3-(4-phenoxyphenyl)pyrazoles: a novel class of sodium channel blockers.

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：:Quantitative structure-activity relationships (QSAR) have been established for the inhibition of dihydrofolate reductase and thymidylate synthetase by 2,4-diaminoquinazoline-glutamic acid analogues. For dihydrofolate reductase from both human acute lymphocytic leukemia cells and murine L1210R cells, QSAR's obtained wi...

journal_title：Journal of medicinal chemistry

authors： Chen BK,Horváth C,Bertino JR

更新日期：1979-05-01 00:00:00

abstract：:A series of UTP, UDP, and UMP derivatives and analogues were synthesized and evaluated at the human pyrimidinergic P2Y receptor subtypes P2Y2, P2Y4, and P2Y6 stably expressed in 1321N1 astrocytoma cells. Substituents at N3 of UTP were poorly tolerated by P2Y2 and P2Y4 receptors. In contrast, a large phenacyl substitue...

journal_title：Journal of medicinal chemistry

authors： El-Tayeb A,Qi A,Müller CE

更新日期：2006-11-30 00:00:00

abstract：:A new class of potential antitumor agents inspired by the enediyne antitumor antibiotics has been synthesized: the 1,2-dialkynylimidazoles. The aza-Bergman rearrangement of these 1,2-dialkynylimidazoles has been investigated theoretically at the B3LYP/6-31G(d,p) level and experimentally by measuring the kinetics of re...

journal_title：Journal of medicinal chemistry

authors： Laroche C,Li J,Kerwin SM

更新日期：2011-07-28 00:00:00

abstract：:The sponge-derived polyketide macrolides fijianolides A (1) and B (2), isolaulimalide and laulimalide, have taxol-like microtubule-stabilizing activity, and the latter exhibits potent cytotoxicity. Insight on the biogeographical and phenotypic variations of Cacospongia mycofijiensis is presented that will enable a fut...

journal_title：Journal of medicinal chemistry

authors： Johnson TA,Tenney K,Cichewicz RH,Morinaka BI,White KN,Amagata T,Subramanian B,Media J,Mooberry SL,Valeriote FA,Crews P

更新日期：2007-08-09 00:00:00

abstract：:The cannabinoid type 2 (CB2) receptor has emerged as a valuable target for therapy and imaging of immune-mediated pathologies. With the aim to find a suitable radiofluorinated analogue of the previously reported CB2 positron emission tomography (PET) radioligand [11C]RSR-056, 38 fluorinated derivatives were synthesize...

journal_title：Journal of medicinal chemistry

authors： Haider A,Kretz J,Gobbi L,Ahmed H,Atz K,Bürkler M,Bartelmus C,Fingerle J,Guba W,Ullmer C,Honer M,Knuesel I,Weber M,Brink A,Herde AM,Keller C,Schibli R,Mu L,Grether U,Ametamey SM

更新日期：2019-12-26 00:00:00

abstract：:A new structurally distinct class of 14-membered-ring macrolides is characterized by a keto-function instead of the cladinose sugar, well-known for its fragility even in weakly acidic media. This new class called ketolides is endowed with remarkable antibacterial activity against macrolide-resistant strains. A complet...

journal_title：Journal of medicinal chemistry

authors： Bertho G,Gharbi-Benarous J,Delaforge M,Lang C,Parent A,Girault JP

更新日期：1998-08-27 00:00:00

abstract：:Using an NMR-based fragment screening and X-ray crystal structure-based assembly, starting with millimolar ligands for both the catalytic site and the second phosphotyrosine binding site, we have identified a small-molecule inhibitor of protein tyrosine phosphatase 1B with low micromolar inhibition constant, high sele...

journal_title：Journal of medicinal chemistry

authors： Liu G,Xin Z,Pei Z,Hajduk PJ,Abad-Zapatero C,Hutchins CW,Zhao H,Lubben TH,Ballaron SJ,Haasch DL,Kaszubska W,Rondinone CM,Trevillyan JM,Jirousek MR

更新日期：2003-09-25 00:00:00

abstract：:The concept of bioisosterism between benzimidazole and catechol was applied to the design and synthesis of benzimidazole analogues of norepinephrine, (R,S)-1-[5(6)-benzimidazolyl]-2-aminoethanol (2), and of isoproterenol, (R,S)-1-[5(6)-benzimidazolyl]-2-isopropylaminoethanol (4). Compound 2 was shown to be a partial b...

journal_title：Journal of medicinal chemistry

authors： Arnett CD,Wright J,Zenker N

更新日期：1978-01-01 00:00:00

abstract：:Deltorphin analogues were substituted by a series of achiral C alpha,alpha-dialkyl cyclic alpha-amino acids (1-aminocycloalkane-1-carboxylic acids, Ac chi c, where chi = a hexane, pentane, or propane cycloalkane ring) in position 2, 3, 4, or 2 and 3 in deltorphin C, and in position 2 in [Ac6c2,-des-Phe3]deltorphin C h...

journal_title：Journal of medicinal chemistry

authors： Breveglieri A,Guerrini R,Salvadori S,Bianchi C,Bryant SD,Attila M,Lazarus LH

更新日期：1996-02-02 00:00:00

abstract：:An imidazo[4,5-h]isoquinolin-7,9-dione (1) was identified as an adenosine 5'-triphosphate competitive inhibitor of lck by high throughput screening. Initial structure-activity relationship studies identified the dichlorophenyl ring and the imide NH as important pharmacophores. A binding model was constructed to unders...

journal_title：Journal of medicinal chemistry

authors： Snow RJ,Cardozo MG,Morwick TM,Busacca CA,Dong Y,Eckner RJ,Jacober S,Jakes S,Kapadia S,Lukas S,Panzenbeck M,Peet GW,Peterson JD,Prokopowicz AS 3rd,Sellati R,Tolbert RM,Tschantz MA,Moss N

更新日期：2002-08-01 00:00:00

abstract：:G-protein coupled receptor (GPCR) GPR109a is a molecular target for nicotinic acid and is expressed in adipocytes, spleen, and immune cells. Nicotinic acid has long been used for the treatment of dyslipidemia due to its capacity to positively affect serum lipids to a greater extent than other currently marketed drugs....

journal_title：Journal of medicinal chemistry

authors： Boatman PD,Lauring B,Schrader TO,Kasem M,Johnson BR,Skinner P,Jung JK,Xu J,Cherrier MC,Webb PJ,Semple G,Sage CR,Knudsen J,Chen R,Luo WL,Caro L,Cote J,Lai E,Wagner J,Taggart AK,Carballo-Jane E,Hammond M,Collett

更新日期：2012-04-26 00:00:00

abstract：:Ac-Tyr298-Ala299-Gly300-Thr301-Val302-I le303-Asn304-Asp305-Leu306-OH (Ac-VZV R2-(298-306)) represents the acetylated form of the C-terminus of varicella-zoster virus (VZV) ribonucleotide reductase subunit 2 (R2). This peptide possesses a high degree of homology with the C-terminus nonapeptide of the herpes simplex vi...

journal_title：Journal of medicinal chemistry

authors： Gaudreau P,Brazeau P,Richer M,Cormier J,Langlois D,Langelier Y

更新日期：1992-01-24 00:00:00

abstract：:Aberrant activation of the MAPK pathway drives cell proliferation in multiple cancers. Inhibitors of BRAF and MEK kinases are approved for the treatment of BRAF mutant melanoma, but resistance frequently emerges, often mediated by increased signaling through ERK1/2. Here, we describe the fragment-based generation of E...

journal_title：Journal of medicinal chemistry

authors： Heightman TD,Berdini V,Braithwaite H,Buck IM,Cassidy M,Castro J,Courtin A,Day JEH,East C,Fazal L,Graham B,Griffiths-Jones CM,Lyons JF,Martins V,Muench S,Munck JM,Norton D,O'Reilly M,Palmer N,Pathuri P,Reader M,R

更新日期：2018-06-14 00:00:00

abstract：:The synthesis and biological evaluation of three classes of chain-modified derivatives of (+)-EHNA are described. Among the 5', 6'-unsaturated derivatives, the Z-isomer was the most potent inhibitor of adenosine deaminase (ADA) but 3-fold less active than (+)-EHNA. Several 9-aralkyladenines (ARADs) have been prepared,...

journal_title：Journal of medicinal chemistry

authors： Pragnacharyulu PV,Varkhedkar V,Curtis MA,Chang IF,Abushanab E

更新日期：2000-11-30 00:00:00

abstract：:Drugs exert desired and undesired effects based on their binding interactions with protein target(s) and off-target(s), providing evidence for drug efficacy and toxicity. Pioglitazone and rosiglitazone possess a common functional core, glitazone, which is considered a privileged scaffold upon which to build a drug sel...

journal_title：Journal of medicinal chemistry

authors： Hoffmann BR,El-Mansy MF,Sem DS,Greene AS

更新日期：2012-10-11 00:00:00

abstract：:A series of pseudodipeptide amides are described that inhibit Ras protein farnesyltransferase (PFTase). These inhibitors are truncated versions of the C-terminal tetrapeptide (CAAX motif) of Ras that serves as the signal sequence for PFTase-catalyzed protein farnesylation. In contrast to CAAX peptidomimetics previousl...

journal_title：Journal of medicinal chemistry

authors： deSolms SJ,Deana AA,Giuliani EA,Graham SL,Kohl NE,Mosser SD,Oliff AI,Pompliano DL,Rands E,Scholz TH

更新日期：1995-09-29 00:00:00

abstract：:Photodynamic therapy uses a combination of light, oxygen, and a photosensitizer to induce the death of malignant cells. To improve the selectivity of a photosensitizer toward cancerous cells that express gonadotropin-releasing hormone (GnRH) receptors, protoporphyrin IX (PpIX) was conjugated to a GnRH agonist, [d-Lys6...

journal_title：Journal of medicinal chemistry

authors： Rahimipour S,Ben-Aroya N,Ziv K,Chen A,Fridkin M,Koch Y

更新日期：2003-09-11 00:00:00

abstract：:P2X receptor activation protects in heart failure models. MRS2339 3, a 2-chloro-AMP derivative containing a (N)-methanocarba (bicyclo[3.1.0]hexane) system, activates this cardioprotective channel. Michaelis-Arbuzov and Wittig reactions provided phosphonate analogues of 3, expected to be stable in vivo due to the C-P b...

journal_title：Journal of medicinal chemistry

authors： Kumar TS,Zhou SY,Joshi BV,Balasubramanian R,Yang T,Liang BT,Jacobson KA

更新日期：2010-03-25 00:00:00

abstract：:Glycosylation of ethyl 3(5)-(bromomethyl)pyrazole-5(3)-carboxylate (3) and 3(5)-(bromomethyl)pyrazole-5(3)-carboxamide (4) with poly-O-acetylated sugars via an acid-catalyzed fusion method afforded the corresponding ethyl 3-(bromomethyl)pyrazole-5-carboxylate and 3-(bromomethyl)pyrazole-5-carboxamide substituted nucle...

journal_title：Journal of medicinal chemistry

authors： García-López MT,Herranz R,Alonso G

更新日期：1979-07-01 00:00:00

abstract：:Newly synthesized benzamide derivatives were evaluated for their inhibitory activity against histone deacetylase. The structure of these derivatives was unrelated to the known inhibitors, and IC(50) values of the active compounds were in the range of 2-50 microM. Structure-activity relationship on the benzanilide moie...

journal_title：Journal of medicinal chemistry

authors： Suzuki T,Ando T,Tsuchiya K,Fukazawa N,Saito A,Mariko Y,Yamashita T,Nakanishi O

更新日期：1999-07-29 00:00:00

abstract：:The sodium ion site is an allosteric site conserved among many G protein-coupled receptors (GPCRs). Amiloride 1 and 5-(N,N-hexamethylene)amiloride 2 (HMA) supposedly bind in this sodium ion site and can influence orthosteric ligand binding. The availability of a high-resolution X-ray crystal structure of the human ade...

journal_title：Journal of medicinal chemistry

authors： Massink A,Louvel J,Adlere I,van Veen C,Huisman BJ,Dijksteel GS,Guo D,Lenselink EB,Buckley BJ,Matthews H,Ranson M,Kelso M,IJzerman AP

更新日期：2016-05-26 00:00:00

abstract：:A series of cis and trans bicyclic lactones was prepared as congeners of podophyllotoxin (1) and evaluated as antimitotic agents both in cell cultures grown in vitro and in an in vitro protein binding assay. All compounds displayed insignificant activity-a result which may reflect insufficient structural similarity to...

journal_title：Journal of medicinal chemistry

authors： Smissman EE,Murray RJ,McChesney JD,Houston LL,Pazdernik TL

更新日期：1976-01-01 00:00:00

abstract：:Recently, we reported the identification of a novel class of pregnane-X-receptor (PXR) agonists, solomonsterols A and B, isolated from the marine sponge Theonella swinhoei. Preliminary pharmacological studies demonstrated that these natural compounds are potential leads for the treatment of human disorders characteriz...

journal_title：Journal of medicinal chemistry

authors： Sepe V,Ummarino R,D'Auria MV,Mencarelli A,D'Amore C,Renga B,Zampella A,Fiorucci S

更新日期：2011-07-14 00:00:00

abstract：:A series of 1-aminopropan-2-ols were synthesized and evaluated against two strains of malaria, Plasmodium falciparum FCR3 (chloroquine-resistant) and 3D7 (chloroquine-sensitive). Microwave-assisted ring opening of epoxides (aryl and alkyl glycidyl ethers, glycidol, epichlorohydrin) with various amines without catalyst...

journal_title：Journal of medicinal chemistry

authors： Robin A,Brown F,Bahamontes-Rosa N,Wu B,Beitz E,Kun JF,Flitsch SL

更新日期：2007-08-23 00:00:00

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：:A series of heterocyclic quinones, 6-substituted and 6,7-disubstituted 4-(alkylamino)-5,8-quinazolinediones, have been synthesized in order to evaluate their in vitro cytotoxicity on L1210 leukemia cells. Among 14 derivatives that have been prepared and studied for the structure-activity relationship, the most potent ...

journal_title：Journal of medicinal chemistry

authors： Giorgi-Renault S,Renault J,Gebel-Servolles P,Baron M,Paoletti C,Cros S,Bissery MC,Lavelle F,Atassi G

更新日期：1991-01-01 00:00:00

abstract：:Conformational and molecular mechanics studies of a new series of tricyclic ligands with affinity for either the dopamine D2 receptor or the 5-HT1A receptor, or both, has enabled us to elaborate considerably on previous pharmacophore models for these receptors. The new tricyclic ligands are either angular, 2,3,3a,4,5,...

journal_title：Journal of medicinal chemistry

authors： Chidester CG,Lin CH,Lahti RA,Haadsma-Svensson SR,Smith MW

更新日期：1993-05-14 00:00:00

abstract：:A novel series of nonpeptidic angiotensin II (AII) receptor antagonists is reported, derived from linkage of the biphenylcarboxylic acid or biphenylyltetrazole moiety found in previously described antagonists via a methyleneoxy chain to the 4-position of a 2-alkyl quinoline. When evaluated in an in vitro binding assay...

journal_title：Journal of medicinal chemistry

authors： Bradbury RH,Allott CP,Dennis M,Fisher E,Major JS,Masek BB,Oldham AA,Pearce RJ,Rankine N,Revill JM

更新日期：1992-10-30 00:00:00

abstract：:The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and NK cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activat...

journal_title：Journal of medicinal chemistry

authors： Martin MW,Newcomb J,Nunes JJ,McGowan DC,Armistead DM,Boucher C,Buchanan JL,Buckner W,Chai L,Elbaum D,Epstein LF,Faust T,Flynn S,Gallant P,Gore A,Gu Y,Hsieh F,Huang X,Lee JH,Metz D,Middleton S,Mohn D,Morgenster

更新日期：2006-08-10 00:00:00