FURANOPYRIMIDINE CANNABINOID COMPOUNDS AND RELATED METHODS OF USE

• US 20110046163A1
• Filed: 08/20/2010
• Published: 02/24/2011
• Est. Priority Date: 08/20/2009
• Status: Abandoned Application

• Current Assignee: University of Tennessee Research Foundation (University of Teesside)
• Original Assignee: University of Tennessee Research Foundation (University of Teesside)
• Inventors: Gurley, Steven, Moore, Bob M. II, Mustafa, Suni
• Application Number:
  US12/860,749
• Publication Number:
  US 20110046163A1
• Time in Patent Office: Days
• US Class Current: 514/260.1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 491/048 the oxygen-containing ring being five-membered

Abstract

Furanopyrimidine cannabinoid analog compounds of the formula I are disclosed.

• • The compounds are useful to modify the activity of CB1 and CB2 receptors and treat conditions mediated by these receptors.

Claims

1. A compound of the formula

3. A compound according to claim 1 wherein R₂ is selected from the group consisting of substituted and unsubstituted phenyl, and substituted and unsubstituted thiophenyl.

4. A compound according to claim 1 wherein R₁ is selected from H, alkyl, aminoalkyl, morpholinoalkyl, and hemisuccinate.

5. A compound according to claim 1 wherein Y is selected from the group consisting of carbonyl, dimethylmethylene and hydroxymethylene.

6. A compound according to claim 1 wherein Z is selected from the group consisting of substituted and unsubstituted alkyl, phenyl, substituted phenyl, cycloalkyl, substituted cycloalkyl, thiophenyl and substituted thiophenyl.

7. A compound according to claim 6 wherein Z is selected from the group consisting of alkyl, phenyl, thiophenyl and cycloalkyl.

8. A compound according to claim 5 wherein Y is selected from the group consisting of dimethylmethylene or carbonyl.

9. A compound according to claim 1 wherein

R₂ is selected from the group consisting of substituted or unsubstituted phenyl, and substituted or unsubstituted thiophen-2-yl;

R₁ is selected from the group consisting of hydrogen, methyl and ethyl;

Y is selected from the group consisting of C(O), CH₂, CH(CH₃), CH(OH), C(CH₃)(OH) and C(CH₃)₂; and

Z is selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted thiophen-2-yl, alkyl and substituted or unsubstituted cyclohexyl.

10. A compound according to claim 9 wherein Y is C(CH₃)₂.

11. A compound according to claim 10 wherein R₁ is hydrogen.

12. A compound according to claim 1 selected from the group consisting of

a) 2-(2-cyclohexylpropan-2-yl)-5-phenylfuro[2,3-d]pyrimidin-4-ol;

b) 2-(2-cyclohexylpropan-2-yl)-5-m-tolylfuro[2,3-d]pyrimidin-4-ol;

c) 2-(2-cyclohexylpropan-2-yl)-5-(thiophen-2-yl)furo[2,3-d]pyrimidin-4-ol;

d) 2-(2-cyclohexylpropan-2-yl)-5-(3,5-dichlorophenyl)furo[2,3-d]pyrimidin-4-ol;

e) 2-(2-phenylpropan-2-yl)-5-(thiophen-2-yl)furo[2,3-d]pyrimidin-4-ol;

f) 5-phenyl-2-(2-phenylpropan-2-yl)furo[2,3-d]pyrimidin-4-ol;

g) 2-(2-phenylpropan-2-yl)-5-m-tolylfuro[2,3-d]pyrimidin-4-ol;

h) 5-(3,5-dichlorophenyl)-2-(2-phenylpropan-2-yl)furo[2,3-d]pyrimidin-4-ol;

i) 5-phenyl-2-(2-(thiophen-2-yl)propan-2-yl)furo[2,3-d]pyrimidin-4-ol;

j) 2-(2-(thiophen-2-yl)propan-2-yl)-5-m-tolylfuro[2,3-d]pyrimidin-4-ol;

k) 5-(3,5-dichlorophenyl)-2-(2-(thiophen-2-yl)propan-2-yl)furo[2,3-d]pyrimidin-4-ol;

l) 5-(thiophen-2-yl)-2-(2-(thiophen-2-yl)propan-2-yl)furo[2,3-d]pyrimidin-4-ol;

m) 2-(2-methyloctan-2-yl)-5-phenylfuro[2,3-d]pyrimidin-4-ol;

n) 2-(2-methyloctan-2-yl)-5-m-tolylfuro[2,3-d]pyrimidin-4-ol;

o) 5-(3,5-Dichlorophenyl)-2-(2-methyloctan-2-yl)furo[2,3-d]pyrimidin-4-ol;

and

p) 2-(2-methyloctan-2-yl)-5-(thiophen-2-yl)furo[2,3-d]pyrimidin-4-ol.

13. A pharmaceutical composition comprising a compound of claim 1, or a salt or a pro-drug thereof, and a pharmaceutically acceptable carrier component.

14. A method of treating a cannabinoid receptor-mediated condition comprising administering to a patient an amount of compound of claim 1 that is at least partially effective to treat the cannabinoid receptor-mediated condition.

15. A method according to claim 14 wherein the condition is cancer.

16. A method according to claim 14 wherein

R₂ is selected from the group consisting of substituted or unsubstituted phenyl, and substituted or unsubstituted thiophen-2-yl;

R₁ is selected from the group consisting of hydrogen, methyl and ethyl;

Y is selected from the group consisting of C(O), CH₂, CH(CH₃), CH(OH), C(CH₃)(OH) and C(CH₃)₂; and

Z is selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted thiophen-2-yl, alkyl and substituted or unsubstituted cyclohexyl.

17. A method according to claim 16 wherein Y is C(CH₃)₂.

18. A method according to claim 17 wherein R₁ is hydrogen.

19. A method according to claim 18 wherein the compound is selected from the group consisting of

a) 2-(2-cyclohexylpropan-2-yl)-5-phenylfuro[2,3-d]pyrimidin-4-ol;

b) 2-(2-cyclohexylpropan-2-yl)-5-m-tolylfuro[2,3-d]pyrimidin-4-ol;

c) 2-(2-cyclohexylpropan-2-yl)-5-(thiophen-2-yl)furo[2,3-d]pyrimidin-4-ol;

d) 2-(2-cyclohexylpropan-2-yl)-5-(3,5-dichlorophenyl)furo[2,3-d]pyrimidin-4-ol;

e) 2-(2-phenylpropan-2-yl)-5-(thiophen-2-yl)furo[2,3-d]pyrimidin-4-ol;

f) 5-phenyl-2-(2-phenylpropan-2-yl)furo[2,3-d]pyrimidin-4-ol;

g) 2-(2-phenylpropan-2-yl)-5-m-tolylfuro[2,3-d]pyrimidin-4-ol;

h) 5-(3,5-dichlorophenyl)-2-(2-phenylpropan-2-yl)furo[2,3-d]pyrimidin-4-ol;

i) 5-phenyl-2-(2-(thiophen-2-yl)propan-2-yl)furo[2,3-d]pyrimidin-4-ol;

j) 2-(2-(thiophen-2-yl)propan-2-yl)-5-m-tolylfuro[2,3-d]pyrimidin-4-ol;

k) 5-(3,5-dichlorophenyl)-2-(2-(thiophen-2-yl)propan-2-yl)furo[2,3-d]pyrimidin-4-ol;

l) 5-(thiophen-2-yl)-2-(2-(thiophen-2-yl)propan-2-yl)furo[2,3-d]pyrimidin-4-ol;

m) 2-(2-methyloctan-2-yl)-5-phenylfuro[2,3-d]pyrimidin-4-ol;

n) 2-(2-methyloctan-2-yl)-5-m-tolylfuro[2,3-d]pyrimidin-4-ol;

o) 5-(3,5-Dichlorophenyl)-2-(2-methyloctan-2-yl)furo[2,3-d]pyrimidin-4-ol;

and

p) 2-(2-methyloctan-2-yl)-5-(thiophen-2-yl)furo[2,3-d]pyrimidin-4-ol.

2. A compound of formula I wherein n is from 1 to 6.