Novel ester derivatives of buprenorphine and their preparation processes, and long acting analgestic pharmaceutical compositions

[0108] The following examples are given for the purpose of illustration only and are not intended to limit the scope of the present invention.

[0109] The following Table 1 shows the chemical structures of the preferred buprenorphine ester derivatives according to this invention

TABLE 1The molecular structures of buprenorphine HCl,buprenorphine base and the ester derivativesof according to this inventionCompoundMolecular structureBuprenorphine HClBup · HClBuprenorphine baseBupBuprenorphine propionateBuprenorphine pivalateBuprenorphine benzoateBuprenorphine enanthateBuprenorphine decanoateBuprenorphine palimitateDibuprenorphine pimelateDibuprenorphine sebacoyl ester

Bup: Buprenorphine

The buprenorphine ester derivatives listed in Table 1 can be synthesized by suitable known methods, such as those disclosed in U.S. Pat. Nos. 5,750,534 and 6,225,321.

Synthesis Ex. 1

Preparation of Buprenorphine Enanthate

[0110] 75 mL of methylene chloride (Mallinckrodt, Baker, U.S.A.) and 0.01 mole of bupr