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US 5,965,694 AGranted
Somatostatin mimics and synthetic methods therefor
AssigneeThe Trustees of the University of Pennsylvania
InventorsRalph F. Hirschmann, Rolando A. Spanevello
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Abstract
Relatively small cyclic peptides that mimic the biological and/or chemical activity of larger cyclic peptide such as somatostatin, as well as synthetic methods therefor. In certain embodiments, cyclic peptides of the invention have structure: ##STR1## wherein R.sub.NP1 is H, an amine protecting group, or a solid support and R.sub.NP2 is H or an amine protecting group.
Claims40
A compound having the structure:
- ##STR15## wherein:
- R.sub.1 is hydroxybenzyl;
- R.sub.2 is --CH.sub.2 -(indole);
- R.sub.3 is --(CH.sub.2).sub.4 NHR.sub.NP2, where R.sub.NP2 is H, or an amine protecting group;
- R.sub.5A is (CH.sub.2).sub.x --R.sub.x where x is 0 to 5 and R.sub.x is alkyl having from 1 to 5 carbon atoms, from 0 to 3 oxygen atoms, from 0 to 3 nitrogen atoms, and from 0 to 3 sulfur atoms;
- R.sub.6 is --(CH.sub.2).sub.y --R.sub.y and y is 0 to 5 and R.sub.y is aryl having 3 to 14 carbon atoms, from 0 to 4 oxygen atoms, from 0 to 4 nitrogen atoms, and from 0 to 4 sulfur atoms;
- R.sub.4A is alkyl having from 1 to 14 carbon atoms;
- R.sub.NP1 is a solid support;
- and
- R.sub.7 is H or alkyl having 1 to 3 carbon atoms.
7 more elements
A compound having the structure:
- wherein:
- R.sub.NP3 is H or an amine protecting group;
- R.sub.CP is a carboxyl protecting group selected from the group consisting of trimethylsilyl, 2-(trimethylsilyl)ethyl, 2,2,2-trichloroethyl, t-butyldimethylsilyl, p-methoxybenzyl, t-butyl, and 2-methylthioethyl;
- R.sub.1 is hydroxybenzyl or hydroxyl-protected forms thereof;
- R.sub.2 is --CH.sub.2 -(indole);
- R.sub.3 is --(CH.sub.2).sub.4 NHR.sub.NP2, where R.sub.NP2 is H, or an amine protecting group;
- R.sub.4A is alkyl having from 1 to 14 carbon atoms;
- R.sub.5A is (CH.sub.2).sub.x --R.sub.x where x is 0 to 5 and R.sub.x is alkyl having from 1 to 5 carbon atoms, from 0 to 3 oxygen atoms, from 0 to 3 nitrogen atoms, and from 0 to 3 sulfur atoms;
- R.sub.6 is --(CH.sub.2).sub.y --R.sub.y and y is 0 to 5 and R.sub.y is aryl having 3 to 14 carbon atoms, from 0 to 4 oxygen atoms, from 0 to 4 nitrogen atoms, and from 0 to 4 sulfur atoms;
- R.sub.NP1 is H, an amine protecting group, or a solid support;
- and
- R.sub.7 is H or alkyl having 1 to 3 carbon atoms.
9 more elements
A compound having the structure:
- ##STR17## wherein:
- R.sub.NP3 is H or an amine protecting group;
- R.sub.CP is 2-(trimethylsilyl) ethyl protecting group;
- R.sub.1 is hydroxybenzyl or hydroxyl-protected forms thereof;
- R.sub.2 is --CH.sub.2 -(indole);
- R.sub.3 is --(CH.sub.2).sub.4 NHR.sub.NP2, where R.sub.NP2 is H or an amine protecting group;
- R.sub.4A is alkyl having from 1 to 14 carbon atoms;
- R.sub.5A is (CH.sub.2).sub.x --R.sub.x where x is 0 to 5 and R.sub.x is alkyl having from 1 to 5 carbon atoms, from 0 to 3 oxygen atoms, from 0 to 3 nitrogen atoms, and from 0 to 3 sulfur atoms;
- R.sub.6 is --(CH.sub.2).sub.y --R.sub.y and y is 0 to 5 and R.sub.y is aryl having 3 to 14 carbon atoms, from 0 to 4 oxygen atoms, from 0 to 4 nitrogen atoms, and from 0 to 4 sulfur atoms;
- R.sub.NP1 is H, an amine protecting group, or a solid support;
- and
- R.sub.7 is H or alkyl having 1 to 3 carbon atoms.
9 more elements
A compound having the structure, ##STR18## wherein:
- R.sub.NP3 is H or an amine protecting group:
- R.sub.CP is H or a carboxyl protecting group;
- R.sub.1 is hydroxybenzyl or hydroxyl-protected forms thereof;
- R.sub.2 is --CH.sub.2 -(indole);
- R.sub.3 is --(CH.sub.2).sub.4 NHR.sub.NP2, where R.sub.NP2 is H;
- R.sub.4A is alkyl having from 1 to 14 carbon atoms;
- R.sub.5A is (CH.sub.2).sub.x --R.sub.x where x is 0 to 5 and R.sub.x is alkyl having from 1 to 5 carbon atoms, from 0 to 3 oxygen atoms, from 0 to 3 nitrogen atoms, and from 0 to 3 sulfur atoms;
- R.sub.6 is --(CH.sub.2).sub.y --R.sub.y and y is 0 to 5 and R.sub.y is aryl having 3 to 14 carbon atoms, from 0 to 4 oxygen atoms, from 0 to 4 nitrogen atoms, and from 0 to 4 sulfur atoms;
- R.sub.NP1 is H, an amine protecting group, or a solid support;
- and
- R.sub.7 is H or alkyl having 1 to 3 carbon atoms.
8 more elements
A compound having the structure:
- ##STR19## wherein:
- R.sub.NP3 is H or an amino protecting group;
- R.sub.CP is H or a carboxyl protecting group;
- R.sub.1 is hydroxybenzyl or hydroxyl-protected forms thereof;
- R.sub.2 is --CH.sub.2 -(indole);
- R.sub.3 is --(CH.sub.2).sub.4 NHR.sub.NP2, where R.sub.NP2 is H or an amine protecting group;
- R.sub.4A is alkyl having from 1 to 14 carbon atoms;
- R.sub.5A is (CH.sub.2).sub.x --R.sub.x where x is 0 to 5 and R.sub.x is alkyl having from 1 to 5 carbon atoms, from 0 to 3 oxygen atoms, from 0 to 3 nitrogen atoms, and from 0 to 3 sulfur atoms;
- R.sub.6 is --(CH.sub.2).sub.y --R.sub.y and y is 0 to 5 and R.sub.y is aryl having 3 to 14 carbon atoms, from 0 to 4 oxygen atoms, from 0 to 4 nitrogen atoms, and from 0 to 4 sulfur atoms;
- R.sub.NP1 is an amine protecting group, or a solid support;
- and
- R.sub.7 is H or alkyl having 1 to 3 carbon atoms.
9 more elements
Dependencies are inferred from the claim text.