- Synthesis of the lipophilic antifolate piritrexim via a palladium(0)-catalyzed cross-coupling reaction
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(Chemical Equation Presented) A regiospecific and convergent route the lipophilic antifolate piritrexim (PTX) is described in which a key step is a Pd(0)-catalyzed cross-coupling reaction between 2-amino-3-cyano-4-methyl-5- bromopyridine and 2,5-dimethoxy
- Chan, David C. M.,Rosowsky, Andre
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p. 1364 - 1368
(2007/10/03)
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- An alternative synthesis of piritrexim, a lipophilic inhibitor of human dihydrofolate-reductase
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An alternative synthesis of the lipophilic antifolate piritrexim (1) is outlined. Starting from ketone 2, treatment with phosphorus oxychloride and dimethylformamide gave the β-chlorocrotonaldehydes 3E/Z, which were reacted with cyanoacetamide (6) in the presence of sodium hydride to yield a 3- cyano-2-pyridone derivative 7. Chlorination of 7 with thionyl chloride and subsequent reaction with guanidine (9) gave rise to piritrexim (1). The reaction of β-chlorocrotonaldehydes 3E/Z, with 2,4,6-triaminopyrimidine (4) yielded iso-piritrexim (5).
- Troschuetz, Reinhard,Zink, Mario,Gnibl, Rainer
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p. 703 - 706
(2007/10/03)
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- Medicaments for the treatment of rheumatoid arthritis
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A method of treatment of rheumatoid arthritis in humans in need thereof which comprises administering to said human an effective rheumatoid arthritis treatment amount of compound 2,4-diamino-6-(2,5-dimethoxybenzyl)--5-methylpyrido[2,3-d]pyrimidine or pharmaceutically acceptable acid addition salt thereof.
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- Treatment with dialkoxy pyridopyrimidines
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Potent psoriasis activity in combination with low inhibition of histamine N-methyltransferase has been found in a class of 2,4-diamino-6-(2,5-dialkoxybenzyl)-5-methylpyrido[2,3-d]pyrimidines.
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- Synthesis and Antitumor Activity of 2,4-Diamino-6-(2,5-dimethoxybenzyl)-5-methylpyridopyrimidine
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The synthesis of 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyridopyrimidine (BW301U, 7) by a route that has general applicability to the preparation of many 6-(substituted benzyl)-5-methylpyridopyrimidines is described.The key intermediate, 2,4-diamino-7,8-dihydro-6-(2,5-dimethoxybenzyl)-5-methyl-7-oxopyridopyrimidine (4), is converted to the 7-chloro compound 5 by treatment with a 1:1 complex of N,N-dimethylformamide-thionyl chloride, and 5 is hydrogenolyzed with palladium on charcoal in the presence of potassium hydroxide to yield 7.BW301U is a potent lipid-soluble inhibitor of mammalian dihydrofolate reductase and has significant activity against the Walker 256 carcinosarcoma in rats.
- Grivsky, Eugene M.,Lee, Shuliang,Sigel, Carl W.,Duch, David S.,Nichol, Charles A.
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p. 327 - 329
(2007/10/02)
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