Combinatorial synthesis of libraries of macrocyclic compounds useful in drug discovery
View Patent ↗A library of macrocyclic compounds of the formula (I) where part (A) is a bivalent radical, a —(CH 2 ) y — bivalent radical or a covalent bond; where part (B) is a bivalent radical, a —(CH 2 ) z — bivalent radical, or a covalent bond; where part (C) is a bivalent radical, a —(CH 2 ) t — bivalent radical, or a covalent bond; and where part (T) is a —Y—L—Z— radical wherein number Y is CH 2 or CO, Z is NH or O and L is a bivalent radical. These compounds are useful for carrying out screening assay or as intermediates for the synthesis of other compound of pharmaceutical interest. A process for their preparation of these compounds in a combinatorial manner, is also disclosed.
1. A macrocyclic compound of the formula (1):
and its pharmaceutically acceptable salts,
wherein
A 1 is:
wherein
X 1 is —CH—, and
R 1 is
A 2 is:
wherein
X 2 is —CH—, and
R 2 is H;
A 3 is:
wherein
X 3 is —CH—, and
R 3 is
W 1 , W 2 , W 3 , and W 5 are each selected from the group consisting of hydrogen and protecting groups used for orthogonal protection in peptide synthesis;
wherein the carbonyl carbon of A 1 is covalently bonded to the nitrogen atom of A 2 , and the carbonyl carbon of A 2 is covalently bonded to the nitrogen atom of A 3 ;
T is a radical selected from the group consisting of:
wherein (N) is the nitrogen atom of A 1 of formula (1) and (C) is the carbonyl carbon of A 3 of formula (1).
2. A macrocyclic compound of the formula (1) as defined in claim 1 , wherein W 1 , W 2 , W 3 , and W 5 are each selected from the group consisting of hydrogen and a compatible protecting group chosen from:
3. A macrocyclic compound of the formula (1) as defined in claim 1 , wherein W 1 , W 2 , W 3 , and W 5 each represents hydrogen.