Title:
LEUCOTRIENE ANTAGONIST SUBSTANCE
Document Type and Number:
Japanese Patent JPS60169432
Kind Code:
A
Abstract:
Compounds having the formula: and their pharmaceutically acceptable salts are antagonists of leukotrienes of C4, D4 and E4, the slow reacting substance of anaphylaxis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory agents, and cyto-protective agents, In the formula, X is O, S, SO, SO2; R is selected from: -CH=CH-(C1 to C14 alkyl), -(CH=CH)2-(C1 to C12 alkyl), -(CH=CH)3-(C1 to C10 alkyl) -(CH=CH)3-(CH2-CH=CH)2-(C1 to C4 alkyl), -(CH=CH)4-(C1 to C8 alkyl), -CH2-(CH=CH)4-(C1 to C7 alkyl), -(CH=CH)3-CH2CH=CH-(CH2)nCH2OH wherein n is 1 to 6, -(CH=CH)3-CH2CH=CH-(CH2)nCOOR<1><1> wherein n is 1 to 6, -(CH=CH)3-CH2CH=CH-(C1 to C7 alkyl); -C=C-(C1 to C14 alkyl), -CH=CH-C IDENTICAL C-(C1 to C12 alkyl), -C IDENTICAL C-(CH=CH)-(C1 to C12 alkyl), -C IDENTICAL C-(CH=CH)2-(C1 to C10 alkyl), and -C IDENTICAL C-(CH=CH)2-CH2-CH=CH-(C1 to C7 alkyl); R<1> is COOR<1><1>, CH2OH, CHO, tetrazole, hydroxymethyl ketone, CN, CON(R<4>)2, CONHSO2R<5> a monocyclic or bicyclic heterocyclic ring containing an acidic hydroxyl group or NHSO2R<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<1><0> wherein W is O, S or NH and R<1><0> 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; and R<8> is independently H or alkyl of 1 to 4 carbons which may be straight chain or branched; R<3> is H, lower alkyl, -(CH2)aCOOR<1> or C1 to C5 acyl; each R<4> 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; CF3; phenyl; or substituted phenyl, wherein the substituents are C1 to C3 alkyl, halogen, CN, CF3, COOR<4> or C1 to C3 alkoxy; R<6> is H, lower alkyl, OH, halogen, C1 to C3 perfluoroalkyl, CN, NO2, C1 to C5 acyl, COOR<4>, SO2N(R<4>)2, N(R)<4>)2, OR<5>, SR<5>, SOR<5>, SO2R<5>, O-aryl, benzyl, benzyl substituted as defined for phenyl in R<5>, or CH2OH; R<7> is H or R<5>; R<1><1> is H, lowr alkyl, phenyl-lower alkyl, lower alkoxy-lower alkyl, lower acyloxy-lower alkyl; a is 0 to 4. l
Inventors:
IBUSU JIRAADO
JIYOSHIYUA ROKATSUCHI
JIYOSHIYUA ROKATSUCHI
Application Number:
JP27422984A
Publication Date:
September 02, 1985
Filing Date:
December 27, 1984
Export Citation:
Assignee:
MERCK FROSST CANADA INC
International Classes:
A61K31/22; A61K31/165; A61K31/19; A61K31/23; A61K31/275; A61K31/335; A61K31/336; A61K31/47; A61P11/00; A61P43/00; C07C1/32; C07C11/28; C07C17/16; C07C21/04; C07C21/19; C07C27/00; C07C29/147; C07C33/02; C07C45/00; C07C45/30; C07C47/21; C07C47/277; C07C67/00; C07C69/52; C07C231/00; C07C235/06; C07C235/28; C07C301/00; C07C303/40; C07C311/17; C07C311/51; C07C313/00; C07C317/18; C07C317/24; C07C317/28; C07C317/38; C07C317/46; C07C317/50; C07C323/12; C07C323/14; C07C323/22; C07C323/40; C07C323/52; C07C323/54; C07C323/56; C07C323/65; C07C323/67; C07D215/48; C07D215/54; C07D303/02; C07D303/42; C07D311/16; C07D311/22; C07D311/24; C07D333/62; C07D335/06; C07F9/40; C07K5/06; (IPC1-7): A61K31/22; A61K31/23; A61K31/275; A61K31/335; A61K31/47; C07/; C07C1/32; C07C11/28; C07C17/16; C07C21/04; C07C21/19; C07C33/02; C07C43/23; C07C47/277; C07C49/24; C07C49/255; C07C49/84; C07C59/125; C07C59/58; C07C59/72; C07C59/90; C07C69/52; C07C103/167; C07D215/48; C07D303/02; C07D311/22; C07D333/62; C07D335/06
Attorney, Agent or Firm:
Masao Okabe