Benzo lipoxin analogues

Patent metadata

Field	Value
Publication number	US-10322102-B2
Application number	US-201715436389-A
Country	US
Kind code	B2
Filing date	Feb 17, 2017
Priority date	Sep 10, 2003
Publication date	Jun 18, 2019
Grant date	Jun 18, 2019

Abstract

Benzolipoxin analogs, methods of their preparation and pharmaceutical compositions containing the compounds are provided. The compounds and compositions are useful in methods for treatment of various diseases, including, inflammation, autoimmune disease and abnormal cell proliferation.

First claim

What is claimed:

1. A pharmaceutical composition comprising:
(a) an active agent comprising a compound having the structure of formula 1:

wherein:
A is hydroxy, alkoxy, aryloxy, amino, alkylamino, dialkylamino or —OM, where M is an ammonium, tetra-alkyl ammonium, sodium, potassium, magnesium or zinc cation;
W is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, halo, hydroxy, alkoxy, aryloxy, carboxy, amino, alkylamino, dialkylamino, acylamino, carboxamido, or sulfonamide;
R a -R c are independently selected from a group consisting of hydrogen, alkyl, aryl, acyl or alkoxyacyl;
the integer n is zero, one or two;
the integer m is one or two; and
the two substituents on ring X are ortho-, meta- or para-; and

(b) an excipient comprising polyalkylene glycol, polyglycolic acid, polylactic acid, or a copolymer or combination thereof.

2. The pharmaceutical composition of claim 1 , wherein the active agent comprises a compound having the structure of any one of formulae 2-7:

wherein
A is hydroxy, alkoxy, aryloxy, amino, alkylamino, dialkylamino or —OM, where M is an ammonium, tetra-alkyl ammonium, sodium, potassium, magnesium or zinc cation;
W is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, halo, hydroxy, alkoxy, aryloxy, carboxy, amino, alkylamino, dialkylamino, acylamino, carboxamido, or sulfonamide;
R a -R c are independently selected from a group costing of hydrogen, alkyl, aryl, acyl or alkoxyacyl;
the integer n is zero, one or two;
the integer m is one or two.

3. The pharmaceutical composition of claim 1 , wherein the active agent comprises a compound having the structure of any one of formulae 8-19:

wherein
A is hydroxy, alkoxy, aryloxy, amino, alkylamino, dialkylamino or —OM, where M is an ammonium, tetra-alkyl ammonium, sodium, potassium, magnesium or zinc cation;
W is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, halo, hydroxy, alkoxy, aryloxy, carboxy, amino, alkylamino, dialkylamino, acylamino, carboxamido, or sulfonamide;
R a -R c are independently selected from a group costing of hydrogen, alkyl, aryl, acyl or alkoxyacyl;
the integer n is zero, one or two;
the integer m is one or two.

4. The pharmaceutical composition of claim 3 , wherein W is alkyl or aryloxy.

5. The pharmaceutical composition of claim 1 , wherein the active agent comprises a compound having the structure of

wherein
A is hydroxy, alkoxy, aryloxy, amino, alkylamino, dialkylamino or —OM, where M is an ammonium, tetra-alkyl ammonium, sodium, potassium, magnesium or zinc cation.

6. The pharmaceutical composition of claim 5 , wherein A is hydroxy or alkoxy.

7. The pharmaceutical composition of claim 1 , wherein the active agent comprises (5S,6R,E)-methyl 5,6-dihydroxy-8-(3-((R,E)-3-hydroxyoct-1-enyl)phenyl)oct-7-enoate

8. The pharmaceutical composition of claim 1 , wherein the excipient comprises polyalkylene glycol.

9. The pharmaceutical composition of claim 1 , wherein the excipient is polyethylene glycol, polypropylene glycol, propylene glycol monostearate, diethylene glycol monolaurate, polyethylene glycol 4000, polyethylene glycol-350-dimethyl ether, polyethylene glycol-550-dimethyl ether, or polyethylene glycol-750-dimethyl ether.

10. The pharmaceutical composition of claim 1 , wherein the excipient is polyethylene glycol.

11. The pharmaceutical composition of claim 1 , wherein the excipient comprises polyglycolic acid.

12. The pharmaceutical composition of claim 1 , wherein the excipient comprises polylactic acid.

13. The pharmaceutical composition of claim 1 , wherein the excipient comprises polyglycolic acid and polylactic acid.

14. The pharmaceutical composition of claim 1 , wherein the excipient comprises a copolymer of polyglycolic acid and polylactic acid.

15. The pharmaceutical composition of claim 1 , in the form of a solution, suspension, tablet, dispersible tablet, pill, capsule, powder, liposome, oil-water emulsion, sustained release formulation or elixir.

16. The pharmaceutical composition of claim 1 , in the form of a chewable lozenge, enteric-coated tablet, sugar-coated tablet, film-coated tablet, hard capsule soft gelatin capsule, non-effervescent granule, effervescent granule, non-effervescent powder or effervescent powder.

17. The pharmaceutical composition of claim 1 , in the form of a liquid solution, liquid suspension, solid form suitable for solution or suspension in liquid prior to injection, or emulsion.

18. The pharmaceutical composition of claim 1 , in the form of a cream, gel, ointment, emulsion, solution, elixir, lotion, suspension, tincture, paste, foam, aerosol, irrigation, spray, suppository, bandage or dermal patch.

19. The pharmaceutical composition of claim 1 , in the form of a lyophilized powder that can be reconstituted for administration as a solution, emulsion, injection, or for parenteral administration.

20. The pharmaceutical composition of claim 1 , in the form of a solution, suspension, emulsion, cream, gel, ointment, solution, elixir, lotion, suspension, tincture, paste, foam, aerosol, irrigation, spray, suppository, bandage, or dermal patch suitable for topical administration or for transdermal delivery.

21. The pharmaceutical composition of claim 1 , in the form of an aerosol for administration to the respiratory tract in the form of an aerosol or solution for a nebulizer, or as a microfine powder for insufflation, alone or in combination with an inert carrier.

22. The pharmaceutical composition of claim 1 , wherein n is one or two, and the two substituents on ring X are meta- or para-.

23. The pharmaceutical composition of claim 1 , wherein m-n is zero or one, and the two substituents on ring X are meta- or para-.

24. The pharmaceutical composition of claim 1 , wherein the two substituents on ring X are meta-.

Assignees

• Univ Southern California

Inventors

• Petasis Nicos A

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07C69/618

  having unsaturation outside the six-membered aromatic ring · CPC title

• A61K31/216 Primary

  of acids having aromatic rings, e.g. benactizyne, clofibrate · CPC title