Claims
- 1. A compound of the formula: ##STR26## wherein: each R.sup.1 is independently hydrogen or C.sub.1 to C.sub.6 alkyl;
- R.sup.2 is C.sub.1 to C.sub.6 alkyl or ##STR27## R.sup.3 is hydroxyl, ##STR28## OCOCH.sub.2 CH.sub.2 COOH, OSO.sub.3 H, or OPO.sub.3 H.sub.2 ; R.sup.4 is C.sub.1 to C.sub.6 alkyl;
- each R.sup.5 is independently H or C.sub.1 to C.sub.6 alkyl;
- Y, Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4 and Z is each independently H, halogen, OH, C.sub.1 to C.sub.6 alkyl, C.sub.2 to C.sub.6 alkenyl, --COOR.sup.1, --COR.sup.1, nitro, C.sub.1 to C.sub.6 alkoxy, C.sub.1 to C.sub.6 alkylthio, --CH.sub.2 SR.sup.1, --CONR.sup.1 R.sup.1, SCF.sub.3, --SO.sub.2 NR.sup.1 R.sup.1, --CN, --CF.sub.3, or --NR.sup.5 R.sup.5 ; and
- n is 0 to 10;
- with the provisos that:
- (a) not all of R.sup.1, Y, Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4, and Z are simultaneously H;
- (b) when up to 2 of R.sup.1, R.sup.2, Y, Y.sup.1, and Z are C.sub.1 to C.sub.2 alkyl, and the others of R.sup.1, R.sup.2, Y, Y.sup.1, and Z are H, then R.sup.3 is not OH;
- (c) when n is 0 and one of R.sup.3, Y, Y.sup.1, or Z is OH, then R.sup.1 is not H or C.sub.1 to C.sub.2 alkyl; and
- (d) at least one of Y, Y.sup.1, and Z is not H;
- or a pharmaceutically acceptable salt thereof.
- 2. A compound of claim 1 wherein:
- each R.sup.1 is C.sub.1 to C.sub.3 alkyl;
- R.sup.2 is C.sub.1 to C.sub.3 alkyl or ##STR29## R.sup.3 is hydroxyl, ##STR30## OCOCH.sub.2 CH.sub.2 COOH, OSO.sub.3 H, or OPO.sub.3 H.sub.2 ; R.sup.4 is C.sub.1 to C.sub.3 alkyl;
- Y, Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4, and Z is each independently H, halogen, C.sub.1 to C.sub.3 alkyl, C.sub.2 or C.sub.3 alkenyl, --COOR.sup.1 --COR.sup.1, C.sub.1 to C.sub.3 alkoxy, C.sub.1 to C.sub.3 alkylthio, --CH.sub.2 SR.sup.1, --CONR.sup.1 R.sup.1, --SCF.sub.3, --SO.sub.2 NR.sup.1 R.sup.1, --CN, or --CF.sub.3 ;
- n is 0 to 4;
- or a pharmaceutically acceptable salt thereof.
- 3. A compound of claim 2 wherein:
- R.sup.1 is methyl;
- R.sup.2 is ##STR31## R.sup.3 is 4-hydroxyl, 4--OSO.sub.3 H, or 4--OPO.sub.3 H.sub.2 ; n is 1 or 2; and
- Y, Y.sup.1, Y.sup.2 Y.sup.3, Y.sup.4, and Z is each independently H, fluorine, chlorine, methyl, propyl, allyl, --COOR.sup.1, --COR.sup.1, methoxy, methylthio, --CH.sub.2 SR.sup.1, or --CF.sub.3 ;
- or a pharmaceutically acceptable salt thereof.
- 4. A compound of claim 3 wherein
- R.sup.2 is ##STR32## U, Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4, and Z is each independently H, fluorine, chlorine, propyl, allyl, methoxy, or CH.sub.2 SR.sup.1 ;
- or a pharmaceutically acceptable salt thereof.
- 5. A compound of claim 3 wherein:
- Y, Y.sup.1, Y.sup.2 Y.sup.3, Y.sup.4, and Z are each independently H, fluorine, chlorine, propyl, allyl, methoxy, or CH.sub.2 SR.sup.1 ;
- or a pharmaceutically acceptable salt thereof.
- 6. A compound of claim 1 of the formula: ##STR33## wherein the substituents are as follows:
- __________________________________________________________________________R.sup.1 R.sup.2 R.sup.3 Y Y.sup.1 Y.sup.2 Y.sup.3 Y.sup.4__________________________________________________________________________ 8 CH.sub.3 C.sub.2 H.sub.5 4-OH 5-allyl H -- -- -- 9 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl H H H H 15 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 5-OH 6-OH H H H H 16 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl H 4-OH H H 17 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl H 4-OCH.sub.3 H H 24 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OCO.sub.2 CH.sub.3 5-propyl H 4-OH H H 25 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OCO.sub.2 CH.sub.3 5-propyl H 4-OCH.sub.3 H H 26 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-F H H H 27 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-F 4-OH H H 28 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-F 4-OCH.sub.3 H H 29 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-F 4-F H H 30 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-F 4-Cl H H 31 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-F 4-N(CH.sub.3).sub.2 H H 32 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl H 4-F H H 33 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl H 4-Cl H H 34 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl H 4-N(CH.sub.3).sub.2 H H 35 C.sub.3 H.sub.7 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl H H H H 36 C.sub.3 H.sub.7 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-F 4-F H H 37 C.sub.3 H.sub.7 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-F 4-OH H H 38 C.sub.3 H.sub.7 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-F 4-OCH.sub.3 H H 39 C.sub.3 H.sub.7 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-F 4-N(CH.sub.3).sub.2 H H 40 C.sub.3 H.sub.7 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl H 4-OCH.sub.3 H H 41 C.sub.3 H.sub.7 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl H 4-OH H H 42 C.sub.3 H.sub.7 CH.sub.2 C.sub.6 H.sub.5 5-OH 6-OH H 4-OCH.sub.3 H H 43 C.sub.3 H.sub.7 CH.sub.2 C.sub.6 H.sub.5 5-OH 6-OH H 4-F H H 45 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 6-OH 5-propyl H 4-OCH.sub.3 H H 46 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-allyl H 4-OCH.sub.3 H H 48 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-CH.sub.2 SCH.sub.3 H 4-OCH.sub.3 H H 57 CH.sub.3 CH.sub.2 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl H 4-OCH.sub.3 H H 58 CH.sub.3 C.sub.6 H.sub.5 4-OH 5-propyl H 4-OCH.sub.3 H H 59 CH.sub.3 C.sub.6 H.sub.5 4-OH 5-propyl H 4-OH H H 60 CH.sub.3 C.sub.6 H.sub.5 4-OH 5-propyl H 4-F H H 69 CH.sub.3 CH.sub.2 C.sub.6 H.sub. 5 4-OH 5-COCH.sub.3 7-F 4-OCH.sub.3 H H 70 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-COCH.sub.3 7-F 4-OCH.sub.3 H H 73 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-Cl 4-OCH.sub.3 3-CHO H 74 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-Cl 4-Br H H 75 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl H 4-Cl H H 76 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 5-OH 4-propyl 7-Cl 4-F H H 78 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OAc 5-propyl H 4-OH H H 79 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 5-OH 4-propyl H 4-OH H H 84 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OAc 5-propyl 7-Cl 4-OCH.sub.3 H H 85 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OAc 5-propyl 7-F 4-OCH.sub.3 H H 87 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OCO.sub.2 CH.sub.3 5-propyl 7-F 4-OCH.sub.3 H H 88 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OCO.sub.2 CH.sub.3 5-propyl 7-Cl 4-OCH.sub.3 H H 89 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-Br 4-OCH.sub.3 H H 90 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-Cl 4-OCH.sub.3 H H 91 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-allyl H 4-OCH.sub.3 H H 93 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 7-propyl H 4-OCH.sub.3 H H 94 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-CH.sub.3 4-OCH.sub.3 H H 95 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-Pr 4-OCH.sub.3 H H 96 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-Cl 7-Pr 4-OCH.sub.3 H H 97 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OPO.sub.3 H.sub.2 5-propyl 7-Cl 4-OCH.sub.3 H H 98 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OCOCH.sub.2 CH.sub.2 CO.sub.2 H 5-propyl 7-F 4-OCH.sub.3 H H 99 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OCOCH.sub.2 CH.sub.2 CO.sub.2 H 5-propyl 7-Cl 4-OCH.sub.3 H H100 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 5-OAc 4-propyl H 4-OCH.sub.3 H H101 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 5-OCO.sub.2 CH.sub.3 4-propyl H 4-OCH.sub.3 H H102 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 5-OH 4-propyl H 4-OCH.sub.3 H H107 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl H H H H108 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-Cl H H H109 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-Cl 4-OH H H112 CH.sub.3 CH.sub.2 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-Cl 4-OCH.sub.3 H H113 CH.sub.3 CH.sub.2 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl H 4-OCH.sub.3 H H114 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OSO.sub.3 H 5-propyl 7-Cl 4-OCH.sub.3 H H115 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-Cl 4-SCH.sub.3 H H116 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH CH.sub.2 SCH.sub.3 7-Cl 4-OCH.sub.3 H H120 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OSO.sub.3 H CH.sub.2 SCH.sub.3 7-Cl 4-OCH.sub.3 H H121 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OCOCH.sub. 2 CH.sub.2 CO.sub.2 H CH.sub.2 SCH.sub.3 7-Cl 4-OCH.sub.3 H H122 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OPO.sub.3 H.sub.2 CH.sub.2 SCH.sub.3 7-Cl 4-OCH.sub.3 H H124 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH CH.sub.2 SCH.sub.3 7-F 4-OCH.sub.3 H H128 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OSO.sub.3 H CH.sub.2 SCH.sub.3 7-F 4-OCH.sub.3 H H129 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OCOCH.sub.2 CH.sub.2 CO.sub.2 H CH.sub.2 SCH.sub.3 7-F 4-OCH.sub.3 H H130 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OPO.sub.3 H.sub.2 CH.sub.2 SCH.sub.3 7-F 4-OCH.sub.3 H H132 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH CH.sub.2 SCH.sub.3 7-Pr 4-OCH.sub.3 H H136 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OSO.sub.3 H CH.sub.2 SCH.sub.3 7-Pr 4-OCH.sub.3 H H137 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OCOCH.sub.2 CH.sub.2 CO.sub.2 H CH.sub.2 SCH.sub.3 7-Pr 4-OCH.sub.3 H H138 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OPO.sub.3 H.sub.2 CH.sub.2 SCH.sub.3 7-Pr 4-OCH.sub.3 H H140 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-CO.sub.2 H 4-OCH.sub.3 H H141 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-Cl 4-CO.sub.2 H H H142 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-F 4-CO.sub.2 H H H149 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-C(CH.sub.3).sub.3 7-Cl 4-CO.sub.2 H H H150 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-C(CH.sub.3).sub.3 7-CH.sub.3 4-CO.sub.2 H H H159 CH(CH.sub.3).sub.2 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-Cl 4-CH.sub.3 O H H160 CH(CH.sub.3).sub.2 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-Cl 4-CH.sub.3 O H H163 CH.sub.3 H 4-OH 5-propyl 7-Cl -- -- --164 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH H 7-Cl 4-CH.sub.3 O H H165 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-C.sub.4 H.sub.9 7-Cl 4-CH.sub.3 O H H166 H CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-Cl 4-CH.sub.3 O H H167 Propyl CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-Cl 4-CH.sub.3 O H H168 CH.sub.3 CH.sub.3 CH--C.sub.6 H.sub.5 4-OH 5-propyl 7-Cl 4-CH.sub.3 O H H169 CH.sub.3 C.sub.7 H.sub.15 4-OH 5-propyl H -- -- --170 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 6-OMe 4-CH.sub.3 O H H171 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-Cl 4-CH.sub.3 O H H172 CH.sub.3 C.sub.6 H.sub.5 4-OH 5-propyl 7-Cl H H H173 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-Cl 7-Cl 4-CH.sub.3 O H H174 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-Cl 4-Cl H H175 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-Cl 2-CH.sub.3 O 4-CH.sub.3 O H176 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-propyl 7-CH.sub.2 NMe.sub.2 4-CH.sub.3 O H H177 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-CH.sub.2 NMe.sub.2 7-Cl 4-CH.sub.3 O H H178 CH.sub.3 CH.sub. 2 C.sub.6 H.sub.5 4-OH 5-Me 7-Cl 4-CH.sub.3 O H H179 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-allyl 7-Cl 4-CH.sub.3 O H H180 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5(CH.sub.2).sub.3 OH 7-Cl 4-CH.sub.3 O H H181 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5(CH.sub.2).sub.2 CO.sub.2 H 7-Cl 4-CH.sub.3 O H H182 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5 4-OH 5-EtO 7-Cl 4-CH.sub.3 O H H__________________________________________________________________________
- 7. A pharmaceutical composition useful in inhibiting leukotriene formation in mammals comprising an amount of a compound of claim 1 effective as a leukotriene inhibitor and a pharmaceutically acceptable carrier.
- 8. A method of inhibiting leukotriene action in mammals which comprises administering to a mammal an effective amount of a compound of claim 1.
- 9. A method of treating or ameliorating allergic conditions, asthma, psoriasis, pain, inflammation, or cardiovascular conditions in mammals or inducing cytoprotection in mammals comprising administering to a mammal in need of said treatment an effective amount of a compound of claim 1.
- 10. A compound of claim 1, wherein at least two of Y, Y.sup.1, and Z are not H.
CROSS REFERENCE
Division of Ser. No. 183,877, Apr. 20, 1988, now U.S. Pat. No. 4,863,958, which is a CIP on Ser. No. 146,822, Jan. 22, 1988, abandoned, which is a continuation of application U.S. Ser. No. 931,751, filed November 17, 1986, abandoned, which is a continuation of application U.S. Ser. No. 741,379, filed June 7, 1985, abandoned, which is a CIP of application U.S. Ser. No. 622,372, filed June 20, 1984, abandoned.
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Divisions (1)
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Parent |
183877 |
Apr 1988 |
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Continuations (2)
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931751 |
Nov 1986 |
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Parent |
741379 |
Jun 1985 |
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Continuation in Parts (2)
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146882 |
Jan 1988 |
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622372 |
Jun 1984 |
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