Molecular design and bioavailability

被引:5
作者
Clark, RD [1 ]
Wolohan, PRN [1 ]
机构
[1] Tripos Inc, St Louis, MO 63144 USA
关键词
D O I
10.2174/1568026033451952
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A "snapshot" of current medicinal chemistry work on bioavailability is drawn from issues of J. Med. Chem. covering the time period between September 2001 and September 2002. An exhaustive compilation of reported absolute oral bioavailability (F) values for this period is included, covering 34 structural series and 107 distinct compounds, with data for multiple species in many cases. This is supplemented with a discussion of more qualitative oral bioavailability results, and with illustrative examples addressing clearance, prodrug design, and blood/brain barrier penetration problems. Papers discussing predictions pertaining to one or another aspect of bioavailability are also discussed, and some thoughts on future directions of work on in silico prediction in this area are presented.
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收藏
页码:1269 / 1288
页数:20
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共 68 条
[1]   Unique overlap in the prerequisites for thrombin inhibition and oral Bioavailability resulting in potent oral antithrombotics [J].
Adang, AEP ;
de Man, APA ;
Vogel, GMT ;
Grootenhuis, PDJ ;
Smit, MJ ;
Peters, CAM ;
Visser, A ;
Rewinkel, JBM ;
van Dinther, T ;
Lucas, H ;
Kelder, J ;
van Aelst, S ;
Meuleman, DG ;
van Boeckel, CAA .
JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (20) :4419-4432
[2]   Arylcyclopropanecarboxyl guanidines as novel, potent, and selective inhibitors of the sodium hydrogen exchanger isoform-1 [J].
Ahmad, S ;
Doweyko, LM ;
Dugar, S ;
Grazier, N ;
Ngu, K ;
Wu, SC ;
Yost, KJ ;
Chen, BC ;
Gougoutas, JZ ;
DiMarco, JD ;
Lan, SJ ;
Gavin, BJ ;
Chen, AY ;
Dorso, CR ;
Serafino, R ;
Kirby, M ;
Atwal, KS .
JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (20) :3302-3310
[3]   Discovery and SAR of a novel selective and orally bioavailable nonpeptide classical competitive inhibitor class of protein-tyrosine phosphatase 1B [J].
Andersen, HS ;
Olsen, OH ;
Iversen, LF ;
Sorensen, ALP ;
Mortensen, SB ;
Christensen, MS ;
Branner, S ;
Hansen, TK ;
Lau, JF ;
Jeppesen, L ;
Moran, EJ ;
Su, J ;
Bakir, F ;
Judge, L ;
Shahbaz, M ;
Collins, T ;
Vo, T ;
Newman, MJ ;
Ripka, WC ;
Moller, NPH .
JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (20) :4443-4459
[4]   Selective ETA antagonists.: 5.: Discovery and structure-activity relationships of phenoxyphenylacetic acid derivatives [J].
Astles, PC ;
Brown, TJ ;
Halley, F ;
Handscombe, CM ;
Harris, NV ;
Majid, TN ;
McCarthy, C ;
McLay, IM ;
Morley, A ;
Porter, B ;
Roach, AG ;
Sargent, C ;
Smith, C ;
Walsh, RJA .
JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (05) :900-910
[5]   Arylsulfonamidothiazoles as a new class of potential antidiabetic drugs.: Discovery of potent and selective inhibitors of the 11β-hydroxysteroid dehydrogenase type 1 [J].
Barf, T ;
Vallgårda, J ;
Emond, R ;
Häggström, C ;
Kurz, G ;
Nygren, A ;
Larwood, V ;
Mosialou, E ;
Axelsson, K ;
Olsson, R ;
Engblom, L ;
Edling, N ;
Rönquist-Nii, Y ;
Öhman, B ;
Alberts, P ;
Abrahmsén, L .
JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (18) :3813-3815
[6]   3-aminopyrrolidinone farnesyltransferase inhibitors: Design of macrocyclic compounds with improved pharmacokinetics and excellent cell potency [J].
Bell, IM ;
Gallicchio, SN ;
Abrams, M ;
Beese, LS ;
Beshore, DC ;
Bhimnathwala, H ;
Bogusky, MJ ;
Buser, CA ;
Culberson, JC ;
Davide, J ;
Ellis-Hutchings, M ;
Fernandes, C ;
Gibbs, JB ;
Graham, SL ;
Hamilton, KA ;
Hartman, GD ;
Heimbrook, DC ;
Homnick, CF ;
Huber, HE ;
Huff, JR ;
Kassahun, K ;
Koblan, KS ;
Kohl, NE ;
Lobell, RB ;
Lynch, JJ ;
Robinson, R ;
Rodrigues, AD ;
Taylor, JS ;
Walsh, ES ;
Williams, TM ;
Zartman, CB .
JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (12) :2388-2409
[7]   Discovery and optimization of a series of carbazole ureas as NPY5 antagonists for the treatment of obesity [J].
Block, MH ;
Boyer, S ;
Brailsford, W ;
Brittain, DR ;
Carroll, D ;
Chapman, S ;
Clarke, DS ;
Donald, CS ;
Foote, KM ;
Godfrey, L ;
Ladner, A .
JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (16) :3509-3523
[8]   Synthesis and pharmacology of benzoxazines as highly selective antagonists at M4 muscarinic receptors [J].
Böhme, TM ;
Augelli-Szafran, CE ;
Hallak, H ;
Pugsley, T ;
Serpa, K ;
Schwarz, RD .
JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (14) :3094-3102
[9]   Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity [J].
Boschelli, DH ;
Ye, F ;
Wang, YD ;
Dutia, M ;
Johnson, SL ;
Wu, BQ ;
Miller, K ;
Powell, DW ;
Yaczko, D ;
Young, M ;
Tischler, M ;
Arndt, K ;
Discafani, C ;
Etienne, C ;
Gibbons, J ;
Grod, J ;
Lucas, J ;
Weber, JM ;
Boschelli, F .
JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (23) :3965-3977
[10]   Descriptors, physical properties, and drug-likeness [J].
Brüstle, M ;
Beck, B ;
Schindler, T ;
King, W ;
Mitchell, T ;
Clark, T .
JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (16) :3345-3355