Triplet drugs

As mentioned above, the twin drug 72 (Fig. 19) was also prepared from naltrexone (1) and showed s receptor antagonist activity [88], In the course of the synthetic investigation of 72, we unexpectedly obtained a triplet drug 73 with a 1,3,5-trioxazatriquinane skeleton (red color in Fig. 19). 

Keywords Dual action Increment of potency Receptor dimerization Twin drug Triplet drug... 

Excellent reviews about twin drugs with opioid pharmacophores have been published [25-27], including those that discuss peptidic twin drugs [27-29]. The following chapter will mainly focus on the twin and triplet drugs whose in vivo pharmacological effects have been evaluated, and will include a description of their pharmacology and synthesis. 

Attempts to prepare triplet drugs 104 having morphinan structures without a 4,5-epoxy bridge gave not the desired compound 104 but the unexpected rearrangement product 105 [162] (Fig. 21). 

Many twin drugs and triplet drugs have been synthesized and evaluated for their pharmacological effects including in vivo pharmacological effects. Some compounds, such as MCL-144 (13b), MCL-145 (17), and triplet drug 95, showed... 

Fig. 19 Structures of triplet drug 95 and twin drug 96 with a capped structure...

Scheme 8 Synthesis of triplet drug 99. Reagents and conditions (a) NH4CI, AcONa, MeOH, reflux, (R)-97 46%, (S)-97 9% (b) CSA, CHC13, reflux, 68% from (R)-97 (c) BBr3, CH2C12, rt, 80%...

The eighth chapter, Twin and Triplet Drugs in Opioid Research, by Hideaki Fujii, presents opioid research that used dimer and trimer ligands as a tool for investigating opioid receptors. The dimer and trimer constructs were able to increase ligand activity and selectivity. 

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