Extending pKa prediction accuracy: High-throughput pK a measurements to understand pKa modulation of new chemical series

European Journal of Medicinal Chemistry

Volumn 45, Issue 9, 2010, Pages 4270-4279

  Milletti, Francesca ^a   Storchi, Loriano ^b   Goracci, Laura ^b   Bendels, Stefanie ^c   Wagner, Bjoern ^c   Kansy, Manfred ^c   Cruciani, Gabriele ^a  

^a UNIVERSITY OF PERUGIA   (Italy)

^b Molecular Discovery Limited   (United Kingdom)

^c F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

Ionization; MoK ; pKa Measurement; pKa Prediction

Indexed keywords

2 AMINO 6,7 DIMETHYL 6,7,8 TETRAHYDRO 4 PTERIDINONE; ADENINE; AMIDE; AMINE; CETIRIZINE; HYDRAZINE DERIVATIVE; HYPOXANTHINE; PTERIN; PURINE; SPERMINE; SULFONAMIDE; TETRACYCLINE; UNCLASSIFIED DRUG; HYDRAZINE; ORGANIC COMPOUND;

ARTICLE; CLINICAL EVALUATION; COMPUTER PROGRAM; IONIZATION; PKA; PREDICTIVE VALIDITY; QUALITY CONTROL; CHEMISTRY; PHYSICAL CHEMISTRY;

AMIDES; AMINES; BENCHMARKING; HYDRAZINES; ORGANIC CHEMICALS; PHYSICOCHEMICAL PROCESSES; SULFONAMIDES;

EID: 77955552577     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2010.06.026     Document Type: Article

References (57)

1. a and steric effects in the optimization of 3-methyl-1,2,3,4- tetrahydroisoquinoline inhibitors by β-fluorination J. Med. Chem. 49 10 2006 2939 2952
2. a on activity vs chloroquine resistant malaria J. Med. Chem. 51 12 2008 3466 3479
3. A. Avdeef Absorption and Drug Development: Solubility, Permeability, and Charge State 2003 Wiley Hoboken
4. P.J. Stansfeld, M.J. Sutcliffe, and J.S. Mitcheson Molecular mechanisms for drug interactions with hERG that cause long QT syndrome Expert Opin. Drug Metab. Toxicol. 2 2006 81 94
5. M.J. Reasor, K.L. Hastings, and R.G. Ulrich Drug-induced phospholipidosis: issues and future directions Expert Opin. Drug Saf. 5 2006 567 583
6. a, and logD J. Chem. Inf. Comput. Sci. 42 4 2002 796 805
7. a prediction of monoprotic small molecules the smarts way J. Chem. Inf. Model. 48 10 2008 2042 2053
8. a for druglike compounds using semiempirical and information-based descriptors J. Chem. Inf. Model. 47 2007 450 459
9. a prediction from "Quantum Chemical Topology" descriptors J. Chem. Inf. Model. 49 8 2009 1914 1924
10. a values of benzoic and alkanoic acids J. Chem. Inf. Comput. Sci. 42 2 2002 184 191
11. a values and steroid CBG binding affinities J. Chem. Inf. Comput. Sci. 43 6 2003 2081 2092
12. a values. A comparison of different theoretical approaches and a novel procedure J. Mol. Struct: THEOCHEM 684 2004 121 128
13. a of phenols in different solvents QSAR Comb. Sci. 27 2007 563 581
14. a for benzoic acids in different solvents QSAR Comb. Sci. 26 2006 385 397
15. a using quantum topological molecular similarity descriptors: application to carboxylic acids, anilines and phenols J. Org. Chem. 69 2 2004 233 241
16. a values for aliphatic carboxylic acids and alcohols with empirical atomic charge descriptors J. Chem. Inf. Model. 46 6 2006 2256 2266
17. a using semiempirical molecular orbital methods. part 1: application to phenols and carboxylic acids QSAR Comb. Sci. 21 2002 457 472
18. a prediction using group philicity J. Phys. Chem. A 110 20 2006 6540 6544
19. a prediction tools on the gold standard dataset QSAR Comb. Sci. 28 2009 1148 1155
20. a estimation methods on 211 druglike compounds J. Chem. Inf. Model. 50 2010 565 571
21. a values of pharmaceutical substances J. Chem. Inf. Model. 49 2009 2801 2812
22. a J. Chem. Inf. Model. 49 2009 2013 2033
23. a prediction method using grid molecular interaction fields J. Chem. Inf. Model. 47 2007 2172 2181
24. a values) of organic compounds by multiplexed capillary electrophoresis using aqueous and cosolvent buffers J. Pharm. Sci. 97 2008 2581 2606
25. A.N. Martin, J. Suarbrick, and A. Cammarata Physical Pharmacy 1969 Lea & Febiger Philadelphia pp 194
26. a values of medical compounds in pharmacy practice Drug. Intell. Clin. Pharm. 12 1978 546 554
27. C.A. Gilligan, and A. Li Wan Po Factors affecting drug release from a pellet system coated with an aqueous colloidal dispersion Int. J. Pharm. 73 1991 51 68
28. 1H NMR and molecular modeling studies J. Pharm. Biomed. Anal. 41 2006 857 865
29. V. Gobry, G. Bouchard, P.A. Carrupt, B. Testa, and H.H. Girault Physicochemical characterization of sildenafil: ionization, lipophilicity behavior, and ionic-partition diagram studied by two-phase titration and electrochemistry Helv. Chim. Acta 83 2000 1465 1474
30. a screening pharmaceuticals by pressure-assisted capillary electrophoresis Electrophoresis 22 6 2001 1112 1118
31. U. Holzgrabe, I. Waver, and B. Diehl NMR Spectroscopy in Drug Development and Analysis 1999 Wiley-VCH Weinheim
32. C.H. Stammer, and C.W. Jones Glycine methoxyamide, acyclic analog of cycloserine Cell. Mol. Life Sci. 22 1966 600 601
33. V. Palm, T. Tenno, M. Tamme, I. Talvik, R. Hiob, M. Luuk, M. Uudam, and T. Rodima Tables of Rate and Equilibrium Constants of Heterolytic Organic Reactions 1978 VINITI Moscow
34. A. Albert Selective Toxicity 1968 Methuen London pp 281
35. G. Girault-Vexlearschi Influence de la ramification des chaines hydrocarbonees sur la basicite des amines. IV. Spectres d'absorption des alcoylarylamines Bull. Soc. Chim. Fr. 23 1956 606 613
36. J.M. Mayer, B. Testa, H. van de Waterbeemd, and A. Bornand-Crausaz Deviations in the logP of protonated arylalkylamines and in their apparent logP Eur. J. Med. Chem. 17 1982 461 466
37. Sybyl. Tripos http://tripos.com (accessed 30.06.09.)
38. D.D. Perrin Dissociation Constants of Organic Bases in Aqueous Solution 1965 Butterworths London
39. L.C. Craig, and R.M. Hixon Electron sharing ability of organic radicals. Nitrogen heterocyclics J. Am. Chem. Soc. 53 1931 4367 4372
40. A. Sierra-Zenteno, C.A. Galan-Vidal, and R. Tapia Benavides Acid base equilibrium studies of 2-(aminomethyl)benzimidazole in acquous solution J. Mexican Chem. Soc. 46 2002 125 130
41. T.B. Paiva, M. Tominaga, and A.C.M. Paiva Ionization of histamine, N-acetylhistamine, and their iodinated derivatives J. Med. Chem. 13 1970 689 692
42. G.E.K. Branch, and J.O. Clayton The strength of acetamide as an acid J. Am. Chem. Soc. 50 1928 1680 1686
43. R.W. King, and A.S.V. Burgen Kinetic aspects of structure-activity relations: the binding of sulphonamides by carbonic anhydrase Proc. R. Soc. B 193 1976 107 125
44. P.B. Madrid, A.P. Liou, J.L. DeRisi, and R.K. Guyac Incorporation of an intramolecular hydrogen-bonding motif in the side-chain of 4-aminoquinolines enhances activity against drug-resistant P. falciparum J. Med. Chem. 49 2006 4535 4543
45. A.B. Teitel'baum, K.A. Derstuganova, N.A. Shishkina, L.A. Kudryavtseva, V.E. Bel'skii, and B.E. Ivanov Tautomerism in the ortho-aminomethylphenols Russ. Chem. Bull. 29 1980 558 562
46. L.G. Chekanova, A.V. Radushev, A.E. Lesnov, and E.A. Sazonova Physicochemical properties of 1,2-diacylhydrazines derived from aliphatic carboxylic acids Russ. J. Gen. Chem. 72 2002 1233 1237
47. O. Enea, K. Houngbssa, and G. Berthon Chaleurs de protonation de la piperazine et de quelques-uns de ses derives Electrochim. Acta 17 1972 1585 1594
48. H.S. Creyf, and L.C. Van Poucke The free energy, enthalpy and entropy changes of the dissociation of diprotonated diamines Thermochim. Acta 4 1972 485 491
49. Specs http://www.specs.net (accessed 30.06.09.)
50. 13C, H spin-spin coupling. 9. Purine J. Am. Chem. Soc. 104 1982 4167 4173
51. A. Albert, and D.J. Brown Purine studies. Part I. stability to acid and alkali. Solubility. Ionization. Comparison with pteridines J. Chem. Soc. 1954 2060 2071
52. N.C. Gonnella, H. Nakanishi, B. Holtwick, D.S. Horowitz, K. Kanamori, N.J. Leonard, and J.D. Roberts Studies of tautomers and protonation of adenine and its derivatives by nitrogen-15 nuclear magnetic resonance spectroscopy J. Am. Chem. Soc. 105 1983 2050 2055
53. I. Shcherbakova, J. Elguero, and A. Katritzky Tautomerism of heterocycles: condensed five-six, five-five, and six-six ring system with heteroatom in both rings A.R. Katritzky, Advances in Heterocyclic Chemistry 2000 Academic Press New York
54. D.J. Brown, and N.W. Jacobsen Pteridine studies. Part XI V.l methylation of 2-amino-4-hydroxypteridine and related compounds J. Chem. Soc. 1961 4413 4420
55. R.G. Kallen, and W.P. Jencks The dissociation constants of tetrahydrofolic acid J. Biol. Chem. 241 1966 5845 5850
56. a studies and condensation of calf thymus DNA Chem. Commun. 1998 1403 1404
57. a determination of water-insoluble compounds: validation study in a new cosolvent system Anal. Chim. Acta. 583 2007 418 428