Design and synthesis of tetrahydroisoquinoline derivatives as potential multidrug resistance reversal agents in cancer.
Exploration for new MDR-modulator utilizing tetrahydroisoquinoline as scaffold disclosed 6,7-dimethoxy-1-(3,4-dimethoxy)benzyl-2-(N-n-octyl-N'-cyano)guanyl-1,2,3,4-tetrahydroisoquinoline (7) as a readily accessible medicinal lead. Compound 7 possessed potent MDR reversal activity in the range of the reference compound verapamil, and had not cardiovascular activity compared to verapamil.
Li
Yu
Y
Center of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu 210009, China.
Zhang
Hui-Bin
HB
Huang
Wen-Long
WL
Li
Yun-Man
YM
D000578:Amidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009200:Myocardial Contraction / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013997:Time Factors; D014700:Verapamil / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
C530876:6,7-dimethoxy-1-(3,4-dimethoxy)benzyl-2-(N-n-octyl-N'-cyano)guanyl-1,2,3,4-tetrahydroisoquinoline; D000578:Amidines; D000889:Anti-Arrhythmia Agents; D000970:Antineoplastic Agents; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D014700:Verapamil