Ong H H, Profitt J A, Spaulding T C, Wilker J C
J Med Chem. 1979 Jul;22(7):834-9. doi: 10.1021/jm00193a016.
A series of 10,11-dihydro-11-oxospiro[dibenz[b,f]oxepin-10,4'-piperdine] derivatives (II) was synthesized and evaluated for analgesic activity in the phenylquinone writhing assay (PQW) and the tail-flick test in mice. Preliminary structure-activity correlations indicate that optimum activity is associated with a short-chain (R less than or equal to C2) N substituent and a nuclear fluorine function, as exemplified by 9b. This compound, when administered orally, was equipotent to morphine in protecting against mouse writhing. The observation that the PQW activity of 9b remained relatively unchanged after naloxone challenge seems to favor a nonnarcotic profile.
合成了一系列10,11-二氢-11-氧代螺[二苯并[b,f]氧杂卓-10,4'-哌啶]衍生物（II），并在苯醌扭体试验（PQW）和小鼠甩尾试验中评估其镇痛活性。初步的构效关系表明，最佳活性与短链（R≤C2）N取代基和核氟官能团有关，如9b所示。该化合物口服给药时，在防止小鼠扭体方面与吗啡等效。纳洛酮激发后9b的PQW活性相对不变，这一观察结果似乎支持其非麻醉特性。
