Hagenow, Stefanie’s team published research in Journal of Medicinal Chemistry in 64 | CAS: 377727-87-2

Hagenow, Stefanie published the artcileAdenosine A_2AR/A₁R Antagonists Enabling Additional H₃R Antagonism for the Treatment of Parkinson’s Disease, Synthetic Route of 377727-87-2, the publication is Journal of Medicinal Chemistry (2021), 64(12), 8246-8262, database is CAplus and MEDLINE.

Adenosine A₁/A_2A receptors (A₁R/A_2AR) represent targets in nondopaminergic treatment of motor disorders such as Parkinson’s disease (PD). As an innovative strategy, multitargeting ligands (MTLs) were developed to achieve comprehensive PD therapies simultaneously addressing comorbid symptoms such as sleep disruption. Recognizing the wake-promoting capacity of histamine H₃ receptor (H₃R) antagonists in combination with the “caffeine-like effects” of A₁R/A_2AR antagonists, we designed A₁R/A_2AR/H₃R MTLs, where a piperidino-/pyrrolidino(propyloxy)phenyl H₃R pharmacophore was introduced with overlap into an adenosine antagonist arylindenopyrimidine core. These MTLs showed distinct receptor binding profiles with overall nanomolar H₃R affinities (K_i < 55 nM). Compound 4 (ST-2001, K_i (A₁R) = 11.5 nM, K_i (A_2AR) = 7.25 nM) (I) and 12 (ST-1992, K_i (A₁R) = 11.2 nM, K_i (A_2AR) = 4.01 nM) (II) were evaluated in vivo. L-DOPA-induced dyskinesia was improved after administration of compound 4 (1 mg kg^-1, i.p. rats). Compound 12 (2 mg kg^-1, p.o. mice) increased wakefulness representing novel pharmacol. tools for PD therapy.

Journal of Medicinal Chemistry published new progress about 377727-87-2. 377727-87-2 belongs to triazoles, auxiliary class GPCR/G Protein,Adenosine Receptor, name is 2-(Furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, and the molecular formula is C25H29N9O3, Synthetic Route of 377727-87-2.

Referemce:
https://en.wikipedia.org/wiki/1,2,3-Triazole,
Triazoles – an overview | ScienceDirect Topics