CYCLIN GROOVE INHIBITORS

摘要

The present invention relates to a compound of formula (I), or a variant thereof, A - (B)m - C - (D)n- E, wherein m and n are each independently 0 or 1 and A, B, C, D and E are each independently linked to the respective adjacent residue by a linker group independently selected from carboxamide, reduced carboxamide, sulfonamide, imine, semicarbazone, oxime and ethanolamine; A is (i) a natural or unnatural amino acid residue having a side chain comprising at least one H-bond acceptor moiety and at least one H-bond donor moiety, or a derivative thereof; or (ii) R(CO), wherein R is a C1-C24 hydrocarbyl group comprising at least one H-bond acceptor moiety and optionally one or more H-bond donor moieties, and where R optionally contains one or more heteroatoms selected from S, O, and N, and is optionally substituted by one or more substituents selected from halogen, OMe, CN, CF3, and NO2; each of B and D is independently an amino acid residue selected from arginine, 4-(guanidinyl)phenylalanine (4-(Gu)Phe), piperidinylglycine (PipGly), piperidinylalanine (PipAla), pyridinylalanine, histamine, N,N-(dimethyl) lysine (DMLys), citrulline, glutamine, serine, lysine, asparagine, isoleucine and alanine, or a derivative thereof; C is NH-X-CO, where X is a C1-C4 alkylene group substituted by a straight-chain or branched C1-C6 alkylene group, said C1-C6 alkylene group optionally containing a H-bond donor or H-bond acceptor moiety; E is (i) a natural or unnatural amino acid residue having an aryl or heteroaryl side chain, or a derivative thereof; or (ii) NHR', where R' is a C1-C24 hydrocarbyl group, optionally containing one or more heteroatoms selected from N, O, and S, and optionally comprising one or more H-bond acceptor or donor moieties; said hydrocarbyl group further comprising a pendent C4-C12 aryl or heteroaryl group, which itself may be optionally substituted by one or more substituents selected from a H-bond donor moiety, a H-bond acceptor moiety, a halogen, Me, Et, Pr, CF3, CN and NO2; wherein at least one of A and E is other than a natural or unnatural amino acid residue when A, B, C, D and E are each linked to the respective adjacent residue by a carboxamide group.