6-AMIDO DERIVATIVES OF 4, 5-a EPOXYMORPHINANS FOR THE TREATMENT OF PAIN
a technology of epoxymorphinans and derivatives, applied in the field of 6amido derivatives of 4, 5aepoxymorphinans, can solve the problems of life-threatening respiratory depression in patients and unwanted peripheral side effects, and achieve the effect of lessening the liability of constipation and respiratory depression
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[0023]Analgesic compounds of the invention fall into two primary classes: compounds of general formula II, in which R1 is cyclopropylmethyl, and compounds of general formula I, in which R1 is not cyclopropylmethyl. The compounds of general formula I include a series in which R1 is allyl and one in which R1 is cyclobutylmethyl. When R1 is —CH2-Het, Het may be tetrahydrofuranyl.
[0024]In one aspect, the invention relates to compounds of formula I:
[0025]Some embodiments of the invention can be represented by the formula:
which is a subset of formula I. In these compounds, R1 is cyclobutylmethyl or allyl;
R2 is chosen from hydrogen, (C1-C6)acyl, (C1-C6)oxaalkyl, and (C1-C6)acyloxaalky;
R3 is hydrogen or methyl;
R4 is chosen from
(a) phenyl substituted at other than 2 or 6 with from one to three substituents chosen from bromo, chloro, iodo, hydroxy, nitro, cyano, (C1-C3)alkyl, (C1-C3)haloalkyl, (C1-C3)haloalkoxy, (C1-C3)alkoxy and R10;
(b) optionally substituted naphthylene;
(c) optionally subst...
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