Synthesis of a methylenebis(phosphonate) analogue of mycophenolic adenine dinucleotide: a glucuronidation-resistant MAD analogue of NAD.

abstract：:The receptor CRM1 is responsible for the nuclear export of many tumor-suppressor proteins and viral ribonucleoproteins. This renders CRM1 an interesting target for therapeutic intervention in diverse cancer types and viral diseases. Structural studies of Saccharomyces cerevisiae CRM1 ( Sc ...

journal_title：Journal of medicinal chemistry

authors： Shaikhqasem A,Dickmanns A,Neumann P,Ficner R

更新日期：2020-07-23 00:00:00

abstract：:The low oral bioavailability and rapid biliary excretion of peptide-derived HIV protease inhibitors have limited their utility as potential therapeutic agents. Our broad screening program to discover nonpeptidic HIV protease inhibitors had previously identified compound II (phenprocoumon, K(i) = 1 muM) as a lead templ...

journal_title：Journal of medicinal chemistry

authors： Thaisrivongs S,Watenpaugh KD,Howe WJ,Tomich PK,Dolak LA,Chong KT,Tomich CC,Tomasselli AG,Turner SR,Strohbach JW

更新日期：1995-09-01 00:00:00

abstract：:Phenyl-substituted analogues of 2-[(phenylmethyl)sulfonyl]pyridine 1-oxide preemergent herbicides were examined in order to determine quantitative relationships between structure and activity against the following three weed species: switch grass (Panicum virgatum L.), barnyard grass (Echinochloa crusgalli L. Beauv.),...

journal_title：Journal of medicinal chemistry

authors： Doweyko AM,Bell AR,Minatelli JA,Relyea DI

更新日期：1983-04-01 00:00:00

abstract：:Three ellipticine-estradiol conjugates were synthesized in an effort to target the cytotoxicity of ellipticine to estrogen-receptor positive cells. The three conjugates were prepared with linker chains extending from the 17 alpha position of the estradiol to N-2 (compound 3), N-6 (compound 4), and C-9 (compound 5) pos...

journal_title：Journal of medicinal chemistry

authors： Devraj R,Barrett JF,Fernandez JA,Katzenellenbogen JA,Cushman M

更新日期：1996-08-16 00:00:00

abstract：:Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11-64%. The compounds are potent and selective inhibitors of NR2B-containing recombinant NMDA receptors...

journal_title：Journal of medicinal chemistry

authors： Tahirovic YA,Geballe M,Gruszecka-Kowalik E,Myers SJ,Lyuboslavsky P,Le P,French A,Irier H,Choi WB,Easterling K,Yuan H,Wilson LJ,Kotloski R,McNamara JO,Dingledine R,Liotta DC,Traynelis SF,Snyder JP

更新日期：2008-09-25 00:00:00

abstract：:The final stages of polio eradication are proving more difficult than the early phases, and the development of effective drugs and treatments is considered a priority; thus, the research is ongoing. A screening of our in-house chemical library against poliovirus Sabin strains led to the identification of compounds 5 a...

journal_title：Journal of medicinal chemistry

authors： Madia VN,Messore A,Pescatori L,Saccoliti F,Tudino V,De Leo A,Scipione L,Fiore L,Rhoden E,Manetti F,Oberste MS,Di Santo R,Costi R

更新日期：2019-01-24 00:00:00

abstract：:1-(Tetrahydro-2-furanyl)-5-fluorouracil (Thf-FU), which is named Ftorafur or FT-207 and is used clinically as an antitumor agent, was conveniently synthesized by condensation of the trimethylsilyl derivative of 5-fluorouracil with 2-acetoxytetrahydrofuran using NaI as a catalyst. This optically inactive Thf-FU was res...

journal_title：Journal of medicinal chemistry

authors： Yasumoto M,Moriyama A,Unemi N,Hashimoto S,Suzue T

更新日期：1977-12-01 00:00:00

abstract：:A series of [(heteroarylamino)phenyl]alkanoic acids having pyridine, quinoline, or pyrimidine as the heteroaryl moiety was prepared as potential antiinflammatory agents. Among them, 2-[4-(2-pyridylamino)phenyl]propionic acid (14b) showed excellent antiinflammatory and analgesic activities with less tendency to cause g...

journal_title：Journal of medicinal chemistry

authors： Hino K,Nakamura H,Nagai Y,Uno H,Nishimura H

更新日期：1983-02-01 00:00:00

abstract：:Focal adhesion kinase (FAK) is a nonreceptor kinase that is overexpressed in many types of tumors. We developed a novel cancer-therapy approach, targeting the main autophosphorylation site of FAK, Y397, by computer modeling and screening of the National Cancer Institute (NCI) small molecule compounds database. More th...

journal_title：Journal of medicinal chemistry

authors： Golubovskaya VM,Nyberg C,Zheng M,Kweh F,Magis A,Ostrov D,Cance WG

更新日期：2008-12-11 00:00:00

abstract：:2-(p-Nitrophenyl)-4-isopropylmorphine (V), an analog of 1-(p-nitrophenyl)-2-isopropylaminoethanol (INPEA, I) in which the OCHCHN chain of I is locked in a morpholine ring, loses the beta-receptor blocking activity of I on various isolated preparations. The same ineffectiveness is observed in the O-methyl (II), N-methy...

journal_title：Journal of medicinal chemistry

authors： Del Tacca M,Bertelli A,Mazzanti L,Stacchini B,Balsamo A,Crotti P,Macchia B,Macchia F

更新日期：1975-08-01 00:00:00

abstract：:The binding structures of 11 human oxidosqualene cyclase inhibitors designed as cholesterol-lowering agents were determined for the squalene-hopene cyclase from Alicyclobacillus acidocaldarius, which is the only structurally known homologue of the human enzyme. The complexes were produced by cocrystallization, and the...

journal_title：Journal of medicinal chemistry

authors： Lenhart A,Reinert DJ,Aebi JD,Dehmlow H,Morand OH,Schulz GE

更新日期：2003-05-22 00:00:00

abstract：:Pan assay interference compounds (PAINS) have become a paradigm for compound classes that might cause artifacts in biological assays. PAINS-defining substructures are typically contained in larger compounds. We have systematically examined X-ray structures of protein-ligand complexes for compounds containing PAINS mot...

journal_title：Journal of medicinal chemistry

authors： Gilberg E,Gütschow M,Bajorath J

更新日期：2018-02-08 00:00:00

abstract：:The plant metabolite 3,4,5-tri-O-galloylquinic acid methyl ester (TGAME, compound 6) was synthesized, and its potential effect on calcium oxalate monohydrate (COM) crystal binding to the surface of Madin-Darby canine kidney cells type I (MDCKI) and crystal growth in a Drosophila melanogaster Malpighian tubule (MT) mod...

journal_title：Journal of medicinal chemistry

authors： Abd El-Salam M,Bastos JK,Han JJ,Previdi D,Coelho EB,Donate PM,Romero MF,Lieske J

更新日期：2018-02-22 00:00:00

abstract：:To improve the biological profile of 20(S)-camptothecin, a novel class of 20-O-linked camptothecin glycoconjugates has been designed for preferential cellular uptake into tumor cells by an active transport mechanism. Such conjugates have been optimized for enhanced solubility, stabilization of the camptothecin lactone...

journal_title：Journal of medicinal chemistry

authors： Lerchen HG,Baumgarten J,von dem Bruch K,Lehmann TE,Sperzel M,Kempka G,Fiebig HH

更新日期：2001-11-22 00:00:00

abstract：:We disclose the first selective, nonpeptidic, small-molecule somatostatin receptor subtype 5 (SST5R) antagonists that were identified by a chemogenomics approach based on the analysis of the homology of amino acids defining the putative consensus drug binding site of SST5R. With this strategy, opioid, histamine, dopam...

journal_title：Journal of medicinal chemistry

authors： Martin RE,Green LG,Guba W,Kratochwil N,Christ A

更新日期：2007-12-13 00:00:00

abstract：:A novel bitriazolyl acyclonucleoside was discovered to exhibit powerful antiproliferative effects on different cancer cell lines through caspase-dependent apoptosis and at the same time stimulate the immune response in dendritic cells via Toll-like receptor 7 (TLR7) signaling. This promising compound with dual antican...

journal_title：Journal of medicinal chemistry

authors： Xia Y,Wang M,Demaria O,Tang J,Rocchi P,Qu F,Iovanna JL,Alexopoulou L,Peng L

更新日期：2012-06-14 00:00:00

abstract：:Certain phenylalkylamine derivatives have been considered to bind selectively at 5-HT2 serotonin receptors. It is now recognized that the most widely used derivatives, i.e., 1-(2,5-dimethoxy-4-X-phenyl)-2-aminopropanes where X = Me (DOM), Br (DOB), and I (DOI) (1-3, respectively) also bind at the more recently identif...

journal_title：Journal of medicinal chemistry

authors： Glennon RA,Raghupathi R,Bartyzel P,Teitler M,Leonhardt S

更新日期：1992-02-21 00:00:00

abstract：:The synthesis and antiviral activity of a number of 3'-C-difluoromethyl and 3'-deoxy-3'-C-fluoromethyl nucleosides are reported. The 3'-C-difluoromethyl nucleosides 26a and 26b were obtained by treatment of the corresponding 2',5'-di-O-protected-3'-C-formyl nucleosides 25a and 25b with (diethylamino)sulfur trifluoride...

journal_title：Journal of medicinal chemistry

authors： Bamford MJ,Coe PL,Walker RT

更新日期：1990-09-01 00:00:00

abstract：:1-(3'-Diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines were synthesized and evaluated for CQ-resistant reversal activity. In general the compounds of the series elicit better biological response than their phenylmethyl analogues. The most active compound 4b has been evaluated in vivo in detail, and the ...

journal_title：Journal of medicinal chemistry

authors： Batra S,Srivastava P,Roy K,Pandey VC,Bhaduri AP

更新日期：2000-09-07 00:00:00

abstract：:A unique strategy for the enhancement of secondary binding of an inhibitor to an enzyme has been demonstrated in the design of new human immunodeficiency virus (HIV) protease inhibitors. When the planar benzene ring of a 4-hydroxycoumarin lead compound (1a, Ki = 0.800 microM) was replaced with medium-sized (i.e., 7-9)...

journal_title：Journal of medicinal chemistry

authors： Romines KR,Watenpaugh KD,Tomich PK,Howe WJ,Morris JK,Lovasz KD,Mulichak AM,Finzel BC,Lynn JC,Horng MM

更新日期：1995-05-26 00:00:00

abstract：:Analogues of the antimycotic allylamine terbinafine were prepared in which the naphthalene and the tert-butyl-acetylene moieties were preserved, but the spacer between these two groups was varied, and the antifungal activity of the new compounds was evaluated. All modifications of the original spacer such as reduction...

journal_title：Journal of medicinal chemistry

authors： Nussbaumer P,Leitner I,Stütz A

更新日期：1994-03-04 00:00:00

abstract：:The mechanism of action of a general class of mechanism-based inhibitors of serine proteases, including human neutrophil elastase (HNE), has been elucidated by determining the X-ray crystal structure of an enzyme-inhibitor complex. The captured intermediate indicates that processing of inhibitor by the enzyme generate...

journal_title：Journal of medicinal chemistry

authors： Huang W,Yamamoto Y,Li Y,Dou D,Alliston KR,Hanzlik RP,Williams TD,Groutas WC

更新日期：2008-04-10 00:00:00

abstract：:Stabilization of protein-protein interactions (PPIs) holds great potential for therapeutic agents, as illustrated by the successful drugs rapamycin and lenalidomide. However, how such interface-binding molecules can be created in a rational, bottom-up manner is a largely unanswered question. We report here how a fragm...

journal_title：Journal of medicinal chemistry

authors： Guillory X,Wolter M,Leysen S,Neves JF,Kuusk A,Genet S,Somsen B,Morrow JK,Rivers E,van Beek L,Patel J,Goodnow R,Schoenherr H,Fuller N,Cao Q,Doveston RG,Brunsveld L,Arkin MR,Castaldi P,Boyd H,Landrieu I,Chen H,O

更新日期：2020-07-09 00:00:00

abstract：:A series of 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives, substituted at the 7-position with functionalized side chains, was synthesized and evaluated as inhibitors of human blood platelet cAMP phosphodiesterase (PDE) as well as ADP- and collagen-induced platelet aggregation, in vitro. Structural modificati...

journal_title：Journal of medicinal chemistry

authors： Meanwell NA,Pearce BC,Roth HR,Smith EC,Wedding DL,Wright JJ,Buchanan JO,Baryla UM,Gamberdella M,Gillespie E

更新日期：1992-07-10 00:00:00

abstract：:We present Fleksy, a new approach to consider both ligand and receptor flexibility in small molecule docking. Pivotal to our method is the use of a receptor ensemble to describe protein flexibility. To construct these ensembles, we use a backbone-dependent rotamer library and implement the concept of interaction sampl...

journal_title：Journal of medicinal chemistry

authors： Nabuurs SB,Wagener M,de Vlieg J

更新日期：2007-12-27 00:00:00

abstract：:Ghrelin, a gut-derived orexigenic hormone, is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R). Centrally administered ghrelin has been shown to cause hunger and increase food intake in rodents. Inhibition of ghrelin actions with ghrelin antibody, peptidyl GHS-R antagonists, and antisense oligo...

journal_title：Journal of medicinal chemistry

authors： Serby MD,Zhao H,Szczepankiewicz BG,Kosogof C,Xin Z,Liu B,Liu M,Nelson LT,Kaszubska W,Falls HD,Schaefer V,Bush EN,Shapiro R,Droz BA,Knourek-Segel VE,Fey TA,Brune ME,Beno DW,Turner TM,Collins CA,Jacobson PB,Sham H

更新日期：2006-04-20 00:00:00

abstract：:Oxadiazoles are five-membered heteroaromatic rings containing two carbons, two nitrogens, and one oxygen atom, and they exist in different regioisomeric forms. Oxadiazoles are frequently occurring motifs in druglike molecules, and they are often used with the intention of being bioisosteric replacements for ester and ...

journal_title：Journal of medicinal chemistry

authors： Boström J,Hogner A,Llinàs A,Wellner E,Plowright AT

更新日期：2012-03-08 00:00:00

abstract：:D-Alanine:D-alanine ligase (Ddl) is an essential ATP-dependent bacterial enzyme involved in peptidoglycan biosynthesis. Discovery of Ddl inhibitors not competitive with ATP has proven to be difficult because the Ddl bimolecular d-alanine binding pocket is very restricted, as is accessibility to the active site for lar...

journal_title：Journal of medicinal chemistry

authors： Hrast M,Vehar B,Turk S,Konc J,Gobec S,Janežič D

更新日期：2012-08-09 00:00:00

abstract：:A series of nitroimidazoles incorporating sulfonamide/sulfamide/sulfamate moieties were designed and synthesized as radio/chemosensitizing agent targeting the tumor-associated carbonic anhydrase (CA) isoforms IX and XII. Most of the new compounds were nanomolar inhibitors of these isoforms. Crystallographic studies on...

journal_title：Journal of medicinal chemistry

authors： Rami M,Dubois L,Parvathaneni NK,Alterio V,van Kuijk SJ,Monti SM,Lambin P,De Simone G,Supuran CT,Winum JY

更新日期：2013-11-14 00:00:00

abstract：:The synthesis of a series of substituted heterocyclic alkoxypropionic acids is described. They were evaluated for antiinflammatory effects in two animal models of chronic inflammation; adjuvant arthritis and type II collagen arthritis in the rat. The desired profile of biological activity was characterized by the redu...

journal_title：Journal of medicinal chemistry

authors： Self CR,Barber WE,Machin PJ,Osbond JM,Smithen CE,Tong BP,Wickens JC,Bloxham DP,Bradshaw D,Cashin CH

更新日期：1991-02-01 00:00:00