Discovery of (5S,6S,9R)-5-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate (BMS-927711): an oral calcitonin gene-related peptide (CGRP) antagonist in c

abstract：:Isocitrate dehydrogenases 1 and 2 (IDH1/2) are homodimeric enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG) in the tricarboxylic acid cycle. However, mutant IDH1/2 (mIDH1/2) reduces α-KG to the oncometabolite 2-hydroxyglutarate (2-HG). High levels of 2-HG competitively inhibit the α-KG-depe...

journal_title：Journal of medicinal chemistry

authors： Ma T,Zou F,Pusch S,Xu Y,von Deimling A,Zha X

更新日期：2018-10-25 00:00:00

abstract：:N,N-Dialkylated leucine enkephalin analogues containing melphalan (Mel) in place of Phe4 were synthesized as potentially irreversible antagonists of the delta opioid receptor. These compounds, along with the corresponding Phe4 peptides, were tested for both agonist and antagonist activity in the GPI and MVD smooth mus...

journal_title：Journal of medicinal chemistry

authors： Lovett JA,Portoghese PS

更新日期：1987-09-01 00:00:00

abstract：:The synthesis and the biological and pharmacological evaluation of several 14-phenylpropoxy analogues of 14-methoxymetopon are described. Most of the new compounds were nonselective and exhibited binding affinities in the subnanomolar or low nanomolar range at opioid receptors mu, kappa, delta), with 14-phenylpropoxym...

journal_title：Journal of medicinal chemistry

authors： Schütz J,Spetea M,Koch M,Aceto MD,Harris LS,Coop A,Schmidhammer H

更新日期：2003-09-11 00:00:00

abstract：:MMP-12 plays a significant role in airway inflammation and remodeling. Increased expression and production of MMP-12 have been observed in the lungs of asthmatic patients. Compound 27 was identified as a potent and selective MMP-12 inhibitor possessing good physicochemical properties. In pharmacological studies, the c...

journal_title：Journal of medicinal chemistry

authors： Li W,Li J,Wu Y,Rancati F,Vallese S,Raveglia L,Wu J,Hotchandani R,Fuller N,Cunningham K,Morgan P,Fish S,Krykbaev R,Xu X,Tam S,Goldman SJ,Abraham W,Williams C,Sypek J,Mansour TS

更新日期：2009-09-10 00:00:00

abstract：:The limited number of drug classes licensed for treatment of influenza virus (Flu), together with the continuous emergence of viral variants and drug resistant mutants, highlights the urgent need to find antivirals with novel mechanisms of action. In this context, the viral RNA-dependent RNA polymerase (RdRP) subunits...

journal_title：Journal of medicinal chemistry

authors： Massari S,Nannetti G,Goracci L,Sancineto L,Muratore G,Sabatini S,Manfroni G,Mercorelli B,Cecchetti V,Facchini M,Palù G,Cruciani G,Loregian A,Tabarrini O

更新日期：2013-12-27 00:00:00

abstract：:A number of bis(diazeniumdiolates) that we designed to release up to 4 mol of nitric oxide (NO) and that are structural analogues of the NO prodrug and anticancer lead compound O(2)-{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N,N-dimethylamino)diazen-1-ium-1,2- diolate (PABA/NO) were synthesized and studied...

journal_title：Journal of medicinal chemistry

authors： Andrei D,Maciag AE,Chakrapani H,Citro ML,Keefer LK,Saavedra JE

更新日期：2008-12-25 00:00:00

abstract：:Intervention in integrin-mediated cell adhesion and integrin signaling pathways is an ongoing area of research in medicinal chemistry and drug development. One key element in integrin-ligand interaction is the coordination of the bivalent cation at the metal ion-dependent adhesion site (MIDAS) by a carboxylic acid fun...

journal_title：Journal of medicinal chemistry

authors： Bollinger M,Manzenrieder F,Kolb R,Bochen A,Neubauer S,Marinelli L,Limongelli V,Novellino E,Moessmer G,Pell R,Lindner W,Fanous J,Hoffman A,Kessler H

更新日期：2012-01-26 00:00:00

abstract：:The synthesis of hybrid "cationic metalloporphyrin-intercalator" molecules is reported. These molecules are based on 9-methoxyellipticine as intercalator and tris-(4-N-methylpyridiniumyl)metalloporphyrins having a 4-aminophenyl or a 4-hydroxyphenyl group for the attachment of the linker. The effect of the length of li...

journal_title：Journal of medicinal chemistry

authors： Ding L,Etemad-Moghadam G,Cros S,Auclair C,Meunier B

更新日期：1991-03-01 00:00:00

abstract：:Structure for the adduct of carbonic anhydrase II with 1-N-(4-sulfamoylphenyl-ethyl)-2,4,6-trimethylpyridinium perchlorate, a membrane-impermeant antitumor sulfonamide, is reported. The phenylethyl moiety fills the active site, making van der Waals interactions with side chains of Gln192, Val121, Phe131, Leu198, Thr20...

journal_title：Journal of medicinal chemistry

authors： Menchise V,De Simone G,Alterio V,Di Fiore A,Pedone C,Scozzafava A,Supuran CT

更新日期：2005-09-08 00:00:00

abstract：:We synthesized 5-substituted pyrrolo[2,3-d]pyrimidine antifolates (compounds 5-10) with one-to-six bridge carbons and a benozyl ring in the side chain as antitumor agents. Compound 8 with a 4-carbon bridge was the most active analogue and potently inhibited proliferation of folate receptor (FR) α-expressing Chinese ha...

journal_title：Journal of medicinal chemistry

authors： Mitchell-Ryan S,Wang Y,Raghavan S,Ravindra MP,Hales E,Orr S,Cherian C,Hou Z,Matherly LH,Gangjee A

更新日期：2013-12-27 00:00:00

abstract：:We have found that (R,S)-1-(phenylthio)-aminopropane (4a), a synthetic alternate substrate for the terminal enzyme of norepinephrine biosynthesis, dopamine beta-monooxygenase (DBM), is both an indirect sympathomimetic and a potent antihypertensive agent in spontaneously hypertensive rats. We demonstrate herein that th...

journal_title：Journal of medicinal chemistry

authors： Herman HH,Husain PA,Colbert JE,Schweri MM,Pollock SH,Fowler LC,May SW

更新日期：1991-03-01 00:00:00

abstract：:A structure-based virtual screening (SBVS) was conducted on a ligand-supported homology model of the human histamine H4 receptor (hH4R). More than 8.7 million 3D structures derived from different vendor databases were investigated by docking to the hH4R binding site using FlexX. A total of 255 selected compounds were ...

journal_title：Journal of medicinal chemistry

authors： Kiss R,Kiss B,Könczöl A,Szalai F,Jelinek I,László V,Noszál B,Falus A,Keseru GM

更新日期：2008-06-12 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：:Aromatic side-chain analogues (arocalciferols 6-9) of the steroid hormone 1 alpha,25-dihydroxyvitamin D3 (1) were synthesized and biologically evaluated. The analogues were prepared by coupling the vitamin D A-ring enyne 14 with the appropriate enol triflate of a modified CD steroid fragment of the type 22. The result...

journal_title：Journal of medicinal chemistry

authors： Figadère B,Norman AW,Henry HL,Koeffler HP,Zhou JY,Okamura WH

更新日期：1991-08-01 00:00:00

abstract：:We have identified RWJ-671818 (8) as a novel, low molecular weight, orally active inhibitor of human alpha-thrombin (K(i) = 1.3 nM) that is potentially useful for the acute and chronic treatment of venous and arterial thrombosis. In a rat deep venous thrombosis model used to assess antithrombotic efficacy, oral admini...

journal_title：Journal of medicinal chemistry

authors： Lu T,Markotan T,Ballentine SK,Giardino EC,Spurlino J,Crysler CS,Brown K,Maryanoff BE,Tomczuk BE,Damiano BP,Shukla U,End D,Andrade-Gordon P,Bone RF,Player MR

更新日期：2010-02-25 00:00:00

abstract：:Novel classes of antimalarial drugs are needed due to emerging drug resistance. Azithromycin, the first macrolide investigated for malaria treatment and prophylaxis, failed as a single agent and thus novel analogues were envisaged as the next generation with improved activity. We synthesized 42 new 9a-N substituted 15...

journal_title：Journal of medicinal chemistry

authors： Perić M,Fajdetić A,Rupčić R,Alihodžić S,Ziher D,Bukvić Krajačić M,Smith KS,Ivezić-Schönfeld Z,Padovan J,Landek G,Jelić D,Hutinec A,Mesić M,Ager A,Ellis WY,Milhous WK,Ohrt C,Spaventi R

更新日期：2012-02-09 00:00:00

abstract：:A series of cyclopropane-based conformationally restricted analogues of histamine, the "folded" cis-analogues, i.e., (1S,2R)-2-(aminomethyl)-1-(1H-imidazol-4-yl)cyclopropane (11), (1S,2S)-2-(2-aminoethyl)-1-(1H-imidazol-4-yl)cyclopropane (13), and their enantiomers ent-11 and ent-13, and the "extended" trans-analogues...

journal_title：Journal of medicinal chemistry

authors： Kazuta Y,Hirano K,Natsume K,Yamada S,Kimura R,Matsumoto S,Furuichi K,Matsuda A,Shuto S

更新日期：2003-05-08 00:00:00

abstract：:The problem of structure-activity relationships in sulfonamide type compounds is tackled on the ground that both bacteriostatic activities and structural indices must be referred to the specific individual forms assumed by sulfa drugs in the active solutions. The frequency value of the symmetric stretching mode of the...

journal_title：Journal of medicinal chemistry

authors： Rastelli,De Benedetti P,Battistuzzi GG,Albasini A

更新日期：1975-10-01 00:00:00

abstract：:Cyclin-dependent kinase 2 (CDK2) drives the progression of cells into the S- and M-phases of the cell cycle. CDK2 activity is largely dispensable for normal development, but it is critically associated with tumor growth in multiple cancer types. Although the role of CDK2 in tumorigenesis has been controversial, emergi...

journal_title：Journal of medicinal chemistry

authors： Tadesse S,Caldon EC,Tilley W,Wang S

更新日期：2019-05-09 00:00:00

abstract：:Molecular modeling methods have been used to design a novel series of conformationally constrained cyclic peptide inhibitors of human renin. Three goals were defined: enhanced inhibitory potency, high specificity for renin, and increased metabolic stability. Three cyclic compounds were synthesized with ring sizes 10, ...

journal_title：Journal of medicinal chemistry

authors： Sham HL,Bolis G,Stein HH,Fesik SW,Marcotte PA,Plattner JJ,Rempel CA,Greer J

更新日期：1988-02-01 00:00:00

abstract：:Starting from a simple chalcone template, structure-activity relationship (SAR) studies led to a series of carboxylated, heteroaryl-substituted chalcone derivatives as novel, potent inhibitors of vascular cell adhesion molecule-1 (VCAM-1) expression. Correlations between lipophilicity determined by calculated logP val...

journal_title：Journal of medicinal chemistry

authors： Meng CQ,Ni L,Worsencroft KJ,Ye Z,Weingarten MD,Simpson JE,Skudlarek JW,Marino EM,Suen KL,Kunsch C,Souder A,Howard RB,Sundell CL,Wasserman MA,Sikorski JA

更新日期：2007-03-22 00:00:00

abstract：:A series of 7 alpha-methoxy-7 beta-amido-3-chloro-3-cephem-4-carboxylic acids was prepared and evaluated for biological activity. When compared with the parent 7-non-methoxy analogues, these new 7 alpha-methoxy-3-chloro cephalosporins displayed diminished antimicrobial activity. ...

journal_title：Journal of medicinal chemistry

authors： Pfeil-Doyle J,Kukolja S

更新日期：1988-10-01 00:00:00

abstract：:As part of a continuing search for specific inhibitors of the enzymes involved in polyamine biosynthesis, we have designed and synthesized a multisubstrate adduct inhibitor, S-adenosyl-1,12-diamino-3-thio-9-azadodecane (AdoDATAD), in which critical portions of the nucleophilic aminopropyl acceptor are covalently linke...

journal_title：Journal of medicinal chemistry

authors： Woster PM,Black AY,Duff KJ,Coward JK,Pegg AE

更新日期：1989-06-01 00:00:00

abstract：:The inclusion of an azaspiroketal Mannich base in the membrane targeting antitubercular 6-methoxy-1- n-octyl-1 H-indole scaffold resulted in analogs with improved selectivity and submicromolar activity against Mycobacterium tuberculosis H37Rv. The potency enhancing properties of the spiro-fused ring motif was affirmed...

journal_title：Journal of medicinal chemistry

authors： Nyantakyi SA,Li M,Gopal P,Zimmerman M,Dartois V,Gengenbacher M,Dick T,Go ML

更新日期：2018-07-12 00:00:00

abstract：:The identification of a series of imidazo[1,2-b][1,2,4]triazines with high affinity and functional selectivity for the GABA(A) alpha3-containing receptor subtype is described, leading to the identification of a clinical candidate, 11. Compound 11 shows good bioavailability and half-life in preclinical species, and it ...

journal_title：Journal of medicinal chemistry

authors： Russell MG,Carling RW,Street LJ,Hallett DJ,Goodacre S,Mezzogori E,Reader M,Cook SM,Bromidge FA,Newman R,Smith AJ,Wafford KA,Marshall GR,Reynolds DS,Dias R,Ferris P,Stanley J,Lincoln R,Tye SJ,Sheppard WF,Sohal B,

更新日期：2006-02-23 00:00:00

abstract：:The specificity of nucleic acids' binders is crucial for developing this kind of drug, especially for novel G-quadruplexes' binders. Quindoline derivatives have been developed as G-quadruplex stabilizers with good interactive activities. In order to improve the selectivity and binding affinity of quindoline derivative...

journal_title：Journal of medicinal chemistry

authors： Zeng DY,Kuang GT,Wang SK,Peng W,Lin SL,Zhang Q,Su XX,Hu MH,Wang H,Tan JH,Huang ZS,Gu LQ,Ou TM

更新日期：2017-07-13 00:00:00

abstract：:To find Delta(8)-Delta(7) sterol isomerase (EBP) selective ligands, various arylpiperazines previously studied and structurally related to some sigma receptors ligands were preliminarily screened. Consequently, a novel series of 2- or 2,6-disubstituted (CH(3), CH(3)O, Cl, F) cis- and trans-4-(4-aryl)cyclohexyl-1-(2-py...

journal_title：Journal of medicinal chemistry

authors： Berardi F,Abate C,Ferorelli S,de Robertis AF,Leopoldo M,Colabufo NA,Niso M,Perrone R

更新日期：2008-12-11 00:00:00

abstract：:A series of cyclic pseudopeptides of the formula cyclo(Leu psi[CH2NH]Xaa-Gln-Trp-Phe-beta Ala), where Xaa represents the residue of an alpha-amino acid, has been synthesized in order to establish the role of the Xaa side chain for tachykinin NK-2 receptor antagonist activity. Syntheses have been carried out in solid p...

journal_title：Journal of medicinal chemistry

authors： Quartara L,Fabbri G,Ricci R,Patacchini R,Pestellini V,Maggi CA,Pavone V,Giachetti A,Arcamone F

更新日期：1994-10-14 00:00:00

abstract：:On the basis of our finding that the antitumor effect of 5-{4-[(1-methylcyclohexyl)methoxy]benzyl}thiazolidine-2,4-dione, a thiazolidinedione peroxisome proliferator-activated receptor (PPAR)γ agonist, was, in part, attributable to its ability to block glucose uptake independently of PPARγ, we used its PPARγ-inactive ...

journal_title：Journal of medicinal chemistry

authors： Wang D,Chu PC,Yang CN,Yan R,Chuang YC,Kulp SK,Chen CS

更新日期：2012-04-26 00:00:00

abstract：:We disclose a novel series of indenopyrazole-based cyclin-dependent kinase (CDK) inhibitors. Kinetic experiments confirmed our initial molecular modeling studies that the compounds are competitive with respect to adenosine 5'-triphosphate (ATP) and bind in the kinase ATP pocket. A unique combination of active pharmaco...

journal_title：Journal of medicinal chemistry

authors： Nugiel DA,Vidwans A,Etzkorn AM,Rossi KA,Benfield PA,Burton CR,Cox S,Doleniak D,Seitz SP

更新日期：2002-11-21 00:00:00