Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis and evaluation of 6-(¹¹C-methyl(4-(pyridin-2-yl)thiazol-2-yl)amino)benzo[d]thiazol-2(3H)-one for imaging ?-8 dependent transmembrane AMPA receptor regulatory protein by PET.

ABSTRACT: Transmembrane AMPA receptor regulatory proteins (TARPs) are a recently discovered family of proteins that modulate AMPA receptors activity. Based on a potent and selective TARP subtype ?-8 antagonist, 6-(methyl(4-(pyridin-2-yl)thiazol-2-yl)amino)benzo[d]thiazol-2(3H)-one (compound 9), we perform the radiosynthesis of its ¹¹C-isotopologue 1 and conduct preliminary PET evaluation to test the feasibility of imaging TARP ?-8 dependent receptors in vivo.

SUBMITTER: Yu Q

PROVIDER: S-EPMC7045276 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis and evaluation of 6-(11C-methyl(4-(pyridin-2-yl)thiazol-2-yl)amino)benzo[d]thiazol-2(3H)-one for imaging γ-8 dependent transmembrane AMPA receptor regulatory protein by PET.

Yu Qingzhen Q Kumata Katsushi K Li Hua H Zhang Yiding Y Chen Zhen Z Zhang Xiaofei X Shao Tuo T Hatori Akiko A Yamasaki Tomoteru T Xie Lin L Hu Kuan K Wang Gangqiang G Josephson Lee L Sun Shaofa S Zhang Ming-Rong MR Liang Steven H SH

Bioorganic & medicinal chemistry letters 20191217 4

Transmembrane AMPA receptor regulatory proteins (TARPs) are a recently discovered family of proteins that modulate AMPA receptors activity. Based on a potent and selective TARP subtype γ-8 antagonist, 6-(methyl(4-(pyridin-2-yl)thiazol-2-yl)amino)benzo[d]thiazol-2(3H)-one (compound 9), we perform the radiosynthesis of its 11C-isotopologue 1 and conduct preliminary PET evaluation to test the feasibility of imaging TARP γ-8 dependent receptors in vivo. ...[more]

PMID: 31879207

Similar Datasets

Synthesis, structure and antifungal activity of new 3-[(5-aryl-1,3,4-oxadiazol-2-yl)methyl]benzo[d]thiazol-2(3H)-ones.

Project description:A series of new 3-[(5-aryl-1,3,4-oxadiazol-2-yl)methy])benzo[d]thiazol-2(3H)-ones were synthesized by reaction of (5-substituted-2-oxobenzothiazolin-3-yl)-acetohydrazide with various aromatic acids in POCl(3) under reflux conditions. The structures of the title compounds were confirmed by ¹H-NMR, ¹³C-NMR, IR, MS and elemental analysis. Furthermore, the structure of compound 4i was determined by single-crystal X-ray diffraction. The preliminary bioassy results indicated that some of them showed moderate inhibition activity against Colletotrichum orbiculare, Botrytis cinerea and Rhizoctonia solani.

| S-EPMC6268515 | biostudies-literature

Synthesis, pharmacology and preclinical evaluation of 11C-labeled 1,3-dihydro-2H-benzo[d]imidazole-2-ones for imaging γ8-dependent transmembrane AMPA receptor regulatory protein.

Project description:a-Amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are implicated in the pathology of neurological diseases such as epilepsy and schizophrenia. As pan antagonists for this target are often accompanied with undesired effects at high doses, one of the recent drug discovery approaches has shifted to subtype-selective AMPA receptor (AMPAR) antagonists, specifically, via modulating transmembrane AMPAR regulatory proteins (TARPs). The quantification of AMPARs by positron emission tomography (PET) would help obtain insights into disease conditions in the living brain and advance the translational development of AMPAR antagonists. Herein we report the design, synthesis and preclinical evaluation of a series of TARP γ-8 antagonists, amenable for radiolabeling, for the development of subtype-selective AMPAR PET imaging agents. Based on the pharmacology evaluation, molecular docking studies and physiochemical properties, we have identified several promising lead compounds 3, 17-19 and 21 for in vivo PET studies. All candidate compounds were labeled with [11C]COCl2 in high radiochemical yields (13-31% RCY) and high molar activities (35-196 GBq/μmol). While tracers 30 ([11C]17) &32 ([11C]21) crossed the blood-brain barrier and showed heterogeneous distribution in PET studies, consistent with TARP γ-8 expression, high nonspecific binding prevented further evaluation. To our delight, tracer 31 ([11C]3) showed good in vitro specific binding and characteristic high uptake in the hippocampus in rat brain tissues, which provides the guideline for further development of a new generation subtype selective TARP γ-8 dependent AMPAR tracers.

| S-EPMC6245653 | biostudies-literature

Structure activity relationship study of benzo[d]thiazol-2(3H)one based σ receptor ligands.

Project description:Herein we report the SAR study which involved structural modifications to the linker length, aryl substitution and alkylamine ring size of the benzo[d]thiazol-2(3H)one based sigma receptor (σ) ligands. Many compounds in this series displayed low nanomolar affinity for the σ receptor subtypes. In particular, 8a showed high affinity (σ-1 Ki = 4.5 nM) for σ-1 receptors and moderately high selectivity (483-fold) over σ-2 receptors.

| S-EPMC3762478 | biostudies-literature

4-(pyridin-2-yl)thiazol-2-yl thioglycosides as bidentate ligands for oligosaccharide synthesis via temporary deactivation.

Project description:This study focusses on a new concept for oligosaccharide synthesis based on 4-(pyridin-2-yl)thiazol-2-yl thioglycosides that can either act as effective glycosyl donors or can be deactivated by stable bidentate complexation with palladium(II) bromide.

| S-EPMC3150469 | biostudies-literature

{2-[(Benzo-yloxy)meth-yl]-1-oxo-3H-pyrrolizin-2-yl}methyl benzoate.

Project description:The title compound, C(23)H(19)NO(5), was prepared by esterification of 2,2-bis-(hy-droxy-meth-yl)-2,3-dihydro-1H-pyrrolizin-1-one with benzoyl chloride in pyridine·The pyrrolizine ring system is approximately planar with a maximum deviation of 0.008?(2)?Å from the least-squares plane; the two phenyl rings are oriented at dihedral angles of 64.26?(11) and 70.75?(10)° with respect to the pyrrolizine ring system. Weak inter-molecular C-H?O hydrogen bonding occurs in the crystal structure.

| S-EPMC3050358 | biostudies-literature

3-(1,3-Benzodioxol-5-yl)-3H-benzo[f]isobenzofuran-1-one.

Project description:In the title compound, C(19)H(12)O(4), the dioxole ring adopts a flattened envelope conformation with the methyl-ene C at the flap [deviation = 0.104 (2) Å]. The benzene ring of the benzodioxole ring system makes a dihedral angle of 76.45 (5)° with the planar [maximum deviation = 0.016 (1) Å] 3H-benzo[f]isobenzofuran-1-one ring system. In the crystal structure, the mol-ecules are linked into C(5) chains running along the b axis by inter-molecular C-H⋯O hydrogen bonds. In addition, C-H⋯π inter-actions are observed.

| S-EPMC2983915 | biostudies-literature

1-(4-Chloro-benzo-yl)-3-(3-methyl-pyridin-2-yl)thio-urea.

Project description:The mol-ecule of the title compound, C(14)H(12)ClN(3)OS, consists of three approximately planar fragments: the central thio-urea group, the chloro-phenyl group and the picolyl (3-methyl-pyridin-2-yl) group with a maximum of 0.035 (2)° for an N atom from the mean square plane of the central thiourea group. The central fragment forms dihedral angles of 33.30 (8) and 76.78 (8)° with the chloro-phenyl and picolyl groups, respectively. With respect to the thio-urea C-N bonds, the 4-chloro-benzoyl group is positioned trans to the thiono S atoms, whereas the picolyl group lies in a cis position to it. The mol-ecular conformation is stabilized by an intra-molecular N-H⋯O hydrogen bond. In the crystal, mol-ecules are linked by inter-molecular C-H⋯N hydrogen bonds, forming chains along the a axis.

| S-EPMC3200797 | biostudies-literature

3-Benzyl-6-(2-chloro-benzo-yl)-1,3-benzoxazol-2(3H)-one.

Project description:In the title compound, C(21)H(14)ClNO(3), the benzoxazolone ring system is planar (r.m.s. deviation = 0.022 Å) and forms dihedral angles of 75.38 (10) and 65.92 (13)° with the mean planes of the chloro-benzoyl (r.m.s. deviation = 0.045 Å, excluding O atom) and benzyl (r.m.s. deviation = 0.023 Å) groups. The observed structure is stabilized by weak C-H⋯O hydrogen bonds and weak inter-molecular C-H⋯π inter-actions.

| S-EPMC3011399 | biostudies-literature

2-(5,6-Dibromo-7-methyl-3H-imidazo[4,5-b]pyridin-2-yl)phenol.

Project description:In the title compound, C(13)H(9)Br(2)N(3)O, the mol-ecular skeleton, influenced by an intra-molecular O-H?N hydrogen bond, is roughly planar, with a mean deviation of 0.033?Å. In the crystal, inter-molecular N-H?O hydrogen bonds link the mol-ecules into chains propagating in [100]. Weak inter-molecular ?-? inter-actions [centroid-centroid distances = 3.760?(3) and 3.723?(3)?Å] further consolidate the packing.

| S-EPMC3011805 | biostudies-literature

1-(3-Chloro-phen-yl)-5-(2,4-di-hydroxy-benzo-yl)pyridin-2(1H)-one.

Project description:The chloro-phenyl group of the title compound, C18H12ClNO4, is disordered over two orientations with occupancies of 0.331 (8) and 0.669 (8). An intra-molecular hydrogen bond is formed between a hy-droxy group and the acyclic carbonyl group. In the crystal, molecules are linked into chains along [110] by O-H⋯O and C-H⋯O hydrogen bonds, forming a ladder motif.

| S-EPMC3648264 | biostudies-literature