Ortho-Mcneil Pharmaceutical Corp.

Pierre Raboisson

Tianbao Lu

Kristi A Leonard

Maxwell David Cummings

Daniel J Parks

Karen L Milkiewicz

Raul R Calvo

Juan J Marugan Sanchez

Louis V LaFrance

Joan Gushue

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: R, R, R, R, R, Rand 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; and Ris &#x2014;COR, &#x2014;COM, &#x2014;OH, &#x2014;NHR, &#x2014;SOR, &#x2014;NHCONHR, optionally-substituted amidino or optionally-substituted guanidino; or R&#x2014;X&#x2014; is hydrogen or an electron pair; Ris oxygen or &#x2014;NRR; Ris cycloalkyl, aryl, heteroaryl, cycloalkylalkyl, aralkyl, heteroarylalkyl, or a saturated or partially unsaturated heterocycle, each of which is optionally substituted; and R, Rand Rare independently hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, a saturated or partially unsaturated heterocycle, cycloalkylalkyl, aralkyl or heteroarylalkyl, each of which is optionally substituted; or Rand R, together with the carbon atom to which they are attached form a 3- to 7-membered carbocyclic ring optionally substituted 1 to 3 times with R.

Substituted 1,4-diazepines and uses thereof

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Mechelen, Belgium

Pierre Raboisson