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The five lowest homologues [(CH<jats:sub>2<\/jats:sub>)<jats:sub>2\u22126<\/jats:sub>] are selective MMP\u20102 inhibitors, whereas the two with the longest linkers [(CH<jats:sub>2<\/jats:sub>)<jats:sub>7,\u20098<\/jats:sub>] lack inhibitory activity. The most potent homologues are those with (CH<jats:sub>2<\/jats:sub>)<jats:sub>5,\u20096<\/jats:sub>; these two were evaluated for antimetastatic activity in a murine melanoma model and showed good potency both by oral and intraperitoneal administration without any toxic\u2014including musculoskeletal\u2014side effects. In contrast to the previously reported <jats:italic>cis<\/jats:italic>\u2010ACCP, which was shown to inhibit MMP\u20102 for \u223c30\u2005min, the new compounds inhibit MMP activity for the duration of measurement, lasting several hours. Pharmacokinetic evaluation revealed, on the one hand, low oral bioavailability; on the other hand, a relatively large calculated volume of distribution, consistent with the observed reversible absorption of CPO <jats:bold>5<\/jats:bold> to hydroxyapatite, as a model for bone.<\/jats:p>","DOI":"10.1002\/cmdc.201100153","type":"journal-article","created":{"date-parts":[[2011,6,8]],"date-time":"2011-06-08T09:04:51Z","timestamp":1307523891000},"page":"1471-1477","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Orally Active, Antimetastatic, Nontoxic Diphenyl Ether\u2010Derived Carbamoylphosphonate Matrix Metalloproteinase Inhibitors"],"prefix":"10.1002","volume":"6","author":[{"given":"Julia","family":"Frant","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ainelly","family":"Veerendhar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamir","family":"Chernilovsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shlomo","family":"Nedvetzki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Vaksman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amnon","family":"Hoffman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eli","family":"Breuer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reuven","family":"Reich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,6,8]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2010.09.048"},{"key":"e_1_2_7_2_2","unstructured":"\u00a0"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.2174\/092986709789178037"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.2174\/187152009788451842"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.200600204"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2308"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-006-7894-9"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.2174\/156802606776287045"},{"key":"e_1_2_7_9_2","unstructured":"\u00a0"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780390919"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(95)06172-X"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.3109\/14756369809035829"},{"key":"e_1_2_7_13_2","unstructured":"\u00a0"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)42227-7"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00133484"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650110111"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1994.tb24720.x"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1997.tb04278.x"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410440404"},{"key":"e_1_2_7_20_2","unstructured":"\u00a0"},{"key":"e_1_2_7_21_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.2174\/138161280301221005125150","volume":"3","author":"White A. 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