Medicinal chemical properties of successful central nervous system drugs

NeuroRX - 2005
Hassan Pajouhesh1, George R. Lenz2
1Department of Medicinal Chemistry, Neuromed Technologies Inc., V6T 1Z4, Vancouver, British Columbia, Canada
2GRLEN R&D Associates, 01810-5402, Andover, Massachusetts

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Pardridge WM. The blood-brain barrier and neurotherapeutics. NeuroRx 2: 1–2, 2005.

Mouritsen OG, Jorgensen K. A new look at lipid membrane structure in relation to drug research. Pharm Res 15: 1507–1519, 1998.

Lin JH, Lu A-Y. Role of pharmacokinetics and metabolism in drug discovery and development. Pharmacol Rev 49: 403–449, 1997.

Bannon WW, Deceker MW, Holladay MW, Curzon P, Donelly-Roberts D, Puttfarcken PS, Bitner RS, Diaz A, Dickenson AH, Porsolt RD, Williams M, Arneric SP. Broad spectrum, non-opioid analgesic activity by selective modulation of neuronal nicotinic acetylcholine receptors. Science 279: 77–81, 1998.

Daly JW, Myers CW, Whittaker N. Further classification of skin alkaloids from neotropical poison frogs (Dendrobatidae), with a general survey of toxic/noxious substances in the amphia. Toxicon 25: 1023–1095, 1987.

Lenz GR. Technical problems in getting results. In: From data to drugs: strategies for benefiting from the new drug discovery technologies (Haberman AB, Lenz GR, Vaccaro DE, eds.), pp 95–114. London: Scrip Reports, 1999.

Williams M, Coyle JT, Shaikh S, Decker MW. Same brain, new decade: challenges in CNS drug discovery in the postgenomic, proteomic era. Annu Rep Med Chem 36: 1–10, 2001.

Schneeberger EE, Lynch RD. Structure, function, and regulation of cellular tight junctions. Am J Physiol (Lond) 262: L647-L661, 1992.

Faasen F, Vogel G, Spanings H, Vromans H. Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm 263: 113–122, 2003.

Graff CL, Pollack GM. Drug transport at the blood-brain barrier and the choroid plexus. Curr Drug Metab 5: 95–108, 2004.

Pardridge WM. CNS drug design based on principles of blood-brain barrier transport. J Neurochem 70: 1781–1792, 1998.

Schlosshauer B, Steuer H. Comparative anatomy, physiology and in vitro models of the blood-brain and blood-retina barrier. Curr Med Chem — Central Nervous System Agents 2: 175–186, 2002.

Sippl W. Computational approaches for the prediction of blood-brain barrier permeation. Curr Med Chem —Central Nervous System Agents, 2: 211–227, 2002.

Dennis M. Absorption processes, In: Comprehensive medicinal chemistry. Vol. 5 (Sammes PG, Taylor JB, eds.), pp 1–44. Oxford, UK: Pergamon, 1990.

Kerns EH, Di L. Pharmaceutical profiling in drug discovery. Drug Discov Today 8: 316–323, 2003.

Faller B, Wohnsland F. Physicochemical parameters as tool in drug discovery and lead optimization. In: Testa B, Van de Waterbeemd H, Folker G, Guy R. Pharmacokinetics optimization in drug research. Zurich, Switzerland: Wiley-VCH; 257–273, 2001.

Ellingboe J. Application of statistical analysis techniques for discovery compound property optimization. AAPS Workshop on Optimization of Drug-Like Properties during Lead Optimization. Parsippany, NJ, 19–22 September, 2004.

Gupta SP. QSAR studies on drugs acting at the central nervous system. Chem Rev 89: 1765–1800, 1989.

Van de Waterbeemd H, Smith DA, Beaumont K, Walker DK. Property-based design: optimization of drug absorption and pharmacokinetics. J Med Chem 44: 1313–1333, 2001.

Ekins S. Predicting undesirable drug interactions with promiscuous proteins in silico. Drug Discov Today 9: 276–285, 2004.

Leo A, Hansch C, Elkins D. Partition coefficients and their uses. Chem Rev 71: 525–615, 1971.

Hansch C, Steward AR, Anderson SM, Bentley D. The parabolic dependence of drug action upon lipophilic character as revealed by a study of hypnotics. J Med Chem 11: 1–11, 1967.

Gao H, Hansch C. QSAR of P450 oxidation: on the value of comparing kcat and Km with kcat/Km. Drug Metab Rev 28: 513–526, 1996.

Mertsch K, Maas J. Blood-brain barrier penetration and drug development from an industrial point of view. Curr Med Chem — Central Nervous System Agents 2: 187–201, 2002.

Darvas F, Dorman G, Urge L, Szabo I, Ronai Z, Sasavari-Szekely M. Combinatorial chemistry. Facing the challenge of chemical genomics. Pure Appl Chem 73: 1487–1498, 2001.

Strausberg RL, Schreiber SL. From knowing to controlling: a path from genomics to drugs using small molecule probes. Science 30:294–295.

Schreiber SL. The small molecule approach to biology. Chem Eng News, pp 51–61, 3 March 2003.

Ekins S, Waller CL, Swaan PW, Cruciani G, Wrighton SA, Wikel JH. Progress in predicting human ADME parameters in silico. J Pharmacol Toxicol Methods 44: 251–272, 2000.

Tute MS. History and objectives of quantitative drug design. In: Comprehensive medicinal chemistry. Vol. 4 (Sammes PG, Taylor JB, eds.), pp 1–32. Oxford, Pergamon, 1990.

Levin VA. Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability. J Med Chem 23: 682–684, 1980.

Young RC, Durant GJ, Emmett JC, Ganellin CR, Graham MJ, Mitchell RC, Prain HD, Roantree ML. Dipole moment in relation to hydrogen receptor histamine antagonist activity for cimetidine analogs. J Med Chem 29: 44–49, 1986.

Young RC, Mitchell RC, Brown TH, Ganellin CR, Griffiths R, Jones M, Rana KK, Saunders D, Smith IR, Sore NE, Wilks TJ. Development of a new physicochemical model for brain penetration and its application to the design of centrally acting H2 receptor antagonists. J Med Chem 31: 656–671, 1988.

ter Laak AM, Tsai RS, Donné-Op den Kelder GM, Carrupt P-A, Testa B, Timmerman H. Lipophilicity and hydrogen-bonding capacity of H1-antihistaminic agents in relation to their central sedative side-effects. Eur J Pharm Sci 2: 373–384, 1994.

Goodwin JT, Conradi RA, Ho NFH, Burton PS. Physicochemical determinants of passive membrane permeability: role of solute hydrogen-bonding potential and volume. J Med Chem 44: 3721–3729, 2001.

Taylor PJ. Hydrophobic properties of drugs. In: Comprehensive medicinal chemistry. Vol. 4 (Sammes PG, Taylor JB, eds.), pp 241–294. Oxford, UK: Pergamon, 1990.

Taylor PJ. Hydrophobic properties of drugs. In: Comprehensive medicinal chemistry. Vol. 4 (Sammes PG, Taylor JB, eds.), p 263. Oxford, UK: Pergamon, 1990.

Fischer H, Gottschlich R, Seelig A. Blood-brain barrier permeation: molecular parameters governing passive diffusion. J Membrane Biol 165: 201–211, 1998.

Palm K, Luthman K, Ros J, Gråsjo J, Artursson P. Effect of molecular charge on intestinal epithelial drug transport: pH-dependent transport of cationic drugs. J Pharmacol Exp Ther 291: 435–443, 1999.

Clark DE. Prediction of intestinal absorption and blood-brain barrier penetration by computational methods. Comb Chem High Throughput Screening 4: 477–496, 2001.

Ecker GF, Noe CR. In silico prediction models for blood-brain barrier permeation. Curr Med Chem 11: 1617–1628, 2004.

Jorgenson WL. The many roles of computation in drug discovery. Science 303: 1813–1818, 2004.

van de Waterbeemd H, Kansy M. Hydrogen bonding capacity and brain penetration. Chimia 46: 299–303, 1992.

Abraham MH. Scales of solute hydrogen-bonding: their construction and application to physicochemical and biochemical processes. Chem Soc Rev 22: 72–83, 1993.

Palm K, Luthman K, Ungell A-L, Strandlund G, Artursson P. Correlation of drug absorption with molecular surface properties. J Pharm Sci 85: 32–39, 1996.

Kelder J, Grootenhuis PDJ, Bayada DM, Delbressine LPC, Ploemen J-P. Polar molecular surface as a dominating determinant for oral absorption and brain penetration of drugs. Pharm Res 16: 1514–1519, 1999.

van de Waterbeemd H, Camenish G, Folkers G, Chretien JR, Raevsky OA. Estimation of blood-brain barrier crossing of drugs using molecular size and shape, and H-bonding characteristics. J Drug Target 6: 151–165, 1998.

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: 807–814, 1999.

Ertl P, Rohde B, Selzer P. Fast calculation of molecular surface area as a sum of fragments-based contributions and its application to prediction of drug transport properties. J Med Chem 42: 3714–3717, 2000.

Österberg T, Norinder U. Prediction of polar surface area and drug transport processes using simple parameters and PLS statistics. J Chem Inf Comput Sci 40: 1408–1411, 2000.

Iyer M, Mishra R, Han Y, Hopfinger AJ. Predicting blood-brain barrier partitioning of organic molecules using membrane-interaction QSAR analysis. Pharm Res 19: 1611–1621, 2002.

Veber DF, Johnson SR, Cheng H-Y, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 45: 2515–2623, 2002.

Pan D, Iyer M, Liu J, Li Y, Hopfinger AJ. Constructing optimum blood brain barrier QSAR models using a combination of 4D-molecular similarity measures and cluster analysis. J Chem Inf Comput Sci 44: 2083–2098, 2004.

Leeson PD, Davis AM. Tine-related differences in the physical property profiles of oral drugs. J Med Chem 47: 6338–6348, 2004.

Hansch C, Leo AJ. Substituent constant for correlation analysis in chemistry and biology. New York: Wiley, 1979.

Fichert T, Yazdanian M, Proudfoot JR. A structure-permeability study of small drug-like molecules. Bioorganic Med Chem Lett 13: 719–722, 2003.

Van de waterbeemed, Atkinson F, Cole S, Green C. Lipophilicity and other parameters affecting brain penetration. Curr Med Chem-Central Nervous System Agents 2: 229–240, 2002.

Hansch C, Bjorkroth J, Leo AJ. Hydrophobicity and central nervous system agents: on the principle of minimal hydrophobicity in drug design. Pharm Sci 76: 663, 1987.

Feng RM. Assessment of blood-brain barrier penetration: in silico, in vitro and in vivo. Curr Drug Metab 3: 647–657, 2002.

Skaaeda T, Okamura N, Nagata S, Yagami T, Horinouchi M, Okumura K, Yamahita F, Hashida M. Molecular and pharmacokinetic properties of 222 commercially available oral drugs in humans. Biol Pharm Bull 24: 935–940, 2001.

Abraham MH, Chadha HS, Martins F, Mitchell RC, Bradbury MW, Gratton JA. Hydrogen bonding part 46: a review of the correlation and prediction of transport properties by an LFER method: physicochemical properties brain penetration and skin permeability. Pestic Sci 55: 78–88, 1999.

Clark DE. In silico prediction of blood-brain barrier permeation, Drug Discovery Today 8: 927–933, 2003.

Austin RP, Davis AM, Manners CN. Partitioning of ionizing molecules between aqueous buffers and phospholipids vesicles. J Pharm Sci 84: 1180–1183, 1995.

Lin JH, Rodrigues AD. In vitro model for early studies of drug metabolism. In: Pharmacokinetics optimization in drug research: biological, physicochemical and computational strategies (Testa, Van de Waterbeemed H, Folker G, Guy R, eds.), pp 217–243. New York: Wiley-VCH, 2001.

Graaf deC, Vermeulen EPN, Feenstra NK. Cytochrome P450 in silico: an integrative modeling approach. J Med Chem 48: 2726–2755, 2005.

Ertel SI, Ertel EA, Clozel JP. T-type Ca2+ channels and pharmacological blockade: potential pathophysiological relevance. Cardioavasc Drugs Ther 11: 723–739, 1997.

Van de waterbeemed H. The fundamental variables of the biopharmaceutics classification system (BCS): a commentary. Eur J Pharm Sci 7: 1–3, 1998.

Liljebris CJ, Larson SD, Ogg D, Palazuk JB, Bleasdale E. Investigation of potential bioisosteric replacements for the carboxyl groups of peptidomimetic inhibitors of protein tyrosine phosphatase 1B: identification of a tetrazole-containing inhibitor with cellular activity. J Med Chem 45: 1785–1798, 2002.

Feng RM, Assessment of blood-brain barrier penetration: in silico, in vitro and in vivo. Curr Drug Metab 3: 647–657, 2002.

Raub JT. Early preclinical evaluation in support of hit identification and lead optimization for brain exposure. AAPS Workshop on Optimization of Drug-Like Properties During Lead Optimization. Parsippany, NJ, 19–22 September, 2004.

Recanatini M, Poluzzi E, Masetti M, Cavalli A, De Ponti F. QT prolongation through hERG K+ channel blockade: current knowledge and strategies for the early prediction during drug development. Med Res Rev 25: 133–166, 2005.

Redfern SW, Carlsson L, Davis SA, Lynch GW, MacKenzie I, Palethorpe S, Siegl SKP, Strang I, Sullivan TA, Wallis R. Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc Res 58: 32–45, 2003.

Adenot M, Lahana R. Blood-brain barrier permeation models: discriminating between potential CNS and non-CNS drugs including P-glycoprotein substrates. J Chem Inf Comp Sci 44: 239–248, 2004.

Sadowski J, Kubinyi H. A scoring scheme for discriminating between drugs and nondrugs. J Med Chem 41: 3325–3329, 1998.

Ajay, Walters WP, Murcko MA. Can we learn to distinguish between “drug-like” and “nondrug-like” molecules? J Med Chem 41: 3314–3324, 1998.

Ajay, Walters WP, Murcko MA. Designing libraries with CNS activity. J Med Chem 41: 4942–4951, 1998.

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: 3–25, 1997.

Wenlock MC, Austin RP, Barton P, Davis AM, Leeson PD. A comparison of physiochemical property profiles of development and marketed oral drugs. J Med Chem 46: 1250–1256, 2003.

Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Methods 44: 235–249, 2000.

Vieth M, Siegel MG, Higgs RE, Watson IA, Robertson DH, Savin KA, Durst GL, Hipskind PA. Characteristic physical properties and structural fragments of marketed oral drugs. J Med Chem 47: 224–232, 2004.

Lipinski CA. Drew University Medical Chemistry Special Topics Course. July 1999.

Lipinski CA. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol 1: 337–341, 2004.

Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabit-Singh CJ, Adkinson KK, Polli JW. Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther 303: 1029–1037, 2002.