利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

56 条记录 (耗时 0.024 秒)

    4,7-Benzofurandione derivatives
    22.
    发明公开
    4,7-Benzofurandione derivatives 失效
    4,7-苯并呋喃二酮衍生物

    公开(公告)号：EP0301692A3

    公开(公告)日：1989-03-15

    申请号：EP88305388.6

    申请日：1988-06-13

    申请人： MERCK FROSST CANADA INC.

    发明人： Adams, Julian ,  Belanger, Patrice C. ,  Rokach, Joshua ,  Guindon, Yvan ,  Belly, Michel L.

    IPC分类号： C07D307/06 ,  C07D407/06 ,  C07D407/04 ,  C07D407/12 ,  A61K31/34 ,  A61K31/36

    CPC分类号： C07D407/06 ,  C07D307/86

    摘要： 4,7-Benzofurandione derivatives of Formula I, pharmaceutical compositions, and methods of treatment are disclosed. These compounds are useful as inhibitors of mammalian leukotriene biosynthesis. As such, these compounds are useful therapeutic agents for treating allergic conditions, asthma, cardio­vascular disorders, inflammation, psoriasis and allergic conjunctivitis. The compounds are also useful as analgesics and as cytoprotective agents. Also disclosed are novel intermediates useful for the preparation of the 4,7-benzofurandiones of this invention.

    摘要翻译： 公开了式I的4,7-苯并呋喃二酮衍生物，药物组合物和治疗方法。 这些化合物可用作哺乳动物白三烯生物合成的抑制剂。 因此，这些化合物是用于治疗变应性病症，哮喘，心血管病症，炎症，牛皮癣和变应性结膜炎的有用的治疗剂。 该化合物也可用作止痛剂和细胞保护剂。 还公开了可用于制备本发明的4,7-苯并呋喃二酮的新颖中间体。

    Leukotriene antagonists
    24.
    发明公开
    Leukotriene antagonists 失效
    白藜芦醇拮抗剂

    公开(公告)号：EP0147217A3

    公开(公告)日：1986-08-13

    申请号：EP84309045

    申请日：1984-12-21

    申请人： MERCK FROSST CANADA INC.

    发明人： Rokach, Joshua ,  Girard, Yves

    IPC分类号： C07D311/24 ,  C07D311/22 ,  C07D215/54 ,  C07D311/16 ,  C07D303/00 ,  A61K31/335 ,  A61K31/47 ,  C07C149/40 ,  C07C149/42

    CPC分类号： C07K5/0606 ,  A61K31/335 ,  C07C33/02 ,  C07C45/305 ,  C07C47/21 ,  C07C323/00 ,  C07D215/54 ,  C07D303/42 ,  C07D311/16 ,  C07D311/22 ,  C07D311/24 ,  C07F9/4015

    摘要： Compounds having the formula:
    and their pharmaceutically acceptable salts are antagonists of leukotrienes of C 4 , D 4 and E 4 , the slow reacting substance of anaphylaxis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory agents, and cytoprotective agents. In the formula,
    X is 0, S, SO, S0 2 ; R is selected from:
    -CH=CH-(C 1 to C 14 alkyl), -(CH=CH) 2 -(C 1 to C 12 alkyl), -(CH=CH) 3 -(C, to C 10 alkyl), -(CH=CH) 3 -(CH 2 -CH=CH) 2 -(C 1 to C 4 alkyl), -(CH=CH) 4 -(C, to C 8 alkyl), -CH 2 -(CH=CH) 4 -(C 1 to C 7 alkyl), -(CH=CH) 3 -CH 2 CH=CH-(CH 2 ) n CH 2 OH wherein n is 1 to 6, -(CH=CH) 3 -CH 2 CH=CH-(CH 2 ) n COOR 1 wherein n is 1 to 6, -(CH=CH) 3 -CH 2 CH=CH-(C 1 to C 7 alkyl); -C≡C-(C 1 to C 14 alkyl), -CH=CH-C≡C-(C 1 to C 12 alkyl), -C≡C-(CH=CH)-(C 1 to C 12 alkyl), -C≡C-(CH-CH) 2 -(C 1 to C lo alkyl), and -C≡C-(CH=CH) 2 -CH 2 -CH=CH-(C 1 to C 7 alkyl); R 1 is COOR", CH 2 OH, CHO, tetrazole, hydroxymethyl ketone, CN, CON(R 4 ) 2 , CONHSO 2 R 5 a monocyclic or bicyclic heterocyclic ring containing an acidic hydroxyl group or NHSO 2 R 5 ; or
    wherein each s is independently 0 to 3; R 9 is
    A) a monocyclic or bicyclic heterocyclic radical containing from 3 to 12 nuclear carbon atoms and 1 or 2 nuclear heteroatoms selected from N and S with at least one being N, and with each ring in the heterocyclic radical being formed of 5 or 6 atoms, or B) the radical W-R 10 wherein W is O, S or NH and R 10 contains up to 21 carbon atoms which may be straight chain or branched and is (1) a hydrocarbon radical or (2) an acyl radical of an organic cyclic or monocyclic carboxylic acid containing not more than 1 heteroatom selected from N, O or S in the ring;
    each R 8 is independently H or alkyl of 1 to 4 carbons which may be straight chain or branched;
    or
    R 3 is H, lower alkyl, -(CH 2 ) a COOR 1 or C 1 to C 5 acyl; each R" is independently H, lower alkyl or two R 4 radicals may be joined to from a ring of from 5 to 8 members; each R 5 is independently lower alkyl; CF 3 ; phenyl; or substituted phenyl, wherein the substituents are C, to C 3 alkyl, halogen, CN, CF 3 , COOR 4 or C, to C 3 alkoxy; R 6 is H, lower alkyl, OH, halogen, C, to C 3 perfluoroalkyl, CN, NO 2 , C 1 to C 5 acyl, COOR 4 , SO 2 N(R 4 ) 2 , N(R 4 ) 2 , OR S , SR S , SOR S , SO 2 R 5 , 0-aryl, benzyl, benzyl substituted as defined for phenyl in R 5 , or CH 2 OH; R 7 is H or R 5 ; R" is H, lower alkyl, phenyl-lower alkyl, lower alkoxy-lower alkyl, lower acyloxy-lower alkyl; a is 0 to 4.

    摘要翻译： 具有下式的化合物及其药学上可接受的盐是C4，D4和E4的白三烯，慢性反应物质的过敏反应的拮抗剂。 这些化合物可用作抗哮喘，抗过敏，抗炎剂和细胞保护剂。在该配方中，X是O，S，SO，SO 2; R选自：-CH = CH-（C1至C14烷基）， - （CH = CH）2-（C1至C12烷基）， - （CH = CH）3-（C1至C10烷基） - （CH = CH（CH = CH）2 - （C 1 -C 4烷基）， - （CH = CH）4 - （C 1 -C 8烷基） ）， - （CH = CH）3 -CH 2 CH = CH-（CH 2）n CH 2 OH其中n为1至6， - （CH = CH）3 -CH 2 CH = CH-（CH 2）n COOR 1其中n为 1〜6， - （CH = CH）3 -CH 2 CH = CH-（C 1〜C 7烷基）; -C = C-（C 1至C 14烷基）， - CH = CH-C标识C（C 1至C 12烷基）， - C标识C（CH = CH） - （C 1至C 12烷基）， - C - （CH = CH）2 - （C 1至C 10烷基）和-C≡C-（CH = CH）2 -CH 2 -CH = CH-（C 1至C 7烷基） R 1是含有酸性羟基或NHSO 2 R的单环或双环杂环的COOR 1，CH 2 OH，CHO，四唑，羟甲基酮，CN，CON（R 4）2，CONHSO 2 R 5 <5>; 或，其中每个s独立地为0至3; R 9是A）含有3至12个核碳原子和1或2个选自N和S的核杂原子的单环或双环杂环基，其中至少一个是N，杂环基中的每个环由 5或6个原子，或B）基团WR 1其中W是O，S或NH，R 1至0含有至多21个碳原子，其可以是直链或支链的，并且是（1 ）烃基或（2）在环中含有不超过1个选自N，O或S的杂原子的有机环状或单环羧酸的酰基; R 8独立地是H或可以是直链或支链的1至4个碳的烷基; R 3是H，低级烷基， - （CH 2）a COOR 1或C 1至C 5酰基; 每个R 4独立地为H，低级烷基或两个R 4基团可以从5至8个成员的环连接; 每个R 5独立地为低级烷基; CF3; 苯基; 或取代的苯基，其中取代基是C1-C3烷基，卤素，CN，CF3，COOR4或C1-C3烷氧基; R 6是H，低级烷基，OH，卤素，C 1至C 3全氟烷基，CN，NO 2，C 1至C 5酰基，COOR 4，SO 2 N（R 4）2，N（R） 2，OR 5，SR 5，SOR 5，SO 2 R 5，O-芳基，苄基，R 5中苯基取代的苄基或CH 2 OH; R 7是H或R 5; R 1是H，低级烷基，苯基 - 低级烷基，低级烷氧基 - 低级烷基，低级酰氧基 - 低级烷基; a是0到4. l

    5-Lipoxygenase inhibitors
    26.
    发明公开
    5-Lipoxygenase inhibitors 失效
    5 Lipoxigenaseinhibitoren。

    公开(公告)号：EP0140709A2

    公开(公告)日：1985-05-08

    申请号：EP84307480.8

    申请日：1984-10-30

    申请人： MERCK FROSST CANADA INC.

    发明人： Atkinson, Joseph G. ,  Belanger, Patrice C. ,  Guindon, Yvan ,  Rokach, Joshua

    IPC分类号： A61K31/54 ,  A61K31/535 ,  A61K31/495 ,  C07D513/04

    CPC分类号： C07D513/04 ,  A61K31/495 ,  A61K31/535 ,  A61K31/54 ,  C07D241/18

    摘要： Compounds of the Formula I:
    and their pharmaceutically acceptable salts are inhibitors of the mammalian 5-lipoxygenase enzyme system of the arachidonic acid cascade. As such, these compounds are useful therapeutic agents for treating allergic conditions, asthma, cardiovascular disorders and inflammation and are incorporated into pharmaceutical compositions. Certain of the compounds are novel.
    In the formula,

    Z is O, NCN, SO or SO 2 ;
    R, is H, C 1-6 alkyl, benzyl, C 1-6 acyl, C 1-6 aminoacyl, (C 1-6 alkylacyloxy)-(C 1-6 alkyl), (C 1-6 alkoxy)-(C 1-6 alkyl), -(CH 2 ) n COOR 6 where n is, 0, 1, 2, 3 or 4, CN, (C 1-6 alkyl)acyloxy-(C 1-6 alkoxy)carbonyl, -C(R 7 ) = C(R 7 )COOR 6 or SO 2 R 10 ;
    each of R 2 , R 3 , R 4 and R 5 , independently of the others, is hydrogen, C 1-6 alkyl, C 2-6 alkenyl or -(CH 2 ) n M, where n is 0 or an integer from 1 to 6 and
    M is(a) OR 16

    (b) halogen;
    (c) CF 3 .
    (d) SR 16 ;
    (e) phenyl;
    (f) substituted phenyl where the substituents(s) is/are C 1-3 alkyl, halogen, CN, C 1-3 alkoxy, OH, (CH 2 ) n NR 8 R 9 where n is 0, 1 or 2, CF 3 , COOR 6 or CH 2 COOR 6 ; (herein called «substituted phenyl as defined»);
    (g) COOR 6 ;
    (h) -CO-R 14 ;
    (i) tetrazolyl;
    (j) NH-CO-R 7 ;
    (k) NR 8 R 9 ;
    (I) NHSO 2 R 10 ;
    (m) -CO-CH 2 0H;
    (n) SOR 11 where R 11 is C 1-6 alkyl, phenyl, substituted phenyl as defined, (CH 2 ) m COOR 6 , where m is an integer from 1 to 6, or CF 3 ;
    (o) CONR 8 R 9 ;
    (p) SO 2 NR 8 R 9 ;
    (q) S0 2 R 13 where R 13 is OH, C 1-6 alkyl, H phenyl, substituted phenyl as defined, (CH 2 ) m COOR 6 or CF 3 ;
    (r) N0 2 ;
    (s) -OCO-R 14 ;
    (t) -OCO-NR 8 R 9 ;
    (u)-OCO-OR 7 ; or
    (v) -CN;

    each R 16 , independently of any other, is H; (C 1-6 alkoxy)-(C 1-6 alkyl); (C 1-6 alkyl)acyloxy(C 1-6 alkyl); C 1-6 alkyl; substituted phenyl as defined; -CH 2 ) m COOR 6 ; CN: C 1-5 alkylacyl; C 1-4 perfluoroalkyl; phenyl; benzyl; or CH 2 -R 12 where R 12 is C 1-5 alkyldimethylamino;
    each R 6 , independently of any other, is H, C 1-6 alkyl, benzyl or phenyl;
    each R 14 , independently of any other, is H, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkyl)acyloxy(C 1-6 alkoxy), (CH 2 ) n COOR 6 where n is 0 or an integer from 1 to 4, phenyl or substituted phenyl as defined or is such that R 14 COOH is an essential amino acid;
    each of R 8 and R 9 , independently of the others, is H, phenyl, substituted phenyl as defined or C 1-4 alkyl, or NR 8 R 9 is a heterocycloalkyl of 5 to 8 ring atoms; and
    each R 7 , independently of the others, is H, C 1-6 alkyl, benzyl, phenyl or (C 1-6 alkyl)acyloxy-(C 1-6 alkoxy);
    each R 10 is independently OH, C 1-6 alkyl, C 1-6 alkoxy, phenyl or p-tolyl;
    or any two of R,, R 2 , R 3 , R 4 or R 5 are joined to form an additional ring of 5 to 7 members that optionally contains a carbonyl group and/or a hydroxyl group as substituent(s), and that has 0, 1 or 2 double bonds, and such that, if R, is a constituent of the ring, one member is nitrogen and the others are carbon and if R 1 is not a constituent of the ring, all the members are carbon; and
    T is hydrogen or OR 15 where R 15 is hydrogen, C 1-6 alkyl, C 1-6 alkylacyl, phenyl-(C 1-8 alkyl)acyl, SO 2 R 10 , arylsulfonyl, -CO-phenyl or substituted phenyl as defined.

    摘要翻译： 式I化合物：及其药学上可接受的盐是花生四烯酸级联的哺乳动物5-脂肪氧合酶系统的抑制剂。 因此，这些化合物是用于治疗过敏性疾病，哮喘，心血管疾病和炎症的有用的治疗剂，并且被并入药物组合物中。 某些化合物是新颖的。 在该式中，Z为O，NCN，SO或SO2; R1为H，C1-6烷基，苄基，C1-6酰基，C1-6氨基酰基，（C1-6烷基酰氧基） - （C1-6烷基），（C1-6烷氧基） - （C1-6烷基） （C 1 -C 6烷氧基）羰基，-C（R 7）= C（R 7）COOR 6或SO 2 R 10;（C 1 -C 6）烷氧基羰基， R2，R3，R4和R5独立地为氢，C1-6烷基，C2-6烯基或 - （CH2）nM，其中n为0或1-6的整数，M为（（ ）OR16（b）卤素; （c）CF3。 （d）SR16; （e）苯基; （f）取代的苯基，其中取代基是C 1-3烷基，卤素，CN，C 1-3烷氧基，OH，（CH 2）n NR 8 R 9，其中n是0,1或2，CF 3，COOR 6或CH 2 COOR 6; （这里称为“定义的取代苯基”）; （g）COOR6; （h）-CO-R14; （i）四唑基; （j）NH-CO-R7; （k）NR8R9; （l）NHSO2R10; （m）-CO-CH 2 OH; （n）SOR11，其中R11为C1-6烷基，苯基，定义的取代苯基，（CH2）mCOOR6，其中m为1至6的整数，或CF 3; （o）CONR8R9; （p）SO2NR8R9; （q）SO 2 R 13，其中R 13是OH，C 1-6烷基，H苯基，如所定义的取代苯基，（CH 2）m COOR 6或CF 3; （r）NO2; （S）-OCO-R14; （t）-OCO-NR8R9; （u）-OCO-OR 7; 或（v）-CN; 每个R16独立地为H; （C 1-6烷氧基）（C 1-6烷基）; （C 1-6烷基）酰氧基（C 1-6烷基）; C 1-6烷基; 取代的苯基; -CH 2）mCOOR6; CN：C 1-5烷基酰基; C1-4全氟烷基; 苯基; 苄基; 或CH 2 -R 12，其中R 12是C 1-5烷基二甲基氨基; 每个R 6独立地为H，C 1-6烷基，苄基或苯基; 每个R 14独立地为H，C 1-6烷基，C 1-6烷氧基，C 1-6烷基）酰氧基（C 1-6烷氧基），（CH 2）n COOR 6，其中n为0或1至4的整数， 苯基或取代的苯基，或使得R 14 COOH是必需氨基酸; R 8和R 9各自独立地是H，苯基，如所定义的取代的苯基或C 1-4烷基，或NR 8 R 9是5至8个环原子的杂环烷基; 并且每个R 7独立地为H，C 1-6烷基，苄基，苯基或（C 1-6烷基）酰氧基 - （C 1-6烷氧基）; 每个R 10独立地是OH，C 1-6烷基，C 1-6烷氧基，苯基或对甲苯基; 或R 1，R 2，R 3，R 4或R 5中的任何两个连接以形成任选地含有羰基和/或羟基作为取代基的5至7个成员的另外的环，并且具有0,1或 2个双键，并且如果R1是环的成分，则一个是氮，另一个是碳，如果R 1不是环的成分，则所有的成员都是碳; 并且T是氢或OR 15，其中R 15是氢，C 1-6烷基，C 1-6烷基酰基，苯基 - （C 1-8烷基）酰基，SO 2 R 10，芳基磺酰基，-CO-苯基或如所定义的取代的苯基。

    Leukotriene antagonists
    27.
    发明公开
    Leukotriene antagonists 失效
    白三烯，Antagonisten。

    公开(公告)号：EP0140684A2

    公开(公告)日：1985-05-08

    申请号：EP84307390.9

    申请日：1984-10-26

    申请人： MERCK FROSST CANADA INC.

    发明人： Frenette, Richard ,  Rokach, Joshua ,  Young, Robert N. ,  Kakushima, Masatoshi

    IPC分类号： C07C69/738 ,  C07C59/90 ,  C07D307/93 ,  C07C321/28 ,  C07C381/10 ,  C07C317/00 ,  A61K31/34 ,  A61K31/35 ,  A61K31/215

    CPC分类号： C07D307/93 ,  C07C59/90 ,  C07C317/00 ,  C07C323/00

    摘要： Compounds having the formula:
    and their salts, including acid-addition salts, are novel. These compounds are antagonists of leukotrienes of C 4 , D 4 and E 4 , the slow reacting substance of anaphylaxis. The compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory and cytoprotective agents and are made into suitable pharmaceutical compositions.

    In the formula, each R, independently of the other(s), is H, OH or OR 2 , or C(R) 2 represents C=C(R 4 ) 2 ;
    R 1 is H, OH, acyl, formyl, R 5 CO; or R 5 OCO; each of R 2 and R 3 , independently of the others, is H, OH,
    C 1-6 alkyl, C 2-6 alkenyl, trifluoromethyl, C 1-6 alkoxy, SH, C 1-6 thioalkyl, phenyl, phenyl having C 1-3 alkyl halogen substitution, benzyl, phenethyl, halogen, amino, N(R 4 ) 2 , COOR 4 , CH 2 0R 4 , formyl, CN, trifluoromethylthio or nitro;
    .each of X 1 and X 2 , independently of the other, is oxygen, sulfur, sulfoxide, sulfone, -SO=NR 5 , NR e , N-CO-R 7 , N-CN or NCONHR 6 ;
    each of R 4 and R 6 , independently of the other(s), is H or C 1-6 alkyl;
    each R 5 is C 1-6 alkyl; each R 7 , independently of the other, if any, is C 1-6 alkyl or C 1-6 alkoxy;
    W is H or C 1-6 alkyl or is combined with Y to form an unsaturated bond;
    Z is H, OH or C 1-6 alkoxy, or is combined with Y to form an oxo residue;
    Y, of not combined with Z or W, is hydrogen;
    A is -[C(R 4 ) 2]s- R 8 where S is 0,1, 2, or 3 and R 8 isCOOR 4 , CH 2 0H, CHO, tetrazolyl, NHSO 2 R 9 , CONHSO 2 R 9 , hydroxymethylketone, CN, CON(R 7 ) 2 , a monocyclic heterocyclic ring containing an acidic hydroxyl group, or
    where each s, independently, of the others, is 0, 1, 2 or 3 and R 10 is (A) a monocyclic or bicyclic radical containing from 3 to 12 nuclear carbon atoms and, as nuclear heteroatoms, two Ns or one N and one S, and with each ring in the heterocyclic radical being formed of 5 or 6 atoms, or (B) the radical X'-R 11 where X' is O, S or NH and R 11 contains up to 21 carbon atoms and is a hydrocarbon radical or an acryl radical of an organic acyclic or monocyclic carboxylic acid containing not more than 1 heteroatom in the ring;
    each n, independently of the others, is 0,1, or 3;
    R 9 is OH, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 perfluoroalkyl, phenyl, or phenyl having one or more R 2 substituents.

    摘要翻译： 具有下式的化合物：及其盐，包括酸加成盐，是新颖的。 这些化合物是C4，D4和E4的白细胞三烯的拮抗剂，过敏反应的缓慢反应物质。 该化合物可用作抗哮喘，抗过敏，抗炎和细胞保护剂，并制成合适的药物组合物。 在该式中，每个R独立地为H，OH或OR 2，或者C（R）2表示C = C（R 4）2; R1是H，OH，酰基，甲酰基，R5CO; 或R5OCO; R 2和R 3各自独立地为H，OH，C 1-6烷基，C 2-6烯基，三氟甲基，C 1-6烷氧基，SH，C 1-6硫代烷基，苯基，具有C 1-3烷基卤素取代基的苯基 ，苄基，苯乙基，卤素，氨基，N（R4）2，COOR4，CH2OR4，甲酰基，CN，三氟甲硫基或硝基; X1和X2分别独立地为氧，硫，亚砜，砜，-SO = NR5，NR6，N-CO-R7，N-CN或NCONHR6; R 4和R 6各自独立地为H或C 1-6烷基; 每个R 5是C 1-6烷基; 每个R 7，独立于另一个，如果有的话是C 1-6烷基或C 1-6烷氧基; W是H或C 1-6烷基或与Y结合形成不饱和键; Z是H，OH或C 1-6烷氧基，或与Y结合形成氧代残基; Y不与Z或W组合，是氢; A是 - [C（R4）2] s-R8，其中S是0,1,2或3，R8是COOR4，CH2OH，CHO，四唑基，NHSO2R9，CONHSO2R9，羟甲基酮，CN，CON（R7）2， 含有酸性羟基的单环杂环，或，其中各自独立地为0,1,2或3，R 10为（A）含有3至12个核碳原子的单环或双环基团 和作为核杂原子的两个N或一个N和一个S，杂环基中的每个环由5或6个原子形成，或（B）基团X min -R11，其中X min为O，S或NH 并且R 11含有至多21个碳原子，并且是在环中含有不超过1个杂原子的烃基或丙烯基或有机非环或单环羧酸; 每个n独立于其他n是0,1,2或3; R 9是OH，C 1-6烷基，C 1-6烷氧基，C 1-6全氟烷基苯基或具有一个或多个R 2取代基的苯基。

    Phenothiazone derivatives and analogs
    28.
    发明公开
    Phenothiazone derivatives and analogs 失效
    苯并噻唑衍生物和类似物

    公开(公告)号：EP0115394A3

    公开(公告)日：1985-01-30

    申请号：EP84300239

    申请日：1984-01-16

    申请人： MERCK FROSST CANADA INC.

    发明人： Guindon, Yvan ,  Fortin, Rejean ,  Lau, Cheuk K. ,  Rokach, Joshua ,  Yoakim, Christiane

    IPC分类号： A61K31/54 ,  A61K31/535 ,  A61K31/495 ,  C07D279/18 ,  C07D265/38 ,  C07D241/46 ,  C07D293/10 ,  C07D279/34 ,  C07D279/36 ,  C07D265/34

    CPC分类号： C07D293/10 ,  A61K31/495 ,  A61K31/535 ,  A61K31/54 ,  C07C46/06 ,  C07D241/46 ,  C07D265/34 ,  C07D265/38 ,  C07D279/18 ,  C07D279/34 ,  C07D279/36 ,  C07C50/28

    摘要： Phenothiazine compounds of formula
    where
    X is in the 1 or 3 position and is O, S or NR; R is H, C 1 -C 6 branched or linear alkyl, CN or phenyl; Y is 0, Se, S, SO, SO 2 or NR; and the broken line represents an optional double bond between the 1 and 2 or 2 and 3 position; each of R 1 , R 2 , R 3 and R 4 , independently of the others, is
    (1) hydrogen (2) C 1-6 alkyl, (3) C 2-6 alkenyl, (4) -(CH 2 ) n M where n is 0 or an integer from 1 to 6 and M is
    (a) OR 5 , (b) halogen, (c) CF 3 , (d) SR 5 where R 5 is H;
    alkoxyalkyl; acyloxyalkyl; C 1-6 alkyl; benzyl;
    phenyl or substituted phenyl where the substituents are C 1-3 alkyl, halogen, CN, CF 3 , COOR 6 , CH 2 COOR 6 , (CH 2 ) n NR 8 R 9 where n is 0, 1 or 2, C 1-3 alkoxy, OH, C 1-6 haloalkyl, -(CH 2 ) m COOR 6 , where m is 0 or an integer from 1 to 6 and R 6 is H, phenyl or C 1-6 alkyl; CN, formyl; perfluoroalkyl; or CH 2 -R 12 , where R 12 is C 1-5 alkyl, phenyl or dimethylamino; (e) phenyl or substituted phenyl as defined above for R 5 ; (f) COOR 6 ; (g)
    where R 14 is H, (CH 2 ) n COOR 6 where n is 0 or an integer from 1 to 4, C 1-6 alkyl, CF 3 , phenyl, or substituted phenyl as defined above for R 5 ; (h) tetrazole; (i)
    where R 7 is C 1-8 alkyl, benzyl or phenyl; (j) -NR 8 R 9 where R e and R 9 are independently selected from H, phenyl or substituted phenyl as defined above for R 5 , C 1 -C 4 alkyl or C 1 -C 4 alkylaminoalkyl, or are joined through the N to form a heterocycloalkyl of 5-8 ring atoms; (k) -NHSO 2 R 10 where R 10 is OH, C 1 -C 6 alkyl, C 1 -C 6 - alkoxy, phenyl or CF 3 ;
    (m) -SOR 11 where R 11 is C 1 -C 6 alkyl, phenyl or substituted phenyl as defined above for R 5 , (CH 2 ) m COOR 6 where m is 1 to 6, CN, formyl or C 1-4 perfluoroalkyl;
    (p) -SO 2 R 13 where R 13 is OH, H, C 1 -C 6 alkyl, phenyl or substituted phenyl as defined above for R 5 , (CH 2 ) m COOR 6 where m is 1 to 6, CN or C 1-4 perfluoroalkyl; (q) NO 2 ; (r)
    (s)
    (t)
    (u) -CN; or (v) NR 15 R 16 where R 15 and R 16 are such that HNR 15 R 16 is an essential amino acid;
    or any two of R 1 , R 2 , R 3 and R 4 are joined to form a fourth saturated or unsaturated C 5-6 ring, and T is H, halogen or CF 3 . are useful as inhibitors of mammalian leukotriene biosynthesis and therefore are useful therapeutic agents for treatng pain, skin conditions, allergic conditions, pulmonary conditions, asthma, cardiovascular disorders and inflammation. They are included in pharmaceutical compositions. Certain of the compounds are novel.

    Leukotriene antagonists
    29.
    发明公开
    Leukotriene antagonists 失效
    Leukotrienantagonisten。

    公开(公告)号：EP0123541A1

    公开(公告)日：1984-10-31

    申请号：EP84302718.6

    申请日：1984-04-19

    申请人： MERCK FROSST CANADA INC.

    发明人： Belanger, Patrice ,  Guindon, Yvan ,  Fortin, Rejean ,  Yaokim, Christiane ,  Rokach, Joshua

    IPC分类号： C07C59/90 ,  C07C51/347 ,  C07C149/40 ,  C07C147/107 ,  C07D317/14 ,  C07D233/78 ,  C07D207/44 ,  C07D303/02 ,  A61K31/19

    CPC分类号： C07D285/10 ,  C07C45/71 ,  C07C49/84 ,  C07C49/86 ,  C07C59/90 ,  C07C255/00 ,  C07D257/04

    摘要： Compounds of the formula:
    and their pharmaceutically acceptable salts, which are novel, are antagonists of leukotrienes of C4, D4 and E., the slow reacting substance of anaphylaxis. These compounds are useful as anti-asthmatic, anti-allergic and anti-inflammatory agents and are made into pharmaceutical compositions.
    In the formula, R, is a radical of formula COOR 3 , where R 3 is hydrogen or an alkyl or cycloalkyl group containing not more than six carbon atoms; CH 2 OH; CHO; CH 2 NHSO 2 R 4 , where R 4 is OH; C 1-6 alkyl, C 1-6 alkoxy phenyl, phenyl substituted by Ci-3 alkyl or Ci- 3 alkoxy, halogen, hydroxy, haloalkyl, COOH, CN, formyl, C 1-6 acyl or C 1-4 perfluoroalkyl; CN; or CON(R 5 ) 2 , where each R 5 , independently of the other, is H, OH or C 1-4 alkyl; a tetrazolyl radical, a monocyclic or bicyclic heterocyclic ring containing an acidic hydroxyl group; or a radical of formula
    where each s, independently of the other, is 0,1, 2 or 3; R 7 is

    (A) a monocyclic or bicyclic heterocyclic radical containing from 3 to 12 nuclear carbon atoms and 1 or 2 nuclear heteroatoms, one being N, and the other (if any) being N or S, each ring in the heterocyclic radical having 5 or 6 atoms, or
    (B) a radical X-R 8 where X is O, S or NH and R 8 contains up to 21 carbon atoms and is (1) a hydrocarbon radical or (2) an acyl radical derived from an organic acyclic or monocyclic carboxylic acid containing not more than 1 heteroatom that is N, 0 or S in the ring; and each R 10 , independently of the other is H or Ci-4 alkyl;
    R 6 is H or Ci-4 alkyl;
    R 2 is a halogen atom; and
    R 9 is a hydrogen atom or hydroxyl group.

    摘要翻译： 下式的化合物及其药物上可接受的盐是C4，D4和E4的白三烯拮抗剂，即过敏反应缓慢的物质。 这些化合物可用作抗哮喘，抗过敏和抗炎剂并制成药物组合物。 在该式中，R 1是式COOR 3的基团，其中R 3是氢或含有不超过6个碳原子的烷基或环烷基; CH2OH; CHO; CH2NHSO2R4，其中R4是OH; C 1-6烷基，C 1-6烷氧基苯基，被C 1-3烷基或C 1-3烷氧基取代的苯基，卤素，羟基，卤代烷基，COOH，CN，甲酰基，C 1-6酰基或C 1-4四氟烷基; CN; 或CON（R5）2，其中每个R5独立于H，OH或C1-4烷基; 四唑基，含有酸性@羟基的单环或双环杂环; 或式的基团，其中每个s独立于0,2,2或3; R2是（A）含有3至12个核碳原子和1或2个核杂原子的单环或双环杂环基，一个为N，另一个为N或S，杂环基中的每个环均为5 或6个原子，或（B）基团X-R8，其中X是O，S或NH和R8含有至多21个碳原子，并且是（1）烃基或（2）衍生自有机非环或 在环中含有不多于1个N，O或S的杂原子的单环羧酸; 每个R 10独立地为H或C 1-4烷基; R6是H或C1-4烷基; R2是卤原子; R9为氢原子或羟基。