Thomas H. Althuis

Selective and potent analgetics derived from cannabinoids.

Abstract: Based on the hypothesis that analgetic activity is a dissociable feature of the cannabinoid molecule, we examined modifications of the side chain, the phenolic moiety, and, most significantly, structures that lack the benzopyran functionality present in THC and (—)‐9‐nor‐9β‐hydroxyhexahydrocannabinol (HHC). A new grouping, the 1‐methyl‐4‐phenylbutyloxy C‐3 side chain, elaborates a unique lipopholic region. Replacement of the phenol substituent produced several derivatives which retain analgetic activity in the codeine potency range. Introduction of a weakly basic nitrogen at C‐5 and deletion of the axial methyl group in the B ring, two structural changes forbidden by traditional cannabinoid SAR, resulted in a unique family of benzoquinolines with potent analgetic activity. The prototype of this series, levonantradol, exhibits potent and stereospecific analgetic and antiemetic activity.

A Therapeutic and Economic Comparison of the Top Innovative New Drugs of the 1970s and 1980s

The economically most important drugs introduced in the US in the 1980s represented distinct therapeutic advances over those of the 1970s. However, most recently, the strong post- World War II technological leadership of US based companies is clearly being challenged. Of the top 36 new chemical entities (NCEs) approved and marketed in the US in the 1980s, US based companies received a significantly smaller market share than they did for those NCEs approved in the 1970s, while during the same period, foreign based companies more than doubled their share of NCEs in this critical portion of the US market. Furthermore, discoveries of top drugs by US based companies decreased even more markedly from the 1970s to the 1980s. US based companies were able to continue to maintain their dominance in the upper end of the US market in the 1980s only by licensing more drugs from foreign sources. A cohesive set of national policies is needed to assure strong US leadership through the 1990s.