Antagonists of slow-reacting substance of anaphylaxis. 1. Pyrido[2,1-b]quinazolinecarboxylic acid derivatives.

abstract：:The voltage-gated sodium channel Na(V)1.7 is believed to be a critical mediator of pain sensation based on clinical genetic studies and pharmacological results. Clinical utility of nonselective sodium channel blockers is limited due to serious adverse drug effects. Here, we present the optimization, structure-activity...

journal_title：Journal of medicinal chemistry

authors： Macsari I,Besidski Y,Csjernyik G,Nilsson LI,Sandberg L,Yngve U,Ahlin K,Bueters T,Eriksson AB,Lund PE,Venyike E,Oerther S,Hygge Blakeman K,Luo L,Arvidsson PI

更新日期：2012-08-09 00:00:00

abstract：:Thiol-containing diketopiperazines have been recently identified as novel heterocyclic inhibitors of matrix metalloproteinase (MMPs). The compounds described had similar activities against the MMPs collagenase-1 and gelatinase-B. An inhibitor that showed greater than 10-fold selectivity for collagenase-1 over gelatina...

journal_title：Journal of medicinal chemistry

authors： Szardenings AK,Antonenko V,Campbell DA,DeFrancisco N,Ida S,Shi L,Sharkov N,Tien D,Wang Y,Navre M

更新日期：1999-04-22 00:00:00

abstract：:Adverse drug reactions (ADRs) are a common cause of attrition in drug discovery and development and drug-induced liver injury (DILI) is a leading cause of preclinical and clinical drug terminations. This perspective outlines many of the known DILI mechanisms and assessment methods used to evaluate and mitigate DILI ri...

journal_title：Journal of medicinal chemistry

authors： Norman BH

更新日期：2020-10-22 00:00:00

abstract：:The directional properties of hydrogen bonds play a major role in determining the specificity of intermolecular interactions. An energy function which takes explicit account of these properties has been developed for use in the determination of energetically favorable ligand binding sites on molecules of known structu...

journal_title：Journal of medicinal chemistry

authors： Wade RC,Clark KJ,Goodford PJ

更新日期：1993-01-08 00:00:00

abstract：:A series of 3-acylbenzamidine (amidino)hydrazones 7a-h, the corresponding (hetero)aromatic congeners 7i-p, and 3,3'-bis-amidino-biaryls 25a-e were synthesized. The hydrazones 7a-p were prepared by conversion of the corresponding acyl nitriles 1a,c-d,i,n-p to the imido esters 3a,c-d,i and the amidines 5a,c-d,h-i, follo...

journal_title：Journal of medicinal chemistry

authors： Stanek J,Caravatti G,Capraro HG,Furet P,Mett H,Schneider P,Regenass U

更新日期：1993-01-08 00:00:00

abstract：:2-, 6-, And 8-alkylated (methyl, ethyl, and vinyl) adenosine analogues were synthesized by a palladium-catalyzed cross-coupling of a tetraalkyltin with the halogenated purine nucleosides. The synthesis of the 8-substituted analogues was accomplished using a transient protection procedure. The 6-alkylated-9-beta-D-ribo...

journal_title：Journal of medicinal chemistry

authors： Van Aerschot AA,Mamos P,Weyns NJ,Ikeda S,De Clercq E,Herdewijn PA

更新日期：1993-10-01 00:00:00

abstract：:A series of new 5-(1-hydroxy-2-haloethyl)-2'-deoxyuridines (3, 6, 8) were synthesized in 60-70% yields by addition of HOX (X = Br, Cl, I) to the vinyl substituent of the respective 5-vinyl-2'-deoxyuridines (2, 5, 7). Treatment of 3a,b with methanolic sulfuric acid afforded the corresponding 5-(1-methoxy-2-haloethyl)-2...

journal_title：Journal of medicinal chemistry

authors： Kumar R,Wiebe LI,Hall TW,Knaus EE,Tovell DR,Tyrrell DL,Allen TM,Fathi-Afshar R

更新日期：1989-05-01 00:00:00

abstract：:As part of an effort to identify novel opioid receptor interactive agents, we recently prepared a series of 8-(substituted)amino analogues of cyclazocine. We found the chiral 8-phenylamino (NHC(6)H(5)) cyclazocine derivative to have subnanomolar affinity for kappa opioid receptors and a 2-fold lower affinity for mu, o...

journal_title：Journal of medicinal chemistry

authors： Wentland MP,Duan W,Cohen DJ,Bidlack JM

更新日期：2000-09-21 00:00:00

abstract：:In an attempt to determine which conformational parameters are important for the biological activity of ovine corticotropin-releasing factor (oCRF), we have synthesized in significant amounts (50-200 mg) and characterized chemically, structurally (CD), and biologically, oCRF analogues with substitution of each amino a...

journal_title：Journal of medicinal chemistry

authors： Rivier J,Rivier C,Galyean R,Miranda A,Miller C,Craig AG,Yamamoto G,Brown M,Vale W

更新日期：1993-10-01 00:00:00

abstract：:Antimicrobial peptides (AMPs) are amphipathic molecules displaying broad-spectrum bactericidal activity, providing opportunities to develop a new generation of antibiotics. However, their use is limited either by poor metabolic stability or by high hemolytic activity. We herein addressed the potential of thiazole-base...

journal_title：Journal of medicinal chemistry

authors： Bonnel C,Legrand B,Simon M,Clavié M,Masnou A,Jumas-Bilak E,Kang YK,Licznar-Fajardo P,Maillard LT,Masurier N

更新日期：2020-09-10 00:00:00

abstract：:We report analogues of N-Ac-D-Nal-D-Cpa-D-Pal-Ser-Lys(Pic)-D-Lys(Pic)-Leu-Ilys-Pro-D-Ala- NH2, the parent antagonist (PA), which is a potent antagonist of LHRH. To simplify future radioactive labeling we prepared N-Ac-D-Nal-D-Cpa-D-Pal-Ser-Lys(Pic)-D-Lys(Pic)-Leu-Arg-Pro-D-Ala-NH2 (4), [Arg8]PA, which had good activit...

journal_title：Journal of medicinal chemistry

authors： Flouret G,Mahan K,Majewski T

更新日期：1992-02-21 00:00:00

abstract：:To probe the space at the floor of the orthosteric ligand binding site in the dopamine D(1) receptor, four methylated analogues of dihydrexidine (DHX) were synthesized with substitutions at the 7 and 8 positions. The 8α-axial, 8β-equatorial, and 7α-equatorial were synthesized by photochemical cyclization of appropriat...

journal_title：Journal of medicinal chemistry

authors： Cueva JP,Gallardo-Godoy A,Juncosa JI,Vidi PA,Lill MA,Watts VJ,Nichols DE

更新日期：2011-08-11 00:00:00

abstract：:A group of nitro and amino derivatives of lucanthone was prepared and tested for antitumor activity. Reaction of 1-chloro-4-methyl-7-nitrothioxanthenone and N,N-diethylethylenediamine gave the 7-amino analogue (11) directly, accompanied by 7-amino-1-chloro-4-methylthioxanthenone. The antitumor activity of 11 was infer...

journal_title：Journal of medicinal chemistry

authors： Archer S,Rej R

更新日期：1982-03-01 00:00:00

abstract：:Two natural occurring melanotropins, camel betaC2-MSH and bovine beta-MSH, have been synthesized by improved solid-phase procedures. The coupling reaction of tert-butyloxycarbonylamino acids was achieved by using their preformed symmetrical anhydrides. The synthetic hormones were purified by gel filtration on Sephadex...

journal_title：Journal of medicinal chemistry

authors： Lemaire S,Yamashiro D,Li CH

更新日期：1976-03-01 00:00:00

abstract：:Janus kinases (JAK1, JAK2, JAK3, and TYK2) are involved in the signaling of multiple cytokines important in cellular function. Blockade of the JAK-STAT pathway with a small molecule has been shown to provide therapeutic immunomodulation. Having identified JAK1 as a possible new target for arthritis at Galapagos, the c...

journal_title：Journal of medicinal chemistry

authors： Menet CJ,Fletcher SR,Van Lommen G,Geney R,Blanc J,Smits K,Jouannigot N,Deprez P,van der Aar EM,Clement-Lacroix P,Lepescheux L,Galien R,Vayssiere B,Nelles L,Christophe T,Brys R,Uhring M,Ciesielski F,Van Rompaey L

更新日期：2014-11-26 00:00:00

abstract：:A group of oligopeptides has been synthesized that are structurally related to the natural antiviral antitumor agents netropsin and distamycin but which bear alkylating functions. Cytostatic activity against both human and murine tumor cell lines as well as their in vitro activity against a range of viruses is reporte...

journal_title：Journal of medicinal chemistry

authors： Krowicki K,Balzarini J,De Clercq E,Newman RA,Lown JW

更新日期：1988-02-01 00:00:00

abstract：:alpha-Fluoromethyl amino acids are enzyme-activated irreversible inhibitors of amino acid decarboxylases. Aromatic L-amino acid decarboxylase (AADC) is the enzyme responsible for the final step in the biosynthesis of both dopamine and serotonin via decarboxylation of L-dopa and 5-hydroxy-L-tryptophan, respectively. Ou...

journal_title：Journal of medicinal chemistry

authors： Zembower DE,Gilbert JA,Ames MM

更新日期：1993-02-05 00:00:00

abstract：:We have rationally designed a sLe(x) mimetic based on molecular modeling, synthesized type II and type II' beta-turn dipeptides (3a,b), and evaluated their biological profiles both in vitro and in vivo. Against E-selectin-sLe(x) binding, the type II beta-turn dipeptide L-Ser-D-Glu 3a (IC50, 13 microM) and the type II'...

journal_title：Journal of medicinal chemistry

authors： Tsukida T,Hiramatsu Y,Tsujishita H,Kiyoi T,Yoshida M,Kurokawa K,Moriyama H,Ohmoto H,Wada Y,Saito T,Kondo H

更新日期：1997-10-24 00:00:00

abstract：:Twenty homodetic cyclic peptides based on the C-terminal sequence of substance P were prepared (Table I) by a combination of solid-phase techniques and cyclizations using azide coupling procedures. Incorporation of dipeptide mimics based on substituted gamma-lactams were used in some cases to restrict their conformati...

journal_title：Journal of medicinal chemistry

authors： Williams BJ,Curtis NR,McKnight AT,Maguire JJ,Young SC,Veber DF,Baker R

更新日期：1993-01-08 00:00:00

abstract：:A series of analogues of 4,5-bis(((N-methylcarbamoyl)oxy)methyl)-1-methyl-2-(methylthio)-im idazole (1, carmethizole) were synthesized. The chemical reactivities of the analogues (as electrophiles) were evaluated and related to the antitumor activity (in vivo and in vitro). Changes in the alkylthio moiety had a signif...

journal_title：Journal of medicinal chemistry

authors： Jarosinski MA,Reddy PS,Anderson WK

更新日期：1993-11-12 00:00:00

abstract：:The mTOR protein is a master regulator of cell growth and proliferation, and inhibitors of its kinase activity have the potential to become new class of anticancer drugs. Starting from quinoline 1, which was identified in a biochemical mTOR assay, we developed a tricyclic benzonaphthyridinone inhibitor 37 (Torin1), wh...

journal_title：Journal of medicinal chemistry

authors： Liu Q,Chang JW,Wang J,Kang SA,Thoreen CC,Markhard A,Hur W,Zhang J,Sim T,Sabatini DM,Gray NS

更新日期：2010-10-14 00:00:00

abstract：:A series of thymidylate synthetase inhibitors was synthesized, some of which were potential irreversible inhibitors. 5-Formyl-2'-deoxyuridine (9) and its dithiolane derivative 11 were prepared by condensation of the bis(trimethylsilyl) derivative of 5-formyluracil dimethyl acetal and the protected chloro sugar followe...

journal_title：Journal of medicinal chemistry

authors： Kampf A,Pillar CJ,Woodford WJ,Mertes MP

更新日期：1976-07-01 00:00:00

abstract：:The synthetic chemical nuclease, [Cu(1,10-phenanthroline)2](2+), has stimulated research within metallonuclease development and in the area of cytotoxic metallodrug design. Our analysis reveals, however, that this agent is "promiscuous" as it binds both dsDNA and protein biomolecules, without specificity, and induces ...

journal_title：Journal of medicinal chemistry

authors： Prisecaru A,McKee V,Howe O,Rochford G,McCann M,Colleran J,Pour M,Barron N,Gathergood N,Kellett A

更新日期：2013-11-14 00:00:00

abstract：:Lead-like drugs, or drugs below molecular weight 300, are an important and sometimes overlooked component of the current pharmacopeia and contemporary medicinal chemistry practice. To examine the recent state-of-the-art in lead-like drug discovery, we surveyed recent drug approvals from 2011 to 2017 and top 200 prescr...

journal_title：Journal of medicinal chemistry

authors： Raymer B,Bhattacharya SK

更新日期：2018-12-13 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

abstract：:A new series of N-aryl-N'-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)ureas bearing an alkoxycarbonylamino group at the 6-position were synthesized and examined as putative anticancer agents targeting sirtuins in glioma cells. On the basis of computational docking combined to in vitro sirtuin 1/2 inhibition assays, ...

journal_title：Journal of medicinal chemistry

authors： Schnekenburger M,Goffin E,Lee JY,Jang JY,Mazumder A,Ji S,Rogister B,Bouider N,Lefranc F,Miklos W,Mathieu V,de Tullio P,Kim KW,Dicato M,Berger W,Han BW,Kiss R,Pirotte B,Diederich M

更新日期：2017-06-08 00:00:00

abstract：:Analogues of the anticonvulsant agent milacemide (1,2-(n-pentylamino)acetamide), in which the carboxamide group is changed to a nitrile (2), a carbethoxy group (3), a carboxylic acid (4), a cyanomethyl group (5), and a trifluoromethyl group (6), were synthesized and tested as substrates and inactivators of monoamine o...

journal_title：Journal of medicinal chemistry

authors： Nishimura K,Lu X,Silverman RB

更新日期：1993-02-19 00:00:00

abstract：:We have introduced topographical constraints at the 9 position of a superpotent cyclic alpha-melanotropin analogue, Ac-Nle4-Asp5-His6-DPhe7-Arg8-Trp9-Lys10-NH2, by incorporating a methyl group at the beta-carbon of Trp9. These studies were performed on the Trp side chain pharmacophore to identify the bioactive topogra...

journal_title：Journal of medicinal chemistry

authors： Haskell-Luevano C,Boteju LW,Miwa H,Dickinson C,Gantz I,Yamada T,Hadley ME,Hruby VJ

更新日期：1995-11-10 00:00:00

abstract：:The preparation and antitubercular properties of a series of 2,8-bis(alkylaminomethyl)phenazines are described. These compounds all inhibited the growth of Mycobacterium smegmatis ATCC 607 in vitro. 2,8-Bis(dibutylaminomethyl)phenazine (5c) was also active against a lethal Mycobacterium tuberculosis H37Rv infection in...

journal_title：Journal of medicinal chemistry

authors： Murdock KC,Lin Y,Thomas JP,Lang SA Jr

更新日期：1978-04-01 00:00:00

abstract：:We present a novel method to better investigate adverse drug reactions in chemical space. By integrating data sources about adverse drug reactions of drugs with an established cheminformatics modeling method, we generate a data set that is then visualized with a systems biology tool. Thereby new insights into undesire...

journal_title：Journal of medicinal chemistry

authors： Scheiber J,Jenkins JL,Sukuru SC,Bender A,Mikhailov D,Milik M,Azzaoui K,Whitebread S,Hamon J,Urban L,Glick M,Davies JW

更新日期：2009-05-14 00:00:00