Design and Synthesis of a Series of (2R)-N 4-Hydroxy-2-(3-hydroxybenzyl)-N - [(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden- 1-yl]butanediamide Derivatives as Potent, Selective, and Orally Bioavailable Aggrecanase Inhibitors
A pharmacophore model of the P1‘ site, specific for aggrecanase, was defined using the specificity studies of the matrix metalloproteinases and the similar biological activity of aggrecanase and MMP-8. Incorporation of the side chain of a tyrosine residue into compound 1 as the P1‘ group provided mo...
Saved in:
| Published in | Journal of medicinal chemistry Vol. 44; no. 21; pp. 3347 - 3350 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
American Chemical Society
11.10.2001
|
| Online Access | Get full text |
Cover
Loading…
| Abstract | A pharmacophore model of the P1‘ site, specific for aggrecanase, was defined using the specificity studies of the matrix metalloproteinases and the similar biological activity of aggrecanase and MMP-8. Incorporation of the side chain of a tyrosine residue into compound 1 as the P1‘ group provided modest selectivity for aggrecanase over MMP-1, -2, and -9. A cis-(1S)(2R)-amino-2-indanol scaffold was incorporated as a tyrosine mimic (P2‘) to conformationally constrain 2. Further optimization resulted in compound 11, a potent, selective, and orally bioavailable inhibitor of aggrecanase. |
|---|---|
| AbstractList | A pharmacophore model of the P1‘ site, specific for aggrecanase, was defined using the specificity studies of the matrix metalloproteinases and the similar biological activity of aggrecanase and MMP-8. Incorporation of the side chain of a tyrosine residue into compound 1 as the P1‘ group provided modest selectivity for aggrecanase over MMP-1, -2, and -9. A cis-(1S)(2R)-amino-2-indanol scaffold was incorporated as a tyrosine mimic (P2‘) to conformationally constrain 2. Further optimization resulted in compound 11, a potent, selective, and orally bioavailable inhibitor of aggrecanase. |
| Author | Reddy, Gade Pratta, Michael A Liu, Rui-Qin Newton, Robert Arner, Elizabeth C Chao, Michael Christ, David Yao, Wenqing Qian, MingXin Decicco, Carl P Wasserman, Zelda R Covington, Maryanne B Magolda, Ronald L Wexler, Ruth R Ribadeneira, Maria D Tortorella, Micky Shi, Eric |
| Author_xml | – sequence: 1 givenname: Wenqing surname: Yao fullname: Yao, Wenqing – sequence: 2 givenname: Zelda R surname: Wasserman fullname: Wasserman, Zelda R – sequence: 3 givenname: Michael surname: Chao fullname: Chao, Michael – sequence: 4 givenname: Gade surname: Reddy fullname: Reddy, Gade – sequence: 5 givenname: Eric surname: Shi fullname: Shi, Eric – sequence: 6 givenname: Rui-Qin surname: Liu fullname: Liu, Rui-Qin – sequence: 7 givenname: Maryanne B surname: Covington fullname: Covington, Maryanne B – sequence: 8 givenname: Elizabeth C surname: Arner fullname: Arner, Elizabeth C – sequence: 9 givenname: Michael A surname: Pratta fullname: Pratta, Michael A – sequence: 10 givenname: Micky surname: Tortorella fullname: Tortorella, Micky – sequence: 11 givenname: Ronald L surname: Magolda fullname: Magolda, Ronald L – sequence: 12 givenname: Robert surname: Newton fullname: Newton, Robert – sequence: 13 givenname: MingXin surname: Qian fullname: Qian, MingXin – sequence: 14 givenname: Maria D surname: Ribadeneira fullname: Ribadeneira, Maria D – sequence: 15 givenname: David surname: Christ fullname: Christ, David – sequence: 16 givenname: Ruth R surname: Wexler fullname: Wexler, Ruth R – sequence: 17 givenname: Carl P surname: Decicco fullname: Decicco, Carl P |
| BookMark | eNptUV1r20AQPEoKsdM-5B_cS8EGbXpfsuzHNF8OhKTU7VMpYqVb2WfkU7hTTJR_mn8T2W77lKfd2Rl2BmbIjnzjibFTKc6kUPLreiNkmmpdfmADmSoBZirMERsIoRSoidLHbBjjWgihpdID9npJ0S09R2_5ovPtqoeRNxVHvqDgaL-P1I8x3HMD886G5rkDBSMNqwMoyL909Y4H_nskF8lOrP6xoBIN1u0RyDk4b8kDl9DVf4qnFj1ZhxtniV_2dlts3bb3xMi_Ny35NulT1FTursk-40PAuu74N9fgFl2NRU38fLkMVKLHSPzWr1zh2ibET-xjhXWkz3_nCft1ffXzYg53Dze3F-d3gFKYErDIRCZTm2GPrc7QVNZURlezSiltlZimcqZLFMbOCkmTqdSkCpwYmWZEYqZP2PjwtwxNjIGq_DG4DYYulyLfdZL_76TXfjlosYz5unkKvk_2ju4NYeaL5Q |
| CitedBy_id | crossref_primary_10_1016_j_bmcl_2007_07_048 crossref_primary_10_1021_acsptsci_2c00023 crossref_primary_10_1046_j_1432_1033_2003_03607_x crossref_primary_10_1016_j_bbapap_2011_06_020 crossref_primary_10_1038_nmat2116 crossref_primary_10_1186_s12964_019_0443_2 crossref_primary_10_1172_JCI30765 crossref_primary_10_1021_jm101609j crossref_primary_10_1002_art_20101 crossref_primary_10_1074_jbc_M303737200 crossref_primary_10_1016_j_ejmech_2012_12_058 crossref_primary_10_2106_JBJS_F_01437 crossref_primary_10_1016_j_bmcl_2005_10_001 crossref_primary_10_1016_j_ab_2007_09_014 crossref_primary_10_1016_j_bmcl_2006_12_027 crossref_primary_10_1016_j_matbio_2015_01_014 crossref_primary_10_1002_fsn3_601 crossref_primary_10_1002_art_10726 crossref_primary_10_1016_S0306_4522_02_00347_0 crossref_primary_10_1074_jbc_M200431200 crossref_primary_10_1002_ddr_20166 crossref_primary_10_1016_j_matbio_2005_12_003 crossref_primary_10_1007_s40520_018_0953_6 crossref_primary_10_1016_j_joca_2006_01_012 crossref_primary_10_1074_jbc_M109_029116 crossref_primary_10_1021_ol102756m crossref_primary_10_1080_10799893_2019_1710848 crossref_primary_10_1016_S0960_894X_01_00704_1 crossref_primary_10_1016_j_tetasy_2003_08_040 crossref_primary_10_2116_analsci_21_61 crossref_primary_10_1002_cmdc_200900523 crossref_primary_10_1016_j_ejmech_2013_08_027 crossref_primary_10_1016_S0960_894X_03_00124_0 crossref_primary_10_1016_j_bmcl_2006_12_020 crossref_primary_10_1016_j_rechem_2023_101135 crossref_primary_10_1021_acs_jmedchem_2c01177 crossref_primary_10_1186_s13075_014_0429_9 crossref_primary_10_1002_jcb_23298 crossref_primary_10_1517_14728222_7_1_19 crossref_primary_10_1002_minf_201100131 crossref_primary_10_1016_j_bmcl_2011_09_036 crossref_primary_10_1021_cr050970a crossref_primary_10_1016_j_bmc_2008_08_058 crossref_primary_10_1016_j_joca_2008_10_005 crossref_primary_10_1002_ejoc_202301143 crossref_primary_10_1016_j_bmcl_2009_02_024 crossref_primary_10_1016_j_bmcl_2011_06_009 crossref_primary_10_4155_fmc_14_84 |
| Cites_doi | 10.2174/1381612805666230111211438 10.1002/(SICI)1097-0282(1996)40:4<399::AID-BIP5>3.0.CO;2-R 10.1016/S0021-9258(18)48387-1 10.1021/jo00036a004 10.1021/cr9804543 10.1074/jbc.272.14.9294 10.2106/00004623-197052030-00002 10.1110/ps.48401 10.1016/S0021-9258(18)41799-1 10.1021/jm00014a010 10.1111/j.1749-6632.1999.tb07676.x 10.1016/S0021-9258(18)45559-7 10.1016/S0968-0896(97)00028-X 10.1074/jbc.274.10.6594 10.1074/jbc.M001065200 10.1016/S0960-894X(01)00137-8 10.1126/science.284.5420.1664 10.1074/jbc.270.6.2550 10.1021/jm960871c 10.1016/0014-5793(95)01539-6 10.1021/jm00047a001 10.1042/bj2950273 10.1042/bj3040347 |
| ContentType | Journal Article |
| Copyright | Copyright © 2001 American Chemical Society |
| Copyright_xml | – notice: Copyright © 2001 American Chemical Society |
| DBID | AAYXX CITATION |
| DOI | 10.1021/jm015533c |
| DatabaseName | CrossRef |
| DatabaseTitle | CrossRef |
| DatabaseTitleList | |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Chemistry Pharmacy, Therapeutics, & Pharmacology |
| EISSN | 1520-4804 |
| EndPage | 3350 |
| ExternalDocumentID | 10_1021_jm015533c b586369922 |
| GroupedDBID | - .K2 3EH 53G 55A 5GY 5RE 5VS 7~N 9M8 AABXI ABFLS ABMVS ABOCM ABPTK ABUCX ACGFS ACJ ACS ADKFC AEESW AENEX AFEFF AFFNX ALMA_UNASSIGNED_HOLDINGS ANTXH AQSVZ BAANH CS3 DU5 EBS ED ED~ EJD F5P GJ GNL IH9 IHE JG JG~ K2 L7B LG6 MVM NHB P2P ROL TN5 UI2 VF5 VG9 W1F WH7 X XFK YZZ ZE2 ZGI ZY4 --- -~X .GJ AAHBH AAYOK AAYXX ABJNI ABQRX ABTAH ACGFO ADHLV AGXLV AHGAQ CITATION CUPRZ GGK IH2 XSW YQT |
| ID | FETCH-LOGICAL-a104c-ab70715d7aa10d37a4fd4f43f9f223d2085193ca04d9b1e6813e2ba64157ee093 |
| IEDL.DBID | ACS |
| ISSN | 0022-2623 |
| IngestDate | Fri Aug 23 02:29:23 EDT 2024 Thu Aug 27 13:42:21 EDT 2020 |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 21 |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-a104c-ab70715d7aa10d37a4fd4f43f9f223d2085193ca04d9b1e6813e2ba64157ee093 |
| PageCount | 4 |
| ParticipantIDs | crossref_primary_10_1021_jm015533c acs_journals_10_1021_jm015533c |
| ProviderPackageCode | JG~ 55A AABXI GNL VF5 7~N ACJ VG9 W1F ANTXH ACS AEESW AFEFF .K2 ABMVS ABUCX IH9 BAANH AQSVZ ED~ UI2 |
| PublicationCentury | 2000 |
| PublicationDate | 20011011 |
| PublicationDateYYYYMMDD | 2001-10-11 |
| PublicationDate_xml | – month: 10 year: 2001 text: 20011011 day: 11 |
| PublicationDecade | 2000 |
| PublicationTitle | Journal of medicinal chemistry |
| PublicationTitleAlternate | J. Med. Chem |
| PublicationYear | 2001 |
| Publisher | American Chemical Society |
| Publisher_xml | – name: American Chemical Society |
| References | Dunten P. (jm015533cb00019/jm015533cb00019_1) 2001; 10 Dorsey B. D. (jm015533cb00014/jm015533cb00014_1) 1994; 37 Sandy J. D. (jm015533cb00004/jm015533cb00004_3) 1991; 266 Fosang A. J. (jm015533cb00002/jm015533cb00002_4) 1996; 380 Moy F. J. (jm015533cb00019/jm015533cb00019_3) 2000; 302 Van Meurs B. J. (jm015533cb00004/jm015533cb00004_5) 1999; 42 Fields G. B. (jm015533cb00011/jm015533cb00011_1) 1987; 262 Askin D. (jm015533cb00023/jm015533cb00023_1) 1992; 57 Zhang D. (jm015533cb00015/jm015533cb00015_1) 1994; 91 Compound (jm015533cb00008/jm015533cb00008_1) 1986 Arner E. C. (jm015533cb00004/jm015533cb00004_4) 1999; 274 Tortorella M. (jm015533cb00018/jm015533cb00018_1) 2000; 275 Xue C.-B. (jm015533cb00018/jm015533cb00018_2) 1998; 41 Luty B. A. (jm015533cb00017/jm015533cb00017_1) 1995; 16 Whittaker M. (jm015533cb00007/jm015533cb00007_1) 1999; 99 Mankin H. J. (jm015533cb00001/jm015533cb00001_1) 1970; 52 Tortorella M. D. (jm015533cb00003/jm015533cb00003_1) 1999; 284 Pikul S. (jm015533cb00019/jm015533cb00019_2) 2001; 11 Fosang A. J. (jm015533cb00009/jm015533cb00009_1) 1994; 304 Gowravaram M. R. (jm015533cb00013/jm015533cb00013_1) 1995; 38 Miller J. A. (jm015533cb00018/jm015533cb00018_3) 1998 Nagase H. (jm015533cb00010/jm015533cb00010_1) 1996; 40 Lark W. (jm015533cb00004/jm015533cb00004_6) 1995; 270 Baenteli R. (jm015533cb00022/jm015533cb00022_1) 1999; 40 Lohamnder L. S. (jm015533cb00004/jm015533cb00004_2) 1993; 36 Gomis-Ruth F. X. (jm015533cb00016/jm015533cb00016_1) 1994; 239 Fosang A. J. (jm015533cb00002/jm015533cb00002_1) 1992; 267 Fosang A. J. (jm015533cb00002/jm015533cb00002_3) 1993; 295 Hirayama R. (jm015533cb00020/jm015533cb00020_1) 1997; 5 MacPherson L. J. (jm015533cb00021/jm015533cb00021_1) 1997; 40 Flannery C. R. (jm015533cb00002/jm015533cb00002_2) 1992; 267 Tortorella M. (jm015533cb00012/jm015533cb00012_1) 2000; 275 Arner E. C. (jm015533cb00004/jm015533cb00004_1) 1998 Arner E. C. (jm015533cb00005/jm015533cb00005_1) 1999; 878 Arner C. (jm015533cb00009/jm015533cb00009_2) 1997; 272 Michaelides M. R. (jm015533cb00006/jm015533cb00006_1) 1999; 5 |
| References_xml | – volume: 5 start-page: 819 year: 1999 ident: jm015533cb00006/jm015533cb00006_1 publication-title: Curr. Pharm. Des. doi: 10.2174/1381612805666230111211438 contributor: fullname: Michaelides M. R. – volume: 40 start-page: 416 year: 1996 ident: jm015533cb00010/jm015533cb00010_1 publication-title: Biopolymers doi: 10.1002/(SICI)1097-0282(1996)40:4<399::AID-BIP5>3.0.CO;2-R contributor: fullname: Nagase H. – volume: 40 start-page: 2112 year: 1999 ident: jm015533cb00022/jm015533cb00022_1 publication-title: Tetrahedron Lett. contributor: fullname: Baenteli R. – volume: 267 start-page: 1014 year: 1992 ident: jm015533cb00002/jm015533cb00002_2 publication-title: J. Biol. Chem. doi: 10.1016/S0021-9258(18)48387-1 contributor: fullname: Flannery C. R. – volume-title: Cytokine-induced cartilage proteoglycan degradation is meadiated by aggrecanase Osteoarthritis Cartilage year: 1998 ident: jm015533cb00004/jm015533cb00004_1 contributor: fullname: Arner E. C. – volume: 57 start-page: 2773 year: 1992 ident: jm015533cb00023/jm015533cb00023_1 publication-title: J. Org. Chem. doi: 10.1021/jo00036a004 contributor: fullname: Askin D. – volume: 99 start-page: 2776 year: 1999 ident: jm015533cb00007/jm015533cb00007_1 publication-title: Chem. Rev. doi: 10.1021/cr9804543 contributor: fullname: Whittaker M. – volume: 272 start-page: 9299 year: 1997 ident: jm015533cb00009/jm015533cb00009_2 publication-title: J. Biol. Chem. doi: 10.1074/jbc.272.14.9294 contributor: fullname: Arner C. – volume: 52 start-page: 434 year: 1970 ident: jm015533cb00001/jm015533cb00001_1 publication-title: J. Bone Joint Surg doi: 10.2106/00004623-197052030-00002 contributor: fullname: Mankin H. J. – volume: 10 start-page: 926 year: 2001 ident: jm015533cb00019/jm015533cb00019_1 publication-title: Protein Sci. doi: 10.1110/ps.48401 contributor: fullname: Dunten P. – volume: 302 start-page: 89 year: 2000 ident: jm015533cb00019/jm015533cb00019_3 publication-title: J. Mol. Biol. contributor: fullname: Moy F. J. – volume: 239 start-page: 544 year: 1994 ident: jm015533cb00016/jm015533cb00016_1 publication-title: J. Mol. Biol. contributor: fullname: Gomis-Ruth F. X. – volume: 267 start-page: 19474 year: 1992 ident: jm015533cb00002/jm015533cb00002_1 publication-title: J. Biol. Chem. doi: 10.1016/S0021-9258(18)41799-1 contributor: fullname: Fosang A. J. – volume: 275 start-page: 25797 year: 2000 ident: jm015533cb00012/jm015533cb00012_1 publication-title: J. Biol. Chem contributor: fullname: Tortorella M. – volume: 38 start-page: 2581 year: 1995 ident: jm015533cb00013/jm015533cb00013_1 publication-title: J. Med. Chem. doi: 10.1021/jm00014a010 contributor: fullname: Gowravaram M. R. – volume-title: Assays and peptide substrate for determining aggrecan-degrading metalloprotease activity. WO 0005256 year: 1998 ident: jm015533cb00018/jm015533cb00018_3 contributor: fullname: Miller J. A. – volume: 878 start-page: 107 year: 1999 ident: jm015533cb00005/jm015533cb00005_1 publication-title: N. Y. Acad. Sci. doi: 10.1111/j.1749-6632.1999.tb07676.x contributor: fullname: Arner E. C. – volume: 42 start-page: 1139 year: 1999 ident: jm015533cb00004/jm015533cb00004_5 publication-title: Arthritis Rheum. contributor: fullname: Van Meurs B. J. – volume: 262 year: 1987 ident: jm015533cb00011/jm015533cb00011_1 publication-title: J. Biol. Chem. doi: 10.1016/S0021-9258(18)45559-7 contributor: fullname: Fields G. B. – volume: 5 start-page: 778 year: 1997 ident: jm015533cb00020/jm015533cb00020_1 publication-title: Bioorg. Med. Chem. doi: 10.1016/S0968-0896(97)00028-X contributor: fullname: Hirayama R. – volume: 274 start-page: 6601 year: 1999 ident: jm015533cb00004/jm015533cb00004_4 publication-title: J. Biol. Chem. doi: 10.1074/jbc.274.10.6594 contributor: fullname: Arner E. C. – volume: 275 start-page: 25791 year: 2000 ident: jm015533cb00018/jm015533cb00018_1 publication-title: J. Biol. Chem doi: 10.1074/jbc.M001065200 contributor: fullname: Tortorella M. – volume: 11 start-page: 13 year: 2001 ident: jm015533cb00019/jm015533cb00019_2 publication-title: Bioorg. Med. Chem. Lett. doi: 10.1016/S0960-894X(01)00137-8 contributor: fullname: Pikul S. – volume: 284 start-page: 1666 year: 1999 ident: jm015533cb00003/jm015533cb00003_1 publication-title: Science doi: 10.1126/science.284.5420.1664 contributor: fullname: Tortorella M. D. – volume: 270 start-page: 6 year: 1995 ident: jm015533cb00004/jm015533cb00004_6 publication-title: J. Biol. Chem. doi: 10.1074/jbc.270.6.2550 contributor: fullname: Lark W. – volume: 40 start-page: 2532 year: 1997 ident: jm015533cb00021/jm015533cb00021_1 publication-title: J. Med. Chem. doi: 10.1021/jm960871c contributor: fullname: MacPherson L. J. – volume: 380 start-page: 20 year: 1996 ident: jm015533cb00002/jm015533cb00002_4 publication-title: FEBS Lett. doi: 10.1016/0014-5793(95)01539-6 contributor: fullname: Fosang A. J. – volume: 266 start-page: 205 year: 1991 ident: jm015533cb00004/jm015533cb00004_3 publication-title: J. Biol. Chem. contributor: fullname: Sandy J. D. – volume: 37 start-page: 51 year: 1994 ident: jm015533cb00014/jm015533cb00014_1 publication-title: J. Med. Chem. doi: 10.1021/jm00047a001 contributor: fullname: Dorsey B. D. – volume: 295 start-page: 276 year: 1993 ident: jm015533cb00002/jm015533cb00002_3 publication-title: Biochem. J. doi: 10.1042/bj2950273 contributor: fullname: Fosang A. J. – volume: 16 start-page: 464 year: 1995 ident: jm015533cb00017/jm015533cb00017_1 publication-title: J. Comput. Chem. contributor: fullname: Luty B. A. – volume: 304 start-page: 351 year: 1994 ident: jm015533cb00009/jm015533cb00009_1 publication-title: Biochem. J. doi: 10.1042/bj3040347 contributor: fullname: Fosang A. J. – volume-title: Patent 4,599,361 year: 1986 ident: jm015533cb00008/jm015533cb00008_1 contributor: fullname: Compound – volume: 41 start-page: 1748 year: 1998 ident: jm015533cb00018/jm015533cb00018_2 publication-title: J. Med. Chem. contributor: fullname: Xue C.-B. – volume: 91 start-page: 8451 year: 1994 ident: jm015533cb00015/jm015533cb00015_1 publication-title: Proc. Natl. Acad. Sci. U.S.A. contributor: fullname: Zhang D. – volume: 36 start-page: 1222 year: 1993 ident: jm015533cb00004/jm015533cb00004_2 publication-title: Arthritis Rheum. contributor: fullname: Lohamnder L. S. |
| SSID | ssj0003123 |
| Score | 1.6923633 |
| Snippet | A pharmacophore model of the P1‘ site, specific for aggrecanase, was defined using the specificity studies of the matrix metalloproteinases and the similar... |
| SourceID | crossref acs |
| SourceType | Aggregation Database Publisher |
| StartPage | 3347 |
| Title | Design and Synthesis of a Series of (2R)-N 4-Hydroxy-2-(3-hydroxybenzyl)-N - [(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden- 1-yl]butanediamide Derivatives as Potent, Selective, and Orally Bioavailable Aggrecanase Inhibitors |
| URI | http://dx.doi.org/10.1021/jm015533c |
| Volume | 44 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwhV1bb9MwFLbGeIAXGAPEuExHgKYixZsvuT52LVNBYlR0kyYhVNmxswWyFC3tpOyf7t_sOGlYpQl4ixXHOZJP_H2Oz_kOIe8R8gRXKqHGRpKiUzCquOU0CnRklVapNO5E98thODr2P58EJ2vk3V9O8AXf-3ne1LaR6T1yXyAeuh1WfzD5s9xKLmQnCS4QzDv5oNVHHfSk1Qr0rGDIwWMy7DJx2tCRX7uLud5Nr-4KM_7LvA3yaMkhod9O-hOyZstN8mDQlW7bJDvjVpC69uDoNr-q8mAHxrdS1fVTcj1sAjhAlQYmdYlksMormGWgwP02s811T3z7QA_Bp6PaOMupoD1Jz9qGtuVVXbj7FL73-MRznUV3lwpPUpM3LcpH1GkzlhQ4rYsfeoG81OWtnOfGwhBfd9mIkFegKhjPkMvPPbSiaFdkr7Hx64Uqihr285m6VHnh0r6gf3qKq7YqEY7hU3mW69wVEHpGjg8-Hg1GdFnsAX2D-SlVOkK2E5hIYdvISPmZ8TNfZkmGDMa4UqLINVPFfJNobsOYSyu0CpGARNayRD4n6-WstC8IRH7MwowFcZimfsCYZjoQcZxlmcDBgmSLbKM3TJcfazVtzuEF7oO6qdwibztHmf5uRT_udnr5v1FekYdNwJoLf-Gvyfr8YmHfIIOZ6-3Gg28A6lnpEw |
| link.rule.ids | 315,786,790,2782,27107,27955,27956,57091,57141 |
| linkProvider | American Chemical Society |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1bb9MwFLZgPIwXLgPEBgwLoalI8fAl18fRMWWwlYp20qQJVXbsbBlZipZ2UvZP-TccOw2t4AHeYsVxTuQTf1_ic76D0FuAPM6kTIg2kSDgFJRIZhiJAhUZqWQmtN3RPR6E6Yn_6TQ4Xcjk2FwYMKKGkWq3ib9UF2DvL69ciRuR3UX3gghQztKg_uj3qisYF50yOAdM71SEVi-1CJTVKwi0AiUHD9uaRM4IF0HyfXc-U7vZ7R_6jP9n5SP0YMEo8V7rAo_RHVNtoPV-V8htA-0MW3nqxsPjZbZV7eEdPFwKVzdP0M99F86BZaXxqKmAGtZFjac5ltj-RDPuuMe_viMD7JO00fYBCCc9QS7ahjLVbVPa8wSf9djIs515d5ZwTxBduBZhKbFKjRXBjDTlNzUHlmqzWK4KbfA-3O7GSZLXWNZ4OAVmP_PAirJdnz1n45drWZYN_lBM5Y0sSpsEhvfOz2ENlxWAMz6sLgpV2HJCT9HJwcdxPyWL0g_gKdTPiFQRcJ9ARxLaWkTSz7Wf-yJPcuAz2hYWBeaZSerrRDETxkwYrmQIdCQyhibiGVqrppV5jnDkxzTMaRCHWeYHlCqqAh7HeZ5zGCxINtE2zORk8erWE7crz-GrqJvKTfSm85fJj1YC5O9OW_8a5TVaT8fHR5Ojw8HnF-i-C2WzgTHsJVqbXc_NK-A2M7XtnPoXrgDxfg |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1bb9MwFLZgSMALlwFiXIaF0FSkeMR2ro-lpeq4dBXdpEkIVXZsb4EsnZZ2UvZP-TccO8lWwQO8xbLjnMjHPp_tc76D0BsweYwKkRKlY05AKXwiqKYkDmWshRQZV_ZG98skGh8GH4_Co3ajaGNhQIgKeqrcJb6d1WfKtAwD9N2PU5fmhmc30a0wpoGdiP3B7Grl5ZTxjh2cgV3vmITWX7VWKKvWrNCaORndR_tXgjgvkp-7q6XczS7_4Gj8f0kfoHstssT9RhUeohu63ER3Bl1Ct020M21oqmsPH1xHXVUe3sHTawLr-hH6NXRuHViUCs_qEiBilVd4YbDA9jBNu-ce-_qWTHBAxrWyP0EY6XFy0hSkLi_rwtYT_K1HZ55tzLpawjxOVO5KhI6JZWwsCaakLr7LFaBVG81ymiuNh_C5C0dNXmFR4ekCEP7SAymKZp32nIz756Ioavw-X4gLkRc2GAz3j49hLRclGGm8V57kMrdphR6jw9GHg8GYtCkgQGP8ICNCxoCBQhULKCsei8CowATcpAZwjbIJRgGBZsIPVCqpjhLKNZMiAlgSa-2n_AnaKBelfopwHCR-ZPwwibIsCH1f-jJkSWKMYdBZmG6hbRjNeTuFq7m7nWewO-qGcgu97nRmftZQgfzd6Nm_enmFbk-Ho_nnvcmn5-iu82iz_jH0BdpYnq_0S4A4S7nt9Po3i3fz-A |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Design+and+Synthesis+of+a+Series+of+%282+R+%29-+N+4+-Hydroxy-2-%283-hydroxybenzyl%29-+N+-+%5B%281+S+%2C2+R+%29-2-hydroxy-2%2C3-dihydro-1+H+-inden-+1-yl%5Dbutanediamide+Derivatives+as+Potent%2C+Selective%2C+and+Orally+Bioavailable+Aggrecanase+Inhibitors&rft.jtitle=Journal+of+medicinal+chemistry&rft.au=Yao%2C+Wenqing&rft.au=Wasserman%2C+Zelda+R.&rft.au=Chao%2C+Michael&rft.au=Reddy%2C+Gade&rft.date=2001-10-11&rft.issn=0022-2623&rft.eissn=1520-4804&rft.volume=44&rft.issue=21&rft.spage=3347&rft.epage=3350&rft_id=info:doi/10.1021%2Fjm015533c&rft.externalDBID=n%2Fa&rft.externalDocID=10_1021_jm015533c |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0022-2623&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0022-2623&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0022-2623&client=summon |