1193-22-2Relevant articles and documents
6-[2-(Phosphonomethoxy)alkoxy]pyrimidines with antiviral activity
Holy, Antonin,Votruba, Ivan,Masojídková, Milena,Andrei, Graciela,Snoeck, Robert,Naesens, Lieve,De Clercq, Erik,Balzarini, Jan
, p. 1918 - 1929 (2002)
6-Hydroxypyrimidines substituted at positions 2 and 4 by hydrogen, methyl, amino, cyclopropylamino, dimethylamino, methylsulfanyl, or hydroxyl group afford by the reaction with diisopropyl 2-(chloroethoxy)methylphosphonate in the presence of NaH, CS2CO3, or DBU a mixture of N1- and O6-[2-(diisopropylphosphorylmethoxy)ethyl] isomers which were converted to the free phosphonic acids by treatment with bromotrimethylsilane followed by hydrolysis. Analogously, 2,4-diamino-6-hydroxypyrimidine gave on reaction with [(R)- and (S)-2-(diisopropylphosphorylmethoxy)propyl] tosylate, followed by deprotection, the enantiomeric 6-[2-(phosphonomethoxy)propoxy]pyrimidines. 2,4-Diamino-6-sulfanylpyrimidine gave, on treatment with diisopropyl 2-(chloroethoxy)methylphosphonate in the presence of NaH and subsequent deprotection, 2,4-diamino-6-{[2-(phosphonomethoxy)ethyl]sulfanyl}pyrimidine. 2-Amino-4-hy-droxy-6-[2-(phosphonomethoxy)ethyl]pyrimidine was obtained from the appropriate 2-amino-4-chloropyrimidine derivative by alkaline hydrolysis and ester cleavage. Direct alkylation of 2-amino-4,6-dihydroxypyrimidine afforded a mixture of 2-amino-4,6-bis[2-(phosphonomethoxy)-ethyl]- and 2-amino-1,4-bis[2-(phosphonomethoxy)ethyl]pyrimidine. None of the N1-[2-(phosphonomethoxy)ethyl] isomers exhibited any antiviral activity against DNA viruses or RNA viruses tested in vitro. On the contrary, the O6-isomers, namely the compounds derived from 2,4-diamino-, 2-amino-4-hydroxy-, or 2-amino-4-[2-(phosphonomethoxy)ethoxy]l-6-hydroxypyrimidine, inhibited the replication of herpes viruses [herpes simplex type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus (VZV), and cytomegalovirus (CMV)] and retroviruses [Moloney sarcoma virus (MSV) and human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2)], their activity being most pronounced against the latter. The antiviral activity was lower if the oxygen at the position 6 was replaced by a sulfur atom, as in 2,4-diamino-6-[2-(phosphonomethoxy)ethylsulfanyl]pyrimidine. In analogy to N9-[2-(phosphonomethoxy)propyl]-2,6-diaminopurine (PMPDAP), solely the (R)-2,4-diamino-6-[2-(phosphonomethoxy)propoxy]-pyrimidine exerted antiviral activity, whereas its (S)-enantiomer was essentially inactive.
Production process 4 -chloropyrrolo [2, 3 - d] pyrimidine
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Paragraph 0108; 0111, (2021/10/27)
The production process of 4 - chloropyrrolo [2, 3 - d] pyrimidine comprises the following steps: S1, adding the compound I and the compound II to the mixed solvent I, carrying out temperature rise reaction under the catalysis of the base I to obtain the compound III. S2, sodium alkoxide I was added to alcoholic solvent II, compound IV and compound III were added to raise the temperature, and organic solvent III, organic solvent IV and compound V were added to raise the temperature to give 4 - chloropyrrolo [2, 3 - d] pyrimidine crude product. Among them, compound I is. . Compound II was obtained. . Compound III was obtained. . The compound IV is formamidine. Compound V was POCl. 3 To the method, bromoacetaldehyde dimethyl acetal and cyanoethyl acetate are subjected to reflux reaction, and 2 - cyano -4, 4 - methoxybutyric acid ethyl ester and formamidine acetate are subjected to one-pot chlorofluorination reaction, so that the reaction period is greatly shortened.
6-[2-(PHOSPHONOMETHOXY)ALKOXY] PYRIMIDINE DERIVATIVES HAVING ANTIVIRAL ACTIVITY
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Paragraph 00382; 00383, (2016/03/04)
Novel compounds are provided having formula (I)whereR1, R2, R3, R4, Z, X and * are defined herein. Also provided are antiviral methods for use and processes for synthesis of the compounds of formula (I).
