Compounds binding to the bacterial beta ring

摘要

The present invention relates to compounds which bind to the hydrophobic pocket of the β clamp, i.e., to the surface of the β ring with which said protein interacts with other proteins of the bacterial replication complex during DNA replication. These compounds are derived from the acetylated peptide AcQLDLF (P6) to improve their affinity to their target.

主权项

1. A compound of formula (I)wherein
Gln is glutamine; R is selected from the group consisting of a C1-12-alkyl group optionally substituted by a C6-10-aryl group, a C2-12-alkenyl group optionally substituted by a C6-10-aryl group, a C3-6-cycloalkyl group, a C6-10-aryl group optionally substituted by a C1-4-alkyl, and a C1-5-alkyl-(O—CH2—CH2)t— group with t being an integer from 0 to 20 inclusive; R1 is the side chain of arginine or lysine; R2 is a —(CH2)—C3-6-cycloalkyl group optionally substituted by a halogen and/or by a group selected from the group consisting of —NH2, —NH—CO—Ra, —CO2H, —NHRa and —NRaRb, wherein Ra and Rb are independently a C1-4-alkyl group; R3 is selected from the group consisting of a C1-8-alkyl group, the side chain of arginine or lysine, —(CH2)q—CO2R7a, —(CH2)q—CO—NHR7b, —CH2OR8 and —(CH2)qNHR9, wherein
q is 1, 2, 3 or 4,R7a is a hydrogen atom, a C1-8-alkyl group, a C4-12-alkylene group forming together with R6 a lactone or a polyether ring, or a C4-12-alkenylene, forming together with R6 a lactone or a polyether ring,R7b is a hydrogen atom, a C1-8-alkyl group, or —(CH2)q′—NH— with q′ being an integer between 2 and 8 inclusive and forming together with R6 a lactam,R8 is a hydrogen atom, a C1-8-alkyl group, a C4-12-alkylene group forming together with R6 a lactone or a polyether ring, or a C4-12-alkenylene, forming together with R6 a lactone or a polyether ring,R9 is a hydrogen atom, or R9 together with R6 form a lactam; R4 is a C1-8-alkyl group optionally substituted by a C3-6-cycloalkyl group, or a halogen-C1-4-alkyl group; R5 is selected from the group consisting of a —(CH2)—C3-6-cycloalkyl group; —(CH2—CH2)—C3-6-cycloalkyl group; a —(CH2)—C6-10-aryl group optionally substituted by a halogen, a C1-2 alkyl group and/or a C1-2 alkoxy group; a —(CH2—CH2)—C6-10-aryl group optionally substituted by a halogen, a C1-2 alkyl group and/or a C1-2 alkoxy group; a —(CH2)—C6-10-heteroaryl group optionally substituted by a halogen and/or a C1-2 alkyl group; and a —(CH2—CH2)—C5-10-heteroaryl group optionally substituted by a halogen and/or a C1-2 alkyl group; R6 is —CO2H, —CO2R10, —CO—NH2, —CO—NHR10, —OR10 when r is 1 or 2, —NH—CO—NHR10 when r is 1 or 2, or R6 is —CO—, —CO—O— or —O— and forms a lactam, a lactone, or a polyether ring with R7a, R7b, R8 or R9; wherein
R10 is a C1-8-alkyl group optionally substituted by a C6-10-aryl group; a C3-6-cycloalkyl group; a C6-10-aryl group optionally substituted by a halogen, a C1-2-alkyl group and/or a C1-2-alkoxy group; m is 0 or 1; n is an integer from 0 to 9 inclusive; p is an integer from 0 to 10 inclusive; r is 0, 1 or 2.