Nirogi, Ramakrishna; Mohammed, Abdul Rasheed; Shinde, Anil Karbhari; Gagginapally, Shankar Reddy; Kancharla, Durga Malleshwari; Ravella, Srinivasa Rao; Bogaraju, Narsimha; Middekadi, Vanaja Reddy; Subramanian, Ramkumar; Palacharla, Raghava Choudary; Benade, Vijay; Muddana, Nageswararao; Abraham, Renny; Medapati, Rajesh Babu; Thentu, Jagadeesh Babu; Mekala, Venkat Reddy; Petlu, Surendra; Lingavarapu, Bujji Babu; Yarra, Sivasekhar; Kagita, Narendra; Goyal, Vinod Kumar; Pandey, Santosh Kumar; Jasti, Venkat published their research in Journal of Medicinal Chemistry in 2021. The article was titled 《Discovery and Preclinical Characterization of Usmarapride (SUVN-D4010): A Potent, Selective 5-HT4 Receptor Partial Agonist for the Treatment of Cognitive Deficits Associated with Alzheimer’s Disease》.SDS of cas: 25637-16-5 The article contains the following contents:
A series of oxadiazole derivatives were synthesized and evaluated as 5-hydroxytryptamine-4 receptor (5-HT4R) partial agonists for the treatment of cognitive deficits associated with Alzheimer’s disease. Starting from a reported 5-HT4R antagonist, a systematic structure-activity relationship was conducted, which led to the discovery of potent and selective 5-HT4R partial agonist 1-isopropyl-3-{5-[1-(3-methoxypropyl) piperidin-4-yl]-[1,3,4]oxadiazol-2-yl}-1H-indazole oxalate (Usmarapride, 12l)(I). It showed balanced physicochem.-pharmacokinetic properties with robust nonclin. efficacy in cognition models. It also showed disease-modifying potential, as it increased neuroprotective soluble amyloid precursor protein alpha levels, and dose-dependent target engagement and correlation of efficacy with oral exposures. Phase 1 clin. studies have been completed and projected efficacious concentration was achieved without any major safety concerns. Phase 2 enabling long-term safety studies have been completed with no concerns for further development. In the experiment, the researchers used 4-Bromotetrahydropyran(cas: 25637-16-5SDS of cas: 25637-16-5)
4-Bromotetrahydropyran(cas: 25637-16-5) is often used as reactant for: nickel-catalyzed alkyl-alkyl Suzuki coupling reactions with boron reagents, preparation of a selective small-molecule melanocortin-4 receptor agonist with efficacy in a pilot study of sexual dysfunction in humans; preparation of aliphatic hydrocarbons via nickel-catalyzed Suzuki cross-coupling with alkylboranes.SDS of cas: 25637-16-5
Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics