Design strategies for the identification of MMP-13 and TACE inhibitors

Current Opinion in Drug Discovery and Development

Volumn 6, Issue 5, 2003, Pages 742-759

  Skotnicki, Jerauld S ^a   DiGrandi, Martin J ^a   Levin, Jeremy I ^a  

^a PFIZER INC   (United States)

Author keywords

Collagenase; Hydroxamate; MMP 13; Osteoarthritis; Rheumatoid arthritis; Selectivity; TACE

Indexed keywords

4 [[[4 (4 CHLOROPHENOXY)PHENYL]SULFONYL]METHYL]TETRAHYDRO 2H PYRAN 4 CARBOHYDROXAMIC ACID; ABT 518; AMIDE; ANTHRANILIC ACID DERIVATIVE; AZIRIDINE DERIVATIVE; BENZODIAZEPINE DERIVATIVE; BIPHENYL DERIVATIVE; BMS 561392; CGS 27023A; CHELATING AGENT; COLLAGENASE 3; FENBUFEN; GW 3333; HYDROXAMIC ACID; IK 682; IMIDAZOLIDINE DERIVATIVE; MARIMASTAT; MATRIX METALLOPROTEINASE INHIBITOR; NAPHTHYL GROUP; PHOSPHINIC ACID DERIVATIVE; PIPERAZINE DERIVATIVE; PIPERIDINE DERIVATIVE; PKF 242 484; PROPARGYLGLYCINE; PYRROLIDINE DERIVATIVE; RO 32 7315; SUCCINIC ACID DERIVATIVE; SULFONAMIDE; SULFONE DERIVATIVE; THIADIAZINE DERIVATIVE; TUMOR NECROSIS FACTOR ALPHA CONVERTING ENZYME; TUMOR NECROSIS FACTOR ALPHA CONVERTING ENZYME INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG;

CLINICAL TRIAL; DRUG DESIGN; DRUG EFFICACY; DRUG POTENCY; DRUG SAFETY; DRUG SELECTIVITY; DRUG SPECIFICITY; DRUG SYNTHESIS; FIBROUS DYSPLASIA; HUMAN; MUSCULOSKELETAL DISEASE; NONHUMAN; OSTEOARTHRITIS; REVIEW; RHEUMATOID ARTHRITIS; SIDE EFFECT; TENDINITIS;

ADAM PROTEINS; ANIMALS; ARTHRITIS, RHEUMATOID; CHELATING AGENTS; COLLAGENASES; DRUG DESIGN; HUMANS; HYDROXAMIC ACIDS; MATRIX METALLOPROTEINASE 13; METALLOENDOPEPTIDASES; OSTEOARTHRITIS; PROTEASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP; ZINC;

EID: 0142123136     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (94)

1. Woessner JF, Nagase H (Eds): Matrix Metalloproteinases and TIMPS. Oxford University Press, New York, NY, USA (2000). An excellent review of the structure and function of MMPs and their inhibitors.
2. Birkedal-Hansen H, Moore WG, Bodden MK, Windsor LJ, Birkedal-Hansen B, DeCarlo A, Engler JA: Matrix metalloproteinases: A review. Crit Rev Oral Biol Med (1993) 4(2):197-250.
3. Clark IM, Parker AE: Metalloproteinases: Their role in arthritis and potential as therapeutic targets. Exp Opin Ther Targets (2003) 7(1):19-34.
4. George SJ: Therapeutic potential of matrix metalloproteinase inhibitors in atherosclerosis. Expert Opin Investig Drugs (2000) 9(5):993-1007.
5. Figleton B, Matrisian LM: Matrix metalloproteinases in cancer. In: Matrix Metalloproteinases in Cancer Therapy. Clendeninn NJ, Appelt K (Eds), Humana Press, Totowa, NJ, USA (2001):85-112.
6. Baker AH, Edwards DR, Murphy G: Metalloproteinase inhibitors: Biological actions and therapeutic opportunities. J Cell Sci (2002) 115(Pt 19):3719-3727.
7. Bode W, Fernandez-Catalan C, Tschesche H, Grams F, Nagase H, Maskos K: Structural properties on matrix metalloproteinases. Cell Mol Life Sci (1999) 55(4):639-652. A review focusing on the three-dimensional structures of MMPs.
8. Borkakoti N: Structural characteristics of the matrix metalloproteinases. In: Metalloproteinases as Targets for Anti-inflammatory Drugs. Bottomley KM, Bradshaw D, Nixon JS (Eds), Birkhauser Verlag, Basel, Switzerland (1999):1-16. A review of MMP structures, and of critical features defining MMP selectivity.
9. Nagase H: Substrate specificity of MMPs. In: Matrix Metalloproteinases in Cancer Therapy. Clendeninn NJ, Appelt K (Eds), Humana Press, Totowa, NJ, USA (2001):39-66.
10. Michaelides MR, Curtin ML: Recent advances in matrix metalloproteinase inhibitors research. Curr Pharm Design (1999) 5(10):787-819.
11. Skotnicki JS, Levin JI, Zask A, Killar LM: Matrix metalloproteinase inhibitors. In: Metalloproteinases as Targets for Anti-inflammatory Drugs. Bottomley KM, Bradshaw D, Nixon JS (Eds), Birkhauser Verlag, Basel, Switzerland (1999):17-57.
12. Whittaker M, Floyd CD, Brown P, Gearing AJ: Design and therapeutic application of matrix metalloproteinase inhibitors. Chem Rev (1999) 99(9):2735-2776.
13. Skiles JW, Gonnella NC, Jeng AY: The design, structure, and therapeutic application of matrix metalloproteinase inhibitors. Curr Med Chem (2001) 8(4):425-474. A comprehensive review of MMPIs.
14. Henrotin Y, Sanchez C, Reginster JY: The inhibition of metalloproteinases to treat osteoarthritis: Reality and new perspectives. Exp Opin Ther Pat (2002) 12(1):29-43.
15. Montana J, Baxter A: The design of selective non-substrate-based matrix metalloproteinase inhibitors. Curr Opin Drug Discovery Dev (2000) 3(4):353-361.
16. Black RA: Tumor necrosis factor-α converting enzyme. Int J Biochem Cell Biol (2002) 34(1):1-5.
17. Moss M, Becherer JD, Milla M, Pahel G, Lambert M, Andrews R, Frye S, Haffner C, Cowan D, Maloney P, Dixon EP et al: TNFα converting enzyme. In: Metalloproteinases as Targets for Anti-inflammatory Drugs. Bottomley KM, Bradshaw D, Nixon JS (Eds), Birkhauser Verlag, Basel, Switzerland (1999):187-203.
18. Killar L, White J, Black R, Peschon J: Adamalysins. A family of metzincins including TNF-α converting enzyme (TACE). Ann NY Acad Sci (1999) 878:442-452.
19. Maskos K, Fernandez-Catalan C, Huber R, Bourenkov GP, Bartunik H, Ellestad GA, Reddy P, Wolfson MF, Rauch CT, Castner BJ, Davis R et al: Crystal structure of the catalytic domain of human tumor necrosis factor-α -converting enzyme. Proc Natl Acad Sci USA (1998) 95(7):3408-3412. The X-ray crystal structure of TACE is described.
20. Newton RC, Decicco CP: Therapeutic potential and strategies for inhibiting tumor necrosis factor-α. J Med Chem (1999) 42(13):2295-2314. A review of the pathways and inhibitors affecting TNFα synthesis and release.
21. Reimold AM: TNFα as a therapeutic target: New drugs, more applications. Curr Drug Targets - Inflamm Allergy (2002) 1(4):377-392.
22. Moreland LM: Inhibitors of tumor necrosis factor for rheumatoid arthritis. J Rheumatol (1999) 26(Suppl 57):7-15.
23. Nelson FC, Zask A: The therapeutic potential of small molecule TACE inhibitors. Expert Opin Investig Drugs (1999) 8(4):383-392. A review of MMP/ TACE inhibitors in the patent and primary literature.
24. Moss ML, White JM, Lambert MH, Andrews RC: TACE and other ADAM proteases as targets for drug discovery. Drug Disc Today (2001) 6(8):417-426.
25. Skotnicki JS, Levin JI: TNF-α converting enzyme (TACE) as a therapeutic target. Ann Rep Med Chem (2003): in press. The most recent review of TACE as a drug target, and reported inhibitors.
26. Newton RC, Solomon KA, Covington MB, Decicco CP, Haley PJ, Friedman SM, Vaddi K: Biology of TACE inhibition. Ann Rheum Dis (2001) 60(Suppl 3):11125-11132. An excellent review on the pharmacology of MMP/TACE inhibitors and selective TACE inhibitors.
27. Fingleton B: Matrix metalloproteinase inhibitors for cancer therapy: The current situation and future prospects. Exp Opin Ther Targets (2003) 7(3):385-397.
28. Nelson AR, Fingleton B, Rothenberg ML, Matrisian LM: Matrix metalloproteinases: Biologic activity and clinical implications. J Clin Oncol (2000) 18(5):1135-1149.
29. Sternlicht MD, Bergers G: Matrix metalloproteinases as emerging targets in anticancer therapy: Status and prospects. Exp Opin Ther Targets (2000) 4(5):609-633.
30. Brown PD: Ongoing trials with matrix metalloproteinase inhibitors. Expert Opin Investig Drugs (2000) 9(9):2167-2177.
31. Shaw T, Nixon JS, Bottomley KM: Metalloproteinase inhibitors: New opportunities for the treatment of rheumatoid arthritis and osteoarthritis. Expert Opin Investig Drugs (2000) 9(7):1469-1478.
32. Elliott S, Cawston T: The clinical potential of matrix metalloproteinase inhibitors in the rheumatic diseases. Drugs Aging (2001) 18(2):87-99.
33. Renkiewicz R, Qiu L, Lesch C, Sun X, Devalaraja R, Cody T, Kaldjian E, Welgus H, Baragi V: Broad-spectrum matrix metalloproteinase inhibitor marimastat-induced musculoskeletal side effects in rats. Arthritis Rheum (2003) 48(6):1742-1749.
34. MacPherson LJ, Bayburt EK, Capparelli MP, Carroll BJ, Goldstein R, Justice MR, Zhu L, Hu S, Melton RA, Fryer L, Goldberg RL et al: Discovery of CGS-27023A, a non-peptidic, potent and orally active stromelysin inhibitor that blocks cartilage degradation in rabbits. J Med Chem (1997) 40(16):2525-2532. The first disclosure of a sulfonamide-hydroxamate MMPI.
35. Barta TE, Becker DP, Bedell LJ, De Crescenzo GA, McDonald JJ, Munie GE, Rao S, Shieh HS, Stegeman R, Stevens AM, Villamil CI: Synthesis and activity of selective MMP inhibitors with an aryl backbone. Bioorg Med Chem Lett (2000) 19(24):2815-2817.
36. Barta TE, Becker DP, Bedell LJ, De Crescenzo GA, McDonald JJ, Mehta P, Munie GE, Villamil CI: Selective, orally active MMP inhibitors with an aryl backbone. Bioorg Med Chem Lett (2000) 11(18):2481-2483.
37. Dack KN, Dickinson RP, Lewis ML, Whitlock GA: Design and synthesis of a novel series of matrix metalloproteinase inhibitors with high selectivity for MMP-3. 222nd ACS Meeting, Chicago, IL, USA (2001):MEDI 260.
38. Levin JI, Du MT, DiJoseph JF, Killar LM, Sung A, Walter T, Sharr MA, Roth CE, Moy FJ, Powers R, Jin G et al: The discovery of anthranilic acid-based MMP inhibitors. Part 1: SAR of the 3-position. Bioorg Med Chem Lett (2001) 11(2):235-238.
39. 13CO assignments and secondary structure determination of collagenase-3 (MMP-13) complexed with a hydroxamic acid inhibitor. J Biomol NMR (2000) 17(3):269-270.
40. Moy FJ, Chanda PK, Chen JM, Cosmi S, Edris W, Levin JI, Powers R: High resolution solution structure of the catalytic fragment of human collagenase-3 (MMP-13) complexed with a hydroxamic acid inhibitor. J Mol Biol (2000) 302(3):671-689.
41. 1 groups. Bioorg Med Chem Lett (2001) 11(16):2189-2192.
42. Levin JI, Chen JM, Du MT, Nelson FC, Wehr T, DiJoseph JF, Killar LM, Skala S, Sung A, Sharr MA, Roth CE et al: The discovery of anthranilic acid-based MMP inhibitors. Part 3: Incorporation of basic amines. Bioorg Med Chem Lett (2001) 11(22):2975-2978.
43. Levin JI, Gu Y, Nelson FC, Zask A, DiJoseph JF, Sharr MA, Sung A, Jin G, Cowling R, Chanda P, Cosmi S et al: Heteroaryl and cycloalkyl sulfonamide hydroxamic acid inhibitors of matrix metalloproteinases. Bioorg Med Chem Lett (2001) 11(2):239-242.
44. Zask A, Gu Y, Albright JD, Du X, Hogan M, Levin JI, Chen JM, Killar LM, Sung A, DiJoseph JF, Sharr MA et al: Synthesis and SAR of bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors. Bioorg Med Chem Lett (2003) 13(8):1487-1490.
45. Chen JM, Nelson FC, Levin JI, Mobilio D, Moy FJ, Nilakantan R, Zask A, Powers RJ: 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(40):9648-9654.
46. Hajduk PJ, Shuker SB, Nettesheim DG, Craig R, Augeri DJ, Betebenner D, Albert DH, Guo Y, Meadows RP, Xu L, Michaelides M et al: NMR-based modification of matrix metalloproteinase inhibitors with improved bioavailability. J Med Chem (2002) 45(26):5628-5639.
47. Hanessian S, Moitessier N, Cantin LD: Design and synthesis of MMP inhibitors using N-arylsulfonylaziridine hydroxamic acids as constrained scaffolds. Tetrahedron (2001) 57(32):6885-6900.
48. Robinson RP, Laird ER, Blake JF, Bordner J, Donahue KM, Lopresti-Morrow LL, Mitchell PG, Reese MR, Reeves LM, Stam EJ, Yocum SA: Structure-based design and synthesis of a potent matrix metalloproteinase-13 inhibitor based on a pyrrolidinone scaffold. J Med Chem (2000) 43(12):2293-2296.
49. Robinson RP, Laird ER, Donahue KM, Lopresti-Morrow LL, Mitchell PG, Reese MR, Reeves LM, Rouch AI, Stam EJ, Yocum SA: Design and synthesis of 2-oxo-imidazolidine-4-carboxylic acid hydroxyamides as potent matrix metalloproteinase-13 Inhibitors. Bioorg Med Chem Lett (2001) 11(9):1211-1213.
50. Nelson FC, Delos Santos E, Levin JI, Chen JM, Skotnicki JS, DiJoseph JF, Sharr MA, Sung A, Killar LM, Cowling R, Jin G et al: Benzodiazepine inhibitors of the MMPs and TACE. Bioorg Med Chem Lett (2002) 12(20):2867-2870.
51. Cheng M, De B, Pikul S, Almstead NG, Natchus MG, Anastasio MV, McPhail SJ, Snider CE, Taiwo YO, Chen L, Dunaway CM et al: Design and synthesis of piperazine-based matrix metalloproteinase inhibitors. J Med Chem (2000) 43(3):369-380.
52. Pikul S, Dunham KM, Almstead NG, De B, Natchus MG, Taiwo YO, Williams LE, Hynd BA, Hsieh LC, Janusz MJ, Gu F et al: Heterocycle-based MMP inhibitors with P2′ substituents. Bioorg Med Chem Lett (2001) 11(8):1009-1013.
53. Hanessian S, Moitessier N, Gauchet C, Viau M: N-Aryl sulfonyl homocysteine hydroxamate inhibitors of matrix metalloproteinases: Further probing of the S1, S1′ and S2′ pockets. J Med Chem (2001) 44(19):3066-3073.
54. Chollet AM, Le Diguarher T, Murray L, Bertrand M, Tucker GC, Sabatini M, Pierre A, Atassi G, Bonnet J, Casara P: General synthesis of α-substituted 3-bisaryloxy propionic acid derivatives as specific MMP inhibitors. Bioorg Med Chem Lett (2001) 11(3):295-299.
55. Chollet AM, Le Diguarher T, Kucharczyk N, Loynel A, Bertrand M, Tucker G, Guilbaud N, Burbridge M, Pastoureau P, Fradin A, Sabatini M et al: Solid-phase synthesis of α-substituted 3-bisarylthio N-hydroxy propionamides as specific MMP inhibitors. Bioorg Med Chem (2002) 10(3):531-544.
56. Becker DP, Barta TE, Bedell L, DeCrescenzo G, Freskos J, Getman DP, Hockerman SL, Li M, Mehta P, Mischke B, Munie GE et al: α-Amino-β -sulphone hydroxamates as potent MMP-13 inhibitors that spare MMP-1. Bioorg Med Chem Lett (2001) 11(20):2719-2722.
57. Becker DP, DeCrescenzo G, Freskos J, Getman DP, Hockerman SL, Li M, Mehta P, Munie GE, Swearingen C: α-Alkyl-α-amino-β-sulphone hydroxamates as potent MMP inhibitors that spare MMP-1. Bioorg Med Chem Lett (2001) 11(20):2723-2725.
58. Aranapakam V, Grosu GT, Davis JM, Hu B, Ellingboe J, Baker JL, Skotnicki JS, Zask A, DiJoseph JF, Sung A, Sharr MA et al: Synthesis and structure-activity relationship of α-sulfonylhydroxamic acids as novel, orally active matrix metalloproteinase inhibitors for the treatment of osteoarthritis. J Med Chem (2003) 46(12):2361-2375.
59. Aranapakam V, Davis JM, Grosu GT, Baker J, Ellingboe J, Zask A, Levin JI, Sandanaka VP, Du M, Skotnicki JS, DiJoseph JF et al: Synthesis and structure-activity relationship of N-substituted 4-aryisulfonylpiperidine-4-hydroxamic acids as novel, orally active matrix metalloproteinase inhibitors for the treatment of osteoarthritis. J Med Chem (2003) 46(12):2376-2396. A description of the discovery of a class of MMP-13 inhibitors with selectivity over MMP-1 and oral activity in animal models of OA.
60. Curtin ML, Florjancic AS, Heyman HR, Michaelides MR, Garland RB, Holms JH, Steinman DH, Dellaria JF, Gong J, Wada CK, Guo Y et al: Discovery and characterization of the potent, selective and orally bioavaialble MMP inhibitor ABT-770. Bioorg Med Chem Lett (2001) 11(12):1557-1560.
61. Michaelides MR, Dellaria JF, Gong J, Holms JH, Bouska JJ, Stacey J, Wada CK, Heyman HR, Curtin ML, Guo Y, Goodfellow CL et al: Biaryl ether retrohydroxamtes as potent, long-lived, orally bioavailable MMP inhibitor. Bioorg Med Chem Lett (2001) 11(12):1553-1556.
62. Wada CK, Holms JH, Curtin ML, Dai Y, Florjancic AS, Garland RB, Guo Y, Heyman HR, Stacey JR, Steinman DH, Albert DH et al: Phenoxyphenyl sulfone N-formylhydroxylamines (retrohydroxamates) as potent, selective, orally bioavailable matrix metalloproteinase inhibitors. J Med Chem (2002) 45(1):219-232. A description of the identification of ABT-518, an oncology clinical candidate.
63. O'Brien PM, Ortwine DF, Pavlovsky AG, Picard JA, Sliskovic DR, Roth BD, Dyer RD, Johnson LL, Man CF, Hallak H: Structure-activity relationships and pharmacokinetic analysis for a series of potent, systemically available biphenylsulfonamide matrix metalloproteinase inhibitors. J Med Chem (2000) 43(2):156-166. A report of potent non-peptide, non-hydroxamate MMPIs.
64. Natchus MG, Bookland RG, Laufersweiler MJ, Pikul S, Almstead NG, De B, Janusz MJ, Hsieh LC, Gu F, Pokross ME, Patel VS et al: Development of new carboxylic acid-based MMP inhibitors derived from functionalized propargylglycines. J Med Chem (2001) 44(7):1060-1071.
65. Tullis JS, Laufersweiler MJ, VanRens JC, Natchus MG, Bookland RG, Almstead NG, Pikul S, De B, Hseih LC, Janusz MJ, Branch TM et al: The development of new carboxylic acid-based MMP inhibitors derived from a cyclohexylglycine scaffold. Bioorg Med Chem Lett (2001) 11(15):1975-1979.
66. Pikul S, Ohler NE, Ciszewski G, Laufersweiler MC, Almstead NG, De B, Natchus MG, Hsieh LC, Janusz MJ, Peng SX, Branch TM et al: Potent and selective carboxylic acid-based inhibitors of matrix metalloproteinases. J Med Chem (2001) 44(16):2499-2502.
67. Schroder J, Henke A, Wenzel H, Brandstetter H, Stamler HG, Stammler A, Pfeiffer WD, Tschesche H: Structure-based design and synthesis of potent matrix metalloproteinase inhibitors derived from a 6H-1,3,4-thiadiazine scaffold. J Med Chem (2001) 44(20):3231-3243.
68. Reiter LA, Mitchell PG, Martinelli GJ, Lopresti-Morrow LL, Yocum SA, Eskra, JD: Phosphinic acid-based MMP-13 inhibitors that spare MMP-1 and MMP-3. Bioorg Med Chem Lett (2003) 13(14):2331-2336.
69. Garrison L, McDonnell ND: Etanercept: Therapeutic use in patients with rheumatoid arthritis. Ann Rheum Dis (1999) 58(Suppl 1):165-169.
70. Newton RC, Decicco CP: Therapeutic potential and strategies for inhibiting tumor necrosis factor-α. J Med Chem (1999) 42(13):2295-2314.
71. Yoshihara Y, Nakamura H, Obata K, Yamada H, Hayakawa T, Fujikawa K, Okada Y: Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluid from patients with rheumatoid arthritis or osteoarthritis. Ann Rheum Dis (2000) 59(6):455-461.
72. Fujisawa T, Igeta K, Odake S, Morita Y, Yasuda J, Morikawa T: Highly water-soluble matrix metalloproteinases inhibitors and their effects in a rat adjuvant-induced arthritis model. Bioorg Med Chem (2002) 10(8):2569-2581.
73. Kottirsch G, Koch G, Feifel R Neumann U: β-Aryl-succinic acid hydroxamates as dual inhibitors of matrix metalloproteinases and tumor necrosis factor α converting enzyme. J Med Chem (2002) 45(11):2289-2293.
74. Trifilieff A, Walker C, Keller T, Kottirsch G, Neumann U: Pharmacological profile of PKF242-484 and PKF241-466, novel dual inhibitors of TNF-α converting enzyme and matrix metalloproteinases, in models of airway inflammation. Br J Pharmacol (2002) 135(7):1655-1664.
75. Conway JG, Andrews RC, Beaudet B, Bickett DM, Boncek V, Brodie TA, Clark RL, Crumrine RC, Leenitzner MA, McDougald DL, Han B et al: Inhibition of tumor necrosis factor-α (TNF-α) production and arthritis in the rat by GW3333, a dual inhibitor of TNF-α converting enzyme and matrix metalloproteinases. J Pharmacol Exp Ther (2001) 298(3):900-908. Disclosure of the pharmacology of a potent, in vivo-active, long-lasting MMP/TACE inhibitor.
76. Rabinowitz MH, Andrews RC, Becherer JD, Bickett DM, Bubacz DG, Conway JG, Cowan DJ, Gaul M, Glennon K, Lambert MH, Leesnitzer MA et al: Design of selective and soluble inhibitors of tumor necrosis factor-α converting enzyme (TACE). J Med Chem (2001) 44(24):4252-4267.
77. Holms J, Mast K, Marcotte P, Elmore I, Li J, Pease L, Glaser K, Morgan D, Michealides M, Davidsen S: Discovery of selective hydroxamic acid inhibitors of tumor necrosis factor-α converting enzyme. Bioorg Med Chem Lett (2001) 11 (22):2907-2910.
78. Levin JI: New approaches to the medicinal chemistry of anti-inflammatory drugs. Inflammation Research Association Symposium, New York Academy of Sciences, New York, NY, USA (2001).
79. Chen JM, Jin G, Sung A, Levin JI: Anthranilate sulfonamide hydroxamate TACE inhibitors. Part 1: Structure-based design of novel acetylenic P1′ groups. Bioorg Med Chem Lett (2002) 12(8):1195-1198. The construction of a TACE homology model, and subsequent structure-based design of inhibitors, are described.
80. Levin JI, Chen JM, Du MT, Nelson FC, Killar LM, Skala S, Sung A, Jin G, Cowling R, Barone D, March CJ et al: Anthranilate-based sulfonamide hydroxamate TACE inhibitors. 2. SAR of the acetylenic P1′ group. Bioorg Med Chem Lett (2002) 12(8):1199-1202.
81. Letavic MA, Axt MZ, Barberia JT, Carty TJ, Danley DE, Geoghegan KF, Halim NS, Hoth LR, Kamath AV, Laird ER, Lopresti-Morrow LL et al: Synthesis and biological activity of selective pipecolic acid-based TNF-α converting enzyme (TACE) inhibitors. Bioorg Med Chem Lett (2002) 12(10):1387-1390.
82. Xue CB, He X, Corbett RL, Roderick J, Wasserman ZR, Liu RQ, Jaffee BD, Covington MB, Qian M, Trzaskos JM, Newton RC et al: Discovery of macrocyclic hydroxamic acids containing biphenylmethyl derivatives at P1′, a series of selective TNF-α converting enzyme inhibitors with potent cellular activity in the inhibition of TNF-α release. J Med Chem (2001) 44(21):3351-3354.
83. Duan JJ, Chen L, Wasserman ZR, Lu Z, Liu RQ, Covington MB, Qian M, Hardman KD, Magolda RL, Newton RC, Christ DD et al: Discovery of γ-lactam hydroxamic acids as selective inhibitors of tumor necrosis factor α converting enzyme: Design, synthesis, and structure-activity relationships. J Med Chem (2002) 45(23):4954-4957. The structure-based design of TACE inhibitors with excellent cell activity and selectivity over many MMPs is described.
84. Duan JJ, Lu Z, Xue CB, He X, Seng JL, Roderick JJ, Wasserman ZR, Liu RQ, Covington MB, Magolda RL, Newton RC et al: Discovery of N-hydroxy-2-(2-oxo-3-pyrrolidinyl)acetamides as potent and selctive inhibitors of tumor necrosis factor-α converting enzyme (TACE). Bioorg Med Chem Lett (2003) 13(12):2035-2040.
85. Wasserman ZR, Duan JJ, Voss ME, Xue CB, Cherney RJ, Nelson DJ, Hardman KD, Decicco CP: Identification of a selectivity determinant for inhibition of tumor necrosis factor-α converting enzyme by comparative modeling. Chem Biol (2003) 10(3):215-223.
86. Cherney RJ, Duan JJ, Voss ME, Chen L, Wang L, Meyer DT, Wasserman ZR, Hardman KD, Liu RQ, Covington MB, Qian M et al: Design, synthesis and evaluation of benzothiadiazepine hydroxamates as selective tumor necrosis factor-α converting enzyme inhibitors. J Med Chem (2003) 46(10):1811-1823.
87. Vaddi KG, Magolda RL, Haley PJ, Collins RJ, Taylor TL, Madsukuie TP, Decicco CP, Newton RC, Friedman SF: Characterization of the anti-inflammatory effects of a selective TACE inhibitor, DPC 333 (BMS-561392). American College of Rheumatology 65th Annual Scientific Meeting, San Francisco, CA, USA (2001):Abs 255.
88. Grootveld M, McDermott MF: BMS-561392. Curr Opin Invest Drugs (2003) 4(5):598-602.
89. Sawa M, Kiyoi T, Kurokawa K, Kumihara H, Yamamoto M, Miyasaka T, Ito Y, Hirayama R, Inoue T, Kirii Y, Nishiwaki E et al: New type of metalloproteinase inhibitor: Design and synthesis of new phosphonamide-based hydroxamic acids. J Med Chem (2002) 45(4):919-929.
90. Sawa M, Kurokawa K, Inoue Y, Kondo H, Yoshino K: Discovery of selective phosphonamide-based inhibitors of tumor necrosis factor-α converting enzyme (TACE). Bioorg Med Chem Lett (2003) 13(12):2021-2024.
91. Hirata T, Itoh K, Misumi K, Kuramoto Y, Inokuma K, Amano H, Aoki S, Yoshimatsu T: Discovery of potent, highly selective, and orally active propenohydroxamate TNF-α converting enzyme (TACE) inhibitors. 222nd ACS National Meeting, Chicago, IL, USA (2001):MEDI 262.
92. PHARMACIA (McDonald JJ, Barta TE, Arner E, Boehm TL, Becker DP, De Crescenzo GA): Use of sulfonyl aryl or heteroaryl hydroxamic acids and derivatives thereof as aggrecanase inhibitors. WO-03007930 (2003).
93. PHARMACIA (Barta TE, Becker DP, Bedell LJ, Boehm TL, Fobian YM, Freskos JN, Hockerman SL, Kassab DJ, Kolodziej SA, McDonald JJ, Norton MB et al): Aromatic sulfone hydroxamates and their use as protease inhibitors. WO-02092588 (2002).
94. WARNER-LAMBERT COMPANY (Bunker AM, Harter WG, Hicks JL, O'Brien PM, Pham LT, Picard JA, Roark WH): Alkyne matrix metalloproteinase inhibitors. WO-03032999 (2003). A series of patent applications describing allosteric inhibitors of MMP-13.