Radiosynthesis of [11C]BBAC and [11C]BBPC as potential PET tracers for orexin2 receptors

Radiosynthesis of [N-methyl-(11)C](S)-N-([1,1'-biphenyl]-2-yl)-1-(2-((1-methyl-1H-benzo[d]imidazol-2-yl)thio)acetyl)pyrrolidine-2-carboxamide ([(11)C]BBAC or [(11)C]3) and [N-methyl-(11)C] (S)-N-([1,1'-biphenyl]-2-yl)-1-(3-(1-methyl-1H-benzo[d]imidazol-2-yl)propanoyl)pyrrolidine-2-carboxamide ([(11)C]BBPC or [(11)C]-4), two potential PET tracers for orexin2 receptors are described. Syntheses of non-radioactive standards 3, 4 and corresponding desmethyl precursors 1, 2 were achieved from common intermediate (S)-2-([1,1'-biphenyl]-2-yl)-1-(pyrrolidin-2-yl)ethanone. Methylation using [(11)C]CH(3)OTf in the presence of base in acetone afforded [(11)C]3 and [(11)C]4 in 30±5% yield (EOS) with >99 % radiochemical purities with a specific activity ranged from 2.5±0.5 Ci/μmol (EOB). The logP of [(11)C]3 and [(11)C]4 were determined as 3.4 and 2.8, respectively. The total synthesis time was 30 min from EOB. However, PET scans performed in a rhesus monkey did not show tracer retention or appropriate brain uptake. Hence [(11)C]3 and [(11)C]4 cannot be used as PET tracers for imaging orexin2 receptors.     

Synthesis of [O-methyl-11C]1-(2-chlorophenyl)-5-(4-methoxyphenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide: a potential PET ligand for CB1 receptors

Synthesis and in vitro evaluation of [O-methyl-(11)C]1-(2-chlorophenyl)-5-(4-methoxyphenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide ([(11)C]-1), a potential imaging agent for CB(1) receptors using PET is described. 1-(2-Chlorophenyl)-5-(4-hydroxyphenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide (5), the precursor for radiolabeling, was synthesized from 4-OTBDPS-propiophenone (2) in five steps with 30% overall yield. The reaction of alcohol 5 with [(11)C]MeOTf at 60 degrees C afforded [(11)C]-1 with an average radiochemical yield of 14.5% (EOS) and >2000 Ci/mmol specific activity. The radiotracer was found to selectively label CB(1) receptors in slide-mounted sections of postmortem human brain containing prefrontal cortex as demonstrated by in vitro autoradiography using phosphor imaging.     

Synthesis of carbon-11-labeled 5-HT6R antagonists as new candidate PET radioligands for imaging of Alzheimer’s disease

Carbon-11-labeled serotonin (5-hydroxytryptamine) 6 receptor (5-HT₆R) antagonists, 1-[(2-bromophenyl)sulfonyl]-5-[¹¹C]methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole (O-[¹¹C]2a) and 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-[¹¹C]methyl-1-piperazinyl)methyl]-1H-indole (N-[¹¹C]2a), 5-[¹¹C]methoxy-3-((4-methylpiperazin-1-yl)methyl)-1-(phenylsulfonyl)-1H-indole (O-[¹¹C]2b) and 5-methoxy-3-((4-[¹¹C]methylpiperazin-1-yl)methyl)-1-(phenylsulfonyl)-1H-indole (N-[¹¹C]2b), 1-((4-isopropylphenyl)sulfonyl)-5-[¹¹C]methoxy-3-((4-methylpiperazin-1-yl)methyl)-1H-indole (O-[¹¹C]2c) and 1-((4-isopropylphenyl)sulfonyl)-5-methoxy-3-((4-[¹¹C]methylpiperazin-1-yl)methyl)-1H-indole (N-[¹¹C]2c), 1-((4-fluorophenyl)sulfonyl)-5-[¹¹C]methoxy-3-((4-methylpiperazin-1-yl)methyl)-1H-indole (O-[¹¹C]2d) and 1-((4-fluorophenyl)sulfonyl)-5-methoxy-3-((4-[¹¹C]methylpiperazin-1-yl)methyl)-1H-indole (N-[¹¹C]2d), were prepared from their O- or N-desmethylated precursors with [¹¹C]CH₃OTf through O- or N-[¹¹C]methylation and isolated by HPLC combined with SPE in 40–50% radiochemical yield, based on [¹¹C]CO₂ and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (MA) at EOB was 370–740?GBq/μmol with a total synthesis time of ～40-min from EOB.     

Novel benzodiazepines derivatives as analgesic modulating for Transient receptor potential vanilloid 1

A new series of derivatives of 3-(7-chloro-5-(2-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)propanoic acid were designed and synthesized as analgesic modulating for Transient receptor potential vanilloid 1. They were investigated for TRPV1 antagonistic activity in vitro, analgesic activity and sedative activity in vivo and aqueous solubility. Preliminary studies identified 3-(7-chloro-5-(2-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-N,N-dimethylpropanamide(Compound 11), as a potent analgesic modulating for TRPV1 with potent activity and good aqueous solubility.     

Synthesis of [¹¹C]uric acid, using [¹¹C]phosgene, as a possible biomarker in PET imaging for diagnosis of gout

The synthesis and in vivo evaluation of (11)C -labeled uric acid ([(11)C]1), a potential imaging agent for the diagnosis of urate-related life-style diseases, was performed using positron emission tomography (PET) image analysis. First, the synthesis of [(11)C]1 was achieved by reacting 5,6-diaminouracil (2) with (11)C-labeled phosgene ([(11)C]COCl(2)). The radiochemical yield of [(11)C]1 was 37±7% (decay-corrected based on [(11)C]COCl(2)) with specific radioactivities of 96-152GBq/μmol at the end of synthesis (n=6). The average time of radiosynthesis from the end of bombardment, including formulation, was about 30min with >98% radiochemical purity. Second, the synthetic approach to [(11)C]1 was optimized using 5,6-diaminouracil sulfate (3) with [(11)C]COCl(2) in the presence of 1,8-bis(dimethylamino)naphthalene. [(11)C]1 was synthesized in 36±6% radiochemical yield, 89-142GBq/μmol of specific radioactivities, and 98% radiochemical purity by this method (n=5). This allowed the synthesis of [(11)C]1 to be carried out repeatedly and the radiochemical yield, specific radioactivities, average time of synthesis, and radiochemical purity of [(11)C]1 were similar to those obtained using 2. PET studies in rats showed large differences in the accumulation of radioligand in the limbs under normal and hyperuricemic conditions. Thus, an efficient and convenient automated synthesis of [(11)C]1 has been developed, and preliminary PET evaluation of [(11)C]1 confirmed the increased accumulation of radioactivity in the limbs of a rat model of hyperuricemia.     

The first radiosynthesis of [11C]AZD8931 as a new potential PET agent for imaging of EGFR,HER2 and HER3 signaling

The reference standard AZD8931{2-(4-((4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)-N-methylacetamide} (11a) was synthesized from methyl 4,5-dimethoxy-2-nitrobenzoate or ethyl 4,5-dimethoxy-2-nitrobenzoate and 2-chloro-N-methylacetamide in 11 steps with 2–5% overall chemical yield. The precursor N-desmethyl-AZD8931{2-(4-((4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)acetamide} (11b) was synthesized from methyl 4,5-dimethoxy-2-nitrobenzoate or ethyl 4,5-dimethoxy-2-nitrobenzoate and 2-bromoacetamide in 11 steps with 2–4% overall chemical yield. The target tracer [¹¹C]AZD8931 {2-(4-((4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)-N-[¹¹C]methylacetamide} ([¹¹C]11a) was prepared from N-desmethyl-AZD8931 (11b) with [¹¹C]CH₃OTf under basic condition (NaH) through N-[¹¹C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 40–50% radiochemical yield based on [¹¹C]CO₂ and decay corrected to end of bombardment (EOB) with 370–1110 GBq/μmol specific activity at EOB.     

5-(5-(6-[(11)C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole as a potential PET radioligand for imaging cerebral α7-nAChR in mice

The radiosynthesis and in vivo evaluation of 5-(5-(6-[(11)C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole [(11)C]rac-(1), a potential PET tracer for α7 nicotinic acetylcholine receptors (α7-nAChR), are described. Syntheses of the nonradioactive standard rac-1 and corresponding desmethyl precursor 7 were achieved in several reaction steps. Radiomethylation of 7 with [(11)C]CH(3)I afforded [(11)C]rac-1 in an average radiochemical yield of 30 ± 5% (n=5) with high radiochemical purity and an average specific radioactivity of 444 ± 74 GBq/μmol (n=5). The total synthesis time was 30 min from end-of-bombardment. Biodistribution studies in mice showed that [(11)C]rac-1 penetrates the blood-brain barrier and specifically labels neuronal α7-nAChRs.     

Synthesis and evaluation of [¹¹C]Cimbi-806 as a potential PET ligand for 5-HT₇ receptor imaging

2-(2',6'-Dimethoxy-[1,1'-biphenyl]-3-yl)-N,N-dimethylethanamine has been identified as a potent ligand for the serotonin 7 (5-HT(7)) receptor. In this study, we describe the synthesis, radiolabeling and in vivo evaluation of [(11)C]2-(2',6'-dimethoxy-[1,1'-biphenyl]-3-yl)-N,N-dimethylethanamine ([(11)C]Cimbi-806) as a radioligand for imaging brain 5-HT(7) receptors with positron emission tomography (PET). Precursor and reference compound was synthesized and subsequent (11)C-labelling with [(11)C]methyltriflate produced [(11)C]Cimbi-806 in specific activities ranging from 50 to 300 GBq/μmol. Following intravenous injection, brain uptake and distribution of [(11)C]Cimbi-806 was assessed with PET in Danish Landrace pigs. The time-activity curves revealed high brain uptake in thalamic and striatal regions (SUV ～2.5) and kinetic modeling resulted in distribution volumes (V(T)) ranging from 6 mL/cm(3) in the cerebellum to 12 mL/cm(3) in the thalamus. Pretreatment with the 5-HT(7) receptor antagonist SB-269970 did not result in any significant changes in [(11)C]Cimbi-806 binding in any of the analyzed regions. Despite the high brain uptake and relevant distribution pattern, the absence of appropriate in vivo blocking with a 5-HT(7) receptor selective compounds renders the conclusion that [(11)C]Cimbi-806 is not an appropriate PET radioligand for imaging the 5-HT(7) receptor in vivo.     

Synthesis and biological evaluation of some novel triazol-3-ones as antimicrobial agents

A new series of triazol-3-one derivatives bearing 4-methyl-4H-thieno[3',2': 5,6]thiopyrano[4,3-d][1,3]thiazolyl or 4-(thiophene-3-yl) thiazolyl moiety at 4-position and alkyl substitution at 2-position are synthesized. All the synthesized compounds are characterized by elemental analysis, IR, (1)H NMR, (13)C NMR, and mass spectral data. The newly synthesized compounds are screened for antifungal and antibacterial activities.     

A rhodamine-labeled citalopram analogue as a high-affinity fluorescent probe for the serotonin transporter

A novel fluorescent ligand was synthesized as a high-affinity, high specificity probe for visualizing the serotonin transporter (SERT). The rhodamine fluorophore was extended from an aniline substitution on the 5-position of the dihydroisobenzofuran ring of citalopram (2, 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile), using an ethylamino linker. The resulting rhodamine-labeled ligand 8 inhibited [³H]5-HT uptake in COS-7 cells (K_i = 225 nM) with similar potency to the tropane-based JHC 1-064 (1), but with higher specificity towards the SERT relative to the transporters for dopamine and norepinephrine. Visualization of the SERT with compound 8 was demonstrated by confocal microscopy in HEK293 cells stably expressing EGFP–SERT.     

PET imaging and optical imaging with D-luciferin [11C]methyl ester and D-luciferin [11C]methyl ether of luciferase gene expression in tumor xenografts of living mice

New carbon-11 labeled D-luciferin analogs D-luciferin [(11)C]methyl ester ([(11)C]LMEster, [(11)C]1) and D-luciferin [(11)C]methyl ether ([(11)C]LMEther, [(11)C]2) were synthesized in 25-55% radiochemical yield. PET studies with [(11)C]LMEster and [(11)C]LMEther demonstrate a lower retention of the C-11 label at 45 min post-injection in luciferase expression tumor. Optical imaging with unlabeled substrate D-luciferin and radiotracers [(11)C]LMEster and [(11)C]LMEther gave tumor luciferase images within a few minutes of photon counting.     

Synthesis and optimization of 2-pyridin-3-yl-benzo[d][1,3]oxazin-4-one based inhibitors of human neutrophil elastase

The hit-to-lead optimization of the HNE inhibitor 5-methyl-2-(2-phenoxy-pyridin-3-yl)-benzo[d][1,3]oxazin-4-one is described. A structure–activity relationship study that focused on the 5 and 7 benzoxazinone positions yielded the optimized 5-ethyl-7-methoxy-benzo[d][1,3]oxazin-4-one core structure. 2-[2-(4-Methyl-piperazin-1-yl)-pyridin-3-yl] derivatives of this core were shown to yield HNE inhibitors of similar potency with significantly different stabilities in rat plasma.     

Synthesis and in vivo evaluation of [11C]SN003 as a PET ligand for CRF1 receptors

Synthesis and evaluation of [O-methyl-11C](4-methoxy-2-methylphenyl)[1-(1-methoxymethylpropyl)-6-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-4-yl]amine or [11C]SN003 ([11C]6), as a PET imaging agent for CRF1 receptors, in baboons is described. 4-[1-(1-Methoxymethylpropyl)-6-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-4-ylamino]-3-methylphenol (5), the precursor molecule for the radiolabeling, was synthesized from 2,4-dichloro-6-methyl-3-nitropyridine in seven steps with 20% overall yield. The total time required for the synthesis of [11C]SN003 is 30 min from EOB using [11C]methyl triflate in the presence of NaOH in acetone. The yield of the synthesis is 22% (EOS) with >99% chemical and radiochemical purities and a specific activity of >2000 Ci/mmol. PET studies in baboon show that [11C]6 penetrates the BBB and accumulates in brain. No detectable specific binding was observed, likely due to the rapid metabolism or low density of CRF1 receptors in primate brain.     

Facile synthesis and PET imaging of a novel potential heart acetylcholinesterase tracer N-[11C]methyl-3-[[(dimethylamino)carbonyl]oxy]-2-(2',2'-diphenylpropionoxymethyl)pyridinium

A new AChE tracer N-[(11)C]methyl-3-[[(dimethylamino)carbonyl]oxy]-2-(2',2'-diphenylpropionoxymethyl)pyridinium ([(11)C]MDDP, [(11)C]1) has been synthesized in 40-65% radiochemical yield. Initial PET dynamic studies of [(11)C]MDDP in rat heart showed rapid heart uptake and blood pool clearance to give high-quality heart images. Blocking studies of [(11)C]MDDP with pretreatment drug neostigmine in rats found only minor reductions in rat heart [(11)C]MDDP retention. The results suggest that [(11)C]MDDP delineates the heart very clearly, and the uptakes of [(11)C]MDDP in rat heart might be related to non-specific binding.     

Synthesis of carbon-11-labeled CK1 inhibitors as new potential PET radiotracers for imaging of Alzheimer’s disease

The reference standards methyl 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoate (5a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-methoxybenzamide (5c), and their corresponding desmethylated precursors 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoic acid (6a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-hydroxybenzamide (6b), were synthesized from 5-amino-2,2-difluoro-1,3-benzodioxole and 3-substituted benzoic acids in 5 and 6 steps with 33% and 11%, 30% and 7% overall chemical yield, respectively. Carbon-11-labeled casein kinase 1 (CK1) inhibitors, [¹¹C]methyl 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoate ([¹¹C]5a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-[¹¹C]methoxybenzamide ([¹¹C]5c), were prepared from their O-desmethylated precursor 6a or 6b with [¹¹C]CH₃OTf through O-[¹¹C]methylation and isolated by HPLC combined with SPE in 40–45% radiochemical yield, based on [¹¹C]CO₂ and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (MA) at EOB was 370–740?GBq/μmol with a total synthesis time of ～40-min from EOB.     

Discovery and in vitro evaluation of potent TrkA kinase inhibitors: oxindole and aza-oxindoles

The discovery, synthesis, potential binding mode, and in vitro kinase profile of 3-(3-bromo-4-hydroxy-5-(2'-methoxyphenyl)-benzylidene)-5-bromo-1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one, 3-[(1-methyl-1H-indol-3-yl)methylene]-1,3-dihydro-2H-pyrrolo[3,2-b]-pyridin-2-one as potent TrkA inhibitors are discussed.     

Synthesis and biodistribution of [11C]R107474, a new radiolabeled alpha2-adrenoceptor antagonist

R107474, 2-methyl-3-[2-(1,2,3,4-tetrahydrobenzo[4,5]furo[3,2-c]pyridin-2-yl)ethyl]-4H-pyrido[1,2-a]pyrimidin-4-one, was investigated using in vitro and in vivo receptor assays and proved to be a potent and relatively selective alpha(2)-adrenoceptor antagonist. Performed assays in vitro were inhibition of binding to a large number of neurotransmitter receptor sites, drug receptor binding sites, ion channel binding sites, peptide receptor binding sites, and the monoamine transporters in membrane preparations of brain tissue or of cells expressing the cloned human receptors. The compound has subnanomolar affinity for halpha(2A)- and halpha(2C)-adrenoceptors (K(i) = 0.13 and 0.15 nM, respectively) and showed nanomolar affinity for the halpha(2B)-adrenoceptors and 5-hydroxytryptamine(7) (h5-HT(7)) receptors (K(i) = 1 and 5 nM, respectively). R107474 interacted weakly (K(i) values ranging between 81 and 920 nM) with dopamine-hD(2L), -hD(3) and -hD(4), h5-HT(1D)-, h5-HT(1F)-, h5-HT(2A)-, h5-HT(2C)-, and h5-HT(5A) receptors. The compound, tested up to 10 microM, interacted only at micromolar concentrations or not at all with any of the other receptor or transporter binding sites tested in this study. In vivo alpha(2A)- and alpha(2C)-adrenoceptor occupancy was measured by ex vivo autoradiography 1h after subcutaneous (sc) administration of R107474. It was found that R107474 occupies the alpha(2A)- and alpha(2C)-adrenoceptors with an ED(50) (95% confidence limits) of 0.014 mg/kg sc (0.009-0.019) and 0.026 mg/kg sc (0.022-0.030), respectively. Radiolabeled 2-methyl-3-[2-([1-(11)C]-1,2,3,4-tetrahydrobenzo[4,5]furo[3,2-c]pyridin-2-yl)ethyl]-4H-pyrido[1,2-a]pyrimidin-4-one ([(11)C]R107474) was prepared and evaluated as a potential positron emission tomography (PET) ligand for studying central alpha(2)-adrenoceptors. [(11)C]R107474 was obtained via a Pictet-Spengler reaction with [(11)C]formaldehyde in 33 +/- 4% overall decay-corrected radiochemical yield. The total synthesis time was 55 min and the specific activity was 24-28 GBq/micromol. The biodistribution of [(11)C]R107474 in rats revealed that the uptake of [(11)C]R107474 after in vivo intravenous administration is very rapid; in most tissues (including the brain) it reaches maximum concentration at 5 min after tracer injection. In agreement with the known distribution of alpha(2)-adrenoceptors in the brain, highest uptake of radioactivity was observed in septum (3.54 +/- 0.52 ID/g, 5 min pi) and entorhinal cortex (1.57 +/- 0.10 ID/g, 5 min pi). Tissue/cerebellum concentration ratios for septum (5.38 +/- 0.45, 30 min pi) and entorhinal cortex (3.43+/-0.24, 30 min pi) increased with time due to rapid uptake followed by a slow washout. In vivo blocking experiments using the non-selective alpha(2)-adrenoceptor antagonist mirtazapine demonstrated specific inhibition of [(11)C]R107474 binding in selective brain areas. The receptor binding profile of mirtazapine is reported and the selectivity of inhibition of binding is discussed. These results suggest that [(11)C]R107474 deserves further investigation as a potential radioligand for studying alpha(2)-adrenoceptors using PET.     

Synthesis, in vitro and in vivo evaluation of [O-methyl-11C] 2-{4-[4-(3-methoxyphenyl)piperazin-1-yl]-butyl}-4-methyl-2H-[1,2,4]-triazine-3,5-dione: a novel agonist 5-HT1A receptor PET ligand

Synthesis and in vivo evaluation of 2-{4-[4-(3-methoxyphenyl)piperazin-1-yl]-butyl}-4-methyl-2H-[1,2,4]triazine-3,5-dione (5 or MMT), a high affinity and selective serotonin 5-HT1AR agonist PET tracer, are described. GTPgammaS assay shows that MMT is an agonist with an EC50 comparable to 5-HT. Radiolabeling of 5 was achieved in 30% yield (EOS) from desmethyl-MMT (4) with >99% chemical and radiochemical purities and a specific activity >1000 Ci/mmol. PET studies in baboon show that [11C]5 penetrates the blood-brain barrier but, because of low specific binding and fast clearance of radioactivity it is not a suitable PET tracer for the in vivo quantification of 5-HT1AR.     

Evaluation of [11C]hemicholinium-15 and [18F]hemicholinium-15 as new potential PET tracers for the high-affinity choline uptake system in the heart

[(11)C]Hemicholinium-15 ([(11)C]HC-15) and [(18)F]hemicholinium-15 ([(18)F]HC-15) have been synthesized as new potential PET tracers for the heart high-affinity choline uptake (HACU) system. [(11)C]HC-15 was prepared by N-[(11)C]methylation of the appropriate precursor, 4-methyl-2-phenyl-morpholin-2-ol, using [(11)C]CH(3)OTf in 55-70% radiochemical yield decay corrected to end of bombardment (EOB) and 2-3Ci/mumol specific activity at end of synthesis (EOS). [(18)F]HC-15 was prepared by N-[(18)F]fluoromethylation of the precursor using [(18)F]FCH(2)OTf in 20-30% radiochemical yield decay corrected to EOB and >1.0Ci/mumol specific activity at EOS. The biodistribution of both compounds was determined in rats at 20min post-intravenous injection, and the results show the heart region uptakes 1.32+/-0.75%ID/g in R-ventricle for [(11)C]HC-15 and 1.28+/-0.81%ID/g in L-ventricle for [(18)F]HC-15, respectively. The dynamic PET imaging studies of [(11)C]HC-15 in rats were acquired 60min post-intravenous injection of the tracer using the IndyPET-II scanner. For the blocking experiments, the rats were intravenously pretreated with 3.0mg/kg of unlabeled HC-15 prior to [(11)C]HC-15 injection. [(11)C]HC-15 rat heart PET studies show rapid heart uptake to give clear heart images. The rat heart PET blocking studies found no significant blocking effect. The dynamic PET studies in normal and ablated dogs were performed using Siemens PET scanner with [(13)N]NH(3), [(11)C]HC-15, and [(18)F]HC-15. PET studies in dogs of both [(11)C]HC-15 and [(18)F]HC-15 also show significant heart uptake and give images of the heart. However, there is no significant change in [(11)C]HC-15 L-ventricle uptake following radiofrequency ablation in the dog. These results suggest that the localization of HC-15 tracers in the heart is mediated by non-specific processes, and the visualization of HC-15 tracers on the heart is related to non-specific binding of HACU.     

Molecular docking based screening of neem-derived compounds with the NS1 protein of Influenza virus

AbbreviationsNS1 protein - Non Structural 1 proteinNA - Neuraminidase, HA - Hemagglutinin, M - Matrix, 127-40-2 - 4-[(1E, 3E, 5E,7Z, 9E, 11E, 13E, 15E, 17E)-18-(4-hydroxy-2,6,6-trimethylcyclohex-2-en-1-yl)-3,7,12,16-tetramethyloctadeca-1,3,5,7,9,11,13,15,17- nonaenyl]-3, 5, 5-trimethylcyclohex-3-en-1-ol, Quercitrin 2 - (3,4-dihydroxyphenyl)-5,7-dihydroxy-3- [(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxychromen-4-one, Tiplasinin 2 - [1-benzyl-5-[4-(trifluoromethoxy) phenyl] indol-3-yl]-2-oxoacetic acid, Hyperoside 2 - (3,4-dihydroxyphenyl)-5,7-dihydroxy-3- [(2S,3R,4S,5R,6R)-3, 4, 5-trihydroxy-6- (hydroxymethyl)oxan-2- yl]oxychromen-4-one LGH 4-(2-chloro-4-nitrophenyl)piperazin-1-yl][3-(2-methoxyphenyl)-5-methyl-1,2-oxazol-4-yl]methanone, nRUTIN 2 - (3, 4-dihydroxyphenyl) -5, 7-dihydroxy-3-[(2S, 3R, 4S, 5S, 6R)-3, 4, 5-trihydroxy-6-[[(2R, 3R, 4R, 5R, 6S)-3,4,5-trihydroxy- 6-methyloxan-2-yl]oxymethyl]oxan-2-yl]oxychromen-4-one.