119 results about "Diazepine" patented technology

The present invention provides substituted 10,11-Dihydro-5H-benzo[e]-pyrrolo[1,2-a][1,4]diazepine and 9,10-Dihydro-4H-3a,5,9-triaza-benzo[f]azulene compounds as well as methods and pharmaceutical compositions utilizing these compounds for the treatment and/or prevention and/or suppression of disorders which may be remedied or alleviated by oxytocin antagonist activity, including prevention and/or suppression of preterm labor, suppression labor at term prior to caesarean deliver, and for the treatment of dysmenorrhea. These compounds are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals.

This invention provides novel tricyclic diazepine compounds as well as methods and pharmaceutical compositions utilizing these compounds for the treatment and/or prevention and/or suppression of disorders which may be remedied or alleviated by oxytocin antagonist activity, including treatment of preterm labor, dysmenorrhea, endometritis, and for suppressing labor prior to caesarean delivery. These compounds are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and may be useful in the prevention and treatment of disfunctions of the oxytocin system in the central nervous system including obsessive compulsive disorder (OCD) and neuropsychiatric disorders.

The invention discloses a 5,8-dioxo-pyrimido[4,5-e][1,4]diazepine compound of a structural formula (1) or a pharmaceutically acceptable salt or stereoisomer or prodrug molecule thereof. The 5,8-dioxo-pyrimido[4,5-e][1,4]diazepine compound has the effects of effectively inhibiting the growth of various tumor cells and the generation of the EGFR (epidermal growth factor receptor), can be used for preparing anticancer medicaments and can overcome the resistance of the existing medicaments including the gefitinib, the erlotinib and the like.

Particulate formulations of benzodiazepines, such as diazepam, are used for nasal administration of diazepine drugs to patients. Multimodal particulate formulations of benzodiazepines and methods for their use, e.g. by nasal administration for the treatment of seizure, are also provided.

The present invention provides a novel diazepine compound that blocks the I_Kur current or the Kv1.5 channel potently and more selectively than other K⁺ channels. The present invention relates to a diazepine compound represented by General Formula (1)

There is provided novel diazepines that function as agonists at the melanocortin 4 receptor and as agonists at the melanocortin 1 receptor, pharmaceutical compositions containing them, methods for their use in treatment, and processes for their preparation.

The present invention relates to substituted benzo-pyrido-triazolo-diazepine compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted benzo-pyrido-triazolo-diazepine compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds or pharmaceutical compositions to subjects in need thereof.

The present application relates to 1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,4]benzodiazepine, 1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1,5]benzodiazepine, 2,3,4,4a,5,6,7,11b-octahydro-1H-pyrido[3,4-d][2]benzazepine, 1,2,3,4,4a,5,6,7-octahydropyrazino[1,2-a][1]benzazepine, 1,2,3,4,4a,5-hexahydro-7H-pyrazino[1,2-a][4,1]benzoxazepine, and 2,3,4,4a,5,6-hexahydro-1H-pyrazino[2,1-d][1,5]benzoxazepine, and 5,6,7,7a,8,9,10,11-octahydropyrazino[1,2-d]pyrido[3,2-b][1,4]diazepine derivatives of formula (I)

wherein R¹, R², R³, R⁴, R⁵, R⁶, X¹, X², X³, X⁴, Y¹, Y², and Y³ are as defined in the specification. The present application also relates to compositions comprising such compounds, and methods of treating disease conditions using such compounds and compositions, and methods for identifying such compounds.

The present invention relates to substituted benzo-imidazo-pyrido-diazepine compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted benzo-imidazo-pyrido-diazepine compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

The aryl- and heteroaryl-substituted tetrahydrobenzo-1,4-diazepine derivative compounds of the present invention are represented by formulae 1(A-D) having the following structure: where the substituents X and R¹-R⁸ are as defined herein.

The present invention relates to substituted dipyrido-pyrimido-diazepine compounds, substituted benzo-pyrido-pyrimido-diazepine compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted dipyrido-pyrimido-diazepine compounds, substituted benzo-pyrido-pyrimido-diazepine compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

The invention discloses a preparation method of 2-benzo diazepine anthrone. The method comprises the following steps: anthranone, dichloromethane and concentrated sulfuric acid are filled in a reaction bulb according to a certain proportion, mechanical stirring is carried out, and sodium azide is slowly filled in the reaction bulb under room temperature to obtain yellow solid; the yellow solid and ammonia water are put in the reaction bulb to heat up to 80 DEG C to 90 DEG C, then zinc powder and copper sulfate are filled in batches, and the solution is stirred for 24 hours to 40 hours. Thin-layer chromatography (TLC) detection is carried out to confirm that no raw materials is left, the solution is cooled to room temperature, the zinc power is filtered out, and the zinc powder is washed for 3 to 4 times by ammonia water of 10%. PH is adjusted to 4 to 5 through acid under the room temperature, the solution is cooled to the temperature lower than 5 DEG C, and is stirred, and suction filtration is carried out, mother solution is extracted through ethyl acetate, organic phase is washed with Na2S solution, Na2SO4 is dried and concentrated, and crude products are obtained through filter cakes and the organic phase; and the crude products and toluene are put into the reaction bulb, and products are obtained after a series of reactions. The purity of the raw materials of the preparation method of the 2-benzo diazepine anthrone is high, and the yield coefficient of the obtained product is quite high.

BET protein-inhibitory, especially BRD2-, BRD3- and BRD4-inhibitory, 4-substituted pyrrolo- and pyrazolodiazepines of the general formula I

are described, in which X, Y, n, m, p, R¹, R², R³, R⁴ and R⁵ are each as defined in the description, as are pharmaceutical compositions comprising the inventive compounds, and the prophylactic and therapeutic use thereof in the case of hyperproliferative disorders, especially in the case of neoplastic disorders. Also described is the use of the inventive compounds as BET protein inhibitors in benign hyperplasias, in atherosclerotic disorders, in sepsis, in autoimmune disorders, in vascular disorders, in viral infections, in neurodegenerative disorders, in inflammatory disorders and in male fertility control.

The present invention provides one step processes for the preparation of substituted dibenzo[b,e][1,4]-diazepine-11-ones by the reaction of substituted isatoic anhydrides with substituted 1,2-phenylenediamines in the presence of aqueous acetic acid.

The invention provides a synthesis method of a suvorexant intermediate (5S)-hexahydro-5-methyl-1H-1,4-diazepine-1-carboxylic t-butyl ester. The synthesis method of the suvorexant intermediate (5S)-hexahydro-5-methyl-1H-1,4-diazepine-1-carboxylic t-butyl ester comprises the following steps: (1) enabling a compound Suvor-1 to react with vitride solution to obtain a compound Suvor-2; enabling the compound Suvor-2 to react with 4,4-dimethoxy-2-butanone to obtain Suvor-3; (3) enabling the compound Suvor-3 to react with methanesulfonic acid to obtain a compound Suvor-4; (4) enabling the compound Suvor-4 to react with di-tert-butyl dicarbonate to obtain a compound Suvor-5; (5) enabling the compound Suvor-5 to react with hydrogen to obtain the suvorexant intermediate. The synthesis method of the suvorexant intermediate (5S)-hexahydro-5-methyl-1H-1,4-diazepine-1-carboxylic t-butyl ester provided by the invention has the advantages that the reaction is simple, starting materials are cheap and easy to obtain, the reaction condition is mild, and the production safety is high; in addition, the reaction steps are less, the reaction yield is high, and the production cost is lower; moreover, by introducing a chiral functional group, the purity of a target product obtained after induced synthesis and ring closure is high, the amount of impurities in enantiomer is small, the ee% is greater than97%, and the method is suitable for commercial large-scale production.

The present invention relates to paramagnetic solid lipid nanoparticles (pSLNs) comprising an amphiphilic paramagnetic metal chelating moiety selected from: a diazepine derivative of Formula I and a tetraazocyclododecane derivative of Formula (II): being said chelating moiety complexed to a paramagnetic metal ion selected from the group consisting of: Gd(III), Mn(II), Cr(III), Cu(II), Fe(III), Pr(III), Nd(III), Sm(III), Tb(III), Yb(III), Dy(III), Ho(III) and Er(III), or salts thereof. The invention further relates to the process for preparation of said solid lipid nanoparticles comprising amphiphilic complexes of paramagnetic metals (pSLNs) and to the use of pSLNs as MRI contrast agents in the diagnostic field.

An improved process for preparing 6-aryl-4H-s-triazolo[3,4-c]-thieno[2,3-e]-1,4-diazepines of formula I,

wherein:

• • R¹ is a hydrogen or halogen atom or a C₁-C₆ alkyl group,
  • R² is a hydrogen or halogen atom or a C₁-C₆ alkyl, C₁-C₆ hydroxyalkyl, C₃-C₆ cycloalkyl group or a 5- or 6-membered oxygen-, sulphur- or nitrogen-containing heterocyclic group which may optionally be substituted at the nitrogen atom by a C₁-C₃ alkyl group, and
  • R³ is a hydrogen or halogen atom.

The invention relates to a synthesis method of 3-carbonyl-2,8-diazepine helix[4.5]decane-8-carboxylic acid tert-butyl ester, mainly solving the technical problems of difficult reactant purification and the like in the traditional synthesis method and additionally providing a route for synthesizing an important intermediate, i.e. 8-(tert-butoxycarbonyl)-3-carbonyl-2,8-diazepine helix[4.5]decane-4-carboxylic acid. The synthesis method comprises the steps of: carrying out Micheal addition on an intermediate, i.e. tertiary butyl-4-(2,2-dimethyl-4,6-dicarbonyl-1,3-dioxan-5-ylene)piperidine-1-carboxylic ester and nitromethane to obtain a compound, i.e. tertiary butyl-4-(2,2-dimethyl-4,6-dicarbonyl-1,3-dioxan-5-group)-4-(nitromethyl)piperidine-1-carboxylic ester, then carrying out catalytic hydrogenation and lactamization to obtain a compound, i.e. 8-(butylcarbonyl)-3-carbonyl-2,8-diazepine helix[4.5]decane-4-carboxylic acid, and finally carrying out decarboxylation to obtain the final product, i.e. 3-carbonyl-2,8-diazepine helix[4.5]decane--8-carboxylic acid tert-butyl ester. The product of the invention is used as a template micromolecule for synthesizing various compound libraries.

The invention provides a preparation method of a nevirapine intermediate spherical crystal. The method concretely comprises the following steps: heating a reaction solution of a nevirapine intermediate 11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido-[3,2-b:2,3-e][1,4]diazepine to make the solution clarified, slowly dropwise adding the reaction solution to a crystallization solvent with the temperature controlled to be 10-40 DEG C, controlling the temperature of the crystallization system to be 0-50 DEG C during the dropwis adding, cooling the system to -10-10 DEG C after the dropwise adding is finished, filtering the solution, and drying the filtered solution to obtain the nevirapine intermediate spherical crystal. The method fills the gap in the prior art, the prepared spherical crystal has the advantages of small density and good fluidity of a crystal slurry, easiness in separation and drying, single solvent, low solvent rate, high crystallization yield, simple preparation method and high purity, and the preparation method has the advantages of easiness in commercial large-scale production, and very high promotion and application values.

The present invention relates to a synthesis method of tert butyl-7-(hydroxymethyl)-7, 8-dihydrogen-4H-pyrazolo[1,5-a][1,4] diazepine-5(6H)-formyl ester, and mainly solves the technical problems of low imperfect rate, no easiness in control of reaction, experimental operation inconvenience and the like of a middle-yield route of the synthesis process in the prior art. The tert butyl-7-(hydroxymethyl)-7, 8-dihydrogen-4H-pyrazolo[1,5-a][1,4] diazepine-5(6H)-formyl ester is prepared from raw material1H-pyrazole-3-formaldehyde which is cheap and easily available and capable of large-scale production by five steps, synthesis cost is saved, and mass production can be realized. The reaction formula is as shown in the specification, and the product obtained by the method is a useful intermediate or product for synthesis of many pharmaceuticals.

The invention discloses deuterated estazolam and a preparation method thereof. The preparation method comprises following steps of (1) adding 6-phenyl-8-chlorine-4H-[1,2,4] triazole-[4,3-a][1,4] benzo-diazepine into dimethyl sulfoxide or N,N-dimethylformamide, mixing and stirring; (2) adding a catalyst cesium carbonate or potassium carbonate as well as deuterated chloroform, stirring and heating up to over 40DEG C; and (3) separating so as to obtain deuterated estazolam. The preparation method is concise, is simple and convenient to operate, has low cost, and is easy for purification. Commercially available non-deuterated estazolam can be converted into deuterated estazolam by a little deuterated reagent used as a deuterium source in the non-deuterated solvent atmosphere in shorter time, and a pure product can be obtained through simple purification by column chromatography. The standard deuterated estazolam prepared by the method has high purity and stable chemical property, and is convenient for preparing standard substances for analysis. The preparation method can be used for producing, analyzing and detecting the deuterated internal standard substance used by estazolam.

The present invention relates to heterocyclic compounds useful for antagonizing angiotensin II Type 2 (AT₂) receptor. More particularly the invention relates to piperazine and diazepine compounds, compositions containing them and their use in methods of treating or preventing disorders or diseases associated with AT₂ receptor function including neuropathic pain, inflammatory pain, conditions associated with neuronal hypersensitivity, impaired nerve conduction velocity, cell proliferation disorders, disorders associated with an imbalance between bone resorption and bone formation and disorders associated with aberrant nerve regeneration.

The invention belongs to the technical field of drugs, and relates to a triazole-diazepine-5-ketone compound and application thereof, in particular to application of the compound, which serves as a tumor cell proliferation inhibitor, in the aspect of preparing antineoplastic drugs. According to the compound, the pharmaceutically accepted salt, solvate or isomer thereof has a structural formula asshown in the description, wherein the definitions of R1 to R8 are as described in the claims and the description.

The present invention relates to substituted benzo-pyrimido-tetrazolo-diazepine compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing substituted benzo-pyrimido-tetrazolo-diazepine compounds and methods of treating cell proliferative disorders, such as cancer, by administering these compounds and pharmaceutical compositions to subjects in need thereof.