New sulfanyl butanoyl derivatives as inhibitors of Botulinum Type B activity, useful for e.g. the treatment of botulism and dystonias

摘要

Sulfanyl butanoyl derivatives (I) and their derivatives are new. Sulfanyl butanoyl derivatives of formula (I) and their derivatives are new; X = H, NH2, or NHR; R = alkyl or aralkyl; R1 = H, -S-R', or -SCH(CH(R2)X)-CO-R3; R' = alkyl, aryl, arylalkyl, cycloalkyl, or cycloalkyl alkyl, optionally substituted by one or more groups selected from halogen and CF3; R2 = alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkyl alkyl, aryl, arylalkyl, optionally substituted by a group selected from -COOH, -COOR, -SO3H, -SO3R, -PO3H2, and -PO3R2; R2 = alkyl, aryl, arylalkyl, cycloalkyl, or cycloalkyl alkyl, optionally substituted by halogens or CF3; R3 = -NHR4, or -(AA)nR5; R4 = alkyl, cycloalkyl, cycloalkyl alkyl, aryl, arylalkyl, heteroaryl or heteroaryl alkyl; n = 1 or 2 such that when n is 2 the two groups AA may be the same or different; R5 = OH, NH2, or NHR'; R' = alkyl, aryl, cycloalkyl, cycloalkyl alkyl, arylalkyl, heteroaryl, or heteroaryl alkyl; AA = an amino acid residue of formula (II) m = 0 or 1; p = 0 or 1; R6 = H or alkyl; R7 = alkyl, arylalkyl, or heteroaryl alkyl optionally substituted by one or more halogens, OH, alkoxy or CF3 groups. Independent claims are also included for: (1) pharmaceutical compositions containing (I) optionally with a clostridial toxin, and optionally covalently linked to a vectorizing peptide; (2) the preparation of (I); and (3) a diagnostic system for the detection of botulinum neurotoxins that contain a compound of formula (I).