46 results about "Azabicyclane" patented technology

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.

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.

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 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.

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 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 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.

The invention belongs to the technical field of medicines, and particularly relates to a 3-benzimidazole-3-aza-bicyclohexyl-2-ketone compound and application of the 3-benzimidazole-3-aza-bicyclohexyl-2-ketone compound. The invention discloses a compound as shown in a formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a deuterated compound thereof, or a solvate thereof, or a crystal form thereof, which can be used for preparing a glutamine cyclase (sQC / gQC) inhibitor, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a deuterated compound thereof, or a solvate thereof, or a crystal form thereof. A new medication choice is provided for clinical treatment of diseases (such as Alzheimer's disease) related to abnormal activity of glutamine cyclase.

A method for preparing SSTR4 agonist compounds. A method for preparing SSTR4 agonist compounds by a diastereomer-selective cyclization reaction that does not require a separate epimerization step. Novel intermediates for preparing SSTR4 agonist compounds. Novel salts of specific SSTR4 agonists such as (1R,5S,6r)-N-(2-(1-methyl-1H-indazole-3-yl)propan-2-yl)-3-azabicyclo[3.1.0]hexane-6-carboxamide xiccinate and (1R,5S,6r)-N-(2-(1-methyl-1H-indazole-3-yl)propan-2-yl)-3-azabicyclo[3.1.0]hexane-6-carboxamide adipate. A method for treating pain such as osteoarthritis pain, neuropathic pain, and lower back pain by administering specific SSTR4 agonists and their pharmaceutically acceptable salts.

The present invention relates to compounds of Formula (I) or an agronomically acceptable stereoisomers and / or salt of said compounds wherein Q, X, Y, Z, R1, R5, R6 and n are as defined herein. The invention further relates to herbicidal compositions which comprise a compound of Formula (I) and to the use of compounds of Formula (I) for controlling weeds, in particular in crops of useful plants.

The 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 (velusetrag) or a pharmaceutically acceptable salt thereof for use in a method of treating idiopathic chronic intestinal pseudo-obstruction (CIPO), neuropathic chronic intestinal pseudo-obstruction, or chronic intestinal pseudo-obstruction being secondary to neurodegeneration or to demyelinating conditions in a patient suffering from said diseases or conditions.

The present disclosure relates to a process for the preparation of 3-ethoxy-8-azabicyclo [3.2. 1] octane-1-yl) benzoic acid and derivatives thereof. Specifically, the invention provides a preparation method for chiral synthesis of 4-((1S, 3S, 5R)-3-ethoxy-8-azabicyclo [3.2. 1] octane-1-yl benzoic acid and a derivative thereof, and an application of the intermediate in preparation of a Factor B inhibitor.

The invention belongs to the technical field of preparation of medical intermediates, and particularly relates to a preparation method of a monomethyl impurity of an intermediate (S, S)-2, 8-diazabicyclo [4.3. 0] nonane of a quinolone antibacterial drug moxifloxacin hydrochloride, which comprises the following steps: by taking (S, R) 8-benzyl-7, 9-dioxo-2, 8-diazabicyclo [4.3. 0] nonane as an initial raw material, reacting at the temperature of 60-80 DEG C to obtain a monomethyl impurity of the intermediate (S, S)-2, 8-diazabicyclo [4.3. 0] nonane; a crude compound is obtained through condensation, reduction and debenzylation, and the crude compound is rectified, separated and purified to obtain the high-purity moxifloxacin side chain monomethyl impurity. The method has the characteristics that the synthesis route is short, the operation is simple, and the obtained moxifloxacin side chain monomethyl impurity product is high in purity and can be applied to research of impurity reference substances.

Compounds that can inhibit KRAS G12D are provided. Also provided are pharmaceutical compositions and medical uses thereof, including in the treatment or prophylaxis of a condition such as cancer.

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 present invention provides a pharmaceutical composition of a benzoaza aromatic ring derivative and its pharmaceutical application, the pharmaceutical composition comprising an active ingredient A and a pharmaceutical excipient, wherein the active ingredient A is selected from the group consisting of a compound represented by general formula (I) and a stereoisomer, tautomer, deuterated product, solvate, prodrug, metabolite, pharmaceutically acceptable salt, and cocrystal thereof, and the pharmaceutical composition contains 1 to 1000 mg of the active ingredient A, the content of which is selected from the range of 1.0% to 90.0%. The present invention further relates to the application of the pharmaceutical composition to the manufacture of a related medicament for treating kidney diseases. [C1] TIFF2026507026000044.tif50156

To provide a method for synthesis of diazabicyclo[6.2.0]decane compounds.SOLUTION: The synthesis proceeds by stereoselective synthesis of a chiral lactone followed by azetidine formation via a series of chemoselective reactions. Bicyclization results with the formation of diazobicyclo[6.2.0]decane related compounds.SELECTED DRAWING: None

The invention provides a preparation method of a 3-pyridyl-3, 9-diazabicyclo [3.3. 1] nonane compound, which comprises the following steps: (1) preparing a compound 3 from a compound 1 in the presence of alkali, Pd2 (dba) 3 and a ligand; (2) preparing a compound 4 from the compound 3 in the presence of a reducing agent; wherein R1 is selected from H, C1-C6 straight chain or branched chain alkoxy or R3 is selected from methoxycarbonyl, ethoxycarbonyl, t-butyloxycarbonyl, carbobenzoxy and trimethylsilyethoxycarbonyl, and R1 is selected from H, C1-C6 straight chain or branched chain alkoxy or R3 is selected from methoxycarbonyl, ethoxycarbonyl, t-butyloxycarbonyl and trimethylsilyethoxycarbonyl; when R2 is H, X is selected from Cl, Br and I; when R2 is Br, X is selected from I; the ligand in the step (1) is selected from one or more of Xphos, Sphos, Xantphos and Ruphos. The route is a brand new synthesis route, has the advantages of short synthesis route, mild reaction conditions, simplicity and convenience in operation, cheap and easily available raw materials and higher reaction yield, and overcomes the technical difficulty that a closed steel container and high temperature are required in the prior art.