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The cyclopropylmethyl group in classical δ opioid receptor (DOR) antagonist NTI, BNTX, and NTB was replaced with various electron-withdrawing groups to develop DOR inverse agonists. N-Benzyl NTB derivative SYK-657 was a potent DOR full inverse agonist and its potency was over 10-fold potent than that of a reference compound ICI-174,864. Intraperitoneal administration of SYK-657 induced the short-term memory improving effect in mice without abnormal behaviors.

Transgender women—individuals assigned a male sex at birth who identify as women, female, or on the male-to-female (MTF) trans feminine spectrum—are at high-risk of HIV worldwide. Prior research has suggested that transgender women more frequently engage in condomless sex with primary cisgender (i.e. non-transgender) male partners compared with casual or paying partners, and that condomless sex in this context might be motivated by relationship dynamics such as trust and intimacy. The current study examined sexual agreement types and motivations as factors thatshape HIV risk behaviors in a community sample of 191 transgender women and their cisgenderprimary male partners who completed a cross-sectional survey. Overall, 40% of couples had monogamous, 15% open, and 45% discrepant sexual agreements (i.e., partners disagreed on their type of agreement). Actor-partner interdependence models (APIM) were fit to examine the influence of sexual agreement type and motivations on extra-dyadic HIV risk (i.e., condomless sex with outside partners) and intra-dyadic HIV serodiscordant risk (i.e., condomless sex with serodiscordant primary partners). Formale partners, extra-dyadic risk was associated with their own and their partners' sexual agreement motives, and male partners who engaged in extra-dyadic HIV risk had an increased odds of engaging in HIV serodiscordant intra-dyadic risk. Study findings supportinclusion ofthe male partners of transgender women into HIV prevention efforts. Future research is warranted to explore the interpersonal and social contexts of sexual agreement types and motivations in relationships between transgender women and their male partners to develop interventions that meet their unique HIV prevention needs.

We synthesized derivatives of the δ opioid receptor (DOR) antagonists naltrindole (NTI) and compound 1 that were modified with small alkyl or fluorinated ethyl substituents on the 17-nitrogen. Although the derivatives showed decreased binding affinities for the opioid receptors, their selectivities for the DOR were higher than the parent compounds NTI and compound 1. Surprisingly, 17-fluoroethyl NTI derivatives exerted DOR inverse agonistic activities. The DOR inverse agonism of compounds 4c–e was less efficacious but significant, as compared with a standard DOR inverse agonist ICI-174864. On the other hand, compound 1 and its derivatives with small alkyl or monofluoroethyl substituents were partial agonists, but the derivatives having di- or trifluoroethyl group showed neither agonistic nor inverse agonistic activities.

As the reports about C-homomorphinans with the seven-membered C-ring are much fewer than those of morphinan derivatives with a six-membered C-ring, we attempted to synthesize C-homomorphinan derivatives and to evaluate their opioid activities. C-Homomorphinan 5 showed sufficient binding affinities to the opioid receptors. C-Homomorphinan derivatives possessing the δ address moiety such as indole (NTI-type), quinoline, or benzylidene (BNTX-type) functionalities showed the strongest binding affinities for the δ receptor among the three types of opioid receptors, which indicated that the C-homomorphinan skeleton sufficiently functions as a message-part in the ligand. Although NTI-type compound 8 and quinoline compound 9 with C-homomorphinan scaffold exhibited lower affinities and selectivities for the δ receptor than the corresponding morphinan derivatives did, both the binding affinity and selectivity for the δ receptor of BNTX-type compound 12 with a seven-membered C-ring were improved compared with the corresponding compounds with a six-membered C-ring including BNTX itself. BNTX-Type compound 12 was the most selective δ receptor antagonist among the tested compounds.