{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T16:34:55Z","timestamp":1770136495786,"version":"3.49.0"},"reference-count":55,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Thirty-five analogues of a promising antiosteoporotic drug, incadronate, have been synthesized and evaluated for their antiproliferative activity against mouse macrophage-like J774E cells. These cells originated from identical precursors as osteoclasts and served to select the most active compounds. Two of them, n-heptyl- and n-octyl-aminomethylenebispohosphonic acids, were then used for the medication of sheep with induced osteoporosis. They demonstrated mild antiosteoporotic activity that was documented using bone histopathology. Additionally, a decrease in the immunological response to Corynebacterium pseudotuberculosis was observed as a major side effect accompanied by this medication. Methods: Aminomethylenebisphosphonates may be obtained in the three-component reaction of aliphatic amine, triethyl orthoformate and diethyl phosphite with the further acid hydrolysis of crude esters. The obtained N-substituted alkiloaminomethylenebisphosphonic acids are presented alongside with their in vitro activity toward mouse macrophages J774E. Results: The new families of aminomethylenebisphosphonic compounds synthesized by our approach may be of practical importance due to the significant cytotoxic activity in the cell cultures investigated. Two of them were chosen for further evaluation in the treatment of induced osteoporosis in sheep. Conclusions: In vivo studies confirmed the mild therapeutic effects of compounds 4 (N-(n-heptylamino)methylenebisphosphonic acid and 5 (N-(n-octylamino)methylenebisphosphonic acid; however, they are not suitable analogues of incadronate for consideration as potential drugs.<\/jats:p>","DOI":"10.3390\/ph19020256","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:00:47Z","timestamp":1770033647000},"page":"256","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Probing the Hydrophobic Part of Analogues of the Incadronate-Evidence of Their Interaction with Immunological System of Sheep"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9210-9841","authenticated-orcid":false,"given":"Ewa","family":"Chmielewska","sequence":"first","affiliation":[{"name":"Department of Bioorganic Chemistry, Faculty of Chemistry, Wroc\u0142aw University of Science and Technology, Wybrze\u017ce Wyspia\u0144skiego 27, 50-370 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4980-6606","authenticated-orcid":false,"given":"Joanna","family":"Wietrzyk","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Anticancer Therapy, Department of Experimental Oncology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Kuryszko","sequence":"additional","affiliation":[{"name":"The Faculty of Veterinary Medicine, Wroc\u0142aw University of Environmental and Life Sciences, Norwida 31, 50-375 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zdzis\u0142aw","family":"Kie\u0142bowicz","sequence":"additional","affiliation":[{"name":"The Faculty of Veterinary Medicine, Wroc\u0142aw University of Environmental and Life Sciences, Norwida 31, 50-375 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8019-4797","authenticated-orcid":false,"given":"Pawe\u0142","family":"Kafarski","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Agriculture and Forestry, University of Warmia and Mazury, Plac \u0141\u00f3dzki 4, 10-721 Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,1]]},"reference":[{"key":"ref_1","first-page":"46","article-title":"An overview and management of osteoporosis","volume":"4","year":"2017","journal-title":"Eur. 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