such as N-Hydroxy-3-[1-(toluene-4-sulfonyl)-1)-H-pyrrol-3-yl]-acrylamide, used as histone deacetylase inhibitors; antitumor agents; anticarcinogenic agents; antiproliferative agents
Inventors
Maier, Thomas • Beckers, Thomas • Baer, Thomas • Gimmnich, Petra • Dullweber, Frank • Vennemann, Matthias
Assignees
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Publication Number
US-7842820-B2
Publication Date
2010-11-30
Expiration Date
Abstract
Compounds of the formula I in which the substitutents have the definitions provided in the specification, are novel, effective HDAC inhibitors.
Core Innovation
The invention describes novel N-sulphonylpyrrole derivatives of formula I, including pharmaceutically acceptable salts thereof, defined by substituents R1–R7. In formula I, R6 is a sulphonyl-linked aryl group according to -T1-Q1 or an alternative -T2-N(R611)R612 variant with detailed constraints on T1, T2, Ar1, and the allowable heteroaromatic or aryl groups, and R7 is hydroxyl or Cyc1, where Cyc1 is a ring system of formula Ia.
The compounds include exemplary members consistent with the formula I scaffold, including (E)-N-hydroxy-3-[1-(toluene-4-sulfonyl)-1H-pyrrol-3-yl]-acrylamide and other sulfonamide or acrylamide analogs with substituted benzenesulfonyl and related aryl or heteroaryl groups. The document also states expanded structural definitions of ring-containing substituent options and covers the compounds and their salts.
The patent positions these formula I compounds as histone deacetylase (HDAC) inhibitors and relates them to prior art HDAC inhibitors, including TSA, SAHA, MS-275, and Tubacin. The background frames the problem as the need for improved HDAC inhibitors and motivates the discovery of a new class of N-sulphonylpyrrole derivatives with defined structural variability.
Claims Coverage
The partial content includes two independent claims: a formula I compound claim and a selected group claim for specific (E)-N-hydroxy acrylamide members, including salts. Across the independent claims, the coverage is based on the substituent-defining options R1–R7 in formula I and, in the selected group claim, on explicit named compounds and salt forms.
Formula I N-sulphonylpyrrole scaffold
A compound of formula I in which R1–R5 are restricted to hydrogen, 1-4C-alkyl, halogen, or 1-4C-alkoxy, R6 is -T1-Q1 or -T2-N(R611)R612 with detailed definitions of T1/T2, Q1/Ar1, and allowable heteroaromatic or aryl ring options, R7 is hydroxyl or Cyc1, and the compound includes a salt thereof.
Selected (E)-N-hydroxy acrylamide members with sulfonyl-linked 1H-pyrrol-3-yl
A compound selected from the group consisting of multiple specified (E)-N-hydroxy-3-[1-(substituted sulfonyl)-1H-pyrrol-3-yl]-acrylamide or related named (E)-3-[1-(substituted sulfonyl)-1H-pyrrol-3-yl]-N-hydroxy-acrylamide structures, together with the salts thereof.
Claim coverage centers on formula I N-sulphonylpyrrole derivatives defined by the substituent framework R1–R7, and on an explicit group claim listing particular (E)-N-hydroxy acrylamide members with substituted sulfonyl-linked 1H-pyrrol-3-yl moieties, including salt forms.
Stated Advantages
Presented as HDAC inhibitors.
Therapeutic indications are described for cancers and other diseases.
Documented Applications
HDAC inhibition use in therapies for cancers and other diseases, supported by enzymatic and cell-based biological assay testing including histone H3K23 hyperacetylation and apoptosis/cytotoxicity assays.
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