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 Chemjournal_title
Journal of medicinal chemistryauthors
Leopoldo M,Lacivita E,Passafiume E,Contino M,Colabufo NA,Berardi F,Perrone Rdoi
10.1021/jm070721+subject
Has Abstractpub_date
2007-10-04 00:00:00pages
5043-7issue
20eissn
0022-2623issn
1520-4804journal_volume
50pub_type
杂志文章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
更新日期:1996-07-19 00:00:00
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
更新日期:2009-04-23 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
pub_type: 杂志文章
doi:10.1021/jm9804533
更新日期:1999-03-11 00:00:00
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
更新日期:2009-12-10 00:00:00
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
更新日期:2013-12-27 00:00:00
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
更新日期:1979-06-01 00:00:00
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
更新日期:2013-06-13 00:00:00
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
更新日期:2006-09-07 00:00:00
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
更新日期:1975-05-01 00:00:00
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
更新日期:2014-09-11 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
pub_type: 杂志文章
doi:10.1021/jm00188a019
更新日期:1979-02-01 00:00:00
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
更新日期:2014-07-10 00:00:00
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
更新日期:1984-09-01 00:00:00
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
更新日期:1991-07-01 00:00:00
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
更新日期:1975-02-01 00:00:00
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
更新日期:2003-10-09 00:00:00
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
更新日期:2001-09-13 00:00:00
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
更新日期:2019-02-28 00:00:00
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
更新日期:2012-06-14 00:00:00
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
更新日期:2011-09-22 00:00:00
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
更新日期:2006-06-01 00:00:00
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
更新日期:2005-05-05 00:00:00
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
更新日期:1997-05-09 00:00:00
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
更新日期:2009-02-26 00:00:00
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
更新日期:2002-02-28 00:00:00
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
更新日期:1980-08-01 00:00:00
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
更新日期:2001-02-15 00:00:00
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
更新日期:2020-05-14 00:00:00
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
更新日期:1981-11-01 00:00:00
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
更新日期:2008-11-13 00:00:00