| 摘要 |
Disclosed is a pharmaceutically acceptable base addition salt, other than a multivalent metal salt, of a boronic acid of formula (I) wherein: Y comprises a hydrophobic moiety which, together with the aminoboronic acid residue -NHCH(R9)-B(OH)2, has affinity for the substrate binding site of thrombin; and R9 is a straight chain alkyl group interrupted by one or more ether linkages and in which the total number of O and C atoms is 3, 4, 5 or 6 or R9 is -(CH2)m-W where m is 2, 3, 4 or 5 and W is -OH or halogen; and when YCO- is an optionally N-terminally protected dipeptide residue, the peptide linkages in the acid are optionally and independently N-substituted by a C1-C13 hydrocarbyl group optionally containing in-chain or in-ring N, O or S and optionally substituted by a substituent selected from halo, OH and trifluoromethyl. Also disclosed is an oral medicament comprising a salt of a boronic acid which is a selective thrombin inhibitor and has a neutral aminoboronic acid residue capable of binding to the thrombin S1 subsite linked through a peptide linkage to a hydrophobic moiety capable of binding to the thrombin S2 and S3 subsites, the salt comprising a boronate species derived from the boronic acid and a cation other than a multivalent metal action having a valency n and having an observed stoichiometry consistent with a notional stoichiometry (boronic acid:cation) of n:1. Compounds and medicaments of the type disclosed are useful for treating thrombosis by way of prophylaxis or therapy.
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