In 2016,Brullo, Chiara; Ricciarelli, Roberta; Prickaerts, Jos; Arancio, Ottavio; Massa, Matteo; Rotolo, Chiara; Romussi, Alessia; Rebosio, Claudia; Marengo, Barbara; Pronzato, Maria Adelaide; van Hagen, Britt T. J.; van Goethem, Nick P.; D’Ursi, Pasqualina; Orro, Alessandro; Milanesi, Luciano; Guariento, Sara; Cichero, Elena; Fossa, Paola; Fedele, Ernesto; Bruno, Olga published 《New insights into selective PDE4D inhibitors: 3-(Cyclopentyloxy)-4-methoxybenzaldehyde O-(2-(2,6-dimethylmorpholino)-2-oxoethyl) oxime (GEBR-7b) structural development and promising activities to restore memory impairment》.European Journal of Medicinal Chemistry published the findings.Category: bromides-buliding-blocks The information in the text is summarized as follows:
Phosphodiesterase type 4D (PDE4D) has been indicated as a promising target for treating neurodegenerative pathologies such as Alzheimer’s Disease (AD). By preventing cAMP hydrolysis, PDE4 inhibitors (PDE4Is) increase the cAMP response element-binding protein (CREB) phosphorylation, synaptic plasticity and long-term memory formation. Pharmacol. and behavioral studies on the authors’ hit GEBR-7b demonstrated that selective PDE4DIs could improve memory without causing emesis and sedation. The hit development led to new mol. series, herein reported, characterized by a catechol structure bonded to five member heterocycles. Mol. modeling studies highlighted the pivotal role of a polar alkyl chain in conferring selective enzyme interaction. Compound 1-{3-[3-(cyclopentyloxy)-4-methoxyphenyl]-1H-pyrazol-1-yl}-3-morpholin-4-ylpropan-2-oldihydrochloride (8a) showed PDE4D3 selective inhibition and was able to increase intracellular cAMP levels in neuronal cells, as well as in the hippocampus of freely moving rats. Furthermore, 8a was able to readily cross the blood-brain barrier and enhanced memory performance in mice without causing any emetic-like behavior. These data support the view that PDE4D is an adequate mol. target to restore memory deficits in different neuropathologies, including AD, and also indicate compound 8a as a promising candidate for further preclin. development. After reading the article, we found that the author used Methyl 3-bromopropanoate(cas: 3395-91-3Category: bromides-buliding-blocks)
Methyl 3-bromopropanoate(cas: 3395-91-3) belongs to bromides. One prominent application of synthetic organobromine compounds is the use of polybrominated diphenyl ethers as fire-retardants, and in fact fire-retardant manufacture is currently the major industrial use of the element bromine.Category: bromides-buliding-blocks
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary