1-(2-카르보메톡시아크릴로일)-5-플루오르우라실과 초산비닐, 메틸메타크릴레이트 및 스티렌과의 공중합

이능주; 하창식; 조원제

Polymer(Korea), Vol.15, No.2, 211-217, April, 1991

Export Citation

1-(2-카르보메톡시아크릴로일)-5-플루오르우라실과 초산비닐, 메틸메타크릴레이트 및 스티렌과의 공중합

Copolymerization of 1-(2-Carbomethoxy acryloyl)-5-fluorouracil with Vinyl Acetate, Methyl Methacrylate, and Styrene

이능주, 하창식, 조원제

초록

1-(2-Carbomethoxyacryloyl)-5-fluorouracil(CMAFU)과 초산비닐(VAc), 메틸메타크릴레이트(MMA) 및 스티렌을 tetrahydrofuran을 용매로 사용하여 50℃에서 라디칼 공중합을 하였다. 공중합체내의 단량체조성은 공중합체의 IR 스펙트럼으로부터 정량분석하여 구하였다. Kelen-Tudos법에 의해 구한 각각의 단량체 반응성비의 값은 r₁(CMAFU)= 0.04 r₂(VAc)=0.19 ; r₁ (CMAFU)=0.01 r₂ (MMA)=32.11 ; r₁(CMAFU)=0.01과 r₂(St)=7.65이었다. 얻어진 단량체 반응성비의 값들로부터 CMAFU와 VAc, MMA 및 St 공중합에서 CMAFU의 입체장애 효과가 큰 영향을 미치는 것을 알 수 있었다. 노랑초파리(Drosophila melanogaster)를 이용하여 5-플루오르우라실(5-FU), 합성한 CMAFU 단량체 및 공중합체들의 독성을 조사한 결과, 5-FU>공중합체>CMAFU순으로 독성이 감소하였다.

Copolymerizations of 1-(2-carbomethoxyacryloyl)-5-fluorouracil(CMAFU) with vinyl acetate. methyl methacrylate, and styrene were carried out with 2,2'-azobisisobutyronitrile in tetrahydrofuran at 50℃. The copolymer compositions were determined by quantitative infrared(IR) analysis. The monomer reactivity ratios, r₁ and r₂ were determined by the Kelen-Tudos method. The values of r₁ and r₂ for each monomer pair were as follows; r₁(CMAFU)=0.04 and r₂(VAc)=0.19 ; r₁ (CMAFU)=0.01 and r₂(MMA)=32.11 ; r₁(CMAFU)=0.01 and r₂(St)=7.65. These values imply that the copolymerizations were significantly affected by the steric hindrance of CMAFU. Toxicity of 5-fluorouracil(5-FU), CMAFU and its copolymers obtained for this work was tested in Drosophila melanogaster. It was observed that the toxicity decreased in the order of 5-FU> copolymer>CMAFU.

[References]

Donaruma LG, "Anionic Polymeric Drugs," L.G. Donaruma, R.M. Ottenbrite and O. Vogl, Eds., John Wiley & Sons, Icn., New York, Vol. 1, p. 50 (1980)
Merigan TC, Regelson W, N. Engl. J. Med., 277, 1283 (1967)
Morahan PS, Regelson W, Munson AE, "Antimicrobiological Agents and Chemotheraphy," p. 16 (1972)
Ottenbrite RM, "The Antitumor and Antiviral Effects of Polycarboxylic Acid Polymers," in biological Activities of Polymers, ACS Symposium Series 186, Amer. Chem. Soc., Washington, D.C. (1982)
Ottenbrite RM, Goodell E, Munson A, Polymer, 18, 461 (1977)
Butler GB, J. Macromol. Sci.-Rev. Macromol. Chem. Phys., C22, 89 (1982)
Breslow DS, Pure Appl. Chem., 46, 103 (1979)
DcClereq E, Merigan TC, Arch. Int. Med., 126, 94 (1970)
Mohr SJ, Chirigos MA, Fuhrman FS, Pryor JW, Cancer Res., 35, 3750 (1975)
Regelson W, Munson A, Wooles W, International Symposium on Standards of Interferon and Interferon Inducers, London (1969)
Regelson W, Munson A, Wooles W, Symposium Series Immunobiological Standards, Vol. 14, Korger, Basel, p. 227 (1970)
Roberts PS, Regelson W, Kingsbury B, J. Lab. Clin. Med., 2, 822 (1973)
Han MJ, Lee DH, Lee WY, Hahn BS, Bull. Korean Chem. Soc., 10, 212 (1989)
Han MJ, Kang SD, Lee WY, Bull. Korean Chem. Soc., 11, 154 (1990)
Han MJ, Choi KB, Kim KH, Cho TJ, Lee WY, Shim WN, J. Bioactive Compatible Polym., 5, 420 (1990)
Akashi M, Tanaka Y, Miyazaki T, Miyauchi N, J. Bioactive Compatible Polym., 2, 120 (1987)
Lewis EB, Bacher F, Dorosophila Inform. Ser., 43, 193 (1968)
Duschinsky R, Gabrel TF, U.S. Patent, No. 3,354,160 (1967)
Umrigar PP, Ohashi S, Butler GB, J. Polym. Sci. A: Polym. Chem., 17, 351 (1979)
Cho WJ, Ph.D. Dissertation, University of Paris VI (1978)
Das S, Rodriguez F, J. Appl. Polym. Sci., 39, 1309 (1990)
Kelen T, Tudos F, J. Macromol. Sci.-Chem., A9, 1 (1975)

[Referenced By]

[1] Donaruma LG, "Anionic Polymeric Drugs," L.G. Donaruma, R.M. Ottenbrite and O. Vogl, Eds., John Wiley & Sons, Icn., New York, Vol. 1, p. 50 (1980)

[2] Merigan TC, Regelson W, N. Engl. J. Med., 277, 1283 (1967)

[3] Morahan PS, Regelson W, Munson AE, "Antimicrobiological Agents and Chemotheraphy," p. 16 (1972)

[4] Ottenbrite RM, "The Antitumor and Antiviral Effects of Polycarboxylic Acid Polymers," in biological Activities of Polymers, ACS Symposium Series 186, Amer. Chem. Soc., Washington, D.C. (1982)

[5] Ottenbrite RM, Goodell E, Munson A, Polymer, 18, 461 (1977)

[6] Butler GB, J. Macromol. Sci.-Rev. Macromol. Chem. Phys., C22, 89 (1982)

[7] Breslow DS, Pure Appl. Chem., 46, 103 (1979)

[8] DcClereq E, Merigan TC, Arch. Int. Med., 126, 94 (1970)

[9] Mohr SJ, Chirigos MA, Fuhrman FS, Pryor JW, Cancer Res., 35, 3750 (1975)

[10] Regelson W, Munson A, Wooles W, International Symposium on Standards of Interferon and Interferon Inducers, London (1969)

[11] Regelson W, Munson A, Wooles W, Symposium Series Immunobiological Standards, Vol. 14, Korger, Basel, p. 227 (1970)

[12] Roberts PS, Regelson W, Kingsbury B, J. Lab. Clin. Med., 2, 822 (1973)

[13] Han MJ, Lee DH, Lee WY, Hahn BS, Bull. Korean Chem. Soc., 10, 212 (1989)

[14] Han MJ, Kang SD, Lee WY, Bull. Korean Chem. Soc., 11, 154 (1990)

[15] Han MJ, Choi KB, Kim KH, Cho TJ, Lee WY, Shim WN, J. Bioactive Compatible Polym., 5, 420 (1990)

[16] Akashi M, Tanaka Y, Miyazaki T, Miyauchi N, J. Bioactive Compatible Polym., 2, 120 (1987)

[17] Lewis EB, Bacher F, Dorosophila Inform. Ser., 43, 193 (1968)

[18] Duschinsky R, Gabrel TF, U.S. Patent, No. 3,354,160 (1967)

[19] Umrigar PP, Ohashi S, Butler GB, J. Polym. Sci. A: Polym. Chem., 17, 351 (1979)

[20] Cho WJ, Ph.D. Dissertation, University of Paris VI (1978)

[21] Das S, Rodriguez F, J. Appl. Polym. Sci., 39, 1309 (1990)

[22] Kelen T, Tudos F, J. Macromol. Sci.-Chem., A9, 1 (1975)