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US 4,054,558 AGranted
Cyclic dodecapeptide and intermediates therefor
AssigneeAmerican Home Products Corporation
InventorVictor M. Garsky
Life of this patent
Estimating the term…
Abstract
Compounds of the forumla: ##STR1## in which m and n are independently one of the integers from 1 to 5, inclusive, and pharmaceutically acceptable salts thereof, inhibit the release of growth hormone, insulin and glucagon and are useful in the treatment of diabetes mellitus and acromegaly.
Claims12
A compound selected from the group consisting of ##STR18## and ##STR19## and pharmaceutically acceptable salts thereof, wherein:
- R.sup.2 and R.sup.3 are, independently, protecting groups for the side chain amino substituent of lysine selected from benzyloxycarbonyl, tosyl, t-amyloxycarbonyl, t-butyloxycarbonyl, diisopropylmethoxycarbonyl and substituted benzyloxycarbonyl where in said substituent is selected from halo and nitro;
- R.sup.4, r.sup.5 and R.sup.6 are selected from the group consisting of hydrogen and a protecting group for the alcoholic hydroxyl group of threonine and serine selected from acetyl, benzoyl, tert-butyl, trityl, benzyl, 2,6 dichlorobenzyl and benzyloxycarbonyl;
- R.sup.11 is selected from the group consisting of hydrogen and an .alpha.-carboxyl protecting group selected from C.sub.1 -C.sub.6 alkyl, benzyl, substituted benzyl, phenacyl, phthalimidomethyl, benzhydryl, trichloroethyl, 4-picolyl, .beta.-methylthioethyl, 4-(methylthio)phenyl, said substituent on benzyl being selected from nitro, methyl and methoxy;
- and
- each of m and n is an integer of from 1 through 5, inclusive;
- and all chiral amino acids other than D-Trp are of the L-configuration.
3 more elements
A compound of the formula:
- ##STR20## and pharmaceutically acceptable salts thereof, wherein each of m and n is a whole number from 1 through 5;
- and all chiral amino acids other than D-Trp are in the L-configuration.
A compound of the formula:
- ##STR21## wherein:
- R.sup.1 is an acid labile or photolytic labile protecting group that is cleavable under conditions that will not remove the R.sup.2 and R.sup.3 protecting groups;
- R.sup.2 and R.sup.3 are, independently, protecting groups for the side chain amino substituent of lysine selected from the class consisting of benzyloxycarbonyl, tosyl, t-amyloxycarbonyl, t-butyloxycarbonyl, diisopropylmethoxycarbonyl and substituted benzyloxycarbonyl, said substituent selected from halo and nitro and said R.sup.2 and R.sup.3 groups being stable to cleavage under conditions that result in cleavage of said R.sup.1 group;
- R.sup.4, r.sup.5 and R.sup.6 are, independently, selected from the group consisting of hydrogen and a protecting group for the alcoholic hydroxyl group of threonine and serine selected from acetyl, benzoyl, tert-butyl, trityl, benzyl, 2,6 dichlorobenzyl and benzyloxycarbonyl;
- and
- R.sup.7 is selected from the group consisting of OH, NHNH.sub.2, N.sub.3, OCH.sub.3 and --O--CH.sub.2 --;
- m is a whole number from 1 through 5;
- and all chiral amino acids in said compound other than D-Trp are in the L-configuration.
5 more elements
A compound selected from those of the formula:
- ##STR22## wherein:
- R.sup.2 and R.sup.3 are protecting groups for the side chain amino substituent of lysine selected from the class consisting of benzyloxycarbonyl, tosyl, t-amyloxycarbonyl, t-butyloxycarbonyl, diisopropylmethoxycarbonyl and substituted benzyloxycarbonyl, said substituent being selected from halo and nitro, said R.sup.2 and R.sup.3 groups being stable to cleavage under conditions that result in cleavage of said R.sup.10 group;
- R.sup.4, r.sup.5 and R.sup.6 are selected from the group consisting of hydrogen and a protecting group for the alcoholic hydroxyl group of threonine and serine selected from acetyl, benzoyl, tert-butyl, trityl, benzyl, 2,6-dichlorobenzyl and benzyloxycarbonyl;
- R.sup.8 is hydrogen or a side chain carboxyl protecting group which is removable under conditions that will not remove the R.sup.9 carboxyl protecting group;
- R.sup.9 is an .alpha.-carboxyl protecting group which is stable under reaction conditions which cleave said R.sup.10 and R.sup.8 protecting groups, said .alpha.-carboxyl protecting group being selected from the class consisting of C.sub.1 -C.sub.6 alkyl, benzyl, phenacyl, phthalimidomethyl, benzhydryl, trichloroethyl, 4-picolyl, .beta.-methylthioethyl, 4-(methylthio)phenyl and substituted benzyl, said substituent being selected from the group consisting of nitro, methoxy and methyl;
- R.sup.10 is hydrogen or an acid labile or photolytic labile protecting group that is cleavable under conditions that will not remove said R.sup.2 and R.sup.3 protecting groups;
- each of m and n is a whole number from 1 through 5;
- all chiral amino acids in said compounds other than D-Trp being of the L-configuration.
5 more elements
A compound of the formula:
- ##STR23## wherein:
- R.sup.1 is an acid labile or photolytic labile protecting group that is cleavable under conditions that will not remove the R.sup.2 and R.sup.3 protecting groups;
- R.sup.2 and R.sup.3 are protecting groups for the side chain amino substituent of lysine selected from the class consisting of benzyloxycarbonyl, tosyl, t-amyloxycarbonyl, t-butyloxycarbonyl, diisopropylmethoxycarbonyl and substituted benzyloxycarbonyl, said substituent being selected from halo and nitro, said R.sup.2 and R.sup.3 groups being stable to cleavage under conditions that result in cleavage of said R.sup.1 group;
- R.sup.4, r.sup.5 and R.sup.6 are selected from the group consisting of hydrogen and a protecting group for the alcoholic hydroxyl group of threonine and serine selected from acetyl, benzoyl, tert-butyl, trityl, benzyl, 2,6-dichlorobenzyl and benzyloxycarbonyl;
- R.sup.12 is selected from the class consisting of hydrogen and an .alpha.-carboxyl protecting group selected from the group consisting of C.sub.1 -C.sub.6 alkyl, benzyl, phenacyl, phthalimidomethyl, benzhydryl, trichloroethyl, 4-picolyl, .beta.-methylthioethyl, 4-(methylthio)phenyl and substituted benzyl, said substituent being selected from the group consisting of nitro, methoxy and methyl;
- each of m and n is a whole number from 1 through 5;
- all chiral amino acids in said compound other than D-Trp being of the L-configuration.
4 more elements
Dependencies are inferred from the claim text.