METHOD OF TREATING MUCOEPIDERMOID CARCINOMA

• US 20140243396A1
• Filed: 09/27/2012
• Published: 08/28/2014
• Est. Priority Date: 09/30/2011
• Status: Abandoned Application

• Current Assignee: Dana-Farber Cancer Institute
• Original Assignee: Dana-Farber Cancer Institute
• Inventors: Griffin, James D., Wu, Lizi, Chen, Jie
• Application Number:
  US14/347,961
• Publication Number:
  US 20140243396A1
• Time in Patent Office: Days
• US Class Current: 514/44.A
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/4015 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

Imidazoquinolines, as set forth in formula (I), are useful for inhibiting growth or proliferation of mucoepidermoid carcinoma cells. The therapeutic and prophylactic treatments provided by this invention are practiced by administering to a patient in need thereof an amount of a compound of formula (I) that is effective to inhibit growth or proliferation of the mucoepidermoid carcinoma cells.

Claims

1. A method for inhibiting growth or proliferation of mucoepidermoid carcinoma cells comprising administering to a patient in need thereof in an amount that is effective to inhibit growth or proliferation of the mucoepidermoid carcinoma cells a compound of the formula

2. A method according to claim 1 wherein R¹, R², and R³ are all methyl.

3. A method according to claim 2 wherein R⁴ is pyridyl unsubstituted or substituted by lower alkyl or lower alkoxy.

4. A method according to claim 2 wherein R⁴ is quinolinyl unsubstituted or substituted by halogen.

5. A method according to claim 1 wherein the compound of formula (I) is 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydroimidazo[4,5-c]quinolin-1-yl)-phenyl]propionitrile or a pharmaceutically acceptable salt thereof.

6. A method according to claim 1 wherein the amount of the compound or salt of formula (I) that is effective to inhibit growth or proliferation of the mucoepidermoid carcinoma cells is an administered amount ranging from 0.001 to 1000 mg/kg.

13. A method according to claim 1 further comprising administering to the patient

a PDE4B inhibitor.

17. A method according to claim 13 wherein said PDE4B inhibitor is rolipram.

7. A method for treating mucoepidermoid carcinoma comprising administering to a patient in need thereof in an amount that is effective to inhibit growth or proliferation of the mucoepidermoid carcinoma cells a compound of the formula

8. A method according to claim 7 wherein R¹, R², and R³ are all methyl.

11. A method according to claim 8 wherein the compound of formula (I) is 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydroimidazo[4,5-c]quinolin-1-yl)-phenyl]propionitrile or a pharmaceutically acceptable salt thereof.

12. A method according to claim 8 wherein the amount of the compound or salt of formula (I) that is effective to inhibit growth or proliferation of the mucoepidermoid carcinoma cells is an administered amount ranging from 0.001 to 1000 mg/kg.

18. A method according to claim 7 further comprising administering to the patient

a PDE4B inhibitor.

22. A method according to claim 18 wherein said PDE4B inhibitor is rolipram.

9. A method according to claim 9 wherein R⁴ is pyridyl unsubstituted or substituted by lower alkyl or lower alkoxy.

10. A method according to claim 9 wherein R⁴ is quinolinyl unsubstituted or substituted by halogen.

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33. A method for inhibiting growth or proliferation of mucoepidermoid carcinoma cells comprising administering to a patient in need thereof in an amount that is effective to inhibit growth or proliferation of the mucoepidermoid carcinoma cells a PDE4B inhibitor, a PI3-kinase inhibitor or a PDE4B inhibitor and a PI3-kinase inhibitor.

34. The method according to claim 33, wherein the PDE4B inhibitor comprises an shRNA, rolipram or forskolin and combinations thereof.

35. The method according to claim 34, wherein the shRNA is selected from the group comprising SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 3, SEQ ID NO 4 and combinations thereof.

36. The method according to claim 33, further comprising administering to a patient an effective amount of a compound of the formula

37. The method according to claim 35, wherein the PI3-kinase inhibitor comprises a shRNA.

38. The method according to claim 37, wherein the shRNA comprises SEQ ID NO 6, SEQ ID NO 7, SEQ ID NO 8, SEQ ID NO 9, and combinations thereof.