Steroidal alpha-methylene delta-lactones as potential antitumor agents.

abstract：:9,11-Secoestradiol (9) and 11-hydroxy-9,11-secoestradiol (12) have been synthesized starting from 17-acetoxyestradiol 3-methyl ether (1) and found to possess significant antifertility activity in rats. 3-Methoxy-9,11-seco-9-oxo-17beta-acetoxyestra-1,3,5(10)-trien-11-oic acid (2), prepared by CrO3 oxidation of 1, on h...

journal_title：Journal of medicinal chemistry

authors： Kole P,Ray S,Kamboj VP,Anand N

更新日期：1975-07-01 00:00:00

abstract：:A series of 4-amino[1,2,4]triazolo[4,3-a]quinoxalines has been prepared. Many compounds from this class reduce immobility in Porsolt's behavioral despair model in rats upon acute administration and may therefore have therapeutic potential as novel and rapid acting antidepressant agents. Optimal activity in this test i...

journal_title：Journal of medicinal chemistry

authors： Sarges R,Howard HR,Browne RG,Lebel LA,Seymour PA,Koe BK

更新日期：1990-08-01 00:00:00

abstract：:Malaria represents a significant health issue, and novel and effective drugs are needed to address parasite resistance that has emerged to the current drug arsenal. Antimalarial drug discovery has historically benefited from a whole-cell (phenotypic) screening approach to identify lead molecules. This approach has bee...

journal_title：Journal of medicinal chemistry

authors： Chatterjee AK

更新日期：2013-10-24 00:00:00

abstract：:The Mediterranean tunicate Stolonica socialis contains a new class of powerful cytotoxic acetogenins, generically named stolonoxides. In this paper, which also details the isolation and chemical characterization of a minor component (3a) of the tunicate extract, we report the potent inhibitory activity (IC(50) < 1 mic...

journal_title：Journal of medicinal chemistry

authors： Fontana A,Cimino G,Gavagnin M,González MC,Estornell E

更新日期：2001-07-05 00:00:00

abstract：:A class of drugs in use for treating type II diabetes mellitus (T2D), typified by the pseudotetrasaccharide acarbose, act by inhibiting the alpha-glucosidase activity present in pancreatic secretions and in the brush border of the small intestine. Herein, we report the synthesis of a series of 4-substituted 1,2,3-tria...

journal_title：Journal of medicinal chemistry

authors： Ferreira SB,Sodero AC,Cardoso MF,Lima ES,Kaiser CR,Silva FP,Ferreira VF

更新日期：2010-03-25 00:00:00

abstract：:Recently we have described the antitumor activities of 2-benzoxazolylhydrazones derived from 2-formyl and 2-acetylpyridines. In search of a more efficacious analogue, compounds in which the 2-acetylpyridine moiety has been replaced by 2-acylpyridine and alpha-(N)-acetyldiazine/quinoline groups have been synthesized. T...

journal_title：Journal of medicinal chemistry

authors： Easmon J,Pürstinger G,Thies KS,Heinisch G,Hofmann J

更新日期：2006-10-19 00:00:00

abstract：:2,9beta-Dimethyl-2'-hydroxy-6,7-benzomorphan (18) has been synthesized from m-methoxyphenylacetone (6a) or m-methoxyphenylacetonitrile (1) via bromo-alpha-tetralone (10). Isomeric bromo-alpha-tetralone 9, instead of undergoing cyclization to a 6,7-benzomorphan, gave aromatization product 12. The structures and stereoc...

journal_title：Journal of medicinal chemistry

authors： Inoue H,O-ishi T,May EL

更新日期：1975-08-01 00:00:00

abstract：:Multiple recent studies have focused on unraveling the content of the medicinal chemist's toolbox. Here, we present an investigation of chemical reactions and molecules retrieved from U.S. patents over the past 40 years (1976-2015). We used a sophisticated text-mining pipeline to extract 1.15 million unique whole reac...

journal_title：Journal of medicinal chemistry

authors： Schneider N,Lowe DM,Sayle RA,Tarselli MA,Landrum GA

更新日期：2016-05-12 00:00:00

abstract：:c-Met has emerged as an attractive target for targeted cancer therapy because of its abnormal activation in many cancer cells. To identify high potent and selective c-Met inhibitors, we started with profiling the potency and in vitro metabolic stability of a reported hit 7. By rational design, a novel sulfonylpyrazolo...

journal_title：Journal of medicinal chemistry

authors： Ma Y,Sun G,Chen D,Peng X,Chen YL,Su Y,Ji Y,Liang J,Wang X,Chen L,Ding J,Xiong B,Ai J,Geng M,Shen J

更新日期：2015-03-12 00:00:00

abstract：:An application of the neural network to quantitative structure-activity relationship (QSAR) analysis has been studied. The new method was compared with the linear multiregression analysis in various ways. It was found that the neural network can be a potential tool in the routine work of QSAR analysis. The mathematica...

journal_title：Journal of medicinal chemistry

authors： Aoyama T,Suzuki Y,Ichikawa H

更新日期：1990-09-01 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：:Structure and energetics of the Src Src Homology 2 (SH2) domain binding with the recognition phosphopeptide pYEEI and its mutants are studied by a hierarchical computational approach. The proposed structure prediction strategy includes equilibrium sampling of the peptide conformational space by simulated tempering dyn...

journal_title：Journal of medicinal chemistry

authors： Verkhivker GM,Bouzida D,Gehlhaar DK,Rejto PA,Schaffer L,Arthurs S,Colson AB,Freer ST,Larson V,Luty BA,Marrone T,Rose PW

更新日期：2002-01-03 00:00:00

abstract：:New acetamidines structurally related to N-(3-(aminomethyl)benzyl)acetamidine (1, W1400) were designed as inhibitors of inducible nitric oxide synthase (iNOS). Six compounds were found to be selective for iNOS over endothelial nitric oxide synthase (eNOS), and among them, the most active and selective compound was the...

journal_title：Journal of medicinal chemistry

authors： Maccallini C,Patruno A,Besker N,Alì JI,Ammazzalorso A,De Filippis B,Franceschelli S,Giampietro L,Pesce M,Reale M,Tricca ML,Re N,Felaco M,Amoroso R

更新日期：2009-03-12 00:00:00

abstract：:Five series of pyrrolo[3,2-d]pyrimidines were synthesized and evaluated with respect to potency and selectivity toward multidrug resistance-associated protein 1 (MRP1, ABCC1). This transport protein is a major target to overcome multidrug resistance in cancer patients. We investigated differently substituted pyrrolopy...

journal_title：Journal of medicinal chemistry

authors： Schmitt SM,Stefan K,Wiese M

更新日期：2016-04-14 00:00:00

abstract：:Anthraquinone derivatives related to the moderately potent, nonselective P2Y(12) receptor antagonist reactive blue 2 (6) have been synthesized and optimized with respect to P2Y(12) receptor affinity. A radioligand binding assay utilizing human blood platelet membranes and the P2Y(12) receptor-selective antagonist radi...

journal_title：Journal of medicinal chemistry

authors： Baqi Y,Atzler K,Köse M,Glänzel M,Müller CE

更新日期：2009-06-25 00:00:00

abstract：:Self-organizing maps were trained to separate high- and low-active propafenone-type inhibitors of P-glycoprotein. The trained maps were subsequently used to identify highly active compounds in a virtual screen of the SPECS compound library. ...

journal_title：Journal of medicinal chemistry

authors： Kaiser D,Terfloth L,Kopp S,Schulz J,de Laet R,Chiba P,Ecker GF,Gasteiger J

更新日期：2007-04-05 00:00:00

abstract：:When cephalosporins exert their biological activity by reacting with bacterial enzymes, opening of the beta-lactam ring can lead to expulsion of the 3'-substituent. A series of cephalosporins was prepared in which antibacterial quinolones were linked to the 3'-position through a quaternary nitrogen. Like the 3'-ester-...

journal_title：Journal of medicinal chemistry

authors： Albrecht HA,Beskid G,Christenson JG,Durkin JW,Fallat V,Georgopapadakou NH,Keith DD,Konzelmann FM,Lipschitz ER,McGarry DH

更新日期：1991-02-01 00:00:00

abstract：:We present an analysis of the chemical fragments from lead-like ligands in the Protein Data Bank (PDB) that form hydrogen bonds to the side chains of Asp, Glu, Arg, and His, which are the most common residues found in ligand binding sites. A fragment is defined as the largest ring assembly containing the atoms involve...

journal_title：Journal of medicinal chemistry

authors： Chan AW,Laskowski RA,Selwood DL

更新日期：2010-04-22 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：:The endogenous peptides somatostatin (SRIF) and substance P comprise very different structures. Although both bind G-protein-coupled receptors, the SRIF receptors (SSTR 1-5) recognize SRIF and related peptides which retain its beta-turn such as the potent cyclic hexapeptide SRIF agonist L-363,301 (6a), but not substan...

journal_title：Journal of medicinal chemistry

authors： Hirschmann R,Yao W,Cascieri MA,Strader CD,Maechler L,Cichy-Knight MA,Hynes J Jr,van Rijn RD,Sprengeler PA,Smith AB 3rd

更新日期：1996-06-21 00:00:00

abstract：:Recently, FXIIa was highlighted as an original attractive target for the development of new anticoagulant drugs with low rates of therapy-related hemorrhages. In this work, we describe the development of a new series of 3-carboxamide-coumarins that are the first potent and selective nonpeptidic inhibitors of FXIIa. ...

journal_title：Journal of medicinal chemistry

authors： Robert S,Bertolla C,Masereel B,Dogné JM,Pochet L

更新日期：2008-06-12 00:00:00

abstract：:The 18 kDa translocator protein (TSPO) is a mitochondrial protein whose basal density is altered in several diseases, with the result that the evaluation of its expression levels by means of molecular imaging techniques represents a promising diagnostic approach. Experimental procedures using a labeled ligand often ca...

journal_title：Journal of medicinal chemistry

authors： Taliani S,Da Pozzo E,Bellandi M,Bendinelli S,Pugliesi I,Simorini F,La Motta C,Salerno S,Marini AM,Da Settimo F,Cosimelli B,Greco G,Novellino E,Martini C

更新日期：2010-05-27 00:00:00

abstract：:Multifunctional ligands with agonist bioactivities at μ/δ opioid receptors (MOR/DOR) and antagonist bioactivity at the neurokinin-1 receptor (NK1R) have been designed and synthesized. These peptide-based ligands are anticipated to produce better biological profiles (e.g., higher analgesic effect with significantly les...

journal_title：Journal of medicinal chemistry

authors： Giri AK,Apostol CR,Wang Y,Forte BL,Largent-Milnes TM,Davis P,Rankin D,Molnar G,Olson KM,Porreca F,Vanderah TW,Hruby VJ

更新日期：2015-11-12 00:00:00

abstract：:In an effort to identify selective ligands for the estrogen receptor subtype ERbeta, a series of aryl benzthiophenes was synthesized. In a radioligand binding assay and reporter gene assays in HeLa and SH-SY5Y cells, compounds were characterized as ERbeta-selective agonists. By targeting ERbeta in the brain, these com...

journal_title：Journal of medicinal chemistry

authors： Schopfer U,Schoeffter P,Bischoff SF,Nozulak J,Feuerbach D,Floersheim P

更新日期：2002-03-28 00:00:00

abstract：:Multidrug resistance (MDR) mediated by P-glycoprotein (Pgp) remains the major obstacle for successful treatment of cancer. Inhibition of Pgp transport is important for higher efficacy of anticancer drugs. Lipophilic cationogenic amines with at least one tertiary N atom, such as verapamil, are classical PgP-blocking ag...

journal_title：Journal of medicinal chemistry

authors： Sidorova TA,Nigmatov AG,Kakpakova ES,Stavrovskaya AA,Gerassimova GK,Shtil AA,Serebryakov EP

更新日期：2002-11-21 00:00:00

abstract：:Regioisomeric 3-carboxyisoxazolinyl prolines [CIP-A (+/-)-6 and CIP-B (+/-)-7] and 3-hydroxyisoxazolinyl prolines [(+/-)-8 and (+/-)-9] were synthesized and assayed for glutamate receptor activity. The tests were carried out in vitro by means of receptor binding techniques, second messenger assays, and the rat cortica...

journal_title：Journal of medicinal chemistry

authors： Conti P,De Amici M,De Sarro G,Rizzo M,Stensbøl TB,Bräuner-Osborne H,Madsen U,Toma L,De Micheli C

更新日期：1999-10-07 00:00:00

abstract：:HDM2 binds to an alpha-helical transactivation domain of p53, inhibiting its tumor suppressive functions. A miniaturized thermal denaturation assay was used to screen chemical libraries, resulting in the discovery of a novel series of benzodiazepinedione antagonists of the HDM2-p53 interaction. The X-ray crystal struc...

journal_title：Journal of medicinal chemistry

authors： Grasberger BL,Lu T,Schubert C,Parks DJ,Carver TE,Koblish HK,Cummings MD,LaFrance LV,Milkiewicz KL,Calvo RR,Maguire D,Lattanze J,Franks CF,Zhao S,Ramachandren K,Bylebyl GR,Zhang M,Manthey CL,Petrella EC,Pantoliano MW

更新日期：2005-02-24 00:00:00

abstract：:The compounds N6-allyl-, N6-isopropyl-, N6-propargyl-, and N6-(2-methylallyl)adenosine were prepared by reacting 6-chloropurine riboside with an excess of the corresponding amines in ethanol, in the presence of two acid acceptors resulting in virtually quantitative yields. The compounds showed biological activity in a...

journal_title：Journal of medicinal chemistry

authors： Fleysher MH,Bernacki RJ,Bullard GA

更新日期：1980-12-01 00:00:00

abstract：:Two 12-amino-6,7,8,11-tetrahydro-7,11-methanocycloocta[b]quinoline derivatives [9-Me(Et)] (syn-huprines) have been obtained by condensation of known 7-alkylbicyclo[3.3.1]non-6-en-3-ones with 2-(trifluoromethyl)aniline, followed by basic cyclization of the resulting imine, and chromatographic separation of the regioiso...

journal_title：Journal of medicinal chemistry

authors： Camps P,Gómez E,Muñoz-Torrero D,Badia A,Vivas NM,Barril X,Orozco M,Luque FJ

更新日期：2001-12-20 00:00:00

abstract：:The simulated binding profiles of acetylcholine, ACh, and the inhibitor (+/-)-2,3-dihydro-5,6- dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-on e hydrochloride (E2020), 1, and some of its analogs to acetylcholinesterase, AChE, were determined using full force field energetics and allowing complete co...

journal_title：Journal of medicinal chemistry

authors： Inoue A,Kawai T,Wakita M,Iimura Y,Sugimoto H,Kawakami Y

更新日期：1996-10-25 00:00:00