113 results about "Quinuclidine" patented technology

Compounds of formula (I)

wherein n is 0, 1, or 2; A is N or N⁺—O—; X is O, S, —NH—, and —N-alkyl-; Ar¹ is a 6-membered aromatic ring; and Ar² is a fused bicycloheterocycle. The compounds are useful in treating conditions or disorders prevented by or ameliorated by α7 nAChR ligands. Also disclosed are pharmaceutical compositions having compounds of formula (I) and methods for using such compounds and compositions.

Compounds of formula (I)

wherein n is 0, 1, or 2; A is N or N⁺—O⁻; X is O, S, —NH—, and —N-alkyl-; Ar¹ is a 6-membered aromatic ring; and Ar² is a fused bicycloheterocycle. The compounds are useful in treating conditions or disorders prevented by or ameliorated by α7 nAChR ligands. Also disclosed are pharmaceutical compositions having compounds of formula (I) and methods for using such compounds and compositions.

The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands for the nicotinic α7 receptor and may be useful for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.

The invention relates to the use of agmatine, in the treatment of acute neurotrauma (such as stroke) and degenerative disorders of the central and peripheral nervous system (such as dementia). The invention further provides novel compounds of general formula I (which are quinuclidine derivatives), formula II (which are norbornane derivatives), formula III (which are adamantane derivatives), and formula IV (which are phenothiazine derivatives): wherein R1, R2 and R3 are each independently hydrogen, hydroxy, substituted or unsubstituted C1-4 alkyl, substituted or unsubstituted C1-4 alkoxy, halogeno, amino, phenyl, or R4NR5; R4 and R5 are each independently hydrogen, or (CH2)n-[NH(CH2)x]y-NHR6, or (CH2)n-[NH(CH2)x]y-NH-NHR6, or (CH2)n-[NH(CH2)x]y-(NR7=)CNHR6, or (CH2)n-[NH(CH2)x]y-NH(NR7=)CNHR6 wherein n is from 0-5, y is from 0-5 and each x is independently from 1-5; R6, and R7 are each independently hydrogen, hydroxy, substituted or unsubstituted C1-4 alkyl, substituted or unsubstituted C1-4 alkoxy, or halogeno; and pharmaceutically acceptable salts and optically active isomers thereof.

The invention provides compounds of Formula I:

where in W is

These compounds may be in the form of pharmaceutical salts or compositions, racemic mixtures, or pure enantiomers thereof. The compounds of Formula I are useful to treat diseases or conditions in which α7 is known to be involved.

The present invention is directed to novel spiro-quinuclidinyl derivatives, pharmaceutical compositions containing them and their use in the treatment of central nervous system disorders.

The invention discloses a novel synthesis method of palonosetron hydrochloride, which comprises that (1) (S)-tetralin formic acid is reacted with thionyl chloride and (S)-3-amido-quinine cyclic amine, to obtain (S, S)-quinuclidine tetralin formamide, (2), (S, S)-quinuclidine tetralin formamide is reacted with reductant and boron trifluoride diethyl etherate, to obtain (S, S)-tetralin methyl quinine cyclic amine, (3), (S, S)-tetralin methyl quinine cyclic amine is reacted with diphosgene to be added and reacted in boron trifluoride diethyl etherate solution, while the product is added and reacted with alcaine and water, to obtain palonosetron hydrochloride. And the synthesis route is represented as above: a: SOCI2, (S)-3-aminoquinuclidine, b: NaBH4, BF3OEt2, c: BF3OEt2, CICO2CCI3.

The invention belongs to the field of medicinal chemistry, and discloses a technology for preparing aclidinium bromide. By adopting the technology, (R)-3-quinuclidinol, (C1)methyl-2,2-dithienyl glycolate and 3-phenoxy propyl bromide are taken as raw materials, and the aclidinium bromide is prepared by adopting a one-pot process. The method is simple to operate, and convenient for post-treatment, and has good application value.

The invention belongs to the technical field of pharmaceutical chemical engineering, and in particular relates to a method for measuring the optical purity of (R)-3-quinuclidinol. The method for measuring the optical purity of (R)-3-quinuclidinol comprises the steps of (a) preparing a sample; (b) preparing a test solution; (c) preparing a chromatographic condition, and performing detection. According to the method, a precolumn derivatization chiral chromatography method is adopted to measure the optical purity of (R)-3-quinuclidinol; specifically, the precolumn derivatization method is used for enabling (RS)-3-quinuclidinol racemate and paratoluensulfonyl chloride to react to generate (RS)-3-quinuclidinol paratoluensulfonyl chloride derivative, namely quinuclidinol 3-paratoluene sulfonate; then the chiral chromatography method is used for measuring the optical purity; therefore, the technical difficulty in measurement of the optical purity of (R)-3-quinuclidinol is creatively solved.

The invention relates to a preparation technology of solifenacin succinate. According to the preparation technology, (S)-1-phenyl-1, 2, 3, 4-tetrahydroisoquinoline carbamyl chloride (II) and (R)-3-quinuclidine alcohol metal salt (III) are reacted to generate solifenacin alkali, and then the solifenacin alkali is prepared into solifenacin succinate. With the adoption of the preparation technology provided by the invention, nucleophilic species which lead to a reverse reaction can be avoided during condensation process, namely, the reverse reaction cannot be generated in the preparation technology, therefore, a transformation rate of the solifenacin succinate is improved, a reaction is greatly promoted, a reaction process is quickly carried out under a mild condition, and the preparation technology is suitable for large-scale production.

A medicament used for prophylactic and/or therapeutic treatment of xerostomia, which is in the form for oral mucosal administration comprising a spirooxathiolane quinuclidine derivative represented by the following general formula (I) or an acid addition salt thereof:

[Formula 1]

(wherein R¹ and R² may be the same or different, and independently represent a hydrogen atom, an alkyl group, a cyclopentyl group, a cyclohexyl group, a monoaryl- or diaryl-substituted methylol group, or an aryl-substituted alkyl group) as an active ingredient.

The invention discloses a preparation method of an impurity in penehyclidine hydrochloride. The preparation method comprises the following steps: taking alpha-phenyl-alpha-cyclopentyl-alpha-hydroxyl ethyl p-toluene sulfonate and 3-quinuclidinol as the raw materials, carrying out reactions for a while under an alkaline condition, performing a post treatment to obtain 3-[2-cyclopentyl-2-phenyl-2-(2-cyclopentyl-2-hydroxyl-2-phenyl-ethyoxyl)ethyoxyl] quinuclidine hydrochloride free alkali, carrying out salt forming reactions between the free alkali and hydrogen chloride, and performing refinement to obtain hydrochloride of the free alkali. The preparation method can prominently increase the impurity content during the preparation process, the operation difficulty is reduced, moreover, the preparation method is suitable for massive production and is capable of obtaining a qualified high purity impurity; and the impurity purity measured by HPLC is 100%.

The invention discloses a method for resolving R/S-3-quinuclidinol by adopting a precolumn derivation high performance liquid chromatography. The method comprises the following steps of firstly, carrying out precolumn derivation esterification reaction on R/S-3-quinuclidinol to obtain R/S-3-quinuclidinol ester; then, preparing a 1.0mg/mL sample solution from R/S-3-quinuclidinol ester by using a high performance liquid chromatograph, wherein an amylose chiral column is used as a chromatographic column, a mixed solution of n-hexane, an alcohol and an alkaline additive is used as a positive mobile phase, and the flow rate, the sample volume, the detection wavelength and the chromatographic column temperature are controlled at 0.6-1mL/min, 5mul, 220-280nm and 20-35 DEG C respectively; and resolving the R/S-3-quinuclidinol ester chirally. The chromatographic peak obtained by adopting the method is good in pattern and symmetry and high in degree of resolving, and the method can be used for detecting and resolving R/S-3-quinuclidinol efficiently, rapidly and sensitively.

Quinuclidine carbonate derivatives act as muscarinic receptor antagonists and are effective for the prevention and/or treatment of a broncho-obstructive or inflammatory diseases.

The present invention relates to novel geminal substituted quinuclidine amide compounds, and pharmaceutical compositions of the same, that are suitable as agonists or partial agonists of α7-nAChR, and methods of preparing these compounds and compositions, and the use of these compounds and compositions in methods of maintaining, treating and/or improving cognitive function. In particular, methods of administering the compound or composition to a patient in need thereof, for example a patient with a cognitive deficiency and/or a desire to enhance cognitive function, that may derive a benefit therefrom.

This invention relates to novel quinuclidine derivatives and their use as pharmaceuticals. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.

The invention discloses an application of fluoro-diphenyl sulfimide as a nitrogen heterocyclic Diels-Alder reaction catalyst and has the advantages of high catalytic activity, good three-dimensional selectivity, low cost, easy acquisition, and the like. The invention also provides a method for synthesizing an iso-quinuclidine compound (I) by using the fluoro-diphenyl sulfimide as the nitrogen heterocyclic Diels-Alder reaction catalyst and catalyzing cyclonene, aromatic aldehyde (ii) and aromatic amine (iii) in an inorganic solvent or an organic solvent to carry out a nitrogen heterocyclic Diels-Alder reaction. The invention has the advantages of simple, convenient and rapid operation, high product yield, good three-dimensional selectivity, less environmental pollution, low production cost, and the like, thereby having good prospects.

The invention discloses a nitrogen oxide purification CHA zeolite molecular sieve as well as a preparation method and application of a catalyst thereof, and belongs to the field of chemical synthesistechnologies and application thereof. The CHA zeolite molecular sieve is synthesized by adopting an N,N,N-trialkyl-quinuclidine-4-quaternary ammonium onium compound as an organic template agent, the molar ratio range of silicon dioxide to aluminum oxide is 6-80, the average grain diameter is less than or equal to 500 nm, the total specific surface area is more than or equal to 400m2/g, the total pore volume is more than or equal to 0.20 ml/g, the micropore volume is more than or equal to 0.10 ml/g, and the grain diameter in the crystal face (-210) direction of the molecular sieve is 50-160 nm.After hydrothermal treatment of the molecular sieve at 600-800 DEG C, the tetra-coordinated aluminum accounts for more than or equal to 90% of the total aluminum amount, and the hexa-coordinated aluminum accounts for less than or equal to 10% of the total aluminum amount. The molecular sieve provided by the invention has high hydrothermal stability without large crystal grains, shows high nitrogen oxide reduction characteristics after being exposed at high temperature and high humidity, and especially shows a catalyst with high nitrogen oxide reduction characteristics in a temperature range of 200-550 DEG C.

The invention discloses a method of detecting two impurities containing a quinuclidine ring in a penehyclidine hydrochloride injection. The method adopts a gas chromatographic method to detect the contents of the impurities, namely the content of 3-quinuclidone and the content of 3-quinuclidinol. During detection, a sample of the penehyclidine hydrochloride injection is subjected to vacuum rotary evaporation to remove the solvent in the injection, is dissolved with an alkaline organic solvent so as to convert all the hydrochlorides into free alkalis and is dried by blowing nitrogen, and then dimethylformamide is added to prepare a sample solution to be detected; and impurity reference substances are salified by adding an acid firstly, then is processed as the same processing manner for the sample solution to be detected, and is prepared into impurity reference substance solutions. The sample solution to be detected and the impurity reference substance solutions are directly injected respectively, chromatograms are collected, and the contents of the impurities are calculated based on peak areas by an external standard method. The method of detecting the impurities has characteristics of simple and convenient operation, high sensitivity, capability of quantitative measurement, high accuracy and good reproducibility, effectively controls the product quality of the penehyclidine hydrochloride injection, and guarantees safety and effectiveness of clinical medication.