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EP0219308A2 Expired / Lapsed EP ⏱️ 0.0 years remaining

2-Substituted quinolines

Assignee: Merck Frosst Canada and Co
•
Filing: 1986-10-08
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Granted: —
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Expires: 2006-10-08
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Abstract

Abstract Novel compounds have the formula: or are pharmaceutically acceptable salts thereof. In the formula: Y is -(CR²=CR²) n -, -(C≡C) n -, -CR²R²-X-, -X-CR²R²-, -CR²R²-X-CR²R²-, X, C=O, -NR²--, or --NR²-; R¹ is H, halogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, -CF₃, -OR², -SR², -SOR², -SO₂R², -NR²R², -CHO, -COOR², -(C=O)R², -C(OH)R²R², -CN, -NO₂, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, or substituted or unsubstituted phenethyl; R² is H, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, -CF₃, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, or substituted or unsubstituted phenethyl; R³ is -(A) m -(CR⁶=CR⁶) p -(CR²R⁴) m -Q; R⁴ is H, halogen, -NO₂, -CN, -OR², -SR², NR²R², or C 1-8 alkyl; R⁵ is R⁶ is H or C 1-4 alkyl; R⁷ is A) a monocyclic or bicyclic heterocyclic radical containing from 3 to 12 nuclear carbon atoms and 1 or 2 nuclear heteroatoms from N, S or O, each ring in the hererocyclic radical being formed of 5 or 6 atoms, or B) the radical W-R⁸; R⁸ contains up to 21 carbon atoms and is (1) a hydrocarbon radical or (2) an acyl radical of an organic acyclic or monocyclic carboxylic acid containing not more than 1 heteroatom in the ring; R⁹ is -OR¹⁰, -SR¹⁰, or NR¹⁰R¹⁰; R¹⁰ is H, C 1-6 alkyl, -(C=O)R¹¹, unsubstituted phenyl or unsubstituted benzyl; R¹¹ is H, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, -CF₃, or unsubstituted phenyl, benzyl, or phenethyl; R¹² is R² or halogen; m is 0-8; n is 1 or 2; p is 0 or 1; s is 0-3; A is -CR⁴R⁴-, or =C=O; Q is -COOR², tetrazole, -COOR⁵, -CONHSO₂R¹¹, -CN, -CONR¹⁰R¹⁰, -NHSO₂R¹¹ (but only when the sum of m, m and P in R³ is greater than 0); or if Q is COOH and R³ contains an R⁴ which is -OH, -SH, or -NHR² then Q and R⁴ and the carbons through which they are attached may form a heterocyclic ring with loss of water; w is O, S, or NH; and X is O, S, -SO, -SO₂, or -NR². The compounds are antagonists of leukotrienes and inhibitors of their biosynthesis and are useful as anti-asthmatic, anti-allergic, anti-­inflammatory, and cytoprotective agents.

Inventors

  • 👤 Robert N. Young
  • 👤 Robert Zamboni
  • 👤 Serge Leger

Bibliographic Details

Application Number —
Jurisdiction EP
Data Source google_patents
Last Synchronized 2026-11-09 03:12
CPC Classifications
C; C07; C07D; C07D215/00; C07D215/02; C07D215/12; A; A61; A61P; A61P29/00; A61P37/00; A61P37/08; C07D215/16; C07D215/18

Claims Analysis

Total Claims: 11
Claim 1
Independent Claim 368 words
A compound of the formula: in which Y is -(CR²=CR²) n -, -(C≡C) n -, -CR²R²-X-, -X-CR²R²-, -CR²R²-X-CR²R²-, C=O, -NR²- -, or - -NR²-; R¹ is H, halogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, -CF₃, -OR², -SR², -SOR², -SO₂R², -NR²R², -CHO, -COOR², -(C=O)R², -C(OH)R²R², -CN, -NO₂, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, or substituted or unsubstituted phenethyl; R² is H, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, -CF₃, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, or substituted or unsubstituted phenethyl; R³ is -(A) m -(CR⁶=CR⁶) p -(CR²R⁴) m -Q; R⁴ is H, halogen, -NO₂, -CN, -OR², -SR², NR²R², or C 1-8 alkyl; R⁵ is R⁶ is H or C 1-4 alkyl; R⁷ is A) a monocyclic or bicyclic heterocyclic radical containing from 3 to 12 nuclear carbon atoms and 1 or 2 nuclear heteroatoms from N, S or O, each ring in the hererocyclic radical being formed of 5 or 6 atoms, or B) the radical W-R⁸; R⁹ contains up to 21 carbon atoms and is (1) a hydrocarbon radical or (2) an acyl radical of an organic acyclic or monocyclic carboxylic acid containing not more than 1 heteroatom in the ring; R⁹ is -OR¹⁰, -SR¹⁰, or NR¹⁰R¹⁰; R¹⁰ is H, C 1-6 alkyl, -(C=O)R¹¹, unsubstituted phenyl or unsubstituted benzyl; R¹¹ is H, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, -CF₃, or unsubstituted phenyl, benzyl, or phenethyl; R¹² is R² or halogen; m is 0-8; n is 1 or 2; p is 0 or 1; s is 0-3; A is -CR⁴R⁴-, or =C=O; Q is -COOR², tetrazole, -COOR⁵, -CONHSO₂R¹¹, -CN, -CONR¹⁰R¹⁰,-NHSO₂R¹¹ (but only when the sum of m, m and P in R³ is greater than 0); or if Q is COOH and R³ contains an R⁴ which is -OH, -SH, or -NHR² then Q and R⁴ and the carbons through which they are attached may form a heterocyclic ring with loss of water; w is O, S, or NH; and X is O, S, -SO, -SO₂, or -NR²; provided that where two or more of any variable are present, each is the same as or different from the other(s); and compounds that are pharmaceutically acceptable salts thereof.
Claim 2
Dependent Claim 368 words
A compound of the formula: in which Y is -(CR²=CR²) n -, -(C≡C) n -, -CR²R²-X-, -X-CR²R²-, -CR²R²-X-CR²R²-, C=O, -NR²- -, or - -NR²-; R¹ is H, halogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, -CF₃, -OR², -SR², -SOR², -SO₂R², -NR²R², -CHO, -COOR², -(C=O)R², -C(OH)R²R², -CN, -NO₂, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, or substituted or unsubstituted phenethyl; R² is H, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, -CF₃, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, or substituted or unsubstituted phenethyl; R³ is -(A) m -(CR⁶=CR⁶) p -(CR²R⁴) m -Q; R⁴ is H, halogen, -NO₂, -CN, -OR², -SR², NR²R², or C 1-8 alkyl; R⁵ is R⁶ is H or C 1-4 alkyl; R⁷ is A) a monocyclic or bicyclic heterocyclic radical containing from 3 to 12 nuclear carbon atoms and 1 or 2 nuclear heteroatoms from N, S or O, each ring in the hererocyclic radical being formed of 5 or 6 atoms, or B) the radical W-R⁸; R⁹ contains up to 21 carbon atoms and is (1) a hydrocarbon radical or (2) an acyl radical of an organic acyclic or monocyclic carboxylic acid containing not more than 1 heteroatom in the ring; R⁹ is -OR¹⁰, -SR¹⁰, or NR¹⁰R¹⁰; R¹⁰ is H, C 1-6 alkyl, -(C=O)R¹¹, unsubstituted phenyl or unsubstituted benzyl; R¹¹ is H, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, -CF₃, or unsubstituted phenyl, benzyl, or phenethyl; R¹² is R² or halogen; m is 0-8; n is 1 or 2; p is 0 or 1; s is 0-3; A is -CR⁴R⁴-, or =C=O; Q is -COOR², tetrazole, -COOR⁵, -CONHSO₂R¹¹, -CN, -CONR¹⁰R¹⁰,-NHSO₂R¹¹ (but only when the sum of m, m and P in R³ is greater than 0); or if Q is COOH and R³ contains an R⁴ which is -OH, -SH, or -NHR² then Q and R⁴ and the carbons through which they are attached may form a heterocyclic ring with loss of water; w is O, S, or NH; and X is O, S, -SO, -SO₂, or -NR²; provided that where two or more of any variable are present, each is the same as or different from the other(s); and compounds that are pharmaceutically acceptable salts thereof.
Claim 3
Dependent Claim 38 words
A compound of the Formula Ia: in which Y is -(CR²=CR²) n - or -(C≡C) n - and R¹ to R¹¹, m,n,p,s,A,Q,W and X are as defined in claim 1 and compounds that are pharmaceutically acceptable salts thereof.
Claim 4
Dependent Claim 55 words
A compound of the Formula Ib: in which R¹ is H, halogen, CH₃, -CF₃ or SCF₃; R² is H, C 1-3 alkyl, C 2-3 alkenyl, or -CF₃; p is 0; and R³ to R¹¹, m, s, A, Q, W and X are as defined in claim 1 and compounds that are pharmaceutically acceptable salts thereof.
Claim 5
Dependent Claim 24 words
A compound of the Formula Ic: in which the variables are as defined in claim 3, and compounds that are pharmaceutically acceptable salts thereof.
Claim 6
Dependent Claim 21 words
A compound of the formula: in which Y' is S or O; and R ³ is as defined in claim 1.
Claim 7
Dependent Claim 59 words
The following compounds as claimed in claim 1; 4-(2-(quinolin-2-yl)ethenyl)benzoic acid methyl ester; 4-(2-(quinolin-2-yl)ethenyl)benzoic acid; 3-(2-(quinolin-2-yl)ethenyl)benzenepropanoic acid ethyl ester; 3-(2-(Quinolin-2-yl)ethenyl)benzenepropanoic acid 3-(2-(quinolin-2-yl)ethenyl)-γ-oxo-β-methylbenzene butanoic acid methyl ester; 3-(2-(quinolin-2-yl)ethenyl)-γ-hydroxy-β-methyl­benzenebutanoic acid methyl ester; [βR,γS and βS,γR]-3-(2-quinolin-2-yl)-ethenyl-γ-­hydroxy-β-methylbenzenebutanoic acid lactone; [βS,γS and βR,γR]-3-(2-quinolin-2-yl)-ethenyl)-γ-­hydroxy-β-methylbenzenebutanoic acid lactone; [βR,γS and β,SγR]-3-(2-(Quinolin-2-yl)ethenyl)-γ-­hydroxy-β-methylbenzenebutanoic acid sodium salt; [βS,γS and βR,γR]-3-(2-quinolin-2-yl)ethenyl)-γ-­hydroxy-β-methylbenzenebutanoic acid sodium salt; 3-(2-(7-Chloroquinolin-2-yl)ethenyl)-β-methylbenzene­propanoic acid; [βS,γR and βR,γS]-4-((quinolin-2-yl)methylthio)-γ-­hydroxy-β-methylbenzenebutanoic acid sodium salt;
Claim 8
Dependent Claim 36 words
A pharmaceutical composition useful in antagonizing leukotriene action in mammals comprising a compound as claimed in any one of claims 1 to 6 in an amount effective as a leukotriene antagonist and a pharmaceutically acceptable carrier.
Claim 9
Dependent Claim 48 words
A composition as claimed in claim 7 additionally comprising an effective amount of a second active ingredient that is a non-steroidal anti-­inflammatory drug; a peripheral analgesic agent; cyclooxygenase inhibitor; a leukotriene antagonist; a leukotriene inhibitor; an H₂-receptor antagonist; an antihistaminic agent; a prostaglandin antagonist or a thromboxane antagonist.
Claim 10
Dependent Claim 30 words
A compound as claimed in any one of claims 1 to 6 for use in preventing the synthesis, the action, or the release of SRS-A or leukotriene D₄ in mammals.
Claim 11
Dependent Claim 23 words
A compound as claimed in any one of claims 1 to 6 for use in treating inflammatory diseases of the eye in mammals.

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