Antiviral and cytostatic evaluation of the novel 6-acyclic chain substituted thymine derivatives

Antiviral Chemistry and Chemotherapy

Volumn 16, Issue 5, 2005, Pages 327-338

  Prekupec, Svjetlana ^a   Makuc, Damjan ^b   Plavec, Janez ^b   Kraljević, Sandra ^c   Kralj, Marijeta ^c   Pavelić, Krešimir ^c   Andrei, Graciela ^d   Snoeck, Robert ^d   Balzarini, Jan ^d   De Clercq, Erik ^d   Raić Malić, Silvana ^a   Mintas, Mladen ^a  

^a UNIVERSITY OF ZAGREB   (Croatia)

^b NATIONAL INSTITUTE OF CHEMISTRY   (Slovenia)

^c RUDER BO KOVI INSTITUTE   (Croatia)

^d REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

Antiviral activity; Apoptosis; C 6 fluoroalkylated pyrimidine derivatives; Conformational analysis; Cytostatic activity

Indexed keywords

2,4 DIMETHOXY 5,6 DIMETHYLPYRIMIDINE; 5 METHYLPYRIMIDINE DERIVATIVE; 6 (2 ACETOXYPROPYL) 2,4 DIHYDROXY 5 METHYLPYRIMIDINE; 6 (2 ACETOXYPROPYL) 2,4 DIMETHOXY 5 METHYLPYRIMIDINE; 6 (2 FLUOROMETHYL 2 ACETOXYPROPYL) 2,4 DIHYDROXY 5 METHYLPYRIMIDINE; 6 (2 FLUOROMETHYL 2 ACETOXYPROPYL) 2,4 DIMETHOXY 5 METHYLPYRIMIDINE; 6 (2 FLUOROMETHYL 2 HYDROXYPROPYL) 2,4 DIHYDROXY 5 METHYLPYRIMIDINE; 6 (2 FLUOROMETHYL 2 HYDROXYPROPYL) 2,4 DIMETHOXY 5 METHYLPYRIMIDINE; 6 (2 HYDROXY 3,3,3 TRIFLUORO 1 PROPENYL) 2,4 DIMETHOXY 5 METHYLPYRIMIDINE; 6 (2 HYDROXYPROPYL) 2,4 DIHYDROXY 5 METHYLPYRIMIDINE; 6 (2 HYDROXYPROPYL) 2,4 DIMETHOXY 5 METHYLPYRIMIDINE; 6 (2 TRIFLUOROMETHYL 2 HYDROXYPROPYL) 2,4 DIMETHOXY 5 METHYLPYRIMIDINE; 6 (3 ACETOXY 4 CHLOROBUTYL) 2,4 DIHYDROXY 5 METHYLPYRIMIDINE; 6 (3 ACETOXY 4 CHLOROBUTYL) 2,4 DIMETHOXY 5 METHYLPYRIMIDINE; 6 (3 HYDROXY 4 CHLOROBUTYL) 2,4 DIHYDROXY 5 METHYLPYRIMIDINE; 6 (4 CHLORO 3 HYDROXYBUTYL) 2,4 DIMETHOXY 5 METHYLPYRIMIDINE; ACETALDEHYDE; EPICHLOROHYDRIN; ESTER DERIVATIVE; KETONE DERIVATIVE; ORGANOLITHIUM COMPOUND; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ADDITION REACTION; ALKYLATION; ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ANTIVIRAL ACTIVITY; APOPTOSIS; ARTICLE; BIOLOGICAL ACTIVITY; BREAST CARCINOMA; CANCER INHIBITION; CELL CYCLE; COLUMN CHROMATOGRAPHY; CONTROLLED STUDY; CYTOMEGALOVIRUS INFECTION; CYTOSTASIS; CYTOTOXICITY TEST; DOSE RESPONSE; DRUG STRUCTURE; DRUG SYNTHESIS; FLOW CYTOMETRY; FLUORINATION; HUMAN; HUMAN CELL; IN VITRO STUDY; LITHIATION; NONHUMAN; NUCLEAR OVERHAUSER EFFECT; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; SUBSTITUTION REACTION; UTERINE CERVIX CARCINOMA;

EID: 26044438174     PISSN: 09563202     EISSN: None     Source Type: Journal    
DOI: 10.1177/095632020501600505     Document Type: Article

References (23)

1. Baba M, De Clercq E, Tanaka H, Ubasawa M, Takashima H, Sekiya K, Nitta I, Umezu K, Walker R-T, Mori S, Ito M, Shigeta S & Miyasaka T (1991) Highly potent and selective inhibition of human immunodeficiency virus type 1 by a novel series of 6-substituted acyclouridine derivatives. Molecular Pharmacology 39:805-810.
2. Balzarini J, Naesens L, Slachmuylders J, Niphuis H, Rosenberg I, Hol? A, Schellekens H, & De Clercq E (1991) 9-(2-Phosphonylmethoxyethyl)adenine (PMEA) efficiently inhibits retrovirus replication in vitro and simian immunodeficiency virus infection in rhesus monkeys. AIDS 5:21-28.
3. Balzarini J, Karlsoon A & De Clercq E (1993) Human immunodeficiency virus type 1 drug-resistance patterns with different 1-[(2-hydroxyethoxy)methyl] -6-(phenylthio)thymine derivatives. Molecular Pharmacology 44:694-701.
4. Botta M, Occhionero F, Nicoletti P-M, Conti C, Magrini M & Saladino R (1999) Synthesis and biological evaluation of 2-methoxy- and 2-methylthio-6-[(2′-alkylamino)ethyl]-4(3H)-pyrimidones with anti-rubella virus activity. Bioorganic & Medicinal Chemistry 7:1925-1931.
5. Brandt K, Haas A, Hardt T, Mayer-Figge H, Merz K & Wallmichrath T (1999) Synthesis of geminal-bis(trifluoromethyl)-substituted dienes, heterodienes, 7,7,7,8,8,8-hexafluoro-cyclocitral and -safranal. Journal of Fluorine Chemistry 97:115-125.
6. Cetina M, Nagl A, Prekupec S, Raiç-Maliç S & Mintas M (2005) Hydrogen Bonding and C-H⋯π interactions in 7-hydroxy-3-methoxy- 4-methyl-piperido[1,2-c]pyrimidine-1-one. Acta Crystallographica Section C 61:158-160.
7. De Clercq E, Holy A, Rosenberg I, Sakuma T, Balzarini J & Maudgal P-C (1986) A novel selective broad-spectrum anti-DNA virus agent. Nature 323:464-467.
8. Hsu L-Y, Wise D-S, Kucera L-S, Drach J-C & Townsend L-B (1992) Synthesis of antirestricted pyrimidine acyclic nucleosides. Journal of Organic Chemistry 57:3354-3358.
9. Hsu L-Y & Lin C-H (1996) Synthesis and biological evaluation of 3-hydroxymethylpyrimido[1,6-c][1,3]oxazine derivatives. Heterocycles 43:2687-2689.
10. Kim D-K, Gam J, Kim Y-W, Lim J, Kim H-T & Kim K-H (1997) Synthesis and anti-HIV-1 activity of a series of 1-alkoxy-5-alkyl-6-(arylthio)uracils. Journal of Medicinal Chemistry 40:2363-2373.
11. Klein R-S, Lenzi M, Lim T-H, Hotchkiss K-A, Wilson P & Schwartz E-L (2001) Novel 6-substituted uracil analogs as inhibitors of the angiogenic action of thymidine phosphorylase. Biochemical Pharmacology 62:1257-1263.
12. Kundu G-N & Das P (1995) Palladium-catalyzed synthesis of 6-(2-acylvinyl)uracil, a group of novel 6-substituted uracils of biological significance. Journal of the Chemical Society: Chemical Communications 99-100.
13. Kundu N-G, Das P, Balzarini J & De Clercq E (1997) Palladium-catalyzed synthesis of [E]-6-(2-acylvinyl)uracil and [E]-6-(2-acylvinyl)-1-[(2-hydroxyethoxy)methyl]uracil - their antiviral and cytostatic activities. Bioorganic Medicinal Chemistry 5:2011-2018.
14. Mai A, Artico M, Sbardella G, Quartarone S, Massa S, Loi A-G, De Montis A, Scintu F, Putzolu M & La Colla P (1997) Dihydro(alkylthio) (naphthylmethyl)oxopyrimidines: novel non-nucleoside reverse transcriptase inhibitors of the S-DABO series. Journal of Medicinal Chemistry 40:1447-1454.
15. Middleton W-J (1975) New fluorinating reagents. Dialkylaminosulfur fluorides. Journal of Organic Chemistry 40:574-578.
16. Mossman T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods 65:55-63.
17. Pontikis R, Benhinda R, Aubertin A-M, Grierson D-S & Monneret C (1997) Synthesis and anti-HIV activity of novel N-1 side chain-modified analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (Hept). Journal of Medicinal Chemistry 40:1845-1854.
18. Saladino R, Danti M-C, Minicone E, Crestini C, Palamara A-T, Savini P, Marini S & Botta M (1998) A potent and selective inhibition of parainfluenza 1 (Sendai) virus by new 6-oxiranyl-, 6-methyloxiranyluracils, and 4(3H)-pyrimidinone derivatives. Bioorganic & Medicinal Chemistry Letters 8:1833-1838.
19. Saladino R, Ciambecchini U, Maga G, Mastromarino P, Conti C & Botta M (2002) A new and efficient synthesis of substituted 6-[(2′-dialkylamino) ethyl] pyrimidine and 4-N,N-dialkyl-6-vinyl-cytosine derivatives and evaluation of their anti-rubella activity. Bioorganic & Medicinal Chemistry 10:2143-2153.
20. Schlenker J (1901) Über 4,5-dimethylpyrimidin. Berichte 34:2812-2829.
21. Tanaka H, Matsuda A, Ilijima S, Hayakawa H & Miyasaka T (1983) Synthesis and biological activities of 5-substituted 6-phenylthio and 6-iodouridines, a new class of antileukemic nucleosides. Chemical Pharmaceutical Bulletin 31:2164-2167.
22. Tanaka H, Takashima H, Ubasawa M, Sekiya K, Nitta I, Baba M, Shigeta S, Walker R-T, De Clercq E & Miyasaka T (1992) Synthesis and antiviral activity of deoxy analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents. Journal of Medicinal Chemistry 35:4713-4719.
23. Tanaka H, Takashima H, Ubasawa M, Sekiya K, Inouye N, Baba M, Shigeta, Walker R-T, De Clercq E & Miyasaka T (1995) Synthesis and antiviral activity of 6-benzyl analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents. Journal of Medicinal Chemistry 38:2860-2865.