68 results about "Oxazepine" patented technology

The present invention relates to 1,4 Oxazepines of formula I

having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes.

The invention relates to the area of medicinal chemistry, pharmacology and medicine and includes description of pharmaceutical compositions and combined medicaments on the base of secretion stimulators and protectors of incretin hormones for treatment of metabolic diseases (among them, diabetes, obesity, metabolic syndrome and the like). The invention consists in that that pharmaceutical composition or combined medicament comprises a derivative of tetrahydrobenzo[f][1,4]oxazepine—either nonsteroidal agonist of bile aids receptor TGR5, or one of endogenous bile acids which stimulate incretin hormones secretion, and also one of the known inhibitors of DPP-IV proteinase. In this case administration of TGR5 agonists is carried out peroral, and administration of endogenous bile acids is exercised rectal in the form of suppository or gel. As proteinase DPP-IV inhibitors could be used Vildagliptin, Saxagliptin, Sitagliptin, Teneligliptin, Linagliptin, Dutogliptin, Alogliptin, Gemigliptin, Carmegliptin and the like. Besides, the invention includes description of novel tetrahydrobenzo[f][1,4]oxazepine derivatives—nonsteroidal agonist of bile aids receptors TGR5, and also methods for their preparation. The invention provides enhancement of therapy effectiveness owing to synergetic action of the components, thus making possible simultaneous treatment of diabetes, and obesity, other metabolic diseases and their cardiovascular and renal complications.

Compounds represented by the general formula (I):

wherein each symbol is as defined in the description [with the proviso that 9-chloro-7-(1,1-dimethylethyl)-2,3,4,5-tetrahydro-1,4-benz-oxazepine and N-[[(5S)-2-oxo-3-(2,3,4,5-tetrahydro-1,4-benz-oxazepin-7-yl)-5-oxazolidinyl]methyl]acetamide are excluded], salts of the same, and prodrugs thereof have selective activation effect on serotonin 5-HT_2C receptor and are useful as preventive and therapeutic agents for lower urinary tract diseases, obesity, and/or pelvic organ prolapse.

Described herein are antipyschotic compounds of formula (I)

wherein:

is an optionally benzo-fused five or six member aromatic ring having zero to three hetero atoms independently selected from N, O, and S;

• • R¹ is hydrogen, (C_1-6) fluoroalkyl, (C_3-6) cycloalkyl, or (C_1-4) alkyl, wherein the (C_1-4) alkyl is unsubstituted or substituted with hydroxy, methoxy, ethoxy, OCH₂CH₂OH, —CN, imidazolidin-2-one, phenyl, or tetrazole wherein tetrazole is unsubstituted or substituted with (C_1-4) alkyl;
  • R² is H, halogen, (C_1-6) fluoroalkyl, (C_3-6) cycloalkyl, OR⁶, SR⁶, NO₂, CN, COR⁶, C(O)OR⁶, C(OH)R⁶, CONR⁷R⁸, phenyl or (C_1-6) alkyl, wherein the (C_1-6) alkyl is unsubstituted or substituted with a hydroxy;
  • R³ is hydrogen, (C_1-6)fluoroalkyl , (C_3-6) cycloalkyl, (C_2-6) alkenyl, phenyl, monocyclic heteroaromatic, bicyclic heteroaromatic, or (C_1-4)alkyl wherein (C_1-4) alkyl is unsubstituted or substituted with a phenyl;
  • R⁴ and R⁵ are independently selected from hydrogen, halogen, (C_1-6) alkyl, (C_1-6) fluoroalkyl, OR⁹, SR⁹, NO₂, CN, or COR⁹;
  • R⁶ is hydrogen, (C_1-6) fluoroalkyl, or (C_1-6) alkyl;
  • R⁷ and R⁸ are independently hydrogen, or (C_1-6) alkyl;
  • R⁹ is hydrogen, (C_1-6) fluoroalkyl, (C_1-6) alkyl;
  • Alk is (C_1-4) alkylene unsubstituted or substituted with a hydroxy;
  • Y is oxygen, sulfur, SO₂, or a bond;
  • X is CH₂, C═O, S, O, or SO₂;
  • Z is hydrogen, halogen, (C_1-6) alkyl, (C_1-6)fluoroalkyl, —OH, (C_1-6) alkoxy, (C_1-6) fluoroalkoxy, (C_1-6) alkylthio, (C_1-6) acyl, (C_1-4)alkylsulfonyl, —OCF₃, —NO₂, —CN, carboxamido which may be substituted on the nitrogen by one or two (C_1-4) alkyl groups, and —NH₂ in which one of the hydrogens may be replaced by a (C_1-4) alkyl group and the other hydrogen may be replaced by either a (C_1-4) alkyl group, a (C_1-6) acyl group, or a (C_1-4) alkylsulfonyl group;
  • the phenyl of R¹, R² or R³ is independently unsubstituted or substituted with one to three substituents independently selected from Z;
  • the monocyclic heteroaromatic of R³ is unsubstituted or substituted with one to three substituents independently selected from Z;
  • the bicyclic heteroaromatic of R³ is unsubstituted or substituted with one to three substituents independently selected from Z; and salts, solvates, and crystal forms thereof.

Also described are the use of the compounds of formula (I) as antagonists of the dopamine D₂ receptor and as agents for the treatment of psychosis and bipolar disorders, and pharmaceutical formulations of the compounds of formula (I).

Novel compounds of formula (I): suitable for use as in vivo imaging agents are provided as well as precursors suitable for the preparation of said compounds. The present invention also provides pharmaceuticals comprising the compounds and kits for the preparation of the pharmaceuticals. Furthermore, use of the compounds for imaging peripheral benzodiazepine receptors in a subject is provided, in particular for imaging pathological conditions in which PBR are upregulated, e.g. Parkinson's disease, multiple sclerosis, Alzheimer's disease and Huntington's disease, neuropathic pain, arthritis, asthma, atherosclerosis and cancer.

The invention discloses a polysubstituted benzo[b][1,4] oxazepine derivative and a preparation method thereof. The polysubstituted benzo[b][1,4] oxazepine derivative has the structural formula as shown in the description. The benzo[b][1,4] oxazepine derivative with multiple substituents, which cannot be synthesized by other methods, is synthesized, and profound and lasting significance is achieved from the angle of medical chemistry; the method has the advantages of easily available raw materials, high yield, mild reaction conditions, short reaction time, wide substrate range, strong reaction specificity, simple post-treatment and greenness.

The invention discloses a synthesis method of a pyrazolidinone-fused benzo 1,3-oxazepine compound, and belongs to the technical field of organic synthesis. 1-aryl pyrazolidinone 1 and a diazonaphthalene ketone compound 2 are used as raw materials, and in the presence of a catalyst, an oxidizing agent and an additive, a heating reaction is performed in an organic solvent to obtain the pyrazolidinone-fused benzo 1,3-oxazepine compound 3. According to the method, the pyrazolidinone-fused benzo 1,3-oxazepine compound is efficiently and regioselectively synthesized through cascade reaction between the 1-aryl pyrazolidinone compound and the diazonaphthalene ketone compound, and the method has the advantages that the raw materials are simple and easy to obtain, the operation is simple and convenient, the condition is mild, the selectivity is good, the substrate application range is wide, and the like.

The invention discloses tricyclo-pyrazole [1,5-d] [1,4] benzo oxazepine-one derivatives of which the structure is shown in a general formula of a figure in the abstract. The invention simultaneously discloses the preparation method of the tricyclo-pyrazole [1,5-d] [1,4] benzo oxazepine-one derivatives. The invention further discloses the application of the tricyclo-pyrazole [1,5-d] [1,4] benzo oxazepine-one derivatives as a reversible and selective monoamine oxidase inhibitor drug, specifically, the tricyclo-pyrazole [1,5-d] [1,4] benzo oxazepine can be applied to drugs or drug compositions for treating and preventing diseases related to aging, alzheimer's disease and parkinson's disease.

The invention discloses a 5-aryl-7-methoxycarbonyl dibenzo [b, e][1, 4] oxazepine-11(5H)-ketone compound and a preparation method thereof. The preparation method comprises the steps of carrying out condensation, isomerization and dehydration reaction on 3-dehydrogenated methyl shikimate and an aryl amine compound in the presence of an organic solvent and a catalyst in the microwave condition to obtain an aryl-substituted o-aminophenol intermediate; further adding o-halogen benzoic acid and an alkali neutralization catalyst in the microwave condition, cooling, pumping filtering, and carrying out recrystallization to obtain an N, N-diaryl-substituted o-aminophenol intermediate; and in the organic solvent, carrying out molecular lactonization cyclization reaction on the N, N-diaryl-substituted o-aminophenol intermediate in the presence of the catalyst and alkali to obtain the 5-aryl-7-methoxycarbonyl dibenzo [b, e][1, 4] oxazepine-11(5H)-ketone compound. The preparation method is simple, is short in the reaction time, is convenient for postprocessing and is high in the yield.

The invention discloses a synthetic method of an oxazepine [3, 2-b] indole compound, and belongs to the technical field of organic synthesis. The synthetic method comprises the following steps: performing [4 + 3] cycloaddition reaction on a crotonate-derived sulfur ylide reagent shown as a formula (2) and a 3-oxindolone substrate shown as a formula (1) under an alkaline condition to obtain the oxazepine [3, 2-b] indole compound shown as a formula (3), the invention also provides the oxazepine [3, 2-b] indole compound. The synthetic method is simple, convenient and efficient, large instrumentsand expensive raw materials are not needed, the reaction conditions are mild, the derivatization range of the substrate is wide, and a foundation is laid for industrial production.

The invention relates to a 6, 7, 8, 9-tetrahydro-[1, 4]oxazepine[3, 2-g] quinazoline derivative with a structure shown as formula I, tautomers, stereisomers and pharmaceutically acceptable salts thereof, especially pharmaceutically acceptable salts formed by the derivative and inorganic or organic acids or alkalis, and also relates to a preparation method, and application of the receptor tyrosine kinase inhibition property of the compounds in preparation of drugs treating proliferative diseases like cancer. (formula I).

The invention belongs to the technical field of medicine synthesis, and discloses a synthesis method of olanzapine related substances like namely a compound I and a compound II. The preparation methodcomprises the following steps: S1, synthesis of a compound I: adding olanzapine, an organic solvent and water into a reaction flask, sequentially adding Oxone and sodium hydroxide, continuously reacting until olanzapine spots disappear, then adjusting the pH of the system to 6-7, and carrying out extraction and recrystallization to obtain the compound I; S2, synthesis of a compound II: dissolvingthe compound I in an organic solvent, adding inorganic alkali liquor at 0 DEG C, then adding acetyl chloride, continuing to stir and react at 0 DEG C until the compound I disappears, carrying out liquid separation extraction, and carrying out silica gel column chromatography purification to obtain the compound II. The preparation method provided by the invention has the advantages of short reaction route, mild conditions, low overall cost and high yield and purity, and provides reliable material guarantee for subsequent quality control research and safety property research in the olanzapine preparation process.

Belonging to the field of medical technology, the invention specifically relates to a new preparation method of a DGAT1 inhibitor 4-amino-6-(3, 5-dimethyl-4-(3-methyl-1-(2, 2, 2-trifluoroethyl)-1H-pyrazole-4-yl)phenyl)-7, 8-dihydropyrimidine[5, 4-f][1, 4]oxazepine-5(6H)-one-hydrochloride. The method includes: taking 3, 5-dimethyl-4-(3-methyl-1-(2, 2, 2-trifluoroethyl)-1hydro-pyrazole-4-yl)aniline-hydrochloride as the starting raw material for condensation reaction with chloroethyl chloroformate to generate an intermediate 1; alkylating the intermediate 1 in an alcohol and alkali solution and then performing hydrolysis to generate an intermediate 2; subjecting the intermediate 2 to condensation reaction with 4, 6-dichloropyrimidine-5-acyl chloride to generate an intermediate 3; alkylating the intermediate 3, then carrying out intramolecular ring closure reaction to generate an intermediate 4; subjecting the intermediate 4 to ammoniation in a dioxane solution of ammonia to generate an intermediate 5; and subjecting the intermediate 5 to salt formation in an acetone solution to obtain a finished product. All the reaction intermediates involved in the invention are all solids, thus being easy for purification.

The invention discloses a preparation method of an oxazepine compound, and particularly discloses a preparation method and an intermediate of a compound shown as a formula (I) in the specification.

The invention provides an industrial method for clean recovery of olanzapine mother solution. According to the method, on the basis of a production process in the prior art, a mother solution is distilled and concentrated to recycle a solvent, distillation residues are dissolved with water and acid, macromolecules and insoluble impurities are intercepted through an ultrafiltration membrane assembly, the pH value of the filtrate is adjusted with alkali, and the product olanzapine is separated out. The HPLC purity of the recovered olanzapine reaches 99.5% or above, and the recovered olanzapine can be directly refined to obtain qualified olanzapine. The clean and environment-friendly recycling and reusing process for the olanzapine mother solution solves the difficulty in recycling and reusing of the solvent and olanzapine in the mother solution, relieves heavy environmental protection burden for production enterprises, brings potential considerable economic benefits for manufacturers, and has high economic value and social value.