The Experts below are selected from a list of 12 Experts worldwide ranked by ideXlab platform
John J Mcguire - One of the best experts on this subject based on the ideXlab platform.
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design synthesis and biological activities of classical n 4 2 2 amino 4 Ethylpyrrolo 2 3 d pyrimidin 5 yl Ethyl benzoyl l glutamic acid and its 6 mEthyl derivative as potential dual inhibitors of thymidylate synthase and dihydrofolate reductase and a
Journal of Medicinal Chemistry, 2003Co-Authors: Aleem Gangjee, Jianming Yu, Roy L Kisliuk, William H Haile, Giulia Sobrero, John J McguireAbstract:Two novel analogues, N-{2-amino-4-Ethyl[(pyrrolo[2,3-d]pyrimidin-5-yl)Ethyl]benzoyl}-l-glutamic acid (2) and N-{2-amino-4-Ethyl-6-mEthyl[(pyrrolo[2,3-d]pyrimidin-5-yl)Ethyl]benzoyl}-l-glutamic acid (4), were designed and synthesized as potent dual inhibitors of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) and as antitumor agents. Compound 2 had inhibitory potency against human DHFR similar to N-{4-[2-(amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)Ethyl]benzoyl}-L-glutamic acid (LY231514) and 1, whereas 4 was inactive against human DHFR. Both 2 and 4 were more potent than LY231514 against E. coli TS. Against human TS, 2 was 7-fold less potent than LY231514 and 4 showed similar inhibitory activity as LY231514. In contrast to 2, which was an efficient substrate of human folypolyglutamate synthetase (FPGS), 4 was a poor substrate of FPGS. Compound 2 showed GI50 values in the nanomolar range against more than 18 human tumor cell lines in the standard NCI preclinical in vitro screen.
Aleem Gangjee - One of the best experts on this subject based on the ideXlab platform.
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design synthesis and biological activities of classical n 4 2 2 amino 4 Ethylpyrrolo 2 3 d pyrimidin 5 yl Ethyl benzoyl l glutamic acid and its 6 mEthyl derivative as potential dual inhibitors of thymidylate synthase and dihydrofolate reductase and a
Journal of Medicinal Chemistry, 2003Co-Authors: Aleem Gangjee, Jianming Yu, Roy L Kisliuk, William H Haile, Giulia Sobrero, John J McguireAbstract:Two novel analogues, N-{2-amino-4-Ethyl[(pyrrolo[2,3-d]pyrimidin-5-yl)Ethyl]benzoyl}-l-glutamic acid (2) and N-{2-amino-4-Ethyl-6-mEthyl[(pyrrolo[2,3-d]pyrimidin-5-yl)Ethyl]benzoyl}-l-glutamic acid (4), were designed and synthesized as potent dual inhibitors of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) and as antitumor agents. Compound 2 had inhibitory potency against human DHFR similar to N-{4-[2-(amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)Ethyl]benzoyl}-L-glutamic acid (LY231514) and 1, whereas 4 was inactive against human DHFR. Both 2 and 4 were more potent than LY231514 against E. coli TS. Against human TS, 2 was 7-fold less potent than LY231514 and 4 showed similar inhibitory activity as LY231514. In contrast to 2, which was an efficient substrate of human folypolyglutamate synthetase (FPGS), 4 was a poor substrate of FPGS. Compound 2 showed GI50 values in the nanomolar range against more than 18 human tumor cell lines in the standard NCI preclinical in vitro screen.
Yuji Kurokawa - One of the best experts on this subject based on the ideXlab platform.
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toxicity studies of a synthetic antioxidant 2 2 mEthylenebis 4 Ethyl 6 tert butylphenol in rats 2 uncoupling effect on oxidative phosphorylation of liver mitochondria
Journal of Toxicological Sciences, 1993Co-Authors: Atsuya Takagi, Nana Kawasaki, Junko Momma, Yoshitaka Aida, Yasuo Ohno, Ryuichi Hasegawa, Yuji KurokawaAbstract:Effects of 2,2'-mEthylenebis (4-Ethyl-6-tert-butylphenol) (MBEBP) on hepatic mitochondrial oxidative phosphorylation in vitro, and on hepatic peroxisomal enzymes activities and microsomal mixed-function oxidase activities were studied. 1. A low concentration of MBEBP, less than 50 microM, increased state 4 respiration and decreased state 3 respiration. However, a higher concentration of MBEBP, greater than 100 microM, acted as a respiratory inhibitor. Therefore, MBEBP was found to act as an uncoupler of oxidative phosphorylation in rat liver mitochondria. 2. MBEBP significantly decreased peroxisomal enzymes, cyanide-insensitive palmitoyl-CoA oxidizing activity and catalase activity in the livers of rats fed 0.2, 1.0 or 5.0% MBEBP for 4 weeks. 3. In microsomal enzyme assay, NADPH cytochrome c reductase activity was significantly increased, however, cytochrome P-450, cytochrome b5 levels, aminopyrine N-demEthylase and benzo [a] pyrene hydroxylase activities were not significantly increased in the livers of rats fed 1.0 or 5.0% MBEBP for 4 weeks. The weight loss and the decrease of serum triglyceride level observed in the MBEBP-treated rats seemed to be caused by its uncoupling effects, which might also be the cause of the testicular damage induced by MBEBP.
Jianming Yu - One of the best experts on this subject based on the ideXlab platform.
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design synthesis and biological activities of classical n 4 2 2 amino 4 Ethylpyrrolo 2 3 d pyrimidin 5 yl Ethyl benzoyl l glutamic acid and its 6 mEthyl derivative as potential dual inhibitors of thymidylate synthase and dihydrofolate reductase and a
Journal of Medicinal Chemistry, 2003Co-Authors: Aleem Gangjee, Jianming Yu, Roy L Kisliuk, William H Haile, Giulia Sobrero, John J McguireAbstract:Two novel analogues, N-{2-amino-4-Ethyl[(pyrrolo[2,3-d]pyrimidin-5-yl)Ethyl]benzoyl}-l-glutamic acid (2) and N-{2-amino-4-Ethyl-6-mEthyl[(pyrrolo[2,3-d]pyrimidin-5-yl)Ethyl]benzoyl}-l-glutamic acid (4), were designed and synthesized as potent dual inhibitors of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) and as antitumor agents. Compound 2 had inhibitory potency against human DHFR similar to N-{4-[2-(amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)Ethyl]benzoyl}-L-glutamic acid (LY231514) and 1, whereas 4 was inactive against human DHFR. Both 2 and 4 were more potent than LY231514 against E. coli TS. Against human TS, 2 was 7-fold less potent than LY231514 and 4 showed similar inhibitory activity as LY231514. In contrast to 2, which was an efficient substrate of human folypolyglutamate synthetase (FPGS), 4 was a poor substrate of FPGS. Compound 2 showed GI50 values in the nanomolar range against more than 18 human tumor cell lines in the standard NCI preclinical in vitro screen.
Roy L Kisliuk - One of the best experts on this subject based on the ideXlab platform.
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design synthesis and biological activities of classical n 4 2 2 amino 4 Ethylpyrrolo 2 3 d pyrimidin 5 yl Ethyl benzoyl l glutamic acid and its 6 mEthyl derivative as potential dual inhibitors of thymidylate synthase and dihydrofolate reductase and a
Journal of Medicinal Chemistry, 2003Co-Authors: Aleem Gangjee, Jianming Yu, Roy L Kisliuk, William H Haile, Giulia Sobrero, John J McguireAbstract:Two novel analogues, N-{2-amino-4-Ethyl[(pyrrolo[2,3-d]pyrimidin-5-yl)Ethyl]benzoyl}-l-glutamic acid (2) and N-{2-amino-4-Ethyl-6-mEthyl[(pyrrolo[2,3-d]pyrimidin-5-yl)Ethyl]benzoyl}-l-glutamic acid (4), were designed and synthesized as potent dual inhibitors of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) and as antitumor agents. Compound 2 had inhibitory potency against human DHFR similar to N-{4-[2-(amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)Ethyl]benzoyl}-L-glutamic acid (LY231514) and 1, whereas 4 was inactive against human DHFR. Both 2 and 4 were more potent than LY231514 against E. coli TS. Against human TS, 2 was 7-fold less potent than LY231514 and 4 showed similar inhibitory activity as LY231514. In contrast to 2, which was an efficient substrate of human folypolyglutamate synthetase (FPGS), 4 was a poor substrate of FPGS. Compound 2 showed GI50 values in the nanomolar range against more than 18 human tumor cell lines in the standard NCI preclinical in vitro screen.
