149 results about "Benzazepines" patented technology

4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine derivatives, which have excellent arginine vasopressin V₂ activity and are useful for a drug for the treatment of central diabetes insipidus and/or nocturia.

The present invention provides processes, methods and intermediates for the preparation of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, salts, hydrates and crystal forms thereof which are useful as serotonin (5-HT) receptor agonists for the treatment of, for example, central nervous system disorders such as obesity.

The present invention relates to substituted-2,3,4,5-tetrahydro-3-benzazepine derivatives that are modulators of the 5HT_2C receptor. Accordingly, compounds of the present invention are useful for the prophylaxis treatment of 5HT_2C receptor associated diseases, conditions or disorders, such as, obesity and related disorders.

A novel 4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine derivative or a pharmaceutically acceptable salt thereof, which is useful as an agent for treating or preventing nocturia and/or diabetes insipidus, is provided.

The present invention relates to substituted-2,3,4,5-tetrahydro-3-benzazepine derivatives that are modulators of the 5HT_2C receptor. Accordingly, compounds of the present invention are useful for the prophylaxis or treatment of 5HT_2C receptor associated diseases, conditions or disorders, such as, obesity and related disorders.

The present invention provides processes and intermediates for the preparation of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine and salts thereof which are useful as serotonin-2C (5-HT2C) receptor agonists for the treatment of, for example, obesity.

This invention relates to substituted 1-benzazepines and derivatives thereof useful as anti-infective agents, to compositions, including pharmaceutical compositions, comprising such compounds, to processes for making these compounds and to methods of using these compounds for killing bacteria and other microorganisms or inhibiting bacterial and other microorganism growth.

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 invention provides a method for preparing tolvaptan intermediate 7-chloro-1-[2-methyl-4-(2-methylbenzoylamino)-benzoyl]2,3,4,5-tetrahydro-1H-1-benzazepine-5-ketone, which comprises the following steps of: reacting a general formula (3) with thionyl chloride to form acetyl chloride solution; and then performing amidation reaction on a general formula (2) and the acetyl chloride solution in an organic solvent in the presence of de-acidifying agent, and treating the reaction product to obtain the tolvaptan intermediate shown in a general formula (1). The tolvaptan intermediate prepared by adopting the method of the invention has the characteristics of low cost, little impurity and high yield, and is more suitable for large-scale industrialized production.

A method for treating severe heart failure, comprising administering to a patient an effective amount of a benzazepine compound (1): wherein R₁ is H or halogen, R₂ is OH, or —NR₅R₆ (R₅ and R₆ are H or lower alkyl, R₃ is H, halogen, lower alkyl, or lower alkoxy, R₄ is halogen, lower alkyl or lower alkoxy, or a salt thereof, and a pharmaceutical composition containing the benzazepine compound (1) or a salt thereof and use of the compound (1) or a salt thereof for preparing a medicament for treatment of severe heart failure.

Benzazepine compounds, conjugates, and pharmaceutical compositions for use in the treatment of disease, such as cancer, are disclosed herein. The disclosed benzazepine compounds are useful, among other things, in the treating of cancer and modulating TLR8. Additionally, benzazepine compounds incorporated into a conjugate with an antibody construct are described herein.

The object of the present invention is to provide a prophylactic and/or therapeutic drug for obesity and obesity-associated diseasestor diabetes with a reduced risk for central side effects and high universality in usage. Another object of the present invention is to provide a pharmaceutical composition comprising a compound of the following formula:wherein Ar represents phenyl which may be substituted and/or condensed; n represents an integer of 1 to 10; R represents hydrogen or a hydrocarbon group which may be substituted, which may not be the same in its n occurrences; R may be bound to either Ar or a substituent for Ar; Y represents an amino group which may be subsituted or a nitrogen-containing saturated heterocyclic group which may be substituted, or a salt thereof, which can be used for a thermogenic agent, an antiobesity agent, a lipolytic agent, or a prophylactic and/or treating drug for obesity-associated diseases.

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.

A preparing method of (R,S)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine that is a lorcaserin intermediate is disclosed. The method includes (1) dehydrating a compound 1 and a compound 2 under catalysis by boric acid to generate an amide 3, (2) reducing the intermediate 3 with a borane dimethylsulfide complex to obtain a compound 4, and (3) subjecting the compound 4 to direct ring closing with the existence of aluminum chloride to generate the lorcaserin intermediate that is the (R,S)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine that is the compound 6. The method avoids use of 3,4,5-trimethoxyphenylboronic acid that is an expensive reagent, thus reducing the cost. The method avoids use of thionyl chloride so that the method is environmental friendly. A step of hydroxy chlorination is reduced so that the method is simple in process. The conversion ratio of raw materials and the total yield of reactions are increased. The yield of the compound 6 is increased from 60% in a patent to 82%. The method is suitable for industrial production. A reaction equation is shown in the description.

The invention relates to a preparation method of 7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine, which is an important intermediate for preparing arginine vasopressin V2 receptor antagonist Tolvaptan. The preparation method comprises the following steps: with methyl 2-amido-5-chlorobenzoate and ethyl 4-bromobutyrate as starting raw materials, reacting at a low temperature under the effect of an acid binding agent to generate secondary amine first, then carrying out Dieckman condensation reaction at a raised temperature to generate an intermediate mixture III, and finally carrying out hydrolysis to obtain the target compound 7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine. Compared with the existing method, the method provided by the invention has the advantages that the reaction steps are reduced, the two-step reaction is simplified to one-step reaction through temperature control, so the operation is simple, the processing is convenient, the product purity is high, and the yield is also greatly improved, thus the production cost can be reduced, and the benefits are increased.

The invention discloses a benzoazepine compound containing five-membered heterocycle with a structure shown in a formula I as well as a pharmaceutically acceptable salt of the derivative. In the formula I, n is equal to 1, 2, 3 or 4; X is N, O or S; R1 and R2 are simultaneously or separately hydrogen, fluorine, chlorine, bromine, methyl, ethyl, propyl, isopropyl, tertiary butyl, trifluoromethyl, methylalkoxyl, ethylalkoxyl, phenyl, fluorine, chlorine or bromine substituted phenyl, alkoxylphenyl, ester group, formyl, carboxyl and cyano. The invention also discloses a preparation method of the compound and discloses a medicinal composition with the compound or the pharmaceutically acceptable salt thereof as an active ingredient and application of the compound or the pharmaceutically acceptable salt thereof as anti-tumor medicaments, particularly application in preparation of medicaments for treating breast cancer, lung cancer and gastric cancer.