IP Library Granted Patent US 8,987,315
Granted Patent B2
US 8,987,315 · App. 13/519,801 · Granted Mar 24, 2015

Metalloenzyme inhibitor compounds

Inventors: William J. Hoekstra (Durham, NC); Robert J. Schotzinger (Raleigh, NC); Stephen W. Rafferty (Durham, NC)
Assignee: Innocrin Pharmaceuticals, Inc.
C07D257/04A61K31/165A61K31/41A61K31/415A61K31/4196A61K45/06
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Quick Facts
Patent No.
US 8,987,315
App. No.
13/519,801
Granted
Mar 24, 2015
Kind
B2
Abstract

The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.

Claims (21)

1. A compound of formula (I), or salt, solvate, hydrate, or prodrug thereof:

wherein R 1 is optionally substituted naphthyl, R 2 is unsubstituted alkyl, and R 3 is H.

2. The compound of claim 1 , wherein R 1 is substituted naphthyl, R 2 is unsubstituted alkyl, and R 3 is H.

3. The compound of claim 2 , wherein R 1 is naphthyl substituted with 1, 2, 3 or 4 substituents, independently selected from alkyl, alkoxy, haloalkoxy, cyano, halo, amino, mono-alkylamino, di-alkylamino, or heteroaryl.

4. The compound of claim 1 , wherein R 2 is selected from the group consisting of methyl; ethyl; n-propyl; isopropyl; n-butyl; 2-butyl; isobutyl; tert-butyl; n-pentyl; 2-pentyl; 3-methyl-2-butyl; 3-pentyl; 2-methyl-3-butyl; 2-methyl-1-butyl; neopentyl; isopentyl; n-hexyl; 2-hexyl; 3-methyl-2-pentyl; 4-methyl-2-pentyl; 3-hexyl; 2-methyl-3-pentyl; 2,2-dimethyl-3-butyl; 2-methyl-1-pentyl; 2,3-dimethyl-1-butyl; 1,1-dimethyl-1-butyl; 1,1,2-trimethyl-1-propyl; 2,2-dimethyl-1-butyl; 2,2-dimethyl-3-butyl; 2,2-dimethyl-4-butyl; 2-ethyl-1-butyl; isohexyl; and 3-methyl-1-pentyl.

5. A compound having the structure of formula (III):

wherein X is CH;

Y is CH;

R 2 is optionally substituted aryl, optionally substituted naphthyl, optionally substituted heteroaryl, unsubstituted alkyl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted heteroaryl-alkyl, or optionally substituted heteroaryl-(di)fluoroalkyl;

R 3 is H, optionally substituted alkyl, or optionally substituted cycloalkyl;

and R 4 and R 5 are independently H, halogen, alkoxy, fluoroalkoxy containing 1-5 fluorines, cyano, carboxamido, optionally substituted aryl, or optionally substituted heteroaryl.

6. The compound of claim 5 , wherein R 2 is selected from the group consisting of methyl; ethyl; n-propyl; isopropyl; n-butyl; 2-butyl; isobutyl; tert-butyl; n-pentyl; 2-pentyl; 3-methyl-2-butyl; 3-pentyl; 2-methyl-3-butyl; 2-methyl-1-butyl; neopentyl; isopentyl; n-hexyl; 2-hexyl; 3-methyl-2-pentyl; 4-methyl-2-pentyl; 3-hexyl; 2-methyl-3-pentyl; 2,2-dimethyl-3-butyl; 2-methyl-1-pentyl; 2,3-dimethyl-1-butyl; 1,1-dimethyl-1-butyl; 1,1,2-trimethyl-1-propyl; 2,2-dimethyl-1-butyl; 2,2-dimethyl-3-butyl; 2,2-dimethyl-4-butyl; 2-ethyl-1-butyl; isohexyl; and 3-methyl-1-pentyl.

7. A compound that is:

2-(1-(6,7-bis(difluoro methoxy)naphthalen-2-yl)-2-methylpropyl)-2H-tetrazole (1);

2-(2-Methyl-1-(6-(2,2,2-trifluoroethoxy)naphthalen-2-yl)propyl)-2H-tetrazole (2);

2-(1-(6,7-Dimethoxynaphthalen-2-yl)-2-methylpropyl)-2H-tetrazole (3);

2-(1-(6-(difluoromethoxy)naphthalen-2-yl)-2-methylpropyl)-2H-tetrazole (4);

or salt, solvate, hydrate or prodrug thereof.

8. A composition comprising a compound of claim 5 and a pharmaceutically acceptable carrier.

9. The composition of claim 8 further comprising a therapeutic agent in addition to the compound of formula (III).

10. The composition of claim 8 further comprising a therapeutic agent in addition to the compound of formula (III), wherein the therapeutic agent is an anti-cancer agent, antifungal agent, cardiovascular agent, antiinflammatory agent, chemotherapeutic agent, an anti-angiogenesis agent, cytotoxic agent, an anti-proliferation agent, metabolic disease agent, opthalmologic disease agent, central nervous system (CNS) disease agent, urologic disease agent, or gastrointestinal disease agent.

Assignments (2)
CHANGE OF NAME Recorded Oct 27, 2014
From: VIAMET PHARMACEUTICALS, INC.
To: INNOCRIN PHARMACEUTICALS, INC.
Reel/Frame 034066/0759 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 7, 2012
From: HOEKSTRA, WILLIAM J.; SCHOTZINGER, ROBERT J.; RAFFERTY, STEPHEN W.
To: VIAMET PHARMACEUTICALS, INC.
Reel/Frame 028737/0725 →
Continuity (2)
Provisional Application 61291491 · Dec 31, 2009
Related Publication 20120309800A1 · Dec 6, 2012