5'-Phenyl-3'H-spiro[indoline-3,2'-[1,3,4]thiadiazol]-2-one inhibitors of ADAMTS-5 (aggrecanase-2)
5'-Phenyl-3'H-spiro[indoline-3,2'-[1,3,4]thiadiazol]-2-one inhibitors of ADAMTS-5 (Aggrecanase-2) have been prepared via commercially available starting materials. Selected compounds 23, 33-35 show sub-micromolar ADAMTS-5 potency and strong SAR trends with selectivity over the related...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2007-10, Vol.17 (20), p.5630-5633 |
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| container_issue | 20 |
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| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 17 |
| creator | Bursavich, Matthew G Gilbert, Adam M Lombardi, Sabrina Georgiadis, Katy E Reifenberg, Erica Flannery, Carl R Morris, Elisabeth A |
| description | 5'-Phenyl-3'H-spiro[indoline-3,2'-[1,3,4]thiadiazol]-2-one inhibitors of ADAMTS-5 (Aggrecanase-2) have been prepared via commercially available starting materials. Selected compounds 23, 33-35 show sub-micromolar ADAMTS-5 potency and strong SAR trends with selectivity over the related metalloproteases ADAMTS-4 (Aggrecanase-1), MMP12, and MMP13. This series of compounds represents progress toward a selective ADAMTS-5 inhibitor as a disease modifying osteoarthritis drug. |
| doi_str_mv | 10.1016/j.bmcl.2007.07.048 |
| format | Article |
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| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2007-10, Vol.17 (20), p.5630-5633 |
| issn | 0960-894X |
| language | eng |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Endopeptidases - metabolism Indoles - chemistry Molecular Structure Protease Inhibitors - chemical synthesis Protease Inhibitors - chemistry Protease Inhibitors - pharmacology Spiro Compounds - chemical synthesis Spiro Compounds - chemistry Spiro Compounds - pharmacology Structure-Activity Relationship Thiadiazoles - chemical synthesis Thiadiazoles - chemistry Thiadiazoles - pharmacology |
| title | 5'-Phenyl-3'H-spiro[indoline-3,2'-[1,3,4]thiadiazol]-2-one inhibitors of ADAMTS-5 (aggrecanase-2) |
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