Cardiotonic agents. 5. 1,2-Dihydro-5-[4-(1H-imidazol-1-yl)phenyl]-6-methyl-2-oxo-3- pyridinecarbonitriles and related compounds. Synthesis and inotropic activity.

abstract：:Malaria continues to be a major global health problem, being particularly devastating in the African population under the age of five. Artemisinin-based combination therapies (ACTs) are the first-line treatment recommended by the WHO to treat Plasmodium falciparum malaria, but clinical resistance against them has alre...

journal_title：Journal of medicinal chemistry

authors： Keurulainen L,Vahermo M,Puente-Felipe M,Sandoval-Izquierdo E,Crespo-Fernández B,Guijarro-López L,Huertas-Valentín L,de las Heras-Dueña L,Leino TO,Siiskonen A,Ballell-Pages L,Sanz LM,Castañeda-Casado P,Jiménez-Díaz MB,Martínez

更新日期：2015-06-11 00:00:00

abstract：:A small library of boron-cluster- and metallacarborane-cluster-based ligands was designed, prepared, and tested for isoform-selective activation or inhibition of the three nitric oxide synthase isoforms. On the basis of the concept of creating a hydrophobic analogue of a natural substrate, a stable and nontoxic basic ...

journal_title：Journal of medicinal chemistry

authors： Kaplánek R,Martásek P,Grüner B,Panda S,Rak J,Masters BS,Král V,Roman LJ

更新日期：2012-11-26 00:00:00

abstract：:The synthesis and structure-activity relationships of a new class of vinylcephalosporins substituted with a lactamyl residue are described. These compounds show excellent activity against enterococci and retain the broad spectrum activity of third-generation cephalosporins such as ceftriaxone. ...

journal_title：Journal of medicinal chemistry

authors： Heinze-Krauss I,Angehrn P,Guerry P,Hebeisen P,Hubschwerlen C,Kompis I,Page MG,Richter HG,Runtz V,Stalder H,Weiss U,Wei CC

更新日期：1996-04-26 00:00:00

abstract：:We have previously identified phenylguanidine and phenyl-2-aminoimidazoline compounds as high affinity ligands with conflicting functional activity at the α2-adrenoceptor, a G-protein-coupled receptor with relevance in several neuropsychiatric conditions. In this paper we describe the design, synthesis, and pharmacolo...

journal_title：Journal of medicinal chemistry

authors： Kelly B,McMullan M,Muguruza C,Ortega JE,Meana JJ,Callado LF,Rozas I

更新日期：2015-01-22 00:00:00

abstract：:A systematic exploration of bioisosteric replacements for furan and thiophene cores in a series of potent A2BAR antagonists has been carried out using the nitrogen-walk approach. A collection of 42 novel alkyl 4-substituted-2-methyl-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylates, which contain 18 differe...

journal_title：Journal of medicinal chemistry

authors： Mallo-Abreu A,Prieto-Díaz R,Jespers W,Azuaje J,Majellaro M,Velando C,García-Mera X,Caamaño O,Brea J,Loza MI,Gutiérrez-de-Terán H,Sotelo E

更新日期：2020-07-23 00:00:00

abstract：:An approach to the development of new anticandidal drugs is described that employs peptides as carriers of toxic agents into cells. 5-Flurorcytosine (5-FC) was chosen as a toxic agent with which to prepare 5-FC-peptide conjugates as models to test the carrier proposal. Model compounds were synthesized and then tested ...

journal_title：Journal of medicinal chemistry

authors： Steinfeld AS,Naider F,Becker JM

更新日期：1979-09-01 00:00:00

abstract：:The synthesis and biological activities of a series of N-substituted cis-4a,5,6,7,8,8a-hexa- and cis-4a,5,8,8a-tetrahydro-2H-phthalazin-1-ones are described. It was found that compounds bearing a cycloalkyl group at the 2-position exhibit the highest PDE4 inhibitory activities (pIC(50) = 8.6-9.4). The N-cycloheptyl- a...

journal_title：Journal of medicinal chemistry

authors： Van der Mey M,Boss H,Hatzelmann A,Van der Laan IJ,Sterk GJ,Timmerman H

更新日期：2002-06-06 00:00:00

abstract：:We have developed a fast and robust computational method for prediction of antiviral activity in automated de novo design of HIV-1 reverse transcriptase inhibitors. This is a structure-based approach that uses a linear relation between activity and interaction energy with discrete orientation sampling and with localiz...

journal_title：Journal of medicinal chemistry

authors： de Jonge MR,Koymans LM,Vinkers HM,Daeyaert FF,Heeres J,Lewi PJ,Janssen PA

更新日期：2005-03-24 00:00:00

abstract：:A series of coumarins and the corresponding 2-thioxocoumarines were prepared and tested for their inhibition profiles against four physiologically relevant human carbonic anhydrases (hCAs, EC 4.2.1.1), isoforms hCA I, II, IX, and XII. The X-ray crystal structure of 6-hydroxy-2-thioxocoumarin bound to hCA II revealed a...

journal_title：Journal of medicinal chemistry

authors： Ferraroni M,Carta F,Scozzafava A,Supuran CT

更新日期：2016-01-14 00:00:00

abstract：:A series of 9-(hydroxyalkenyl)purines (adenines and 3-deazaadenines), which are analogues of neplanocin A, were synthesized. The analogues were tested as inhibitors of bovine liver and murine L929 cell S-adenosyhomocysteine (AdoHcy) hydrolase (EC 3.3.1.1) and as inhibitors of vaccinia virus replication in murine L929 ...

journal_title：Journal of medicinal chemistry

authors： Borcherding DR,Narayanan S,Hasobe M,McKee JG,Keller BT,Borchardt RT

更新日期：1988-09-01 00:00:00

abstract：:In a search for structurally new alpha(1)-adrenoreceptor (alpha(1)-AR) antagonists, prazosin (1)-related compounds 2-11 were synthesized and their affinity profiles were assessed by functional experiments in isolated rat vas deferens (alpha(1A)), spleen (alpha(1B)), and aorta (alpha(1D)) and by binding assays in CHO c...

journal_title：Journal of medicinal chemistry

authors： Rosini M,Antonello A,Cavalli A,Bolognesi ML,Minarini A,Marucci G,Poggesi E,Leonardi A,Melchiorre C

更新日期：2003-11-06 00:00:00

abstract：:Thymidylate kinase (TMK), an essential enzyme in bacterial DNA biosynthesis, is an attractive therapeutic target for the development of novel antibacterial agents, and we continue to explore TMK inhibitors with improved potency, protein binding, and pharmacokinetic potential. A structure-guided design approach was emp...

journal_title：Journal of medicinal chemistry

authors： Kawatkar SP,Keating TA,Olivier NB,Breen JN,Green OM,Guler SY,Hentemann MF,Loch JT,McKenzie AR,Newman JV,Otterson LG,Martínez-Botella G

更新日期：2014-06-12 00:00:00

abstract：:There is reported the first four members of heteroarotinoids, the names of which are ethyl (E)-p-[2-(4,4-dimethylthiochroman-6-yl)propenyl]benzoate (1b), ethyl (E)-p-[2-(4,4-dimethylchroman-6-yl)propenyl]benzoate (1c), ethyl (E)-p-[2-(4,4-dimethyl-1-oxothiochroman-6-yl)propenyl]benzoate (1d), and (E)-p-[2-(4,4-dimethy...

journal_title：Journal of medicinal chemistry

authors： Waugh KM,Berlin KD,Ford WT,Holt EM,Carrol JP,Schomber PR,Thompson MD,Schiff LJ

更新日期：1985-01-01 00:00:00

abstract：:Verrucarin A (2) was epoxidized to give the beta-9,10-epoxide 7 (major product) and alpha-9,10-epoxide 9 (minor product). The beta-epoxide 7 and its acetate 8 exhibit high in vivo antileukemic activity against P-388 mouse leukemia, whereas 2 and 9 are inactive. Epoxidation of verrucarin B (3) and roridin A (1) to thei...

journal_title：Journal of medicinal chemistry

authors： Jarvis BB,Stahly GP,Pavanasasivam G,Mazzola EP

更新日期：1980-09-01 00:00:00

abstract：:Protein arginine methylation is a posttranslational modification critical for a variety of biological processes. Misregulation of protein arginine methyltransferases (PRMTs) has been linked to many pathological conditions. Most current PRMT inhibitors display limited specificity and selectivity, indiscriminately targe...

journal_title：Journal of medicinal chemistry

authors： Yan L,Yan C,Qian K,Su H,Kofsky-Wofford SA,Lee WC,Zhao X,Ho MC,Ivanov I,Zheng YG

更新日期：2014-03-27 00:00:00

abstract：:In a previous study, we described affinity labeling of the lamb uterine estrogen receptor by 17 alpha-[(bromoacetoxy)alkyl/alkynyl]estradiols. However, the intrinsic receptor-alkylating activities of these compounds were probably very hampered by their poor hydrolytic stability in estrogen receptor-containing tissue e...

journal_title：Journal of medicinal chemistry

authors： el Garrouj D,Aliau S,Aumelas A,Borgna JL

更新日期：1995-06-23 00:00:00

abstract：:Chemical probes of microRNA (miRNA) function are potential tools for understanding miRNA biology that also provide new approaches for discovering therapeutics for miRNA-associated diseases. MicroRNA-21 (miR-21) is an oncogenic miRNA that is overexpressed in most cancers and has been strongly associated with driving ch...

journal_title：Journal of medicinal chemistry

authors： Naro Y,Ankenbruck N,Thomas M,Tivon Y,Connelly CM,Gardner L,Deiters A

更新日期：2018-07-26 00:00:00

abstract：:Evidence indicating that modifications at the 5- and 10-positions of classical folic acid antimetabolites lead to compounds with favorable differential membrane transport in tumor vs. normal proliferative tissue prompted an investigation of 5-alkyl-5-deaza analogues. 2-Amino-4-methyl-3,5-pyridinedicarbonitrile, prepar...

journal_title：Journal of medicinal chemistry

authors： Piper JR,McCaleb GS,Montgomery JA,Kisliuk RL,Gaumont Y,Sirotnak FM

更新日期：1986-06-01 00:00:00

abstract：:A novel series of oxime ligands has been synthesized that displays potent, specific activation of the retinoid X receptors (RXRs). The oximes of 3-substituted (tetramethyltetrahydronaphthyl)carbonylbenzoic acids are readily available by condensation with hydroxyl- or methoxylamine; alkylation of the hydroxyl oxime pro...

journal_title：Journal of medicinal chemistry

authors： Canan Koch SS,Dardashti LJ,Cesario RM,Croston GE,Boehm MF,Heyman RA,Nadzan AM

更新日期：1999-02-25 00:00:00

abstract：:A novel synthetic route to the cyclostellettamines 1 using as the key step a microwave-mediated macrocyclic ring-closing metathesis of precursors bispyridinium dienes 10 followed by catalytic hydrogenation has been developed. The open-chain bispyridinium dienes 10 showed uniformly higher histone deacetylase (HDAC) inh...

journal_title：Journal of medicinal chemistry

authors： Pérez-Balado C,Nebbioso A,Rodríguez-Graña P,Minichiello A,Miceli M,Altucci L,de Lera AR

更新日期：2007-05-17 00:00:00

abstract：:In order to define the role of the cholestane moiety in the anti-HIV agent cosalane, a series of cosalane analogs was synthesized in which the cholestane ring system was replaced by normal alkenyl and phosphodiester substituents having varied chain lengths and lipophilicities. The compounds containing simple alkenyl s...

journal_title：Journal of medicinal chemistry

authors： Keyes RF,Golebiewski WM,Cushman M

更新日期：1996-01-19 00:00:00

abstract：:A unique strategy for the enhancement of secondary binding of an inhibitor to an enzyme has been demonstrated in the design of new human immunodeficiency virus (HIV) protease inhibitors. When the planar benzene ring of a 4-hydroxycoumarin lead compound (1a, Ki = 0.800 microM) was replaced with medium-sized (i.e., 7-9)...

journal_title：Journal of medicinal chemistry

authors： Romines KR,Watenpaugh KD,Tomich PK,Howe WJ,Morris JK,Lovasz KD,Mulichak AM,Finzel BC,Lynn JC,Horng MM

更新日期：1995-05-26 00:00:00

abstract：:A novel series of diaminoanthraquinones was discovered initially as protein kinase C inhibitors with IC50s in the 50-100 microM range. They exhibited potent tumor cell growth inhibitory activity in vitro without cross resistance to adriamycin. Further evaluation of two of the most active compounds NSC 639365 (3) and N...

journal_title：Journal of medicinal chemistry

authors： Jiang JB,Johnson MG,Defauw JM,Beine TM,Ballas LM,Janzen WP,Loomis CR,Seldin J,Cofield D,Adams L

更新日期：1992-11-13 00:00:00

abstract：:Benzopyran selective estrogen receptor beta agonist-1 (SERBA-1) shows potent, selective binding and agonist function in estrogen receptor beta (ERbeta) in vitro assays. X-ray crystal structures of SERBA-1 in ERalpha and beta help explain observed beta-selectivity of this ligand. SERBA-1 in vivo demonstrates involution...

journal_title：Journal of medicinal chemistry

authors： Norman BH,Dodge JA,Richardson TI,Borromeo PS,Lugar CW,Jones SA,Chen K,Wang Y,Durst GL,Barr RJ,Montrose-Rafizadeh C,Osborne HE,Amos RM,Guo S,Boodhoo A,Krishnan V

更新日期：2006-10-19 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：: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：:17β-HSD14 is a SDR enzyme able to oxidize estradiol and 5-androstenediol using NAD(+). We determined the crystal structure of this human enzyme as the holo form and as ternary complexes with estrone and with the first potent, nonsteroidal inhibitor. The structures reveal a conical, rather large and lipophilic binding ...

journal_title：Journal of medicinal chemistry

authors： Bertoletti N,Braun F,Lepage M,Möller G,Adamski J,Heine A,Klebe G,Marchais-Oberwinkler S

更新日期：2016-07-28 00:00:00

abstract：:Following the observation that the activity of gonadotropin-releasing hormone III (GnRH-III) in the suppression of growth of MDA-MB-231 and MCF-7 breast cancer cells surpasses that of GnRH and other analogs thereof, analogs of GnRH-III were synthesized to investigate the structural basis for the improved antitumor act...

journal_title：Journal of medicinal chemistry

authors： Mezö I,Lovas S,Pályi I,Vincze B,Kálnay A,Turi G,Vadász Z,Seprödi J,Idei M,Tóth G,Gulyás E,Otvös F,Mák M,Horváth JE,Teplán I,Murphy RF

更新日期：1997-10-10 00:00:00

abstract：:Twenty-three acrylonitriles, substituted at position 2 with either triazoles or benzimidazoles and at position 3 with various substituted furan, thiophene, or phenyl rings, were prepared by Knoevenagel condensation and tested for in vitro cytotoxic potency on 11 human cancer cell lines. X-ray crystal analysis of two r...

journal_title：Journal of medicinal chemistry

authors： Saczewski F,Reszka P,Gdaniec M,Grünert R,Bednarski PJ

更新日期：2004-06-17 00:00:00

abstract：:In recent papers (Catarzi, D.; et al. J. Med. Chem. 2000, 43, 3824-3826; 2001, 44, 3157-3165) we reported chemical and biological studies on 4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates (TQXs) bearing different nitrogen-containing heterocycles at position-8. In particular, from these studies it em...

journal_title：Journal of medicinal chemistry

authors： Catarzi D,Colotta V,Varano F,Calabri FR,Filacchioni G,Galli A,Costagli C,Carlà V

更新日期：2004-01-01 00:00:00