2. Academic Validation
  3. A potent, orally bioavailable benzazepinone growth hormone secretagogue

A potent, orally bioavailable benzazepinone growth hormone secretagogue

  • J Med Chem. 1998 May 7;41(10):1716-28. doi: 10.1021/jm970816j.
R J DeVita 1,  R Bochis,  A J Frontier,  A Kotliar,  M H Fisher,  W R Schoen,  M J Wyvratt,  K Cheng,  W W Chan,  B Butler,  T M Jacks,  G J Hickey,  K D Schleim,  K Leung,  Z Chen,  S L Chiu,  W P Feeney,  P K Cunningham,  R G Smith
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065-0900, USA.
PMID: 9572898 DOI: 10.1021/jm970816j
Abstract

The identification of L-739,943 (8b), a potent, orally bioavailable benzolactam growth hormone secretagogue, is obtained from zwitterionic L-692,429 through modification of its amino acid side chain and replacement of the acidic 2'-tetrazole with the neutral and potency enhancing 2'-(N-methylaminocarbonylamino)methyl substituent. L-739,943 is orally active for the release of growth hormone in beagle dogs at doses as low as 0.5 mg/kg. Oral bioavailability in dogs of 8b is 24% at a dose of 2 mg/kg with a mean drug Cmax of 145 +/- 46 ng/mL. L-739,943 represents a significant breakthrough in terms of both potency and oral bioavailability as compared to the prototype benzolactam L-692,429.

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