Claims
- 1. A compound of the formula: ##STR14## wherein: each of R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.10 is independently hydrogen, halogen, lower alkyl, lower alkenyl, lower alkynyl, --CF.sub.3, --CN, --NO.sub.2, --N.sub.3, --C(OH)R.sup.6 R.sup.6, --C(O)OR.sup.12, --SR.sup.13, --S(O)R.sup.13, --S(O).sub.2 R.sup.13, --S(O).sub.2 NR.sup.15 R.sup.15, --C(O)NR.sup.15 R.sup.15, --OR.sup.15, --NR.sup.15 R.sup.15, --C(O)R.sup.16 or --(CH.sub.2).sub.r R.sup.21 ;
- R.sup.5 is hydrogen or X--R.sup.9,
- R.sup.6 is independently hydrogen or lower alkyl, or two R.sup.6 groups on the same carbon atom are joined to form a cycloalkyl ring of 3 to 6 carbon atoms;
- R.sup.7 is --(CR.sup.6 R.sup.6).sub.s Q;
- R.sup.8 is hydrogen, R.sup.9, --CR.sup.23 .dbd.CR.sup.24 R.sup.25, --C(Cl).dbd.CCl.sub.2 or R.sup.6 plus R.sup.8 on the same carbon atom may be a double bonded oxygen (.dbd.O);
- R.sup.9 is alkyl, alkenyl, --(CH.sub.2).sub.t Ph(R.sup.10).sub.2 or --(CH.sub.2).sub.t Th(R.sup.10).sub.2 ;
- R.sup.11 is the structure of a standard amino acid except for the amino group .alpha. to the carboxy group, or R.sup.11 and R.sup.18 attached to the same nitrogen can cyclize to form a proline residue;
- R.sup.12 is hydrogen, lower alkyl or --CH.sub.2 R.sup.21 ;
- R.sup.13 is --CF.sub.3 or R.sup.14 ;
- R.sup.14 is lower alkyl or --(CH.sub.2).sub.u R.sup.21 ;
- R.sup.15 is hydrogen, --C(O)R.sup.16, R.sup.14, or two R.sup.15 groups on the same nitrogen may be joined to form a heterocyclic ring of 4 to 6 atoms containing up to 2 heteroatoms chosen from O, S or N;
- R.sup.16 is hydrogen, lower alkenyl, lower alkynyl, or R.sup.13 ;
- R.sup.17 is --(CH.sub.2).sub.v --C(R.sup.18 R.sup.18)--(CH.sub.2).sub.v --R.sup.19 or --CH.sub.2 C(O)NR.sup.15 R.sup.15 ;
- R.sup.18 is hydrogen or lower alkyl;
- R.sup.19 is
- a) a monocyclic or bicyclic heterocyclic radical containing from 3 to 9 nuclear carbon atoms and 1 or 2 nuclear hetero-atoms selected from N, S or O and with each ring in the heterocyclic radical being formed of 5 or 6 atoms, or
- b) the radical W-R.sup.20 ;
- R.sup.20 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;
- R.sup.21 is phenyl substituted with 1 or 2 R.sup.22 groups;
- R.sup.22 is hydrogen, halogen, lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfonyl, lower alkylcarbonyl, --CF.sub.3, --CN, --NO.sub.2 or --N.sub.3 ;
- R.sup.23 is R.sup.18 or R.sup.23 and R.sup.24 may form a bond;
- R.sup.24 is R.sup.6 or R.sup.23 and R.sup.24 may form a bond;
- R.sup.25 is R.sup.6 ;
- m is 0 to 3;
- p is 1 to 3
- q is 0 or 1;
- m+p+q is 2 to 4;
- m+q is 0 to 3;
- r is 0 to 2;
- s is 0 to 4;
- t is 0 to 3;
- u is 0 to 3;
- v is 0 to 3;
- W is O, S, or NR.sup.15 ;
- X is C(O), CR.sup.6 R.sup.6, S(O).sub.2, or a bond;
- X.sup.2 --X.sup.3 is CH.sub.2 O, CH.sub.2 S, CH.sub.2 S(O).sub.2, CH.sub.2 CH.sub.2, or CH.dbd.CH;
- Y is O, NR.sup.15, S, S(O), or S(O).sub.2 ;
- Q is --C(O)NR.sup.11 R.sup.18 --C(O)OR.sup.12, --C(O)NHS(O).sub.2 R.sup.13, --NHS(O).sub.2 R.sup.13, --S(O).sub.2 NHR.sup.15, --C(O)NR.sup.15 R.sup.15, --C(O)OR.sup.17, --CH.sub.2 OH, or 1H- or 2H-tetrazol-5-yl;
- or the pharmaceutically acceptable salts thereof.
- 2. A compound of claim 1 wherein:
- each of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is hydrogen;
- R.sup.5 is X-R.sup.9 ;
- R.sup.8 is R.sup.9 ;
- R.sup.10 is hydrogen or halogen;
- the CH.sub.2 O is attached to the 2-position of the quinoline ring;
- X is a bond; and
- X.sup.2 --X.sup.3 is CH.sub.2 O;
- Q is --C(O)OR.sup.12.
- 3. A compound of claim 1 of formula Ib wherein the substituents are as follows:
- __________________________________________________________________________ ##STR15## IbR.sup.5 R.sup.7 (CR.sup.6 R.sup.6).sub.p Y (CR.sup.6 R.sup.6).sub.m (R.sup.6 CR.sup.8).sub.q__________________________________________________________________________1 p-ClBz 1-CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 O -- HCH2 p-ClBz 1-CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 O -- HC-p-ClPh3 p-MeSBz 1-CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 S -- HCH4 p-MeS(O).sub.2 Bz 1-CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 S(O).sub.2 -- HCH5 p-ClBz 1-CH.sub.2 CO.sub.2 H (CH.sub.2).sub. 3 S -- --6 p-ClBz 1-CH.sub.2 CO.sub.2 H (CH.sub.2).sub.3 S(O).sub.2 -- --7 p-ClBz 1-CH.sub.2 CO.sub.2 H CHEt O CH.sub.2 HCH8 p-ClBz 1-CH.sub.2 CO.sub.2 H CHEt O CH.sub.2 HCBz__________________________________________________________________________
- 4. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
- 5. A method of preventing the synthesis, the action, or the release of SRS-A or leukotrienes in a mammal which comprises administering to said mammal an effective amount of a compound of claim 1.
- 6. The method of claim 5 wherein the mammal is man.
- 7. A method of treating asthma in a mammal comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 1.
CROSS-REFERENCE
This is a continuation-in-part of Ser. No. 558,724, Jul. 26, 1990, pending now abandoned.
US Referenced Citations (10)
Foreign Referenced Citations (4)
Number |
Date |
Country |
0238226 |
Sep 1987 |
EPX |
0307077 |
Mar 1989 |
EPX |
WO9106537 |
May 1991 |
WOX |
1382513 |
Feb 1975 |
GBX |
Non-Patent Literature Citations (1)
Entry |
Mobilio et al., J. Med. Chem., 31, 2211-2217 (1988). |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
558724 |
Jul 1990 |
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