Výsledky vyhledávání

Development of substituted pyrido[3,2-d]pyrimidines as potent and selective dihydrofolate reductase inhibitors for pneumocystis pneumonia infection

Autor: Jim Pace, Vivian Cody, Sherry F. Queener, Khushbu Shah, Aleem Gangjee

Publikováno v: Bioorg Med Chem Lett

Pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii (pj) can lead to serious health consequences in patients with an immunocompromised system. Trimethoprim (TMP), used as first-line therapy in combination with sulfamethoxazole, is a selecti

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e744915d2e688f2fdb992d6c0080432d
https://doi.org/10.1016/j.bmcl.2019.06.004

Zobrazit plný text záznamu

Targeting species specific amino acid residues: Design, synthesis and biological evaluation of 6-substituted pyrrolo[2,3-d]pyrimidines as dihydrofolate reductase inhibitors and potential anti-opportunistic infection agents

Autor: Khushbu Shah, Vivian Cody, Xin Lin, Aleem Gangjee, Jim Pace, Sherry F. Queener

Publikováno v: Bioorganic & Medicinal Chemistry. 26:2640-2650

To combine the potency of trimetrexate (TMQ) or piritrexim (PTX) with the species selectivity of trimethoprim (TMP), target based design was carried out with the X-ray crystal structure of human dihydrofolate reductase (hDHFR) and the homology model

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::088269170c1eeb27b9ebef9d199b0298
https://doi.org/10.1016/j.bmc.2018.04.032

Zobrazit plný text záznamu

Kinetic and Structural Analysis for Potent Antifolate Inhibition of Pneumocystis jirovecii, Pneumocystis carinii, and Human Dihydrofolate Reductases and Their Active-Site Variants

Autor: Vivian Cody, Aleem Gangjee, Jim Pace, Sherry F. Queener, Ona O. Adair

Publikováno v: Antimicrobial Agents and Chemotherapy. 57:2669-2677

A major concern of immunocompromised patients, in particular those with AIDS, is susceptibility to infection caused by opportunistic pathogens such as Pneumocystis jirovecii , which is a leading cause of pneumonia in immunocompromised patients. We re

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bed13ad82c657357fa6d5562b6d5c769
https://doi.org/10.1128/aac.00172-13

Zobrazit plný text záznamu

Crystallographic analysis reveals a novel second binding site for trimethoprim in active site double mutants of human dihydrofolate reductase

Autor: Jennifer Piraino, Jim Pace, Sherry F. Queener, Vivian Cody

Publikováno v: Journal of Structural Biology. 176:52-59

In order to produce a more potent replacement for trimethoprim (TMP) used as a therapy for Pneumocystis pneumonia and targets dihydrofolate reductase from Pneumocystis jirovecii (pjDHFR), it is necessary to understand the determinants of potency and

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::13fd253b1772af038bb770108e0d8078
https://doi.org/10.1016/j.jsb.2011.06.001

Zobrazit plný text záznamu

Structural analysis of human dihydrofolate reductase as a binary complex with the potent and selective inhibitor 2,4-diamino-6-{2′-O-(3-carboxypropyl)oxydibenz[b,f]-azepin-5-yl}methylpteridine reveals an unusual binding mode

Autor: Vivian Cody, Jessica Nowak, Jim Pace

Publikováno v: Acta Crystallographica Section D Biological Crystallography. 67:875-880

In order to understand the structure–activity profile observed for a series of substituted dibenz[b,f]azepine antifolates, the crystal structure of the binary complex of human dihydrofolate reductase (hDHFR) with the potent and selective inhibito

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6e9845fd857039580ce31e7768a9cecd
https://doi.org/10.1107/s0907444911030071

Zobrazit plný text záznamu

Preferential selection of isomer binding from chiral mixtures: alternate binding modes observed for theEandZisomers of a series of 5-substituted 2,4-diaminofuro[2,3-d]pyrimidines as ternary complexes with NADPH and human dihydrofolate reductase

Autor: Jennifer Piraino, Jim Pace, Aleem Gangjee, Vivian Cody, Wei Li

Publikováno v: Acta Crystallographica Section D Biological Crystallography. 66:1271-1277

The crystal structures of six human dihydrofolate reductase (hDHFR) ternary complexes with NADPH and a series of mixed E/Z isomers of 5-substituted 5-[2-(2-methoxyphenyl)-prop-1-en-1-yl]furo[2,3-d]pyrimidine-2,4-diamines substituted at the C9 positio

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1d4312969b05002a7100307a08b580f6
https://doi.org/10.1107/s0907444910035808

Zobrazit plný text záznamu

Design, synthesis, and X-ray crystal structures of 2,4-diaminofuro[2,3-d]pyrimidines as multireceptor tyrosine kinase and dihydrofolate reductase inhibitors

Autor: Sherry F. Queener, Vivian Cody, Jim Pace, Dixy W. Green, Linda A. Warnke, Michael A. Ihnat, Yibin Zeng, Lu Lin, Wei Li, Aleem Gangjee

Publikováno v: Bioorganic & Medicinal Chemistry. 17:7324-7336

To optimize dual receptor tyrosine kinase (RTK) and dihydrofolate reductase (DHFR) inhibition, the E- and Z-isomers of 5-[2-(2-methoxyphenyl)prop-1-en-1-yl]furo[2,3-d]pyrimidine-2,4-diamines (1a and 1b) were separated by HPLC and the X-ray crystal st

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8fb30c9e6b007559f2d20b90bf070a20
https://doi.org/10.1016/j.bmc.2009.08.044

Zobrazit plný text záznamu

TheZisomer of 2,4-diaminofuro[2,3-d]pyrimidine antifolate promotes unusual crystal packing in a human dihydrofolate reductase ternary complex

Autor: Jim Pace, Aleem Gangjee, Vivian Cody, Lu Lin

Publikováno v: Acta Crystallographica Section F Structural Biology and Crystallization Communications. 65:762-766

The crystal structure of the ternary complex of human dihydrofolate reductase (hDHFR) with NADPH and the Z isomer of 2,4-diamino-5-[2-(2'-methoxyphenyl)propenyl]-furo[2,3-d]pyrimidine (Z1) shows that the Z isomer binds in the normal antifolate orient

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2043dae92934dba8d06a19a38d3fc265
https://doi.org/10.1107/s1744309109025548

Zobrazit plný text záznamu

Design, Synthesis, and X-ray Crystal Structure of Classical and Nonclassical 2-Amino-4-oxo-5-substituted-6-ethylthieno[2,3-d]pyrimidines as Dual Thymidylate Synthase and Dihydrofolate Reductase Inhibitors and as Potential Antitumor Agents

Autor: Aleem Gangjee, Vivian Cody, Jim Pace, J. Makin, Roy L. Kisliuk, Wei Li, Jennifer Piraino

Publikováno v: Journal of Medicinal Chemistry. 52:4892-4902

N-{4-[(2-amino-6-ethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-5-yl)thio]benzoyl}-L-glutamic acid 2 and thirteen nonclassical analogues 2a–2m were synthesized as potential dual thymidylate synthase (TS) and dihydrofolate reductase (DHFR) inhibitors

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::849b459819eeae05ad8f676627780c9e
https://doi.org/10.1021/jm900490a

Zobrazit plný text záznamu

Structural analysis of a holoenzyme complex of mouse dihydrofolate reductase with NADPH and a ternary complex with the potent and selective inhibitor 2,4-diamino-6-(2′-hydroxydibenz[b,f]azepin-5-yl)methylpteridine

Autor: Jim Pace, Andre Rosowsky, Vivian Cody

Publikováno v: Acta Crystallographica Section D: Biological Crystallography

The structures of mouse DHFR holo enzyme and a ternary complex with NADPH and a potent inhibitor are described.
It has been shown that 2,4-diamino-6-arylmethylpteridines and 2,4-diamino-5-arylmethylpyrimidines containing an O-carboxylalkyloxy gr

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::44b4aaa1c6c56fbc6d0df9574b7ac331
http://europepmc.org/articles/PMC2615397

Zobrazit plný text záznamu

Vyhledávací nástroje:

Upřesnit hledání