公开(公告)号：EP0508425A1

公开(公告)日：1992-10-14

申请号：EP92106148.7

申请日：1992-04-09

申请人： SCHERING CORPORATION

发明人： Clader, John W. ,  Fevig, Thomas ,  Vaccaro, Wayne ,  Berger, Joel G.

IPC分类号： C07C233/23 ,  C07C233/14 ,  C07C233/41 ,  C07C275/32 ,  C07D311/68 ,  C07D213/40 ,  C07C231/02 ,  A61K31/165 ,  A61K31/35 ,  A61K31/44

CPC分类号： C07D213/75 ,  C07C233/06 ,  C07C233/14 ,  C07C233/23 ,  C07C233/41 ,  C07C2602/08 ,  C07C2602/10 ,  C07D311/68

摘要： Novel bicyclic amides of the formula

wherein Ar¹ and Ar² are phenyl, R²-substituted phenyl, heteroaryl or R²-substituted heteroaryl, wherein R² is 1 to 3 substituents independently selected from the group consisting of halogeno, hydroxy, lower alkyl, lower alkoxy, nitro, amino, lower alkylamino and lower dialkylamino;
   X, Y and Z are -CH₂-, -CH(alkyl)-, -C(alkyl)₂-, -NH-, -N(alkyl)-, -O- or SO r , wherein r is 0, 1 or 2, and m, n and p are 0 or 1;
   R¹ is an alkyl chain of 1 to 25 carbon atoms; an alkyl chain substituted by one or more optionally substituted phenyl or heteroaryl groups; an alkyl chain -O-, -SO r , phenylene, R²-substituted phenylene, heteroarylene or R²-substituted heteroarylene groups; an interrupted alkyl chain substituted by one or more optionally substituted phenyl or heteroaryl groups; an alkyl chain of 4 to 25 carbon atoms, interrupted by one or more -NH-, -C(O)- or -N(lower alkyl)- groups; an interrupted alkyl chain of 4 to 25 carbon atoms substituted by one or more phenyl, R²-substituted phenyl, heteroaryl or R²-substituted heteroaryl groups; a diphenylamino group; a di-(R²-substituted phenyl)amino group; a diheteroarylamino group; or a di-(R²-substituted heteroaryl)amino group;
   or a pharmaceutically acceptable salt thereof, useful in the treatment of artherosclerosis are disclosed.

摘要翻译： 式的新型双环酰胺，其中Ar 1和Ar 2是苯基，R 2 - 取代的苯基，杂芳基或R 2 - 取代的杂芳基，其中R 2是1至3个取代基 羟基，低级烷基，低级烷氧基，硝基，氨基，低级烷基氨基和低级二烷基氨基; X，Y和Z是-CH 2 - ， - CH（烷基） - ， - C（烷基）2 - ， - NH - ， - N（烷基） - ， - O-或SOr，其中r是0,1或2 ，m，n和p为0或1; R 1是1至25个碳原子的烷基链; 被一个或多个任选取代的苯基或杂芳基取代的烷基链; 烷基链-O-，-SOr，亚苯基，R 2 - 取代亚苯基，杂亚芳基或R 2取代的亚杂芳基; 被一个或多个任选取代的苯基或杂芳基取代的间断烷基链; 4个至25个碳原子的烷基链，被一个或多个-NH-，-C（O） - 或-N（低级烷基）基团间隔; 被一个或多个苯基，R 2取代的苯基，杂芳基或R 2取代的杂芳基取代的4至25个碳原子的中断的烷基链; 二苯基氨基; 二（R 2取代苯基）氨基; 二杂芳基氨基; 或二（R 2 - 取代杂芳基）氨基; 或其药学上可接受的盐，其可用于治疗动脉粥样硬化。

公开(公告)号：EP0524595A1

公开(公告)日：1993-01-27

申请号：EP92112425.1

申请日：1992-07-21

申请人： SCHERING CORPORATION

发明人： Burnett, Duane A. ,  Clader, John W. ,  Thiruvengadam, Tiruvettipuram K. ,  Tann, Chou-Hong ,  Lee, Junning ,  McAllister, Timothy ,  Colon, Cesar ,  Barton, Derek H.R. ,  Breslow, Ronald ,  Dugar, Sundeep ,  Vaccaro, Wayne

IPC分类号： C07D205/08 ,  C07D205/085 ,  C07D401/04 ,  C07D403/04 ,  C07D405/10 ,  C07D405/04 ,  C07D409/04 ,  A61K31/395

CPC分类号： C07D401/04 ,  C07D205/08 ,  C07D205/085 ,  C07D403/04 ,  C07D405/04 ,  C07D405/10 ,  C07D409/04 ,  C07F7/0812 ,  C07F7/186 ,  C07F7/1892

摘要： Novel compounds of the formula

wherein
   A is -CH=CH-B; -C≡C-B; -(CH₂) p -X-B, wherein p is 0-2 and X is a bond, -NH- or-S(O)₀₋₂; optionally substituted heteroaryl or benzofused heteroaryl; -C(O)-B; or

wherein k is 1-2;
   D is B'-(CH₂) m C(O)-, wherein m is 1-5; B'-(CH₂) q -, wherein q is 2-6; B'-(CH₂) e -Z-(CH₂) r -, wherein Z is -O-, -C(O)-, phenylene, -NR₈- or -S(O)₀₋₂-, e is 0-5 and r is 1-5, provided that the sum of e and r is 1-6; B'-(alkenylene)-; B'-(alkadienylene)-; B'-(CH₂) t -Z-(alkenylene), wherein t is 0-3, provided that the sum of t and the number of carbon atoms in the alkenylene chain is 2-6; B'-(CH₂) f -V-(CH₂) g -, wherein V is cycloalkylene, f is 1-5 and g is 0-5, provided that the sum of f and g is 1-6; B'-(CH₂) t -V-(alkenylene) or B'-(alkenylene)-V-(CH₂) t -, provided that the sum of t and the number of carbon atoms in the alkenylene chain is 2-6; B'-(CH₂)a-Z-(CH₂)b-V-(CH₂)d-, wherein a, b and d are 0-6, provided that the sum of a, b and d is 0-6; T(CH₂) s -, wherein T is cycloalkyl and s is 1-6; naphthylmethyl or optionally substituted heteroarylmethyl;
   B is optionally substituted phenyl;
   B' is naphthyl, optionally substituted heteroaryl or optionally substituted phenyl;
   R is hydrogen, fluoro, alkyl, alkenyl, alkynyl, or B-(CH₂)h-, wherein h is 0-3;
   R4 is optionally substituted phenyl, indanyl, benzofuranyl, tetrahydronaphthyl, pyridyl, pyrazinyl, pyrimidinyl or quinolyl;
are disclosed, as well as their use as hypocholesterolemic agents; the method of using compounds of the formula II

wherein
   R₂₀ is optionally substituted phenyl, optionally substituted naphthyl, optionally substituted heteroaryl, or optionally substituted benzofused heteroaryl,
   R₂₁, R₂₂ and R₂₃ are independently selected from H or R₂₀;
   E, F and G are independently a bond; cycloalkylene; alkylene; alkenylene; alkynylene; a substituted alkylene, alkenylene or alkynylene chain ; an interrupted alkylene, alkenylene or alkynylene chain ; or an interrupted alkylene, alkenylene or alkynylene chain substituted by one or more substituents; or one of R₂₁-E and R₂₂-F is selected from the group consisting of halogeno, OH, alkoxy, -OC(O)R₅, -NR₁₀R₁₁, -SH or -S(alkyl);
   R₅ is alkyl, phenyl, R₁₄-phenyl, benzyl or R₁₄-benzyl;
   R₁₀ and R₁₁ are independently selected from H and lower alkyl, or a pharmaceutically acceptable salt thereof, in a pharmaceutically aceptable carrier as hypocholesterolemic agents is also disclosed.

摘要翻译： 式的新型化合物，其中A为-CH = CH-B; -C标识C-B; - （CH 2）p -X-B，其中p为0-2且X为键，-NH-或-S（O）0-2; 任选取代的杂芳基或苯并稠合的杂芳基; -C（O）-B; 或，其中k为1-2; D是B' - （CH 2）m C（O） - ，其中m是1-5; B' - （CH 2）q - ，其中q为2-6; B' - （CH2）eZ-（CH2）r-，其中Z是-O - ， - C（O） - ，亚苯基，-NR8-或-S（O）0-2-，e是0-5， r为1-5，条件是e和r之和为1-6; B' - （亚烯基） - ; B' - （亚二烯） - ; B' - （CH 2）t-Z-（亚烯基），其中t为0-3，条件是亚烯基链中t和碳原子数之和为2-6; B' - （CH 2）f-V-（CH 2）g - ，其中V为亚环烷基，f为1-5且g为0-5，条件是f和g之和为1-6; B' - （CH 2）t-V-（亚烯基）或B' - （亚烯基）-V-（CH 2）t - ，条件是亚链烯基链中t和碳原子数之和为2-6; B' - （CH 2）a-Z-（CH 2）b -V-（CH 2）d - ，其中a，b和d为0-6，条件是a，b和d之和为0-6; T（CH 2）s - ，其中T是环烷基且s是1-6; 萘基甲基或任选取代的杂芳基甲基; B是任选取代的苯基; B'是萘基，任选取代的杂芳基或任选取代的苯基; R是氢，氟，烷基，烯基，炔基或B-（CH 2）h - ，其中h是0-3; R4是任选取代的苯基，茚满基，苯并呋喃基，四氢萘基，吡啶基，吡嗪基，嘧啶基或喹啉基。 被公开，以及它们用作低胆固醇血药剂; 使用式II 的化合物的方法，其中R 20是任选取代的苯基，任选取代的萘基，任选取代的杂芳基或任选取代的苯并稠合的杂芳基，R 21，R 22和R 23独立地选自H或R 20; E，F和G独立地为键; 环烷基; 亚; 烯基; 炔基; 取代的亚烷基，亚烯基或亚炔基链; 中间亚烷基，亚烯基或亚炔基链; 或被一个或多个取代基取代的中断的亚烷基，亚烯基或亚炔基链; 或R 21 -E和R 22 -F之一选自卤代，OH，烷氧基，-OC（O）R 5，-NR 10 R 11，-SH或-S（烷基）。 R5是烷基，苯基，R14-苯基，苄基或R14-苄基; R10和R11独立地选自H，低级烷基或其药学上可接受的盐在药学上可接受的载体中，作为降血胆固醇剂也被公开。