Antiinflammatory activity of some 2,3-dihydrobenzofuran-5-acetic acids and related compounds.

abstract：:A series of 6-beta-thiosaccharide analogues of morphine-6-glucuronide (M6G) and codeine-6-glucuronide (C6G) were synthesized and evaluated with the objective of preparing an analogue of M6G with improved biological activity. The affinity of the thiosaccharide analogues of M6G and C6G was examined by competitive bindin...

journal_title：Journal of medicinal chemistry

authors： MacDougall JM,Zhang XD,Polgar WE,Khroyan TV,Toll L,Cashman JR

更新日期：2004-11-04 00:00:00

abstract：:The N- and C-terminal domains of human somatic angiotensin I converting enzyme (sACE-1) demonstrate distinct physiological functions, with resulting interest in the development of domain-selective inhibitors for specific therapeutic applications. Herein, the activity of lisinopril-coupled transition metal chelates was...

journal_title：Journal of medicinal chemistry

authors： Hocharoen L,Joyner JC,Cowan JA

更新日期：2013-12-27 00:00:00

abstract：:Monosubstituted derivatives of adenosine 5'-phosphate (AMP) with substituents of 1-3 atoms or group replacements at any of 11 positions have been synthesized and examined as substrates and inhibitors of the rat muscle adenylate kinase isozyme (AK-M), and the rat AK II and III isozymes predominant in poorly differentia...

journal_title：Journal of medicinal chemistry

authors： Hai TT,Picker D,Abo M,Hampton A

更新日期：1982-07-01 00:00:00

abstract：:Methyllycaconitine (MLA, 1) is a novel, potent probe for mammalian and insect nicotinic acetylcholine receptors (nAChR) and displays remarkable selectivity toward neuronal [125I]-alpha-bungarotoxin (alpha BgTX) binding sites that correspond to alpha 7-type nAChR in mammalian brain. We have shown that, among a number o...

journal_title：Journal of medicinal chemistry

authors： Hardick DJ,Blagbrough IS,Cooper G,Potter BV,Critchley T,Wonnacott S

更新日期：1996-11-22 00:00:00

abstract：:New thioamide derivatives of 2-(2-pyridyl)tetrahydrothiophene-2-carbothioamide (29) and related compounds (in which the tetrahydrothiophene ring was replaced by tetrahydrothiopyran, tetrahydrofuran, 1,3-dithiane, or 1,3-oxathiane and where the pyridine ring was replaced by other nitrogen heterocycles) were synthesized...

journal_title：Journal of medicinal chemistry

authors： Aloup JC,Bouchaudon J,Farge D,James C,Deregnaucourt J,Hardy-Houis M

更新日期：1987-01-01 00:00:00

abstract：:The mechanism-based risk for hyperkalemia has limited the use of mineralocorticoid receptor antagonists (MRAs) like eplerenone in cardio-renal diseases. Here, we describe the structure and property-driven lead generation and optimization, which resulted in identification of MR modulators ( S)-1 and ( S)-33. Both compo...

journal_title：Journal of medicinal chemistry

authors： Granberg KL,Yuan ZQ,Lindmark B,Edman K,Kajanus J,Hogner A,Malmgren M,O'Mahony G,Nordqvist A,Lindberg J,Tångefjord S,Kossenjans M,Löfberg C,Brånalt J,Liu D,Selmi N,Nikitidis G,Nordberg P,Hayen A,Aagaard A,Hansson E

更新日期：2019-02-14 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：:A series of (substituted amino)-1,2,4-benzothiadiazine 1-oxides has been synthesized and most members of the series have been shown to have blood pressure lowering effects in normotensive rabbits and in spontaneously hypertensive rats. The most active member of the series was 3-[4-(2-furoyl)-1-piperazinyl]-6,7-dimetho...

journal_title：Journal of medicinal chemistry

authors： Dillard RD,Yen TT,Stark P,Pavey DE

更新日期：1980-07-01 00:00:00

abstract：:A physiologically based model for gastrointestinal transit and absorption in humans is presented. The model can be used to study the dependency of the fraction dose absorbed (F(abs)) of both neutral and ionizable compounds on the two main physicochemical input parameters (the intestinal permeability coefficient (P(int...

journal_title：Journal of medicinal chemistry

authors： Willmann S,Schmitt W,Keldenich J,Lippert J,Dressman JB

更新日期：2004-07-29 00:00:00

abstract：:A series of DNA-intercalating potential antitumor agents, 1-[(omega-aminoalkyl)amino]-4-[N-(omega-aminoalkyl)carbamoyl]-9-oxo-9, 10-dihydroacridines, has been prepared by aminolysis of the corresponding 4-[N-(omega-aminoalkyl)carbamoyl]-1-chloro derivative with a suitable omega-aminoalkylamine. The noncovalent DNA-bin...

journal_title：Journal of medicinal chemistry

authors： Antonini I,Polucci P,Jenkins TC,Kelland LR,Menta E,Pescalli N,Stefanska B,Mazerski J,Martelli S

更新日期：1997-11-07 00:00:00

abstract：:The JmjC oxygenases catalyze the N-demethylation of N(ε)-methyl lysine residues in histones and are current therapeutic targets. A set of human 2-oxoglutarate analogues were screened using a unified assay platform for JmjC demethylases and related oxygenases. Results led to the finding that daminozide (N-(dimethylamin...

journal_title：Journal of medicinal chemistry

authors： Rose NR,Woon EC,Tumber A,Walport LJ,Chowdhury R,Li XS,King ON,Lejeune C,Ng SS,Krojer T,Chan MC,Rydzik AM,Hopkinson RJ,Che KH,Daniel M,Strain-Damerell C,Gileadi C,Kochan G,Leung IK,Dunford J,Yeoh KK,Ratcliffe PJ

更新日期：2012-07-26 00:00:00

abstract：:Despite the availability of large amounts of data for HIV-protease inhibitors and their effectiveness with wild type and resistant enzyme, there is limited knowledge about how this and other information can be systematically applied to the development of new antiviral compounds. To identify in vitro parameters that co...

journal_title：Journal of medicinal chemistry

authors： Shuman CF,Vrang L,Danielson UH

更新日期：2004-11-18 00:00:00

abstract：:The chemokine receptor CXCR4 is a critical regulator of inflammation and immune surveillance, and it is specifically implicated in cancer metastasis and HIV-1 infection. On the basis of the observation that several of the known antagonists remarkably share a C(2) symmetry element, we constructed symmetric dimers with ...

journal_title：Journal of medicinal chemistry

authors： Demmer O,Dijkgraaf I,Schumacher U,Marinelli L,Cosconati S,Gourni E,Wester HJ,Kessler H

更新日期：2011-11-10 00:00:00

abstract：:Elevated plasma levels of low-density lipoprotein (LDL) cholesterol are a major risk factor for atherosclerosis leading to coronary artery disease (CAD), which remains the main cause of mortality in Western society. We believe that by preventing the reabsorption of bile acids, a minimally absorbed apical sodium-codepe...

journal_title：Journal of medicinal chemistry

authors： Tremont SJ,Lee LF,Huang HC,Keller BT,Banerjee SC,Both SR,Carpenter AJ,Wang CC,Garland DJ,Huang W,Jones C,Koeller KJ,Kolodziej SA,Li J,Manning RE,Mahoney MW,Miller RE,Mischke DA,Rath NP,Fletcher T,Reinhard EJ,Tol

更新日期：2005-09-08 00:00:00

abstract：:Inhibitors of the PI3-kinase/AKT (protein kinase B) pathway are under investigation as anticancer and antiviral agents. The benzimidazole derivative AKT inhibitor-IV (ChemBridge 5233705) affects this pathway and exhibits potent anticancer and antiviral activity. To probe its biological activity, we synthesized AKT inh...

journal_title：Journal of medicinal chemistry

authors： Sun Q,Wu R,Cai S,Lin Y,Sellers L,Sakamoto K,He B,Peterson BR

更新日期：2011-03-10 00:00:00

abstract：:A new class of acyclic adenosine analogues is described which exhibit broad-spectrum antiviral activity and are apparently targeted at S-adenosyl-L-homocysteine hydrolase. The compounds are all alkyl (i.e., methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, 2-methylpropyl, tert-butyl, 1-pentyl, 3-methylbutyl, 1-octy...

journal_title：Journal of medicinal chemistry

authors： De Clercq E,Holý A

更新日期：1985-03-01 00:00:00

abstract：:Class A-class C mechanism-based beta-lactamase inhibitors were designed on the basis of the intermediacy of an oxycarbenium species capable of cross-linking with amino acids residues in the active site. Penams 24 and 27 were very potent against AmpC in vitro. The MIC values of 24 in combination with piperacillin again...

journal_title：Journal of medicinal chemistry

authors： Sandanayaka VP,Prashad AS,Yang Y,Williamson RT,Lin YI,Mansour TS

更新日期：2003-06-19 00:00:00

abstract：:The potent inhibitory activity of novel 2-benzyltetralone and 2-benzylidenetetralone derivatives vs liver microsomal retinoic acid metabolizing enzymes and a MCF-7 CYP26A1 cell assay is described. In the liver microsomal assay, the 2-biphenylmethyl-6-hydroxytetralone derivatives 16a and 16b were found to be potent inh...

journal_title：Journal of medicinal chemistry

authors： Yee SW,Jarno L,Gomaa MS,Elford C,Ooi LL,Coogan MP,McClelland R,Nicholson RI,Evans BA,Brancale A,Simons C

更新日期：2005-11-17 00:00:00

abstract：:This report describes the syntheses and structure-activity relationships of 8-(4-methoxyphenyl)pyrazolo[1,5-a]-1,3,5-triazine corticotropin releasing factor receptor-1 (CRF(1)) receptor antagonists. CRF(1) receptor antagonists may be potential anxiolytic or antidepressant drugs. This research culminated in the discove...

journal_title：Journal of medicinal chemistry

authors： Gilligan PJ,He L,Clarke T,Tivitmahaisoon P,Lelas S,Li YW,Heman K,Fitzgerald L,Miller K,Zhang G,Marshall A,Krause C,McElroy J,Ward K,Shen H,Wong H,Grossman S,Nemeth G,Zaczek R,Arneric SP,Hartig P,Robertson DW,T

更新日期：2009-05-14 00:00:00

abstract：:Human thymidylate synthase (hTS), a target for antiproliferative drugs, is an obligate homodimer. Single-point mutations to alanine at the monomer-monomer interface may enable the identification of specific residues that delineate sites for drugs aimed at perturbing the protein-protein interactions critical for activi...

journal_title：Journal of medicinal chemistry

authors： Salo-Ahen OM,Tochowicz A,Pozzi C,Cardinale D,Ferrari S,Boum Y,Mangani S,Stroud RM,Saxena P,Myllykallio H,Costi MP,Ponterini G,Wade RC

更新日期：2015-04-23 00:00:00

abstract：:Multivalent ligands are promising pharmacological tools that may be more efficacious for several diseases than highly selective single-target drugs. A combined therapy using dopaminergic agonists and adenosinergic antagonists is currently being evaluated for the treatment of Parkinson's disease. [(a) Kanda, T.; et al....

journal_title：Journal of medicinal chemistry

authors： Vendrell M,Angulo E,Casadó V,Lluis C,Franco R,Albericio F,Royo M

更新日期：2007-06-28 00:00:00

abstract：:The use of privileged structures in drug discovery has proven to be an effective strategy, allowing the generation of innovative hits/leads and successful optimization processes. Chromone is recognized as a privileged structure and a useful template for the design of novel compounds with potential pharmacological inte...

journal_title：Journal of medicinal chemistry

authors： Reis J,Gaspar A,Milhazes N,Borges F

更新日期：2017-10-12 00:00:00

abstract：:A series of N alpha-(arylsulfonyl)-L-arginine amide derivatives with substituted or unsubstituted naphthalene and heterocyclic compounds as the N alpha-substituent was prepared and tested as inhibitors of the clotting activity of thrombin. N-n-Butyl and N-n-butyl-N-methyl derivatives of N alpha-dansyl-L-arginine amide...

journal_title：Journal of medicinal chemistry

authors： Kikumoto R,Tamao Y,Ohkubo K,Tezuka T,Tonomura S,Okamoto S,Funahara Y,Hijikata A

更新日期：1980-08-01 00:00:00

abstract：:The recently described potent and selective GABAA antagonist SR 95531 (gabazine) is compared to six other GABAA antagonists: (+)-bicuculline, (-)-securinine, (+)-tubocurarine, iso-THAZ, R-5135, and pitrazepine. Starting from ab initio molecular orbital calculations performed on crystal atomic coordinates, attempts wer...

journal_title：Journal of medicinal chemistry

authors： Rognan D,Boulanger T,Hoffmann R,Vercauteren DP,Andre JM,Durant F,Wermuth CG

更新日期：1992-05-29 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：:Benzofuran, indan and tetrahydronaphthalene analogs of 3,4-(methylenedioxy)amphetamine (MDA) were prepared in order to examine the role of the dioxole ring oxygen atoms of MDA in interacting with the serotonin and catecholamine uptake carriers. The series of compounds was evaluated for discriminative stimulus effects ...

journal_title：Journal of medicinal chemistry

authors： Monte AP,Marona-Lewicka D,Cozzi NV,Nichols DE

更新日期：1993-11-12 00:00:00

abstract：:Benzimidazoles carrying the 2-hydroxy-3-(isopropylamino)propoxy side chain at either the C-4 or C-5 ring positions were synthesized and investigated for beta-adrenergic blocking activity. Both compounds demonstrated beta2 selectivity when evaluated in guinea pig atrial and tracheal preparations. The C-4 isomer was 17 ...

journal_title：Journal of medicinal chemistry

authors： Crooks CR,Wright J,Callery PS,Moreton JE

更新日期：1979-02-01 00:00:00

abstract：:Because of the double-edged nature of NO, the development of isoform-selective NOS substrates is a highly desirable goal. Given the striking similarity in the heme active sites of the three NOS isoforms, it presents an challenging problem. Several N-aryl-N'-hydroxyguanidines have recently been shown as substrates that...

journal_title：Journal of medicinal chemistry

authors： Jia Q,Cai T,Huang M,Li H,Xian M,Poulos TL,Wang PG

更新日期：2003-06-05 00:00:00

abstract：:Several 4-alkyl-1-arylpiperazines that present a tetralin moiety on the terminal part of the side chain were synthesized in order to increase the selectivity on the 5-HT1A versus D-2, alpha 1, sigma, and other 5-HT receptors. Many changes have been effected on previous structures of type 3(1-aryl-4-[3-(1,2-dihydronaph...

journal_title：Journal of medicinal chemistry

authors： Perrone R,Berardi F,Colabufo NA,Leopoldo M,Tortorella V,Fiorentini F,Olgiati V,Ghiglieri A,Govoni S

更新日期：1995-03-17 00:00:00

abstract：:Adenosine receptor-binding profiles in rat brain tissues and antihypertensive effects in spontaneously hypertensive rats (SHR) of a series of 2-(cycloalkylalkynyl)adenosines (2-CAAs) and their congeners are described. The structure-activity relationship of this series of compounds is discussed, focusing on the length ...

journal_title：Journal of medicinal chemistry

authors： Abiru T,Miyashita T,Watanabe Y,Yamaguchi T,Machida H,Matsuda A

更新日期：1992-06-12 00:00:00