32 results about "Thiomorpholine" patented technology

The present invention is relates to a compound of formula (I), wherein X1, X2 and X3 are, independently of each other, N or CH; with the proviso that at least two of X1 X2 and X3 are N; Y is N or CH; W is H or F; with the proviso that when W is F, then X1, X2 and X3 are N; R1 and R2 are independently of each other (i) a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein R3 and R4 are independently of each other H, C1-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxy, C1alkoxyC1-C3alkyl, CN, or C(O)O-C1-C2alkyl; or R3 and R4 form together a bivalent residue -R5R6- selected from C1-C3alkylene optionally substituted with 1 to 4 F, -CH2-O-CH2-, -CH2-NH-CH2-, or any of the structures wherein the arrows denote the bonds in formula (II); or (ii) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R7; wherein R7 is independently at each occurrence C1-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxyC1-C3alkyl, C3-C6cycloalkyl; or two R7 substituents form together a bivalent residue-R8R9- selected from Ci-C3alkylene optionally substituted with 1 to 4 F, -CH2-O-CH2- or -O-CH2CH2-O-; with the proviso that at least one of R1 and R2 is a morpholinyl of formula II; and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in the prevention or treatment of a skin lesion in a subject.

The invention belongs to the field of pharmacology, and discloses a crystal form I of an oxazolidinone antibacterial candidate new drug OTB-658, a preparation method of the crystal form I, a composition of the crystal form I and application of the crystal form I. Specifically, the invention relates to a crystal form I of N-(((3S, 3aS)-8-fluoro-1-oxo-7-thiomorpholinyl-3a, 4-dihydro-1H, 3H-benzo [b] oxazole [3, 4-d] [1, 4] oxazine-3-yl) methyl) acetamide, namely OTB-658, and a preparation method thereof. The OTB-658 crystal form I is used as an active pharmaceutical ingredient to prepare drugs for treating and / or preventing bacteria, especially mycobacterium tuberculosis infectious diseases. # imgabs0 #

Disclosed herein are certain therapeutic substituted heterocyclic bridged ring compounds, including substituted morpholine, thiomorpholine, and piperidine compounds and their homologues, having various advantages over current compounds used in certain methods of drug-assisted therapy, such as MDMA, together with pharmaceutical compositions containing such compounds, and methods of their use to treat mental health disorders and CNS disorders.

The invention discloses a flavonol-based fluorescent probe for continuously detecting hydrogen sulfide and hypochlorous acid as well as a preparation method and application of the flavonol-based fluorescent probe. The flavonol-based fluorescent probe is 3-(2, 4-dinitrophenoxy)-7-(4-(diphenylamino) phenyl)-2-(4-(thiomorpholinophenyl) chromone, and the structural formula of the flavonol-based fluorescent probe is shown in the specification. According to the invention, 7-(4-(diphenylamino) phenyl)-3-hydroxy-2-(4-thiomorpholinophenyl) chromone is used as an initial raw material, and the 7-(4-(diphenylamino) phenyl)-3-hydroxy-2-(4-thiomorpholinophenyl) chromone and 2, 4-dinitrofluorobenzene are subjected to nucleophilic substitution reaction to obtain the compound 3-(2, 4-dinitrophenoxy)-7-(4-(diphenylamino) phenyl)-2-(4-(thiomorpholinophenyl) chromone. The compound is firstly subjected to selective thiolysis reaction under the action of hydrogen sulfide, the fluorescence color of a solution of the compound is changed from colorless to bright orange under the irradiation of ultraviolet light with the wavelength of 365 nm, then hypochlorous acid is continuously added into the solution, and the compound can be further subjected to specific oxidation reaction with the hypochlorous acid, so that the compound can be obtained. And the fluorescence color of the solution is changed from bright orange to bright cyan. Therefore, the compound can be used as a fluorescent probe for continuously detecting hydrogen sulfide and hypochlorous acid, has the advantages of low detection limit, high response speed, good light stability, wide pH application range and the like, and shows a good application prospect.

The present invention relates to compounds that are cyclic carbamate and ureas benzo-morpholine and benzo-thiomorpholine derivatives of general formula (I) inhibiting the JAK family of non-receptor tyrosine protein kinases (JAK1, JAK2, JAK3, and TYK2); methods of preparing such compounds, pharmaceutical compositions containing them and therapeutic use thereof. The compounds of the invention may be useful in the treatment of diseases or conditions associated with a dysregulation of the JAK family non-receptor kinases; in particular for the treatment of various inflammatory disease including asthma, COPD and other respiratory diseases.

Disclosed herein are certain therapeutic substituted heterocyclic bridged ring compounds, including substituted morpholine, thiomorpholine, and piperidine compounds and their homologues, having various advantages over current compounds used in certain methods of drug-assisted therapy, such as MDMA, together with pharmaceutical compositions containing such compounds, and methods of their use to treat mental health disorders and CNS disorders.

The present invention relates to antisense oligonucleotides (ASO) for use in treating, preventing, or ameliorating the progression of conditions such as type 2 diabetes mellitus (T2DM) and insulin resistance, leptin resistance, and obesity, Rater Syndrome, and cancer. Specifically, a thiomorpholino-containing ASO targets a protein tyrosine phosphatase non-receptor type 1 (PTPN1) gene transcript and induces exon skipping (including exon 2) of the transcript during RNA processing, thereby inhibiting expression of the protein tyrosine phosphatase-1B (PTP1B) protein.

The present invention discloses a carbon dot that can respond to phosgene quickly and sensitively, and through the loading effect of carbon dot on related carriers, a portable material that can be visually monitored in real time and can effectively remove phosgene is constructed. Carbon dots are prepared with 4-(4-aminophenyl)thiomorpholine-1,1-dioxide as a precursor, and the carbon dots not only have a sensitive, rapid and specific response to phosgene, but also have excellent photostability and thermal stability, which are very suitable for long-term real-time monitoring. By loading the prepared carbon dots on a carrier with large holes and high specific surface area, a fluorescent carbon dot functional material with real-time sensitive monitoring and effective removal of gaseous phosgene is designed. The functional material can achieve a visual response to 2ppm phosgene within 1min, and the functional material also has the performance of adsorbing and reacting phosgene. The functional material is made into physical objects such as masks and hats, and is expected to achieve real-time monitoring and effective removal of phosgene, providing a more excellent choice for the safety monitoring of phosgene.

The invention belongs to the field of pharmacology, and discloses a crystal form II of an oxazolidinone antibacterial candidate new drug OTB-658, and a preparation method, a composition and application of the crystal form II of the oxazolidinone antibacterial candidate new drug OTB-658. In particular to a crystal form II of N-(((3S, 3aS)-8-fluoro-1-oxo-7-thiomorpholinyl-3a, 4-dihydro-1H, 3H-benzo [b] oxazole [3, 4-d] [1, 4] oxazine-3-yl) methyl) acetamide, namely OTB-658, and a preparation method of the crystal form II of N-(((3S, 3aS)-8-fluoro-1-oxo-7-thiomorpholinyl-3a, 4-dihydro-1H, 3H-benzo [b] oxazole [3, 4-d] [1, 4] oxazine-3-yl) methyl) acetamide. The OTB-658 crystal form II is used as an active pharmaceutical ingredient to prepare drugs for treating and / or preventing bacteria, especially mycobacterium tuberculosis infectious diseases.

The present invention relates to a Crystalline Form A of a compound of Chemical Formula 1 having physically and chemically outstanding characteristics compared to amorphous forms and other crystalline forms of the compound of Chemical Formula 1. Crystalline Form A of the compound of Chemical Formula 1 according to the present invention, compared to amorphous forms or other crystalline forms, does not denature even at prolonged exposure to harsh conditions, has low water sorption, is advantageous for formulation as the crystalline form does not change even under pressure or when pulverized, and the crystalline form itself has excellent stability, being useful for storage for extended periods.

The invention discloses a near-infrared fluorescent probe for detecting hypochlorous acid as well as a preparation method and application of the near-infrared fluorescent probe, and belongs to the technical field of fluorescent probe detection and analysis of hypochlorous acid. The near-infrared fluorescent probe for detecting hypochlorous acid is (E)-2-(5, 5-dimethyl-3-(4-thiomorpholine styryl) cyclohex-2-ene-1-subunit) malononitrile (NMS), and the structural formula of the near-infrared fluorescent probe is shown in the specification. The invention also specifically discloses a preparation method of the near-infrared fluorescent probe for detecting hypochlorous acid and application of the near-infrared fluorescent probe for detecting hypochlorous acid in simultaneous rapid and high-selectivity recognition of hypochlorous acid and preparation of an imaging detection reagent for hypochlorous acid in an organism. The fluorescent probe prepared by the invention can realize colorimetric and fluorescence detection of hypochlorous acid, and has the advantages of fast response, low detection limit and high selectivity.

The application belongs to the technical field of bulk drug preparation and relates to a synthesis method of Filgotinib. The synthesis method of Filgotinib takes bromobenzaldehyde (compound 1) as a starting material, and boron esterification reaction is carried out under the catalysis of palladium to obtain intermediate 3. Intermediate 3 is subjected to Suzuki coupling reaction with 2-amino-6-bromopyridine (compound 4) to obtain intermediate 5. Intermediate 5 is reacted with thiomorpholine-1,1-dioxide (compound 6) to generate intermediate 7. Intermediate 7 is condensed with cyclopropylcarbonyl chloride (compound 8) and potassium thiocyanate (compound 9) to obtain intermediate 10. Intermediate 10 is subjected to cyclization with hydroxylamine hydrochloride (compound 11) to obtain the final product Filgotinib. The synthesis method solves the problems of the prior art, such as difficulty in obtaining starting materials, harsh reaction conditions and complicated process route, and has the advantages of a short synthesis route, easy availability of materials used in the reaction and simple reaction operation.

The present invention relates to a novel method for preparing N-((5-(5-(difluoromethyl)-1,3,4- oxadiazol-2-yl)pyridin-2-yl)methyl)-N-phenylthiomorpholin-4-carboxamide 1,1-dioxide and a novel synthetic pathway for a main intermediate used in the method, and a novel crystalline form of the compound and the method thereof.

The invention discloses a small organic molecule eutectic crystal photoresist, a preparation method thereof and application of the small organic molecule eutectic crystal photoresist in near ultraviolet photoetching. The small organic molecule eutectic crystal photoresist disclosed by the invention is obtained by co-assembling 9, 10-anthracene dicarboxylic acid and amine small molecules; the co-assembly is realized through intermolecular hydrogen bonds and electrostatic interaction combination; the amine small molecules are selected from at least one of morpholine, thiomorpholine, triethylamine, triethanolamine and methyl piperazine. The small organic molecule eutectic crystal photoresist disclosed by the invention can be used for forming a forward photoetching structure through photo-induced molecular cascade decarboxylation and oxidation reaction in an absorbable low-energy ultraviolet wavelength range. The organic micromolecule eutectic crystal photoresist has the advantages of simple preparation process, high photoetching efficiency, high controllability of a three-dimensional structure and the like, and has a wide application prospect in the field of micro-nano processing.

The present invention discloses a flavonoid-based quenching fluorescent probe for specific detection of hypochlorous acid, and a preparation method and application thereof. The fluorescent probe is: 3-hydroxy-2-(4-thiomorpholinephenyl)-6-(4-(1,2,2-triphenylvinyl)phenyl)-4H-methene-4-one. The present invention uses 1-(4-hydroxy-4'-(1,2,2-triphenylvinyl)-[1,1'-biphenyl]-3-yl)ethane-1-one as a raw material, and carries out aldol condensation reaction and cyclization reaction with 4-thiomorpholinebenzaldehyde to obtain a target compound. The compound can specifically identify hypochlorous acid and can sensitively detect the content of hypochlorous acid in a solution. As a fluorescent probe for detecting hypochlorous acid, it has the advantages of convenient synthesis, good selectivity, high sensitivity, and a detection limit as low as 5.7×10 ‑8 mol / L and many other advantages, and has good application prospects.

The invention belongs to the technical field of precious metal separation, and particularly relates to ionic liquid, a preparation method and application thereof and a method for extracting gold (III) and / or palladium (II). The structural formula of the ionic liquid is as shown in the formula 1, and the ionic liquid is difunctional thiomorpholine ionic liquid, is low in cost, simple in structure and high in stability, and has good biodegradability, low toxicity and high recoverability. At room temperature, the ionic liquid and water are two phases which are immiscible, gold (III) and palladium (II) can be efficiently extracted, the extraction efficiency is high, the balance time is short, and the problems that mass transfer in the extraction process is blocked and depends on an organic solvent due to the fact that the viscosity of the ionic liquid is large are solved. Functional atom sulfur is introduced to a cation framework of the ionic liquid, so that the ionic liquid not only has an ion exchange function on gold (III) and palladium (II), but also has a coordination function, and shows excellent selectivity and reusability on the gold (III) and the palladium (II). # imgabs0 #

The present invention discloses a method for detecting H 2 S gas signal molecule fluorescent probe and its preparation method and application. The fluorescent probe has the following structural expression. The preparation method of the fluorescent probe comprises the following steps: 1) dissolving 4-bromo-1,8-naphthalene dicarboxylic anhydride and 4-(2-aminoethyl)-thiomorpholine in solvent A, stirring and reacting under reflux conditions to obtain an intermediate product; 2) mixing the intermediate product and sodium azide in solvent B, stirring and reacting under reflux conditions to generate the target product fluorescent probe. The preparation method of the fluorescent probe is simple, and it reacts with H at body temperature. 2 S responds quickly, has strong fluorescence, and has high detection sensitivity. #imgabs0#

The present invention relates to antisense oligonucleotides (ASOs) used to treat, prevent, or mitigate the progression of conditions such as type 2 diabetes mellitus (T2DM) and insulin resistance, leptin resistance and obesity, Rett syndrome, and cancer. Specifically, thiomorpholino-containing ASOs target the protein tyrosine phosphatase non-receptor type 1 (PTPN1) gene transcript during RNA processing and induce exon skipping (including exon 2), thereby inhibiting the expression of protein tyrosine phosphatase-1B (PTP1B) protein.

To provide a synthesis method that is efficient and desirable in terms of green chemistry for producing 6-(4,4-dimethylcyclohexyl)-4-[(1,1-dioxo-1λ6-thiomorpholin-4-yl)methyl]-2-methylthieno[2,3-d]pyrimidine and a salt thereof.SOLUTION: 6-(4,4-dimethylcyclohexyl)-4-[(1,1-dioxo-1λ6-thiomorpholin-4-yl)methyl]-2-methylthieno[2,3-d]pyrimidine is safely and efficiently synthesized by a method including a step of adding 4,4-dimethylcyclohexanone to the 6-position of the compound represented by the following formula [where Hal represents a halogen].SELECTED DRAWING: None

The present invention relates to compounds that are cyclic carbamate and urea benzo-morpholine and benzo-thiomopoline derivatives of general formula (I) that inhibit the JAK family (JAK1, JAK2, JAK3 and TYK2) of non-receptor tyrosine protein kinases, methods for preparing the compounds, pharmaceutical compositions comprising the compounds, and therapeutic use thereof. The compounds of the present invention may be useful in the treatment of diseases or conditions associated with dysregulation of JAK family non-receptor kinases, particularly in the treatment of various inflammatory diseases including asthma, COPD, and other respiratory diseases.

The present invention provides carvacrol quaternary ammonium salt derivatives, their synthesis methods, and their use as antibacterial agents, belonging to the field of pharmaceutical chemistry technology. The structure of the carvacrol quaternary ammonium salt derivatives of the present invention is shown in Formula (I), where n is the number of carbon atoms between the oxygen and nitrogen atoms, and is 3, 4, or 5; and R is selected from n-propylamine, n-butylamine, n-pentylamine, n-hexylamine, dipropylamine, dibutylamine, diisopropylamine, diisobutylamine, morpholine, or thiomorpholinyl. This series of carvacrol quaternary ammonium salt derivatives exhibits excellent antibacterial activity and can be used as a potential antibacterial agent. #imgabs0#

The application belongs to the field of pharmacy, and discloses a crystal form I of an oxazolidinone antibacterial candidate new drug OTB-658, a preparation method of the crystal form I, and a composition and application of the crystal form I. Specifically, the application relates to a crystal form I of N-(((3S,3aS)-8-fluoro-1-oxo-7-thiomorpholinyl-3a,4-dihydro-1H,3H-benzo[b]oxazol[3,4-d][1,4]oxazin-3-yl)methyl)acetamide, i.e. OTB-658, and a preparation method of the crystal form I. The crystal form I of OTB-658 is used as a pharmaceutical active ingredient to prepare a drug for treating and / or preventing a bacterial, in particular Mycobacterium tuberculosis, infectious disease.

The invention belongs to the field of pharmacology, and discloses a crystal form III of an oxazolidinone antibacterial candidate new drug OTB-658, a preparation method of the crystal form III, a composition of the crystal form III and application of the crystal form III. Specifically, the invention relates to a crystal form III of N-(((3S, 3aS)-8-fluoro-1-oxo-7-thiomorpholinyl-3a, 4-dihydro-1H, 3H-benzo [b] oxazole [3, 4-d] [1, 4] oxazine-3-yl) methyl) acetamide, namely OTB-658, and a preparation method thereof. The OTB-658 crystal form III is used as an active pharmaceutical ingredient to prepare drugs for treating and / or preventing bacteria, especially mycobacterium tuberculosis infectious diseases.

The invention belongs to the technical field of raw material medicine preparation, and relates to a synthesis method of agometinib. The invention relates to a method for synthesizing non-gogotinib, which comprises the following steps of: carrying out boron esterification reaction on p-bromobenzaldehyde (compound 1) serving as a starting raw material and bis (pinacolato) diboron (compound 2) under the catalysis of palladium to obtain an intermediate 3, carrying out Suzuki coupling reaction on the intermediate 3 and 2-amino-6-bromopyridine (compound 4) to obtain an intermediate 5, and carrying out reaction on the intermediate 5 and thiomorpholine-1, 3, 5, 6-tetramethyl-4-piperidine (compound 4) to obtain the non-gogotinib. The preparation method comprises the following steps: reacting 1, 1-dioxide (compound 6) to generate an intermediate 7, condensing the intermediate 7 with cyclopropylformyl chloride (compound 8) and potassium thiocyanate (compound 9) to obtain an intermediate 10, and cyclizing the intermediate 10 with hydroxylamine hydrochloride (compound 11) to obtain the final product Figotinib. The synthesis method provided by the invention solves the problems of difficult acquisition of initial raw materials, harsh reaction conditions, tedious process route and the like of the synthesis method for preparing Filgotinib in the prior art, and has the advantages of short synthesis route, easy acquisition of materials used in the reaction, and simple reaction operation.

The present invention relates to a new process for the preparation of N-((5-(5-(difluoromethyl)-1, 3, 4-oxadiazol-2-yl) pyridin-2-yl) methyl)-N-phenylthiomorpholine-4-carboxamide 1, 1-dioxide, and a new synthetic route of the main intermediates used in the process, as well as a new crystalline form of the compound and a process thereof.

The present invention discloses a stable crystal form of a novel PARP inhibitor and a preparation method thereof. The novel PARP inhibitor is 4-(3-(1,1-dioxothiomorpholine-4-carbonyl)-4-fluorobenzyl)phthalazine-1(2H)-one, and the stable crystal form is crystal form B. The powder X-ray diffraction pattern of the crystal form B shows main peaks at 2θ of 16.439°, 18.512°, 20.008°, 21.594°, 24.070°, 26.094°, and 27.940°. The crystal form B has high purity, good stability, good powder fluidity, and the like.

The present invention relates to a compound of formula (I),whereinX1, X2 and X3 are, independently of each other, N or CH; with the proviso that at least two of X1, X2 and X3 are N;Y is N or CH;W is H or F; with the proviso that when W is F, then X1, X2 and X3 are N;R1 and R2 are independently of each other(i) a morpholinyl of formula (II)wherein the arrow denotes the bond in formula (I); andwherein R3 and R4 are independently of each other H, C1-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxy, C1-C2alkoxyC1-C3alkyl, CN, or C(O)O—C1-C2alkyl; or R3 and R4 form together a bivalent residue—R5R6— selected from C1-C3alkylene optionally substituted with 1 to 4 F, —CH2—O—CH2—, —CH2—NH—CH2—, or any of the structureswherein the arrows denote the bonds in formula (II); or(ii) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R7; wherein R7 is independently at each occurrence C1-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxyC1-C3alkyl, C3-C6cycloalkyl; or two R7 substituents form together a bivalent residue —R8R9— selected from C1-C3alkylene optionally substituted with 1 to 4 F, —CH2—O—CH2— or —O—CH2CH2—O—;with the proviso that at least one of R1 and R2 is a morpholinyl of formula II;and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in a method of treating a skin disorder in a subject, wherein said skin disorder is a genodermatosis, a vascular anomaly or a skin disorder selected from scleroderma, sclerodermatous chronic graft-versus-host disease, lichen sclerosus, lichen planus, lichen ruber planus and scars.

The present invention relates to a compound of formula (I), wherein X1, X2 and X3 are, independently of each other, N or CH; with the proviso that at least two of X1X2 and X3 are N; Y is N or CH; W is H or F; with the proviso that when W is F, then X1, X2 and X3 are N; R1 and R2 are independently of each other (i) a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein R3 and R4 are independently of each other H, C1-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxy, C1-C2alkoxyC1-C3alkyl, CN, or C(0)0-C1-C2alkyl; or R3 and R4 form together a bivalent residue —R5R6— selected from C1-C3alkylene optionally substituted with 1 to 4 F, —CH2-0-CH2—, —CH2—NH—CH2—, or any of the structures wherein the arrows denote the bonds in formula (II); or (ii) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R7; wherein R7 is independently at each occurrence C1-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxyC1-C3alkyl, C3-C6cycloalkyl; or two R7 substituents form together a bivalent residue —R8R9— selected from C1-C3alkylene optionally substituted with 1 to 4 F, —CH2-0-CH2— or -0-CH2CH2-0- with the proviso that at least one of R1 and R2 is a morpholinyl of formula II; and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in a method of treating a skin disorder in a subject, wherein said skin disorder is a genodermatosis, a vascular anomaly or a skin disorder selected from scleroderma, sclerodermatous chronic graft-versus-host disease, lichen sclerosus, lichen planus, lichen ruber planus and scars.

Use of antisense thiomorpholino oligonucleotides to treat, prevent, or ameliorate the progression of inflammatory skin diseases or conditions such as psoriasis. Specifically, thiomorpholino¬ containing ASOs that target pre-mRNAs associated with inflammatory skin diseases or conditions such as psoriasis.