73931-64-3Relevant articles and documents
Metal-chelating benzothiazole multifunctional compounds for the modulation and 64Cu PET imaging of Aβ aggregation
Bandara, Nilantha,Cho, Hong-Jun,Huang, Yiran,Mirica, Liviu M.,Rogers, Buck E.,Sun, Liang,Tran, Diana
, p. 7789 - 7799 (2020/08/19)
While Alzheimer's Disease (AD) is the most common neurodegenerative disease, there is still a dearth of efficient therapeutic and diagnostic agents for this disorder. Reported herein are a series of new multifunctional compounds (MFCs) with appreciable affinity for amyloid aggregates that can be potentially used for both the modulation of Aβ aggregation and its toxicity, as well as positron emission tomography (PET) imaging of Aβ aggregates. Firstly, among the six compounds tested HYR-16 is shown to be capable to reroute the toxic Cu-mediated Aβ oligomerization into the formation of less toxic amyloid fibrils. In addition, HYR-16 can also alleviate the formation of reactive oxygen species (ROS) caused by Cu2+ ions through Fenton-like reactions. Secondly, these MFCs can be easily converted to PET imaging agents by pre-chelation with the 64Cu radioisotope, and the Cu complexes of HYR-4 and HYR-17 exhibit good fluorescent staining and radiolabeling of amyloid plaques both in vitro and ex vivo. Importantly, the 64Cu-labeled HYR-17 is shown to have a significant brain uptake of up to 0.99 ± 0.04 percentID per g. Overall, by evaluating the various properties of these MFCs valuable structure-activity relationships were obtained that should aid the design of improved therapeutic and diagnostic agents for AD. This journal is
Phosphodiesterase inhibitors. Part 3: Design, synthesis and structure-activity relationships of dual PDE3/4-inhibitory fused bicyclic heteroaromatic-dihydropyridazinones with anti-inflammatory and bronchodilatory activity
Ochiai, Koji,Takita, Satoshi,Eiraku, Tomohiko,Kojima, Akihiko,Iwase, Kazuhiko,Kishi, Tetsuya,Fukuchi, Kazunori,Yasue, Tokutaro,Adams, David R.,Allcock, Robert W.,Jiang, Zhong,Kohno, Yasushi
experimental part, p. 1644 - 1658 (2012/04/23)
(-)-6-(7-Methoxy-2-trifluoromethylpyrazolo[1,5-a]pyridin-4-yl)-5-methyl-4, 5-dihydro-3-(2H)-pyridazinone (KCA-1490) is a dual PDE3/4 inhibitor that exhibits potent combined bronchodilatory and anti-inflammatory activity. A survey of potential bicyclic heteroaromatic replacement subunits for the pyrazolo[1,5-a]pyridine core of KCA-1490 has identified the 4-methoxy-2- (trifluoromethyl)benzo[d]thiazol-7-yl and 8-methoxy-2-(trifluoromethyl)quinolin- 5-yl analogues as dual PDE3/4-inhibitory compounds that potently suppress histamine-induced bronchoconstriction and exhibit anti-inflammatory activity in vivo.
Synthesis and biological evaluation of alkyl, alkoxy, alkylthio, or amino-substituted 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones
Inoue, Hirozumi,Konda, Mikihiko,Hashiyama, Tomiki,Otsuka, Hisao,Watanabe, Akishige,Gaino, Mitsunori,Takahashi, Kaoru,Date, Tadamasa,Okamura, Kimio,Takeda, Mikio,Narita, Hiroshi,Murata, Sakae,Odawara, Akio,Sasaki, Haruhiko,Nagao, Taku
, p. 1008 - 1026 (2007/10/03)
2,3-Dihydro-1,5-benzothiazepin-4(5H)-ones substituted with an alkyl, alkoxy, alkylthio, hydroxy, or amino group on the fused benzene ring of the 1,5-benzothiazepine skeleton were synthesized and their vasodilating, antihypertensive, and platelet aggregation-inhibitory activities were investigated. (-)-cis-3-Acetoxy-5-[2-(dimethylamino)ethyl]-2,3-dihydro-8- methyl-2-(4-methylphenyl)-1,5-benzothiazepin-4(5H)-one ((-)-13e) was selected for further studies as a potent inhibitor of platelet aggregation.
