Erratum: Noncovalent Mutant Selective Epidermal Growth Factor Receptor Inhibitors: A Lead Optimization Case Study (Journal of Medicinal Chemistry (2015) 58 (8877-8895) DOI: 10.1021/acs.jmedchem.5b01412);Noncovalent Mutant Selective Epidermal Growth Factor Receptor Inhibitors: A Lead Optimization Case Study

Journal of Medicinal Chemistry

Volumn 58, Issue 22, 2015, Pages 8877-8895

  Heald, Robert ^a   Bowman, Krista K ^h   Bryan, Marian C ^b   Burdick, Daniel ^b   Chan, Bryan ^b   Chan, Emily ^g   Chen, Yuan ^d   Clausen, Saundra ^e   Dominguez Fernandez, Belen ^a   Eigenbrot, Charles ^c   Elliott, Richard ^a   Hanan, Emily J ^b   Jackson, Philip ^a   Knight, Jamie ^a   La, Hank ^d   Lainchbury, Michael ^a   Malek, Shiva ^e   Mann, Sam ^a   Merchant, Mark ^g   Mortara, Kyle ^h   Purkey, Hans ^b   Schaefer, Gabriele ^f   Schmidt, Stephen ^e   Seward, Eileen ^a   Sideris, Steve ^e   Shao, Lily ^f   Wang, Shumei ^b   Yeap, Kuen ^a   Yen, Ivana ^e   Yu, Christine ^c   Heffron, Timothy P ^b   more..

^a Early Discovery Charles River   (United Kingdom)

^b Discovery Chemistry   (United States)

^c Departments of Structural Biology   (United States)

^d Departments of Pharmacokinetics and Drug Metabolism   (United States)

^e Genentech   (United States)

^f Molecular Oncology   (United States)

^g Genentech   (United States)

^h GENENTECH INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; AZABENZIMIDAZOLE DERIVATIVE; BENZIMIDAZOLE DERIVATIVE; BRIGATINIB; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; FLUOROPIPERIDINE DERIVATIVE; N [3 [[5 CHLORO 2 [[2 METHOXY 4 (4 METHYL 1 PIPERAZINYL)PHENYL]AMINO] 4 PYRIMIDINYL]OXY]PHENYL]ACRYLAMIDE; OSIMERTINIB; PIPERIDINE DERIVATIVE; UNCLASSIFIED DRUG; LIPID;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BINDING AFFINITY; CASE STUDY; CELL PROLIFERATION; CONTROLLED STUDY; DIASTEREOISOMER; DRUG ABSORPTION; DRUG CLEARANCE; DRUG CONFORMATION; DRUG DESIGN; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG HYDROXYLATION; DRUG METABOLISM; DRUG SYNTHESIS; GLUCURONIDATION; HEPATIC CLEARANCE; HUMAN; HUMAN CELL; HYDROGEN BOND; HYDROPHOBICITY; IN VITRO STUDY; IN VIVO STUDY; LIPOPHILICITY; LIVER CELL; LIVER MICROSOME; METABOLIC STABILITY; NONHUMAN; PHYSICAL CHEMISTRY; PLASMA CLEARANCE; PROTEIN PHOSPHORYLATION; RAT; STRUCTURE ACTIVITY RELATION; THERMODYNAMICS; TUMOR XENOGRAFT; ANIMAL; ANTAGONISTS AND INHIBITORS; CARCINOMA, NON-SMALL-CELL LUNG; CHEMICAL STRUCTURE; CHEMISTRY; DOG; DRUG EFFECTS; DRUG SCREENING; ENZYME SPECIFICITY; GENE SILENCING; LUNG NEOPLASMS; MACACA FASCICULARIS; METABOLISM; MUTATION; PROTO ONCOGENE; STEREOISOMERISM; SYNTHESIS; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE, TUMOR; DOGS; DRUG DESIGN; GENE KNOCKDOWN TECHNIQUES; GENES, ERBB-1; HUMANS; IN VITRO TECHNIQUES; LIPIDS; LUNG NEOPLASMS; MACACA FASCICULARIS; MICROSOMES, LIVER; MODELS, MOLECULAR; MUTATION; RATS; RECEPTOR, EPIDERMAL GROWTH FACTOR; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84948693706     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.6b00301     Document Type: Erratum

References (65)

1. Gazdar, A. F.; Minna, J. D. Inhibition of EGFR signaling: all mutations are not created equal PLoS Med. 2005, 2, e377 10.1371/journal.pmed.0020377
2. Sharma, S. V.; Bell, D. W.; Settleman, J.; Haber, D. A. Epidermal growth factor receptor mutations in lung cancer Nat. Rev. Cancer 2007, 7, 169-81 10.1038/nrc2088
3. Sordella, R.; Bell, D. W.; Haber, D. A.; Settleman, J. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways Science 2004, 305, 1163-7 10.1126/science.1101637
4. Tracy, S.; Mukohara, T.; Hansen, M.; Meyerson, M.; Johnson, B. E.; Janne, P. A. Gefitinib induces apoptosis in the EGFRL858R non-small-cell lung cancer cell line H3255 Cancer Res. 2004, 64, 7241-4 10.1158/0008-5472.CAN-04-1905
5. Sharma, S. V.; Settleman, J. Oncogene addiction: setting the stage for molecularly targeted cancer therapy Genes Dev. 2007, 21, 3214-31 10.1101/gad.1609907
6. Jackman, D. M.; Miller, V. A.; Cioffredi, L. A.; Yeap, B. Y.; Janne, P. A.; Riely, G. J.; Ruiz, M. G.; Giaccone, G.; Sequist, L. V.; Johnson, B. E. Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated non-small cell lung cancer patients: results of an online tumor registry of clinical trials Clin. Cancer Res. 2009, 15, 5267-73 10.1158/1078-0432.CCR-09-0888
7. Rosell, R.; Moran, T.; Queralt, C.; Porta, R.; Cardenal, F.; Camps, C.; Majem, M.; Lopez-Vivanco, G.; Isla, D.; Provencio, M.; Insa, A.; Massuti, B.; Gonzalez-Larriba, J. L.; Paz-Ares, L.; Bover, I.; Garcia-Campelo, R.; Moreno, M. A.; Catot, S.; Rolfo, C.; Reguart, N.; Palmero, R.; Sanchez, J. M.; Bastus, R.; Mayo, C.; Bertran-Alamillo, J.; Molina, M. A.; Sanchez, J. J.; Taron, M. Screening for epidermal growth factor receptor mutations in lung cancer N. Engl. J. Med. 2009, 361, 958-67 10.1056/NEJMoa0904554
8. Lynch, T. J.; Bell, D. W.; Sordella, R.; Gurubhagavatula, S.; Okimoto, R. A.; Brannigan, B. W.; Harris, P. L.; Haserlat, S. M.; Supko, J. G.; Haluska, F. G.; Louis, D. N.; Christiani, D. C.; Settleman, J.; Haber, D. A. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib N. Engl. J. Med. 2004, 350, 2129-39 10.1056/NEJMoa040938
9. Paez, J. G.; Janne, P. A.; Lee, J. C.; Tracy, S.; Greulich, H.; Gabriel, S.; Herman, P.; Kaye, F. J.; Lindeman, N.; Boggon, T. J.; Naoki, K.; Sasaki, H.; Fujii, Y.; Eck, M. J.; Sellers, W. R.; Johnson, B. E.; Meyerson, M. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy Science 2004, 304, 1497-500 10.1126/science.1099314
10. Pao, W.; Miller, V.; Zakowski, M.; Doherty, J.; Politi, K.; Sarkaria, I.; Singh, B.; Heelan, R.; Rusch, V.; Fulton, L.; Mardis, E.; Kupfer, D.; Wilson, R.; Kris, M.; Varmus, H. EGF receptor gene mutations are common in lung cancers from »never smokers» and are associated with sensitivity of tumors to gefitinib and erlotinib Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 13306-11 10.1073/pnas.0405220101
11. Pao, W.; Chmielecki, J. Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer Nat. Rev. Cancer 2010, 10, 760-74 10.1038/nrc2947
12. Kobayashi, S.; Boggon, T. J.; Dayaram, T.; Janne, P. A.; Kocher, O.; Meyerson, M.; Johnson, B. E.; Eck, M. J.; Tenen, D. G.; Halmos, B. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib N. Engl. J. Med. 2005, 352, 786-92 10.1056/NEJMoa044238
13. Pao, W.; Miller, V. A.; Politi, K. A.; Riely, G. J.; Somwar, R.; Zakowski, M. F.; Kris, M. G.; Varmus, H. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain PLoS Med. 2005, 2, e73 10.1371/journal.pmed.0020073
14. Yu, H. A.; Arcila, M. E.; Rekhtman, N.; Sima, C. S.; Zakowski, M. F.; Pao, W.; Kris, M. G.; Miller, V. A.; Ladanyi, M.; Riely, G. J. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers Clin. Cancer Res. 2013, 19, 2240-7 10.1158/1078-0432.CCR-12-2246
15. Kosaka, T.; Yatabe, Y.; Endoh, H.; Yoshida, K.; Hida, T.; Tsuboi, M.; Tada, H.; Kuwano, H.; Mitsudomi, T. Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib Clin. Cancer Res. 2006, 12, 5764-9 10.1158/1078-0432.CCR-06-0714
16. Balak, M. N.; Gong, Y.; Riely, G. J.; Somwar, R.; Li, A. R.; Zakowski, M. F.; Chiang, A.; Yang, G.; Ouerfelli, O.; Kris, M. G.; Ladanyi, M.; Miller, V. A.; Pao, W. Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors Clin. Cancer Res. 2006, 12, 6494-501 10.1158/1078-0432.CCR-06-1570
17. Kwak, E. L.; Sordella, R.; Bell, D. W.; Godin-Heymann, N.; Okimoto, R. A.; Brannigan, B. W.; Harris, P. L.; Driscoll, D. R.; Fidias, P.; Lynch, T. J.; Rabindran, S. K.; McGinnis, J. P.; Wissner, A.; Sharma, S. V.; Isselbacher, K. J.; Settleman, J.; Haber, D. A. Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib Proc. Natl. Acad. Sci. U. S. A. 2005, 102, 7665-70 10.1073/pnas.0502860102
18. Shah, N. P.; Nicoll, J. M.; Nagar, B.; Gorre, M. E.; Paquette, R. L.; Kuriyan, J.; Sawyers, C. L. Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia Cancer Cell 2002, 2, 117-25 10.1016/S1535-6108(02)00096-X
19. Quintas-Cardama, A.; Kantarjian, H.; Cortes, J. Flying under the radar: the new wave of BCR-ABL inhibitors Nat. Rev. Drug Discovery 2007, 6, 834-48 10.1038/nrd2324
20. Yun, C. H.; Mengwasser, K. E.; Toms, A. V.; Woo, M. S.; Greulich, H.; Wong, K. K.; Meyerson, M.; Eck, M. J. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 2070-5 10.1073/pnas.0709662105
21. Janne, P. A.; Schellens, J. H.; Engelman, J. A.; Eckhardt, S. G.; Millham, R.; Denis, L. J.; Britten, C. D.; Wong, S. G.; Boss, D. S.; Camidge, D. R. Preliminary activity and safety results from a phase I clinical trial of PF-00299804, an irreversible pan-HER inhibitor, in patients (pts) with NSCLC J. Clin. Oncol. 2008, 26 (May 20) 8027
22. Sequist, L. V.; Besse, B.; Lynch, T. J.; Miller, V. A.; Wong, K. K.; Gitlitz, B.; Eaton, K.; Zacharchuk, C.; Freyman, A.; Powell, C.; Ananthakrishnan, R.; Quinn, S.; Soria, J. C. Neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor: results of a phase II trial in patients with advanced non-small-cell lung cancer J. Clin. Oncol. 2010, 28, 3076-83 10.1200/JCO.2009.27.9414
23. Kim, Y.; Ko, J.; Cui, Z.; Abolhoda, A.; Ahn, J. S.; Ou, S. H.; Ahn, M. J.; Park, K. The EGFR T790M mutation in acquired resistance to an irreversible second-generation EGFR inhibitor Mol. Cancer Ther. 2012, 11, 784-91 10.1158/1535-7163.MCT-11-0750
24. Sos, M. L.; Rode, H. B.; Heynck, S.; Peifer, M.; Fischer, F.; Kluter, S.; Pawar, V. G.; Reuter, C.; Heuckmann, J. M.; Weiss, J.; Ruddigkeit, L.; Rabiller, M.; Koker, M.; Simard, J. R.; Getlik, M.; Yuza, Y.; Chen, T. H.; Greulich, H.; Thomas, R. K.; Rauh, D. Chemogenomic profiling provides insights into the limited activity of irreversible EGFR Inhibitors in tumor cells expressing the T790M EGFR resistance mutation Cancer Res. 2010, 70, 868-74 10.1158/0008-5472.CAN-09-3106
25. Soria, J.-C.; Sequist, L. V.; Gadgeel, S.; Goldman, J.; Wakelee, H.; Varga, A.; Fidias, P.; Wozniak, A. J.; Neal, J. W.; Doebele, R. C.; Garon, E. B.; Jaw-Tsai, S.; Caunt, L.; Kaur, P.; Rolfe, L.; Allen, A.; Camidge, D. R. First-in-human evaluation of CO-1686, an irreversible, highly selective tyrosine kinase inhibitor of mutations of EGFR (activating and T790M). Presented at the 15th World Conference on Lung Cancer, Sydney, Australia, 2013.
26. Ranson, M. Preliminary results from a phase I study with AZD9291. Presented at the European Cancer Congress, 2013.
27. Cross, D. A. E.; Ashton, S. E.; Ghiorghiu, S.; Eberlein, C.; Nebhan, C. A.; Spitzler, P. J.; Orme, J. P.; Finlay, M. R. V.; Ward, R. A.; Mellor, M. J.; Hughes, G.; Rahi, A.; Jacobs, V. N.; Brewer, M. R.; Ichihara, E.; Sun, J.; Jin, H.; Ballard, P.; Al-Kadhimi, K.; Rowlinson, R.; Klinowska, T.; Richmond, G. H. P.; Cantarini, M.; Kim, D.-W.; Ranson, M. R.; Pao, W. AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer Cancer Discovery 2014, 4, 1046-1061 10.1158/2159-8290.CD-14-0337
28. Sjin, R. T. T.; Lee, K.; Walter, A. O.; Dubrovskiy, A.; Sheets, M.; Martin, T. S.; Labenski, M. T.; Zhu, Z.; Tester, R.; Karp, R.; Medikonda, A.; Chaturvedi, P.; Ren, Y.; Haringsma, H.; Etter, J.; Raponi, M.; Simmons, A. D.; Harding, T. C.; Niu, D.; Nacht, M.; Westlin, W. F.; Petter, R. C.; Allen, A.; Singh, J. In Vitro and In Vivo Characterization of Irreversible Mutant-Selective EGFR Inhibitors That Are Wild-Type Sparing Mol. Cancer Ther. 2014, 13, 1468 10.1158/1535-7163.MCT-13-0966
29. Janne, P. A.; Ramaligam, S. S.; Yang, J. C. H.; Ahn, M.-J.; Kim, D.-W.; Kim, S.-W.; Planchard, D.; Ohe, Y.; Felip, E.; Watkins, C.; Cantarini, M.; Ghiorghiu, S.; Ranson, M. Clinical activity of the mutant-selective EGFR inhibitor AZD9291 in patients (pts) with EGFR inhibitor-resistant non-small-cell lung cancer (NSCLC) J. Clin. Oncol. 2014, 32, 8009
30. Jänne, P. A.; Yang, J. C.-H.; Kim, D.-W.; Planchard, D.; Ohe, Y.; Ramalingam, S. S.; Ahn, M.-J.; Kim, S.-W.; Su, W.-C.; Horn, L.; Haggstrom, D.; Felip, E.; Kim, J.-H.; Frewer, P.; Cantarini, M.; Brown, K. H.; Dickinson, P. A.; Ghiorghiu, S.; Ranson, M. AZD9291 in EGFR Inhibitor Resistant Non Small-Cell Lung Cancer N. Engl. J. Med. 2015, 372, 1689-1699 10.1056/NEJMoa1411817
31. Finlay, M. R. V.; Anderton, M.; Ashton, S.; Ballard, P.; Bethel, P. A.; Box, M. R.; Bradbury, R. H.; Brown, S. J.; Butterworth, S.; Campbell, A.; Chorley, C.; Colclough, N.; Cross, D. A. E.; Currie, G. S.; Grist, M.; Hassall, L.; Hill, G. B.; James, D.; James, M.; Kemmitt, P.; Klinowska, T.; Lamont, G.; Lamont, S. G.; Martin, N.; McFarland, H. L.; Mellor, M. J.; Orme, J. P.; Perkins, D.; Perkins, P.; Richmond, G.; Smith, P.; Ward, R. A.; Waring, M. J.; Whittaker, D.; Wells, S.; Wrigley, G. L. Discovery of a Potent and Selective EGFR Inhibitor (AZD9291) of Both Sensitizing and T790M Resistance Mutations That Spares the Wild Type Form of the Receptor J. Med. Chem. 2014, 57, 8249-8267 10.1021/jm500973a
32. Walter, A. O.; Sjin, R. T. T.; Haringsma, H. J.; Ohashi, K.; Sun, J.; Lee, K.; Dubrovskiy, A.; Labenski, M.; Zhu, Z.; Wang, Z.; Sheets, M.; Martin, T. S.; Karp, R.; van Kalken, D.; Chaturvedi, P.; Niu, D.; Nacht, M.; Petter, R. C.; Westlin, W.; Lin, K.; Jaw-Tsai, S.; Raponi, M.; Dyke, T. V.; Etter, J.; Weaver, Z.; Pao, W.; Singh, J.; Simmons, A. D.; Harding, T. C.; Allen, A. Discovery of a mutant-selective covalent inhibitor of EGFR that overcomes T790M-mediated resistance in NSCLC Cancer Discovery 2013, 3, 1404-1415 10.1158/2159-8290.CD-13-0314
33. Thress, K. S.; Paweletz, C. P.; Felip, E.; Cho, B. C.; Stetson, D.; Dougherty, B.; Lai, Z.; Markovets, A.; Vivancos, A.; Kuang, Y.; Ercan, D.; Matthews, S. E.; Cantarini, M.; Barrett, J. C.; Janne, P. A.; Oxnard, G. R. Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M Nat. Med. 2015, 21, 560-562 10.1038/nm.3854
34. Yu, H. A.; Tian, S. K.; Drilon, A. E.; Borsu, L.; Riely, G. J.; Arcila, M. E.; Ladanyi, M. Acquired Resistance of EGFR-Mutant Lung Cancer to a T790M-Specific EGFR Inhibitor: Emergence of a Third Mutation (C797S) in the EGFR Tyrosine Kinase Domain JAMA Oncol. 2015, 1, 982-984 10.1001/jamaoncol.2015.1066
35. Niederst, M. J.; Hu, H.; Mulvey, H. E.; Lockerman, E. L.; Garcia, A. R.; Piotrowska, Z.; Sequist, L. V.; Engelman, J. A. The allelic context of the C797S mutation acquired upon treatment with third generation EGFR inhibitors impacts sensitivity to subsequent treatment strategies Clin. Cancer Res. 2015, 21, 3924 10.1158/1078-0432.CCR-15-0560
36. AP26113 is a dual ALK/EGFR inhibitor: Characterization against EGFR T790M in cell and mouse models of NSCLC. http://www.ariad.com/pdf/Rivera-2012-AACR-POSTER-AP26113-noQRcode.pdf.
37. About brigatinib (AP26113). http://www.ariad.com/AP26113.
38. Hanan, E. J.; Eigenbrot, C.; Bryan, M. C.; Burdick, D. J.; Chan, B. K.; Chen, Y.; Dotson, J.; Heald, R. A.; Jackson, P. S.; La, H.; Lainchbury, M. D.; Malek, S.; Purkey, H. E.; Schaefer, G.; Schmidt, S.; Seward, E. M.; Sideris, S.; Tam, C.; Wang, S.; Yeap, S. K.; Yen, I.; Yin, J.; Yu, C.; Zilberleyb, I.; Heffron, T. P. Discovery of Selective and Noncovalent Diaminopyrimidine-Based Inhibitors of Epidermal Growth Factor Receptor Containing the T790M Resistance Mutation J. Med. Chem. 2014, 57, 10176-10191 10.1021/jm501578n
39. Bissantz, C.; Kuhn, B.; Stahl, M. A medicinal chemist's guide to molecular interactions J. Med. Chem. 2010, 53, 5061-84 10.1021/jm100112j
40. Hughes, J. D.; Blagg, J.; Price, D. A.; Bailey, S.; Decrescenzo, G. A.; Devraj, R. V.; Ellsworth, E.; Fobian, Y. M.; Gibbs, M. E.; Gilles, R. W.; Greene, N.; Huang, E.; Krieger-Burke, T.; Loesel, J.; Wager, T.; Whiteley, L.; Zhang, Y. Physiochemical drug properties associated with in vivo toxicological outcomes Bioorg. Med. Chem. Lett. 2008, 18, 4872-4875 10.1016/j.bmcl.2008.07.071
41. Leeson, P. D.; Springthorpe, B. The influence of drug-like concepts on decision-making in medicinal chemistry Nat. Rev. Drug Discovery 2007, 6, 881-890 10.1038/nrd2445
42. Lovering, F.; Bikker, J.; Humblet, C. Escape from Flatland: Increasing Saturation as an Approach to Improving Clinical Success J. Med. Chem. 2009, 52, 6752-6756 10.1021/jm901241e
43. Ritchie, T. J.; Macdonald, S. J. The impact of aromatic ring count on compound developability: further insights by examining carbo- and hetero-aromatic and -aliphatic ring types Drug Discovery Today 2011, 16, 164-171 10.1016/j.drudis.2010.11.014
44. Lee, H. J.; Schaefer, G.; Heffron, T. P.; Shao, L.; Ye, X.; Sideris, S.; Malek, S.; Chan, E.; Merchant, M.; La, H.; Ubhayakar, S.; Yauch, R. L.; Pirazzoli, V.; Politi, K.; Settleman, J. Noncovalent wild-type-sparing inhibitors of EGFR T790M Cancer Discovery 2013, 3, 168-81 10.1158/2159-8290.CD-12-0357
45. Shultz, M. D. Setting expectations in molecular optimizations: Strengths and limitations of commonly used composite parameters Bioorg. Med. Chem. Lett. 2013, 23, 5980-5991 10.1016/j.bmcl.2013.08.029
46. Tarcsay, á.; Nyíri, K.; Keseru?, G. M. Impact of Lipophilic Efficiency on Compound Quality J. Med. Chem. 2012, 55, 1252-1260 10.1021/jm201388p
47. Shultz, M. D. Improving the Plausibility of Success with Inefficient Metrics ACS Med. Chem. Lett. 2014, 5, 2-5 10.1021/ml4004638
48. Hopkins, A. L.; Keserü, G. M.; Leeson, P. D.; Rees, D. C.; Reynolds, C. H. The role of ligand efficiency metrics in drug discovery Nat. Rev. Drug Discovery 2014, 13, 105-121 10.1038/nrd4163
49. Shultz, M. D. The thermodynamic basis for the use of lipophilic efficiency (LipE) in enthalpic optimizations Bioorg. Med. Chem. Lett. 2013, 23, 5992-6000 10.1016/j.bmcl.2013.08.030
50. Pryde, D. C.; Dalvie, D.; Hu, Q.; Jones, P.; Obach, R. S.; Tran, T.-D. Aldehyde Oxidase: An Enzyme of Emerging Importance in Drug Discovery J. Med. Chem. 2010, 53, 8441-8460 10.1021/jm100888d
51. Conformational energies (A-values). http://www.chem.wisc.edu/areas/reich/handouts/a-values/a-values.htm.
52. van Niel, M. B.; Collins, I. B.; Beer, M. S.; Broughton, H.; Cheng, S. K. F.; Goodacre, S. C.; Heald, A.; Locker, K.; MacLeod, A. M.; Morrison, D.; Moyes, C. R.; O'Connor, D.; Pike, A.; Rowley, M.; Russell, M. G. N.; Sohal, B.; Stanton, J..; Thomas, S.; Verrier, H.; Watt, A. P.; Castro, J. L. Fluorination of 3-(3-(Piperidin-1-yl)propyl)indoles and 3-(3-(Piperazin-1-yl)propyl)indoles Gives Selective Human 5-HT1D Receptor Ligands with Improved Pharmacokinetic Profiles J. Med. Chem. 1999, 42, 2087-2104 10.1021/jm981133m
53. Müller, K.; Faeh, C.; Diederich, F. Fluorine in pharmaceuticals: looking beyond intuition Science 2007, 317, 1881-6 10.1126/science.1131943
54. Vulpetti, A.; Dalvit, C. Fluorine local environment: from screening to drug design Drug Discovery Today 2012, 17, 890-7 10.1016/j.drudis.2012.03.014
55. Rosenberg, R. E. Does fluoromethane form a hydrogen bond with water? J. Phys. Chem. A 2012, 116, 10842-9 10.1021/jp308533b
56. Giuffredi, G. T.; Gouverneur, V.; Bernet, B. Intramolecular OHrFC Hydrogen Bonding in Fluorinated Carbohydrates: CHF is a Better Hydrogen Bond Acceptor than CF2 Angew. Chem., Int. Ed. 2013, 52, 10524-10528 10.1002/anie.201303766
57. Meanwell, N. A. Synopsis of some recent tactical application of bioisosteres in drug design J. Med. Chem. 2011, 54, 2529-91 10.1021/jm1013693
58. Böhm, H. J.; Banner, D.; Bendels, S.; Kansy, M.; Kuhn, B.; Müller, K.; Obst-Sander, U.; Stahl, M. Fluorine in Medicinal Chemistry ChemBioChem 2004, 5, 637-643 10.1002/cbic.200301023
59. Sun, A.; Lankin, D. C.; Hardcastle, K.; Snyder, J. P. 3-Fluoropiperidines and N-methyl-3-fluoropiperidinium salts: the persistence of axial fluorine Chem.-Eur. J. 2005, 11, 1579-91 10.1002/chem.200400835
60. Zürcher, M.; Diederich, F. Structure-based drug design: exploring the proper filling of apolar pockets at enzyme active sites J. Org. Chem. 2008, 73, 4345-61 10.1021/jo800527n
61. Poulin, P.; Hop, C. E.; Ho, Q.; Halladay, J. S.; Haddad, S.; Kenny, J. R. Comparative Assessment of In Vitro-In Vivo Extrapolation Methods used for Predicting Hepatic Metabolic Clearance of Drugs J. Pharm. Sci. 2012, 101, 4308-4326 10.1002/jps.23288
62. Lee, H.-J.; Schaefer, G.; Heffron, T. P.; Shao, L.; Ye, X.; Sideris, S.; Malek, S.; Chan, E.; Merchant, M.; La, H.; Ubhayakar, S.; Yauch, R. L.; Pirazzoli, V.; Politi, K.; Settleman, J. Noncovalent Wild-type-Sparing Inhibitors of EGFR T790M Cancer Discovery 2013, 3, 168-181 10.1158/2159-8290.CD-12-0357
63. Halladay, J. S.; Wong, S.; Jaffer, S. M.; Sinhababu, A. K.; Khojasteh-Bakht, S. C. Metabolic Stability Screen for Drug Discovery Using Cassette Analysis and Column Switching Drug Metab. Lett. 2014, 1, 67-72 10.2174/187231207779814364
64. Ndubaku, C. O.; Heffron, T. P.; Staben, S. T.; Baumgardner, M.; Blaquiere, N.; Bradley, E.; Bull, R.; Do, S.; Dotson, J.; Dudley, D.; Edgar, K. A.; Friedman, L. S.; Goldsmith, R.; Heald, R. A.; Kolesnikov, A.; Lee, L.; Lewis, C.; Nannini, M.; Nonomiya, J.; Pang, J.; Price, S.; Prior, W. W.; Salphati, L.; Sideris, S.; Wallin, J. J.; Wang, L.; Wei, B.; Sampath, D.; Olivero, A. G. Discovery of 2-{3-[2-(1-Isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl]-1H-pyrazol-1-yl}-2-methylpropanamide (GDC-0032): A β-Sparing Phosphoinositide 3-Kinase Inhibitor with High Unbound Exposure and Robust in Vivo Antitumor Activity J. Med. Chem. 2013, 56, 4597-4610 10.1021/jm4003632
65. Stamos, J.; Sliwkowski, M. X.; Eigenbrot, C. Structure of the Epidermal Growth Factor Receptor Kinase Domain Alone and in Complex with a 4-Anilinoquinazoline Inhibitor J. Biol. Chem. 2002, 277, 46265-46272 10.1074/jbc.M207135200