What has polar surface area ever done for drug discovery?

Future Medicinal Chemistry

Volumn 3, Issue 4, 2011, Pages 469-484

  Clark, David E ^a  

^a Argenta Discovery Ltd   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2 [4 (2 DIMETHYLAMINOETHOXY)PHENYL] 4 (1 HYDROXYIMINO 5 INDANYL) 5 (4 PYRIDINYL) 1H IMIDAZOLE; B RAF KINASE INHIBITOR; BETA SECRETASE INHIBITOR; CALCITONIN GENE RELATED PEPTIDE RECEPTOR ANTAGONIST; CANNABINOID 1 RECEPTOR ANTAGONIST; CHECKPOINT KINASE 1 INHIBITOR; IBODUTANT; LIVER X RECEPTOR AGONIST; MK 3207; OLCEGEPANT; PROTEIN TYROSINE KINASE INHIBITOR; PYRROLO[2,3 D]PYRIMIDINE; RIMONABANT; SB 699393; SILDENAFIL; TACHYKININ; UNCLASSIFIED DRUG; WAY 252623; WAY 25401;

ANXIETY DISORDER; BLOOD BRAIN BARRIER; CALCULATION; CELL MEMBRANE PERMEABILITY; CELL STRAIN CACO 2; CLINICAL TRIAL; DEPRESSION; DRUG BIOAVAILABILITY; DRUG PENETRATION; DRUG STRUCTURE; HUMAN; INTESTINE ABSORPTION; INTESTINE MUCOSA PERMEABILITY; MEDICINAL CHEMISTRY; MIGRAINE; MOLECULAR WEIGHT; OBESITY; PERIPHERAL CIRCULATION; PHYSICAL CHEMISTRY; POLAR SURFACE AREA; PRIORITY JOURNAL; QUANTITATIVE STRUCTURE ACTIVITY RELATION; REVIEW; SPLEEN; SURFACE PROPERTY; TOPOGRAPHY;

BLOOD-BRAIN BARRIER; COMBINATORIAL CHEMISTRY TECHNIQUES; DRUG DISCOVERY; PROTEIN KINASE INHIBITORS; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; SURFACE PROPERTIES;

EID: 79953668499     PISSN: 17568919     EISSN: None     Source Type: Journal    
DOI: 10.4155/fmc.11.1     Document Type: Review

References (37)

1. Mezey PG. Molecular surfaces. In: Reviews in Computational Chemistry Vol. 1. Boyd DB, Lipkowitz KB (Eds). Wiley-VCH, NY, USA, 265-294 (1990).
2. Ertl P. Polar surface area. In: Molecular Drug Properties: Methods and Prediction (Methods and Principles in Medicinal Chemistry, Vol. 37). Mannhold R (Ed.). Wiley-VCH, Weinheim, Germany, 111-126 (2008).
3. Artursson P, Bergström CAS. Intestinal absorption: the role of polar surface area. In: Drug Bioavailability: Estimation of Solubility, Permeability, Absorption and Bioavailability (Methods and Principles in Medicinal Chemistry, Vol. 18). Van de Waterbeemd H, Lennernäs H, Artursson P (Eds). Wiley-VCH, Weinheim, Germany, 341-357 (2003).
4. Winter B. QSAR in olfaction: ambergris-type odorants. Prog Clin. Biol. Res. 291, 401-405 (1989).
5. Lipkowitz KB, Gilardi RD, Aprison MH. Electronic and structural features of γ-aminobutyric acid (GABA) and four of its direct agonists. J. Mol. Struct. 195, 65-77 (1989).
6. McCracken RO, Lipkowitz KB. Structure-activity relationships of benzothiazole and benzimidazole anthelmintics: a molecular modeling approach to in vivo drug effcacy J. Parasitol. 76(6), 853-864 (1990).
7. van de Waterbeemd H, Kansy M. Hydrogen-bonding capacity and brain penetration. Chimia 46(7-8), 299-303 (1992).
8. van de Waterbeemd H, Camenisch G, Folkers G, Raevsky OA. Estimation of Caco-2 cell permeability using calculated molecular descriptors. Quant. Struct. Act. Relat. 15(6), 480-490 (1996). (Pubitemid 27023202)
9. Palm K, Luthman K, Ungell AL, Strandlund G, Artursson P. Correlation of drug absorption with molecular surface properties. J. Pharm. Sci. 85(1), 32-39 (1996). (Pubitemid 26029068)
10. Palm K, Stenberg P, Luthman K, Artursson P. Polar molecular surface properties predict the intestinal absorption of drugs in humans. Pharm. Res. 14(5), 568-571 (1997). (Pubitemid 27220272)
11. Clark DE. Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 1. Prediction of intestinal absorption. J. Pharm. Sci. 88(8), 807-814 (1999).
12. Kelder J, Grootenhuis PDJ, Bayada DM, Delbressine LPC, Ploemen JP. Polar molecular surface as a dominating determinant for oral absorption and brain penetration of drugs. Pharm. Res. 16(10), 1514-1519 (1999). (Pubitemid 29510546)
13. Pearlman RS. Rapid generation of high quality approximate 3D molecular structures. Chem. Des. Auto. News 2, 1-7 (1987).
14. Ertl P, Rohde B, Selzer P. Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J. Med. Chem. 43(20), 3714-3717 (2000).
15. Stenberg P, Norinder U, Luthman K, Artursson P. Experimental and computational screening models for the prediction of intestinal drug absorption. J. Med. Chem. 44(12), 1927-1937 (2001). (Pubitemid 32884517)
16. Saunders RA, Platts JA. Scaled polar surface area descriptors: development and application to three sets of partition coeffcients. New J. Chem. 28(1), 166-172 (2004). (Pubitemid 38223586)
17. Bytheway I, Darley MG, Popelier PLA. The calculation of polar surface area from frst principles: an application of quantum chemical topology to drug design. ChemMedChem 3(3), 445-453 (2008).
18. Prasanna S, Doerksen RJ. Topological polar surface area: a useful descriptor in 2D-QSAR. Curr. Med. Chem. 16(1), 21-41 (2009).
19. Winiwarter S, Bonham NM, Ax F, Hallberg A, Lennernäs H, Karlén A. Correlation of human jejunal permeability (in vivo) of drugs with experimentally and theoretically derived parameters. A multivariate data ana lysis approach. J. Med. Chem. 41(25), 4939-4949 (1998). (Pubitemid 28555452)
20. Lai JYQ, Cox PJ, Patel R et al. Potent small molecule inhibitors of spleen tyrosine kinase (Syk). Bioorg. Med. Chem. Lett. 13(18), 3111-3114 (2003). (Pubitemid 36993648)
21. Huang S, Garbaccio RM, Fraley ME et al. Development of 6-substituted indolylquinolinones as potent Chek1 kinase inhibitors. Bioorg. Med. Chem. Lett. 16(22), 5907-5912 (2006). (Pubitemid 44486723)
22. Garbaccio RM, Huang S, Tasber ES et al. Synthesis and evaluation of substituted benzoisoquinolinones as potent inhibitors of Chk1 kinase. Bioorg. Med. Chem. Lett. 17(22), 6280-6285 (2007). (Pubitemid 47552817)
23. Bingham AH, Davenport RJ, Fosbeary R et al. Synthesis and structure-activity relationship of aminopyrimidine IKK2 inhibitors. Bioorg. Med. Chem. Lett. 18(12), 3622-3627 (2008). (Pubitemid 351795595)
24. Tumey LN, Bhagirath N, Brennan A et al. 5-vinyl-3-pyridinecarbonitrile inhibitors of PKCΘ: optimization of enzymatic and functional activity. Bioorg Med. Chem. 17(23), 7933-7948 (2009).
25. Papageorgiou C, Camenisch G, Borer X. Cell permeability as a parameter for lead generation in the protein tyrosine kinase inhibition feld. Bioorg Med. Chem. Lett. 11(12), 1549-1552 (2001). (Pubitemid 32703560)
26. Bell IM, Bednar RA, Fay JF et al. Identifcation of novel, orally bioavailable spirohydantoin CGRP receptor antagonists. Bioorg Med. Chem. Lett. 16(24), 6165-6169 (2006). (Pubitemid 44709924)
27. Bell IM, Bednar RA, Corcoran HA et al. The identifcation of potent, orally bioavailable tricyclic CGRP receptor antagonists. Bioorg Med. Chem. Lett. 19(16), 4740-4742 (2009).
28. Stump CA, Bell IM, Bednar RA et al. Identifcation of potent, highly constrained CGRP receptor antagonists. Bioorg Med. Chem. Lett. 20(8), 2572-2576 (2010).
29. Bell IM, Gallicchio SN, Wood MR et al. Discovery of MK-3207: a highly potent, orally bioavailable CGRP receptor antagonist. ACS Med. Chem. Lett. 1(1), 24-29 (2010).
30. Thomson Reuters Integrity Database, (September 2010).
31. Fedi V, Altamura M, Catalioto RM et al. Discovery of a new series of potent and selective linear tachykinin NK2 receptor antagonists. J. Med. Chem. 50(20), 4793-4807 (2007). (Pubitemid 47525465)
32. Takle AK, Bamford MJ, Davies S et al. The identifcation of potent, selective and CNS penetrant furan-based inhibitors of B-raf kinase. Bioorg Med. Chem. Lett. 18(15), 4373-4376 (2008).
33. Malamas MS, Barnes K, Hui Y et al. Novel pyrrolyl 2-aminopyridines as potent and selective human ß-secretase (BACE1) inhibitors. Bioorg Med. Chem. Lett. 20(7), 2068-2073 (2010).
34. Receveur JM, Murray A, Linget JM et al. Conversion of 4-cyanomethyl-pyrazole-3-carboxamides into CB1 antagonists with lowered propensity to pass the blood-brain barrier. Bioorg Med. Chem. Lett. 20(2), 453-457 (2010).
35. Hortala L, Rinaldi-Carmona M, Congy C et al. Rational design of a novel peripherally restricted, orally active CB1 cannabinoid antagonist containing a 2,3-diarylpyrrole motif. Bioorg Med. Chem. Lett. 20(15), 4573-4577 (2010).
36. Hu B, Bernotas R, Unwalla R et al. Quinoline-3-carboxamide containing sulfones as liver X receptor (LXR) agonists with binding selectivity for LXRß and low blood-brain penetration. Bioorg Med. Chem. Lett. 20(2), 689-693 (2010).
37. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 23(1-3), 3-25 (1997). (Pubitemid 27046991)