- Synthesis of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP)
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Palladium-catalyzed cross-coupling of methylboronic acid with 2-chloro- 3-nitropyridine produced 2-methyl-3-nitropyridine 4 in one step in high yield. Oxidation of 4 with selenium dioxide gave aldehyde 5. Alternatively, condensation of 4 with DMFDMA followed by oxidation gave 5 in a two step higher yielding conversion. Subsequent direct coupling of 5 with thiosemicarbazide followed by reduction of the nitro group using stannous chloride or sodium sulfide provided 3-AP (3). Reduction with sodium hydrosulfite gave 3-HAP (8). Finally a route which avoids the reduction of a nitro function was devised. Thus direct coupling of styrene with 2-chloro-3- aminopyridine 9 under Heck reaction conditions gave 16 which was converted to 17, oxidized to the aldehyde 18 and converted to 3-AP (3) with in situ deblocking of the t-Boc functionality.
- Niu, Chuansheng,Li, Jun,Doyle, Terrence W.,Chen, Shu-Hui
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p. 6311 - 6318
(2007/10/03)
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- 2-formylpyridine thiosemicarbazone compounds
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A method of treatment of tumors is provided based upon a compound of the formula STR1 Some aspects of the invention were supported in part by U.S. Public Health Service Grant CA-02817 from the National Cancer Institute and support from the Northeast NMR Facility at Yale University insofar as the use of high resolution NMR spectra is concerned that was made possible by a grant from the Chemical Division of the National Science Foundation (Grant No. CHE-7916210).
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- Synthesis and Antitumor Activity of Amino Derivatives of Pyridine-2-carboxaldehyde Thiosemicarbazone
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Variuos substituted pyridine-2-carboxaldehyde thiosemicarbazones (12 compounds) have been synthesized and evaluated for antineoplastic activity in mice bearing the L1210 leukemia.Oxidation of 3-nitro-2-picoline, 5-nitro-2-picoline, 3-nitro-2,4-lutidine, and 5-nitro-2,4-lutidine with selenium dioxide was employed to generate the corresponding pyridine-2-carboxaldehydes, which were then converted to cyclic ethylene acetals and subsequently reduced to amino and hydroxyamino derivatives by catalytic hydrogenation.Condensation of nitro aldehydes and acetals with thiosemicarbazide afforded the respective thiosemicarbazones.Acetylation of the amino acetals and alkylsulfonation of the 5-amino acetal, followed by condensation with thiosemicarbazide was employed to yield amide thiosemicarbazones.The most active compounds synthesiszed were 3-aminopyridine-2-carboxaldehyde thiosemicarbazone and 3-amino-4-methylpyridine-2-carboxaldehyde thiosemicarbazone which produced against the L1210 leukemia, percent T/C values of 246 and 255, and 40percent 60-day long-term survivors at two daily doses of 40 mg/kg and 10 mg/kg, respectively, for six consecutive days.
- Liu, Mao-Chin,Lin, Tai-Shun,Sartorelli, Alan C.
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p. 3672 - 3677
(2007/10/02)
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