Curcumin and tetrahydrocurcumin derivatives

Patent metadata

Field	Value
Publication number	US-9447023-B2
Application number	US-201313942606-A
Country	US
Kind code	B2
Filing date	Jul 15, 2013
Priority date	Oct 12, 2006
Publication date	Sep 20, 2016
Grant date	Sep 20, 2016

Abstract

The invention relates to novel curcumin and tetrahydrocurcumin derivatives, which have been modified at one phenolic group to incorporate more-reactive groups. The curcumin and tetrahydrocurcumin derivatives are in the form of monomers, dimmers, and polymers.

Z-L n -Y  (I)

wherein: Z is represented by:

First claim

We claim:

1. A curcumin derivative having the formula I:
Z-L n -Y   (I)

wherein:
Z is represented by:

A is —CH 2 —CH 2 — or —CH═CH—;
L is —[C(O)] n1 —R 1 —;
n is 0 or 1;
n1 is 1;
R 1 is R 2 , R 3a , R 4 , or R 5 ;
R 2 is a saturated or unsaturated, branched or unbranched hydrocarbyl with 1 to 18 carbon atoms;
R 3a is —(CH 2 —CH 2 —O) n2 —;
R 3b is —(O—CH 2 —CH 2 ) n2 —;
n2 is an integer between 1 and 2,000;
R 4 is —R 2 —R 3a —, —R 2 —R 3b —, or —R 3a —R 2 —;
R 5 is —R 9 —R 6 —R 9 —;
R 6 is —C(O)—NH—R 3a —;
Y is —CH═CH—C(O)OR 8 , —CH═C(CH 3 )—C(O)OR 8 , —COOR 7 , —N 3 , —C≡C—R 8 , —NH 2 , —CHO, —OH, -epoxide-R 8 , or —SH;
with the proviso that when n is 0, Y is —CH═CH—C(O)OR 8 or —CH═C(CH 3 )—C(O)OR 8 ;
with the proviso that when R 1 is R 3a or —R 2 —R 3a —, Y is —CH═CH—C(O)OR 8 or —CH═C(CH 3 )—C(O)OR 8 ;
R 7 is C 1-4 alkyl, or a moiety such that —COOR 7 is an activated ester;
R 8 is hydrogen or C 1-4 alkyl; and
R 9 is independently C 1-4 alkyl.

2. The curcumin derivative according to claim 1 ,
wherein:
R 2 is a saturated or unsaturated, unbranched hydrocarbyl with 1 to 18 carbon atoms;
n2 is an integer between 1 and 50;
R 7 is C 1-2 alkyl, or a moiety such that —COOR 7 is an activated ester;
R 8 is hydrogen or C 1-2 alkyl; and
R 9 is C 1-2 alkyl.

3. The curcumin derivative according to claim 2 ,
wherein:
R 2 is a saturated, unbranched hydrocarbyl with 1 to 5 carbon atoms; and
Y is —CH═CH—C(O)OR 8 , —CH═C(CH 3 )—C(O)OR 8 , —COOR 7 , —N 3 , or —C≡C—R 8 .

4. The curcumin derivative according to claim 1 , wherein the maximum value for n2 is 12.

5. The curcumin derivative according to claim 1 , wherein the activated ester is an N-hydroxysuccinimide ester or a nitrophenyl ester.

6. A curcumin derivative, selected from the group consisting of:

wherein n2 is an integer between 1 and 2,000, and wherein A is —CH 2 —CH 2 — or —CH═CH—.

7. The curcumin derivative according to claim 1 , wherein Y is —CH═CH—C(O)OR 8 or —CH═C(CH 3 )—C(O)OR 8 .

8. The curcumin derivative according to claim 1 , wherein Y is —C≡C—R 8 .

9. The curcumin derivative according to claim 1 , wherein Y is —N 3 .

10. The curcumin derivative according to claim 1 , wherein Y is NH 2 .

11. A curcumin derivative that is curcumin acrylate, selected from the group consisting of:

wherein A is —CH 2 —CH 2 — or —CH═CH—.

12. A curcumin derivative having the formula:

wherein A is —CH 2 —CH 2 — or —CH═CH—.

13. A curcumin derivative having the formula I:
Z-L n -Y   (I)

wherein:
Z is represented by:

A is —CH 2 —CH 2 — or —CH═CH—;
L is —[C(O)] n1 —R 1 —;
n is 0 or 1;
n1 is 0 or 1;
R 1 is R 2 , R 3a , R 4 , or R 5 ;
R 2 is a saturated or unsaturated, branched or unbranched hydrocarbyl with 1 to 18 carbon atoms;
R 3a is —(CH 2 —CH 2 —O) n2 —;
R 3b is —(O—CH 2 —CH 2 ) n2 —;
n2 is an integer between 1 and 2,000;
R 4 is —R 2 —R 3a —, —R 2 —R 3b —, or —R 3a —R 2 —;
R 5 is —R 9 —R 6 —R 9 —;
R 6 is —C(O)—NH—R 3a —;
Y is —CH═CH—C(O)OR 8 , —CH═C(CH 3 )—C(O)OR 8 , —N 3 , —C≡C—R 8 , or —NH 2 ;
with the proviso that when n is 0, Y is —CH═CH—C(O)OR 8 or —CH═C(CH 3 )—C(O)OR 8 ;
with the proviso that when R 1 is R 3a or —R 2 —R 3a —, Y is —CH═CH—C(O)OR 8 or CH═C(CH 3 )—C(O)OR 8 ;
R 8 is hydrogen or C 1-4 alkyl; and
R 9 is independently C 1-4 alkyl.

14. A curcumin derivative having the formula I:
Z-L n -Y   (I)

wherein:
Z is represented by:

A is —CH 2 —CH 2 — or —CH═CH—;
L is —[C(O)] n1 —R 1 —;
n is 0 or 1;
n1 is 0 or 1;
R 1 is R 2 , R 3a , R 4 , or R 5 ;
R 2 is a saturated or unsaturated, branched or unbranched hydrocarbyl with 1 to 18 carbon atoms;
R 3a is —(CH 2 —CH 2 —O) n2 —;
R 3b is —(O—CH 2 —CH 2 ) n2 —;
n2 is an integer between 1 and 2,000;
R 4 is —R 2 —R 3a —, —R 2 —R 3b —, or —R 3a —R 2 —;
R 5 is —R 9 —R 6 —R 9 —;
R 6 is —C(O)—NH—R 3a —;
Y is —CHO, —OH, -epoxide-R 8 , or —SH;
with the proviso that when n is 0, Y is —CH═CH—C(O)OR 8 or —CH═C(CH 3 )—C(O)OR 8 ;
with the proviso that when R 1 is R 3a or —R 2 —R 3a —, Y is —CH═CH—C(O)OR 8 or CH═C(CH 3 )—C(O)OR 8 ;
R 8 is hydrogen or C 1-4 alkyl; and
R 9 is independently C 1-4 alkyl.

Assignees

• Raja Krishnaswami
• Banerjee Probal
• Auerbach Andrew
• Shi Wei
• L'Amoreaux William
• Univ City New York Res Found

Inventors

• Raja Krishnaswami
• Banerjee Probal
• Auerbach Andrew
• Shi Wei
• L'Amoreaux William

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P39/06

  Free radical scavengers or antioxidants · CPC title

• C07C247/04

  being saturated · CPC title

• C07C49/248

  having unsaturation outside the aromatic rings · CPC title

• A61K8/496

  Triazoles or their condensed derivatives, e.g. benzotriazoles · CPC title