Optically active fluorinated vasoconstrictors, methods for making them, and anesthetic formulations comprising them
申请人:——
公开号:US20040002549A1
公开(公告)日:2004-01-01
(R)-6F-phenylephrine, essentially free of (S)-6F-phenylephrine, and an anesthetic formulation comprising (R)-6F-epinephrin or (R)-6F-phenylephrine and having improved stability compared to formulations containing their non-fluorinated analog, are disclosed. Further disclosed is a method of providing vasoconstriction in a mammal by administering the anesthetic formulation. The anesthetic composition can include an anesthetic, an (R)-chiral compound having the structure:
1
wherein R
1
, R
2
, and R
4
are independently selected from —H or —F, at least one of R
1
, R
2
, and R
4
is —F, and R
3
is selected from —OH, —H or —F, or a pharmaceutically acceptable salt or ester thereof, said vasoconstrictor being essentially free of the (S)-chiral form. Also, a method of chiral addition of cyanide to a ring-fluorinated phenaldehyde, employing an almond hydroxynitrile lyase enzyme, provided in the form of a reversibly soluble polymer conjugate ((R)-Finezyme™-H series biocatalysts) is disclosed. Several such biocatalysts are disclosed.
(R)-6F-苯肾上腺素,基本上不含(S)-6F-苯肾上腺素,并且包括(R)-6F-肾上腺素或(R)-6F-苯肾上腺素的麻醉制剂,其相比含有它们非氟化类似物的制剂具有改善的稳定性,已被披露。此外,还披露了通过给予哺乳动物麻醉制剂来提供血管收缩的方法。麻醉组合物可以包括麻醉剂、具有结构的(R)-手性化合物:其中R1、R2和R4独立地选择自—H或—F,R1、R2和R4中至少一个是—F,R3选择自—OH、—H或—F,或其药用可接受的盐或酯,所述血管收缩剂基本上不含(S)-手性形式。此外,还披露了一种利用杏仁羟基亚硝基酰酶酶将氰化物立体加到环氟化苯甲醛的方法,采用可逆溶解聚合物共轭形式提供(R)-Finezyme™-H系列生物催化剂。还披露了几种这样的生物催化剂。