公开(公告)号：EP0144804A3

公开(公告)日：1986-01-08

申请号：EP84113600

申请日：1984-11-12

申请人： MERCK & CO. INC.

发明人： Biftu, Tesfaye ,  Hwang, San-Bao ,  Doebber, Thomas W. ,  Beattie, Thomas R. ,  Shen, Tsung-Ying

IPC分类号： C07D307/12 ,  C07D307/18 ,  C07D307/20 ,  A61K31/34

CPC分类号： C07D307/18 ,  C07C45/00 ,  C07C45/72 ,  C07D307/12 ,  C07D307/14 ,  C07D307/20 ,  C07C49/84

摘要： Compounds of formula:
are disclosed wherein R and R' independently are
(a) hydrogen; (b) haloloweralkyl; (c) halo; (d) CONR 2 R 3 wherein R 2 and R 3 independently represent C 1-6 alkyl and hydrogen; (e) loweralkenyl; (f) -COR 2 (g) -CH 2 OR 2 ; (h) loweralkynyl; (i) -CH 2 -NR 2 R 3 ; (j) -CH 2 SR 2 ; (k) =0; or (I) -OR 2 ; Ar and Ar' are the same or different from each other and are (a) phenyl or substituted phenyl of formula
where R 4 -R 8 independently represent H, RO-, R 2 S-, R 2 SO 2 -,CF 3 O-, CF 3 S-, R 2 R 3 N-, -OCH 2 CO 2 R 2 , -SO 2 NR 2 R 3 , -C0 2 R 2 , -NR 2 SO 2 R 3 , COR 2 , N0 2 , or CN or R 4 -R 5 , R 5 -R 6 , R 6 -R 7 and R 7 -R 8 are joined together forming a bridge;
(b) pyrryl or substituted pyrryl; (c) furyl or substituted furyl; (d) pyridyl or substituted pyridyl; or (e) thiophene or substituted thiophene. These compounds are found to have potent and specific PAF (Platelet Activating Factor) antagonistic activities and thereby are useful in the treatment of varous diseases or disorders mediated by the PAF, for example, inflammation, cardiovascular disorder, asthma, lung edema, adult respiratory distress syndrome, pain, and aggregation of platelets.

公开(公告)号：EP0199324A3

公开(公告)日：1988-02-10

申请号：EP86105471

申请日：1986-04-21

申请人： MERCK & CO. INC.

发明人： Biftu, Tesfaye ,  Hwang, San-Bao ,  Doebber, Thomas W. ,  Beattie, Thomas R. ,  Shen, Tsung-Ying

IPC分类号： C07D307/10 ,  C07D307/18 ,  C07D405/04 ,  C07D405/14 ,  C07D417/04 ,  A61K31/34

CPC分类号： C07D307/18 ,  C07D307/12 ,  C07D307/14 ,  C07D307/16 ,  C07D307/20 ,  C07D307/24 ,  C07D307/34 ,  C07D405/04 ,  C07D405/14 ,  C07D407/12 ,  C07D409/14 ,  C07D417/04

摘要： Compounds of formula:
are disclosed wherein R and R' are
(a) hydrogen; (b) haloloweralkyl; (c) halo; (d) CONR 2 R 3 wherein R 2 and R 3 independently represent hydrogen, C 1-8 alkyl, or C 3-8 cycloalkyl; (e) loweralkenyl; (f) -COR 2 ; (g) -CH 2 OR 2 ; (h) loweralkynyl; (i) -CH 2 NR 2 R 2 ; (j) -CH 2 SR 2 ; (k) = O; or (l) -OR 2 ; (m) -R 2 ; Ar and Ar 1 are (a) phenyl or substituted phenyl of formula where R 4 -R 8 independently where R 4 -R 8 independently represent H; R 2 ; YO-wherein Y is loweralkenyl, loweralkynyl, - CH 2 -, -CH 2 C(O)OR 2 , -CH 2 OR 2 , -CH 2 C 3- 8 cycloalkyl, -CH 2 Ar 2 wherein Ar 2 is phenyl or substituted phenyl, -CH 2 -CH(OH)CH 2 OH; R 2 S-(O) n wherein R 2 can only be C 3-8 cycloalkyl and n is 0 to 2; CF 3 SO, CF 3 SO 2 ; - CONR 2 R 3 ; -NR 2 COR 3 ; -OCONH 2 -CR 2 R 3 R 9 wherein R 9 is the same as or different from R Z ; -CH 2 OR 2 ; -CH 2 CO 2 R 2 ; -CH 2 OCOR 3 ; -GH 2 O-CO-OR 2 ; -NHCH 2 COOR 2 ; halo; or N + R 2 R 3 R 9 X- wherein X- is an anion;
(b) monoheteroaryl, di-or polyheteroaryl or fused heteroaryl containing 1 to 3 of any one or more of the heteroatoms N, S or O; (c) heteroarylalkyl; (d) heterocycloalkyl; or (e) heterocycloalkenyl. These compounds are found to have potent and specific PAF - (Platelet Activating Factor) antagonistic activities.

公开(公告)号：EP0144804B1

公开(公告)日：1990-03-07

申请号：EP84113600.5

申请日：1984-11-12

申请人： Merck & Co., Inc.

发明人： Biftu, Tesfaye ,  Hwang, San-Bao ,  Doebber, Thomas W. ,  Beattie, Thomas R. ,  Shen, Tsung-Ying

IPC分类号： C07D307/12 ,  C07D307/18 ,  C07D307/20 ,  A61K31/34

CPC分类号： C07D307/18 ,  C07C45/00 ,  C07C45/72 ,  C07D307/12 ,  C07D307/14 ,  C07D307/20 ,  C07C49/84

公开(公告)号：EP0144804A2

公开(公告)日：1985-06-19

申请号：EP84113600.5

申请日：1984-11-12

申请人： Merck & Co., Inc.

发明人： Biftu, Tesfaye ,  Hwang, San-Bao ,  Doebber, Thomas W. ,  Beattie, Thomas R. ,  Shen, Tsung-Ying

IPC分类号： C07D307/12 ,  C07D307/18 ,  C07D307/20 ,  A61K31/34

CPC分类号： C07D307/18 ,  C07C45/00 ,  C07C45/72 ,  C07D307/12 ,  C07D307/14 ,  C07D307/20 ,  C07C49/84

摘要： Compounds of formula:
are disclosed wherein R and R' independently are

(a) hydrogen;
(b) haloloweralkyl;
(c) halo;
(d) CONR 2 R 3 wherein R 2 and R 3 independently represent C 1-6 alkyl and hydrogen;
(e) loweralkenyl;
(f) -COR 2
(g) -CH 2 OR 2 ;
(h) loweralkynyl;
(i) -CH 2 -NR 2 R 3 ;
(j) -CH 2 SR 2 ;
(k) =0; or
(I) -OR 2 ;

Ar and Ar' are the same or different from each other and are (a) phenyl or substituted phenyl of formula
where R 4 -R 8 independently represent H, RO-, R 2 S-, R 2 SO 2 -,CF 3 O-, CF 3 S-, R 2 R 3 N-, -OCH 2 CO 2 R 2 , -SO 2 NR 2 R 3 , -C0 2 R 2 , -NR 2 SO 2 R 3 , COR 2 , N0 2 , or CN or R 4 -R 5 , R 5 -R 6 , R 6 -R 7 and R 7 -R 8 are joined together forming a bridge;

(b) pyrryl or substituted pyrryl;
(c) furyl or substituted furyl;
(d) pyridyl or substituted pyridyl; or
(e) thiophene or substituted thiophene.

These compounds are found to have potent and specific PAF (Platelet Activating Factor) antagonistic activities and thereby are useful in the treatment of varous diseases or disorders mediated by the PAF, for example, inflammation, cardiovascular disorder, asthma, lung edema, adult respiratory distress syndrome, pain, and aggregation of platelets.

摘要翻译： 式的化合物：... ...被盘游离缺失worin R和R <1>独立地是...（a）氢; ...（B）卤代低级烷基; ...（C）卤素; ...（D）CONR <2> [R <3> worinř<2>和R <3>独立地表示C 1-6烷基和氢; ...（E）低级链烯基; ...（F）-COR <2> ...（G）-CH 2 OR <2>，...（H）loweralkynyl; （I）-CH2-NR <2> [R <3>; ...（J） - CH 2 SR <2>; ...（K）= 0; 或...（L）-O-R <2>; ... Ar和Ar <1>是相同的或彼此不同的并且是...的（a）苯基或式的取代的苯基...... ...其中R <4> -R <8>独立地表示H，RO-，R <2> S-，R <2> SO 2，CF 3 O-，CF3S-，R <2> [R <3> N-，-OCH2CO2R <2>，-SO 2 NR < 2> [R <3>，-CO 2 R <2>，-NR <2> SO 2 <3>，COR <2>，NO 2，或CN或R <4> -R <5>，R <5> -R < 6>，R <6> -R <7>和R <7> -R <8>连接在一起形成一个桥; ...（b）吡咯基或吡咯基substituiertem; ...（C）呋喃基或呋喃基substituiertem; ...（D ）吡啶基或取代的吡啶基; 或者......（五）噻吩或噻吩substituiertem。 ... 被发现这些化合物具有强而特异性的PAF（血小板活化因子）拮抗活性和从而处于varous疾病或病症由PAF介导的治疗中有用，例如，炎症，心血管疾病，哮喘，肺 水肿，成人呼吸窘迫综合征，疼痛，血小板聚集。

公开(公告)号：EP0199324B1

公开(公告)日：1991-10-02

申请号：EP86105471.6

申请日：1986-04-21

申请人： Merck & Co., Inc.

发明人： Biftu, Tesfaye ,  Hwang, San-Bao ,  Doebber, Thomas W. ,  Beattie, Thomas R. ,  Shen, Tsung-Ying

IPC分类号： C07D307/10 ,  C07D307/18 ,  C07D405/04 ,  C07D405/14 ,  C07D417/04 ,  A61K31/34

CPC分类号： C07D307/18 ,  C07D307/12 ,  C07D307/14 ,  C07D307/16 ,  C07D307/20 ,  C07D307/24 ,  C07D307/34 ,  C07D405/04 ,  C07D405/14 ,  C07D407/12 ,  C07D409/14 ,  C07D417/04

公开(公告)号：EP0322033A2

公开(公告)日：1989-06-28

申请号：EP88202879.8

申请日：1988-12-14

申请人： Merck & Co., Inc.

发明人： Biftu, Tesfaye ,  Hwang, San-Boa ,  Doebber, Thomas W. ,  Beattie, Thomas R. ,  Shen, Tsung-Ying

IPC分类号： C07D307/12 ,  C07D307/14 ,  C07D307/18 ,  C07D307/42 ,  C07D405/04 ,  C07D405/14 ,  C07D407/12 ,  C07D405/12 ,  C07D417/04 ,  A61K31/34

CPC分类号： C07D307/18 ,  C07D307/12 ,  C07D307/14 ,  C07D307/16 ,  C07D307/20 ,  C07D307/42 ,  C07D405/04 ,  C07D405/14 ,  C07D407/12 ,  C07D417/04

摘要： A class of 2,5-diaryl tetrahydrofuran derivatives are PAF antagonists and are therefore useful in the treatment of various diseases including prevention of platelet aggregation, hypotension, inflammation, asthma, lung edema, adult respiratory distress syndrome, various shock syndromes, cardiovascular disorders and other related skeletal-muscular disorders.

摘要翻译： 一类2,5-二芳基四氢呋喃衍生物是PAF拮抗剂，因此可用于治疗各种疾病，包括预防血小板聚集，低血压，炎症，哮喘，肺水肿，成人呼吸窘迫综合征，各种休克综合征，心血管疾病和 其他相关的骨骼肌障碍。

公开(公告)号：EP0322033A3

公开(公告)日：1990-08-22

申请号：EP88202879.8

申请日：1988-12-14

申请人： Merck & Co., Inc.

发明人： Biftu, Tesfaye ,  Hwang, San-Boa ,  Doebber, Thomas W. ,  Beattie, Thomas R. ,  Shen, Tsung-Ying

IPC分类号： C07D307/12 ,  C07D307/14 ,  C07D307/18 ,  C07D307/42 ,  C07D405/04 ,  C07D405/14 ,  C07D407/12 ,  C07D405/12 ,  C07D417/04 ,  A61K31/34

CPC分类号： C07D307/18 ,  C07D307/12 ,  C07D307/14 ,  C07D307/16 ,  C07D307/20 ,  C07D307/42 ,  C07D405/04 ,  C07D405/14 ,  C07D407/12 ,  C07D417/04

摘要： A class of 2,5-diaryl tetrahydrofuran derivatives are PAF antagonists and are therefore useful in the treatment of various diseases including prevention of platelet aggregation, hypotension, inflammation, asthma, lung edema, adult respiratory distress syndrome, various shock syndromes, cardiovascular disorders and other related skeletal-muscular disorders.

公开(公告)号：EP0199324A2

公开(公告)日：1986-10-29

申请号：EP86105471.6

申请日：1986-04-21

申请人： Merck & Co., Inc.

发明人： Biftu, Tesfaye ,  Hwang, San-Bao ,  Doebber, Thomas W. ,  Beattie, Thomas R. ,  Shen, Tsung-Ying

IPC分类号： C07D307/10 ,  C07D307/18 ,  C07D405/04 ,  C07D405/14 ,  C07D417/04 ,  A61K31/34

CPC分类号： C07D307/18 ,  C07D307/12 ,  C07D307/14 ,  C07D307/16 ,  C07D307/20 ,  C07D307/24 ,  C07D307/34 ,  C07D405/04 ,  C07D405/14 ,  C07D407/12 ,  C07D409/14 ,  C07D417/04

摘要： Compounds of formula:
are disclosed
wherein R and R' are

(a) hydrogen;
(b) haloloweralkyl;
(c) halo;
(d) CONR 2 R 3 wherein R 2 and R 3 independently represent hydrogen, C 1-8 alkyl, or C 3-8 cycloalkyl;
(e) loweralkenyl;
(f) -COR 2 ;
(g) -CH 2 OR 2 ;
(h) loweralkynyl;
(i) -CH 2 NR 2 R 2 ;
(j) -CH 2 SR 2 ;
(k) = O; or
(l) -OR 2 ;
(m) -R 2 ; Ar and Ar 1 are
(a) phenyl or substituted phenyl of formula

where R 4 -R 8 independently where R 4 -R 8 independently represent H; R 2 ; YO-wherein Y is loweralkenyl, loweralkynyl, - CH 2 -, -CH 2 C(O)OR 2 , -CH 2 OR 2 , -CH 2 C 3- 8 cycloalkyl, -CH 2 Ar 2 wherein Ar 2 is phenyl or substituted phenyl, -CH 2 -CH(OH)CH 2 OH; R 2 S-(O) n wherein R 2 can only be C 3-8 cycloalkyl and n is 0 to 2; CF 3 SO, CF 3 SO 2 ; - CONR 2 R 3 ; -NR 2 COR 3 ; -OCONH 2 -CR 2 R 3 R 9 wherein R 9 is the same as or different from R Z ; -CH 2 OR 2 ; -CH 2 CO 2 R 2 ; -CH 2 OCOR 3 ; -GH 2 O-CO-OR 2 ; -NHCH 2 COOR 2 ; halo; or N + R 2 R 3 R 9 X- wherein X- is an anion;

(b) monoheteroaryl, di-or polyheteroaryl or fused heteroaryl containing 1 to 3 of any one or more of the heteroatoms N, S or O;
(c) heteroarylalkyl;
(d) heterocycloalkyl; or
(e) heterocycloalkenyl. These compounds are found to have potent and specific PAF - (Platelet Activating Factor) antagonistic activities.

摘要翻译： 公开了下式的化合物：其中R和R 1是（a）氢; （b）卤代低级烷基; （c）卤素; （d）CONR 2 R 3其中R 2和R 3独立地表示氢，C 1-8烷基或C 3-8环烷基; （e）低级烯基; （f）-COR 2; （g）-CH 2 OR 2; （h）低级炔基; （i）-CH 2 NR 2 R 3; （j）-CH 2 SR 2; （k）= O; 或（l）-OR 2; （m）-R 2; Ar和Ar 1是（a）苯基或式CHEM的取代的苯基，其中R 4 -R 8独立地表示H; [R <2>; YO-，其中Y是低级烯基，低级炔基，-CH 2，-CH 2 C（O）OR 2，-CH 2 OR 2，-CH 2 C 3-8环烷基，-CH 2 Ar 2，其中Ar 2是苯基或取代的苯基， -CH 2 CH（OH）-CH 2 OH; R 2 -S-（O）n，其中R 2只能是C 3-8环烷基且n是0-2; CF3SO，CF3SO2; -CONR <2> [R <3>; -NR <2> COR <3>; -OCONH2 -CR 2 R 3 R 9其中R 9与R 2相同或不同; -CH 2 OR <2>; -CH2CO2R <2>; -CH2OCOR <3>; -CH2O-CO-OR <2>; -NHCH2COOR <2>; 光环; 或N + R 2 R 3 R 9 X - ，其中X 1为阴离子; （b）含有1至3个任何一个或多个杂原子N，S或O的单杂芳基，二 - 或多杂芳基或稠合杂芳基; （c）杂芳基烷基; （d）杂环烷基; 或（e）杂环烯基。 发现这些化合物具有强效和特异性的PAF（血小板活化因子）拮抗活性。