Phenyl-indole compounds for modulating IgE and Inhibiting cellular proliferation

• US 7,375,118 B2
• Filed: 09/12/2003
• Issued: 05/20/2008
• Est. Priority Date: 09/12/2002
• Status: Expired due to Fees

• Current Assignee: Avanir Pharmaceuticals (Otsuka Holdings Company Limited)
• Original Assignee: Avanir Pharmaceuticals (Otsuka Holdings Company Limited)
• Inventors: Sircar, Jagadish C., Richards, Mark L., Ramnauth, Jailall
• Primary Examiner(s): SHAMEEM, GOLAM M
• Application Number:
  US10/661,139
• Publication Number:
  US 20040180946A1
• Time in Patent Office: 1,712 Days
• Field of Search: 548/465, 548/469, 548/490, 548/491, 546/268.1, 546/277.4, 514/415, 514/336, 514/339
• US Class Current: 514/339
• 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 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 209/10 with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 209/14 Radicals substituted by nitrogen atoms, not forming part of a nitro radical
• CPC Class Codes: C07D 209/18 Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Abstract

The present invention is directed to small molecule inhibitors of the IgE response to allergens, which are useful in the treatment of allergy and/or asthma or any diseases where IgE is pathogenic. This invention also relates to phenyl-indole molecules that are cellular proliferation inhibitors and thus are useful as anticancer agents. This invention further relates to small molecules which suppress cytokines and leukocytes.

Claims

1. A compound or salt thereof having any one of the following formulas:

2. The compound or salt thereof of claim 1, wherein said polycyclic aliphatic group is selected from the group consisting of adamantyl, bicycloheptyl, camphoryl, bicyclo[2,2,2]octanyl and norbomyl.

3. The compound or salt thereof of claim 1, wherein said heteroaryl and said substituted heteroaryl is selected from the group consisting of pyridines, thiazoles, isothiazoles, oxazoles, pyrimidines, pyrazines, furans, thiophenes, isoxazoles, pyrroles, pyridazines, 1,2,3-triazines, 1,2,4-triazines, 1,3,5-triazines, pyrazoles, imidazoles, indoles, quinolines, iso-quinolines, benzothiophines, benzofurans, parathiazines, pyrans, chromenes, pyrrolidines, pyrazolidines, imidazolidines, morpholines, thiomorpholines, and the corresponding heterocyclics.

4. The compound or salt thereof of claim 1, wherein R₁ and R₂ are independently selected from the following:

5. The compound or salt thereof of claim 1 selected from the group consisting of the following compounds:

12. A method of preparing a compound or salt thereof of Genus I as defined in claim 1 comprising:

reacting a compound having formula;

13. A method of preparing a compound or salt thereof of Genus II as defined in claim 1 comprising:

reacting a compound having formula

14. A method of preparing a compound or salt thereof of Genus III as defined in claim 1 comprising:

reacting a compound having formula;

15. A method of preparing a compound or salt thereof of Genus IV as defined in claim 1 comprising:

reacting a compound having formula;

6. A compound or salt thereof represented by one of the following formulas:

7. The compound or salt thereof of claim 6 selected from the group consisting of the following compounds:

8. A compound or salt thereof represented by one of the following formulas:

9. The compound or salt thereof of claim 8 selected from the group consisting of the following compounds:

10. A compound or salt thereof represented by one of the following formulas:

11. The compound or salt thereof of claim 10 selected from the group consisting of the following compounds: