2-(Piperidin-3-yl)phthalimides reduce classical markers of cellular inflammation in LPS-challenged RAW 264.7 cells and also demonstrate potentially relevant sigma and serotonin receptor affinity in membrane preparations

Bioorganic & Medicinal Chemistry Letters, Год журнала: 2024, Номер 110, С. 129885 - 129885

Опубликована: Июль 10, 2024

Herein, we report the synthesis of new 4-amino-2-(piperidin-3-yl)isoindoline-1,3-diones and their biological evaluation in a series vitro experiments. The synthetic production these materials was initiated upon condensation appropriate nitrophthalic acid derivatives with various 3-aminopiperidines; subsequent reduction provided final products moderate to good yields. Readily available chiral pool reagents facilitated entry into optically enriched samples, while piperidine scaffold furnished variety amide alkylated entries. In total, 16 candidates were produced, ensuing treatment LPS-challenged RAW cells effected slight reductions secreted TNF-α but more robust dose-dependent declines nitrite IL-6 levels relative basal amounts, all concurrent maintenance cellular viability across concentration ranges screened. secondary amine cohort including rac-6, (R)-7, (S)-8 rendered most pronounced IL-6. When dosed at 30 μM, (R)-7 demonstrated compelling effects, decreases 32 % 40 for IL-6, respectively. Notable inflammatory markers also observed 19 which (14 %), (19 (11 %) when treated μM. Additionally, four representative compounds further evaluated against numerous CNS receptors, channels, transporters, 6, 9, demonstrating varying degrees nanomolar-to-low-micromolar binding σ-1 σ-2 receptors serotonin 5HT

Язык: Английский

---

Clinical Update on an Anti-Alzheimer Drug Candidate CT1812: A Sigma-2 Receptor Antagonist

Clinical Therapeutics, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

---

Multitarget-Directed Ligands Hitting Serotonin Receptors: A Medicinal Chemistry Survey

Pharmaceuticals, Год журнала: 2024, Номер 17(9), С. 1238 - 1238

Опубликована: Сен. 19, 2024

Serotonin (5-hydroxytryptamine, 5-HT) is a ubiquitous neurotransmitter in the human body. In central nervous system, 5-HT affects sleep, pain, mood, appetite, and attention, while peripheral modulates peristalsis, mucus production, blood vessel dilation. Fourteen membrane receptors mediate activity. agreement with crucial roles played by 5-HT, many drugs target (5-HTRs). Therefore, it unsurprising that efforts have been devoted to discovering multitarget-directed ligands (MTDLs) capable of engaging one or more 5-HTRs plus another phenotypically linked particular disease. this review, we will describe medicinal chemistry designing MTDLs encompassing activity for 5-HTRs, starting atypical antipsychotics moving dual 5-HT1AR/serotonin transporter ligands, 5-HT6R antagonists/acetyl cholinesterases inhibitors, 5-HT4R agonists/acetyl inhibitors. We also provide an outlook on most recent made field.

Язык: Английский

---

Neuroprotective Effect of Sigma-2 Modulator CT2074 in a Mouse Model of Ocular Hypertension

Experimental Eye Research, Год журнала: 2024, Номер 249, С. 110143 - 110143

Опубликована: Окт. 30, 2024

Язык: Английский

---

A review of the mechanisms involved in the neuroprotection and neurotoxicity of Iboga alkaloids

Pharmacological Research - Natural Products, Год журнала: 2023, Номер 1, С. 100006 - 100006

Опубликована: Ноя. 28, 2023

Язык: Английский

---