Synthesis of pyrrolo[2,3- d]pyrimidine derivatives and their antiproliferative activity against melanoma cell line

• Published in: Bioorganic & medicinal chemistry letters Vol. 19; no. 23; pp. 6538 - 6543
• Main Authors: Jung, Myung-Ho, Kim, Hwan, Choi, Won-Kyoung, El-Gamal, Mohammed I., Park, Jin-Hun, Yoo, Kyung Ho, Sim, Tae Bo, Lee, So Ha, Baek, Daejin, Hah, Jung-Mi, Cho, Jung-Hyuck, Oh, Chang-Hyun
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.12.2009; Elsevier
• Subjects: A375; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiproliferative activity; Biological and medical sciences; Cell Line, Tumor; Cell Proliferation - drug effects; Drug Screening Assays, Antitumor; General aspects; HS 27; Humans; Medical sciences; Melanoma; Melanoma - pathology; Molecular Structure; Pharmacology. Drug treatments; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Pyrroles - chemical synthesis; Pyrroles - chemistry; Pyrroles - pharmacology; Pyrrolo[2,3- d]pyrimidine; Stereoisomerism; Structure-Activity Relationship; Antiproliferative activity; Pyrrolo[2,3- d]pyrimidine; HS 27; A375; Melanoma; Antineoplastic agent; Human; Pyrrolo[2,3-d]pyrimidine; Malignant tumor; In vitro; Cell line; Structure activity relation; Sorafenib; Malignant melanoma; Carboxamide; Benzamide derivatives; Ureas; Fluorine Organic compounds; Chemical synthesis; Fibroblast; Tumor cell; Cancer
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.10.051

Synthesis of a new series of diarylureas and amides having pyrrolo[2,3- d]pyrimidine scaffold is described. Their in vitro antiproliferative activities against A375 human melanoma cell line and HS 27 fibroblast cell line were tested and the effect of substituents on pyrrolo[2,3- d]pyrimidine was investigated. The newly synthesized compounds, except N-acetyl derivatives (Id, Ie, and Im), generally showed superior or similar activity against A375 to Sorafenib. Among all of these derivatives, compounds Iq and Ir having imidazole and morpholine moieties, respectively, showed the most potent antiproliferative activity against A375. Synthesis of a new series of diarylureas and amides having pyrrolo[2,3- d]pyrimidine scaffold is described. Their in vitro antiproliferative activities against A375 human melanoma cell line and HS 27 fibroblast cell line were tested and the effect of substituents on pyrrolo[2,3- d]pyrimidine was investigated. The newly synthesized compounds, except N-acetyl derivatives ( Id, Ie, and Im), generally showed superior or similar activity against A375 to Sorafenib. Among all of these derivatives, compounds Iq and Ir having imidazole and morpholine moieties, respectively, showed the most potent antiproliferative activity against A375.