Preparation of N'-Substituted Anilino-N-Methyl-N-Nitorsoureas as Candidate Antitumor Agents

  • Kim, Jack-C (Department of Chemistry, College of Natural Sciences, Pusan National University) ;
  • Kim, Yeon-Gweon (Department of Chemistry, College of Natural Sciences, Pusan National University) ;
  • Min, Byoung-Tack (Department of Chemistry, College of Natural Sciences, Pusan National University) ;
  • Park, Jin-Il (Department of Chemistry, College of Natural Sciences, Pusan National University)
  • 발행 : 1994.12.01

초록

Various N'-substituted anilino-N-methyl-N'-nitrosoureas(2a-n) were easily prepared from the reaction of substituted phenylhydraines $(3, 4-CH_3, {\;} 3-, {\;} 4-OCH_3, {\;} 3-, {\;} 4-F, {\;} 3, {\;} 4-Cl, {\;} 4-Br, {\;} 2-, {\;} 3-, {\;} 4-NO_2, 4-(NO_2)_2)$ with methyl isocyanate, followed by the nitrosation with 99% HCOOH and dry sodium lnitrite powder. Surprisingly, of these series of analogus, the anilino-nitrocosureas substituted with eletron-withdrawing nitro groups (2k-a) showed significantly low $ED_{30}$ values of $1.4-3.4 {\mu}g/ml.$ In addition, none of these copounds subtituted with electron-donating groups exhibited cytotoxicities.

키워드

참고문헌

  1. Cancer Chemotherapy Rep. K.B.Protocol 1600 Cell culture Screen
  2. Current Status and New Development Nitrosoureas Prestayko,A.W.;Crooke,S.T.;Baka,L.H.;Carter,S.K.;Schein,P.S.
  3. J. Med. Chem. v.4 Synthesis and in vitro Cytotoxicity of a Homologous Series 9-[ω-(N'-Me-thyl-N'-Nitrosoureidl)alkyl]purines Kim,J.C.;Bae,S.S.;Kim,S.H.
  4. J. Korean Chem. Soc. v.35 The Reactivity and Regionchemical Effect of Nitrosionium Species in the Nitrosation of N-Methyl-N'-substitued Phenlureas Kim,J.C.;Cho,I.S.;Choi,S.K.
  5. Yakhak Hoeji v.29 Synthesis and Antitumor Evaluation of N-Alkyl-N-nitrosocarbamoyl-3α-Amino-and-3β-Amino-5α-Cholestane Derivatives Kim,J.C.;Choi,S.K.;Cho,I.S.;Yu,D.S.;Ryu,S.H.;Moon,K.H.
  6. Arch. Pharm. Res. v.9 The synthesis of Steroidal Nitrosoureas as Antitumor Activity Kim,J.C.;Choi,S.K.;Moon,S.H.
  7. Yarkhak Hoeji v.24 Preparation of ε-N-[(2-chloroethyl)nitrosocarbamoyl]-L-Lysine Kim,J.C.;Cho,I.S.
  8. Bull. Korean Chem. Soc. v.15 Nitrosoation Products of N-Acyl-N'-substituted Phenylhydrazines Kim,J.C.;Han,S.H.
  9. Arch. Pharm. Res. v.6 Synthesis and Primary Screening for Growth inhibitors of L1210 Cells of Cholesteryl-P-[3-(2-Chloroethyl)-3-Nitrosoureidol]phenylthio Acetate Kim,J.C.;Kim,M.S.;Lee,H.K.
  10. Korea J. Med. Chem. v.3 Synthesis and Antitumor Activity of N'-Aryl-N--2(2-Chloroethyl)-N-nitro-soureas and N'-aryl-N-methyl-N-nitrosoureas Kim,J.C.;Lee,J.C.;Nha,C.S.
  11. J. Med. Chem. v.18 Decomposition of N-)2-chloroethyl)-N-nitrosoureas in Aqueous Media Monthomery,J.A.;James,R.;Mccaleb,G.S.;Kirk,M.C.;Johnston,T.P.
  12. J. Med. Chem. v.22 M Nitrosoureidonucleosides Montgomery,J.A.;Thomas,H.J.
  13. Bull. Korean Chem. Soc. v.14 Synthesis of Steroidal Cyclophosphamide,2-Bis-(2-chloroethyl)amino-2-oxo-6-(5α-Cholestanyl)-1,3,2-oxazaphorinane Kim,J.C.;Paek,H.D.;Moon,S.H.
  14. Bull. Korean Chem. Soc. v.14 Synthesis of 4-Aza-cholestane Derivatives Containing Nitrosoureido Function as Antitumor Activity Kim,J.C.;Park,J.I.;Hur,T.H.
  15. Yakhak Hoeji v.28 The Synthesis of N-alkyl-N'-nitrosocarbamoyl-L-Amino acid Ester Derivatives and their Anticancer Activity Kim,J.C.;Park,M.T.;Shin,H.D.;Koh,Y.S.;Yoon,U.C.;Ryu,S.H.;Moon,K.H.;Kim,M.S.
  16. Yakhak Hoeji v.27 Synthesis and Antitumor Evluation of 3-(2-choloroethyl)Hydantions from Some Amino Acids Kim,J.C.;Youn,I.K.;Koh,Y.S.;Pack,M.Y.;Moon,K.H.
  17. Bull. Korean Chem. Soc. v.13 The Cathodic Reduction of N'-Phenyl-N-alkyl-N-Nitrosoureas Won,M.S.;Kim,J.C.;Shim,Y.B.
  18. J.Korean Chem. Soc. v.35 Electical Behaviors of N'-Phenyl-N-(2-Chloroethyl)-N-Nitrosourea Analogs and Synthesis of N-Aminourea Won,M.S.;Kim,J.C.;Shim,Y.B.