Discovery of bishomo(hetero)arylpiperazines as novel multifunctional ligands targeting dopamine D(3) and serotonin 5-HT(1A) and 5-HT(2A) receptors.

abstract：:Four nucleoside analogues ( 1- 4) containing a common heterocyclic base, 4(7)-amino-6(5) H-imidazo[4,5- d]pyridazin-7(4)one, were screened against calf-intestine adenosine deaminase. Compounds 1 and 3 with K(i) values of 10-12 microM are more than four times as potent inhibitors of ADA compared with 2 and 4, with K(i)...

journal_title：Journal of medicinal chemistry

authors： Ujjinamatada RK,Phatak P,Burger AM,Hosmane RS

更新日期：2008-02-14 00:00:00

abstract：:Partially hydrogenated derivatives of the new heterocyclic ring systems benz[d]indolo[2,3-g]azecine and bisindolo[3,2-d][2, 3-g]azecine were synthesized starting from lactones and amines via the described synthetic methods. In binding assays with rat striatal receptors, 7-methyl-6,7,8,9,14,15-hexahydro-5H-benz[d]indol...

journal_title：Journal of medicinal chemistry

authors： Witt T,Hock FJ,Lehmann J

更新日期：2000-05-18 00:00:00

abstract：:An imidazo[4,5-h]isoquinolin-7,9-dione (1) was identified as an adenosine 5'-triphosphate competitive inhibitor of lck by high throughput screening. Initial structure-activity relationship studies identified the dichlorophenyl ring and the imide NH as important pharmacophores. A binding model was constructed to unders...

journal_title：Journal of medicinal chemistry

authors： Snow RJ,Cardozo MG,Morwick TM,Busacca CA,Dong Y,Eckner RJ,Jacober S,Jakes S,Kapadia S,Lukas S,Panzenbeck M,Peet GW,Peterson JD,Prokopowicz AS 3rd,Sellati R,Tolbert RM,Tschantz MA,Moss N

更新日期：2002-08-01 00:00:00

abstract：:A series of 3-aryloxindole derivatives were synthesized and evaluated as activators of the cloned maxi-K channel mSlo expressed in Xenopus laevis oocytes using electrophysiological methods. The most promising maxi-K openers to emerge from this study were (+/-)-3-(5-chloro-2-hydroxyphenyl)-1,3-dihydro-3-hydroxy-6-(trif...

journal_title：Journal of medicinal chemistry

authors： Hewawasam P,Erway M,Moon SL,Knipe J,Weiner H,Boissard CG,Post-Munson DJ,Gao Q,Huang S,Gribkoff VK,Meanwell NA

更新日期：2002-03-28 00:00:00

abstract：:Optimization of the pharmacokinetic properties for a series of benzoxazolone derivatives led to the identification of 9b, which showed anxiolytic effect in a rat model. However, 9b, like known benzodiazepines, induced motor impairment. Investigation into the cause of this unexpected side effect and management of 9b of...

journal_title：Journal of medicinal chemistry

authors： Fukaya T,Ishiyama T,Baba S,Masumoto S

更新日期：2013-10-24 00:00:00

abstract：:A new series of N'-(pyridinioacetyl)alkanoic and -benzoic acid hydrazides, as chloride salts, and some cyclic analogues produced ring closure have been synthesize and tested in a search for more effective germicides. Physicochemical parameters, such as surface tension, critical micelle concentration, and thermodynamic...

journal_title：Journal of medicinal chemistry

authors： Sicardi SM,Vega CM,Cimijotti EB

更新日期：1980-10-01 00:00:00

abstract：:The possibility that catecholamines can be oxidized via aberrant pathways in vivo is open to question, but in vitro oxidation via aerobic manipulations is established. Assuming oxidation does occur, we have examined quantitatively the fast chemical reactions of the initial oxidation products, the o-quinones. The natur...

journal_title：Journal of medicinal chemistry

authors： Tse DC,McCreery RL,Adams RN

更新日期：1976-01-01 00:00:00

abstract：:Analogues of the potent inhibitor of choline acetyltransferase (CAT) (E)-4-(1-naphthylvinyl)pyridine methiodide were synthesized and evaluated for their ability to inhibit CAT and protect against nerve agent intoxication. Several compounds, notably (E)-1-(2-hydroxyethyl)-(1-naphthylvinyl)pyridinium bromide (3), (E)-1-...

journal_title：Journal of medicinal chemistry

authors： Gray AP,Platz RD,Henderson TR,Chang TC,Takahashi K,Dretchen KL

更新日期：1988-04-01 00:00:00

abstract：:N-Aminated nucleoside complexes of cis-dichloroplatinum(II) were synthesized, and their antitumor activities against L1210 cells in mice and in vitro were studied. While the native nucleosides failed to show any antitumor activity, the complexes exhibited high antitumor activity and had no nephrotoxicity in mice. Stud...

journal_title：Journal of medicinal chemistry

authors： Maeda M,Abiko N,Uchida H,Sasaki T

更新日期：1984-04-01 00:00:00

abstract：:Quantitative structure-activity relationships (QSAR) have been established for the inhibition of dihydrofolate reductase and thymidylate synthetase by 2,4-diaminoquinazoline-glutamic acid analogues. For dihydrofolate reductase from both human acute lymphocytic leukemia cells and murine L1210R cells, QSAR's obtained wi...

journal_title：Journal of medicinal chemistry

authors： Chen BK,Horváth C,Bertino JR

更新日期：1979-05-01 00:00:00

abstract：:A series of 2-(tetrahydroisoquinolin-2-ylmethyl)- and 2-(isoindolin-2-ylmethyl)imidazolines were prepared and tested for alpha 1- and alpha 2-adrenoceptor affinity with radioligand binding. Several compounds, 5-fluoro-(5h), 5-chloro-(5j), 5,8-dimethoxy- (5r), and 5,8-dimethoxy- (5r),1-methyl- (5s) 2-(tetrahydroisoquin...

journal_title：Journal of medicinal chemistry

authors： Clark RD,Berger J,Garg P,Weinhardt KK,Spedding M,Kilpatrick AT,Brown CM,MacKinnon AC

更新日期：1990-02-01 00:00:00

abstract：:Acyclic nucleosides 1-[[2-hydroxy-1-(hydroxymethyl)ethoxy] methyl]-5-benzyluracil (DHPBU) (1) and 1-[[2-hydroxy-1-(aminomethyl)ethoxy]methyl]-5-benzyluracil (AHPBU) (2) have been synthesized by direct coupling of bis(trimethylsilyl)-5-benzyluracil with the corresponding chloromethyl ether, followed by removal of the b...

journal_title：Journal of medicinal chemistry

authors： Lin TS,Liu MC

更新日期：1985-07-01 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：:The weak antiallergic activity of 6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carbox yli c acid (1) in the rat reaginic passive cutaneous anaphylaxis test was enhanced by the introduction of an (arylamino)methylene moiety into position 9 of the pyridopyrimidine ring. Compound 34, (+)-6(S)-methyl-9-[...

journal_title：Journal of medicinal chemistry

authors： Hermecz I,Horváth A,Mészáros Z,De Vos C,Rodriguez L

更新日期：1984-10-01 00:00:00

abstract：:A series of N-substituted 3-aminoglutarimides have been synthesized and tested for inhibitory activity against a range of chemokines in vitro and for suppression of lipopolysaccharide-induced inflammation in vivo. The results show that they represent the first class of small molecules with broad-spectrum chemokine inh...

journal_title：Journal of medicinal chemistry

authors： Fox DJ,Reckless J,Warren SG,Grainger DJ

更新日期：2002-01-17 00:00:00

abstract：:Recently, we reported the identification of a novel class of pregnane-X-receptor (PXR) agonists, solomonsterols A and B, isolated from the marine sponge Theonella swinhoei. Preliminary pharmacological studies demonstrated that these natural compounds are potential leads for the treatment of human disorders characteriz...

journal_title：Journal of medicinal chemistry

authors： Sepe V,Ummarino R,D'Auria MV,Mencarelli A,D'Amore C,Renga B,Zampella A,Fiorucci S

更新日期：2011-07-14 00:00:00

abstract：:Inhibition of inducible T-cell kinase (ITK), a nonreceptor tyrosine kinase, may represent a novel treatment for allergic asthma. In our previous reports, we described the discovery of sulfonylpyridine (SAP), benzothiazole (BZT), indazole (IND), and tetrahydroindazole (THI) series as novel ITK inhibitors and how comput...

journal_title：Journal of medicinal chemistry

authors： Heifetz A,Trani G,Aldeghi M,MacKinnon CH,McEwan PA,Brookfield FA,Chudyk EI,Bodkin M,Pei Z,Burch JD,Ortwine DF

更新日期：2016-05-12 00:00:00

abstract：:Reaction of 3'-acetylthymidine with phosphorus oxychloride in trimethyl phosphate yielded the phosphorodichloridate 5, which was subsequently reacted with aziridine, or 2,2-dimethylaziridine to give compounds 6 and 7, respectively. The 2,2-dimethylaziridine derivative 7 was considerably more active than 6 against leuk...

journal_title：Journal of medicinal chemistry

authors： Hsiao LY,Bardos TJ

更新日期：1981-07-01 00:00:00

abstract：:A set of 2,4-diamino-5-(3-X-phenyl)-s-triazines was used to inhibit the growth of tumor cells (L5178 leukemia) in culture. The molar concentration (C) of triazine causing 50% reduction in the rate of cell growth was used to develop a quantitative structure-activity relationship: log 1/C = 1.32 pi - 1.70 log (beta.10 p...

journal_title：Journal of medicinal chemistry

authors： Khwaja TA,Pentecost S,Selassie CD,Guo Z,Hansch C

更新日期：1982-02-01 00:00:00

abstract：:A dihydropyridine-pyridine type redox pro-drug system was developed for delivering quaternary pyridinium salts through biological membranes. As a first application, the dihydropyridine derivative of N-methylpyridinium-2-carbaldoxime chloride (2-PAM) was synthesized using a reduction-addition-elimination sequence. The ...

journal_title：Journal of medicinal chemistry

authors： Bodor N,Shek E,Higuchi T

更新日期：1976-01-01 00:00:00

abstract：:Deltorphin analogues were substituted by a series of achiral C alpha,alpha-dialkyl cyclic alpha-amino acids (1-aminocycloalkane-1-carboxylic acids, Ac chi c, where chi = a hexane, pentane, or propane cycloalkane ring) in position 2, 3, 4, or 2 and 3 in deltorphin C, and in position 2 in [Ac6c2,-des-Phe3]deltorphin C h...

journal_title：Journal of medicinal chemistry

authors： Breveglieri A,Guerrini R,Salvadori S,Bianchi C,Bryant SD,Attila M,Lazarus LH

更新日期：1996-02-02 00:00:00

abstract：:There is urgent need for new therapeutic strategies to fight the global threat of antibiotic resistance. The focus of this Perspective is on chemical agents that target the most common mechanisms of antibiotic resistance such as enzymatic inactivation of antibiotics, changes in cell permeability, and induction/activat...

journal_title：Journal of medicinal chemistry

authors： Schillaci D,Spanò V,Parrino B,Carbone A,Montalbano A,Barraja P,Diana P,Cirrincione G,Cascioferro S

更新日期：2017-10-26 00:00:00

abstract：:A series of biphenyl analogues of the new tuberculosis drug PA-824 was prepared, primarily by coupling the known (6S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-ol with iodobenzyl halides, followed by Suzuki coupling of these iodides with appropriate arylboronic acids or by assembly of the complete biaryl side...

journal_title：Journal of medicinal chemistry

authors： Palmer BD,Thompson AM,Sutherland HS,Blaser A,Kmentova I,Franzblau SG,Wan B,Wang Y,Ma Z,Denny WA

更新日期：2010-01-14 00:00:00

abstract：:Two new peptides, tailored after Ac-Thr-D-Trp(CHO)-Phe-NMeBzl (TRI), namely, Ac-Thr-D-Trp(CHO)-Phe-NMe alpha MeBzl (TRA) and Ac-Thr-D-Trp(CHO)-Oic-NMeBzl (TOI), in which Phe is replaced by (3aS, 7aS)-octahydroindole-2-carboxylic acid, proved more potent and selective NK1 antagonists. The conformational properties of a...

journal_title：Journal of medicinal chemistry

authors： Caliendo G,Grieco P,Perissutti E,Santagada V,Saviano G,Tancredi T,Temussi PA

更新日期：1997-02-14 00:00:00

abstract：:Inhibition of histone deacetylases (HDACs) leads to growth arrest, differentiation, or apoptosis of tumor cell lines, suggesting HDACs as promising targets for cancer therapy. At present, only one HDAC inhibitor (HDACi) is used in therapy: suberoylanilide hydroxamic acid (SAHA). Here, we describe the synthesis and bio...

journal_title：Journal of medicinal chemistry

authors： Oger F,Lecorgne A,Sala E,Nardese V,Demay F,Chevance S,Desravines DC,Aleksandrova N,Le Guével R,Lorenzi S,Beccari AR,Barath P,Hart DJ,Bondon A,Carettoni D,Simonneaux G,Salbert G

更新日期：2010-03-11 00:00:00

abstract：:The imidazoquinoline (R)-5,6-Dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine [(R)-3] is a potent dopamine agonist when tested in animals but surprisingly shows very low affinity in in vitro binding assays. When incubated with mouse or monkey liver S9 microsomes, (R)-3 is metabolized by N-demethylation and ox...

journal_title：Journal of medicinal chemistry

authors： Heier RF,Dolak LA,Duncan JN,Hyslop DK,Lipton MF,Martin IJ,Mauragis MA,Piercey MF,Nichols NF,Schreur PJ,Smith MW,Moon MW

更新日期：1997-02-28 00:00:00

abstract：:Reports of a high-affinity ligand for E-selectin, sialyl di-Lewis(x) (sLe(x)Le(x), 1), motivated us to incorporate modifications to previously reported biphenyl-based inhibitors that would provide additional interactions with the protein. These compounds were assayed for the ability to inhibit the binding of sialyl Le...

journal_title：Journal of medicinal chemistry

authors： Kogan TP,Dupré B,Bui H,McAbee KL,Kassir JM,Scott IL,Hu X,Vanderslice P,Beck PJ,Dixon RA

更新日期：1998-03-26 00:00:00

abstract：:As a part of our program aimed at exploring the biological activity of symmetrical substitution of side chains into the anthracene-9,10-dione chromophore, we have synthesized a series of 1,5-bisthioanthraquinones 2 and 1,5-bisacyloxyanthraquinones 3 that are related to the antitumor agent mitoxantrone. Since the telom...

journal_title：Journal of medicinal chemistry

authors： Huang HS,Chiou JF,Fong Y,Hou CC,Lu YC,Wang JY,Shih JW,Pan YR,Lin JJ

更新日期：2003-07-17 00:00:00

abstract：:A series of 1-substituted mitosene analogues of the mitomycin antitumor antibiotics was prepared by total synthesis and screened for activity against P388 leukemia in mice. In general, analogues with moderately good leaving groups (mostly esters) at the 1 position were active, whereas analogues without such substituen...

journal_title：Journal of medicinal chemistry

authors： Hodges JC,Remers WA,Bradner WT

更新日期：1981-10-01 00:00:00

abstract：:Discovery of novel effective and safe antimalarials has been traditionally focused on targeting erythrocytic parasite stages that cause clinical symptoms. However, elimination of malaria parasites from the human population will be facilitated by intervention at different life-cycle stages of the parasite, including th...

journal_title：Journal of medicinal chemistry

authors： Ressurreição AS,Gonçalves D,Sitoe AR,Albuquerque IS,Gut J,Góis A,Gonçalves LM,Bronze MR,Hanscheid T,Biagini GA,Rosenthal PJ,Prudêncio M,O'Neill P,Mota MM,Lopes F,Moreira R

更新日期：2013-10-10 00:00:00