Louis J Lombardo

Summary

Affiliation: Bristol-Myers Squibb
Country: USA

Publications

  1. ncbi request reprint Apoptotic and cytostatic farnesyltransferase inhibitors have distinct pharmacology and efficacy profiles in tumor models
    Veeraswamy Manne
    Oncology Drug Discovery and Discovery Chemistry, Bristol Myers Squibb Company Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA
    Cancer Res 64:3974-80. 2004
  2. doi request reprint Discovery of brivanib alaninate ((S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-yl)2-aminopropanoate), a novel prodrug of dual vascular endothelial growth factor receptor-2 and fibroblast growth fa
    Zhen Wei Cai
    Bristol Myers Squibb Research and Development, Princeton, NJ 08543, USA
    J Med Chem 51:1976-80. 2008
  3. ncbi request reprint Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays
    Louis J Lombardo
    Bristol Myers Squibb Pharmaceutical Research Institute, P O Box 4000, Princeton, New Jersey 08543 4000, USA
    J Med Chem 47:6658-61. 2004
  4. ncbi request reprint Design, synthesis, and structure-activity relationships of tetrahydroquinoline-based farnesyltransferase inhibitors
    Louis J Lombardo
    Bristol Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543 4000, United States
    Bioorg Med Chem Lett 15:1895-9. 2005
  5. doi request reprint Discovery of pyrrolopyridine-pyridone based inhibitors of Met kinase: synthesis, X-ray crystallographic analysis, and biological activities
    Kyoung Soon Kim
    Department of Oncology Chemistry, Bristol Myers Squibb Pharmaceutical Research and Development, P O Box 4000, Princeton, New Jersey 08543 4000, USA
    J Med Chem 51:5330-41. 2008
  6. doi request reprint Design, synthesis and structure-activity relationships of novel biarylamine-based Met kinase inhibitors
    David K Williams
    Bristol Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 20:2998-3002. 2010
  7. doi request reprint Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a selective and orally efficacious inhibitor of the Met kinase superfamily
    Gretchen M Schroeder
    Bristol Myers Squibb Research and Development, Princeton, New Jersey, 08543 4000, USA
    J Med Chem 52:1251-4. 2009
  8. doi request reprint Synthesis, SAR, and Evaluation of 4-[2,4-Difluoro-5-(cyclopropylcarbamoyl)phenylamino]pyrrolo[2,1-f][1,2,4]triazine-based VEGFR-2 kinase inhibitors
    Zhen Wei Cai
    Bristol Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 18:1354-8. 2008
  9. doi request reprint Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors
    Zhen Wei Cai
    Bristol Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 18:3224-9. 2008
  10. ncbi request reprint Discovery and evaluation of N-cyclopropyl- 2,4-difluoro-5-((2-(pyridin-2-ylamino)thiazol-5- ylmethyl)amino)benzamide (BMS-605541), a selective and orally efficacious inhibitor of vascular endothelial growth factor receptor-2
    Robert M Borzilleri
    Bristol Myers Squibb Pharmaceutical Research Institute, P O Box 4000, Princeton, New Jersey 08543 4000, USA
    J Med Chem 49:3766-9. 2006

Collaborators

Detail Information

Publications26

  1. ncbi request reprint Apoptotic and cytostatic farnesyltransferase inhibitors have distinct pharmacology and efficacy profiles in tumor models
    Veeraswamy Manne
    Oncology Drug Discovery and Discovery Chemistry, Bristol Myers Squibb Company Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA
    Cancer Res 64:3974-80. 2004
    ..We developed a highly sensitive San-1 murine xenograft tumor model that is particularly useful for evaluating the in vivo activity of cytostatic FTIs such as BMS-225975...
  2. doi request reprint Discovery of brivanib alaninate ((S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-yl)2-aminopropanoate), a novel prodrug of dual vascular endothelial growth factor receptor-2 and fibroblast growth fa
    Zhen Wei Cai
    Bristol Myers Squibb Research and Development, Princeton, NJ 08543, USA
    J Med Chem 51:1976-80. 2008
    ..The l-alanine prodrug 8 (also known as brivanib alaninate/BMS-582664) was selected as a development candidate and is presently in phase II clinical trials...
  3. ncbi request reprint Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays
    Louis J Lombardo
    Bristol Myers Squibb Pharmaceutical Research Institute, P O Box 4000, Princeton, New Jersey 08543 4000, USA
    J Med Chem 47:6658-61. 2004
    ..On the basis of its robust in vivo activity and favorable pharmacokinetic profile, 13 was selected for additional characterization for oncology indications...
  4. ncbi request reprint Design, synthesis, and structure-activity relationships of tetrahydroquinoline-based farnesyltransferase inhibitors
    Louis J Lombardo
    Bristol Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543 4000, United States
    Bioorg Med Chem Lett 15:1895-9. 2005
    ..BMS-316810 (9e), a 0.7 nM FT inhibitor, was orally-active in a nude mouse tumor allograft efficacy study...
  5. doi request reprint Discovery of pyrrolopyridine-pyridone based inhibitors of Met kinase: synthesis, X-ray crystallographic analysis, and biological activities
    Kyoung Soon Kim
    Department of Oncology Chemistry, Bristol Myers Squibb Pharmaceutical Research and Development, P O Box 4000, Princeton, New Jersey 08543 4000, USA
    J Med Chem 51:5330-41. 2008
    ..It possesses a favorable pharmacokinetic profile in mice and demonstrates significant in vivo antitumor activity in the GTL-16 human gastric carcinoma xenograft model...
  6. doi request reprint Design, synthesis and structure-activity relationships of novel biarylamine-based Met kinase inhibitors
    David K Williams
    Bristol Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 20:2998-3002. 2010
    ..Compound 9b demonstrated potent in vivo antitumor activity in the GTL-16 human tumor xenograft model...
  7. doi request reprint Discovery of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (BMS-777607), a selective and orally efficacious inhibitor of the Met kinase superfamily
    Gretchen M Schroeder
    Bristol Myers Squibb Research and Development, Princeton, New Jersey, 08543 4000, USA
    J Med Chem 52:1251-4. 2009
    ..Because of its excellent in vivo efficacy and favorable pharmacokinetic and preclinical safety profiles, 10 has been advanced into phase I clinical trials...
  8. doi request reprint Synthesis, SAR, and Evaluation of 4-[2,4-Difluoro-5-(cyclopropylcarbamoyl)phenylamino]pyrrolo[2,1-f][1,2,4]triazine-based VEGFR-2 kinase inhibitors
    Zhen Wei Cai
    Bristol Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 18:1354-8. 2008
    ..Antitumor efficacy was observed with compound 37 against L2987 human lung carcinoma xenografts in athymic mice...
  9. doi request reprint Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors
    Zhen Wei Cai
    Bristol Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 18:3224-9. 2008
    ..These studies led to the discovery of compounds 3b and 20b, which demonstrated favorable pharmacokinetic properties in mice and significant antitumor activity in a human gastric carcinoma xenograft model...
  10. ncbi request reprint Discovery and evaluation of N-cyclopropyl- 2,4-difluoro-5-((2-(pyridin-2-ylamino)thiazol-5- ylmethyl)amino)benzamide (BMS-605541), a selective and orally efficacious inhibitor of vascular endothelial growth factor receptor-2
    Robert M Borzilleri
    Bristol Myers Squibb Pharmaceutical Research Institute, P O Box 4000, Princeton, New Jersey 08543 4000, USA
    J Med Chem 49:3766-9. 2006
    ..Analogue 14 demonstrated excellent kinase selectivity, favorable pharmacokinetic properties in multiple species, and robust in vivo efficacy in human lung and colon carcinoma xenograft models...
  11. doi request reprint The antiangiogenic activity in xenograft models of brivanib, a dual inhibitor of vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1 kinases
    Rajeev S Bhide
    Bristol Myers Squibb Research and Development, Princeton, New Jersey 08540, USA
    Mol Cancer Ther 9:369-78. 2010
    ..These results show that brivanib alaninate is an effective antitumor agent in preclinical models across a range of doses, and that efficacy is accompanied by changes in cellular and vascular activities...
  12. doi request reprint Identification of pyrrolo[2,1-f][1,2,4]triazine-based inhibitors of Met kinase
    Gretchen M Schroeder
    Bristol Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 18:1945-51. 2008
    ..Acylurea pyrrolotriazines with substitution at C-5 demonstrated single digit nanomolar kinase activity. X-ray crystallography revealed that the C-5 substituted pyrrolotriazines bind to the Met kinase domain in an ATP-competitive manner...
  13. ncbi request reprint Discovery and preclinical studies of (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5- methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan- 2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor
    Rajeev S Bhide
    Bristol Myers Squibb, Pharmaceutical Research Institute, Princeton, New Jersey 08543 4000, USA
    J Med Chem 49:2143-6. 2006
    ..The l-alanine prodrug of 12, BMS-582664 (21), is currently under evaluation in clinical trials for the treatment of solid tumors...
  14. doi request reprint Identification of a phenylacylsulfonamide series of dual Bcl-2/Bcl-xL antagonists
    Heidi L Perez
    Bristol Myers Squibb Research, PO Box 4000, Princeton, NJ 08543, USA
    Bioorg Med Chem Lett 22:3946-50. 2012
    ..Overall weak cellular potency was improved by the incorporation of polar functionality resulting in compounds with moderate antiproliferative activity...
  15. ncbi request reprint The structure of Dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib-resistant ABL mutants
    John S Tokarski
    Bristol Myers Squibb Company, Pharmaceutical Research Institute, Princeton, New Jersey, USA
    Cancer Res 66:5790-7. 2006
    ..The structure also provides an explanation for the activity of dasatinib against imatinib-resistant BCR-ABL mutants...
  16. doi request reprint Pyrazole and pyrimidine phenylacylsulfonamides as dual Bcl-2/Bcl-xL antagonists
    Gretchen M Schroeder
    Bristol Myers Squibb Research, PO Box 4000, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 22:3951-6. 2012
    ..Observation of cytochrome c release from isolated mitochondria in MV-411 cells provides further evidence of target inhibition. Compounds demonstrated submicromolar antiproliferative activity in Bcl-2/Bcl-xL dependent cell lines...
  17. doi request reprint Pyrrolo[1,2-f]triazines as JAK2 inhibitors: achieving potency and selectivity for JAK2 over JAK3
    Lalgudi S Harikrishnan
    Bristol Myers Squibb Co, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 21:1425-8. 2011
    ..SAR studies of pyrrolo[1,2-f]triazines as JAK2 inhibitors is presented. Achieving JAK2 inhibition selectively over JAK3 is discussed...
  18. ncbi request reprint Synthesis and SAR of pyrrolotriazine-4-one based Eg5 inhibitors
    Kyoung Soon Kim
    Department of Drug Discovery, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543 4000, USA
    Bioorg Med Chem Lett 16:3937-42. 2006
    ..In addition, pyrrolotriazine-4-one analogue 26 demonstrated in vivo efficacy in an iv P388 murine leukemia model. Both NMR and X-ray crystallographic studies revealed that these analogues bind to an allosteric site on the Eg5 protein...
  19. doi request reprint Metabolism of 5-isopropyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)-N-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (BMS-645737): identification of an unusual N-acetylglucosamine conjugate in the cynomolgus monkey
    Benjamin M Johnson
    Pharmaceutical Candidate Optimization, Bristol Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA
    Drug Metab Dispos 36:2475-83. 2008
    ....
  20. ncbi request reprint Design, synthesis, and evaluation of orally active 4-(2,4-difluoro-5-(methoxycarbamoyl)phenylamino)pyrrolo[2,1-f][1,2,4]triazines as dual vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1 inhibitors
    Robert M Borzilleri
    Department of Oncology Chemistry, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543 4000, USA
    J Med Chem 48:3991-4008. 2005
    ..A full account of the synthesis, structure-activity relationships, pharmacology, and pharmacokinetic properties of analogues within the series is presented...
  21. ncbi request reprint Inhibitors of human mitotic kinesin Eg5: characterization of the 4-phenyl-tetrahydroisoquinoline lead series
    Christine M Tarby
    Bristol Myers Squibb Company, Route 206 and Province Line Road, Princeton, NJ 08543, USA
    Bioorg Med Chem Lett 16:2095-100. 2006
    ....
  22. ncbi request reprint The identification and optimization of orally efficacious, small molecule VLA-4 antagonists
    Donna M Huryn
    Wyeth Research, Princeton, NJ 08543, USA
    Curr Top Med Chem 4:1473-84. 2004
    ..Finally, through the optimization of physical and pharmacokinetic properties, compounds were identified that exhibited oral activity in animal models of asthma and multiple sclerosis...
  23. ncbi request reprint Protein farnesyltransferase inhibitors exhibit potent antimalarial activity
    Laxman Nallan
    Department of Chemistry, University of Washington, Seattle, Washington 98195, USA
    J Med Chem 48:3704-13. 2005
    ..These studies validate P. falciparum PFT as a target for the development of antimalarials and describe a potent new class of THQ PFTIs with antimalaria activity...
  24. doi request reprint Discovery and preclinical studies of 5-isopropyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)-N-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (BMS-645737), an in vivo active potent VEGFR-2 inhibitor
    Réjean Ruel
    Bristol Myers Squibb, Research and Development, Candiac, Que, Canada J5R 1J1
    Bioorg Med Chem Lett 18:2985-9. 2008
    ....
  25. pmc Efficacy, pharmacokinetics, and metabolism of tetrahydroquinoline inhibitors of Plasmodium falciparum protein farnesyltransferase
    Wesley C Van Voorhis
    Department of Medicine, University of Washington, Room I 104 E, Health Sciences Building, Seattle, WA 98195 7185, USA
    Antimicrob Agents Chemother 51:3659-71. 2007
    ..This model suggests areas of the THQ PFTIs that can be modified to retain efficacy and protect the Zn-binding N-methyl-imidazole from dealkylation...
  26. pmc Second generation tetrahydroquinoline-based protein farnesyltransferase inhibitors as antimalarials
    Pravin Bendale
    Department of Chemistry, University of Washington, Seattle, Washington 98195, USA
    J Med Chem 50:4585-605. 2007
    ..The results of this study provide the basis for selection of antimalarial PFTIs for further evaluation in preclinical drug discovery assays...