Patent ID: 6194380
Filing Date: 2001-02-27
Classification: A61K,A61P,C07C,C07K

Abstract:
A method of promoting bone formation in humans comprising administering to humans an amount of at least one compound selected from the group consisting of kistrin, echstatin and Gly-Arg-Gly-Asp-Ser or a compound having a formula selected from the group consisting of ##STR21##and pharmaceutically acceptable salts thereof sufficient to promote bone formation wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are individually selected from the group consisting essentially of a) hydrogen, b) alkyl of 1 to 8 carbon atoms unsubstituted or substituted with a member of the group consisting of --OH, --COOH, cycloalkyl of 3 to 10 carbon atoms, hydroxy cycloalkyl of 3 to 10 carbon atoms, aryl of 6 to 12 carbon atoms and hydroxy aryl of 6 to 12 carbon atoms, and c) cycloalkyl of 3 to 10 carbon atoms, hydroxy cycloalkyl of 3 to 10 carbon atoms, aryl of 6 to 12 carbon atoms and hydroxy aryl of 6 to 12 carbons, R.sub.7, R.sub.8, R.sub.13, R.sub.14 and R.sub.15 are individually selected from the group consisting of --OH, alkoxy of 1 to 8 carbon atoms, alkenyloxy of 2 to 12 carbon atoms, cycloalkoxy of 3 to 10 carbon atoms and aryloxy of 6 to 12 carbon atoms, X is --S-- or --SO--, R.sub.9, R.sub.10, R.sub.11 , and R.sub.12 are individually selected from the group consisting essentially of hydrogen, alkyl of 1 to 8 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, hydroxyaryl of 6 to 12 carbon atoms and aryl of 6 to 12 carbon atoms, R.sub.16 is selected from the group consisting of --N--(R.sub.20).sub.2, ##STR22##R.sub.17 is hydrogen or alkyl of 1 to 4 carbon atoms or phenyl alkyl of 1 to 4 alkyl carbon atoms, R.sub.18 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms, phenyl and phenyl substituted with --OCH.sub.3 or --COR.sub.21, R.sub.19 is alkyl of 1 to 15 carbon atoms or alkyl of 1 to 5 carbon atoms substituted with a member of the group consisting of --OH, --NH.sub.2, --CONH.sub.2, cyclohexyl, phenyl, naphthyl, indolyl, adamantyl, methyl substituted with --COOH, --NHCOOCH.sub.2 -phenyl, cyclohexyl, methoxy cyclohexyl, aryl of 6 to 10 carbon atoms and methoxy aryl of 6 to 10 carbon atoms or R.sub.18 and R.sub.19 together with the carbon atoms to which they are attached form a member of the group consisting of adamantyl, naphthyl and fluorenyl, R.sub.20 is hydrogen or alkyl of 1 to 4 carbon atoms or alkylphenyl of 1 to 4 alkyl carbon atoms, R.sub.21 is selected from the group consisting of --OH, --NH.sub.2, --NH--CH.sub.2 --CH.sub.2 -phenyl, alkoxy of 1 to 3 carbon atoms, benzyloxy, Pro and Aoc, Y is selected from the group consisting of --NH--, --O-- and a bond, a is an integer from 1 to 3, b is 1 or 2, c is 0 or 1, d is 0 or 1, R.sub.22 is selected from the group consisting of --N(R.sub.23).sub.2, ##STR23##R.sub.23 is hydrogen or alkyl of 1 to 4 carbon atoms or phenyl alkyl of 1 to 4 alkyl carbon atoms and e is an integer from 2 to 6.