- INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND METHODS OF THEIR USE
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The present invention provides a compound of formula (II): an inhibitor of indoleamine 2,3-dioxygenase (IDO), which may be used as medicaments for the treatment of proliferative disorders, such as cancer, viral infections and/or autoimmune diseases. Its prodrugs are disclosed.
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- The total synthesis of chlorotonil A
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(Chemical Equation Presented) Stacking the deck: The natural product chloronitril A contains an unprecedented motif in which a CCl2 unit in a 14-membered macrolide framework is flanked by two carbonyl groups. In the first total synthesis of chl
- Rahn, Nicola,Kalesse, Markus
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p. 597 - 599
(2008/09/20)
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- Streamlined, asymmetric synthesis of 8,4′-oxyneolignans
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Highly direct, modular syntheses of several natural 8,4′- oxyneolignans [(-)-1, (+)-1, (-)-2, and (-)-3] and some related variants [(-)-26, (+)-26, (+)-27, and (-)-28] are reported. Utilizing (S)- or (R)-methyl lactate as the chiral sources, two complementary syn- or anti-oriented routes were designed, encompassing nine and five steps, which were carried out to deliver the targets in an enantiomerically pure form. The embodiment of the two independent aryl and aryloxy moieties onto the lactate frame was performed according to a diversity-oriented protocol from the common precursors, aldehydes 6 and ent-6 for the syn-oriented routes and mesyl esters 19 and ent-19 for the anti-oriented routes. These syntheses set the stage for the generation of a wide and diverse repertoire of 8,4′-oxyneolignan compounds and the broad biological interrogation of its members.
- Curti, Claudio,Zanardi, Franca,Battistini, Lucia,Sartori, Andrea,Rassu, Gloria,Pinna, Luigi,Casiraghi, Giovanni
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p. 8552 - 8558
(2007/10/03)
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- Resistance-modifying agents. 11. Pyrimido[5,4-d]pyrimidine modulators of antitumor drug activity. Synthesis and structure-activity relationships for nucleoside transport inhibition and binding to α1-acid glycoprotein
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The cardiovascular and antithrombotic agent dipyridamole (DP) has potential therapeutic utility as a modulator of the activity of antimetabolite antitumor agents by virtue of its inhibition of nucleoside transport. However, the activity of DP can be compromised by binding to the acute phase serum protein, α1-acid glycoprotein (AGP). Analogues of DP were synthesized and evaluated as inhibitors of 3H-thymidine uptake into L1210 leukamia cells in the presence and absence of 5 mg/mL AGP. Compounds with potency similar to that of DP were identified where the piperidino substituents at the 4,8-positions were replaced by 4?-methoxybenzylamino, 3?,4?-dimethoxybenzylamino, or piperonylamino groups. Replacement of the diethanolamino groups at the 2,6-positions of DP by alkylamino or alkoxy substituents was tolerated, although at least one oxygen-bearing function (hydroxyl or alkoxy) was required in the side chain for activity comparable to that of DP. Whereas AGP completely ablated the activity of DP, the majority of the newer compounds synthesized retained significant activity in the presence of excess AGP, although replacement of the piperidino groups at the 4,8-positions by N-methylbenzylamino substituents did, in some cases, restore susceptibility to AGP. Selected compounds have been demonstrated to prevent rescue from antifolate cytotoxicity, mediated by nucleoside salvage.
- Curtin, Nicola J.,Barlow, Hannah C.,Bowman, Karen J.,Calvert, A. Hilary,Davison, Richard,Golding, Bernard T.,Huang, Bing,Loughlin, Peter J.,Newell, David R.,Smith, Peter G.,Griffin, Roger J.
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p. 4905 - 4922
(2007/10/03)
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- Enantioselective synthesis of the C14-C25 portion of the cytotoxic natural product, amphidinolide B1
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The C14-C25 portion of the cytotoxic natural product, amphidinolide B1 (1), was synthesized enantioselectively using Myers asymmetric alkylation protocol, epoxide opening with higher order cuprate, Sharpless asymmetric epoxidation of allylic alcohol 17, a
- Lee, Duck-Hyung,Rho, Man-Dong
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p. 2573 - 2576
(2007/10/03)
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- Synthesis of the northern hemisphere of epothilone A by a ten-membered ring closing metathesis reaction
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The synthesis of the strained epothilone analog containing a ten- membered ring as well as the northern hemisphere of epothilone A is described. This approach, using the ring closing metathesis reaction, is a solution to the lack of stereocontrol observed
- Gerlach, Kai,Quitschalle, Monika,Kalesse, Markus
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p. 3553 - 3556
(2007/10/03)
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- Improved synthesis of the northern hemisphere of epothilone A by a sharpless asymmetric dihydroxylation
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An improved synthesis of the northern hemisphere of epothilone A is described. This approach utilizes the Sharpless asymmetric dihydroxylation of 5-hexen-2-one (allyl acetone) to generate the precursor for the Wittig reaction and the subsequent ring closing metathesis reaction (RCM). This strategy allows to generate precursor 13 as both enantiomers from ready available starting material in a very efficient manner.
- Quitschalle, Monika,Kalesse, Markus
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p. 7765 - 7768
(2007/10/03)
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- Synthesis of the C7-C17 segment of epothilones by a 10-membered ring closing metathesis reaction
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The synthesis of the C7-C17 segment of epothilones employing a ring closing metathesis is described. Our approach utilizes the stereoselective methylation of the 10-membered lactone, generated by ring closing metathesis, for introducing the methyl group at C8 and provides an efficient access to strained epothilone derivatives, as well as to the C7-C17 segment of epothilones.
- Gerlach, Kai,Quitschalle, Monika,Kalesse, Markus
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p. 1108 - 1110
(2007/10/03)
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