07D277/60

CPC分类号： C07D235/02 ,  C07D263/52 ,  C07D277/60

公开(公告)号：EP0171213A1

公开(公告)日：1986-02-12

申请号：EP85305115.9

申请日：1985-07-18

申请人： PFIZER INC.

发明人： Lipinski, Christopher Andrew

IPC分类号： C07D495/10 ,  C07D491/10 ,  A61K31/415

CPC分类号： C07D409/04 ,  C07D333/24 ,  C07D491/10 ,  C07D495/10

摘要： Spiro-imidazolones of formula are disclosed
wherein:


X is oxygen or sulfur;
Y is hydrogen, halo or alkyl and
R is hydrogen, methyl or ethyl,

which are useful as aldose reductase inhibitors and as therapeutic agents for the treatment of complications arising from diabetes. Pharmaceutical compositions containing the spiro compounds and a method of treating diabetic complications are also disclosed.

公开(公告)号：EP0159143A1

公开(公告)日：1985-10-23

申请号：EP85301809.1

申请日：1985-03-15

申请人： PFIZER INC.

发明人： Lipinski, Christopher Andrew

IPC分类号： C07D235/02 ,  C07D263/52 ,  C07D277/60

CPC分类号： C07D235/02 ,  C07D263/52 ,  C07D277/60

摘要： Spiro-oxazolidinones, -thiazolidinones and -imidazolidi- nones of the formula
or a pharmaceutically acceptable salt thereof, wherein:

U is oxygen, sulfur or nitrogen substituted with hydrogen;
X is hydrogen or alkyl having 1 to 4 carbon atoms;
n is 0 or 1;
Y is hydrogen, halo, nitro, trifluoromethyl, hydroxy, alkoxy or alkylthio having 1 to 4 carbon atoms or alkyl having 1 to 4 carbon atoms; and
Z is hydrogen, halo, nitro, trifluoromethyl, hydroxy, alkoxy having 1 to 4 carbon atoms or alkyl having 1 to 4 carbon atoms, with the proviso that if either Y or Z is nitro the other is hydrogen,

are disclosed which are useful as aldose reductase inhibitors and as therapeutic agents for the treatment of complications arising from diabetes. Pharmaceutical compositions containing the spiro compounds and a method of treating diabetic complications are also disclosed.

摘要翻译： 螺恶唑烷酮，噻唑烷酮和式CHEM的咪唑啉酮或其药学上可接受的盐，其中：U是被氢取代的氧，硫或氮; X是氢或具有1至4个碳原子的烷基; n为0或1; Y是氢，卤素，硝基，三氟甲基，羟基，烷氧基或具有1至4个碳原子的烷硫基或具有1至4个碳原子的烷基; 并且Z是氢原子，卤素，硝基，三氟甲基，羟基，具有1至4个碳原子的烷氧基或具有1至4个碳原子的烷基，条件是如果Y或Z是硝基，另一个是氢， 作为醛糖还原酶抑制剂和用作治疗糖尿病并发症的治疗剂。 还公开了含有螺环化合物的药物组合物和治疗糖尿病并发症的方法。

公开(公告)号：EP0203791A1

公开(公告)日：1986-12-03

申请号：EP86303925.1

申请日：1986-05-23

申请人： PFIZER INC.

发明人： Lipinski, Christopher Andrew

IPC分类号： C07D235/02 ,  C07D491/107 ,  C07D471/10 ,  A61K31/415 ,  A61K31/47

CPC分类号： C07D235/02 ,  C07D471/10 ,  C07D491/10

摘要： Spiro-imidazolidines of the formula:
and the pharmaceutically acceptable salts thereof, wherein X is 0, CH 2 or NH; R is hydrogen, fluoro, chloro, methyl or methoxy; and Y is O or CH 2 .
These compounds are useful in treatment to prevent or alleviate ocular or neuritic diabetes-associated chronic complications.

摘要翻译： 下式的螺 - 咪唑烷：... 及其药学上可接受的盐，其中X是O，CH 2或NH; R是氢，氟，氯，甲基或甲氧基; Y为O或CH2。 ...这些化合物可用于治疗以预防或减轻眼部或神经性糖尿病相关慢性并发症。

公开(公告)号：EP0136143A3

公开(公告)日：1985-05-15

申请号：EP84306332

申请日：1984-09-17

申请人： PFIZER INC.

发明人： Lipinski, Christopher Andrew

IPC分类号： C07D209/96 ,  A61K31/40

CPC分类号： C07C255/00 ,  C07D209/96

摘要： Spiro-succinimides are disclosed which are useful as aldose reductase inhibitors and as therapeutic agents for the treatment of complications arising from diabetes. Pharmaceutical compositions containing the spiro compounds and a method of treating diabetic complications are also disclosed.

公开(公告)号：EP0115133A1

公开(公告)日：1984-08-08

申请号：EP83307340.6

申请日：1983-12-02

申请人： PFIZER INC.

发明人： Lipinski, Christopher Andrew

IPC分类号： C07D235/02 ,  C07D263/52 ,  C07D277/60

CPC分类号： C07D235/02 ,  C07D263/52 ,  C07D277/60

摘要： Compounds of the formula
and their pharmaceutically acceptable salts, wherein:

U is oxygen, sulfur or nitrogen substituted with hydrogen or alkyl having 1-4 carbon atoms;
n is zero or one;
W is carbonyl or hydroxymethylene;
R is hydrogen or alkyl having 1-4 carbon atoms;
X is hydrogen, chloro, bromo, iodo, alkyl having 1-4 carbon atoms, dimethyl or (CH 2 ) m Q wherein m is 1 or 2 and Q is phenyl or halophenyl, with the proviso that when X is dimethyl, n is one;
Y is hydrogen, halo, nitro, trifluoromethyl, alkoxy having 1-4 carbon atoms or alkyl having 1-4 carbon atoms; and
Z is hydrogen, halo, nitro, trifluoromethyl, alkoxy having 1-4 carbon atoms or alkyl having 1-4 carbon atoms, with the proviso that if either Y or Z is nitro the other is hydrogen.

The compounds are useful in the treatment of certain chronic complications arising from diabetes mellitus, such as diabetic cataracts, retinopathy and neuropathy.

摘要翻译： 式...的化合物及其药学上可接受的盐，其中：U是氧，硫或被氢或具有1-4个碳原子的烷基取代的氮; ... n是0或1; ... W是羰基或羟基亚甲基 ; R是氢或具有1-4个碳原子的烷基; X是氢，氯，溴，碘，具有1-4个碳原子的烷基，二甲基或（CH2）mQ，其中m是1或2，Q是苯基或 卤代苯基，条件是当X是二甲基时，n是1; Y是氢，卤素，硝基，三氟甲基，具有1-4个碳原子的烷氧基或具有1-4个碳原子的烷基; 和Z是氢，卤素，硝基，三氟甲基，具有1-4个碳原子的烷氧基或具有1-4个碳原子的烷基，条件是如果Y或Z是硝基，另一个是氢。 该化合物可用于治疗由糖尿病引起的某些慢性并发症，例如糖尿病性白内障，视网膜病变和神经病变。