2730-82-7Relevant academic research and scientific papers
Deacetylcolchicine deriv.
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Paragraph 0059, (2016/10/08)
Provided are 4-modified colchicine compounds and medicines using the same. Specifically provided are colchicine derivatives represented by general formula (1), salts thereof, and solvates of the same. In general formula (1), R1 is a halogen atom, a hydroxyl group, a nitro group, an amino group, or a mono-, di- or tri-fluoromethyl group; R2, R3 and R4 are each a methoxy group or a hydroxyl group, or alternatively R2 and R3, or R3 and R4 together represent a methylenedioxy group; R5 and R6 may be the same or different and are each a hydrogen atom, a C1-6 alkyl group, an arylalkyl group, a C2-6 alkenyl group, -COR7, -COOR8, -SO2R9, -CONR10R11, or -CSNR12R13, or alternatively R5 and R6 together with the nitrogen atom to which R5 and R6 are bonded may form a three- to seven-membered cyclic amino group; R7 is a C1-6 alkyl group or the like; R8 is a C1-6 alkyl group or the like; R9 is a C1-6 alkyl group or the like; R10 and R11 may be the same or different and are each a hydrogen atom, a C1-6 alkyl group, or the like; and R12 and R13 may be the same or different and are each a hydrogen atom, an alkyl group, or the like.
4-Chlorocolchicine derivatives bearing a thiourea side chain at the C-7 position as potent anticancer agents
Nishiyama, Hiroyuki,Ono, Masahiro,Sugimoto, Takuya,Sasai, Toshio,Asakawa, Naoyuki,Ueno, Satoshi,Tominaga, Yoshitaka,Yaegashi, Takashi,Nagaoka, Masato,Matsuzaki, Takeshi,Kogure, Noriyuki,Kitajima, Mariko,Takayama, Hiromitsu
, p. 452 - 458 (2014/04/17)
A series of 4-substituted colchicine derivatives were synthesized and evaluated with an eye toward developing new anticancer agents. As a result, 4-chlorocolchicine derivatives bearing a thioureide side chain at the C-7 position were found to exhibit significant cytotoxicities to three human cancer cell lines (A549, HT-29, and HCT116). In particular, compound 26 having an ethylthioureide group at the C-7 had high antitumor activity in vivo and a broad effective dosage range. Furthermore, compound 58, which has a (5-methylpyrazol-3-yl)thioureide group at the C-7 side chain, exhibited strong cytotoxicity and desirable metabolic stability in vitro.
Design, synthesis, and antitumor activity of 4-halocolchicines and their pro-drugs activated by cathepsin B
Yasobu, Naoko,Kitajima, Mariko,Kogure, Noriyuki,Shishido, Yoshiyuki,Matsuzaki, Takeshi,Nagaoka, Masato,Takayama, Hiromitsu
scheme or table, p. 348 - 352 (2011/07/09)
Novel colchicine derivatives possessing various substituents at the C4 position were prepared. Among them, 4-halo derivatives 3-6 were found to exhibit higher activity against cancer cell lines (A549, HT29, HCT116) as well as on mice transplanted with the HCT116 human colorectal carcinoma cell line than colchicine (1). Further, utilizing the 4-substituted colchicines, we prepared pro-drugs having a dipeptide side chain and demonstrated that these pro-drugs were activated by cathepsin B, an enzyme overexpressed in tumor cells, and exhibited selective toxicity to the tumor cells.
100. From Colchicine and Some of Its Derivatives to 1,2,3,9,10-Pentamethoxybenzoheptalenes
Kouroupis, Pavlos,Hansen, Hans-Jurgen
, p. 1247 - 1277 (2007/10/02)
A two-step synthesis of 4-methylcolchicine (13), starting from colchicine (2), has been developd (Scheme 5).In three steps, 4-ethylcolchicine (28) is also accessible from 2 (Scheme 8).Colchicine (2) and its derivatives 13 and 28 have been transformed into the benzoheptalene derivatives 9,18, and 34, respectively, by Hofmann degradation of the corresponding deacetylcolchiceine 3, 19, and 29, respectively, followed by methylation of the two O-functions first with diazomethane and then with trimethoxonium tetrafluoroborate (Scheme 2 and 6).The thus formed tropylium salts gave, on deprotonation with Me3N in CHCl3, the expected pentamethoxybenzoheptalenes 9, 18, and 34, respectively.X-Ray crystal-structure analysis of 9 (Fig.3) and 18 (Fig.7), determination of the vicinal coupling constants of the H-atoms at the heptalene skeleton as well as the measurement of the racemization rate of the heptalene skeleton.The absolute configuration of the resolved heptalenes was deduced from their long-wavelength CD maxima around 350 nm.The heptalenes with a negative maximum in this range possess (7aP)-configuration.
