81 results about "Azabicyclane" patented technology

The present invention relates to an azabicyclo derivative and a preparation method therefor, and a use of a pharmaceutical composition containing the derivative in medicine. Specifically, the present invention relates to an azabicyclo derivative represented by general formula (I), and a preparation method therefor and a pharmaceutically acceptable salt thereof, as well as a use of the azabicyclo derivative and the pharmaceutically acceptable salt as therapeutic agents, especially as WRN inhibitors, wherein the definition of each substituent in the general formula (I) is the same as that in the description.

Provided is a rubber composition with which it is possible to obtain a vulcanized product and a vulcanized molded product having excellent wear resistance. According to the present invention, there is provided a rubber composition containing a chloroprene rubber, silica, a silane coupling agent, and a hydrate, the rubber composition containing 5-80 parts by mass of silica and 0.5-20 parts by mass or more of hydrate per 100 parts by mass of the chloroprene rubber, and the rubber composition containing 5-80 parts by mass of silica and 0.5-20 parts by mass of hydrate per 100 parts by mass of the chloroprene rubber. The content of a silane coupling agent is 0.5-15 parts by mass per 100 parts by mass of the silica, and the rubber composition satisfies at least one of the following conditions i) and ii): condition i) the rubber composition contains 3-methyl-thiazolidine-2-thione, and in the rubber composition, the content of 3-methyl-thiazolidine-2-thione is 0.5-15 parts by mass per 100 parts by mass of the chloroprene-based rubber, and the content of 3-methyl-thiazolidine-2-thione is 0.5-15 parts by mass per 100 parts by mass of the chloroprene-based rubber. The composition contains 0.1 to 3.0 parts by mass of 3-methyl-thiazolidine-2-thioketone; condition ii) the rubber composition contains a compound A and a compound B. The compound A is at least one compound selected from the group consisting of thiourea compounds, 3-methyl-thiazolidine-2-thione, and bis (5-mercapto-1, 3, 4-thiadiazol-2-yl) disulfides, and the compound B is at least one compound selected from the group consisting of thiourea compounds, 3-methyl-thiazolidine-2-thione, and bis (5-mercapto-1, 3, 4-thiadiazol-2-yl) disulfides. The compound B is at least one compound selected from the group consisting of thiuram-based compounds, sulfinamide-based compounds, thiazole-based compounds, guanidine-based compounds, benzimidazole-based compounds, N-phenyl-N-(trichloromethylthio) benzsulfonamide, and diazabicyclo-undecene-based compounds, and the content of the compound B is 100 parts by mass per 100 parts by mass of the chloroprene rubber. The rubber composition contains 0.1 to 3.0 parts by mass of a compound A and 0.01 to 3.0 parts by mass of a compound B.

In one aspect, the present application provides azabicyclo and diazepine derivatives useful as muscarinic receptor modulators. In another aspect, the present application provides pharmaceutical compositions for the treatment of ocular diseases, the compositions comprising at least one muscarinic receptor modulator. Formulas (I) and (II):

The present invention relates to compounds of formula (I) or formula (II) or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein said compound of formula (I) and said compound of formula II each comprises at least one ONO2 or ONO moiety; R1 is C1-C3alkyl; R2 is H, C1-C6alkyl, C3-C6cycloalkyl, C1-C2alkoxy, C2-C4alkenyl; R3 is C1-C4alkyl optionally substituted with C1-C2alkoxy, C3-C4cycloalkyl, C2-C4alkenyl; R4 and R5 are each independently H or C1-C6alkyl optionally substituted with F, OH, ONO, ONO2, COOH, C1-C3alkoxy, C3-C6cycloalkyl; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrollidine, piperidine, morpholine, piperazine, homo-piperazine, 2,5-diazabicyclo[2,2,1]heptane and 3,7-diazabicyclo[3,3,0]octane, wherein said heterocyclic ring is optionally substituted with independently one or more R6; R6 is C1-C6alkyl optionally substituted with independently one or more halogen, OH, ONO, ONO2, C1-C3alkoxy, C1-C3haloalkoxy, COOR7, NR8R9, C═NR10; R7 is H, or C1-C4alkyl optionally substituted with F, OH, ONO, ONO2, NR8R9; R8 and R9 are independently H, or C1-C4alkyl optionally substituted with ONO, ONO2; R10 is C1-C4alkyl optionally substituted with F, ONO, ONO2; C3-C6cycloalkyl; pharmaceutical compositions thereof, and their use in methods of treating or preventing a disease alleviated by inhibition of PDE5 in a human or in a non-human mammal.

The disclosure relates generally to methods of treating central nervous system disorders using (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane (i.e. centanafadine) or a pharmaceutically acceptable salt thereof. More particularly, the disclosure relates to treating conditions affected by monoamine neurotransmitters.

The invention provides a preparation method of Bainapenem. The preparation method comprises the following steps: by taking 5-N-(4-nitrocarbobenzoxy)-2-thia-5-azabicyclo [2.2. 1] hept-3-one (1) and sulfamirone acetate (2) as initial raw materials, carrying out condensation reaction to form a compound (3); and then combining with MAP (4) to form an important intermediate compound (5). And carrying out hydrogenation reaction deprotection on the compound (5) to obtain the besipenem. The method is short in synthetic route, mild and controllable in reaction condition, safe and reliable in operation process and suitable for industrial production.

Provided is a method for producing an olaparib precursor, said method comprising the step of performing the following steps (a) to (c) continuously without isolating a reaction intermediate. (a) Reacting dimethyl(3-oxo-1,3-dihydro-2-benzofuran-1-yl)phosphonate and 2-fluoro-5-formylbenzoic acid in DMF, acetonitrile, or THF and in the presence of diazabicycloundecene. (b) Reacting the reaction mixture obtained in the reaction of (a) with hydrazine. (c) Adjusting the reaction liquid obtained in the reaction of (b) to a pH of not more than 4, to obtain 2-fluoro-5-(4-oxo-3,4-dihydro-phthalazine-1-ylmethyl)-benzoic acid, which is an olaparib precursor.

The invention discloses a 2-azabicyclo [3.1. 1] heptene derivative as well as a synthesis method and application of the 2-azabicyclo [3.1. 1] heptene derivative. The 2-azabicyclo [3.1. 1] heptene derivative provided by the invention is obtained by exciting a rhodium complex by visible light to catalyze bicyclo [1.1. 0] butane to perform cycloaddition reaction. The 2-azabicyclo [3.1. 1] heptene derivative constructed by the method can be applied to the aspects of simulating bioisosteres and the like, is expected to obtain more innovative achievements in the field of organic synthesis methodology, and also can provide a brand new thought and a structural basis for developing novel drug molecules; and the medicine with better curative effect and less side effect can be designed.

Described herein is a small molecule splicing modulator compound that modulates splicing of mRNA, such as pre-mRNA, encoded by genes, and methods of use of the small molecule splicing modulator compounds for modulating splicing and treating diseases and conditions.

The invention relates to a method for catalytically synthesizing 2, 4-disubstituted phthalazine 1-(2H)-ketone from 1, 5, 7-triazabicyclo [4.4. 0] dec-5-ene. According to the method, 3-alkenyl phthalide and hydrazine compounds are taken as initial raw materials, TBD which is low in price and easy to obtain is taken as a catalyst, sodium tert-butoxide is taken as alkali, reaction is carried out at room temperature, and the 2, 4-disubstituted phthalazine 1-(2H)-ketone is obtained at high yield. According to the method, the cheap TBD is adopted as the catalyst, the reaction is carried out under the room temperature condition, and compared with a traditional reaction strategy, the economic cost is greatly reduced, the steps are simple, heating and a transition metal catalyst are not needed, operation is convenient, the yield is high, the cost is low, and good economic benefits are achieved.

The invention relates to a compound with a structure shown as a formula (I) or a stereoisomer, a tautomer or pharmaceutically acceptable salt or a solvate or a prodrug thereof, a preparation method of the compound, a pharmaceutical composition containing the modulators and application of the pharmaceutical composition in treatment of ROR gamma-mediated inflammatory, metabolic and autoimmune diseases, # imgabs0 #.

The invention relates to the technical field of medicinal chemistry, in particular to a 2-methyl-2-azabicyclo [3.2. 1] octane derivative which has a structure as shown in a general formula I or a general formula II or pharmaceutically acceptable salt, solvate, hydrate, isomer or prodrug of the 2-methyl-2-azabicyclo [3.2. 1] octane derivative, and a preparation method and application of the 2-methyl-2-azabicyclo [3.2. 1] octane derivative. As an acetylcholine receptor agonist, the compound shows high activity and high selectivity to M3 receptor subtypes. In-vitro experiments show that under the concentration of 40 mu M, the receptor excitation rate of the compound (such as 9a, 10a and the like) exceeds 95%, and is obviously superior to that of a positive control drug Aceclidine (48.65%). Due to the characteristic, the compound can generate a powerful pupil contraction pinhole effect by efficiently exciting an eye iris M3 receptor so as to improve near vision, and meanwhile, stimulation to ciliary muscles and related side effects are expected to be reduced due to high selectivity of the compound.

The present disclosure relates to a process for the synthesis of a heterocyclic ketone compound, and in particular a 3'-substituted-3-hydroxy-(8-azabicyclo[3.2.1]oct-8-yl)-[5-(1 h-pyrazol-4-yl)-thiophen-3-yl]-methanone compound and azabicyclic intermediates thereof. In particular, the present disclosure also relates to a process for the synthesis of Xanamem. The present disclosure also relates to a process for the synthesis of optionally protected azabicyclic intermediate compounds. The present disclosure also relates to 3'-substituted-3-hydroxy-(8-azabicyclo[3.2.1]oct-8-yl)-[5-(1 h-pyrazol-4-yl)-thiophen-3-yl]-methanone compounds and azabicyclic intermediate compounds thereof.

This invention provides a method for synthesizing 1,5-diazabicyclo[3.1.0]hexane compounds, their preparation, and their applications, belonging to the fields of organic synthesis and liquid propellant technology. 1,3-Propanediamine is dispersed in a suitable amount of chlorinated hydrocarbon solvent, and the corresponding aldehyde or ketone, a suitable amount of trifluoromethane sulfonate, and diisopropylethylamine are added sequentially. After half an hour, N-chlorosuccinimide is slowly added, and the reaction continues for 6-48 hours. The reaction is quenched with a suitable amount of water, and the mixture is extracted with dichloromethane. After concentrating the filtrate, column chromatography is used to obtain the corresponding 1,5-diazabicyclo[3.1.0]hexane compounds. Experiments have confirmed that 1,5-diazabicyclo[3.1.0]hexane compounds can rapidly and spontaneously ignite with fuming nitric acid and dinitrogen tetroxide, showing promising application prospects as a green fuel to replace methylhydrazine in the field of bicomponent liquid propellants.

Compounds are provided which can inhibit KRAS G12D. Also provided are pharmaceutical compositions and medical uses of the same, including the use in treating or preventing conditions such as cancers.

The application discloses a solution type nasal spray containing 3-[(2-cyclopentyl-2-hydroxy-2-phenyl)ethoxy]-1-(3-phenoxypropyl)-1-azabicyclo[2,2,2]octane or a derivative thereof and a preparation method of the nasal spray. The nasal spray contains a main drug, a solvent, a cosolvent, a bacteriostatic agent, a pH regulator and an osmotic pressure regulator. The nasal spray has good stability, the pharmacodynamic test result shows that the nasal spray has fast effect and small irritation, and can be used for treating various rhinitis and cold accompanied rhinitis.

A method of converting a protected pyrrole into a tetrachlorobicyclic compound. The tetrachlorobicyclic compound may include benzyl 2.2.4.4-tetrachloro-3-oxo-8-azabicyclo[3.2.1]oct-6-ene-8-carboxylate.

The present invention relates to 1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid {(1S,3R,5R)-8-[(R)-2-hydroxy-3-(methanesulfonyl-methyl-amino)propyl]-8-azabicyclo[3.2.1]oct-3-yl}amide (velcetrag) or a pharmaceutically acceptable salt thereof for use in the treatment of idiopathic chronic intestinal pseudo-obstruction (CIPO), neuropathic chronic intestinal pseudo-obstruction, or chronic intestinal pseudo-obstruction secondary to a neurodegenerative or demyelinating condition in patients suffering from said disease or condition.

The present invention relates to (R)-7-(3,5-difluorophenoxy)-N-((1R,5S,8s)-3-(6- methoxypyridazin-4-yl)-3-azabicyclo[3.2.1]octan-8-yl)-6,7-dihydro-5H-pyrrolo[1,2- b][1,2,4]triazol-2-amine, or a pharmaceutically acceptable salt thereof, for use in the treatment of a disease associated with amyloidosis, and its method of treatment thereof.

The present invention relates to compounds of formula (I) or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein R1 is C1-C3alkyl optionally substituted with F, C3-C6cycloalkyl, C1-C3alkoxy; X represents a bond or C1-C3alkylene optionally substituted with OH, ONO, ONO2; R2 is H, OH, ONO, ONO2, C(O)OH, C(O)OC1-C3alkyl, CHO, CN, C1-C3alkoxy, OC(O)H, OC(O)—C1-C3alkyl, C(O)N(R6)OR7, OC1-C3alkylene-C(O)OH, OC1-C3alkylene-C(O)OC1-C3alkyl, OC1-C3alkylene-C(O)N(R6)OR7, S(O0-2)C1-C3alkyl, CR8═N—OR9, CR8═N—NR10R11, CR8═NR12 or CR8═N—ONO2; R3 is C1-C6alkyl optionally substituted with F, OH, ONO, ONO2, C1-C3alkoxy, C3-C6cycloalkyl; C3-C6cycloalkyl, C2-C6alkenyl, C2-C6alkynyl; R4 is C1-C6alkyl optionally substituted with C3-C6cycloalkyl, C1-C6alkoxy, F, ONO, ONO2; C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl; R5 is H, SO2N—R13R14, NHSO2NR13R14; R6 is H or C1-C3alkyl; R7 is H, C1-C3alkyl, C1-C3alkoxy, C1-C3alkyl substituted with phenyl, benzyl or a heterocyclic ring, wherein said phenyl, benzyl or said heterocyclic ring are independently optionally substituted by C1-C3alkyl, F; R8 is H, CH3 or C2H5; R9: H, C1-C3alkyl optionally substituted with OH, ONO, ONO2, CN, COOH, COOC1-C3alkyl, C1-C3alkoxy, OC(O)H, OC(O)—C1-C3alkyl, C(O)N(R6)OR7, OC1-C3alkylene-C(O)OH, OC1-C3alkylene-C(O)OC1-C3alkyl, OC1-C3alkylene-C(O)N(R6)OR7, S(O0-2)C1-C3alkyl; R10 and R11 are each independently H, C1-C3alkyl optionally substituted with OH, ONO, ONO2, CN, COOH, COOC1-C3, C1-C3alkoxy, OC(O)H, OC(O)—C1-C3alkyl, C(O)N(R6)OR7, OC1-C3alkylene-C(O)OH, OC1-C3alkylene-C(O)OC1-C3alkyl, OC1-C3alkylene-C(O)N(R6)OR7, S(O0-2)C1-C3alkyl; i or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrolidine, piperidine, morpholine, piperazine and homopiperazine, wherein said heterocyclic ring is optionally substituted with C1-C3 alkyl; R12 is C1-C3 alkyl optionally substituted with OH, ONO, ONO2, CN, COOH, COOC1-C3alkyl, C1-C3alkoxy, OC(O)H, OC(O)—C1-C3alkyl, C(O)N(R6)OR7, OC1-C3alkylene-C(O)OH, OC1-C3alkylene-C(O)OC1-C3alkyl, OC1-C3alkylene-C(O)N(R6)OR7, S(O0-2)C1-C3alkyl; R13 and R14 are each independently H or C1-C6alkyl optionally substituted with F, OH, ONO, ONO2, COOH, C1-C3alkoxy, C3-C6Cycloalkyl; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrolidine, piperidine, morpholine, piperazine, homopiperazine, 2,5-diazabicyclo[2,2,1]heptane and 3,7-diazabicyclo[3,3,0]octane, wherein said heterocyclic ring is optionally substituted with R15; R15 is C1-C6alkyl optionally substituted with halogen, OH, ONO, ONO2, C1-C3alkoxy, C1-C3haloalkoxy, COOR16, NR17R18, C═NR19, or with a tetrazole group which is optionally substituted with C1-C3alkyl; or a heteroaryl ring which is optionally substituted with F, wherein the at least one heteroatom of said heteroaryl ring is nitrogen; R16 is H, or C1-C4alkyl optionally substituted with F, OH, ONO, ONO2, NR17R18, or with a heteroaryl ring, wherein the at least one heteroatom of said heteroaryl ring is nitrogen, and wherein preferably said heteroaryl ring is selected from pyrrolidine, piperidine, piperazine, morpholine, pyrrole, and imidazole, wherein nitrogen atom is directly bound to C1-C4 alkyl; R17 and R18 are each independently H or C1-C4alkyl optionally substituted with ONO, ONO2; R19 is C1-C4alkyl optionally substituted with F, ONO, ONO2; C3-C6Cycloalkyl; and their use in methods of treating or preventing a disease alleviated by inhibition of PDE-5 in a human or in a non-human mammal.

The invention belongs to the technical field of synthesis of organic drug intermediates, and particularly relates to an azabicyclo [3, 3, 0] octane medical intermediate and a preparation method thereof. The method comprises the following steps: oxidizing 1, 2, 3, 6-tetrahydrophthalimide to obtain an intermediate II; performing Dieckmann cyclization reaction on the intermediate II to obtain an intermediate III; and reducing functional group ketone on the intermediate III into alcohol under the action of a reducing agent a, reducing acylamino into amido under the action of a reducing agent b, and introducing t-butyloxycarboryl onto the amido to obtain the azabicyclo [3, 3, 0] octane medical intermediate. The preparation method comprises the following steps: carrying out oxidation ring opening and Dieckmann cyclization reaction on an initial raw material, and then carrying out one-pot reduction to obtain the target compound azabicyclo [3, 3, 0] octane medical intermediate by only three steps. The method has the advantages of simple raw materials, low cost, mild reaction conditions, high yield and great reduction of the production cost.

The invention relates to a method for preparing SSTR4 agonist compounds. A process for the preparation of SSTR4 agonist compounds via a diastereoisomer selective cyclization reaction does not require a separate epimerization step. Novel intermediates useful in the preparation of SSTR4 agonist compounds. The present invention relates to novel salts of certain SSTR4 agonists, such as salts of (1R, 5S, 6r)-N-(2-(1-methyl-1H-indazol-3-yl) propan-2-yl)-3-azabicyclo [3.1. 0] hexane-6-carboxamide succinate and salts of (1R, 5S, 6r)-N-(2-(1-methyl-1H-indazol-3-yl) propan-2-yl)-3-azabicyclo [3.1. 0] hexane-6-carboxamide adipate. Methods of treating pain, such as osteoarthritis pain, neuropathic pain, and lower back pain, by administering certain SSTR4 agonists and pharmaceutically acceptable salts thereof.

The present invention relates to specific salts of (1S,5R)-(1α,5α,6α)-N-[1,1-dimethyl-2-[(3-methyl-2-pyridyl)oxy]ethyl]-3-azabicyclo[3.1.0]hexane-6-carboxamide, to pharmaceutical compositions comprising said salts, to methods of using said salts to treat physiological disorders, and to intermediates useful in the synthesis of the salts.

The present invention provides novel crystalline solid forms of (R)-7-(3,5-difluorophenoxy)-N-((1R,5S,8s)-3-(6-methoxypyridazin-4-yl)-3-azabicyclo[3.2.1]octan-8-yl)-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-amine. Moreover, the invention relates to pharmaceutical compositions comprising said novel solid forms, to processes for making them and to their use as pharmaceutically active compounds.

The present invention relates to suitable usage, dosage, and use of an optically active azabicyclo ring derivative useful as a medicament, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising it.