Inhibitors of histone deacetylase

• US 7,282,608 B2
• Filed: 10/16/2003
• Issued: 10/16/2007
• Est. Priority Date: 10/17/2002
• Status: Expired due to Fees

• Current Assignee: MethylGene, Inc.
• Original Assignee: MethylGene, Inc.
• Inventors: Raeppel, Stephane, Delorme, Daniel, Gaudette, Frederic
• Primary Examiner(s): Kumar; Shailendra
• Application Number:
  US10/531,406
• Publication Number:
  US 20060020131A1
• Time in Patent Office: 1,461 Days
• Field of Search: 548/161, 548/263.8, 548/469, 549/439, 549/434, 544/297, 544/360, 544/400, 546/337, 564/92, 564/164
• US Class Current: 564/164
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• 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: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07C 233/80 with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 235/84 with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 237/40 having the nitrogen atom of the carboxamide group bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 2601/02 with a three-membered ring
• CPC Class Codes: C07C 2601/08 the ring being saturated
• CPC Class Codes: C07C 311/19 to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
• CPC Class Codes: C07D 209/16 Tryptamines
• CPC Class Codes: C07D 209/44 Iso-indoles; Hydrogenated iso-indoles
• CPC Class Codes: C07D 211/22 by oxygen atoms
• CPC Class Codes: C07D 213/30 Oxygen atoms
• CPC Class Codes: C07D 213/38 having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
• CPC Class Codes: C07D 213/40 Acylated substituent nitrogen atom
• CPC Class Codes: C07D 213/50 Ketonic radicals
• CPC Class Codes: C07D 213/74 Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 239/47 : One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
• CPC Class Codes: C07D 249/14 : Nitrogen atoms
• CPC Class Codes: C07D 277/82 : Nitrogen atoms
• CPC Class Codes: C07D 295/155 : with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 295/185 : from aliphatic carboxylic acids
• CPC Class Codes: C07D 317/66 : Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links

Abstract

The invention provides compoods and methods for treating cell proliferative-diseases. The invention provides new inhibitors of histone deacetylase enzymatic activity, compositions of the compounds comprising the inhibitors and a pharmaceutically acceptable carrier, excipient, or diluent, and methods of using the compounds to inhibit cellular proliferation in vitro and therapeutically.

Claims

1. A compound of formula:

2. The compound according to claim 1 wherein R² and R³ are both —

H.

3. The compound according to claim 1 wherein Y is —

NH—

, —

SO₂—

NH—

, or —

N(R⁴)—

wherein R⁴ is —

C(O)O—

C₁–

C₆-hydrocarbyl.

4. The compound according to claim 1 wherein R¹ is aryl, benzothiazolyl, pyrimidinyl, triazolyl, benzodioxolenyl, or pyridinyl, each of which is optionally substituted with from 1 to 3 substituents.

5. The compound according to claim 4 wherein R¹ is substituted with from 1–

3 substituents independently selected from C1–

C₆-hydrocarbyl, C₁–

C₆-hydrocarbyloxy, halo, methylthio, and acetyl.

6. The compound according to claim 1 wherein R¹—

Y is selected from;