Substituted 1,4-diazepines and uses thereof

US7115598B2 · kind B2 · utility

Assignee

• Ortho-McNeil Pharmaceutical, Inc. · US

Inventors

• Tianbao Lu · Collegeville, US
• Karen L. Milkiewicz · Exton, US
• Pierre Jean-Marie Bernard Raboisson · Sligo, IE
• Maxwell D. Cummings · Strafford, US
• Raul Calvo · Royersford, US
• Daniel Parks · Linglestown, US
• Louis Lafrance · Collegeville, US
• Juan Marugan Sanchez · Downingtown, US
• Joan Gushue · Harleysville, US
• Kristi A. Leonard · West Chester, US

Key dates

• Filing date: Apr 21, 2004
• Grant date: Oct 3, 2006
• Expiry date: Oct 1, 2024

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P37/02
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present invention is directed to novel 1,4-diazepines, pharmaceutical compositions thereof, and the use thereof as inhibitors of HDM2-p53 interactions. Compounds have Formula I:or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein:R1, R2, R9, R10, Ra, Rd and M are defined herein;X is a bivalent radical of: an alkane, a cycloalkane, an optionally-substituted arene, an optionally-substituted heteroarene, an optionally-substituted arylalkane or an optionally-substituted heteroarylalkane; andR3 is —CO2Rd, —CO2M, —OH, —NHRd, —SO2Rd, —NHCONHRd, optionally-substituted amidino or optionally-substituted guanidino;or R3—X— is hydrogen or an electron pair;R4 is oxygen or —NR9R10;R5 is cycloalkyl, aryl, heteroaryl, cycloalkylalkyl, aralkyl, heteroarylalkyl, or a saturated or partially unsaturated heterocycle, each of which is optionally substituted; andR6, R7 and R8 are independently hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, a saturated or partially unsaturated heterocycle, cycloalkylalkyl, aralkyl or heteroarylalkyl, each of which is optionally substituted; or R6 and R7, together with the carbon atom to which they are attached form a 3- to 7-membered carbocyclic …