High-affinity, non-peptide agonists for the ORL1 (orphanin FQ/nociceptin) receptor.

abstract：:A series of 1-aminopropan-2-ols were synthesized and evaluated against two strains of malaria, Plasmodium falciparum FCR3 (chloroquine-resistant) and 3D7 (chloroquine-sensitive). Microwave-assisted ring opening of epoxides (aryl and alkyl glycidyl ethers, glycidol, epichlorohydrin) with various amines without catalyst...

journal_title：Journal of medicinal chemistry

authors： Robin A,Brown F,Bahamontes-Rosa N,Wu B,Beitz E,Kun JF,Flitsch SL

更新日期：2007-08-23 00:00:00

abstract：:2'-Deoxy-2'-isocyano-1-beta-D-arabinofuranosylcytosine (8, NCDAC) has been synthesized as a potential antitumor antimetabolite from a corresponding 2'-azido-2'-deoxy-1-beta-D-arabinofuranosyluracil derivative 2a. Uracil and thymine analogues 6a and 6b of 8 were also prepared. Attempts to synthesize 2'-deoxy-2'-isocyan...

journal_title：Journal of medicinal chemistry

authors： Matsuda A,Dan A,Minakawa N,Tregear SJ,Okazaki S,Sugimoto Y,Sasaki T

更新日期：1993-12-24 00:00:00

abstract：:Accumulation of beta-amyloid aggregates (Abeta) in the brain is linked to the pathogenesis of Alzheimer's disease (AD). We report a novel approach for producing 1,4-diphenyltriazoles as probes for targeting Abeta aggregates in the brain. The imaging probes, a series of substituted tricyclic 1,4-diphenyltriazoles showi...

journal_title：Journal of medicinal chemistry

authors： Qu W,Kung MP,Hou C,Oya S,Kung HF

更新日期：2007-07-12 00:00:00

abstract：:Novel dicationic triazoles 1-60 were synthesized by the Pinner method from the corresponding dinitriles, prepared via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The type and the placement of cationic moieties as well as the nature of aromatic substituents influenced in vitro antiprotozoal activities o...

journal_title：Journal of medicinal chemistry

authors： Bakunov SA,Bakunova SM,Wenzler T,Ghebru M,Werbovetz KA,Brun R,Tidwell RR

更新日期：2010-01-14 00:00:00

abstract：:5-(Ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole (ezutromid, 1) is a first-in-class utrophin modulator that has been evaluated in a phase 2 clinical study for the treatment of Duchenne muscular dystrophy (DMD). Ezutromid was found to undergo hepatic oxidation of its 2-naphthyl substituent to produce two regioisome...

journal_title：Journal of medicinal chemistry

authors： Chatzopoulou M,Claridge TDW,Davies KE,Davies SG,Elsey DJ,Emer E,Fletcher AM,Harriman S,Robinson N,Rowley JA,Russell AJ,Tinsley JM,Weaver R,Wilkinson IVL,Willis NJ,Wilson FX,Wynne GM

更新日期：2020-03-12 00:00:00

abstract：:Efforts were made to improve a series of potent dual ABL/SRC inhibitors based on a 7-azaindole core with the aim of developing compounds that demonstrate a wider activity on selected oncogenic kinases. Multi-targeted kinase inhibitors (MTKIs) were then derived, focusing on kinases involved in both angiogenesis and tum...

journal_title：Journal of medicinal chemistry

authors： Daydé-Cazals B,Fauvel B,Singer M,Feneyrolles C,Bestgen B,Gassiot F,Spenlinhauer A,Warnault P,Van Hijfte N,Borjini N,Chevé G,Yasri A

更新日期：2016-04-28 00:00:00

abstract：:Cyclin-dependent kinases (cdk) have recently raised considerable interest in view of their essential role in the regulation of the cell division cycle. The structure-activity relationships of cdk inhibition showed that the 1, 3; and 7 positions of the purine ring must remain free, probably for a direct interaction, in...

journal_title：Journal of medicinal chemistry

authors： Havlícek L,Hanus J,Veselý J,Leclerc S,Meijer L,Shaw G,Strnad M

更新日期：1997-02-14 00:00:00

abstract：:The binding structures of 11 human oxidosqualene cyclase inhibitors designed as cholesterol-lowering agents were determined for the squalene-hopene cyclase from Alicyclobacillus acidocaldarius, which is the only structurally known homologue of the human enzyme. The complexes were produced by cocrystallization, and the...

journal_title：Journal of medicinal chemistry

authors： Lenhart A,Reinert DJ,Aebi JD,Dehmlow H,Morand OH,Schulz GE

更新日期：2003-05-22 00:00:00

abstract：:From a series of small fragments that was designed to probe the histamine H(4) receptor (H(4)R), we previously described quinoxaline-containing fragments that were grown into high affinity H(4)R ligands in a process that was guided by pharmacophore modeling. With a scaffold hopping exercise and using the same in silic...

journal_title：Journal of medicinal chemistry

authors： Smits RA,de Esch IJ,Zuiderveld OP,Broeker J,Sansuk K,Guaita E,Coruzzi G,Adami M,Haaksma E,Leurs R

更新日期：2008-12-25 00:00:00

abstract：:Tocainide and related optically active chiral alpha-aminoanilides were synthesized and tested in vivo via the hot plate test to evaluate their central analgesic action. The aims of the study were to verify if a) the increase in lipophilicity, obtained by the introduction of an alkyl group on the steric center (3f-i), ...

journal_title：Journal of medicinal chemistry

authors： Corbo F,Franchini C,Lentini G,Muraglia M,Ghelardini C,Matucci R,Galeotti N,Vivoli E,Tortorella V

更新日期：2007-04-19 00:00:00

abstract：:Female sexual arousal disorder (FSAD) is a highly prevalent sexual disorder affecting up to 40% of women. We describe herein our efforts to identify a selective neutral endopeptidase (NEP) inhibitor as a potential treatment for FSAD. The rationale for this approach, together with a description of the medicinal chemist...

journal_title：Journal of medicinal chemistry

authors： Pryde DC,Maw GN,Planken S,Platts MY,Sanderson V,Corless M,Stobie A,Barber CG,Russell R,Foster L,Barker L,Wayman C,Van Der Graaf P,Stacey P,Morren D,Kohl C,Beaumont K,Coggon S,Tute M

更新日期：2006-07-13 00:00:00

abstract：:SHP-2, a nonreceptor protein tyrosine phosphatase encoded by the PTPN11 gene, mediates cell signaling by growth factors and cytokines via the RAS/MAP kinase pathway. Somatic mutations in PTPN11 gene account for approximately 18% of juvenile myelomonocytic leukemia (JMML) patients. Moreover, SHP-2 mutations leading to ...

journal_title：Journal of medicinal chemistry

authors： Geronikaki A,Eleftheriou P,Vicini P,Alam I,Dixit A,Saxena AK

更新日期：2008-09-11 00:00:00

abstract：:Thirteen newly synthesized or resynthesized diamine-platinum(II) complexes were characterized, and their cytotoxic activities (IC50) were tested on parental and resistant ovarian cancer cell lines. They represent models of conjugates between biologically active vectors and cytotoxic Pt(II) moieties within the "drug ta...

journal_title：Journal of medicinal chemistry

authors： Monti E,Gariboldi M,Maiocchi A,Marengo E,Cassino C,Gabano E,Osella D

更新日期：2005-02-10 00:00:00

abstract：:7-Substituted 3-aryl-1,6-naphthyridine-2,7-diamines and related 2-ureas are inhibitors of fibroblast growth factor receptor-1 (FGFR-1) and vascular endothelial growth factor receptor-2 (VEGFR-2). 3-(3,5-Dimethoxyphenyl) and 3-phenyl analogues were prepared from 7-acetamido-2-tert-butylureas by alkylation with benzyl o...

journal_title：Journal of medicinal chemistry

authors： Thompson AM,Delaney AM,Hamby JM,Schroeder MC,Spoon TA,Crean SM,Showalter HD,Denny WA

更新日期：2005-07-14 00:00:00

abstract：:A number of fluorenyl and diphenylmethane analogues of verapamil, chosen as having the same substituents arranged in different ways around the quaternary carbon, were synthesized in order to evaluate the importance of the stereoisomerism at that point of the molecule. The compounds were tested with the Langendorff tec...

journal_title：Journal of medicinal chemistry

authors： Gualtieri F,Teodori E,Bellucci C,Pesce E,Piacenza G

更新日期：1985-11-01 00:00:00

abstract：:Structural simplification of an antimitotic natural product podophyllotoxin with mimetic heterocyclic scaffolds constructed using multicomponent reactions led to the identification of compounds exhibiting low nanomolar antiproliferative and apoptosis-inducing properties. The most potent compounds were found in the dih...

journal_title：Journal of medicinal chemistry

authors： Magedov IV,Frolova L,Manpadi M,Bhoga Ud,Tang H,Evdokimov NM,George O,Georgiou KH,Renner S,Getlik M,Kinnibrugh TL,Fernandes MA,Van slambrouck S,Steelant WF,Shuster CB,Rogelj S,van Otterlo WA,Kornienko A

更新日期：2011-06-23 00:00:00

abstract：:A series of 2-aryl-4-benzoyl-imidazoles (ABI) was synthesized as a result of structural modifications based on the previous set of 2-aryl-imidazole-4-carboxylic amide (AICA) derivatives and 4-substituted methoxylbenzoyl-aryl-thiazoles (SMART). The average IC(50) of the most active compound (5da) was 15.7 nM. ABI analo...

journal_title：Journal of medicinal chemistry

authors： Chen J,Wang Z,Li CM,Lu Y,Vaddady PK,Meibohm B,Dalton JT,Miller DD,Li W

更新日期：2010-10-28 00:00:00

abstract：:Certain phenylalkylamine derivatives have been considered to bind selectively at 5-HT2 serotonin receptors. It is now recognized that the most widely used derivatives, i.e., 1-(2,5-dimethoxy-4-X-phenyl)-2-aminopropanes where X = Me (DOM), Br (DOB), and I (DOI) (1-3, respectively) also bind at the more recently identif...

journal_title：Journal of medicinal chemistry

authors： Glennon RA,Raghupathi R,Bartyzel P,Teitler M,Leonhardt S

更新日期：1992-02-21 00:00:00

abstract：:Glucuronidation and transporter-mediated efflux into bile are important in the elimination of xeno- and endobiotics, including the natural biladienone pigment bilirubin. The mechanisms of these processes and the structural factors that dictate whether cholephilic compounds are excreted directly in bile or require prio...

journal_title：Journal of medicinal chemistry

authors： McDonagh AF,Lightner DA

更新日期：2007-02-08 00:00:00

abstract：:A series of 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives was synthesized and evaluated as inhibitors of cAMP hydrolysis by a crude human platelet phosphodiesterase preparation and as inhibitors of ADP- and collagen-induced aggregation of rabbit blood platelets. The parent structure 7a, demonstrated potent i...

journal_title：Journal of medicinal chemistry

authors： Meanwell NA,Roth HR,Smith EC,Wedding DL,Wright JJ,Fleming JS,Gillespie E

更新日期：1991-09-01 00:00:00

abstract：:To find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) was designed and synthesized. In this series, compound 7, in which the hydroxamic acid of SAHA is replaced by a thiol, was found to be as potent as SAHA, and optimization of t...

journal_title：Journal of medicinal chemistry

authors： Suzuki T,Nagano Y,Kouketsu A,Matsuura A,Maruyama S,Kurotaki M,Nakagawa H,Miyata N

更新日期：2005-02-24 00:00:00

abstract：:In an analogy to the potent catechol dopamine D1 agonists dihydrexidine (1) and dinapsoline (2), benzo rings were fused onto the structures of the dopamine D2-selective agonists quinelorane (3) and quinpirole (4). Each of the phenyl ring-substituted derivatives had significant affinity for D2 receptors, albeit somewha...

journal_title：Journal of medicinal chemistry

authors： Doll MK,Nichols DE,Kilts JD,Prioleau C,Lawler CP,Lewis MM,Mailman RB

更新日期：1999-03-11 00:00:00

abstract：:Basic side chains determine the pharmacology of selective estrogen receptor modulators such as tamoxifen or raloxifene. In this study we tried to turn the hormonal profile of (4R,5S)/(4S,5R)-4,5-bis(4-hydroxyphenyl)-2-imidazolines from agonistic to antagonistic by introduction of a dimethylaminoethane, a piperidin-1-y...

journal_title：Journal of medicinal chemistry

authors： von Rauch M,Busch S,Gust R

更新日期：2005-01-27 00:00:00

abstract：:A series of amide analogues of the 2,2'-dithiobis(1H-indole-3-alkaonic acid) class of tyrosine kinase inhibitors have been prepared, by reaction of 1H-indole-3-alkanamides (8) with S2Cl2, and separation of the desired disulfides from the initial mixtures of mono-, di-, and trisulfides formed. These amides were evaluat...

journal_title：Journal of medicinal chemistry

authors： Thompson AM,Fry DW,Kraker AJ,Denny WA

更新日期：1994-03-04 00:00:00

abstract：:Doxazosin analogues 1-3 and 1a were synthesized and investigated at alpha1-adrenoceptors and PC-3, DU-145, and LNCaP human prostate cancer cells. Compound 1 (cyclodoxazosin) was a potent alpha(1B)-adrenoceptor antagonist displaying antiproliferative activity higher than that of doxazosin in cancer cells in vitro and i...

journal_title：Journal of medicinal chemistry

authors： Giardinà D,Martarelli D,Sagratini G,Angeli P,Ballinari D,Gulini U,Melchiorre C,Poggesi E,Pompei P

更新日期：2009-08-13 00:00:00

abstract：:On the basis of our finding that the antitumor effect of 5-{4-[(1-methylcyclohexyl)methoxy]benzyl}thiazolidine-2,4-dione, a thiazolidinedione peroxisome proliferator-activated receptor (PPAR)γ agonist, was, in part, attributable to its ability to block glucose uptake independently of PPARγ, we used its PPARγ-inactive ...

journal_title：Journal of medicinal chemistry

authors： Wang D,Chu PC,Yang CN,Yan R,Chuang YC,Kulp SK,Chen CS

更新日期：2012-04-26 00:00:00

abstract：:The synthesis and biological evaluation of a series of novel 1-(aryloxy)-2-propanolamines and several related deshydroxy analogues are described. Compounds 4-29 were prepared and investigated for their class III electrophysiological activity in isolated canine Purkinje fibers and in anesthetized open-chest dogs. None ...

journal_title：Journal of medicinal chemistry

authors： Butera JA,Spinelli W,Anantharaman V,Marcopulos N,Parsons RW,Moubarak IF,Cullinan C,Bagli JF

更新日期：1991-11-01 00:00:00

abstract：:Sildenafil (5-[2-ethoxy-5-(4-methyl-1-piperazinylsulfonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one), a potent and selective phosphodiesterase type 5 (PDE5) inhibitor, provided the first oral treatment for male erectile dysfunction. The objective of the work reported in this paper was t...

journal_title：Journal of medicinal chemistry

authors： Allerton CM,Barber CG,Beaumont KC,Brown DG,Cole SM,Ellis D,Lane CA,Maw GN,Mount NM,Rawson DJ,Robinson CM,Street SD,Summerhill NW

更新日期：2006-06-15 00:00:00

abstract：:Following erythrocyte invasion, malaria parasites export a catalogue of remodeling proteins into the infected cell that enable parasite development in the human host. Export is dependent on the activity of the aspartyl protease, plasmepsin V (PMV), which cleaves proteins within the Plasmodium export element (PEXEL; Rx...

journal_title：Journal of medicinal chemistry

authors： Sleebs BE,Gazdik M,O'Neill MT,Rajasekaran P,Lopaticki S,Lackovic K,Lowes K,Smith BJ,Cowman AF,Boddey JA

更新日期：2014-09-25 00:00:00

abstract：:Lofexidine, an alpha 2-agonist, has central hypotensive activity and peripheral intestinal antisecretory activity. Analogues were synthesized with increased polarity in an attempt to prevent penetration of the blood-brain barrier. The compounds were evaluated in the cholera toxin treated ligated jejunum of the rat and...

journal_title：Journal of medicinal chemistry

authors： Moormann AE,Pitzele BS,Jones PH,Gullikson GW,Albin D,Yu SS,Bianchi RG,Sanguinetti EL,Rubin B,Grebner M

更新日期：1990-02-01 00:00:00