Abstract:
The present invention relates to ketamine derivs. of the formula I (wherein Y1 is -C2-6aliphaticC(O)OR1, -C2-6aliphaticOC(O)R1, etc.; Y2 is hydrogen or R2; R1 and R2 are (un)substituted C1-6aliph.; X1 and X2 are each independently hydrogen, R2, halo, NO2, etc.), pharmaceutical compns. comprising them, and methods for treating pain comprising administering them, and their use in the manuf. of medicaments for treating pain. The present invention also relates to methods for anesthetizing and methods for sedating a subject comprising administering ketamine derivs. of the formula II, wherein Y11 is -C1-6aliphaticC(O)OR1, etc. Synthetic procedures for prepg. I and II are exemplified. Example compd. III-HCl was prepd. by a multistep synthesis that culminated in reaction of norketamine with 3-bromopropyl acetate and treatment of the oil formed with HCl to form the salt. Biol. tests showed that short-chain aliph. ester analogs of ketamine broadly retained ketamine's desirable anesthetic and analgesic activities, yet were metabolized to the more polar and inactive acids sufficiently rapidly to minimize the drawbacks of ketamine itself in this capacity.