78326-88-2Relevant articles and documents
Adenosine A2AR/A1R Antagonists Enabling Additional H3R Antagonism for the Treatment of Parkinson’s Disease
Hagenow, Stefanie,Affini, Anna,Pioli, Elsa Y.,Hinz, Sonja,Zhao, Yan,Porras, Gregory,Namasivayam, Vigneshwaran,Müller, Christa E.,Lin, Jian-Sheng,Bezard, Erwan,Stark, Holger
supporting information, p. 8246 - 8262 (2021/06/30)
Adenosine A1/A2Areceptors (A1R/A2AR) 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 H3receptor (H3R) antagonists in combination with the “caffeine-like effects” of A1R/A2AR antagonists, we designed A1R/A2AR/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 (Kii(A1R) = 11.5 nM,Ki(A2AR) = 7.25 nM) and 12( ST-1992,Ki(A1R) = 11.2 nM,Ki(A2AR) = 4.01 nM) were evaluatedin 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 pharmacological tools for PD therapy.
METHODS OF DOSE ADMINISTRATION FOR TREATING OR PREVENTING COGNITIVE IMPAIRMENT USING INDANE ACETIC ACID DERIVATIVES
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Paragraph 0390; 0391, (2018/06/15)
The present invention provides indane acetic acid and their derivatives and methods for the treating and/or preventing of cognitive disorders.
A photo-favorskii ring contraction reaction: The effect of ring size
Kammath, Viju Balachandran,?olomek, Tomá?,Ngoy, Bokolombe Pitchou,Heger, Dominik,Klán, Petr,Rubina, Marina,Givens, Richard S.
, p. 1718 - 1729 (2013/03/29)
The effect of ring size on the photo-Favorskii induced ring-contraction reaction of the hydroxybenzocycloalkanonyl acetate and mesylate esters (7a-d, 8a-c) has provided new insight into the mechanism of the rearrangement. By monotonically decreasing the ring size in these cyclic derivatives, the increasing ring strain imposed on the formation of the elusive bicyclic spirocyclopropanone 20 results in a divergence away from rearrangement and toward solvolysis. Cycloalkanones of seven or eight carbons undergo a highly efficient photo-Favorskii rearrangement with ring contraction paralleling the photochemistry of p-hydroxyphenacyl esters. In contrast, the five-carbon ring does not rearrange but is diverted to the photosolvolysis channel avoiding the increased strain energy that would accompany the formation of the spirobicyclic ketone, the "Favorskii intermediate 20". The six-carbon analogue demonstrates the bifurcation in reaction channels, yielding a solvent-sensitive mixture of both. Employing a combination of time-resolved absorption measurements, quantum yield determinations, isotopic labeling, and solvent variation studies coupled with theoretical treatment, a more comprehensive mechanistic description of the rearrangement has emerged.
