公开(公告)号：EP1810971A1

公开(公告)日：2007-07-25

申请号：EP07009479.2

申请日：2004-03-03

申请人： SCHERING CORPORATION

发明人： Burnett, Duane A. ,  Clader, John W.

IPC分类号： C07D405/12 ,  A61K31/397 ,  A61P3/06

CPC分类号： C07D405/12

摘要： The present invention provides substituted azetidinone compounds of formula (IA), formulations and processes for preparing the same which can be useful for treating vascular conditions such as atherosclerosis or hypercholesterolemia, diabetes, obesity, stroke, demyelination and lowering plasma levels of sterols and/or stanols in a subject.

摘要翻译： 本发明提供了式（IA）的substituiertem氮杂环丁酮化合物，式tions和用于制备相同的其可用于治疗血管病症：诸如动脉粥样硬化或高胆固醇血症，糖尿病，肥胖症，中风，脱髓鞘和降低甾醇的血浆水平和/或 烷醇的主题。

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。