Strategies to prevent N-acetyltransferase-mediated metabolism in a series of piperazine-containing pyrazalopyrimidine compounds

Xenobiotica

Volumn 38, Issue 9, 2008, Pages 1219-1239

  Rawal, J ^a   Jones, R ^a   Payne, A ^a   Gardner, I ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

Drug metabolism; Lead optimization; N acetyltransferase

Indexed keywords

1 METHYL 5 PIPERAZIN 1 YL 3 PROPYL 1H PYRAZOLO[4,3 D]PYRIMIDIN 7 YL) (5 METHYLPYRIDIN 2 YL)AMINE; ACYLTRANSFERASE; ARYLAMINE ACETYLTRANSFERASE; DRUG METABOLITE; N ACETYLPIPERAZINE; PIPERAZINE DERIVATIVE; RECOMBINANT ENZYME; SULFADIMIDINE; SULFAMETHOXAZOLE; UK 469413; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; CORRELATION ANALYSIS; CRYOPRESERVATION; DRUG ACETYLATION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG HALF LIFE; DRUG METABOLISM; DRUG STRUCTURE; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VIVO STUDY; INCUBATION TIME; LIQUID CHROMATOGRAPHY; LIVER CELL; LIVER CYTOSOL; LIVER MICROSOME; MALE; NONHUMAN; PHYSICAL CHEMISTRY; PLASMA CLEARANCE; PROTEIN EXPRESSION; PROTON NUCLEAR MAGNETIC RESONANCE; RAT; TANDEM MASS SPECTROMETRY;

ACETYL COENZYME A; ACETYLATION; ANIMALS; ARYLAMINE N-ACETYLTRANSFERASE; CHROMATOGRAPHY, LIQUID; CYTOSOL; HEPATOCYTES; HUMANS; ISOENZYMES; MALE; MASS SPECTROMETRY; MICROSOMES, LIVER; MOLECULAR STRUCTURE; PYRAZOLES; PYRIDINES; RATS; RATS, SPRAGUE-DAWLEY; RECOMBINANT PROTEINS;

RATTUS;

EID: 50249125416     PISSN: 00498254     EISSN: 13665928     Source Type: Journal    
DOI: 10.1080/00498250802334417     Document Type: Article

References (24)

1. Blum M, Demierre A, Grant DM, Heim M, Meyer UA. 1991. Molecular mechanism of slow acetylation of drugs and carcinogens in humans. Proceedings of the National Academy of Sciences, USA 88:5237-5241.
2. Blum M, Grant DM, McBride W, Heim M, Meyer UA. 1990. Human arylamine N-acetyltransferase genes: Isolation, chromosomal localization, and functional expression. DNA and Cell Biology 9:193-203.
3. Deguchi T. 1992. Sequences and expression of alleles of polymorphic arylamine N-acetyltransferase of human liver. Journal of Biological Chemistry 267:18140-18147.
4. Devadatta S, Gangadharam PR, Andrews RH, Fox W, Ramakrishnan CV, Selkon JB, Velu S. 1960. Peripheral neuritis due to isoniazid. Bulletin of the World Health Organisation 23:587-598.
5. Ganes DA, Midha KK. 1987. Identification in in vivo acetylation pathway for N-dealkylated metabolites of doxylamine in humans. Xenobiotica 17:993-999.
6. Gardner I, Bergin P, Stening P, Kenna JG, Caldwell J. 1996. Immunochemical detection of covalently modified protein adducts in livers of rats treated with methyleugenol. Chemical Research in Toxicology 9:713-721.
7. Glowinski IB, Weber WW. 1982. Biochemical characterization of genetically variant aromatic amine N-acetyltransferases in A/J and C57BL/6J mice. Journal of Biological Chemistry 257:1431-1437.
8. Gobry V, Bouchard G, Carrupt P-A, Testa B, Girault HH. 2000. Physicohcemical characterization of sildenafil: Ionization, lipophilicity behaviour, and ionic-partition diagram studied by two-phase titration and electrochemistry. Helvetica Chimica Acta 83:1465-1474.
9. Grant DM, Blum M, Beer M, Meyer UA. 1991. Monomorphic and polymorphic human arylamine N-acetyltransferases: A comparison of liver isozymes and expressed products of two cloned genes. Molecular Pharmacology 39:184-191.
10. Grant DM, Goodfellow GH, Sugamori K, Durette K. 2000. Pharmacogenetics of the human arylamine N-acetyltransferases. Pharmacology 61:204-211.
11. Grant DM, Hughes NC, Janezic SA, Goodfellow GH, Chen HJ, Gaedigk A, Yu VL, Grewal R. 1997. Human acetyltransferase polymorphisms. Mutation Research 376:61-70.
12. Hearse DJ, Weber WW. 1973. Multiple N-acetyltransferases and drug metabolism. Tissue distribution, characterization and significance of mammalian N-acetyltransferase. Biochemical Journal 132:519-526.
13. Hein DW, Omichinski JG, Brewer JA, Weber WW. 1982. A unique pharmacogenetic expression of the N-acetylation polymorphism in the inbred hamster. Journal of Pharmacology and Experimental Therapeutics 220:8-15.
14. Hein DW, Rustan TD, Bucher KD, Furman EJ, Martin WJ. 1991. Extrahepatic expression of the N-acetylation polymorphism toward arylamine carcinogens in tumor target organs of an inbred rat model. Journal of Pharmacology and Experimental Therapeutics 258:232-236.
15. Hughes HB, Biehl JP, Jones AP, Schmidt LH. 1954. Metabolism of isoniazid in man as related to the occurrence of peripheral neuritis. American Review of Respiratory Disease 70:266-273.
16. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. 1997. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews 23:3-25.
17. Palmer MJ, Bell AS, Fox DNA, Brown DG. 2007. Design of second generation phosphodiesterase 5 inhibitors. Current Topics in Medicinal Chemistry 7:405-419.
18. Payton MA, Sim E. 1998. Genotyping human arylamine N-acetyltransferase type 1 (NAT1): The identification of two novel allelic variants. Biochemical Pharmacology 55:361-366.
19. Perry Jr HM. 1973. Late toxicity to hydralazine resembling systemic lupus erythematosus or rheumatoid arthritis. American Journal of Medicine 54:58-72.
20. Spielberg SP. 1996. N-acetyltransferases: Pharmacogenetics and clinical consequences of polymorphic drug metabolism. Journal of Pharmacokinetics and Biopharmaceutics 24:509-519.
21. Stevens GJ, Payton M, Sim E, McQueen CA. 1999. N-acetylation of the heterocyclic amine batracylin by human liver. Drug Metabolism and Disposition 27:966-971.
22. Vatsis KP, Martell KJ, Weber WW. 1991. Diverse point mutations in the human gene for polymorphic N-acetyltransferase. Proceedings of the National Academy of Sciences, USA 88:6333-6337.
23. Vereczkey KJaL. 2002. Prediction of polymorphic N-acetylation of new drug candidates by correlation with human NAT-1 and NAT-2. Drug Development Research 56:17-22.
24. Weber WW, Cohen SN. 1967. N-acetylation of drugs: Isolation and properties of an N-acetyltransferase from rabbit liver. Molecular Pharmacology 3:266-273.