Opioid Receptor Modulators with a Cinnamyl Group.

To obtain selective and potent opioid receptor ligands, we synthesized dehydro derivatives of alvimopan and found compound (28f), a selective but modest affinity MOR antagonist weaker than alvimopan (1). We replaced the arylpiperidine unit by an arylpiperazine to obtain the 1-(α-carboxycinnamyl)-4-arylpiperazines like 13h, which to our surprise had no MOR or DOR activity but was a KOR agonist with moderate affinity. In contrast, literature examples of arylpiperazines 4 and 5 were reported to be pan opioid receptor antagonists, while 6 was a MOR agonist.

Amodiaquine, an antimalarial drug, inhibits dengue virus type 2 replication and infectivity.

Dengue virus serotypes 1-4 (DENV1-4) are transmitted by mosquitoes which cause most frequent arboviral infections in the world resulting in ∼390 million cases with ∼25,000 deaths annually. There is no vaccine or antiviral drug currently available for human use. Compounds containing quinoline scaffold were shown to inhibit flavivirus NS2B-NS3 protease (NS2B-NS3pro) with good potencies.

Crystal structures of a new polymorphic form of gabapentin monohydrate and the e and z isomers of 4-tertiarybutylgabapentin.

Gabapentin, a widely used antiepileptic drug, crystallizes in multiple polymorphic forms. A new crystal form of gabapentin monohydrate in the space group Pbca is reported and the packing arrangement compared with that of a previously reported polymorph in the space group P2(1)/c [Ibers, J.A.

Chemistry of 1-fluoro-2,3,4-triphenylcyclobutadiene dimers.

The reaction of 2,4-dichloro-1,1-difluoro-3-phenyl-2-cyclobutene 1 with excess phenyllithium and subsequent transformations of the products have been reinvestigated. The phenyllithium reaction appears to proceed through the intermediacy of a fluorotriphenylcyclobutadiene 2 to produce a well-characterized dimeric trans-hexaphenyldifluorotricyclooctadiene 3a. Subsequent transformations of 3a gave a pentaphenyldihydrodifluoropentalene 4, which on acid hydrolysis formed a pentaphenyldihydropentalenone 5.