Abstract:
:D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4-[11C]MMC, [11C]1a; 3-[11C]MMC, [11C]1b; and 2-[11C]MMC, [11C]1c) were synthesized for evaluation as novel potential positron emission tomography (PET) imaging agents for brain D3 receptors. The new tracers 4,3,2-[11C]MMCs were prepared by O-[11C]methylation of corresponding precursors (E)-4,3,2-hydroxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4,3,2-HMCs) using [11C]methyl triflate and isolated by the solid-phase extraction (SPE) purification procedure with 40-65% radiochemical yields, decay corrected to end of bombardment (EOB), and a synthesis time of 15-20 min. The PET dynamic studies of the tracers [11C]1a-c in rats were performed using an animal PET scanner, IndyPET-II, developed in our laboratory. The results show that the brain uptake sequence was 4-[11C]MMC > 3-[11C]MMC > 2-[11C]MMC, which is consistent with their in vitro biological properties. The initial PET blocking studies of the tracers 4,3,2-[11C]MMCs with corresponding pretreatment drugs (E)-4,3,2-methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4,3,2-MMCs, 1a-c) had no effect on 4,3,2-[11C]MMCs-PET rat brain imaging. These results suggest that the localization of 4,3,2-[11C]MMCs in rat brain is mediated by nonspecific processes, and the visualization of 4,3,2-[11C]MMCs-PET in rat brain is related to nonspecific binding.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Gao M,Mock BH,Hutchins GD,Zheng QHdoi
10.1016/j.bmc.2005.06.055subject
Has Abstractpub_date
2005-11-15 00:00:00pages
6233-43issue
22eissn
0968-0896issn
1464-3391pii
S0968-0896(05)00597-3journal_volume
13pub_type
杂志文章abstract::8-Chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(4-pyridinyl)propyl]hydrazide, monohydrochloride (1, SC-51089) is a functional PGE2 antagonist selective for the EP1 receptor subtype with antinociceptive activity. Analogues of SC-51089, in which the diacylhydrazine moiety has been replaced with 2,...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(00)00229-7
更新日期:2001-01-01 00:00:00
abstract::As part of a continuing effort aimed at the development of selective, efficacious, and centrally active m1 muscarinic agonists for the treatment of Alzheimer's disease, a series of amide and hydrazide amidine derivatives (2a-e and 3b-d) was synthesized and examined for muscarinic agonist activity. Preliminary biochemi...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/0968-0896(96)00152-6
更新日期:1996-10-01 00:00:00
abstract::The in vitro antitumor activities of 2,6-di-[2-(heteroaryl)vinyl]pyridines versus the standard National Cancer Institute 60 cell lines panel and of 2,6-di-[2-(heteroaryl)vinyl] pyridinium cations versus MCF7 (human mammary carcinoma) and LNCap (prostate carcinoma) cell lines are reported. Antiproliferative effects in ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(02)00142-6
更新日期:2002-09-01 00:00:00
abstract::In an effort to design inhibitors of human glutaminyl cyclase (QC), we have synthesized a library of N-aryl N-(5-methyl-1H-imidazol-1-yl)propyl thioureas and investigated the contribution of the aryl region of these compounds to their structure-activity relationships as cyclase inhibitors. Our design was guided by the...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.04.005
更新日期:2013-07-01 00:00:00
abstract::Forty six new 1,4-epoxy-2-exo-aryl- and cis-2-aryl-4-hydroxytetrahydro-1-benzazepine derivatives were synthesized and fully characterized. All compounds were tested in vitro against both Trypanosoma cruzi and Leishmania chagasi parasites and also for cytotoxicity using Vero and THP-1 mammalian cell lines. Many of the ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2010.05.018
更新日期:2010-07-01 00:00:00
abstract::Efficient preparations of the titled compounds are described, their antimicrobial activity and mutagenic properties being evaluated. Some of the studied compounds are nonmutagenic and present a MIC as low as some of the usual standards in the field. ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(97)00138-7
更新日期:1997-10-01 00:00:00
abstract::A phytochemical investigation of the leaves of Erythrophleum fordii Oliv. has led to the isolation of three new cassaine-type diterpenoids, erythrofordin A (1), erythrofordin B (2) and erythrofordin C (3), as well as a norcassaine diterpenoid with a novel skeleton, norerythrofordin A (4), and 27 known compounds (5-31)...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.09.021
更新日期:2008-11-15 00:00:00
abstract::This review addresses key pharmacology and virology issues relevant in discovery and development of CCR5 antagonists as anti-HIV drugs, such as target validation, receptor internalization, allosterism, viral resistance and tropism. Recent progress in the discovery and development of CCR5 antagonists, SAR and clinical ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/s0968-0896(03)00161-5
更新日期:2003-07-03 00:00:00
abstract::This paper reports the synthesis of new derivatives (formed by two indole systems separated by a central moiety) analogous of potent antitumor agents previously described. The activity of the bis-indoles bearing a pyridine core confirms the good result described in the previous paper and compound 4c was chosen for the...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2010.03.063
更新日期:2010-05-01 00:00:00
abstract::Several benzaldoximes, benzaldehyde-O-ethyloximes, and acetophenonoximes were synthesized and evaluated as tyrosinase inhibitors by an assay based on tyrosinase catalyzed L-DOPA oxidation. Whereas benzaldoxime itself is only a weak inhibitor, its derivatives with one or two hydroxy or methoxy moieties in para and meta...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(01)00084-0
更新日期:2001-07-01 00:00:00
abstract::We have previously reported the discovery and initial SAR of the [1,7]naphthyridine-3-carbonitriles and quinoline-3-carbonitriles as Tumor Progression Loci-2 (Tpl2) kinase inhibitors. In this paper, we report new SAR efforts which have led to the identification of 4-alkylamino-[1,7]naphthyridine-3-carbonitriles. These...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.06.054
更新日期:2007-10-01 00:00:00
abstract::We have prepared a series of potent antihypertensive 1-benzazepin-2-one calcium channel blockers (CCBs) 1 that are structurally related to diltiazem 2. Structural studies and the preparation of conformationally constrained analogs of 1-benzazepin-2-ones have led us to postulate a receptor-bound conformation for both 1...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(00)82134-3
更新日期:1993-10-01 00:00:00
abstract::CNS diseases such as Parkinson, schizophrenia, and attention deficit hyperactivity disorder (ADHD) are characterized by a significant alteration of dopamine transporter (DAT) density. Thus, the development of compounds that are able to selectively interact with DAT is of great interest. Herein we describe the design a...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.04.019
更新日期:2006-08-01 00:00:00
abstract::Cyanocobalamin (vitamin B12) is an essential nutrient as well as a very useful carrier in drug delivery. Conjugates of vitamin B12 are investigated due to their wide range of therapeutic applications. We report the synthesis of six vitamin B12 conjugates, and the effect of conjugation on their solubilities and stabili...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.11.036
更新日期:2007-02-15 00:00:00
abstract::5-HT(3A) receptor antagonists have been used mainly for the treatment of nausea and vomiting. These days, the antagonists are of special interest due to their therapeutic potential to treat other diseases such as depression, psychotic disorder, drug abuse, and irritable bowel syndrome. To discover novel 5-HT(3A) recep...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2009.04.029
更新日期:2009-07-01 00:00:00
abstract::A series of hairpin oligomers containing benzimidazole (Bi) and imidazopyridine (Ip) rings were synthesized and screened to target 5'-WGGGGW-3', a core sequence in the DNA-binding site of NF-kappaB, a prolific transcription factor important in biology and disease. Five Bi and Ip containing oligomers bound to the 5'-WG...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.10.051
更新日期:2007-01-15 00:00:00
abstract::The present study describes the chemical synthesis and pharmacological evaluation of a new series of eleven compounds stereoisomers of imidobenzenesulfonylaziridines in the forced-swimming test (FST) in mice. The pharmacological results of these compounds show that six of them, given intraperitoneally, reduced the imm...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.03.036
更新日期:2006-08-01 00:00:00
abstract::Cytosolic (TrxR1) and mitochondrial (TrxR2) thioredoxin reductases experience pronounced concentration- and time-dependent inhibition when incubated with the two naphthodianthrones hypericin and pseudohypericin. Pseudohypericin turned out to be a quite strong inhibitor of TrxR1 (IC(50)=4.40μM) being far more effective...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2010.10.045
更新日期:2011-01-01 00:00:00
abstract::The calpains are a conserved family of cysteine proteases that includes several isoforms of which µ-calpain and m-calpain are the most widely distributed in mammalian cells. Calpains have been implicated in normal physiological processes as well as cellular abnormalities such as neurodegenerative disorders, cataract, ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2020.115433
更新日期:2020-05-01 00:00:00
abstract::Human enterovirus (EV) belongs to the picornavirus family, which consists of over 200 medically relevant viruses. A peptidomimetic inhibitor AG7088 was developed to inhibit the 3C protease of rhinovirus (a member of the family), a chymotrypsin-like protease required for viral replication, by forming a covalent bond wi...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.06.015
更新日期:2008-08-01 00:00:00
abstract::Infectious diseases and cancers are leading causes of death and pose major challenges to public health. The human peptidome encompasses millions of compounds that display an enormous structural and functional diversity and represents an excellent source for the discovery of endogenous agents with antimicrobial and/or ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.bmc.2017.10.038
更新日期:2018-06-01 00:00:00
abstract::A new class of compounds, the thiopyrano[2,3-e]indol-2-ones, bioisosters of the angular furocoumarin angelicin, was synthesized with the aim of obtaining new photochemotherapeutic agents. In particular 7,8-dimethyl-thiopyranoindolone 6c s showed a remarkable phototoxicity and a great dose UVA dependence reaching IC(50...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.10.002
更新日期:2008-11-15 00:00:00
abstract::We have developed esonarimod, (+/-)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid, as a new antirheumatic drug. Now we describe herein the preparation of the enantiomers of (+/-)-deacetylesonarimod, the pharmaceutically active metabolites of esonarimod, and comparison of their antirheumatic activities. No s...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(02)00084-6
更新日期:2002-08-01 00:00:00
abstract::Peroxynitrite, a reactive nitrogen species generated from nitric oxide and superoxide anion radical, is an endogenous potential risk factor for human cancer. When 2'-deoxycytidine was incubated with peroxynitrite at neutral pH and 37 degrees C, the reaction was greatly enhanced by the addition of ammonium bromide. Bot...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.03.007
更新日期:2008-05-01 00:00:00
abstract::Numerical values of the testosterone binding globulin affinity have been modeled as a mathematical function of molecular structure in two versions of molecular structure elucidation: first, by hydrogen-filled molecular graphs (HFG); second, by the so-called graphs of atomic orbitals (GAO). Increased orders of Morgan e...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.07.059
更新日期:2005-12-15 00:00:00
abstract::Large series of O-alkyl derivatives (methyl and benzyl) of silybin and 2,3-dehydrosilybin was prepared. Selective alkylation of the silybin molecule was systematically investigated. For the first time we present here, for example, preparation of 19-nor-2,3-dehydrosilybin. All prepared silybin/2,3-dehydrosilybin deriva...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2006.01.035
更新日期:2006-06-01 00:00:00
abstract::We have recently reported the discovery of numerous new compounds that are selective inhibitors of all of the subtypes of the adenosine receptor family via a pharmacophore database searching and screening strategy. During the course of this work we made the unexpected discovery of a potent A(2B) receptor antagonist, 4...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(02)00323-1
更新日期:2003-01-02 00:00:00
abstract::A detailed investigation of the South China Sea soft coral Sarcophyton trocheliophorum Marenzeller yielded, along with six known terpenes (6-11), the new sarcophytonolides N-R (1-5), whose structures have been elucidated by detailed spectroscopic analysis. Sarcophytonolides N-R are mono- or bicyclic cembranoids charac...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.06.043
更新日期:2013-09-01 00:00:00
abstract::We have selectively synthesized by Pictet-Spengler condensation of tryptophan and pyridoxal the four stereoisomers of a pyridoxal β-carboline derivative that was designed to inhibit the proliferation of Plasmodium falciparum. Biological investigation of the four compounds revealed that they all inhibit the growth of P...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2014.01.057
更新日期:2014-03-15 00:00:00
abstract::We designed a phenylglycine (Phg)-incorporated ascidiacyclamide (ASC) analogue, cyclo(-Phg-oxazoline-d-Val-thiazole-Ile-oxazoline-d-Val-thiazole- ([Phg]ASC), with the aim of stabilizing the square conformation of ASC through interactions between amino acid side chains. X-ray diffraction analysis showed that [Phg]ASC h...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2011.04.036
更新日期:2011-06-01 00:00:00