Synthesis of a new series of 1H-pyrazole-1-carboxamide derivatives is described. Their antiproliferative activity against A375 human melanoma cell line was tested and the effect of substituents on the diarylpyrazole scaffold was investigated. The pharmacological results indicated that most of the newly synthesized compounds showed moderate activity against A375, compared with sorafenib.
View Article and Find Full Text PDFThe synthesis of a novel series of aminoquinazoline derivatives 1a-r and their antiproliferative activities against A375 human melanoma cell line were described. Among them, six compounds showed superior antiproliferative activities to Sorafenib as a reference compound. In particular, the representative compound 1q bearing chromen-4-one moiety exhibited excellent antiproliferative activity (IC(50)=0.
View Article and Find Full Text PDFSynthesis of a new series of diarylureas and amides having pyrrolo[3,2-b]pyridine scaffold is described. Their in vitro antiproliferative activity against human melanoma cell line A375 and HS 27 human fibroblast cell line was tested and the effect of substituents on the pyrrolo[3,2-b]pyridine was investigated. The newly synthesized compounds, except meta-substituted derivatives (Ij-k and Iv-w), generally showed superior or similar activity against A375 to Sorafenib.
View Article and Find Full Text PDFSynthesis of a new series of diarylureas and amides having pyrrolo[2,3-d]pyrimidine scaffold is described. Their in vitro antiproliferative activities against A375 human melanoma cell line and HS 27 fibroblast cell line were tested and the effect of substituents on pyrrolo[2,3-d]pyrimidine was investigated. The newly synthesized compounds, except N-acetyl derivatives (Id, Ie, and Im), generally showed superior or similar activity against A375 to Sorafenib.
View Article and Find Full Text PDFThe synthesis of a novel series of aminoquinoline derivatives 1a-p and their antiproliferative activities against A375 human melanoma cell line were described. Most compounds showed superior antiproliferative activities to Sorafenib as a reference compound. Among them, quinolinyloxymethylphenyl compounds 1k and 1l exhibited potent activities (IC(50)=0.
View Article and Find Full Text PDFInhibition of angiogenesis is emerging as a promising strategy for the treatment of cancer. In our study reported here, the effects of 4 highly potent methionine aminopeptidase 2 (MetAP2) inhibitors, IDR-803, IDR-804, IDR-805 and CKD-732 (designed by structure-based molecular modeling), on angiogenesis and tumor growth were assessed. Concentrations of these inhibitors as low as 2.
View Article and Find Full Text PDFReliable technologies for addressing target identification and validation are the foundation of successful drug development. Microarrays have been well utilized in genomics/proteomics approaches for gene/protein expression profiling and tissue/cell-scale target validation. Besides being used as an essential step in analyzing high-throughput experiments such as those involving microarrays, bioinformatics can also contribute to the processes of target identification and validation by providing functional information about target candidates and positioning information to biological networks.
View Article and Find Full Text PDFEnantiomerically pure (1S,3S)- and (1S,3R)-1-amino-3-(hydroxymethyl)cyclopentanes have been efficiently synthesized from L-aspartic acid. The title compounds are isosteres of ribose and may be used to construct nucleoside analogs with important antiviral and antineoplastic activities as demonstrated by a concise total synthesis of (+)-4'-deoxycarbapentostatin nucleoside.
View Article and Find Full Text PDFVarious enantiomerically pure 2-acylaziridines were prepared efficiently from the corresponding aziridine-2-carboxylate via Weinreb's amide and the subsequent treatment of organometallic compounds. The carbonyl group of those 2-acylaziridines was stereoselectively reduced by NaBH4in the presence of ZnCl2 to give erythro-1,2-amino alcohols with high diastereoselectivities and chemical yields. Using this methodology, we prepared (1R,2S)-N-Boc-norephedrine 5, N-Boc-safingol 8, N-Boc-D-erythro-sphinganine 9, and N-Boc-spisulosine 10 in high yields.
View Article and Find Full Text PDFA series of erythrose, ribose, and substituted pyrrolidine containing 2,4-thiazolidinediones were synthesized. Among them, thirteen unsaturated thiazolidinediones, six saturated thiazolidinediones and two unsaturated malonates were evaluated for their ability to enhance glucose utilization in cultured L6 myocytes. On the basis of the in vitro activity, 5-[4-[2-(1-benzyl-3,4-bis-benzyloxypyrrolidin-2-yl)ethoxy]benzylidene]thiazolidine-2,4-dione 24b was selected as the candidate for further pharmacological studies.
View Article and Find Full Text PDFIn this paper we describe enantioselective syntheses of (+)-carbapentostatin (8) and its cyclopentyl analogue 12b. A new and efficient one-pot, two-step preparation of aldehyde 15 has been developed, based on the borane reduction of N-Pf-protected L-aspartic acid gamma-methyl ester (13) and Swern oxidation of the resulting alcohol. Homologation to diester 18 and ring formation by Dieckman cyclization, followed by reduction and dehydration steps, afford the 4-amino-1-cyclopentenemethanol derivative 22.
View Article and Find Full Text PDF5-Funtionalized enantiomerically pure oxazolidin-2-ones were prepared in one pot from commercially available chiral aziridines bearing an electron-withdrawing group at C-2 with retention of the configuration in high yields by regioselective aziridine ring-opening followed by intramolecular cyclization.
View Article and Find Full Text PDFEnantiomerically pure N-(R)-alpha-methylbenzyl-4(R)-(chloromethyl)oxazolidinones (4R)-5a-k were synthesized in one step and high yields from various aziridine-2-methanols (S)-2a-k by intramolecular cyclization with phosgene. The alpha-methylbenzyl substituent on the nitrogen was easily cleaved to give both enanatiomers of 4-(chloromethyl)oxazolidinones (R)-7a and (S)-7a. (R)-7a was used for the efficient syntheses of (L)-homophenylalaninol analogues (S)-12a-j.
View Article and Find Full Text PDFThe radical addition reaction of alkyl iodides with alpha,beta-unsaturated esters, nitriles, and ketones proceeds in moderate to excellent yields (50-95%) using Ni(OAc)(2) (0.05-0.2 equiv)-BER (3-5 equiv) in methanol in 1-9 h at room temperature or at 65 degrees C.
View Article and Find Full Text PDF