Patent ID: 8183202

Claim:
A method for the treatment of a microbial infection of the lower intestine or colon in a subject in need there of, the method comprising administering to the subject a type-B lantibiotic of formula (Ia): wherein: A 1 is —C 1-4 alkyl; B 1 is —C 1-4 alkyl; X 1 is —OH or —NR 1A R 2A , wherein R 1A represents hydrogen, or an alkyl or heteroalkyl group, substituted by at least one hydroxyl substituent, and R 2A represents hydrogen, or an alkyl or heteroalkyl group, substituted by at least one hydroxyl substituent, or R 1A and R 2A taken together with the nitrogen atom represent a heterocyclic group having at least one hydroxyl substituent, wherein the heterocyclic group optionally further contains one or more heteroatoms, or R 1A and R 2A independently represent: (1) hydrogen; (2) a group of formula —(CH 2 ) n —NR 11 R 12 , in which n represents an integer from 2 to 12 and R 11 and R 12 independently represent hydrogen or (C 1 -C 4 ) alkyl or R 11 and R 12 taken together represent a group —(CH 2 ) 3 —, —(CH 2 ) 4 —, —(CH 2 ) 2 —O—(CH 2 ) 2 —, —(CH 2 ) 2 —S—(CH 2 ) 2 — or —(CH 2 ) 5 —; or R 1A and R 2A taken together with the adjacent nitrogen atom represent a piperazine moiety which may be substituted in position 4 with a substituent selected from: (a) (C 1 -C 4 )alkyl; (b) (C 5 -C 7 )-cycloalkyl, (c) pyridyl, (d) —(CH 2 ) p —NR 13 R 14 in which p represents an integer from 1 to 8 and R 13 and R 14 independently represent hydrogen or (C 1 -C 4 ) alkyl; (e) piperidinyl; (f) substituted piperidinyl, wherein the substituted piperidinyl bears a N-substituent which is (C 1-4 )alkyl; (g) benzyl; and (h) substituted benzyl, wherein a phenyl therein bears 1 or 2 substituents selected from chloro, bromo, nitro, (C 1 -C 4 )alkyl and (C 1 -C 4 )alkoxy; Z is an amino acid residue, —NR 3 R 4 , —NR 5 COR 6 , —NR 5 C(O)OR 6 ; —NR 5 SOR 6 , —NR 5 SO 2 R 6 ; —NR 5 C(S)NR 6 R 7 , —NR 5 C(NR 8 )NR 6 R 7 , or —N═R 9 , wherein each of these groups represents modifications of the N-terminus of the amino acid at position 1, and where R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are independently hydrogen, or a group, optionally substituted, selected from alkyl, heteroalkyl, aryl, heteroaryl, aralkyl and heteroaralkyl, with the proviso that R 9 is not hydrogen; and Y is —S— or —S(O)—; or a variant, derivative, pharmaceutically acceptable salt thereof wherein a variant is a compound where 1, 2, 3 or 4 amino acids at positions 2, 3, 4, 5, 8, 10, 11, 13 or 18 are substituted by another amino acid, and the another amino acid is a naturally occurring amino acid or its D-isoform, and a derivative is a compound where the carboxy function of a side chain of an internal residue, is modified from —COOH to a group —COOR 9 in which R 9 represents (C 1 -C 4 )alkyl or (C 1 -C 4 )alkoxy(C 2 -C 4 )alkyl, and wherein the type-B lantibiotic of formula (Ia) has an antimicrobial activity.