| 摘要 |
We describe ultra-short, short, and intermediate duration neuromuscular blocking compounds, reversible by cysteine or similar compounds, that are bisquaternary diesters of chlorofumaric, fumaric, or maleic acids where the quaternary groups are very different, creating a highly asymmetrical molecule where one quaternary includes an isoquinolinium ring system and the other includes a morpholinium, piperidinium, piperazinium, or pyrrolidinium system, pharmaceutical compositions, methods to use such compounds and compositions, and kits. |
| 主权项 |
1. A neuromuscular blocking agent of formula (I) wherein each of R1 and R2 is independently selected from the group hydrogen and halogen, and R1 and R2 can be disposed in a cis or a trans configuration on the two double-bonded carbon atoms to which R1 and R2 are respectively bonded; T is selected from the group CH2 and CH3, wherein if T is CH3, the phenyl group with the X1-X5 substituents is not present; B is selected from the group CH2, O, NR, and a direct single bond, wherein R is H, (C1-6)alkyl, or (C1-6)acyl; n1 and n2 are each independently equal to 0, 1, 2, or 3; each of X1, X2, X3, X4, and X5, is independently at each occurrence hydrogen, hydroxy or methoxy, or any two adjacent X1, X2, X3, X4, or X5, together form a methylenedioxy or ethylenedioxy group; each of Y1, Y2, Y3, Y4, and Y5, is independently at each occurrence hydrogen, hydroxy or methoxy, or any two adjacent Y1, Y2, Y3, Y4, or Y5, together form a methylenedioxy or ethylenedioxy group; each of Z1, Z2, Z3, and Z4, is independently at each occurrence hydrogen, hydroxy or methoxy, or any two adjacent Z1, Z2, Z3, or Z4, together form a methylenedioxy or ethylenedioxy group; W is selected from the group methyl and a benzyl group of formula: wherein each of A1, A2 A3, A4, and A5, is independently at each occurrence hydrogen or methoxy, or any two adjacent A1, A2 A3, A4, or A5, together form a methylenedioxy or ethylenedioxy group, and a wavy line indicates a point of bonding; and, wherein each Q⊖ is an independently selected pharmaceutically acceptable anion. |
