دورية أكاديمية
Novel tricyclic poly(ADP-ribose) polymerase-1 inhibitors with potent anticancer chemopotentiating activity: design, synthesis, and X-ray cocrystal structure.
| العنوان: | Novel tricyclic poly(ADP-ribose) polymerase-1 inhibitors with potent anticancer chemopotentiating activity: design, synthesis, and X-ray cocrystal structure. |
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| المؤلفون: | Canan Koch SS; Pfizer Global Research and Development, La Jolla/Agouron Pharmaceuticals, Inc., 10770 Science Center Drive, San Diego, California 92121, USA. stacie.canan@pfizer.com, Thoresen LH, Tikhe JG, Maegley KA, Almassy RJ, Li J, Yu XH, Zook SE, Kumpf RA, Zhang C, Boritzki TJ, Mansour RN, Zhang KE, Ekker A, Calabrese CR, Curtin NJ, Kyle S, Thomas HD, Wang LZ, Calvert AH, Golding BT, Griffin RJ, Newell DR, Webber SE, Hostomsky Z |
| المصدر: | Journal of medicinal chemistry [J Med Chem] 2002 Nov 07; Vol. 45 (23), pp. 4961-74. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print Cited Medium: Print ISSN: 0022-2623 (Print) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Chemical Society Original Publication: [Easton, Pa.] : American Chemical Society, [c1963- |
| مواضيع طبية MeSH: | Poly(ADP-ribose) Polymerase Inhibitors*, Antineoplastic Agents/*chemical synthesis , Dacarbazine/*analogs & derivatives , Enzyme Inhibitors/*chemical synthesis , Indoles/*chemical synthesis , Isoquinolines/*chemical synthesis, Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Crystallography, X-Ray ; Dacarbazine/pharmacology ; Drug Design ; Drug Screening Assays, Antitumor ; Drug Synergism ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Humans ; Indoles/chemistry ; Indoles/pharmacology ; Isoquinolines/chemistry ; Isoquinolines/pharmacology ; NAD/metabolism ; Poly(ADP-ribose) Polymerases/metabolism ; Structure-Activity Relationship ; Temozolomide ; Topotecan/pharmacology ; Tumor Cells, Cultured |
| مستخلص: | A series of novel compounds have been designed that are potent inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1), and the activity and physical properties have been characterized. The new structural classes, 3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-ones and 3,4-dihydropyrrolo[4,3,2-de]isoquinolin-5-(1H)-ones, have conformationally locked benzamide cores that specifically interact with the PARP-1 protein. The compounds have been evaluated with in vitro cellular assays that measure the ability of the PARP-1 inhibitors to enhance the effect of cytotoxic agents against cancer cell lines. |
| المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (Enzyme Inhibitors) 0 (Indoles) 0 (Isoquinolines) 0 (Poly(ADP-ribose) Polymerase Inhibitors) 0U46U6E8UK (NAD) 7GR28W0FJI (Dacarbazine) 7M7YKX2N15 (Topotecan) EC 2.4.2.30 (Poly(ADP-ribose) Polymerases) YF1K15M17Y (Temozolomide) |
| تواريخ الأحداث: | Date Created: 20021101 Date Completed: 20021209 Latest Revision: 20190710 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1021/jm020259n |
| PMID: | 12408707 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 0022-2623 |
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| DOI: | 10.1021/jm020259n |