Tricyclic indole-2-carboxylic acids: highly in vivo active and selective antagonists for the glycine binding site of the NMDA receptor.

abstract：:Z-D-Phe-Pro-boroMpg-OPin (9a)1,2 has been shown previously to be a highly specific inhibitor of thrombin in spite of lacking an arginine-like guanidino group at the P1 site. A range of compounds have been synthesized based upon this lead compound, varying the neutral side chain at the P1 site. Of the 20 examples based...

journal_title：Journal of medicinal chemistry

authors： Deadman JJ,Elgendy S,Goodwin CA,Green D,Baban JA,Patel G,Skordalakes E,Chino N,Claeson G,Kakkar VV

更新日期：1995-04-28 00:00:00

abstract：:Lymphatic filariasis (elephantiasis) is a global public health problem caused by the parasitic nematodes Wuchereria bancrofti and Brugia malayi. We have previously reported anthraquinones from daylily roots with potent activity against pathogenic trematode Schistosoma mansoni. Here we report the synthesis of novel ant...

journal_title：Journal of medicinal chemistry

authors： Dhananjeyan MR,Milev YP,Kron MA,Nair MG

更新日期：2005-04-21 00:00:00

abstract：:The synthesis of a series of 1-amino-substituted pyrido[4,3-b]carbazole derivatives, based on the substitution of corresponding 1-chloroellipticines, is reported. The cytotoxic properties on tumor cells grown in vitro, the in vivo acute toxicity of the most potent in vitro cytotoxic compounds, and the antitumor proper...

journal_title：Journal of medicinal chemistry

authors： Ducrocq C,Wendling F,Tourbez-Perrin M,Rivalle C,Tambourin P,Pochon F,Bisagni E,Chermann JC

更新日期：1980-11-01 00:00:00

abstract：:A series of compounds containing the 3-hydroxy-4H-pyran-4-one nucleus has been synthesized and tested as potential skeletal muscle relaxants. Reduction of 2-(azidomethyl)-5-hydroxy-4H-pyran-4-one (4) with HBr in HOAc--phenol yielded 2-(aminomethyl)-5-hydroxy-4H-pyran-4-one (kojic amine, 3) in 81% yield. Reaction of 2-...

journal_title：Journal of medicinal chemistry

authors： Atkinson JG,Girard Y,Rokach J,Rooney CS,McFarlane CS,Rackham A,Share NN

更新日期：1979-01-01 00:00:00

abstract：:A series of analogues of the analgesic dipeptide derivative H-Lys-Trp(NPS)-OMe has been designed to determine the influence of the (2-nitrophenyl)sulfenyl (NPS) moiety on the activity. The syntheses and antinociceptive effects of these analogues of general formula H-Lys-Trp(R)-OMe [R = phenylsulfenyl (PS) (9); R = (2-...

journal_title：Journal of medicinal chemistry

authors： Garcia-López MT,González-Muñiz R,Molinero MT,Naranjo JR,Del Rio J

更新日期：1987-09-01 00:00:00

abstract：:A series of phenylenebis(oxy)bis[2,2-dimethylpentanoic acid]s have been synthesized and evaluated as potential hypolipidemic agents. Compound 18 (CI-924) was found to be the most potent compound in this series. In rats, compound 18 not only reduced low-density lipoprotein cholesterol but also increased high-density li...

journal_title：Journal of medicinal chemistry

authors： Sircar I,Hoefle M,Maxwell RE

更新日期：1983-07-01 00:00:00

abstract：:A series of (E)-phenoxyacrylic amide derivatives were synthesized and evaluated as hypoxia inducible factor (HIF) 1α inhibitors. The present structure-activity relationship study on this series identified the morpholinoethyl containing ester 4p as a potent inhibitor of HIF-1α under hypoxic conditions (IC50=0.12 μM in ...

journal_title：Journal of medicinal chemistry

authors： Naik R,Won M,Kim BK,Xia Y,Choi HK,Jin G,Jung Y,Kim HM,Lee K

更新日期：2012-12-13 00:00:00

abstract：:AM1 semiempirical molecular orbital calculations have been used to probe the complexation sites for naked and hydrated magnesium ions to the different conformations and protonation states of tetracycline. The calculations reveal a wealth of possible magnesium complexation sites within a small energy range, but also in...

journal_title：Journal of medicinal chemistry

authors： Othersen OG,Lanig H,Clark T

更新日期：2003-12-18 00:00:00

abstract：:MTH1 is a member of the nudix phosphohydrolase superfamily of enzymes, and it is involved in nucleotide pool homeostasis. The protein exerts its scavenging action by hydrolyzing oxidized nucleotides, thus avoiding their misincorporation into replicating DNA. Recent reports have validated its inhibition as a potential ...

journal_title：Journal of medicinal chemistry

authors： Papeo G

更新日期：2016-03-24 00:00:00

abstract：:1H-Indolo[3',2':4,5]pyrido[3,2-b]-2-penten-5-olide (6) and 1H,5H-indolo[3',2'-c]-6,7-dihydro-2-pyridone (7), rigid analogues of methyl 4-ethyl-beta-carboline-3-carboxylate (8) and N-methyl-4-ethyl-beta-carboline-3-carboxamide (9), respectively, were synthesized and their in vitro binding affinities to the central type...

journal_title：Journal of medicinal chemistry

authors： Dorey G,Poissonnet G,Potier MC,Prado de Carvalho L,Venault P,Chapouthier G,Rossier J,Potier P,Dodd RH

更新日期：1989-08-01 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：:Proton magnetic spectra have been recorded for muscarine and two biologically active cyclopentane analogues. In order to observe homonuclear intramolecular nuclear Overhauser effects, the -N+(CH3)3 signal was irradiated and increases in integrated intensities for other key signals in the molecule were observed. The re...

journal_title：Journal of medicinal chemistry

authors： de Fontaine DL,Ternai B,Zupan JA,Givens RS,Wiley RA

更新日期：1978-07-01 00:00:00

abstract：:In previous reports illustrating the effects of conformational restriction of the N-terminal region of human pancreatic growth hormone releasing factor, we demonstrated that D-amino acid substitutions in either of positions 1, 2, or 3 resulted in greatly increased growth hormone releasing activity both in vivo and in ...

journal_title：Journal of medicinal chemistry

authors： Coy DH,Murphy WA,Sueiras-Diaz J,Coy EJ,Lance VA

更新日期：1985-02-01 00:00:00

abstract：:Glutathione transferase omega-1 (GSTO1-1) is an enzyme whose function supports the activation of interleukin (IL)-1β and IL-18 that are implicated in a variety of inflammatory disease states for which small-molecule inhibitors are sought. The potent reactivity of the active-site cysteine has resulted in reported inhib...

journal_title：Journal of medicinal chemistry

authors： Xie Y,Tummala P,Oakley AJ,Deora GS,Nakano Y,Rooke M,Cuellar ME,Strasser JM,Dahlin JL,Walters MA,Casarotto MG,Board PG,Baell JB

更新日期：2020-03-26 00:00:00

abstract：:A series of 6-benzoxazinylpyridazin-3-ones was prepared and evaluated for inhibition of cardiac phosphodiesterase (PDE) fraction III in vitro and for positive inotropic activity in vivo. 6-[3,4-Dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl]-2,3,4,5-tetrahydro-5 - methylpyridazin-3-one (bemoradan) was found to be an extremely ...

journal_title：Journal of medicinal chemistry

authors： Combs DW,Rampulla MS,Bell SC,Klaubert DH,Tobia AJ,Falotico R,Haertlein B,Lakas-Weiss C,Moore JB

更新日期：1990-01-01 00:00:00

abstract：:Computational ligand-protein docking is routinely used for binding mode prediction. We have quantified the effect of considering multiple docking solutions on the success rate of obtaining the crystallographic binding mode. By selection of a small set of representatives, the experimentally observed binding mode can be...

journal_title：Journal of medicinal chemistry

authors： Källblad P,Mancera RL,Todorov NP

更新日期：2004-06-17 00:00:00

abstract：:The chemical synthesis and structure-activity relationships of a novel series of 17beta-glucocorticoid butyrolactones possessing either a 16alpha,17alpha-isopropylidene or -butylidene group are described. The sulfur-linked gamma-lactone group was incorporated onto the 17beta-position of the androstane nucleus via Bart...

journal_title：Journal of medicinal chemistry

authors： Procopiou PA,Biggadike K,English AF,Farrell RM,Hagger GN,Hancock AP,Haase MV,Irving WR,Sareen M,Snowden MA,Solanke YE,Tralau-Stewart CJ,Walton SE,Wood JA

更新日期：2001-02-15 00:00:00

abstract：:Hydroxyurea, hydroxyguanidine, and some thiosemicarbazones have been shown to have anticancer and antiviral activities. One of their possible sites of action is the enzyme ribonucleotide reductase (RR). Combination of the structural features of these compounds led to the design and synthesis of the Schiff bases of N-h...

journal_title：Journal of medicinal chemistry

authors： T'ang A,Lien EJ,Lai MM

更新日期：1985-08-01 00:00:00

abstract：:A structure-guided design approach using a homology model of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) was used to improve the potency of a series of imidazopyridazine inhibitors as potential antimalarial agents. This resulted in high affinity compounds with PfCDPK1 enzyme IC50 values less tha...

journal_title：Journal of medicinal chemistry

authors： Chapman TM,Osborne SA,Wallace C,Birchall K,Bouloc N,Jones HM,Ansell KH,Taylor DL,Clough B,Green JL,Holder AA

更新日期：2014-04-24 00:00:00

abstract：:A variety of 2,3-disubstituted 5,7-dimethyl-1,8-naphthyridines was synthesized and tested in saline-loaded rats for their diuretic properties. The 2-amino-3-carbomethoxy and four 2-amino-3-N-alkylcarbamoyl compounds exhibited significant activity as measured by volume output; however, they were generally less potent t...

journal_title：Journal of medicinal chemistry

authors： Hawes EM,Gorecki DK,Gedir RG

更新日期：1977-06-01 00:00:00

abstract：:The enantiomers of 6,7,8,9-tetrahydro-N,N-di-n-propyl-3H-benz[e]indol-8- amine (S-(-)-2b and R-(+)-2b) and their corresponding 1-formyl analogs (S-(-)-6 and R-(+)-6) were prepared and evaluated pharmacologically for serotonergic and dopaminergic activity. The introduction of a formyl group in the 1-position shifted th...

journal_title：Journal of medicinal chemistry

authors： Stjernlöf P,Gullme M,Elebring T,Andersson B,Wikström H,Lagerquist S,Svensson K,Ekman A,Carlsson A,Sundell S

更新日期：1993-07-23 00:00:00

abstract：:The enantiomers of reduced haloperidol (3a), azaperol (3b), and the related compound BMY-14802 (3c) were prepared in high optical purity. The affinity of these compounds for dopamine D2 and D3 receptors, and sigma S1 and S2 sites was determined in vitro. Both enantiomers of 3a display greatly decreased affinity for D2...

journal_title：Journal of medicinal chemistry

authors： Jaen JC,Caprathe BW,Pugsley TA,Wise LD,Akunne H

更新日期：1993-11-26 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：:4-(Dimethylamino)- and 4-(methylamino)-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofuran] derivatives were prepared as analogues of previously reported 3-arylspiro[isobenzofuran-1(3H),4'-piperidines]. Metalation of benzanilide with n-butyllithium, addition of 4-(dimethylamino)cyclohexanone, and acidification afforded a...

journal_title：Journal of medicinal chemistry

authors： Martin LL,Worm M,Agnew MN,Kruse H,Wilker JC,Geyer HM 3rd

更新日期：1981-05-01 00:00:00

abstract：:Derivatives of N-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide bearing a wide variety of different groups at the 5-position (and for comparative purposes at the 7-position) have been prepared, and their physicochemical properties and biological activities have been determined. Although both 5- and 7-substitut...

journal_title：Journal of medicinal chemistry

authors： Denny WA,Atwell GJ,Rewcastle GW,Baguley BC

更新日期：1987-04-01 00:00:00

abstract：:We studied the structure-activity relationships of a series of 2'-fluoro-2',3'-unsaturated D-nucleosides against HIV-1 in human peripheral blood mononuclear (PBM) cells. The target compounds 10-21 and 28-33 were prepared by N-glycosylation of the acetate 4, which was readily prepared from 2,3-O-isopropylidene-D-glycer...

journal_title：Journal of medicinal chemistry

authors： Lee K,Choi Y,Gumina G,Zhou W,Schinazi RF,Chu CK

更新日期：2002-03-14 00:00:00

abstract：:The adenovirus serotype Ad37 binds to and infects human corneal epithelial (HCE) cells through attachment to cellular glycoproteins carrying terminal sialic acids. By use of the crystallographic structure of the sialic acid-interacting domain of the Ad37 fiber protein in complex with sialyllactose, a set of N-acyl mod...

journal_title：Journal of medicinal chemistry

authors： Johansson S,Nilsson E,Qian W,Guilligay D,Crepin T,Cusack S,Arnberg N,Elofsson M

更新日期：2009-06-25 00:00:00

abstract：:Developing Janus kinase 2 (Jak2) inhibitors has become a significant focus for small molecule drug discovery programs in recent years due to the identification of a Jak2 gain-of-function mutation in the majority of patients with myeloproliferative disorders (MPD). Here, we describe the discovery of a thienopyridine se...

journal_title：Journal of medicinal chemistry

authors： Schenkel LB,Huang X,Cheng A,Deak HL,Doherty E,Emkey R,Gu Y,Gunaydin H,Kim JL,Lee J,Loberg R,Olivieri P,Pistillo J,Tang J,Wan Q,Wang HL,Wang SW,Wells MC,Wu B,Yu V,Liu L,Geuns-Meyer S

更新日期：2011-12-22 00:00:00

abstract：:In previous studies, we have grouped regions in space occupied by the vitamin D side chain into four: A, G, EA, and EG. We showed that the receptor (VDR) affinity of 1alpha,25-dihydroxyvitamin D3 derivatives increases, in terms of side-chain region, in the order EG, G, A, and EA. We called this the active space group ...

journal_title：Journal of medicinal chemistry

authors： Yamada S,Yamamoto K,Masuno H,Ohta M

更新日期：1998-04-23 00:00:00

abstract：:Mycophenolic alcohol (MPAlc), obtained by reduction of the carboxylic group of mycophenolic acid (MPA), was coupled with 2',3'-O-isopropylideneadenosine 5'-methylenebis(phosphonate) (4) in the presence of diisopropylcarbodiimide (DIC) to give P1-(2',3'-O-isopropylideneadenosin-5'-yl)-P2-(mycophenolic alcohol-6'-yl)met...

journal_title：Journal of medicinal chemistry

authors： Lesiak K,Watanabe KA,Majumdar A,Powell J,Seidman M,Vanderveen K,Goldstein BM,Pankiewicz KW

更新日期：1998-02-12 00:00:00