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US 6,958,358 B2Granted
Inhibitors of cruzipain and other cysteine proteases
AssigneeAmura Therapeutics Limited
InventorsMartin Quibell, Manoj Kumar Ramjee
Life of this patent
Estimating the term…
Abstract
Compounds of general formula (I): wherein R1, Y, (X)o, (W)n, (V)m, Z and U are as defined in the specification, are inhibitors of cruzipain and other cysteine protease inhibitors and are useful as therapeutic agents, for example in Chagas' disease, or for validating therapeutic target compounds.
Claims35
A compound according to general formula (I):
- wherein:
- R1=C0-7-alkyl (when C=0, R1 is simply hydrogen), C3-6-cycloalkyl or Ar—C0-7-alkyl (when C=0, R1 is simply an aromatic moiety Ar);
- Ar is an aromatic moiety which is a 5- or 6-membered monocyclic or 9- or 10-membered bicyclic ring, wherein the aromatic ring is optionally substituted;
- Z=O or S;
- Y=CR5R6—CO, where R5 and R6 are independently chosen from C0-7-alkyl, C3-6-cycloalkyl or Ar—C0-7-alkyl;
- (X)o=CR7R8, where R7 and R8 are independently chosen from C0-7-alkyl, C3-6-cycloalkyl and Ar—C0-7-alkyl and o is a number from zero to three;
- (W)n=O, S, C(O), S(O) or S(O)2 or NR9, where R9 is chosen from C0-7-alkyl, C3-6-cycloalkyl and Ar—C0-7-alkyl and n is zero or one;
- (V)m=C(O), C(S), S(O), S(O)2, S(O)2NH, OC(O), NHC(O), NHS(O), NHS(O)2, OC(O)NH, C(O)NH or CR10OR11, where R10 and R11 are independently chosen from C0-7-alkyl, C3-6-cycloalkyl, Ar—C0-7-alkyl and m is a number from zero to three, provided that when m is greater than one, (V)m contains a maximum of one carbonyl or sulphonyl group;
- U=a stable 5- to 7-membered monocyclic or a stable 8- to 11-membered bicyclic ring which is either saturated or unsaturated and which includes zero to four heteroatoms (as detailed below), said ring selected from:
- wherein R12 is:
- C0-7-alkyl, C3-6-cycloalkyl, Ar—C0-7-alkyl, O—C0-7-alkyl, O—C3-6-cycloalkyl, O—Ar—C0-7-alkyl, S—C0-7-alkyl, S—C3-6-cycloalkyl, S—Ar—C0-7-alkyl, NH—C0-7-alkyl, NH—C3-6-cycloalkyl, NH—Ar—C0-7-alkyl, N(C0-7-alkyl)2, N(C3-6-cycloalkyl)2 or N(Ar—C0-7-alkyl)2 or, when it is part of the group CHR12 or CR12, R12 may be halogen;
- A is chosen from:
- CH2, CHR12, O, S and NR13;
- wherein R12 is as defined above and R13 is chosen from:
- C0-7-alkyl, C3-6-cycloalkyl and Ar—C0-7-alkyl;
- B, D and G are independently chosen from:
- CR12, where R12 is as defined above, or N;
- E is chosen from:
- CH2, CHR12, O, S and NR13, where R12 and R13 are defined as above;
- J, L, M, R, T, T2, T3 and T4 are independently chosen from:
- CR12 and N, where R12 is as defined above;
- T5 is chosen from:
- CH or N;
- q is a number from one to three, thereby defining a 5-, 6- or 7-membered ring.
21 more elements
Dependencies are inferred from the claim text.