- Synthesis of N4-(substituted phenyl)-N4-alkyl/ desalkyl-9H-pyrimido[4,5-b]indole-2,4-diamines and identification of new microtubule disrupting compounds that are effective against multidrug resistant cells
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A series of fourteen N4-(substituted phenyl)-N 4-alkyl/desalkyl-9H-pyrimido[4,5-b]indole-2,4-diamines was synthesized as potential microtubule targeting agents. The synthesis involved a Fisher indole cyclization of 2-amino-6-hydrazin
- Gangjee, Aleem,Zaware, Nilesh,Devambatla, Ravi Kumar Vyas,Raghavan, Sudhir,Westbrook, Cara D.,Dybdal-Hargreaves, Nicholas F.,Hamel, Ernest,Mooberry, Susan L.
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p. 891 - 902
(2013/03/14)
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- PROCESS AND INTERMEDIATES FOR THE PREPARATION OF PRELADENANT AND RELATED COMPOUNDS
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The present invention describes processes for the synthesis of 2-(furan-2-yl)-7-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-l-yl] ethyl]-7H-pyrazolo[ 4,3-e ][1,2,4]- triazolo[1,5c] pyrimidin-5-amine (Preladenant) represented by the structure of formula (1
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Page/Page column 23
(2012/10/08)
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- 5-Arylthio-Substituted 2-Amino-4-oxo-6-methylpyrrolopyrimidine Antifolates as Thymidylate Synthase Inhibitors and Antitumor Agents
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Classical antifolate inhibitors of thymidylate synthase (TS) often require the reduced folate uptake system in order to exert their antitumor effects.In addition, these analogues are polyglutamylated via the enzyme folylpoly-γ-glutamate synthetase (FPGS),
- Gangjee, Aleem,Devray, Rajesh,McGuire, John J.,Kisliuk, Roy L.
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p. 4495 - 4502
(2007/10/03)
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- 5,10-Methylenetetrahydro-5-deazafolic Acid and Analogues: Synthesis and Biological Activities
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The synthesis of 5,10-methylene-5-deazatetrahydrofolic acid (2), a stable, rigid analogue of 5,10-methylenetetrahydrofolate (1), is reported as a potential inhibitor of thymidylate synthase.The target compound was obtained by a Fisher-indole type cyclization of the hydrazone 16 from 2-amino-6-hydrazino-4-oxopyrimidine (10) and diethyl N--L-glutamate (15) followed by catalytic reduction of the product 17.Similarly, modification of the Fisher-indole type cyclization of the appropriate hydrazone precursors 11 and 12 afforded the nonclassical analogues 3-amino-7,8,9-trimethyl-2H-pyrrolopyridopyrimidin-1-one (4) and 3-amino-8-benzyl-7,9-dimethyl-2H-pyrrolopyridopyrimidin-1-one (5), respectively.The target compound 2, its aromatic precursor 18, and the nonclassical analogue 4 were evaluated as inhibitors of the growth of Manca human lymphoma cells and also as inhibitors of human dihydrofolate reductase, human thymidylate synthase, glycinamide ribonucleotide formyltransferase, and aminoimidazole carboxamide ribonucleotide formyltransferase.Compound 18 showed weak inhibition of lymphoma cell growth (IC50 = 42 μM) and of AICAR formylTF (IC50 = 17 μM).Compounds 2 and 4 did not inhibit lymphoma cell growth or thymidylate synthase.The inactivity of 2 was attributed to its lack of flexibility leading to its inability to bind to thymidylate synthase.
- Gangjee, Aleem,Patel, Jasmin,Kisliuk, Roy L.,Gaumont, Yvette
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p. 3678 - 3685
(2007/10/02)
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