Camptothecin analog

Chatterjee A, Digumarti R, Katneni K, Upreti VV, Mamidi RN, Mullangi R, Surath A, Sriniva ML, Uppalapati S, Jiwatani S, Srinivas NR. (2005) Safety, tolerability, and pharmacokinetics of a capsule formulation of DRF-1042, a novel camptothecin analog, in refractory cancer patients in a bridging phase 1 study. J Clin Pharmacol 45 453 60. 

The camptothecin analog CPT-11 has recently been approved for the treatment of... 

A Pd-catalyzed alkoxycarbonylation of 2-chloropyridine 117 to ester 118 was reported in the synthesis of camptothecin analogs <97JOC6588>. Another Pd-catalyzed alkoxycarbonylation was the central feature in Hibino s total synthesis of oxopropaline G (121), a P-carboline isolated from Streptomyces sp G324 <98TL2341>. Triflate 119 was prepared from 2-foimyl-3-iodoindole in seven steps. The Pd-catalyzed alkoxycarbonylation of 119 provided the key intermediate, l-methoxycarbonyl-4-methylcarboline 120, which was then transformed to oxopropaline G (121) in four additional steps. 

In many ways, the development of paclitaxel mirrored that of the camptothecin analogs, both being dogged for many years by supply issues, poor pharmacokinetics, and toxicity, but the subsequent uncovering of novel mechanisms of action fueled renewed efforts to develop these leads into important new anticancer agents (75). 

Synthetic applications of AD which have already appeared and which are of potential industrial interest include the synthesis of propranolol (9) [48], diltiazem (10) [49], carnitine, and 4-amino-3-hydroxybutyric acid (11) [50], azole anti-fungals (12) [51], chloramphenicol (13) [52], reticuline intermediates (14) [53], camptothecin analogs (15) [54], khellactone (16) derivatives [55], taxol C-13 side chain (17) [56], halosarin [64], dehydro- xo-brevicomin [65], and antimalar-ial active cyclopenteno-l,2,4-trioxanes [57], as summarized in Figure 4. 

Camptothecin analogs Irinotecan Topotecan Epipodophyllotoxins Etoposide Teniposide Antitumor antibiotics Bleomycin Dactinomycin Daunorubicin Doxorubicin Epirubicin Idarubicin Mitomycin Mitoxantrone Valrubicin Microtubule agents Docetaxel Paclitaxel Vinblastine Vincristine Vinorelbine Enzymes Asparaginase Pegasparaginase Metals... 

Camptothecin, a plant alkaloid derived from Camptotheca acuminata, is a potent inhibitor of DNA topoisomerase I. Clinical trials failed to show expected antitumor activity, and the drug produced severe, unpredictable toxicity. The camptothecin analogs irinotecan and topotecan were synthesized to reduce toxicity and improve therapeutic... 

Anticancer drugs methotrexate, mitoxantrone, camptothecin analogs (SN-38, etc.), topotecan Glucuronide conjugates 4-methylumbeUiferone glucuronide, estradiol- 17-D-glucuronide... 

Bodley AL, Wani MC, Wall ME et al. Antitrypanosom activity of camptothecin analogs. Structure-activity correlations. Biochem Pharmacol 1995 50 937-942. 

The synthesis of camptothecin analogs substituted by a carbonyl function on position 5 of ring C 208 was realized (Figure 7) (03JHC45,05T7916, 06T3959). 

Evolution in medicinal chemistry of E-ring-modified Camptothecin analogs as anticancer agents 13EMC(63)746. 

Kumazawa, E., Ochi, Y., Tanaka, N., Kajimura, T., and Inoue, K., 2001, A novel macromolecular carrier system for the camptothecin analog DX-8951f T its antitumor activities in the murine Meth A solid tumor model. Proc. Am. Assoc, for Cancer Res. 42 139. 

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