Novel 5-HT3 antagonists. Isoquinolinones and 3-aryl-2-pyridones.

abstract：:Thymidine phosphorylase/platelet-derived endothelial cell growth factor (TP/PD-ECGF) is an enzyme involved in thymidine metabolism and homeostasis, and its catalytic activity appears to play an important role in angiogenesis. Here we describe the cloning and expression of a His-tagged human TP/PD-ECGF and its assay wi...

journal_title：Journal of medicinal chemistry

authors： Focher F,Ubiali D,Pregnolato M,Zhi C,Gambino J,Wright GE,Spadari S

更新日期：2000-06-29 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

abstract：:The proprotein convertases (PCs) play an important role in protein precursor activation through processing at paired basic residues. However, significant substrate cleavage redundancy has been reported between PCs. The question remains whether specific PC inhibitors can be designed. This study describes the identifica...

journal_title：Journal of medicinal chemistry

authors： Levesque C,Fugère M,Kwiatkowska A,Couture F,Desjardins R,Routhier S,Moussette P,Prahl A,Lammek B,Appel JR,Houghten RA,D'Anjou F,Dory YL,Neugebauer W,Day R

更新日期：2012-12-13 00:00:00

abstract：:Studies of molecular structure-carcinogenicity relations for a set of 157 aromatic amines are reported. A computer-assisted approach using pattern-recognition methods was used to develop a series of discriminants for aromatic amino carcinogenic potential. The 157 compounds were divided into subsets according to tumor ...

journal_title：Journal of medicinal chemistry

authors： Yuta K,Jurs PC

更新日期：1981-03-01 00:00:00

abstract：:Several optically active N-(indol-3-ylglyoxylyl)amino acid derivatives were synthesized and tested for [3H]flunitrazepam displacing activity in bovine brain membranes. IC50 values were measured and revealed that the D form of the amino acid moiety of the compounds was more potent than both the L form and racemic form,...

journal_title：Journal of medicinal chemistry

authors： Primofiore G,Marini AM,Da Settimo F,Martini C,Bardellini A,Giannaccini G,Lucacchini A

更新日期：1989-12-01 00:00:00

abstract：:A pair of enantiomeric Pt(II) complexes, [Pt(R-ahaz)Cl2] and [Pt(S-ahaz)Cl2] (ahaz = 3-aminohexahydroazepine), has been investigated for their ability to bind enantioselectively to DNA. Improved synthetic procedures were developed for preparing both the ligands and the Pt complexes. The structure of the complex of the...

journal_title：Journal of medicinal chemistry

authors： Fenton RR,Easdale WJ,Er HM,O'Mara SM,McKeage MJ,Russell PJ,Hambley TW

更新日期：1997-03-28 00:00:00

abstract：:Compound 1 (SKI-606, bosutinib), a 7-alkoxy-4-[(2,4-dichloro-5-methoxyphenyl)amino]-3-quinolinecarbonitrile, is a potent inhibitor of Src kinase activity. We previously reported that analogs of 1 with thiophene groups at C-7 retained the Src activity of the parent compound. The corresponding C-7 furan analogs were pre...

journal_title：Journal of medicinal chemistry

authors： Boschelli DH,Wu B,Ye F,Wang Y,Golas JM,Lucas J,Boschelli F

更新日期：2006-12-28 00:00:00

abstract：:We have previously shown [Cys-Trp-Arg-Nva-Arg-Tyr-NH(2)](2), 1, to be a moderately selective neuropeptide Y (NPY) Y(4) receptor agonist. Toward improving the selectivity and potency for Y(4) receptors, we studied the effects of dimerizing H-Trp-Arg-Nva-Arg-Tyr-NH(2) using various diamino-dicarboxylic acids containing ...

journal_title：Journal of medicinal chemistry

authors： Balasubramaniam A,Mullins DE,Lin S,Zhai W,Tao Z,Dhawan VC,Guzzi M,Knittel JJ,Slack K,Herzog H,Parker EM

更新日期：2006-04-20 00:00:00

abstract：:The labeling of proteins with ubiquitin/ubiquitin-like (Ubl) proteins is crucial for several physiological processes and in the onset of various diseases. Recently, targeting ubiquitin protein labeling has shifted toward the use of allosteric mechanisms over classical activity-based approaches. Allosteric enzyme regul...

journal_title：Journal of medicinal chemistry

authors： Paiva SL,da Silva SR,de Araujo ED,Gunning PT

更新日期：2018-01-25 00:00:00

abstract：:A series of highly potent and specific fibrinogen receptor antagonists have been discovered and optimized through structural modification of the novel amidinoindole and benzofuran compounds, I and II. Systematic linker optimization afforded the amidinobenzofuran-containing inhibitor 29, which displayed an IC50 value o...

journal_title：Journal of medicinal chemistry

authors： Su T,Naughton MA,Smyth MS,Rose JW,Arfsten AE,McCowan JR,Jakubowski JA,Wyss VL,Ruterbories KJ,Sall DJ,Scarborough RM

更新日期：1997-12-19 00:00:00

abstract：:A series of benzyl-substituted phthalonitriles, substituted at the 3-, 4-, and 4,5-positions, underwent varied condensations with phthalonitrile to give a series of protected (monohydroxy- and polyhydroxyphthalocyaninato)zinc(II) derivatives which were readily cleaved to give several hydroxyphthalocyanines (ZnPc) (pht...

journal_title：Journal of medicinal chemistry

authors： Hu M,Brasseur N,Yildiz SZ,van Lier JE,Leznoff CC

更新日期：1998-05-21 00:00:00

abstract：:The currently accepted mechanism of trioxane antimalarial action involves generation of free radicals within or near susceptible sites probably arising from the production of distonic radical anions. An alternative mechanistic proposal involving the ionic scission of the peroxide group and consequent generation of a c...

journal_title：Journal of medicinal chemistry

authors： Drew MG,Metcalfe J,Dascombe MJ,Ismail FM

更新日期：2006-10-05 00:00:00

abstract：:A novel class of 2-(4-heterocyclylphenyl)-1,4-dihydropyridines (2-38) possessing antagonist activity against platelet activating factor (PAF) was prepared by the Hantzsch synthesis from a variety of ethyl 4'-heterocyclic-substituted benzoylacetates, aryl or heteroaryl aldehydes, and substituted 3-aminocrotonamides or ...

journal_title：Journal of medicinal chemistry

authors： Cooper K,Fray MJ,Parry MJ,Richardson K,Steele J

更新日期：1992-08-21 00:00:00

abstract：:A series of analogues of the potent and selective sigma receptor ligand 1,3-ditolylguanidine (DTG) were synthesized and demonstrated to have high affinity for the sigma receptor as measured by in vitro [3H]DTG displacement studies using guinea pig brain tissue. Three of these 1-aryl-3-(1-adamantyl)guanidines were radi...

journal_title：Journal of medicinal chemistry

authors： Wilson AA,Dannals RF,Ravert HT,Sonders MS,Weber E,Wagner HN Jr

更新日期：1991-06-01 00:00:00

abstract：:A novel series of C-3 substituted 4,6-dichloroindole-2-carboxylic acids was synthesized to investigate the influence of different hydrogen-bond donor and acceptor groups at this specific position on the affinity to the glycine site of the NMDA receptor. These novel 3-indolylmethyl derivatives with ring-open (amines, s...

journal_title：Journal of medicinal chemistry

authors： Jansen M,Potschka H,Brandt C,Löscher W,Dannhardt G

更新日期：2003-01-02 00:00:00

abstract：:Despite the availability of numerous antiepileptic drugs, 20-30% of epileptic patients are pharmacoresistant with seizures not appropriately controlled. Consequently, new strategies to address this unmet medical need are required. T-type calcium channels play a key role in neuronal excitability and burst firing, and s...

journal_title：Journal of medicinal chemistry

authors： Siegrist R,Pozzi D,Jacob G,Torrisi C,Colas K,Braibant B,Mawet J,Pfeifer T,de Kanter R,Roch C,Kessler M,Moon R,Corminboeuf O,Bezençon O

更新日期：2016-12-08 00:00:00

abstract：:GPR52 is an orphan G protein-coupled receptor (GPCR) that has been recently implicated as a potential drug target of Huntington's disease (HD), an incurable monogenic neurodegenerative disorder. In this research, we found that striatal knockdown of GPR52 reduces mHTT levels in adult HdhQ140 mice, validating GPR52 as a...

journal_title：Journal of medicinal chemistry

authors： Wang C,Zhang YF,Guo S,Zhao Q,Zeng Y,Xie Z,Xie X,Lu B,Hu Y

更新日期：2021-01-28 00:00:00

abstract：:Both in-house human genetic and literature data have converged on the identification of leukotriene 4 hydrolase (LTA(4)H) as a key target for the treatment of cardiovascular disease. We combined fragment-based crystallography screening with an iterative medicinal chemistry effort to optimize inhibitors of LTA(4)H. Lig...

journal_title：Journal of medicinal chemistry

authors： Sandanayaka V,Mamat B,Mishra RK,Winger J,Krohn M,Zhou LM,Keyvan M,Enache L,Sullins D,Onua E,Zhang J,Halldorsdottir G,Sigthorsdottir H,Thorlaksdottir A,Sigthorsson G,Thorsteinnsdottir M,Davies DR,Stewart LJ,Zembower DE

更新日期：2010-01-28 00:00:00

abstract：:The agonist selectivities of central (medullary) and peripheral (vascular) alpha-adrenoceptors were compared in order to investigate a possible similarity among these two alpha-adrenoceptor populations. Linear regression equations were derived between the alpha-adrenergic potencies, mediated by these two types of alph...

journal_title：Journal of medicinal chemistry

authors： Timmermans PB,de Jonge A,van Meel JC,Slothorst-Grisdijk FP,Lam E,van Zwieten PA

更新日期：1981-05-01 00:00:00

abstract：:Vitamin D receptor (VDR) antagonists prevent the VDR activation function helix 12 from folding into its active conformation, thus affecting coactivator recruitment and antagonizing the transcriptional regulation induced by 1α,25-dihydroxyvitamin D3. Here, we report the crystal structure of the zebrafish VDR ligand-bin...

journal_title：Journal of medicinal chemistry

authors： Belorusova AY,Chalhoub S,Rovito D,Rochel N

更新日期：2020-09-10 00:00:00

abstract：:2,5-Bis(4-guanylphenyl)-1,3-oxazole, 2,5-bis(4-guanylphenyl)-1,3,4-oxadiazole and -1,3,4-thiadiazole, and 3,6-bis(4-guanylphenyl)pyridazine and several of their "cyclic guanyl" analogues have been synthesized. 2,5-Bis(4-guanylphenyl)-1,3-oxazole and -1,3,4-thiadiazole showed good activity, whithout acute toxicity, aga...

journal_title：Journal of medicinal chemistry

authors： Das BP,Wallace RA,Boykin DW Jr

更新日期：1980-05-01 00:00:00

abstract：:In only four chemical steps from naturally occurring artemisinin (1), trioxane dimers 6 and 7 were prepared on a multigram scale in overall 32-44% yields. In mice, both isonicotinate N-oxide dimer 6 and isobutyric acid dimer 7 were considerably more antimalarially efficacious than clinically used sodium artesunate (2)...

journal_title：Journal of medicinal chemistry

authors： Posner GH,McRiner AJ,Paik IH,Sur S,Borstnik K,Xie S,Shapiro TA,Alagbala A,Foster B

更新日期：2004-02-26 00:00:00

abstract：:The ability of a series of substituted kynurenic acids, thienopyridinonecarboxylic acids, and related compounds to inhibit the binding of nerve growth factor (NGF) to the p75 NGF receptor (NGFR) was evaluated in a radioligand binding assay that utilized a biotinylated derivative of the extracellular domain of p75 NGFR...

journal_title：Journal of medicinal chemistry

authors： Jaen JC,Laborde E,Bucsh RA,Caprathe BW,Sorenson RJ,Fergus J,Spiegel K,Marks J,Dickerson MR,Davis RE

更新日期：1995-10-27 00:00:00

abstract：:A series of new spiroglumide amido acid derivatives was synthesized and evaluated for their ability to inhibit the binding of cholecystokinin (CCK) to guinea pig brain cortex (CCKB receptors) and peripheral rat pancreatic acini (CCKA receptors), as well as to inhibit in vitro the gastrin-induced Ca2+ increase in rabbi...

journal_title：Journal of medicinal chemistry

authors： Makovec F,Peris W,Frigerio S,Giovanetti R,Letari O,Mennuni L,Revel L

更新日期：1996-01-05 00:00:00

abstract：:N-Acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. We found that administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure, indicating that this pathway might be useful for treating obesity and associated...

journal_title：Journal of medicinal chemistry

authors： Lin H,Long JZ,Roche AM,Svensson KJ,Dou FY,Chang MR,Strutzenberg T,Ruiz C,Cameron MD,Novick SJ,Berdan CA,Louie SM,Nomura DK,Spiegelman BM,Griffin PR,Kamenecka TM

更新日期：2018-04-12 00:00:00

abstract：:Two complete and two partial structure-activity relationship scans of the active fragment of human growth hormone-releasing hormone, [Nle27]-hGHRH(1-29)-NH2, have identified potent agonists in vitro. Single-point replacement of each amino acid by alanine led to the identification of [Ala8]-, [Ala9]-, [Ala15]- (Felix e...

journal_title：Journal of medicinal chemistry

authors： Cervini LA,Donaldson CJ,Koerber SC,Vale WW,Rivier JE

更新日期：1998-02-26 00:00:00

abstract：:Treatment of the sodium salt of 4-chloro-2-(methylthio)pyrrolo[2,3-d]pyrimidine (2) with (2-acetoxyethoxy)methyl bromide (3) has provided 4-chloro-2-(methylthio)-7[(2-acetoxyethoxy)methyl]pyrrolo[2,3- d]pyrimidine (4). Ammonolysis of 4 at room temperature gave 4-chloro-2-(methylthio)-7-[(2-hydroxyethoxy)methyl]pyrrolo...

journal_title：Journal of medicinal chemistry

authors： Saxena NK,Hagenow BM,Genzlinger G,Turk SR,Drach JC,Townsend LB

更新日期：1988-08-01 00:00:00

abstract：:Four highly charged, water soluble platinum-acridine bisintercalating agents have been synthesized. Depending on the cis/trans isomerism of the metal and the nature of the acridine side chains, bisintercalation induces/stabilizes the classical Watson-Crick B-form or a non-B-form. Circular dichroism spectra and chemica...

journal_title：Journal of medicinal chemistry

authors： Choudhury JR,Guddneppanavar R,Saluta G,Kucera GL,Bierbach U

更新日期：2008-06-12 00:00:00

abstract：:Autoimmune deficiency and destruction in either β-cell mass or function can cause insufficient insulin levels and, as a result, hyperglycemia and diabetes. Thus, promoting β-cell proliferation could be one approach toward diabetes intervention. In this report we describe the discovery of a potent and selective DYRK1A ...

journal_title：Journal of medicinal chemistry

authors： Liu YA,Jin Q,Zou Y,Ding Q,Yan S,Wang Z,Hao X,Nguyen B,Zhang X,Pan J,Mo T,Jacobsen K,Lam T,Wu TY,Petrassi HM,Bursulaya B,DiDonato M,Gordon WP,Liu B,Baaten J,Hill R,Nguyen-Tran V,Qiu M,Zhang YQ,Kamireddy A,

更新日期：2020-03-26 00:00:00

abstract：:Nineteen derivatives of adenosine 5'-phosphate (AMP) bearing acylaminomethyl, acetoxy, or alkylaminomethyl substituents on the phosphate-ribose bridge (5' and O-5' positions) of AMP together with 2',3'-O-ethylidene, 2',3',-O-isopropylidene, and 2',3'-di-O-acetyl derivatives of AMP have been synthesized. Their substrat...

journal_title：Journal of medicinal chemistry

authors： Hampton A,Slotin LA,Kappler F,Sasaki T,Perini F

更新日期：1976-12-01 00:00:00