.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 4,745,127

« Back to Dashboard

Details for Patent: 4,745,127

Title: Benzyl esters of benzofuran-2-carboxylic acids useful as inhibitors of leukotriene biosynthesis
Abstract:Compounds of the Formula I: ##STR1## and pharmaceutically acceptable salts thereof are inhibitors of leukotriene biosynthesis. These compounds inhibit the mammalian 5-lipoxygenase enzyme, thus preventing the metabolism of arachidonic acid to the leukotrienes. These compounds are thus useful in the treatment of asthma, allergic disorders, inflammation, skin diseases and certain cardiovascular disorders.
Inventor(s): Atkinson; Joseph G. (Montreal, CA), Guindon; Yvan (Ile Bizard, CA), Lau; Cheuk K. (Pierrefonds, CA)
Assignee: Merck Frosst Canada, Inc. (CA)
Filing Date:Jan 07, 1987
Application Number:07/001,262
Claims:1. A compound of the Formula Id: ##STR3## wherein R.sub.1 is hydrogen, C.sub.1 to C.sub.6 alkyl, Ar.sub.1 -C.sub.1 to C.sub.3 alkyl, Ar.sub.1 or CH.sub.2 OH;

R.sub.3, R.sub.4 and T are each independently selected from:

(1) hydrogen;

(2) alkyl having 1 to 4 carbon atoms;

(3) alkenyl having 2 to 4 carbon atoms;

(4) --(CH.sub.2).sub.n M

wherein n is 0 or 1, and

M is

(a) --OR.sub.5 ;

(b) halogen;

(c) --CF.sub.3 ;

(d) --SR.sub.5 ;

(e) Ar.sub.1 ;

(f) --COOR.sub.6 ;

(g) ##STR4## wherein R.sub.12 is H, C.sub.1 to C.sub.6 alkyl, or Ar.sub.1 ; (h) ##STR5## (i) ##STR6## (j) ##STR7## (k) ##STR8## (l) NR.sub.8 R.sub.9 ; (m) --NHSO.sub.2 R.sub.10 wherein R.sub.10 is C.sub.1 to C.sub.6 alkyl, phenyl, p-tolyl or CF.sub.3 ;

(n) --SOR.sub.5 ;

(o) --CONR.sub.8 R.sub.9 ;

(p) --SO.sub.2 NR.sub.8 R.sub.9 ;

(q) --SO.sub.2 R.sub.5 ;

(r) --NO.sub.2 ; or

(s) --CN;

or any two of R.sub.3, R.sub.4 and T may be joined to form a saturated ring having 5 or 6 ring atoms, said ring atoms comprising 0, 1 or 2 oxygen atoms, the remaining ring atoms being carbon;

each R.sub.5 is independently H, C.sub.1 to C.sub.6 alkyl, benzyl, Ar.sub.1, perfluoro-C.sub.1 -C.sub.4 alkyl, CH.sub.2 -R.sub.11 wherein R.sub.11 is C.sub.1 to C.sub.5 alkyldimethylamino, hydroxy C.sub.2 to C.sub.5 alkyl, CH.sub.2 COOR.sub.6, or CH.sub.2 CO--R.sub.7 ;

each R.sub.6 is independently H or C.sub.1 to C.sub.6 alkyl;

each R.sub.7 is indenpendently C.sub.1 to C.sub.6 alkyl, benzyl, Ar.sub.1, NR.sub.8 R.sub.9, NHAr.sub.1, or O--C.sub.1 to C.sub.4 alkyl;

each R.sub.8 and each R.sub.9 is independently H or C.sub.1 to C.sub.4 alkyl, or R.sub.8 and R.sub.9 may be joined through the N to which they are attached to form a heterocycloalkyl ring having 5 to 8 ring atoms; and

each Ar.sub.1 is independently 1- or 2-naphthyl, phenyl or mono- or disubstituted phenyl, wherein the substituents on the phenyl are independently selected from C.sub.1 to C.sub.3 alkyl, I, Br, Cl, F, COOR.sub.6, (CH.sub.2).sub.n --NR.sub.8 R.sub.9 wherein n is 0 to 2, methylenedioxy, C.sub.1 to C.sub.3 alkoxy, OH, CN, NO.sub.2, CF.sub.3, C.sub.1 to C.sub.4 acyl, NR.sub.8 R.sub.9, S--C.sub.1 to C.sub.6 alkyl, SO--C.sub.1 to C.sub.6 alkyl, and SO.sub.2 --C.sub.1 to C.sub.6 alkyl; with the proviso that at least one of R.sub.3, R.sub.4 or T is either OR.sub.5 or --OCOR.sub.7 ;

or a pharmaceutically acceptable salt thereof.

2. A compound of Formula I ##STR9## wherein the compound is selected from the following group:

3. A compound of claim 2 which is: 223, 224, 232-235, 239, 240, 255, 256, 258, 290, 333, 364, 368, or 369.

4. A compound of claim 2 which is: 333, 364, 368, or 369.

5. A method of inhibiting mammalian leukotriene biosynthesis or action which comprises administering to a mammal a pharmaceutically effective amount of a compound of claim 2.

6. A method of claim 5 wherein the mammal is a human.

7. A method of treating pulmonary conditions, inflammation, allergies, pain, cardiovascular conditions, or skin conditions which comprises administering to a human in need of such treatment a pharmaceutically effective amount of a compound of claim 2.

8. A pharmaceutical composition useful for inhibiting the biosynthesis of mammalian leukotrienes comprising a pharmaceutically acceptable carrier and an effective amount of a compound of claim 2.

9. A composition of claim 8, wherein the compound is: 223, 224, 232-235, 239, 240, 255, 256, 258, 290, 333, 364, 368, or 369.

10. A composition of claim 8, wherein the compound is: 255, 333, 364, 368, or 369.

11. A method of inhibiting mammalian leukotriene biosynthesis or action which comprises administering to a mammal pharmaceutically effective amount of a composition of claim 8.

12. A method of claim 11 wherein the mammal is a human.

13. A method of treating pulmonary conditions, inflammation, allergies, pain, cardiovascular conditions, or skin conditions which comprises administering to a human in need of such treatment a pharmaceutically effective amount of a composition of claim 8.

14. A pharmaceutical composition according to claim 8 additionally comprising an effective amount of a second active ingredient selected from the group consisting of non-steriodal anti-inflammatory drugs; peripheral analgesic agents; cyclooxygenase inhibitors; leukotriene antagonists; antihistaminic agents; prostaglandin antagonists; and thromboxane antagonists.

15. A pharmaceutical composition according to claim 14, wherein the second active ingredient is a non-steroidal anti-inflammatory drug.

16. A pharmaceutical composition according to claim 15, wherein said non-steroidal anti-inflammatory drug is indomethacin.

17. A pharmaceutical composition according to claim 8 additionally comprising an effective amount of a second active ingredient selected from the group consisting of non-steriodal anti-inflammatory drugs; peripheral analgesic agents; cyclooxygenase inhibitors; leukotriene antagonists; antihistaminic agents; prostaglandin antagonists; and thromboxane antagonists, wherein the weight ratio of the compound described in claim 8 to said second active ingredient ranges from about 1000:1 to 1:1000.

18. A pharmaceutical composition according to claim 17, wherein the weight ratio ranges from about 200:1 to 1:200.

19. A pharmaceutical composition according to claim 17, wherein the second active ingredient is a non-steroidal anti-inflammatory drug.

20. A pharmaceutical composition according to claim 19, wherein the non-steroidal anti-inflammatory drug is indomethacin.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

How are People Using DrugPatentWatch?

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc