Synthesis of a tetronic acid library focused on inhibitors of tyrosine and dual-specificity protein phosphatases and its evaluation regarding VHR and cdc25B inhibition.

abstract：:Tertiary EGFRC797S mutation induced resistance against osimertinib (1) is an emerging "unmet clinical need" for non-small-cell lung cancer (NSCLC) patients. A series of 5-methylpyrimidopyridone derivatives were designed and synthesized as new selective EGFRL858R/T790M/C797S inhibitors. A representative compound, 8r-B,...

journal_title：Journal of medicinal chemistry

authors： Shen J,Zhang T,Zhu SJ,Sun M,Tong L,Lai M,Zhang R,Xu W,Wu R,Ding J,Yun CH,Xie H,Lu X,Ding K

更新日期：2019-08-08 00:00:00

abstract：:Replacement of the catecholic hydroxyl groups of the beta-adrenergic receptor agonist 6,7-dihydroxy-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline (trimetoquinol) with chloro substituents results in a compound with marked beta-adrenoceptor antagonist properties. This, therefore, parallels the similar transf...

journal_title：Journal of medicinal chemistry

authors： Kaiser C,Oh HJ,Garcia-Slanga BJ,Sulpizio AC,Hieble JP,Wawro JE,Kruse LI

更新日期：1986-11-01 00:00:00

abstract：:The modification of 3'-((2-cyclopentyl-6,7-dimethyl-1-oxo-2,3-dihydro-1H-inden-5-yloxy)methyl)biphenyl-4-carboxylic acid (BINA, 1) by incorporating heteroatoms into the structure and replacing the cyclopentyl moiety led to the development of new mGluR2 positive allosteric modulators (PAMs) with optimized potency and s...

journal_title：Journal of medicinal chemistry

authors： Dhanya RP,Sidique S,Sheffler DJ,Nickols HH,Herath A,Yang L,Dahl R,Ardecky R,Semenova S,Markou A,Conn PJ,Cosford ND

更新日期：2011-01-13 00:00:00

abstract：:We have synthesized and evaluated azaquinoxalinediones 3a-c for their activity in inhibiting [3H]AMPA binding from rat whole brain. It was found that the azaquinoxalinedione nucleus functions as a bioisostere for quinoxalinedione in AMPA receptor binding. The detailed structure-activity relationships of 6- and/or 7-su...

journal_title：Journal of medicinal chemistry

authors： Ohmori J,Kubota H,Shimizu-Sasamata M,Okada M,Sakamoto S

更新日期：1996-03-15 00:00:00

abstract：:Agonism of GPR119 is viewed as a potential therapeutic approach for the treatment of type II diabetes and other elements of metabolic syndrome. During progression of a previously disclosed candidate 1 through mice toxicity studies, we observed tonic-clonic convulsions in several mice at high doses. An in vitro hippoca...

journal_title：Journal of medicinal chemistry

authors： Scott JS,Bowker SS,Brocklehurst KJ,Brown HS,Clarke DS,Easter A,Ertan A,Goldberg K,Hudson JA,Kavanagh S,Laber D,Leach AG,MacFaul PA,Martin EA,McKerrecher D,Schofield P,Svensson PH,Teague J

更新日期：2014-11-13 00:00:00

abstract：:Small-molecule fluorescence imaging in the second near-infrared (NIR-II, 1000-1700 nm) window has gained increasing interest in clinical application. Till now, very few studies have been exploited in the small-molecule fluorophores with both excitation and emission in the NIR-II window. Inspired by the indocyanine gre...

journal_title：Journal of medicinal chemistry

authors： Ding B,Xiao Y,Zhou H,Zhang X,Qu C,Xu F,Deng Z,Cheng Z,Hong X

更新日期：2019-02-28 00:00:00

abstract：:Acute lung injury (ALI) and idiopathic pulmonary fibrosis (IPF) are both serious public health problems with high incidence and mortality rate in adults, and with few drugs available for the efficient treatment in clinic. In this study, we identified that two known histone deacetylase (HDAC) inhibitors, suberanilohydr...

journal_title：Journal of medicinal chemistry

authors： Lu W,Yao X,Ouyang P,Dong N,Wu D,Jiang X,Wu Z,Zhang C,Xu Z,Tang Y,Zou S,Liu M,Li J,Zeng M,Lin P,Cheng F,Huang J

更新日期：2017-03-09 00:00:00

abstract：:A series of DNA-intercalating potential antitumor agents, 1-[(omega-aminoalkyl)amino]-4-[N-(omega-aminoalkyl)carbamoyl]-9-oxo-9, 10-dihydroacridines, has been prepared by aminolysis of the corresponding 4-[N-(omega-aminoalkyl)carbamoyl]-1-chloro derivative with a suitable omega-aminoalkylamine. The noncovalent DNA-bin...

journal_title：Journal of medicinal chemistry

authors： Antonini I,Polucci P,Jenkins TC,Kelland LR,Menta E,Pescalli N,Stefanska B,Mazerski J,Martelli S

更新日期：1997-11-07 00:00:00

abstract：:New drugs and molecular targets are urgently needed to address the emergence and spread of drug-resistant tuberculosis. Mycobacterium tuberculosis ( Mtb) inosine 5'-monophosphate dehydrogenase 2 ( MtbIMPDH2) is a promising yet controversial potential target. The inhibition of MtbIMPDH2 blocks the biosynthesis of guani...

journal_title：Journal of medicinal chemistry

authors： Chacko S,Boshoff HIM,Singh V,Ferraris DM,Gollapalli DR,Zhang M,Lawson AP,Pepi MJ,Joachimiak A,Rizzi M,Mizrahi V,Cuny GD,Hedstrom L

更新日期：2018-06-14 00:00:00

abstract：:The 5'-phosphate (1) of the antiviral nucleoside 5-cyano-2'-deoxyuridine was synthesized and evaluated for inhibition of thymidylate synthetase purified from methotrexate-resistant Lactobacillus casei. Compound 1 was a potent competitive inhibitor with a K1 of 0.55 microns. Irreversible enzyme inhibition by this compo...

journal_title：Journal of medicinal chemistry

authors： Chang CT,Edwards MW,Torrence PF,Mertes MP

更新日期：1979-09-01 00:00:00

abstract：:Three analogs of luteinizing hormone-releasing hormone (LH-RH) of the structure less than Glu-His-Trp-Ser-Tyr-Gly-Gly-Leu-Arg-Pro-Gly-NH2, involving substitutions inpositions 1, 3, and 8 with nonprotein amino acids, have been synthesized by the solid-phase method. They are [pyro-L-alpha-(1-aminoadipic)]-LH-RH, [3-(2-n...

journal_title：Journal of medicinal chemistry

authors： Prasad KU,Roeske RW,Weitl FL,Vilchez-Martinez JA,Schally AV

更新日期：1976-04-01 00:00:00

abstract：:The recently discovered nicotinic agonist pyrido[3,4-b]norhomotropane [corrected] (PHT) as well as its N-methyl and 2'-methyl derivatives (syntheses reported herein) were compared with nicotine, nornicotine, and anatoxin a in a series of in vitro and in vivo assays. The results reveal that PHT possesses activity compa...

journal_title：Journal of medicinal chemistry

authors： Kanne DB,Abood LG

更新日期：1988-03-01 00:00:00

abstract：:[4-Threonine, 7-glycine]oxytocin and [1-(L-2-hydroxy-3-mercaptopropanoic acid), 4-threonine, 7-glycine]oxytocin (hydroxy[Thr4, Gly7]oxytocin) were synthesized by a combination of solid-phase and classical methods of peptide synthesis. A protected octapeptide was synthesized by the solid-phase method and following ammo...

journal_title：Journal of medicinal chemistry

authors： Lowbridge J,Manning M,Haldar J,Sawyer WH

更新日期：1977-01-01 00:00:00

abstract：:Regioselective syntheses of substituted 2-chloroquinoxalines and derived 2-(1-piperazinyl)quinoxalines are described. Selectivity in regards to serotonin reuptake blocking and serotoninmimetic activities of the piperazinylquinoxalines is reported. In general, introduction of a 6-substituent into the piperazinylquinoxa...

journal_title：Journal of medicinal chemistry

authors： Lumma WC Jr,Hartman RD,Saari WS,Engelhardt EL,Lotti VJ,Stone CA

更新日期：1981-01-01 00:00:00

abstract：:A series of 3-indoleacrylonitrile tyrphostins, 2-chloro-3-phenylquinolines, and 3-arylquinoxalines were prepared and tested for inhibition of platelet-derived growth factor receptor tyrosine kinase (PDGF-RTK) activity. The potency of the inhibitors was found to be quinoxalines > quinolines > indoles. Lipophilic groups...

journal_title：Journal of medicinal chemistry

authors： Gazit A,App H,McMahon G,Chen J,Levitzki A,Bohmer FD

更新日期：1996-05-24 00:00:00

abstract：:Sulfur mustard (SM) is a highly toxic chemical warfare agent. A satisfactory treatment regimen is not yet available for this toxicant. In a search for an effective antidote against SM, a series of novel S-2(omega-aminoalkylamino)ethyl alkyl/aryl thioethers [H(2)N(CH(2))(n)()NHCH(2)CH(2)SR], where R = alky, alicyclic, ...

journal_title：Journal of medicinal chemistry

authors： Pathak U,Raza SK,Kulkarni AS,Vijayaraghvan R,Kumar P,Jaiswal DK

更新日期：2004-07-15 00:00:00

abstract：:New linear and cyclic guanidines were synthesized and tested in vitro for their antifungal activity toward clinically relevant strains of Candida species, in comparison to fluconazole. Macrocyclic compounds showed a minimum inhibitory concentration in the micromolar range and a biological activity profile in some case...

journal_title：Journal of medicinal chemistry

authors： Manetti F,Castagnolo D,Raffi F,Zizzari AT,Rajamäki S,D'Arezzo S,Visca P,Cona A,Fracasso ME,Doria D,Posteraro B,Sanguinetti M,Fadda G,Botta M

更新日期：2009-12-10 00:00:00

abstract：:The C-terminal "address" sequences of prodynorphin-derived opioid peptides contain an unusually high proportion of basic residues, which are known to be crucial for conferring high activity and selectivity for kappa-opioid receptors. In an effort to investigate the possibility that the polycationic "tails" may be invo...

journal_title：Journal of medicinal chemistry

authors： Jacobson AR,Tam SW,Sayre LM

更新日期：1991-09-01 00:00:00

abstract：:We herein report phosphorodiamidates as a significant new phosphate prodrug motif. Sixty-seven phosphorodiamidates are reported of two 6-O-alkyl 2'-C-methyl guanosines, with significant variation in the diamidate structure. Both symmetrical and asymmetric phosphorodiamidates are reported, derived from various esterifi...

journal_title：Journal of medicinal chemistry

authors： McGuigan C,Madela K,Aljarah M,Bourdin C,Arrica M,Barrett E,Jones S,Kolykhalov A,Bleiman B,Bryant KD,Ganguly B,Gorovits E,Henson G,Hunley D,Hutchins J,Muhammad J,Obikhod A,Patti J,Walters CR,Wang J,Vernachio J,Ra

更新日期：2011-12-22 00:00:00

abstract：:The chemical synthesis and structure-activity relationships of a novel series of 17beta-glucocorticoid butyrolactones possessing either a 16alpha,17alpha-isopropylidene or -butylidene group are described. The sulfur-linked gamma-lactone group was incorporated onto the 17beta-position of the androstane nucleus via Bart...

journal_title：Journal of medicinal chemistry

authors： Procopiou PA,Biggadike K,English AF,Farrell RM,Hagger GN,Hancock AP,Haase MV,Irving WR,Sareen M,Snowden MA,Solanke YE,Tralau-Stewart CJ,Walton SE,Wood JA

更新日期：2001-02-15 00:00:00

abstract：:Novel 19-norvitamin D analogues (ADYW1-4, 5a-d) in which an adamantyl diyne side chain is attached directly to the 17-position of the D ring are designed and stereoselectively synthesized. The adamantane ring of these analogues was expected to interfere with helix 12 (H12, activation function 2) of the vitamin D recep...

journal_title：Journal of medicinal chemistry

authors： Watarai Y,Ishizawa M,Ikura T,Zacconi FC,Uno S,Ito N,Mouriño A,Tokiwa H,Makishima M,Yamada S

更新日期：2015-12-24 00:00:00

abstract：:2-, 6-, And 8-alkylated (methyl, ethyl, and vinyl) adenosine analogues were synthesized by a palladium-catalyzed cross-coupling of a tetraalkyltin with the halogenated purine nucleosides. The synthesis of the 8-substituted analogues was accomplished using a transient protection procedure. The 6-alkylated-9-beta-D-ribo...

journal_title：Journal of medicinal chemistry

authors： Van Aerschot AA,Mamos P,Weyns NJ,Ikeda S,De Clercq E,Herdewijn PA

更新日期：1993-10-01 00:00:00

abstract：:Methionine aminopeptidase-2 (MetAP2) is a novel target for cancer therapy. As part of an effort to discover orally active reversible inhibitors of MetAP2, a series of anthranilic acid sulfonamides with micromolar affinities for human MetAP2 were identified using affinity selection by mass spectrometry (ASMS) screening...

journal_title：Journal of medicinal chemistry

authors： Sheppard GS,Wang J,Kawai M,Fidanze SD,BaMaung NY,Erickson SA,Barnes DM,Tedrow JS,Kolaczkowski L,Vasudevan A,Park DC,Wang GT,Sanders WJ,Mantei RA,Palazzo F,Tucker-Garcia L,Lou P,Zhang Q,Park CH,Kim KH,Petros A,Ol

更新日期：2006-06-29 00:00:00

abstract：:Glucagon-like peptide-1 (GLP-1) has the ability to lower the blood glucose level, and its regulatory functions make it an attractive therapeutic agent for the treatment of type 2 diabetes. However, its rapid degradation by enzymes like dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) 24.11 severely com...

journal_title：Journal of medicinal chemistry

authors： Murage EN,Gao G,Bisello A,Ahn JM

更新日期：2010-09-09 00:00:00

abstract：:Five dipeptidomimetic-based model prodrugs containing ketomethylene amide bond replacements were synthesized from readily available alpha,beta-unsaturated gamma-ketoesters. The model drug (BnOH) was attached to the C-terminus or to one of the side chain positions of the dipeptidomimetic. The stability, the affinity fo...

journal_title：Journal of medicinal chemistry

authors： Våbenø J,Nielsen CU,Ingebrigtsen T,Lejon T,Steffansen B,Luthman K

更新日期：2004-09-09 00:00:00

abstract：:A series of 4(6)-(benzyloxy)-2,6(4)-diamino-5-(nitro or nitroso)pyrimidine derivatives and analogues of which 4(6)-benzyloxy groups were replaced with a (2-, 3-, or 4-fluorobenzyl)oxy or (2-, 3-, or 4-pyridylmethyl)oxy group, was synthesized. The abilities of these compounds to inhibit human O6-alkylguanine-DNA alkylt...

journal_title：Journal of medicinal chemistry

authors： Terashima I,Kohda K

更新日期：1998-02-12 00:00:00

abstract：:The synthetic chemical nuclease, [Cu(1,10-phenanthroline)2](2+), has stimulated research within metallonuclease development and in the area of cytotoxic metallodrug design. Our analysis reveals, however, that this agent is "promiscuous" as it binds both dsDNA and protein biomolecules, without specificity, and induces ...

journal_title：Journal of medicinal chemistry

authors： Prisecaru A,McKee V,Howe O,Rochford G,McCann M,Colleran J,Pour M,Barron N,Gathergood N,Kellett A

更新日期：2013-11-14 00:00:00

abstract：:Resistance to β-lactam antibiotics can be mediated by metallo-β-lactamase enzymes (MBLs). An MBL inhibitor could restore the effectiveness of β-lactams. We report on the evaluation of approved thiol-containing drugs as inhibitors of NDM-1, VIM-1, and IMP-7. Drugs were assessed by a novel assay using a purchasable fluo...

journal_title：Journal of medicinal chemistry

authors： Klingler FM,Wichelhaus TA,Frank D,Cuesta-Bernal J,El-Delik J,Müller HF,Sjuts H,Göttig S,Koenigs A,Pos KM,Pogoryelov D,Proschak E

更新日期：2015-04-23 00:00:00

abstract：:In colorectal cancer, adenomatous polyposis coli (APC) interacts with Rho guanine-nucleotide-exchange factor 4 (Asef), thereby stimulating aberrant colorectal-cancer-cell migration. Consequently, the APC-Asef interaction represents a promising therapeutic target for mitigating colorectal-cancer migration. In this stud...

journal_title：Journal of medicinal chemistry

authors： Yang X,Zhong J,Zhang Q,Qian J,Song K,Ruan C,Xu J,Ding K,Zhang J

更新日期：2018-09-13 00:00:00

abstract：:Every week, articles disclosing new antifungal leads reported as promising starting points for optimization projects are published. In many cases, the mechanism that accounts for their antifungal activity has not been fully elucidated. More significantly, the detrimental impact that could result from certain embedded ...

journal_title：Journal of medicinal chemistry

authors： Pouliot M,Jeanmart S

更新日期：2016-01-28 00:00:00