Paracetamol (acetaminophen) esters of some non-steroidal anti- inflammatory carboxylic acids as mutual prodrugs with improved therapeutic index

Inflammopharmacology

Volumn 6, Issue 2, 1998, Pages 143-157

  Fadl, T A ^a   Omar, F A ^a  

^a Assiut University   (Egypt)

Author keywords

Chemical and enzymatic stability; NSAIDs; Pain threshold latency; Paracetamol (acetaminophen); Prodrugs; Ulcerogenicity

Indexed keywords

2 [[4 (METHYLCARBOXAMIDO)PHENYL]OXYCARBONYL]PHENYLACETATE; 4 (METHYLCARBOXAMIDO)PHENYL 2 (4 ISOBUTYLPHENYL)PROPANOIC ACID; 4 (METHYLCARBOXAMIDO)PHENYL 2 (6 METHOXY 2 NAPHTHYL)PROPRANOIC ACID; 4 (METHYLCARBOXAMIDO)PHENYL 2 [1 (4 CHLOROBENZOYL) 5 METHOXY 2 METHYL 1H INDOLYL]ACETIC ACID; 4 (METHYLCARBOXAMIDO)PHENYL 2 [2 (2,6 DICHLOROANILINO)PHENYL]ACETIC ACID; 4 (METHYLCARBOXAMIDO)PHENYL 2 [3 (TRIFLUOROMETHYL) ANILINO]BENZOIC ACID; CARBOXYLIC ACID DERIVATIVE; DICLOFENAC; IBUPROFEN; NONSTEROID ANTIINFLAMMATORY AGENT; PARACETAMOL; PRODRUG; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG METABOLISM; DRUG STABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN TISSUE; INTRAPERITONEAL DRUG ADMINISTRATION; LATENT PERIOD; LIPOPHILICITY; LIVER HOMOGENATE; MOUSE; NONHUMAN; ORAL DRUG ADMINISTRATION; PAIN THRESHOLD; PRIORITY JOURNAL; RABBIT; RAT; STOMACH MUCOSA INJURY; ULCEROGENESIS;

EID: 0031877764     PISSN: 09254692     EISSN: None     Source Type: Journal    
DOI: 10.1007/s10787-998-0031-3     Document Type: Article

References (24)

1. 1. WS Beck HT Schneider K Dietzel B Nuernberg K Brune 1990 Gastrointestinal ulceration induced by antiinflammatory drugs in rats Arch Toxicol 64 210 17 2115324 10.1007/BF02010727 1:CAS:528:DyaK3cXkvFWisrs%3D Beck WS, Schneider HT, Dietzel K, Nuernberg B, Brune K. Gastrointestinal ulceration induced by antiinflammatory drugs in rats. Arch Toxicol. 1990;64:210–17.
2. 2. KD Rainsford 1988 Gastrointestinal damage from NSAIDs Toxicol Pathol 16 251 259 3142030 1:CAS:528:DyaL1cXlt1Wrsbs%3D 10.1177/019262338801600218 Rainsford KD. Gastrointestinal damage from NSAIDs. Toxicol Pathol. 1988;16:251–259.
3. 3. G Jones 1985 Decreased toxicity and adverse reactions via prodrugs H Bundgaard Design of Prodrugs Elsevier Amsterdam 199 241 Jones G. Decreased toxicity and adverse reactions via prodrugs. In: Bundgaard H, ed. Design of Prodrugs. Amsterdam: Elsevier; 1985:199–241.
4. 4. V Cioli S Putzolu PS Barcellona C Corradino 1979 The role of direct tissue contact in the production of GI ulcers by NSAIDs in rats Toxicol Appl Pharmacol 50 283 9 505458 10.1016/0041-008X(79)90153-4 1:CAS:528:DyaE1MXmtVCmtrY%3D Cioli V, Putzolu S, Barcellona PS, Corradino C. The role of direct tissue contact in the production of GI ulcers by NSAIDs in rats. Toxicol Appl Pharmacol. 1979;50:283–9.
5. 5. VR Shanbhag AM Crider R Gokhale A Harplani RM Dick 1992 Ester and amide prodrugs of ibuprofen and naproxen: Synthesis and antiinflammatory activity, and gastrointestinal toxicity J Pharm Sci 81 149 54 1545354 10.1002/jps.2600810210 1:CAS:528:DyaK38XlvFWnsL8%3D Shanbhag VR, Crider AM, Gokhale R, Harplani A, Dick RM. Ester and amide prodrugs of ibuprofen and naproxen: Synthesis and antiinflammatory activity, and gastrointestinal toxicity. J Pharm Sci. 1992;81:149–54.
6. 6. TD Boyer SC Rouff 1971 Acetaminophen induced hepatic necrosis and renal failure J Am Med Assoc 218 440 1 10.1001/jama.218.3.440 1:STN:280:DyaE38%2Fgt1Gisg%3D%3D Boyer TD, Rouff SC. Acetaminophen induced hepatic necrosis and renal failure. J Am Med Assoc. 1971;218:440–1.
7. 7. NPE Vermeulen RV Straat JM TeKoppele 1990 Molecular mechanisms in toxicology and drug design V Classen Trends in Drug Research, Vol. 13 Elsevier Amsterdam 253 71 Vermeulen NPE, Straat RV, TeKoppele JM et al. Molecular mechanisms in toxicology and drug design. In: Classen V, ed. Trends in Drug Research, Vol. 13. Amsterdam: Elsevier; 1990:253–71.
8. 8. MW Whitehouse KD Rainsford 1980 Esterification of acidic anti-inflammatory drugs supresses their gastrotoxicity without adversely affecting their anti-inflammatory activity in rats J Pharm Pharmacol 32 795 6 6110734 1:CAS:528:DyaL3MXhsFSitbg%3D Whitehouse MW, Rainsford KD. Esterification of acidic anti-inflammatory drugs supresses their gastrotoxicity without adversely affecting their anti-inflammatory activity in rats. J Pharm Pharmacol. 1980;32:795–6.
9. 9. H Bundgaard NM Nielsen 1988 Glycolamide esters as a novel biolabile prodrug type for NSAI carboxylic acid drugs Int J Pharmaceut 43 101 10 10.1016/0378-5173(88)90064-6 1:CAS:528:DyaL1cXit1Kksbg%3D Bundgaard H, Nielsen NM. Glycolamide esters as a novel biolabile prodrug type for NSAI carboxylic acid drugs. Int J Pharmaceut. 1988;43:101–10.
10. 10. Omar FA. Cyclic amide derivatives as potential prodrugs. Synthesis and evaluation of N-hydroxymethylphthalimide esters of some NSAI carboxylic acid drugs. Eur J Med Chem. 1998;33 [in press].
11. 11. T Ogiso M Iwaki T Tanino 1996 Pharmacokinetics of indomethacin ester prodrugs: Gastrointestinal and hepatic toxicity and the hydrolytic capacity of various tissues in rats Biol Pharm Bull 19 1178 83 8889037 1:CAS:528:DyaK28XlvFCnsL0%3D Ogiso T, Iwaki M, Tanino T et al. Pharmacokinetics of indomethacin ester prodrugs: Gastrointestinal and hepatic toxicity and the hydrolytic capacity of various tissues in rats. Biol Pharm Bull. 1996;19:1178–83.
12. 12. IM Kovach IH Pitman T Higuchi 1981 Amino acid esters of phenols as prodrug: synthesis and stability of glycine, β-aspartic, and α-aspartic acid esters of p-acetamidophenol J Pharm Sci 70 881 5 7310656 10.1002/jps.2600700812 1:CAS:528:DyaL38XntVCj Kovach IM, Pitman IH, Higuchi T. Amino acid esters of phenols as prodrug: synthesis and stability of glycine, β-aspartic, and α-aspartic acid esters of p-acetamidophenol. J Pharm Sci. 1981;70:881–5.
13. 13. E Bousquet A Marrazo G Puglisi A Spadaro S Terindi 1996 Synthesis, physical properties, toxicological studies and bioavailability of l-pyroglutamic and l-glutamic acid esters of paracetamol as potentially useful prodrugs J Pharm Pharmacol 48 479 85 8799871 1:CAS:528:DyaK28XjvFars7o%3D Bousquet E, Marrazo A, Puglisi G, Spadaro A, Terindi S. Synthesis, physical properties, toxicological studies and bioavailability of l-pyroglutamic and l-glutamic acid esters of paracetamol as potentially useful prodrugs. J Pharm Pharmacol. 1996;48:479–85.
14. 14. TY Shen 1980 Non steroidal antiinflammatory agents EM Wolf Burger’s Medicinal Chemistry 4th edn John-Willey and Sons New York 1228 1228 Shen TY. Non steroidal antiinflammatory agents. In: Wolf EM, ed. Burger’s Medicinal Chemistry, 4th edn, Part III. New York: John-Willey and Sons; 1980:1228.
15. 15. JAM Christiaans H Timmerman 1996 Cardiovascular hybrid drugs: combination of more than one pharmacological property in one single molecule Eur J Pharm Sci 4 1 22 10.1016/0928-0987(95)00029-1 1:CAS:528:DyaK28XjtVejtQ%3D%3D Christiaans JAM, Timmerman H. Cardiovascular hybrid drugs: combination of more than one pharmacological property in one single molecule. Eur J Pharm Sci. 1996;4:1–22.
16. 16. RR Alex VM Kulkarni 1995 Design and synthesis of penicilloyl oxymethyl quinolone carbamates as a new class of dual-acting antibacterials Eur J Med Chem 30 815 18 10.1016/0223-5234(96)88301-2 1:CAS:528:DyaK2MXptVajtL4%3D Alex RR, Kulkarni VM. Design and synthesis of penicilloyl oxymethyl quinolone carbamates as a new class of dual-acting antibacterials. Eur J Med Chem. 1995;30:815–18.
17. 17. GKE Scriba 1996 3-Hydroxymethylphenytoin valproic acid ester, a new prodrug combining two anticonvulsant drugs Arch Pharm Pharm Med Chem 329 554 5 10.1002/ardp.19963291208 1:CAS:528:DyaK2sXhtFKju7c%3D Scriba GKE. 3-Hydroxymethylphenytoin valproic acid ester, a new prodrug combining two anticonvulsant drugs. Arch Pharm Pharm Med Chem. 1996;329:554–5.
18. 18. MA Zahran L Kovacs I Sakka El EB Pedersen C Nielsen 1996 The potential of aspirin in prodrug synthesis: A new potential delivery system of AZT and FLT Arch Pharm Pharm Med Chem 329 417 20 10.1002/ardp.19963290809 1:CAS:528:DyaK28XmtlWku7o%3D Zahran MA, Kovacs L, El Sakka I, Pedersen EB, Nielsen C. The potential of aspirin in prodrug synthesis: A new potential delivery system of AZT and FLT. Arch Pharm Pharm Med Chem. 1996;329:417–20.
19. 19. A Vigroux M Bergon C Zedde 1995 Cyclization-activated prodrugs: N-(substituted 2-hydroxylphenyl and 2-hydroxypropyl)carbamates based on ring-opened derivatives of active benzoxazolones and oxazolidinones as mutual prodrugs of acetaminophen J Med Chem 38 3983 94 7562932 10.1021/jm00020a012 1:CAS:528:DyaK2MXnvFSqs78%3D Vigroux A, Bergon M, Zedde C. Cyclization-activated prodrugs: N-(substituted 2-hydroxylphenyl and 2-hydroxypropyl)carbamates based on ring-opened derivatives of active benzoxazolones and oxazolidinones as mutual prodrugs of acetaminophen. J Med Chem. 1995;38:3983–94.
20. 20. AC Moffat 1986 Clark’s Isolation and Identification of Drugs Pharmaceutical Press London Moffat AC, ed. Clark’s Isolation and Identification of Drugs. London: Pharmaceutical Press; 1986.
21. 21. AJ Leo 1993 Calculating log P oct from structures Chem Rev 93 1281 1306 10.1021/cr00020a001 1:CAS:528:DyaK3sXktFKjtr4%3D Leo AJ. Calculating log P oct from structures. Chem Rev. 1993;93:1281–1306.
22. 22. AH Khans H Bundgaard 1990 Prodrugs as delivery systems 107. Synthesis and chemical and enzymatic hydrolysis kinetics of various mono and diester prodrugs of N-acetylcysteine Int J Pharmaceut 62 193 205 10.1016/0378-5173(90)90233-T Khans AH, Bundgaard H. Prodrugs as delivery systems 107. Synthesis and chemical and enzymatic hydrolysis kinetics of various mono and diester prodrugs of N-acetylcysteine. Int J Pharmaceut. 1990;62:193–205.
23. 23. FA Omar NM Mahfouz M Rahman 1996 Design, synthesis and antiinflammatory activity of some 1,3,4-oxadiazole derivatives Eur J Med Chem 31 819 25 10.1016/0223-5234(96)83976-6 1:CAS:528:DyaK28XmvFOrtbs%3D Omar FA, Mahfouz NM, Rahman M. Design, synthesis and antiinflammatory activity of some 1,3,4-oxadiazole derivatives. Eur J Med Chem. 1996;31:819–25.
24. 24. ZH Galina CJ Sutherland Z Amit 1983 Effects of heat-stress on behaviour and the pituitary adrenal axis in rats Pharmacol Biochem Behav 19 251 6 6314388 10.1016/0091-3057(83)90048-5 1:CAS:528:DyaL3sXls12rtb8%3D Galina ZH, Sutherland CJ, Amit Z. Effects of heat-stress on behaviour and the pituitary adrenal axis in rats. Pharmacol Biochem Behav. 1983;19:251–6.