Claims
- 1. A compound of the formula ##STR16## or a pharmaceutically acceptable salt thereof, wherein Z is oxygen or sulfur,
- X is selected from the group consisting of
- alkylene of from one to six carbon atoms;
- alkenylene of from two to six carbon atoms;
- alkylene of from one to six carbon atoms substituted by a group selected from
- hydroxy,
- halo,
- cyano,
- alkoxy,
- aminocarbonyl,
- alkylaminocarbonyl,
- dialkylaminocarbonyl,
- carboxyl, and
- alkoxycarbonyl;
- alkenylene of from two to six carbon atoms substituted by a group selected from
- hydroxy,
- halo,
- cyano,
- alkoxy,
- aminocarbonyl,
- alkylaminocarbonyl,
- dialkylaminocarbonyl,
- carboxyl, and
- alkoxycarbonyl;
- R.sup.1 and R.sup.2 are independently selected from the group consisting of
- hydrogen;
- hydroxy;
- alkyl of from one to six carbon atoms;
- alkyl of from one to six carbon atoms substituted with a group selected from
- hydroxy;
- halo;
- cyano;
- alkoxy;
- alkylthio;
- aminocarbonyl;
- alkylaminocarbonyl;
- dialkylaminocarbonyl;
- carboxy;
- alkoxycarbonyl;
- aryl; and
- aryl substituted with a substituent selected from the group consisting of
- hydroxy,
- halo,
- cyano,
- alkoxy,
- alkylthio,
- amino,
- alkylamino,
- dialkylamino,
- aminocarbonyl,
- alkylaminocarbonyl,
- dialkylaminocarbonyl,
- carboxyl, and
- alkoxycarbonyl;
- R.sup.3 is selected from the group consisting of
- thienyl; and
- thienyl substituted by
- alkyl of from one to six carbon atoms,
- alkenyl of from two to six carbon atoms,
- cycloalkyl of from three to ten carbon atoms,
- alkoxy of from one to six carbon atoms,
- alkylthio of from one to six carbon atoms,
- halo,
- nitro,
- hydroxy;
- substituted or unsubstituted aryl,
- substituted or unsubstituted aryloxy,
- substituted or unsubstituted aroyl,
- substituted or unsubstituted arylalkyl wherein the alkyl portion contains from one to six carbon atoms,
- substituted or unsubstituted arylalkenyl wherein the alkenyl portion contains from two to six carbon atoms,
- substituted or unsubstituted arylalkynyl wherein the alkynyl portion contains from two to six carbon atoms,
- substituted or unsubstituted arylalkoxy wherein the alkoxy portion contains from one to six carbon atoms,
- substituted or unsubstituted arylalkylthio wherein the alkylthio portion contains from one to six carbon atoms,
- wherein said substituted aryl groups are optionally substituted by one, two, or three groups independently selected from the group consisting of halo, nitro, cyano, alkyl, alkoxy, and halosubstituted alkyl;
- M is selected from the group consisting of
- hydrogen,
- a pharmaceutically acceptable cation,
- a metabolically cleavable group,
- aroyl,
- --Si(R.sup.5).sub.3 wherein R.sup.5 is independently selected at each occurrence from alkyl of from one to six carbon atoms,
- --C(O)R.sub.4,
- --CH.sub.2 OR.sub.4,
- --C(O)N(R.sup.4).sub.2 and
- --C(O)OR.sup.4
- wherein R.sup.4 is alkyl of one to six carbon atoms;
- with the proviso that R.sup.1 and R.sup.2 are not simultaneously hydroxy.
- 2. A compound as defined by claim 1 having the structure ##STR17## where X and Z are as defined therein; R.sup.6 is selected from the group consisting of
- hydrogen;
- alkyl of from one to six carbon atoms;
- halogen;
- phenyl;
- phenyl substituted by
- alkyl of from one to six carbon atoms,
- alkoxy of from one to six carbon atoms,
- hydroxy, or
- halogen;
- phenoxy;
- phenoxy substituted by
- alkyl of from one to six carbon atoms,
- alkoxy of from one to six carbon atoms,
- hydroxy, or
- halogen;
- phenylthio;
- phenylthio substituted by
- alkyl of from one to six carbon atoms,
- alkoxy of from one to six carbon atoms,
- hydroxy,
- halogen; or
- a pharmaceutically acceptable salt thereof.
- 3. A compound as defined by claim 1 selected from the group consisting of
- N-hydroxy-N-(thien-2-yl)methyl urea;
- N-hydroxy-N-(thien-3-yl)methyl urea;
- N-hydroxy-N-(1-(thien-3-yl)ethyl) urea;
- N-hydroxy-N-(1-(thien-3-yl)ethyl) thiourea;
- N-hydroxy-N-(3-(1-thien-3-yl)propyl)urea;
- N-hydroxy-N-(3-(thien-3-yl)propen-1-yl) urea;
- N-hydroxy-N-(3-methylthien-2-yl)methyl urea;
- N-hydroxy-N-(2-(5-methylthien-2-yl)propyl) urea;
- N-hydroxy-N-(5-bromothien-2-yl)methyl urea;
- N-hydroxy-N-(1-(5-bromothien-2-yl)ethyl]urea;
- N-hydroxy-N-(1-(5-phenylthien-2-yl)methyl) urea;
- N-hydroxy-N-(1-(5-phenylthien-2-yl)ethyl) urea;
- N-hydroxy-N-(4-(phenoxy)thien-2-yl)methyl urea
- N-hydroxy-N-(4-(4-chlorophenoxy)thien-2-yl)methyl urea
- N-hydroxy-N-(3-(phenylthio)thien-2-yl)methyl urea
- N-hydroxy-N-(3-(4-chlorophenylthio)thien-2-yl)methyl urea
- N-hydroxy-N-(4-(phenylthio)thien-2-yl)methyl urea
- N-hydroxy-N-(5-(phenylthio)thien-2-yl)methyl urea
- N-hydroxy-N-((2-(phenylthio)thien-3-yl)methyl urea
- N-hydroxy-N-((5-phenylthio)thien-3-yl)methyl urea
- N-hydroxy-N-(1-(5-(phenylthio)-thien-2-yl)ethyl)urea
- N-hydroxy-N-(3-(5-(phenylthio)thien-2-yl)propen-1-yl) urea
- N-hydroxy-N-(3-(5-(phenylthio)thien-2-yl)butenyl urea
- 4. A pharmaceutical composition for inhibiting lipoxygenase enzymes comprising an effective amount of a compound as defined by claim 1 in combination with a pharmaceutically accpetable carrier.
- 5. A method of inhibiting lipoxygenase enzyme activity in a mammal comprising administering to a mammal in need of such treatment an effective amount of a compound as defined by claim 1.
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation-in-part of copending application Ser. No. 331,566 filed Mar. 30, 1989 now abandoned which, in turn, is a continuation-in-part of application Ser. No. 042,491, filed Apr. 24, 1987, (now abandoned) which is a continuation-in-part of application Ser. No. 856,725, filed Apr. 25, 1986 (now abandoned).
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/US90/01488 |
3/20/1991 |
|
|
9/30/1991 |
9/30/1991 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO90/12008 |
10/18/1990 |
|
|
Foreign Referenced Citations (1)
Number |
Date |
Country |
0196184 |
Oct 1986 |
EPX |
Continuation in Parts (3)
|
Number |
Date |
Country |
Parent |
331566 |
Mar 1989 |
|
Parent |
42491 |
Apr 1987 |
|
Parent |
856725 |
Apr 1986 |
|