A new class of nitrosoureas. I. Synthesis and antitumor activity of 1-(2-chloroethyl)-3,3-disubstituted-1-nitrosoureas having a hydroxyl group at the .BETA.-position of the substituents.
“…Instead, compounds 65 − 71 , with a hydroxy group on the β-carbon, undergo a decomposition to an oxazolidinone (Scheme ). This class of nitrosoureas possessed excellent anticancer activities and higher therapeutic ratios (Table ) than other nitrosoureas 16 17
“…The compound N -(2-chloroethyl)- N ‘-methyl- N -nitroso- N ‘-propylurea ( 60 ) was stable in aqueous solution − and was active against L1210 leukemia only in vivo, lending further support 10 to the concept of an activation of the latent drug by an enzymatic demethylation. Furthermore, compound 60 had the highest therapeutic index of a series of such compounds in which the methyl group was replaced by 2-chloroethyl and cyclohexyl moieties. − A related series of N3,N3-disubstituted nitrosoureas 61 − 73 were prepared and tested for anticancer activities against the L1210 leukemia (Table ) and Ehrlich ascites carcinoma. Since these compounds lack a hydrogen on the N3-position they cannot undergo decomposition to an isocyanate and a diazohydroxide.…”
Section: Aliphatic Analogsmentioning
confidence: 99%
“…The morpholine analog 64 , a cyclic N3,N3-disubstituted compound, possessed excellent antileukemic activity (Table ). Certain β-hydroxyethyl analogs, such as 66 and 71 , had both high antileukemic activity and therapeutic indices (Table ) . In these cases, the β-hydroxyl group can undergo a reaction with the ureido carbonyl group to form an N -substituted oxazolidinone and no isocyanate (Scheme ) …”
“…Furthermore, compound 60 had the highest therapeutic index of a series of such compounds in which the methyl group was replaced by 2-chloroethyl and cyclohexyl moieties. [130][131][132] A related series of N3,N3-disubstituted nitrosoureas 61-73 were prepared and tested 133 for anticancer activities against the L1210 leukemia (Table 3) and Ehrlich ascites carcinoma. Since these compounds lack a hydrogen on the N3-position they cannot undergo decomposition to an isocyanate and a diazohydroxide.…”
Section: Aliphatic Analogsmentioning
confidence: 99%
“…This class of nitrosoureas possessed excellent anticancer activities and higher therapeutic ratios (Table 3) than other nitrosoureas. 133 b. Bis-nitrosoureas. Much attention has been devoted to the synthesis and biological testing of bisnitrosoureas.…”
“…Instead, compounds 65 − 71 , with a hydroxy group on the β-carbon, undergo a decomposition to an oxazolidinone (Scheme ). This class of nitrosoureas possessed excellent anticancer activities and higher therapeutic ratios (Table ) than other nitrosoureas 16 17
“…The compound N -(2-chloroethyl)- N ‘-methyl- N -nitroso- N ‘-propylurea ( 60 ) was stable in aqueous solution − and was active against L1210 leukemia only in vivo, lending further support 10 to the concept of an activation of the latent drug by an enzymatic demethylation. Furthermore, compound 60 had the highest therapeutic index of a series of such compounds in which the methyl group was replaced by 2-chloroethyl and cyclohexyl moieties. − A related series of N3,N3-disubstituted nitrosoureas 61 − 73 were prepared and tested for anticancer activities against the L1210 leukemia (Table ) and Ehrlich ascites carcinoma. Since these compounds lack a hydrogen on the N3-position they cannot undergo decomposition to an isocyanate and a diazohydroxide.…”
Section: Aliphatic Analogsmentioning
confidence: 99%
“…The morpholine analog 64 , a cyclic N3,N3-disubstituted compound, possessed excellent antileukemic activity (Table ). Certain β-hydroxyethyl analogs, such as 66 and 71 , had both high antileukemic activity and therapeutic indices (Table ) . In these cases, the β-hydroxyl group can undergo a reaction with the ureido carbonyl group to form an N -substituted oxazolidinone and no isocyanate (Scheme ) …”
“…Furthermore, compound 60 had the highest therapeutic index of a series of such compounds in which the methyl group was replaced by 2-chloroethyl and cyclohexyl moieties. [130][131][132] A related series of N3,N3-disubstituted nitrosoureas 61-73 were prepared and tested 133 for anticancer activities against the L1210 leukemia (Table 3) and Ehrlich ascites carcinoma. Since these compounds lack a hydrogen on the N3-position they cannot undergo decomposition to an isocyanate and a diazohydroxide.…”
Section: Aliphatic Analogsmentioning
confidence: 99%
“…This class of nitrosoureas possessed excellent anticancer activities and higher therapeutic ratios (Table 3) than other nitrosoureas. 133 b. Bis-nitrosoureas. Much attention has been devoted to the synthesis and biological testing of bisnitrosoureas.…”
Die N‐Nitrosoharnstoffe (IV) werden aus den Aminen (I) durch Umsetzung mit dem Isocyanat (II) zu (III) und anschließende Nitrosierung hergestellt und auf ihre Antitumor‐Aktivität geprüft.
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