UNSYMMETRICAL AROMATIC ETHER DIACIDS AND ABSORBABLE POLYMERS THEREFROM

• US 20100113592A1
• Filed: 01/08/2010
• Published: 05/06/2010
• Est. Priority Date: 10/21/2005
• Status: Active Grant

• Current Assignee: Bezwada Biomedical, LLC
• Original Assignee: Bezwada Biomedical, LLC
• Inventors: Bezwada, Rao S.
• Granted Patent: US 7,902,319 B2
• Time in Patent Office: Days
• US Class Current: 514/533
• CPC Class Codes: A23L 29/288 Synthetic resins, e.g. polyvinylpyrrolidone
• CPC Class Codes: A23L 33/10 using additives addition of substantially indigestible substances A23L33/21
• CPC Class Codes: A23L 33/105 Plant extracts, their artificial duplicates or their derivatives
• CPC Class Codes: A61K 2800/522 Antioxidants; Radical scavengers
• CPC Class Codes: A61K 8/37 Esters of carboxylic acids
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 31/04 Macromolecular materials
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: A61Q 19/08 Anti-ageing preparations
• CPC Class Codes: C07C 205/37 the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
• CPC Class Codes: C07C 217/84 the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
• CPC Class Codes: C07C 233/18 having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
• CPC Class Codes: C07C 233/25 having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
• CPC Class Codes: C07C 65/21 containing ether groups, groups, groups, or groups
• CPC Class Codes: C07C 65/24 polycyclic
• CPC Class Codes: C07C 69/712 the hydroxy group of the ester being etherified with a hydroxy compound having the hydroxy group bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 69/732 : of unsaturated hydroxy carboxylic acids
• CPC Class Codes: C07C 69/734 : Ethers
• CPC Class Codes: C07C 69/92 : with etherified hydroxyl groups
• CPC Class Codes: C07D 311/12 : substituted in position 3 and unsubstituted in position 7
• CPC Class Codes: C07D 311/16 : substituted in position 7
• CPC Class Codes: C07D 311/36 : not hydrogenated in the hetero ring, e.g. isoflavones
• CPC Class Codes: C07D 493/04 : Ortho-condensed systems
• CPC Class Codes: C08G 63/66 : Polyesters containing oxygen in the form of ether groups C08G63/42, C08G63/58 take precedence
• CPC Class Codes: C08G 69/40 : Polyamides containing oxygen in the form of ether groups C08G69/12, C08G69/32 take precedence
• CPC Class Codes: C08G 69/44 : Polyester-amides
• CPC Class Codes: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

The present invention relates to compounds and compositions of formula I, which are unsymmetrical aromatic ether diacids, and polymers formed from the same.

[R′—(Y)_p—O]_q—Ar—[O—(X)_r—R′]_s  I

The compounds are expected to be useful in a variety of medical and/or cosmetics applications. Polymers formed from the functionalized unsymmetrical aromatic ether diacids are expected to have controllable degradation profiles, enabling them to release an active component over a desired time range.

Claims

1. A compound of formula I or a pharmaceutically acceptable salt thereof:

[R′

—

(Y)_p—

O]_q—

Ar—

[O—

(X)_r—

R′

]_s 

 

I

wherein;

Ar is the aromatic portion of a diphenol;

X and Y are independently selected from;

—

CH₂COO—

;

—

CH(CH₃)COO—

;

—

CH₂CH₂OCH₂COO—

;

—

CH₂CH₂CH₂CH₂CH₂COO—

;

—

(CH₂)_yCOO—

where y is independently selected from 2-4 and 6-24; and

—

(CH₂CH₂O)_zCH₂COO—

where z is independently selected from 2-24;

provided that the groups represented by [R′

—

(Y)_p—

O]_q— and

—

[O—

(X)_r—

R′

]_s are different from one another;

R′

is selected from H, benzyl, and C_1-6 alkyl;

p is selected from 1, 2, 3, 4, 5, and 6;

q is selected from 1, 2, and 3;

r is selected from 1, 2, 3, 4, 5, and 6; and

s is selected from 1, 2, and 3.

2. A compound according to claim 1

wherein:

Ar is an optionally substituted diphenolic residue selected from;

3. A compound according to claim 2, wherein

y is independently selected from 2, 3, and 4;

z is independently selected from 2, 3, and 4;

p is selected from 1, 2, and 3;

q is selected from 1, 2, and 3;

r is selected from 1, 2, and 3; and

s is selected from 1, 2, and 3.

4. A compound according to claim 2, wherein

X and Y are independently selected from:

—

CH₂COO—

;

—

CH(CH₃)COO—

;

—

CH₂CH₂OCH₂COO—

; and

—

CH₂CH₂CH₂CH₂CH₂COO—

;

p is selected from 1 and 2;

q is selected from 1 and 2;

r is selected from 1 and 2; and

s is selected from 1 and 2.

5. A compound according to claim 2, wherein Ar is an optionally substituted diphenolic residue selected from:

6. A compound according to claim 5, wherein Ar is an optionally substituted diphenolic residue selected from:

7. A compound according to claim 6, wherein Ar is an optionally substituted diphenolic residue of formula:

8. A compound according to claim 6, wherein Ar is an optionally substituted diphenolic residue of formula:

9. A compound according to claim 8, Ar is a diphenolic residue of formula:

10. A compound according to claim 6, wherein Ar is an optionally substituted diphenolic residue of formula:

11. A compound according to claim 6, wherein Ar is an optionally substituted diphenolic residue of formula.

12. A compound according to claim 5, wherein:

each Ar group is independently substituted with 1, 2, or 3 R groups, wherein;

R is independently selected from ═

O, O-glycosides, —

(CH₂)_0-2—

OR^a, —

(CH₂)_0-2—

C₆H₅, —

(CH₂)_0-2—

CHO, Cl, F, Br, I, —

(CH₂)_0-2—

OC(O)—

R^a, —

(CH₂)_0-2—

CO₂—

R^a, —

(C(CH₃))_0-2—

CO₂—

R^a, —

(CH₂)_0-2—

CO₂—

(CH₂)_1-2—

CO₂—

R^a, —

(C(CH₃))_0-2—

CO₂—

(CH₂)_1-2—

CO₂—

R^a, —

(CH₂)_0-2—

CO—

R^a, —

O(CH₂)_0-2—

C₆H₅, —

O(CH₂)_1-2—

CO₂—

R^a, —

O(C(CH₃))_1-2—

CO₂—

R^a, —

O(CH₂)_1-2—

CO—

R^a, —

CO₂(CH₂)_1-2—

CO₂—

R^a, —

CO₂(C(CH₃))_1-2—

CO₂—

R^a, —

(CH₂)_0-2—

NO₂, —

(CH₂)_0-2—

NR^aR^a, —

(CH₂)_0-2—

NR^aCOR^a, —

(CH₂)_0-2—

NR^aC(O)(CH₂)_1-2OR^a, —

C₆H₅, —

C₆H₅OR^a, and —

C₆H₅—

CH═

CHCO₂R^a; and

,

R^a is independently selected from H and C_1-6 alkyl.

13. A compound according to claim 2, wherein the compound is selected from:

14. A compound according to claim 9, wherein the compound is selected from:

15. A composition, comprising:

at least two different compounds according to claim 1.

16. A solvent for a drug, comprising:

at least one compound according to claim 1.

17. A nutritional composition, comprising at least one compound according to claim 1.

18. The nutritional composition according to claim 17, wherein the diphenolic residue in the compound of formula I was derived from a compound that is a nutritional supplement or a food intermediary.

19. A cosmetic composition, comprising at least one compound according to claim 1 and a cosmetic ingredient.

20. A pharmaceutical composition, comprising at least one compound according to claim 1 and a pharmaceutically acceptable excipient.

21. The composition according to claim 20, wherein the composition is suitable for administration via a route selected from oral, enteral, parenteral, topical, transdermal, ocular, vitreal, rectal, nasal, pulmonary, and vaginal.

22. The composition according to claim 20, wherein the diphenolic residue in the compound of formula I was derived from a cancer preventing diphenol

23. The composition according to claim 22, further comprising:

an anti-cancer agent.

24. The composition according to claim 20, wherein the diphenolic residue in the compound of formula I was derived from a phenolic with antimicrobial properties.

25. The composition according to claim 24, further comprising:

an antimicrobial agent.

26. The composition according to claim 20, wherein the diphenolic residue in the compound of formula I was derived from a phenolic with anti-inflammatory properties.

27. The composition according to claim 26, further comprising:

anti-inflammatory agent.

28. The composition according to claim 20, wherein the diphenolic residue in the compound of formula I was derived from a phenolic with pain-reducing properties.

29. The composition according to claim 28, further comprising:

a pain reducing agent.

30. The composition according to claim 20, wherein the diphenolic residue in the compound of formula I was derived from a phenolic with antioxidant properties.

31. The composition according to claim 30, further comprising:

an antioxidant agent.

32. A compound according to claim 1, wherein Ar is a synthetic or naturally derived flavanoid diphenolic residue.

33. A compound according to claim 32, wherein the flavanoid is selected from:

flavonoids, flavanones, flavones, flavanols, anthocyanidins, proanthocyanidins, procyanidolic oligomers (PCO), catechins, biflavans, polyphenols, rutin, rutinosides, hydroxyethylrutosides (HER), hesperidin, quercetin, quercetrin, polyphenols, catechin, epicatechin, epicatechin gallate, epigallocatechin gallate, leucoanthocyanins, anthocyanins, and isoflavones; and

glucosides or β

-glycosides thereof.

34. A compound according to claim 33, wherein the isoflavone is selected from:

glycitein, daidzein, prunetin, biochanin A, orobol, santal, pratensein, formononetin, genistein, and glycitein; and

glucosides or β

-glycosides thereof.