4-[omega-[4-arylpiperazin-1-yl]alkoxy]phenyl)imidazo[1,2-a]pyridine derivatives: fluorescent high-affinity dopamine D3 receptor ligands as potential probes for receptor visualization.

Abstract:

:Sixteen long-chain arylpiperazines bearing the fluorescent moiety 2-phenylimidazo[1,2-a]pyridine were synthesized as fluorescent dopamine D3 receptors ligands (385 nM < Ki < 0.72 nM). The most potent D3 compounds 15a and 19a (Ki = 1.6 and 0.72 nM, respectively) showed good Stokes shift and high quantum yield in ethanol (Phi = 0.74 and 0.66, respectively). In the first attempt, 15a was unable to visualize D3 receptors expressed in CHO cells by epifluorescence microscopy.

journal_name

J Med Chem

authors

Leopoldo M,Lacivita E,Passafiume E,Contino M,Colabufo NA,Berardi F,Perrone R

doi

10.1021/jm070721+

subject

Has Abstract

pub_date

2007-10-04 00:00:00

pages

5043-7

issue

20

eissn

0022-2623

issn

1520-4804

journal_volume

50

pub_type

杂志文章
  • 7-[3-(1-piperidinyl)propoxy]chromenones as potential atypical antipsychotics.

    abstract::Compound 1 (1-benzyl-3-methyl-4-[4-(4-fluorophenyl)-4-oxobutyl]piperazine), a synthetic intermediate identified as a potential atypical antipsychotic, was selected as the starting point for pharmacological improvement. From 1, sequential structural variations were conducted in order to improve its potency and oral bio...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm950894b

    authors: Bolós J,Gubert S,Anglada L,Planas JM,Burgarolas C,Castelló JM,Sacristán A,Ortiz JA

    更新日期:1996-07-19 00:00:00

  • Pyridoimidazolones as novel potent inhibitors of v-Raf murine sarcoma viral oncogene homologue B1 (BRAF).

    abstract::BRAF is a serine/threonine kinase that is mutated in a range of cancers, including 50-70% of melanomas, and has been validated as a therapeutic target. We have designed and synthesized mutant BRAF inhibitors containing pyridoimidazolone as a new hinge-binding scaffold. Compounds have been obtained which have low nanom...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm801509w

    authors: Niculescu-Duvaz D,Gaulon C,Dijkstra HP,Niculescu-Duvaz I,Zambon A,Ménard D,Suijkerbuijk BM,Nourry A,Davies L,Manne H,Friedlos F,Ogilvie L,Hedley D,Whittaker S,Kirk R,Gill A,Taylor RD,Raynaud FI,Moreno-Farre J,Marais

    更新日期:2009-04-23 00:00:00

  • Synthesis and dopaminergic properties of benzo-fused analogues of quinpirole and quinelorane.

    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

    pub_type: 杂志文章

    doi:10.1021/jm9804533

    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

  • Exploring the importance of piperazine N-atoms for sigma(2) receptor affinity and activity in a series of analogs of 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28).

    abstract::sigma(2)-Agonist 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (7, PB 28), which proved to revert doxorubicin resistance in breast cancer cells, was taken as a template to prepare new analogs. One of the two basic N-atoms was alternatively replaced by a methine or converted into an a...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm9007505

    authors: Berardi F,Abate C,Ferorelli S,Uricchio V,Colabufo NA,Niso M,Perrone R

    更新日期:2009-12-10 00:00:00

  • Two analogues of fenarimol show curative activity in an experimental model of Chagas disease.

    abstract::Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is an increasing threat to global health. Available medicines were introduced over 40 years ago, have undesirable side effects, and give equivocal results of cure in the chronic stage of the disease. We report the development of two compoun...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm401610c

    authors: Keenan M,Chaplin JH,Alexander PW,Abbott MJ,Best WM,Khong A,Botero A,Perez C,Cornwall S,Thompson RA,White KL,Shackleford DM,Koltun M,Chiu FC,Morizzi J,Ryan E,Campbell M,von Geldern TW,Scandale I,Chatelain E,Charman

    更新日期:2013-12-27 00:00:00

  • Conformational effects on the activity of drugs. 7. Synthesis and pharmacological properties of 2-(p-nitrophenyl)-substituted morpholines.

    abstract::A series of 1-(p-nitrophenyl)-2-aminoethanol derivatives and their morpholine analogues have been synthesized and pharmacologically investigated in order to confirm some pharmacological observations made with the N-isopropyl-substituted compounds. In agreement with the previously obtained results, the weak alpha-adren...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00192a023

    authors: Balsamo A,Crotti P,Lapucci A,Macchia B,Macchia F,Del Tacca M,Mazzanti L,Ceserani R

    更新日期:1979-06-01 00:00:00

  • Synthesis of mixed (E,Z)-, (E)-, and (Z)-norendoxifen with dual aromatase inhibitory and estrogen receptor modulatory activities.

    abstract::The first synthesis of the tamoxifen metabolite norendoxifen is reported. This included syntheses of (E)-norendoxifen, (Z)-norendoxifen, and (E,Z)-norendoxifen isomers. (Z)-Norendoxifen displayed affinity for aromatase (Ki 442 nM), estrogen receptor-α (EC50 17 nM), and estrogen receptor-β (EC50 27.5 nM), while the cor...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm400364h

    authors: Lv W,Liu J,Lu D,Flockhart DA,Cushman M

    更新日期:2013-06-13 00:00:00

  • Dissecting the determinants of cyclin-dependent kinase 2 and cyclin-dependent kinase 4 inhibitor selectivity.

    abstract::Cyclin dependent kinases are a key family of kinases involved in cell cycle regulation and are an attractive target for cancer chemotherapy. The roles of four residues of the cyclin-dependent kinase active site in inhibitor selectivity were investigated by producing cyclin-dependent kinase 2 mutants bearing equivalent...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm060216x

    authors: Pratt DJ,Bentley J,Jewsbury P,Boyle FT,Endicott JA,Noble ME

    更新日期:2006-09-07 00:00:00

  • Adenosine cyclic 3',5',-monophosphate phosphodiesterasr inhibitors. 2.3-Substituted 5,7-dialkylpyrazolo [1,5-a]pyrimidines.

    abstract::A number of 3-bromo-, 3-nitro-, and 3-ethoxycarbonyl-5,7-dialkylpyrazolo[1,5-a]pyrimidines were synthesized and screened as in vitro cAMP phosphodiesterase inhibitors. The condensation of 3-aminopyrazole with symmetrical beta-diketones (acetylacetone, heptane-3,5-dione, etc.) afforded symmetrical dialkylpyrazolo[1,5-a...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00239a004

    authors: Novinson T,Miller JP,Scholten M,Robins RK,Simon LN,O'Brien DE,Meyer RB Jr

    更新日期:1975-05-01 00:00:00

  • The identification of perillyl alcohol glycosides with improved antiproliferative activity.

    abstract::A facile route to perillyl alcohol (POH) differential glycosylation and the corresponding synthesis of a set of 34 POH glycosides is reported. Subsequent in vitro studies revealed a sugar dependent antiproliferative activity and the inhibition of S6 ribosomal protein phosphorylation as a putative mechanism of represen...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm500870u

    authors: Nandurkar NS,Zhang J,Ye Q,Ponomareva LV,She QB,Thorson JS

    更新日期:2014-09-11 00:00:00

  • Synthesis and preliminary biological studies of 4- and 5-[2-hydroxy-3-(isopropylamino)propoxy]benzimidazoles: selective beta2 adrenergic blocking agents.

    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

    pub_type: 杂志文章

    doi:10.1021/jm00188a019

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

    更新日期:1979-02-01 00:00:00

  • Property- and structure-guided discovery of a tetrahydroindazole series of interleukin-2 inducible T-cell kinase inhibitors.

    abstract::Interleukin-2 inducible T-cell kinase (ITK), a member of the Tec family of tyrosine kinases, plays a major role in T-cell signaling downstream of the T-cell receptor (TCR), and considerable efforts have been directed toward discovery of ITK-selective inhibitors as potential treatments of inflammatory disorders such as...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm500550e

    authors: Burch JD,Lau K,Barker JJ,Brookfield F,Chen Y,Chen Y,Eigenbrot C,Ellebrandt C,Ismaili MH,Johnson A,Kordt D,MacKinnon CH,McEwan PA,Ortwine DF,Stein DB,Wang X,Winkler D,Yuen PW,Zhang Y,Zarrin AA,Pei Z

    更新日期:2014-07-10 00:00:00

  • Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines.

    abstract::A series of pyridinyltetrahydropyridine derivatives was synthesized and evaluated as adrenoceptor and tetrabenazine antagonists. 4-(3-Fluoro-2-pyridinyl)-1,2,5,6-tetrahydropyridine proved to be the most potent and selective alpha 2-adrenoceptor antagonist of the series as measured in vitro by displacement of [3H]cloni...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00375a017

    authors: Saari WS,Halczenko W,Huff JR,Guare JP Jr,Hunt CA,Randall WC,Lotti VJ,Yarbrough GG

    更新日期:1984-09-01 00:00:00

  • Improvement in potency of an oxytocin antagonist after systematic substitutions with L-tryptophan.

    abstract::We report twelve analogues of [Pmp1,D-Trp2,Arg8]oxytocin, ANTAG (Pmp = beta, beta-pentamethylene-beta-mercaptopropionic acid), which is a potent antagonist (pA2 = 7.77) of the uterotonic effect of oxytocin (OT) in rats, as measured in a uterotonic assay. Nine of the following analogues were designed by replacement of ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00111a025

    authors: Flouret G,Brieher W,Majewski T,Mahan K,Wilson L Jr

    更新日期:1991-07-01 00:00:00

  • Further studies on the metabolism of carbidopa, (minus)-L-alpha-hydrazino-3,4-dihydroxy-alpha-methylbenzenepropanoic acid monohydrate, in the human, Rhesus monkey, dog, and rat.

    abstract::Major urinary metabolites of carbidopa have been identified. Estimates were made based on the recovery or radio activity or by glc analysis of pooled urine of the amounts of the urinary metabolites II (2-methyl-3'-methoxy-4'-hydroxyphenylpropionic acid), III (2-methyl-3,4-dihydroxyphenylpropionic acid), IV (3,4-dihydr...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00236a004

    authors: Vickers S,Stuart EK,Hucker HB

    更新日期:1975-02-01 00:00:00

  • 3,6-dibromocarbazole piperazine derivatives of 2-propanol as first inhibitors of cytochrome c release via Bax channel modulation.

    abstract::There is compelling evidence that Bax channel activity stimulates cytochrome c release leading ultimately to cell death, which is a key event in ischemic injuries and neurodegenerative diseases. Here 3,6-dibromocarbazole piperazine derivatives of 2-propanol are described as the first small and potent modulators of the...

    journal_title:Journal of medicinal chemistry

    pub_type: 信件

    doi:10.1021/jm034107j

    authors: Bombrun A,Gerber P,Casi G,Terradillos O,Antonsson B,Halazy S

    更新日期:2003-10-09 00:00:00

  • Exploration of novel aryl binding sites of farnesyltransferase using molecular modeling and benzophenone-based farnesyltransferase inhibitors.

    abstract::Most non-thiol CAAX-peptidomimetic farnesyltransferase inhibitors bear nitrogen-containing heterocycles in place of the terminal cysteine which are supposed to coordinate the enzyme-bound zinc. However, it has been shown that those nitrogen-containing heterocycles can be replaced by carbocyclic aromatic moieties which...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm010873j

    authors: Böhm M,Mitsch A,Wissner P,Sattler I,Schlitzer M

    更新日期:2001-09-13 00:00:00

  • Photoactivatable Prodrug of Doxazolidine Targeting Exosomes.

    abstract::Natural lipid nanocarriers, exosomes, carry cell-signaling materials such as DNA and RNA for intercellular communications. Exosomes derived from cancer cells contribute to the progression and metastasis of cancer cells by transferring oncogenic signaling molecules to neighboring and remote premetastatic sites. Therefo...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.8b01508

    authors: Tamura R,Balabanova A,Frakes SA,Bargmann A,Grimm J,Koch TH,Yin H

    更新日期:2019-02-28 00:00:00

  • A selective, orally bioavailable 1,2,4-triazolo[1,5-a]pyridine-based inhibitor of Janus kinase 2 for use in anticancer therapy: discovery of CEP-33779.

    abstract::Members of the JAK family of nonreceptor tyrosine kinases play a critical role in the growth and progression of many cancers and in inflammatory diseases. JAK2 has emerged as a leading therapeutic target for oncology, providing a rationale for the development of a selective JAK2 inhibitor. A program to optimize select...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm300248q

    authors: Dugan BJ,Gingrich DE,Mesaros EF,Milkiewicz KL,Curry MA,Zulli AL,Dobrzanski P,Serdikoff C,Jan M,Angeles TS,Albom MS,Mason JL,Aimone LD,Meyer SL,Huang Z,Wells-Knecht KJ,Ator MA,Ruggeri BA,Dorsey BD

    更新日期:2012-06-14 00:00:00

  • Cancer selective metallocenedicarboxylates of the fungal cytotoxin illudin M.

    abstract::The diester 2a obtained from 1,1'-ferrocenedicarboxylic acid and the highly and indiscriminately cytotoxic fungal metabolite illudin M (1) displayed antiproliferative activity at submicromolar IC(50) (72 h) values against a panel of eight cancer cell lines. Compound 2a was about 40 times less toxic than 1 to nonmalign...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm200359n

    authors: Schobert R,Seibt S,Mahal K,Ahmad A,Biersack B,Effenberger-Neidnicht K,Padhye S,Sarkar FH,Mueller T

    更新日期:2011-09-22 00:00:00

  • Synthesis and biological evaluation of novel pyridazinone-based alpha4 integrin receptor antagonists.

    abstract::A novel series of pyridazinone-functionalized phenylalanine analogues was prepared and evaluated for inhibition of cellular adhesion mediated by alpha4beta1/VCAM-1 and alpha4beta7/MAdCAM-1 interactions. Concise syntheses were developed and applied for exploration of structure-activity relationships pertaining to the p...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm060031q

    authors: Gong Y,Barbay JK,Dyatkin AB,Miskowski TA,Kimball ES,Prouty SM,Fisher MC,Santulli RJ,Schneider CR,Wallace NH,Ballentine SA,Hageman WE,Masucci JA,Maryanoff BE,Damiano BP,Andrade-Gordon P,Hlasta DJ,Hornby PJ,He W

    更新日期:2006-06-01 00:00:00

  • Ligand-based prediction of active conformation by 3D-QSAR flexibility descriptors and their application in 3+3D-QSAR models.

    abstract::A conceptionally new 3D molecular descriptor type and methodology are deduced by simple statistical thermodynamic reasoning, based on the free energy change encountered during a transformation of a conformational ensemble of the ligand to an active conformation. The performance of the descriptor was first tested on 37...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm049157i

    authors: Martinek TA,Otvös F,Dervarics M,Tóth G,Fülöp F

    更新日期:2005-05-05 00:00:00

  • A comparison of structure-activity relationships between spermidine and spermine analogue antineoplastics.

    abstract::A systematic investigation of the impact of spermidine analogues both in vitro and in vivo is described. The study characterizes the effects of these analogues on L1210 cell growth, polyamine pools, ornithine decarboxylase, S-adenosyl-L-methionine decarboxylase, spermidine/spermine N1-acetyltransferase, the maintenanc...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm960849j

    authors: Bergeron RJ,Feng Y,Weimar WR,McManis JS,Dimova H,Porter C,Raisler B,Phanstiel O

    更新日期:1997-05-09 00:00:00

  • Directed discovery of agents targeting the Met tyrosine kinase domain by virtual screening.

    abstract::Hepatocyte growth factor (HGF) is an important regulator of normal development and homeostasis, and dysregulated signaling through the HGF receptor, Met, contributes to tumorigenesis, tumor progression, and metastasis in numerous human malignancies. The development of selective small-molecule inhibitors of oncogenic t...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm800791f

    authors: Peach ML,Tan N,Choyke SJ,Giubellino A,Athauda G,Burke TR Jr,Nicklaus MC,Bottaro DP

    更新日期:2009-02-26 00:00:00

  • Feature selection for structure-activity correlation using binary particle swarms.

    abstract::We present a new feature selection algorithm for structure-activity and structure-property correlation based on particle swarms. Particle swarms explore the search space through a population of individuals that adapt by returning stochastically toward previously successful regions, influenced by the success of their n...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm0104668

    authors: Agrafiotis DK,Cedeño W

    更新日期:2002-02-28 00:00:00

  • Fluorinated pyrimidine nucleosides. 4. Synthesis and antitumor testing of a series of 2',5'-dideoxy- and 2',3',5'-trideoxynucleosides of 5-fluorouracil.

    abstract::Dideoxy- and trideoxynucleosides of 5-fluorouracil have been synthesized for antitumor evaluation. 2',5'-Dideoxy-5-fluorouridine (3) was prepared from 2'-deoxy-5-fluorouridine (1) by iodination using methyltriphenoxyphosponium iodide, followed by catalytic reduction. 1-(2',5'-Dideoxy-beta-D-threo-pentofuranosyl)5-fluo...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00182a008

    authors: Cook AF,Holman MJ,Kramer MJ

    更新日期:1980-08-01 00:00:00

  • Improved scoring of ligand-protein interactions using OWFEG free energy grids.

    abstract::A new approach to rapidly score protein-ligand interactions is tested on several protein-ligand systems. Results using this approach - the OWFEG free energy grid - are quite promising and are generally in better agreement with experiment (in some cases much better) than those obtained employing scoring techniques curr...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm000375v

    authors: Pearlman DA,Charifson PS

    更新日期:2001-02-15 00:00:00

  • Discovery and Structure-Activity Relationship Study of (Z)-5-Methylenethiazolidin-4-one Derivatives as Potent and Selective Pan-phosphatidylinositol 5-Phosphate 4-Kinase Inhibitors.

    abstract::Due to their role in many important signaling pathways, phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are attractive targets for the development of experimental therapeutics for cancer, metabolic, and immunological disorders. Recent efforts to develop small molecule inhibitors for these lipid kinases resulted i...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.0c00227

    authors: Manz TD,Sivakumaren SC,Ferguson FM,Zhang T,Yasgar A,Seo HS,Ficarro SB,Card JD,Shim H,Miduturu CV,Simeonov A,Shen M,Marto JA,Dhe-Paganon S,Hall MD,Cantley LC,Gray NS

    更新日期:2020-05-14 00:00:00

  • New dimeric analogues of ethidium; synthesis, interaction with DNA, and antitumor activity.

    abstract::Three new dimeric analogues of ethidium cation in which the monomeric moieties are linked at the 3' positions by alpha,omega-diethers of varying length and composition have been synthesized. The circular dichroism spectra of all three compounds indicate that they double intercalate, and their effects on the thermal he...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00143a014

    authors: Kuhlmann KF,Mosher CW

    更新日期:1981-11-01 00:00:00

  • Synthesis and evaluation of structurally constrained quinazolinone derivatives as potent and selective histamine H3 receptor inverse agonists.

    abstract::A series of structurally constrained derivatives of the potent H 3 inverse agonist 1 was designed, synthesized, and evaluated as histamine H 3 receptor inverse agonists. As a result, the N-cyclobutylpiperidin-4-yloxy group as in 2f was identified as an optimal surrogate structure for the flexible 1-pyrrolidinopropoxy ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm800569w

    authors: Nagase T,Mizutani T,Sekino E,Ishikawa S,Ito S,Mitobe Y,Miyamoto Y,Yoshimoto R,Tanaka T,Ishihara A,Takenaga N,Tokita S,Sato N

    更新日期:2008-11-13 00:00:00