- Photoactivatable Dopamine and Sulpiride to Explore the Function of Dopaminergic Neurons and Circuits
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Kinetic analysis of dopamine receptor activation and inactivation and the study of dopamine-dependent signaling requires precise simulation of the presynaptic release of the neurotransmitter dopamine and tight temporal control over the release of dopamine receptor antagonists. The 8-cyano-7-hydroxyquinolinyl (CyHQ) photoremovable protecting group was conjugated to dopamine and the dopamine receptor antagonist sulpiride to generate "caged" versions of these neuromodulators (CyHQ-O-DA and CyHQ-sulpiride, respectively) that could release their payloads with 365 or 405 nm light or through 2-photon excitation (2PE) at 740 nm. These compounds are stable under physiological conditions in the dark, yet photolyze rapidly and cleanly to yield dopamine or sulpiride and the caging remnant CyHQ-OH. CyHQ-O-DA mediated the light activation of dopamine-1 (D1) receptors on the breast cancer cell line MDA-MB-231 in culture. In mouse brain slice from the substantia nigra pars compacta, localized flash photolysis of CyHQ-O-DA accurately mimicked the natural presynaptic release of dopamine and activation of dopamine-2 (D2) receptors, causing a robust, concentration-dependent, and repeatable G protein-coupled inwardly rectifying potassium channel-mediated outward current in whole-cell voltage clamp recordings that was amplified by cocaine and blocked by sulpiride. Photolysis of CyHQ-sulpiride rapidly blocked synaptic activity, enabling measurement of the unbinding rates of dopamine and quinpirole, a D2 receptor agonist. These tools will enable more detailed study of dopamine receptors, their interactions with other GPCRs, and the physiology of dopamine signaling in the brain.
- Asad, Naeem,Condon, Alec F.,Dore, Timothy M.,Gore, Sangram,Hampton, Shahienaz E.,Mclain, Duncan E.,Vijay, Sauparnika,Williams, John T.
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Read Online
- Sulfonamide compound and synthesis method and application thereof
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The invention discloses a synthesis method of a sulfonamide compound represented in a formula (2). According to the method, diazonium salt is used as a reaction raw material, and under the action of an inorganic nitrogen reagent, an inorganic sulfur dioxide reagent, an additive and a phosphine reagent, the diazonium salt is reacted in a solvent at 60-100 DEG C to obtain various sulfonamide compounds. According to the method inorganic salt is used as a nitrogen atom source and a sulfur dioxide source under a metal-free catalytic condition to construct the sulfonamide compound through one step,thereby avoiding the conventional multi-step synthesis of sulfonamide by condensing unstable acid chloride and amine; and the developed sulfonamide synthesis method can be further applied to the synthesis of the arthritis drug celecoxib and the psychotropic drug sulpiride.
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Paragraph 0146-0149
(2019/04/02)
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- A postoperative or its optical isomers of synthetic and post-processing method
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The invention relates to a synthesis and post-processing method of sulpiride or an optical isomer thereof, and the synthesis and post-processing method include the following steps: under inert gas protection, heating 2-methoxy-5-aminosulfonyl methyl benzoate or 2-methoxy-5-aminosulfonyl ethyl benzoate and 1-ethyl-2-aminomethyl pyrrolidine or an optical isomer thereof at 80-120 DEG C for a plurality of hours, and after the reaction is completed, adding ethanol for processing, cooling, filtering, washing and drying.
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Paragraph 0026; 0027; 0031; 0035
(2018/09/11)
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- Metal-free construction of primary sulfonamides through three diverse salts
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In this report, the first metal-free construction of primary sulfonamides through a direct three-component reaction of sodium metabisulfite, sodium azide and aryldiazonium has been established. Readily available inorganic Na2S2O5 and NaN3 were applied as the sulfur dioxide surrogate and nitrogen source respectively. The widely used sulfonamide drugs Celecoxib and Sulpiride, which possess multiple heteroatoms and active hydrogen containing functional groups, are efficiently installed with -SO2NH2 groups at a late stage. Control experiments and kinetic studies demonstrated that aryl radicals, sulfonyl radicals and conjugated phosphine imine radicals are involved in this transformation.
- Wang, Ming,Fan, Qiaoling,Jiang, Xuefeng
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supporting information
p. 5469 - 5473
(2019/01/03)
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- A method for preparing shu Bili (by machine translation)
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The invention discloses a method for preparing sulpiride. The method comprises the following steps: firstly, carrying out condensation reaction on 2-methoxy-5-aminosulfanoyl methyl benzoate and N-ethyl-2-aminomethyl tetrahydropyrrole to generate a crude sulpiride product; and refining the crude sulpiride product to obtain a refined sulpiride product. The sulpiride prepared by the method has the advantages of good quality, high purity, simple preparation method, low energy consumption and low cost.
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Paragraph 0013; 0014; 0015
(2017/02/17)
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- Process for the enantiomeric resolution of 1-substituted 2-(aminomethyl)-pyrrolidines by amidation in the presence of lipases
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A process for the enantiomeric resolution of 1-substituted 2-(aminomethyl)pyrrolidines of formula (I) in which R is C1-C6 alkyl, which process comprises the reaction of the racemic amine with benzyl acetate in acetonitrile in the presence of a lipase selected from Pseudomonas cepacia, Pseudomonas fluorescens or Candida rugosa lipases, to give the corresponding 1-substituted N-(pyrrolidin-2-yl-methyl)-acetamides of formula (II), with R configuration, and the residual amine with S configuration, and, if desired, the subsequent hydrolysis of the amide to obtain the amine with R configuration.
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- THE OCULAR HYPOTENSIVE ACTIVE COMPOSITIONS
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The present invention is related to the ocular hypotensive active compositions, which comprise clozapine or sulpiride and pharmaceutically acceptable excipients. The ocular preparations of the invention have ocular hypotensive effect (10P). They are new drugs in the therapy of glaucoma which can be easily prepared, and are so safe in clinical practice that no side-effect has been found.
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- Hypotensive intraocular pressure activity of clozapine and sulpiride
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This invention introduces a novel anti-glaucoma solution which comprises of Clozapine or Sulpiride and a pharmaceutical vehicle. This is the first time all the above agents have been prepared in ophthalmologic solutions, which will be able to decrease the IOP in animals.
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- POTENTIAL NEUROLEPTICS OF THE ORTHOPRAMIDE SERIES; SYNTHESIS OF N-SUBSTITUTED 5-(AMINOSULFONYL)-2-METHOXYBENZAMIDES
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The mixed anhydride of 5-(aminosulfonyl)-2-methoxybenzoic acid (VII) and monoethyl carbonate reacted with benzylamine, 1-methylpiperazine, and 1-benzylpiperazine to give the 5-(aminosulfonyl)-2-methoxybenzamides II, IV, and V.Heating the ethyl ester X with 4-amino-1-methylpiperidine resulted in the amide III.Reaction of 5-(chlorosulfonyl)-2-methoxybenzoyl chloride (XI) with 1-benzylpiperazine afforded 5-(4-benzylpiperazinosulfonyl)-2-methoxybenzoic acid 4-benzylpiperazide (VI).Compounds II-VI are analogues of the antidopaminergic and antiemetic agent sulpiride (I) but only the benzylpiperazides V and VI showed indications of psychotropic activity of the neuroleptic type.
- Valenta, Vladimir,Protiva, Miroslav
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p. 2095 - 2106
(2007/10/02)
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- Synthesis and Inhibitory Activity on Carbonic Anhydrase of Some New Sulpiride Analogues Studied by Means of a New Method
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The pharmacological activity of several new sulpiride analogues was studied by means of a new approach, based on a potentiometric technique with a pCO2 sensor, capable of detecting carbonic anhydrase inhibition at equilibrium conditions.This procedure gives results stated as percent of inhibition of enzymatic activity (IP, inhibitory power).To prove the reliability of the proposed approach and to study structure-activity relationships, several new molecules were synthesized and tested in comparison with the two sulpiride enantiomers.A possible inhibition mechanism is discussed in terms of experimental evidence obtained from the interactions between the molecular structures of the new synthesized compounds and carbonic anhydrase.
- Botre, Claudio,Botre, Francesco,Jommi, Giancarlo,Signorini, Roberto
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p. 1814 - 1820
(2007/10/02)
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- Imido carbonate compound, production thereof and uses thereof as reagent for forming active ester of amino acids
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A new carbonate compound which is N,N'-di-succinimidyl carbonate, N,N'-diphthalimidyl carbonate or N,N'-bis(5-norbornene-2,3-dicarboxyimidyl) carbonate is produced by reacting an N-hydroxy compound of the formula wherein R is succinimido, phthalimido or 5-norbornene-2,3-dicarboximido group, with a silylating agent, followed by reacting the resultant silylated product with phosgene, or alternatively by reacting said N-hydroxy compound with trichloromethyl chloroformate either in the molten state or in the presence of a non-polar organic solvent such as xylene. This new carbonate compound is useful not only as a reagent for forming active esters from amino acid but also as a reagent for introducing a carbonyl group between a pair of amino groups, a pair of amino and hydroxyl groups or a pair of amino and mercapto groups, for producing an isothiocyanate from a dithicarbamic acid by removal of hydrogen sulfide from the latter, and for producing acrylic acid derivatives from N-protected serine by dehydration of the latter.
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- Sulfonic acid esters
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A novel process for the amidation or esterification which comprises reacting a compound having a carboxy group with a compound having an amino or imino group which can be acylated or with a compound having a hydroxy group in the presence of a sulfonic acid ester of the formula: wherein R1 is an organic group and R2 O-- is a residue of a strongly acidic N-hydroxy compound as a condensation agent, and a novel sulfonic acid ester useful as such a condensation agent and a process for the preparation thereof.
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