A S Kalgutkar

Summary

Affiliation: Pfizer Global Research and Development
Country: USA

Publications

  1. ncbi Amide derivatives of meclofenamic acid as selective cyclooxygenase-2 inhibitors
    Amit S Kalgutkar
    A B Hancock, Jr, Memorial Laboratory for Cancer Research, Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 12:521-4. 2002
  2. ncbi Inhibition of hepatobiliary transport as a predictive method for clinical hepatotoxicity of nefazodone
    Seva E Kostrubsky
    Department of Safety Science and Pharmacokinetics, Pfizer Global Research and Development, Ann Arbor, Michigan 48105, USA
    Toxicol Sci 90:451-9. 2006
  3. ncbi Application of a linear ion trap/orbitrap mass spectrometer in metabolite characterization studies: examination of the human liver microsomal metabolism of the non-tricyclic anti-depressant nefazodone using data-dependent accurate mass measurements
    Scott M Peterman
    Thermo Electron Corporation, Somerset, New Jersey, USA
    J Am Soc Mass Spectrom 17:363-75. 2006
  4. ncbi A semiquantitative method for the determination of reactive metabolite conjugate levels in vitro utilizing liquid chromatography-tandem mass spectrometry and novel quaternary ammonium glutathione analogues
    John R Soglia
    Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer Central Research, Eastern Point Road, Groton, Connecticut 06340, USA
    Chem Res Toxicol 19:480-90. 2006
  5. ncbi In vitro metabolism studies on the isoxazole ring scission in the anti-inflammatory agent lefluonomide to its active alpha-cyanoenol metabolite A771726: mechanistic similarities with the cytochrome P450-catalyzed dehydration of aldoximes
    Amit S Kalgutkar
    Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer Global Research and Development, Groton, CT 06340, USA
    Drug Metab Dispos 31:1240-50. 2003
  6. ncbi Metabolic activation of the nontricyclic antidepressant trazodone to electrophilic quinone-imine and epoxide intermediates in human liver microsomes and recombinant P4503A4
    Amit S Kalgutkar
    Pharmacokinetics Dynamics and Metabolism Department, Pfizer Global Research and Development, Eastern Point Road, Groton, MA 06340, USA
    Chem Biol Interact 155:10-20. 2005
  7. ncbi A comprehensive listing of bioactivation pathways of organic functional groups
    Amit S Kalgutkar
    Pharmacokinetics, Dynamics and Metabolism Department, PGRD, Groton, CT 06340, USA
    Curr Drug Metab 6:161-225. 2005
  8. ncbi Disposition of CP-671, 305, a selective phosphodiesterase 4 inhibitor in preclinical species
    A S Kalgutkar
    Department of Pharmacokinetics, Pfizer Global Research and Development, Groton, CT 06340, USA
    Xenobiotica 34:755-70. 2004
  9. ncbi Bioactivation of the nontricyclic antidepressant nefazodone to a reactive quinone-imine species in human liver microsomes and recombinant cytochrome P450 3A4
    Amit S Kalgutkar
    Pharmacokinetics, Dynamics, and Metabolism Department, Pfizer Global Research and Development, Groton, CT 06340, USA
    Drug Metab Dispos 33:243-53. 2005
  10. ncbi Identification of an N-methyl-4-phenylpyridinium-like metabolite of the antidiarrheal agent loperamide in human liver microsomes: underlying reason(s) for the lack of neurotoxicity despite the bioactivation event
    Amit S Kalgutkar
    Discovery Pharmacokinetics, Dynamics, and Metabolism Department, Pfizer Global Research and Development, Groton, CT 06340, USA
    Drug Metab Dispos 32:943-52. 2004

Detail Information

Publications51

  1. ncbi Amide derivatives of meclofenamic acid as selective cyclooxygenase-2 inhibitors
    Amit S Kalgutkar
    A B Hancock, Jr, Memorial Laboratory for Cancer Research, Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Bioorg Med Chem Lett 12:521-4. 2002
    ..This paper describes SAR studies involved in the transformation of the NSAID meclofenamic acid into potent and selective cyclooxygenase-2 (COX-2) inhibitors via neutralization of the carboxylate moiety in this nonselective COX inhibitor...
  2. ncbi Inhibition of hepatobiliary transport as a predictive method for clinical hepatotoxicity of nefazodone
    Seva E Kostrubsky
    Department of Safety Science and Pharmacokinetics, Pfizer Global Research and Development, Ann Arbor, Michigan 48105, USA
    Toxicol Sci 90:451-9. 2006
    ..Our findings are consistent with the clinical experience and suggest that described methodology can be applied in the selection of nonhepatotoxic drug candidates...
  3. ncbi Application of a linear ion trap/orbitrap mass spectrometer in metabolite characterization studies: examination of the human liver microsomal metabolism of the non-tricyclic anti-depressant nefazodone using data-dependent accurate mass measurements
    Scott M Peterman
    Thermo Electron Corporation, Somerset, New Jersey, USA
    J Am Soc Mass Spectrom 17:363-75. 2006
    ..The ability to conduct biotransformation profiling via tandem mass spectrometry coupled with accurate mass measurements, all in a single experimental run, is clearly one of the most attractive features of this methodology...
  4. ncbi A semiquantitative method for the determination of reactive metabolite conjugate levels in vitro utilizing liquid chromatography-tandem mass spectrometry and novel quaternary ammonium glutathione analogues
    John R Soglia
    Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer Central Research, Eastern Point Road, Groton, Connecticut 06340, USA
    Chem Res Toxicol 19:480-90. 2006
    ....
  5. ncbi In vitro metabolism studies on the isoxazole ring scission in the anti-inflammatory agent lefluonomide to its active alpha-cyanoenol metabolite A771726: mechanistic similarities with the cytochrome P450-catalyzed dehydration of aldoximes
    Amit S Kalgutkar
    Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer Global Research and Development, Groton, CT 06340, USA
    Drug Metab Dispos 31:1240-50. 2003
    ....
  6. ncbi Metabolic activation of the nontricyclic antidepressant trazodone to electrophilic quinone-imine and epoxide intermediates in human liver microsomes and recombinant P4503A4
    Amit S Kalgutkar
    Pharmacokinetics Dynamics and Metabolism Department, Pfizer Global Research and Development, Eastern Point Road, Groton, MA 06340, USA
    Chem Biol Interact 155:10-20. 2005
    ..It is proposed that the quinone-imine and/or the epoxide intermediate(s) may represent a rate-limiting step in the initiation of trazodone-mediated hepatotoxicity...
  7. ncbi A comprehensive listing of bioactivation pathways of organic functional groups
    Amit S Kalgutkar
    Pharmacokinetics, Dynamics and Metabolism Department, PGRD, Groton, CT 06340, USA
    Curr Drug Metab 6:161-225. 2005
    ....
  8. ncbi Disposition of CP-671, 305, a selective phosphodiesterase 4 inhibitor in preclinical species
    A S Kalgutkar
    Department of Pharmacokinetics, Pfizer Global Research and Development, Groton, CT 06340, USA
    Xenobiotica 34:755-70. 2004
    ....
  9. ncbi Bioactivation of the nontricyclic antidepressant nefazodone to a reactive quinone-imine species in human liver microsomes and recombinant cytochrome P450 3A4
    Amit S Kalgutkar
    Pharmacokinetics, Dynamics, and Metabolism Department, Pfizer Global Research and Development, Groton, CT 06340, USA
    Drug Metab Dispos 33:243-53. 2005
    ....
  10. ncbi Identification of an N-methyl-4-phenylpyridinium-like metabolite of the antidiarrheal agent loperamide in human liver microsomes: underlying reason(s) for the lack of neurotoxicity despite the bioactivation event
    Amit S Kalgutkar
    Discovery Pharmacokinetics, Dynamics, and Metabolism Department, Pfizer Global Research and Development, Groton, CT 06340, USA
    Drug Metab Dispos 32:943-52. 2004
    ..The differences in safety profile of haloperidol and loperamide despite a common bioactivation event supports the notion that not all compounds undergoing bioactivation in vitro will necessarily elicit a toxicological response in vivo...
  11. ncbi Influence of lipophilicity on the interactions of N-alkyl-4-phenyl-1,2,3,6-tetrahydropyridines and their positively charged N-alkyl-4-phenylpyridinium metabolites with cytochrome P450 2D6
    Amit S Kalgutkar
    Pharmacokinetics, Dynamics, and Metabolism Department, Pfizer Global Research and Development, Groton, Connecticut 06340, USA
    Drug Metab Dispos 31:596-605. 2003
    ..This phenomenon appears to be a common theme among several cyclic tertiary amine-containing anti-depressants and should be taken into consideration when designing central nervous system agents devoid of CYP2D6 substrate properties...
  12. ncbi Assessment of the contributions of CYP3A4 and CYP3A5 in the metabolism of the antipsychotic agent haloperidol to its potentially neurotoxic pyridinium metabolite and effect of antidepressants on the bioactivation pathway
    Amit S Kalgutkar
    Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer Global Research and Development, Groton, Connecticut 06340, USA
    Drug Metab Dispos 31:243-9. 2003
    ....
  13. ncbi On the diversity of oxidative bioactivation reactions on nitrogen-containing xenobiotics
    Amit S Kalgutkar
    Pharmacokinetics, Dynamics, and Metabolism Department, Pfizer Global Research and Development, Groton, CT 06340, USA
    Curr Drug Metab 3:379-424. 2002
    ..Potential strategies that could be utilized in the screening of novel bioactivation pathways are also discussed...
  14. ncbi Studies on the metabolism of the novel, selective cyclooxygenase-2 inhibitor indomethacin phenethylamide in rat, mouse, and human liver microsomes: identification of active metabolites
    Rory P Remmel
    Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Drug Metab Dispos 32:113-22. 2004
    ..The glucuronides of 2'hydroxy-LM-4108 and O-desmethyl-2'-hydroxy-LM-4108 were also identified in rat bile...
  15. ncbi Pharmacokinetics and metabolism of a cysteinyl leukotriene-1 receptor antagonist from the heterocyclic chromanol series in rats: in vitro-in vivo correlation, gender-related differences, isoform identification, and comparison with metabolism in human hepa
    A V Kuperman
    Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer Global Research and Development, Groton, CT 06340, USA
    Drug Metab Dispos 29:1403-9. 2001
    ..Considering that O-demethylation is the major route of elimination in humans, the in vivo clearance of CP-199,331 may exhibit moderate variability, depending on CYP3A4 abundance in the human population...
  16. doi Utility of the carboxylesterase inhibitor bis-para-nitrophenylphosphate (BNPP) in the plasma unbound fraction determination for a hydrolytically unstable amide derivative and agonist of the TGR5 receptor
    H Eng
    Pharmacokinetics, Dynamics and Metabolism, Groton, CT, USA
    Xenobiotica 40:369-80. 2010
    ....
  17. ncbi Kinetics of the interaction of nonsteroidal antiinflammatory drugs with prostaglandin endoperoxide synthase-1 studied by limited proteolysis
    A S Kalgutkar
    A B Hancock, Jr, Memorial Laboratory for Cancer Research, Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Biochemistry 35:9076-82. 1996
    ..The results suggest that induction of trypsin resistance is a reflection of the initial association of reversible as well as irreversible inhibitors with the apoprotein...
  18. doi Biochemical basis for differences in metabolism-dependent genotoxicity by two diazinylpiperazine-based 5-HT2C receptor agonists
    Amit S Kalgutkar
    Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA
    Bioorg Med Chem Lett 19:1559-63. 2009
    ..Plausible hypotheses that can collectively account for the differences in mutagenic response of the two piperazine analogs are discussed...
  19. doi Utility of MetaSite in improving metabolic stability of the neutral indomethacin amide derivative and selective cyclooxygenase-2 inhibitor 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-N-phenethyl-acetamide
    David Boyer
    Pharmacokinetics, Dynamics, and Metabolism Department, Pfizer Global Research and Development, Groton, CT 06340, USA
    Drug Metab Dispos 37:999-1008. 2009
    ..Overall, the predictions from MetaSite gave useful information leading to the design of new compounds with improved metabolic properties...
  20. doi Comparison of the bioactivation potential of the antidepressant and hepatotoxin nefazodone with aripiprazole, a structural analog and marketed drug
    Jonathan N Bauman
    Pharmacokinetics, Dynamics, and Metabolism Department, Pfizer Global Research and Development, Groton, CT 06340, USA
    Drug Metab Dispos 36:1016-29. 2008
    ..This attribute probably reduces the total body burden to reactive metabolite exposure and may not exceed a threshold needed for toxicity...
  21. doi Differences in CYP3A4 catalyzed bioactivation of 5-aminooxindole and 5-aminobenzsultam scaffolds in proline-rich tyrosine kinase 2 (PYK2) inhibitors: retrospective analysis by CYP3A4 molecular docking, quantum chemical calculations and glutathione adduct
    Hao Sun
    Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA
    Bioorg Med Chem Lett 19:3177-82. 2009
    ..The value of linear ion/orbitrap mass spectrometry to detect GSH conjugates with greater sensitivity, compared with conventional triple quadrupole mass spectrometry approaches, was also demonstrated in the course of these studies...
  22. ncbi A novel mechanism of cyclooxygenase-2 inhibition involving interactions with Ser-530 and Tyr-385
    Scott W Rowlinson
    Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0146, USA
    J Biol Chem 278:45763-9. 2003
    ..Mutagenesis experiments suggest Ser-530 is also important in time-dependent inhibition by nimesulide and piroxicam...
  23. doi Pharmacokinetics, disposition and lipid-modulating activity of 5-{2-[4-(3,4-difluorophenoxy)-phenyl]-ethylsulfamoyl}-2-methyl-benzoic acid, a potent and subtype-selective peroxisome proliferator-activated receptor alpha agonist in preclinical species and
    K S Frederick
    Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Groton, CT 06340, USA
    Xenobiotica 39:766-81. 2009
    ..First-in-human clinical studies on 1 following oral administration suggested that the human pharmacokinetics/dose predictions were in the range that yielded a favourable pharmacodynamic response...
  24. doi Utility of multivariate analysis in support of in vitro metabolite identification studies: retrospective analysis using the antidepressant drug nefazodone
    R P Schneider
    Pharmacokinetics, Dynamics and Metabolism Department, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA
    Xenobiotica 40:262-74. 2010
    ....
  25. ncbi Indolyl esters and amides related to indomethacin are selective COX-2 inhibitors
    Amit S Kalgutkar
    A B Hancock, Jr, Memorial Laboratory for Cancer Research, Department of Biochemistry and Chemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232 0146, USA
    Bioorg Med Chem 13:6810-22. 2005
    ..7. Overall, this strategy broadens the scope of our previous methodology of neutralizing the carboxylic acid group in NSAIDs as a means of generating COX-2-selective inhibitors and is potentially applicable to other NSAIDs...
  26. ncbi NADPH-dependent covalent binding of [3H]paroxetine to human liver microsomes and S-9 fractions: identification of an electrophilic quinone metabolite of paroxetine
    Sabrina X Zhao
    Pharmacokinetics, Dynamics and Metabolism Department, Pfizer Global Research and Development, Groton, Connecticut, USA
    Chem Res Toxicol 20:1649-57. 2007
    ....
  27. ncbi Bioactivation of phencyclidine in rat and human liver microsomes and recombinant P450 2B enzymes: evidence for the formation of a novel quinone methide intermediate
    James P Driscoll
    Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Groton, CT 06340, USA
    Chem Res Toxicol 20:1488-97. 2007
    ..To our knowledge, this is the first report of a quinone methide reactive intermediate obtained in human-liver microsomal metabolism of PCP...
  28. ncbi Discovery of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide, an agonist of the alpha7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia: synthesis and structure--activity relationsh
    Donn G Wishka
    Pfizer Global Research and Development, Eastern Point Road, Groton, Connecticut 06340, USA
    J Med Chem 49:4425-36. 2006
    ....
  29. ncbi Cyclooxygenase 2 inhibitors: discovery, selectivity and the future
    L J Marnett
    Departments of Biochemistry and Chemistry, Center in Molecular Toxicology and Vanderbilt Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Trends Pharmacol Sci 20:465-9. 1999
    ..In this review, some key points and unresolved issues related to the discovery of COX-2 inhibitors, the kinetic and structural basis for their selectivity, and possible complications in their development and use will be discussed...
  30. ncbi Design of selective inhibitors of cyclooxygenase-2 as nonulcerogenic anti-inflammatory agents
    L J Marnett
    AB Hancock Jr Memorial Laboratory for Cancer Research, Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Curr Opin Chem Biol 2:482-90. 1998
    ..Preclinical and clinical studies suggest cyclooxygenase-2 inhibitors are highly promising new agents for the treatment of pain and inflammation, and for the prevention of cancer...
  31. doi N-(3,4-dimethoxyphenethyl)-4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2[1H]-yl)-6,7-dimethoxyquinazolin-2-amine (CP-100,356) as a "chemical knock-out equivalent" to assess the impact of efflux transporters on oral drug absorption in the rat
    Amit S Kalgutkar
    Pharmacokinetics, Dynamics and Metabolism Department, Pfizer Global Research and Development, Eastern Point Road, Groton, Connecticut 06340, USA
    J Pharm Sci 98:4914-27. 2009
    ..The in vivo methodology should have utility in drug discovery in selective and facile assessment of the role of MDR1 and BCRP efflux transporters in oral absorption of new drug candidates...
  32. doi Structural alerts, reactive metabolites, and protein covalent binding: how reliable are these attributes as predictors of drug toxicity?
    Amit S Kalgutkar
    Pharmacokinetics, Dynamics and Metabolism Department, Pfizer Global Research and Development, Groton, CT 06340, USA
    Chem Biodivers 6:2115-37. 2009
    ....
  33. doi Can in vitro metabolism-dependent covalent binding data distinguish hepatotoxic from nonhepatotoxic drugs? An analysis using human hepatocytes and liver S-9 fraction
    Jonathon N Bauman
    Pharmacokinetics, Dynamics and Metabolism Department, Pfizer Global Research and Development, Groton, Connecticut 06340, USA
    Chem Res Toxicol 22:332-40. 2009
    ..will be essential to any understanding of the problem of metabolism-dependent hepatotoxicity and predicting toxicity from in vitro experiments...
  34. doi Trifluoromethylpyrimidine-based inhibitors of proline-rich tyrosine kinase 2 (PYK2): structure-activity relationships and strategies for the elimination of reactive metabolite formation
    Daniel P Walker
    Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA
    Bioorg Med Chem Lett 18:6071-7. 2008
    ....
  35. doi In vitro metabolism and covalent binding of enol-carboxamide derivatives and anti-inflammatory agents sudoxicam and meloxicam: insights into the hepatotoxicity of sudoxicam
    R Scott Obach
    Pharmacokinetics, Dynamics, and Metabolism Department, Pfizer Global Research and Development, Groton, Connecticut, USA
    Chem Res Toxicol 21:1890-9. 2008
    ....
  36. doi The discovery of novel calcium sensing receptor negative allosteric modulators
    Gayatri Balan
    Pfizer Global Research and Development, Groton New London Laboratories, Pfizer Inc, Eastern Point Road, Groton, CT 06340, USA
    Bioorg Med Chem Lett 19:3328-32. 2009
    ..Evaluation of key analogues using a rat model demonstrate a robust response, significantly improved potency over ronacaleret and have the potential as an oral, anabolic treatment for osteoporosis...
  37. doi Short-acting 5-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4(3H)-one derivatives as orally-active calcium-sensing receptor antagonists
    Mary T Didiuk
    Pfizer Global Research and Development, Groton, CT 06340, United States
    Bioorg Med Chem Lett 19:4555-9. 2009
    ..Orally-active compounds were identified which displayed the desired animal pharmacology (rapid and transient stimulation of parathyroid hormone) essential for bone anabolic effects...
  38. doi Can in vitro metabolism-dependent covalent binding data in liver microsomes distinguish hepatotoxic from nonhepatotoxic drugs? An analysis of 18 drugs with consideration of intrinsic clearance and daily dose
    R Scott Obach
    Pharmacokinetics, Dynamics and Metabolism Department, Pfizer Global Research and Development, Groton, Connecticut 06340, USA
    Chem Res Toxicol 21:1814-22. 2008
    ....
  39. doi Discovery tactics to mitigate toxicity risks due to reactive metabolite formation with 2-(2-hydroxyaryl)-5-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4(3h)-one derivatives, potent calcium-sensing receptor antagonists and clinical candidate(s) for the treatme
    Amit S Kalgutkar
    Pharmacokinetics, Dynamics and Metabolism Department and Department of Medicinal Chemistry, Pfizer Global Research and Development, Groton, Connecticut 06340, USA
    Chem Res Toxicol 23:1115-26. 2010
    ..Herein, the collective findings from our discovery efforts in the CaSR program, which include the incorporation of appropriate derisking steps when dealing with RM issues are summarized...
  40. ncbi A rational chemical intervention strategy to circumvent bioactivation liabilities associated with a nonpeptidyl thrombopoietin receptor agonist containing a 2-amino-4-arylthiazole motif
    Amit S Kalgutkar
    Pharmacokinetics, Dynamics and Metabolism Department, Pfizer Global Research and Development, Groton, Connecticut 06340, USA
    Chem Res Toxicol 20:1954-65. 2007
    ..These structural changes not only abrogated the bioactivation liability associated with 1 but also resulted in compounds that retained the attractive pharmacological and pharmacokinetic attributes of the prototype agent...
  41. ncbi Biotransformation reactions of five-membered aromatic heterocyclic rings
    Deepak K Dalvie
    Pharmacokinetics, Dynamics and Drug Metabolism, Pfizer Global Research and Development, Eastern Point Road, Groton, Connecticut 06340, USA
    Chem Res Toxicol 15:269-99. 2002
  42. ncbi Mechanism-based inactivation of human recombinant P450 2C9 by the nonsteroidal anti-inflammatory drug suprofen
    John P O'Donnell
    Pharmacokinetics, Dynamics, and Metabolism, Pfizer Global Research and Development, Groton, CT 06340, USA
    Drug Metab Dispos 31:1369-77. 2003
    ..This electrophilic alpha, beta-unsaturated aldehyde represents a possible reactive intermediate that bioalkylates P450 2C9...
  43. ncbi Structure-activity relationships of triazolopyridine oxazole p38 inhibitors: identification of candidates for clinical development
    Kim F McClure
    Pfizer Global Research and Development, Groton Laboratories, CT 06340, USA
    Bioorg Med Chem Lett 16:4339-44. 2006
    ..The deficiencies of the lead structure in the series, CP-808844, were overcome by changes to the C4 aryl group and the triazole side-chain culminating in the identification of several potential clinical candidates...
  44. ncbi Minimising the potential for metabolic activation in drug discovery
    Amit S Kalgutkar
    Pfizer Global Research and Development, Pharmacokinetics, Dynamics and Metabolism Department, Groton, CT 06340, USA
    Expert Opin Drug Metab Toxicol 1:91-142. 2005
    ....
  45. ncbi Preclinical pharmacokinetics and metabolism of 6-(4-(2,5-difluorophenyl)oxazol-5-yl)-3-isopropyl-[1,2,4]-triazolo[4,3-a]pyridine, a novel and selective p38alpha inhibitor: identification of an active metabolite in preclinical species and human liver micro
    Amit S Kalgutkar
    Pharmacokinetics, Dynamics and Metabolism Department, Pfizer Global Research and Development, Groton, CT 06340, USA
    Biopharm Drug Dispos 27:371-86. 2006
    ....
  46. ncbi Genotoxicity of 2-(3-chlorobenzyloxy)-6-(piperazinyl)pyrazine, a novel 5-hydroxytryptamine2c receptor agonist for the treatment of obesity: role of metabolic activation
    Amit S Kalgutkar
    Pharmacokinetics, Dynamics, and Metabolism Department, Pfizer Global Research and Development, Groton, CT 06340, USA
    Drug Metab Dispos 35:848-58. 2007
    ..The metabolism studies described herein provide a mechanistic basis for the mutagenicity of 3...
  47. ncbi Mechanism-based inactivation of cytochrome P450 enzymes: chemical mechanisms, structure-activity relationships and relationship to clinical drug-drug interactions and idiosyncratic adverse drug reactions
    Amit S Kalgutkar
    Pharmacokinetics, Dynamics and Metabolism Department, Pfizer Global Research and Development, Groton, CT 06340, USA
    Curr Drug Metab 8:407-47. 2007
    ..In addition, the current state-of-the-art of the methodology used in predicting the magnitude of DDIs using in vitro P450 inactivation data and human pharmacokinetic parameters is discussed in detail...
  48. ncbi Role of transporters in the disposition of the selective phosphodiesterase-4 inhibitor (+)-2-[4-({[2-(benzo[1,3]dioxol-5-yloxy)-pyridine-3-carbonyl]-amino}-methyl)-3-fluoro-phenoxy]-propionic acid in rat and human
    Amit S Kalgutkar
    Pharmacokinetics, Dyamics, and Metabolism Department, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA
    Drug Metab Dispos 35:2111-8. 2007
    ....
  49. ncbi Discovery and design of selective cyclooxygenase-2 inhibitors as non-ulcerogenic, anti-inflammatory drugs with potential utility as anti-cancer agents
    A S Kalgutkar
    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Curr Drug Targets 2:79-106. 2001
    ....
  50. ncbi Intravenous pharmacokinetics and metabolism of the reactive oxygen scavenger alpha-phenyl-N-tert-butyl nitrone (PBN) in the cynomolgus monkey
    Mary E Lame
    Pharmacokinetics, Dynamics, and Metabolism, Pfizer Global Research and Development, Groton, CT 06340, USA
    Drug Metabol Drug Interact 20:11-24. 2004
    ..In conclusion, the pharmacokinetic attributes and the clearance mechanism of PBN in the cynomolgus monkey is similar to that observed in the Sprague-Dawley rat...
  51. ncbi Pharmacokinetics and metabolism of the reactive oxygen scavenger alpha-phenyl-N-tert-butylnitrone in the male Sprague-Dawley rat
    Mary E Trudeau-Lame
    Pharmacokinetics, Dynamics, and Metabolism, Pfizer Global Research and Development, Groton, CT 06340, USA
    Drug Metab Dispos 31:147-52. 2003
    ..We speculate that 4-HOPBN is an "active" PBN metabolite that provides an additive effect to the pharmacological action of PBN in vivo...