Hoffmann-La Roche Inc.

Thomas F Mowles

Arthur M Felix

Edgar P Heimer

Gary L Olson

Leo Berger

Wallace M Dairman

The invention is directed to analogs of GRF or fragments thereof wherein the fragment is reduced in number by one to fifteen amino acids from the carboxyl end wherein the analogs have the formula: ##STR1## wherein R is desNH.sub.2 -Tyr, Tyr, D-Tyr, Ac-Tyr, His or C.sup..alpha. -Methyl-Tyr; R.sub.1 is Ala, N-Methyl-D-Ala or D-Ala; R.sub.2 is Lys, Ala, Leu, Val or Ile; R.sub.3 is Ala, Leu, Val, Ile, Nle, Nval, .beta.-Ala or .alpha.-Aib; R.sub.4 is Lys, Ala, Leu, Val or Ile; R.sub.5 is Met, Leu, Nle or Ile; R.sub.6 is Asn or Ser; X is hydrogen or --COR.sub.7 ; R.sub.7 is hydrogen, C.sub.1-4 alkyl or halo(C.sub.1-4)alkyl; Y is --OR.sub.8 or --NR.sub.9 R.sub.10 ; R.sub.8 is hydrogen or C.sub.1-5 -alkyl; R.sub.9 and R.sub.10 independently equal hydrogen, C.sub.1-7 alkyl, C.sub.2-4 alkenyl or halo(C.sub.1-4)alkyl; and pharmaceutically acceptable acid or base addition salts thereof. The invention is further directed to pharmaceutical compositions and to methods for treating growth hormone deficiencies.

Growth hormone releasing factor analogs

Compounds of the formula ##STR1## wherein R.sub.1 is hydrogen, lower alkyl or acyl; R.sub.2 and R.sub.3 independently are lower alkyl, aralkyl or alkenyl or R.sub.2 and R.sub.3 together form a ring of 5 to 8 carbon atoms; R.sub.4 is phenyl, substituted phenyl, cyclohexyl, substituted cyclohexyl, cyclopentyl, substituted cyclopentyl, cycloheptyl, or substituted cycloheptyl; R.sub.5 is hydrogen or lower alkyl; R.sub.6 is hydrogen, lower alkyl or acyl; and pharmaceutically acceptable acid addition salts thereof are described. The compounds of formula I and pharmaceutically acceptable acid addition salts thereof are anti-emetic agents which lack central nervous system side effects.

Substituted piperidinomethylindolone and cyclopent(b)indolone derivatives

Novel growth hormone releasing factor analogs in which glycine at position 15 is replaced by appropriately selected amino acids demonstrate enhanced potency for the release of growth hormone and the analogs can be administered to a subject having a deficiency of growth hormone.

Growing community of inventors

Pine Brook, NJ, United States of America

Thomas F Mowles