623550-16-3Relevant academic research and scientific papers
Novel 3,4,7-substituted benzofuran derivatives having binding affinity to κ-opioid receptor
Nishiyama, Daisuke,Sakai, Yuki,Sekiguchi, Haruka,Chiba, Hiroaki,Misu, Ryosuke,Oishi, Shinya,Fujii, Nobutaka,Ohno, Hiroaki
, p. 996 - 1003 (2016)
A series of novel 3,4,7-trisubstituted benzofuran derivatives were synthesized, and their binding affinity to κ- (KOR) and μ-opioid receptors (MOR) were evaluated. Several aryl ethers showed moderate binding activities to KOR (IC50=3.9-11 μM) without binding to MOR.
Total Synthesis of Galanthamine and Lycoramine Featuring an Early-Stage C-C and a Late-Stage Dehydrogenation via C-H Activation
Zhang, Yuna,Shen, Shuna,Fang, Hua,Xu, Tao
supporting information, p. 1244 - 1248 (2020/01/31)
Herein, we report a novel strategy toward galanthamine and lycoramine. The concise synthesis was enabled by a Rh-catalyzed gram-scale C-C activation for the tetracyclic carbon framework and a regioselective Pd-catalyzed C-H activation for double-bond introduction. An aqueous-phase Beckmann rearrangement was performed for nitrogen atom insertion. Galanthamine and lycoramine were completed in 11 and 10 steps, respectively.
Synthesis and biological evaluation of cis-restrained carbocyclic combretastatin A-4 analogs: Influence of the ring size and saturation on cytotoxic properties
Nowikow, Christina,Fuerst, Rita,Kauderer, Maria,Dank, Christian,Schmid, Walther,Hajduch, Marian,Rehulka, Jiri,Gurska, Sona,Mokshyna, Olena,Polishchuk, Pavel,Zupkó, István,Dzubak, Petr,Rinner, Uwe
, (2019/08/12)
Combretastatin A-4 (CA-4) is a highly cytotoxic natural product and several derivatives have been prepared which underwent clinical trial. These investigations revealed that the cis-stilbene moiety of the natural product is prone to undergo cis/trans isomerization under physiological conditions, reducing the overall activity of the drug candidates. Herein, we report the preparation of cis-restrained carbocyclic analogs of CA-4. The compounds, which differ by the size and hybridization of the carbocyclic ring have been evaluated for their cytotoxic properties and their ability to inhibit tubulin polymerization. Biological data, supported by molecular docking studies, identified cyclobutenyl and cyclobutyl derivatives of the natural product as highly promising drug candidates.
The synthesis and evaluation of new benzophenone derivatives as tubulin polymerization inhibitors
Zhang, Shun,An, Baijiao,Yan, Jun,Huang, Ling,Li, Xingshu
, p. 88453 - 88462 (2016/09/28)
Inspired by the potent inhibition activity of phenstatin and millepachine against cancer cell growth, a series of new benzophenone derivatives were synthesized and evaluated as tubulin polymerization inhibitors. Among them, compound 10a exhibited 0.029-0.062 μM of IC50 for five human cancer cell lines, which is much better than that of the two leading compounds. Flow cytometric analysis showed that 10a induces G2/M phase arrest and apoptosis in A549 cells. Cellular studies revealed that the induction of apoptosis by 10a was associated with the collapse of the mitochondrial membrane potential (MMP). Overall, the current study demonstrates that the benzophenone derivatives are promising anticancer agents by targeting tubulin.
Synthesis, structure-activity relationships, and mechanism of action of anti-HIV-1 lamellarin α 20-sulfate analogues
Kamiyama, Haruka,Kubo, Yoshinao,Sato, Hironori,Yamamoto, Naoki,Fukuda, Tsutomu,Ishibashi, Fumito,Iwao, Masatomo
supporting information; experimental part, p. 7541 - 7550 (2012/01/13)
Lamellarin α and six different types of lamellarin α 20-sulfate analogues were synthesized and their structure-activity relationships were investigated using a single round HIV-1 vector infection assay. All lamellarin sulfates having pentacyclic lamellarin core exhibited anti-HIV-1 activity at a 10 μM concentration range regardless of the number and position of the sulfate group. On the other hand, non-sulfated lamellarin α and ring-opened lamellarin sulfate analogues did not affect HIV-1 vector infection in similar concentrations. The lamellarin sulfates utilized in this study did not exhibit unfavorable cytotoxic effect under the concentrations tested (IC50 > 100 μM). Confocal laser scanning microscopic analysis indicated that hydrophilic lamellarin sulfates were hardly incorporated in the cell. HIV-1 Env-mediated cell-cell fusion was suppressed by lamellarin sulfates. These results suggested that lamellarin sulfates have a novel anti-HIV-1 activity besides the previously reported integrase activity inhibition, possibly at a viral entry step of HIV-1 replication.
AROMATIC NITROGEN-CONTAINING 6-MEMBERED RING COMPOUNDS AND THEIR USE
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Page/Page column 55-56, (2010/04/06)
The present invention provides aromatic nitrogen-containing 6-membered ring compounds having execellent PDE10 inhibitory activity. The present invention relates to an aromatic nitrogen-containing 6-membered ring compound represented by the following formula [I0] or a pharmaceutically acceptable salt thereof, a method for preparing the same, and use of said compounds for PDE10 inhibitors, and a pharmaceutical composition comprising said compounds as an active ingredient: Formula [I0] wherein: X1, X2 and X3 each independently are N or CH, and at least two of X1, X2 and X3 are N; A is *-CH=CH-, *-C(Alk)=CH-, *-CH2-CH2- or *-O-CH2- (* is a bond with R1); Alk is a lower alkyl group; Ring B is an optionally substituted nitrogen-containing aliphatic heterocyclic group; R1 is an optionally substituted nitrogen-containing heterocyclic group, a nitrogen-containing heterocyclic moiety of which is a moiety selected from the group consisting of quinoxalinyl, quinolyl, isoquinolyl, quinazolinyl, pyrazinyl, pyrimidinyl and a moiety thereof fused with a 5 to 6-membered aliphatic ring thereto; Y0 is a group selected from the group consisting of the following (1) to (5): (1) an optionally substituted phenyl or an optionally substituted aromatic monocyclic 5 to 6-membered heterocyclic group; (2) an optionally substituted aminocarbonyl; (3) an optionally substituted amino lower alkyl; (4) -O-R2 wherein R2 is hydrogen, an optionally substituted lower alkyl, lower cycloalkyl, aliphatic monocyclic 5 to 6-membered heterocyclic group, or Formula [AA]; (5) mono- or di-substituted amino; provided that, when Y0 is mono- or di-substituted amino, the nitrogen-containing heterocyclic moiety of R1 is not quinoxalinyl or quinolyl.
Divergent synthesis of lamellarin α 13-sulfate, 20-sulfate, and 13,20-disulfate
Fukuda, Tsutomu,Ohta, Takeshi,Saeki, Sho,Iwao, Masatomo
scheme or table, p. 841 - 846 (2010/10/05)
A divergent synthesis of three sulfate derivatives of lamellarin α, namely, lamellarin α 13-sulfate (2), 20-sulfate (1), and 13,20-disulfate (4) has been achieved via a common intermediate (6) in which 13-OH and 20-OH of the lamellarin core are differentially protected by MOM and benzyl groups, respectively. Compound (6) in turn was prepared using sequential Suzuki-Miyaura coupling of 3,4-dihydroxypyrrole bistriflate (7) as a key reaction.
Synthesis and antitumor-evaluation of cyclopropyl-containing combretastatin analogs
Fuerst, Rita,Zupko, Istvan,Berenyi, Agnes,Ecker, Gerhard F.,Rinner, Uwe
scheme or table, p. 6948 - 6951 (2010/08/06)
Several derivatives of combretastatin have been prepared bearing a cyclopropyl unit instead of the natural occurring cis-double bond. Final products and synthetic intermediates were evaluated for their cytotoxic properties in two human cancer cell lines.
Total Synthesis and Absolute Configuration of Otteliones A and B, Novel and Potent Antitumor Agents from a Freshwater Plant
Araki, Hiroshi,Inoue, Munenori,Katoh, Tadashi
, p. 3903 - 3906 (2007/10/03)
(Matrix presented) The first enantioselective total synthesis of otteliones A and B, biologically important and structurally novel natural products, has been successfully achieved. This total synthesis fully confirms the absolute configuration of these natural products.
