Dimers for use in synthesis of peptidomimetics
View Patent ↗Dimers for use in synthesis of peptidomimetics are described. Uses of dimers as synthons in synthesis of azapeptides and other peptidomimetics, azapeptides and other peptidomimetics synthesized from the dimers and uses of azapeptides and other peptidomimetics are also described.
1 . A compound of Formula (I):
and salts thereof, wherein
A is N-phthalimidyl or NR 3 R 4 , wherein (i) R 3 is H and R 4 is 9-fluorenylmethoxycarbonyl or 2-(3,5-dimethoxyphenyl) propan-2-yloxycarbonyl or (ii) R 3 and R 1 are connected and together form a side chain radical of proline and R 4 is tert-butoxycarbonyl, 9-fluorenylmethoxycarbonyl or 2-(3,5-dimethoxyphenyl) propan-2-yloxycarbonyl;
A 1 is H or absent;
A 2 is H or absent;
X is selected from the group consisting of imidazolyl, benzotriazolyl, S-D, and O-L;
D is H, Cl, an alkyl, an aryl or a heteroaryl;
L is imidazolyl or benzotriazolyl;
R 1 and R 2 is each independently selected from the group consisting of side chain radicals of amino acids selected from the group consisting of side chain radicals of aspartic acid, phenylalanine, alanine, histidine, glutamic acid, tryptophan, valine, leucine, lysine, methionine, threonine, tyrosine, isoleucine, arginine, glycine, asparagine, serine, and glutamine;
Z 1 and Z 2 is each independently C or N; and
at least one of Z 1 and Z 2 is N.
2 . A compound of Formula (I):
and salts thereof, wherein
A is NR 3 R 4 , wherein (i) R 3 is H and R 4 is 9-fluorenylmethoxycarbonyl or 2-(3,5-dimethoxyphenyl) propan-2-yloxycarbonyl or (ii) R 3 and R 1 are connected and together form a side chain radical of proline and R 4 is tert-butoxycarbonyl, 9-fluorenylmethoxycarbonyl or 2-(3,5-dimethoxyphenyl) propan-2-yloxycarbonyl;
A 1 is H or absent;
A 2 is H or absent;
X is selected from the group consisting of imidazolyl, benzotriazolyl, S-D, and O-L;
D is H, Cl, an alkyl, an aryl or a heteroaryl;
L is imidazolyl or benzotriazolyl;
R 1 and R 2 is each independently selected from the group consisting of side chain radicals of amino acids selected from the group consisting of side chain radicals of aspartic acid, phenylalanine, alanine, histidine, glutamic acid, tryptophan, valine, leucine, lysine, methionine, threonine, tyrosine, isoleucine, arginine, glycine, asparagine, serine, and glutamine; and
Z 1 is N and Z 2 is C, or Z 1 is C and Z 2 is N.
3 . A compound according to claim 1 , wherein A is NR 3 R 4 , wherein R 3 is H and R 4 is 9-fluorenylmethoxycarbonyl or 2-(3,5-dimethoxyphenyl) propan-2-yloxycarbonyl.
4 . A compound according to claim 1 , wherein A is N-phthalimidyl.
5 . A compound according to claim 1 , wherein A is NR 3 R 4 , R 3 is H, R 4 is 9-fluorenylmethoxycarbonyl or 2-(3,5-dimethoxyphenyl) propan-2-yloxycarbonyl, and R 3 and R 1 are connected and together form a side chain radical of proline.
6 . A compound according to claim 1 , wherein X is benzotriazolyl.
7 . A compound according to claim 1 , wherein X is S-D; and D is an alkyl.
8 . A compound according to claim 7 , wherein the alkyl is ethyl.
9 . A compound according to claim 1 , wherein X is selected from a group consisting of S-D and O-L.
10 . A compound according to claim 2 , wherein X is selected from the group consisting of S-D and O-L.
11 . A compound according to claim 1 , wherein Z 1 and Z 2 are both N.
12 . A compound according to claim 1 , wherein Z 1 is C, and Z 2 is N.
13 . A compound according to claim 1 wherein the side chain radicals of amino acids are selected from the group consisting of side chain radicals of aspartic acid, phenylalanine, alanine, histidine, glutamic acid, tryptophan, valine, leucine, lysine, methionine, threonine, tyrosine, isoleucine, arginine, asparagine, serine, and glutamine.
14 . A compound according to claim 2 , wherein A is NR 3 R 4 , R 3 is H and R 4 is 9-fluorenylmethoxycarbonyl or 2-(3,5-dimethoxyphenyl) propan-2-yloxycarbonyl.
15 . A compound according to claim 14 , wherein R 4 is 9-fluorenylmethoxycarbonyl.
16 . A compound according to claim 1 , wherein X is selected from a group consisting of imidazolyl, benzotriazolyl, and S-D.
17 . A compound according to claim 1 , which is (9H-fluoren-9-yl)methyl 2-(2-benzyl-2-((ethylthio) carbonyl) hydrazine-1-carbonyl) pyrrolidine-1-carboxylate.
18 . A compound according to claim 1 , wherein
A is NR 3 R 4 , and R 3 and R 1 are connected and together form a side chain radical of proline and R 4 is 9-fluorenylmethoxycarbonyl;
A 1 is absent;
A 2 is absent;
Z 1 is C;
Z 2 is N;
X is S-D or O-L; and
L is an alkyl.
19 . A compound according to claim 2 , wherein
A is NR 3 R 4 , and R 3 and R 1 are connected and together form a side chain radical of proline and R 4 is 9-fluorenylmethoxycarbonyl;
A 1 is absent;
A 2 is absent;
Z 1 is C;
Z 2 is N;
X is S-D or O-L; and
L is an alkyl.