potential intra-articular Treatment of osteoarthritis. J. Med. Chem. 2011;55:
709-716.
11.
(a) Lauer-Fields JL, Minond D, Chase PS, Baillargeon PE,
References
Saldanha SA, Stawikowska R, Hodder P, Fields GB. High throughput
screening of potentially selective MMP-13 exosite inhibitors utilizing a triple-
helical FRET substrate. Bioorg. Med. Chem. 2009;17:990-1005;
1.
Chen A, Gupte C, Akhtar K, Smith P, Cobb J. The global
economic cost of osteoarthritis: How the UK compares. Arthritis. 2012;
DOI:10.1155/2012/698709.
(b) Roth J, Minond D, Darout E, Liu Q, Lauer J, Hodder P, Fields GB, Roush
WR. Identification of novel, exosite-binding matrix metalloproteinase-13
inhibitor scaffolds. Bioorg. Med. Chem. Lett. 2011;21:7180-7184.
2.
Lee AS, Ellman MB, Yan D, Kroin JS, Cole BJ, Van Wijnen AJ,
Im HJ. A current review of molecular mechanisms regarding osteoarthritis
12.
Spicer TP, Jiang JW, Taylor AB, Choi JY, Hart PJ, Roush WR,
and pain. Gene. 2013;527:440-447.
Fields GB, Hodder PS, Minong D. Characterization of selective exosite-
binding inhibitors of matrix metalloproteinase 13 that prevent articular
cartilage degradation in vitro. J. Med. Chem. 2014;57:9598-9611.
3.
update with relevance for clinical practice. The Lancet 2011;377:2115-2126.
4. (a) Flood J. The role of acetaminophen in the treatment of
Bijlsma JWJ, Berenbaum F, Lafeber PJG. Osteoarthritis: an
13.
Choi JY, Fuerst R, Knapinska AM, Taylor A, Smith L, Cao X,
osteoarthritis. Am. J. Manag. Care 2010;16:48-54;
Hart PJ, Fields GB, Roush WR. Structure-based design and synthesis of
potent and selective matrix metalloproteinase 13 inhibitors. J. Med. Chem.
2017;60:3814-3827.
(b) Chen YF, Jobanputra P, Barton P, Bryan S, Fry-Smith A, Harris G, Taylor
RS. Cycloxygenase-2 selective non-steroidal anti-inflammatory drugs
(etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and
lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review
and economic evaluation. Health Technol. Asses. 2008;12:1-278.
14.
(a) Fields GB. Interstitial collagen catabolism. J. Biol. Chem.
2013;288:8785-8793;
(b) Amar S, Smith L, Fields GB. Matrix metalloproteinase collagenolysis in
health and disease. Biochim. Biophys. Acta Mol. Cell Res. 2017;1864:1940-
1951.
5.
Aigner T, Sachse A, Gebhard PM, Roach HI. Osteoarthritis:
Pathobiology—targets and ways for therapeutic intervention. Adv. Drug
Deliver. Rev. 2006;58:128-149.
15.
Kansy M, Senner F, Gubernator K. Physicochemical high
6.
Mengshol JA, Mix KS, Brinckerhoff CE,
Matrix
throughput screening:ꢀ Parallel artificial membrane permeation assay in the
description of passive absorption processes. J. Med. Chem. 1998;41:1007-
1010.
metalloproteinases as therapeutic targets in arthritic diseases: Bull's-eye or
missing the mark? Arthritis Rheum. 2002;46:13-20.
7.
(a) Takaishi H, Kimura T, Dalal S, Okada Y, D'Armiento J. Joint
16.
Kerns EH, Di Li. Drug-like Properties: Concepts, Structure,
diseases and matrix metalloproteinases: A role for MMP-13. Curr. Pharm.
Biotechnol. 2008;9:47-54;
Design and Methods: From ADME to Toxicity Optimization. Oxford, UK:
Elsevier; 2008.
(b) Neuhold LA, Killar L, Zhao WG, Sung MLA, Warner L, Kulik J, Turner
J, Wu W, Billinghurst C, Meijers T, Poole AR, Babij P, DeGennaro LJ.
Postnatal expression in hyaline cartilage of constitutively active human
collagenase-3 (MMP-13) induces osteoarthritis in mice. J. Clin. Invest.
2001;107:35-44.
17.
Comer JEA. High-Throughput Measurement of logD and pKa. In:
Van de Waterbeemd H, Lennernäs H, Artursson P, eds. Drug Bioavailability:
Estimation of Solubility, Permeability, Absorption and Bioavailability.
Weinheim, D: Wiley-VCH Verlag GmbH & Co. KGaA; 2004:pp21-45.
18.
Madoux F, Li X, Chase P, Zastrow G, Cameron MD, Conkright
8.
(a) Burrage PS, Mix KS, Brinckerhoff CE. Matrix
JJ, Griffin PR, Thacher S, Hodder P. Potent, selective and cell penetrant
Inhibitors of SF-1 by functional ultra-high-throughput screening. Mol.
Pharmacol. 2008;73:1776-1784.
metalloproteinases: Role in arthritis. Front. Biosci. 2006;11:529-543;
(b) Fingleton B. MMPs as therapeutic targets—Still a viable option? Semin.
Cell Dev. Biol. 2008;19:61-68.
19.
Obach RS. Prediction of human clearance of twenty-nine drugs
9.
(a) Chen JM, Nelson FC, Levin JI, Mobilio D, Moy FJ, Nilakantan
from hepatic microsomal intrinsic clearance data: An examination of in vitro
half-life approach and nonspecific binding to microsomes. Drug Metab.
Dispos. 1999;27:1350-1359.
R, Zask A, Powers R. Structure-based design of a novel, potent, and selective
inhibitor for MMP-13 utilizing NMR spectroscopy and computer-aided
molecular design. J. Am. Chem. Soc. 2000;122:9648-9654;
20.
Van de Waterbeemd H, Smith DA, Beaumont K, Walker DK.
(b) Engel CK, Pirard B, Schimanski S, Kirsch R, Habermann J, Klingler O,
Schlotte V, Weithmann KU, Wendt KU. Structural basis for the highly
selective inhibition of MMP-13. Chemistry & Biology 2005;12:181-189;
(c) Reiter LA, Freeman-Cook KD, Jones CS, Martinelli GJ, Antipas AS,
Berliner MA, Datta K, Downs JT, Eskra JD, Forman MD, Greer EM,
Guzman R, Hardink JR, Janat F, Keene NF, Laird ER, Liras JL, Lopresti-
Morrow LL, Mitchell PG, Pandit J, Robertson D, Sperger D, Vaughn-Bowser
ML, Waller DM, Yocum SA. Potent, selective pyrimidinetrione-based
inhibitors of MMP-13. Bioorg. Med. Chem. Lett. 2006;16:5822-5826;
(d) Johnson AR, Pavlovsky AG, Ortwine DF, Prior F, Man CF, Bornemeier
DA, Banotai CA, Mueller WT, Mcconnell P, Yan C, Baragi V, Lesch C,
Roark WH, Wilson M, Datta K, Guzman R, Han HK, Dyer RD. Discovery
and characterization of a novel inhibitor of matrix metalloprotease-13 that
reduces cartilage damage in vivo without joint fibroplasia side effects. J. Biol.
Chem. 2007;282:27781-27791;
Property-based design:ꢀ Optimization of drug absorption and
pharmacokinetics. J. Med. Chem. 2001;44:1313-1333.
21.
Nassar AEF, Kamel AM, Clarimont C. Improving the decision-
making process in the structural modification of drug candidates: Enhancing
metabolic stability. Drug Discovery Today 2004;9:1020-1028.
22.
collagenolytic protease activity. Biol. Chem. 2002;383:1095-1105.
23. Hamman JH, Enslin GM, Kotzé AF. Oral delivery of peptide
drugs. BioDrugs 2005;19:165-177.
Lauer-Fields JL, Fields GB. Triple-helical peptide analysis of
24.
Nelson SD. Metabolic activation and drug toxicity. J. Med. Chem.
1982;25:753-765.
25.
Zhou S, Chan SY, Goh BC, Chan E, Duan W, Huang M, McLeod
HL. Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic
drugs. Clin. Pharmacokinet. 2005;44:279-304.
26.
Song
YH,
Son
HY.
Synthesis
of
New
1-
(e) Gooljarsingh LT, Lakdawala A, Coppo F, Luo L, Fields GB. Tummino
PJ, Gontarek RR. Characterization of an exosite binding inhibitor of matrix
metalloproteinase 13. Protein Sci. 2008;17:66-71;
(f) Li JJ, Nahra J, Johnson AR, Bunker A, O’Brien P, Yue WS, Ortwine DF,
Man CF, Baragi V, Kilgore K, Dyer RD, Han HK. Quinazolinones and
pyrido[3,4-d]pyrimidin-4-ones as orally active and specific matrix
metalloproteinase-13 inhibitors for the treatment of osteoarthritis. J. Med.
Chem. 2008:51:835-841;
(g) Heim-Riether A, Taylor SJ, Liang S, Gao DA, Xiong Z, Michael August
E, Collins BK, Farmer Ii BT, Haverty K, Hill-Drzewi M, Junker HD, Mariana
Margarit S, Moss N, Neumann T, Proudfoot JR, Keenan LS, Sekul R, Zhang
Q, Li J, Farrow NA. Improving potency and selectivity of a new class of non-
Zn-chelating MMP-13 inhibitors. Bioorg. Med. Chem. Lett. 2009;19:5321-
5324.
Phenylthieno[1,2,4]triazolo[4,3-a]pyrimidin-5(4H)-one
Heterocycl. Chem. 2011;48:597-603.
derivatives.
J.
27.
bioactivation of furan. Drug Metab. Rev. 2006:38:615-626.
28. Nara H, Sato K, Kaieda A, Oki H, Kuno H, Santou T, Kanzaki N,
Peterson LA. Electrophilic intermediates produced by
Terauchi J, Uchikawa O, Kori M. Design, synthesis, and biological activity of
novel, potent, and highly selective fused pyrimidine-2-carboxamide-4-one-
based matrix metalloproteinase (MMP)-13 zinc-binding inhibitors. Bioorg.
Med. Chem. 2016;24:6149-6165.
29.
Xie XW, Wan RZ, Liu ZP. Recent research advances in selective
matrix metalloproteinase-13 inhibitors as anti-osteoarthritis agents.
ChemMedChem 2017;12:1157-1168.
30.
Ruminski PG, Massa M, Strohbach J, Hanau CE, Schmidt M,
Scholten JA, Fletcher TR, Hamper BC, Carroll JN, Shieh HS, Caspers N,
Collins B, Grapperhaus M, Palmquist KE, Collins J, Baldus JE, Hitchcock J,
Kleine HP, Rogers MD, McDonald J, Munie GE, Messing DM, Portolan S,
Whiteley LO, Sunyer T, Schnute ME. Discovery of N-(4-fluoro-3-
methoxybenzyl)-6-(2-(((2S,5R)-5-(hydroxymethyl)-1,4-dioxan-2-yl)methyl)-
2H-tetrazol-5-yl)-2-methylpyrimidine-4-carboxamide. A highly selective and
orally bioavailable matrix metalloproteinase-13 inhibitor for the potential
treatment of osteoarthritis. J. Med. Chem. 2016;59:313-327.
10.
(a) Nara H, Kaieda A, Sato K, Naito T, Mototani H, Oki H,
Yamamoto Y, Kuno H, Santou T, Kanzaki N, Terauchi J, Uchikawa O, Kori
M. Discovery of novel, highly potent, and selective matrix metalloproteinase
(MMP)-13 inhibitors with a 1,2,4-triazol-3-yl moiety as a zinc binding group
using a structure-based design approach. J. Med. Chem. 2017;60:608-626;
(b) Gege C, Bao B, Bluhm H, Boer J, Gallagher BM, Korniski B, Powers TS,
Steeneck C, Taveras AG, Baragi VM. Discovery and evaluation of a non-Zn
chelating, selective matrix metalloproteinase 13 (MMP-13) inhibitor for