31 results about "Benzo Quinolizine" patented technology

The chemotherapy of malignant tumours is greatly restricted by the generally slight differentiation of the available cytostatic agents between normal and malignant tissue. In order to achieve an improvement of the selectivity in cancer therapy, novel prodrugs have been developed from 6-hydroxy-2,3-dihydro-1H-indolene, 5-hydroxy-1,2-dihydro-3H-pyrrolo[3,2-e]indolene and 5-hydroxy-1,2-dihydro-3H-benzo[e]indolene as well as from 6-hydroxy-1,2,3,4-tetrahydro-benzo[f]-quinolines, that may be used within the framework of the ADEP therapy (antibody directed enzyme prodrug therapy). The new prodrugs are characterised by a high difference in toxicity between the prodrug and underlying drug and by a very high efficacy of the drug. The high selectivity of the new prodrugs is probably attributed to the fact that, in the new prodrugs, a secondary halide is present in contrast to the prodrugs of a similar type previously produced by us. The direct alkylation of the DNA or RNA by the prodrugs and thus the toxicity of the prodrugs is thereby reduced. After splitting off of the glycosidic and / or acetal group on the phenolic hydroxy groups of the prodrugs, a spirocyclopropacyclohexadiene is formed which, being a highly toxic group, effects an alkylation of the DNA or RNA.

The invention discloses an iridium complex and a synthesis method and application thereof. The synthesis method of the iridium complex comprises the steps that 5-chloro-8-hydroxyquinoline and a 7, 8-benzoquinoline iridium dimer are added in an organic solvent, reaction is conducted under the heating or non-heating condition, and a target compound is obtained; wherein the organic solvent is ethanol, or a composition of ethanol and one or more than two selected from water, acetone, dichloromethane, trichloromethane, dimethyl sulfoxide and N, N-dimethylformamide. It is shown by test results in the invention that the iridium complex has remarkable biological activity (the activity is obviously higher than that of cis-platinum) on cervical cancer and ovarian cancer cells, and meanwhile, the toxicity of the iridium complex on normal hepatocytes of human body is extremely low (IC50 is higher than 80<mu>M).

The present invention relates to new solid forms of the compound (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid with the formula (Id) below.The compound of formula (Id) is a prodrug of a catecholamine for use in treatment of neurodegenerative diseases and disorders such as Parkinson's Disease.

The instant invention relates to novel prodrugs of optically pure benzoquinolizine-2-carboxylic acid and pharmaceutical compositions that include the prodrugs. In particular, the present invention relates to the sulfonic acid salts of L-alanine and L-valine prodrugs of S-(−)-9-fluoro-6,7-dihydro-8-(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acid. The compounds and compositions of the invention can be used to treat bacterial Gram-positive, Gram-negative and anaerobic infections, especially infections caused by resistant Gram-positive organism and Gram-negative organism, mycobacterial infections and emerging nosocomial pathogen infections.

The invention discloses an 8-hydroxyquinoline derivative iridium (III) complex as well as a preparation method and application thereof, and belongs to the field of medicines. The chemical name of the compound is 2-methylpyridino[3,2-a]-pyridino[1',2':1,2]imidazo[4,5-c]phenazine.bisbenzoquinolinyl iridium(III) hexafluorophosphate . The preparation method comprises the following steps: reacting 8-hydroxyquinoline with hydrochloric acid and NaClO3; adding anhydrous potassium carbonate; adding 2-amino-5-methylpyridine; adding o-phenylenediamine; obtaining a compound 3a; reacting 7,8-benzoquinoline with iridium trichloride hydrate to obtain a compound 4; and reacting the compound 3a with a compound 4 to obtain the 8-hydroxyquinoline derivative iridium (III) complex. The in-vitro anti-tumor activity of the compound on a human ovarian cancer drug-resistant strain SK-OV-3 / DDP is greater than that of an 8-hydroxyquinoline derivative ligand and a metal-based anti-cancer drug cis-platinum; and the toxicity to normal cells HL-7702 is very low, and a good effect of targeted inhibition of human ovarian cancer proliferation is reflected.

The present invention relates to a process for manufacturing (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]guinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid with the formula (Id) below and pharmaceutically acceptable salts thereofThe compound of formula (Id) is a prodrug of a catecholamine for use in treatment of neurodegenerative diseases and disorders such as Parkinson's Disease.The invention also relates to a new intermediate of said process.

The invention discloses oxadiazole phosphinic imide / iridium complex, prepared from bis[7,8-benzoquinoline]-{2-(N-diphenylphosphino)-amino-6-phenyl-[1,3,4]-oxadiazole}iridium, bis[2-phenylquinoline]-{2-(N-diphenylphosphino)-amino-5-phenyl-[1,3,4]-oxadiazole}iridium, and bis[1-phenylisoquinoline]-{2-(N-diphenylphosphino)-amino-5-phenyl-[1,3,4]-oxadiazole}iridium. A ligand herein contains two electron transport groups (namely oxadiazole and phosphinoxy), it is possible to improve carrier transport performance of a dye of such complex, and therefore, light-emitting efficiency of an electroluminescent device with the complex is improved and efficiency roll-off thereof is improved.

The present invention relates to a process for manufacturing (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid with the formula (Id) below and salts thereofThe compound of formula (Id) is a prodrug of a catecholamine for use in treatment of neurodegenerative diseases and disorders such as Parkinson's Disease.The invention also relates to new intermediates of said process.

The present invention relates to a new process for manufacturing (6aR,10aR)-7-propyl-6,6 a,7,8,9,10,10a,11-octahydro-[1,3]dioxolo[4′,5′:5,6]benzo[1,2-g]quinoline with formula (Ib) below, (4aR,10aR)-1-Propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[g]quinoline-6,7-diol with formula (I) below and salts thereof.Both compounds are for use in the treatment of neurodegenerative diseases and disorders such as Parkinson's Disease. The invention also relates to new intermediate compounds of said process.

The present invention relates to a process for manufacturing (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid with the formula (Id) below and salts thereofThe compound of formula (Id) is a prodrug of a catecholamine for use in treatment of neurodegenerative diseases and disorders such as Parkinson's Disease.The invention also relates to new intermediates of said process.

The invention discloses a synthesis method of the 3-(2-phenyl ethyl)-5-[2, 3, 6, 7-tetrahydrogen-1H, 5H-dibenzo [ij] quinoline-9-ene]-2, 4-oxazolidine dione; the steps first uses the hydroxy ethyl acetate and urea as the raw materials to make the oxazolidine-2 ,4-dione; then the oxazolidine-2 ,4-dione reacts with the beta-bromophenyl ethane to make the 3-phenethyl-oxazolidine-2, 4-dione; the 3-phenethyl-oxazolidine-2, 4-dione then reacts with the 2,3,6,7-tetrahydrogen-1 H, 5H-pyrido [3,2,1-ij] quinoline-9-formaldehyde to make the product 3-(2-phenyl ethyl)-5-[2,3,6, 7-tetrahydrogen-1 H, 5H-benzo [ij] quinoline-9-ene]-2,4-oxazolidine dione. The invention is of the simple process, the easily accessible and cheap raw materials, the high production rate, the low cost and the suitableness for the industrial production.

The invention provides a nitrogen-containing ligand iridium complex as well as a preparation method and application thereof, and belongs to the technical field of synthesis and application of inorganic materials. According to the iridium complex, firstly, a benzoquinoline iridium dimeric intermediate is synthesized from iridium trichloride and benzoquinoline, 4, 4'-dimethyl-2, 2'-bipyridyl is oxidized into bipyridine formaldehyde by using selenium dioxide at the same time, then hydroxylamine hydrochloride is added to reduce the bipyridine formaldehyde into bipyridine formaldehyde oxime, bipyridine formaldehyde oxime is used as a third ligand and reacts with the benzoquinoline iridium dimer to obtain a nitrogen-containing ligand iridium complex with a novel structure, and the nitrogen-containing ligand iridium complex can be used as a fluorescent probe for rapid identification and even trace detection of hypochlorite ions. The complex is simple in synthesis process, mild in reaction condition, small in reagent dosage, low in manufacturing cost, small in environmental pollution and good in optical property and biocompatibility. A hypochlorite ion fluorescent probe constructed by using the complex is high in sensitivity, good in selectivity, good in anti-interference performance, wide in concentration detection range and low in detection limit.

The invention discloses a method for synthesizing 1-arylbenzo[f]quinoline derivatives, which belongs to the technical field of chemical synthesis. The method is to use aromatic aldehyde, 2-naphthylamine and McFarlandic acid as raw materials, polyethylene glycol PEG400 as solvent and catalyst, reflux reaction at 80~100°C for 14~20h, suction filtration, washing with water, and the obtained crude product is passed through The target product was obtained by recrystallization from absolute ethanol. The present invention synthesizes a series of 1-arylbenzo[f]quinoline derivatives through three-component one-pot reaction, which has the advantages of mild reaction conditions, simple synthesis process, high yield and low cost; environment-friendly, non-toxic , post-processing is simple and safe, and meets the requirements of green chemistry.

The present invention relates to a novel hexahydrodibenzo[a,g]quinoline compound represented by general formula (I) and its derivatives, enantiomer, diastereoisomer, raceme and mixtures thereof, as well as pharmaceutically acceptable salts thereof. The present invention further relates to a method for preparing the compound, and the compound has good prevention and treatment effect on neurological diseases, especially diseases associated with dopamine receptor and 5-hydroxytryptamine receptor. The bioactivity experiment demonstrates that, the compound is expected to be developed into a novel and potent chemical entity for treating diseases associated with dopamine receptor and 5-hydroxytryptamine receptor, especially schizophrenia, Parkinson's disease, drug addiction, migraine and so on.

A novel process for preparation of Deutetrabenazine ((RR, SS)-1,3,4,6,7-11b-Hexahydro-9,10-di(methoxy-d6)-3-(2-methylpropyl)-2H-benzo [a] quinolizin-2-one) of formula I comprises of methylation of N-(2-(3,4-dihydroxy-phenyl)-ethyl)-formamide compound of formula III with deuteriated methanol (CD3OD or CD3OH) to obtain d6-N-(2-(3,4-dimethoxy-phenyl)-ethyl)-formamide compound of formula IV; cyclization of d6-N-(2-(3,4-dimethoxy-phenyl)-ethyl)-formamide in presences of dehydrating agent to obtain d6-6,7-Dimethoxy-3,4-dihydroisoquinoline compound of formula V; reacting d6-6,7-Dimethoxy-3,4-dihydroisoquinoline compound of formula V with 2-acetyl-N,N,N,4-tetramethyl-1-pentanaminium iodide compound of formula VI.

The invention discloses a mixed quinoline derivative iridium (III) complex as well as a preparation method and application thereof, and belongs to the field of medicines. The chemical name of the compound is hexafluorophosphorylate.pyrido [3, 2-a] pyrido [1 ', 2': 1, 2] imidazo [4, 5-c] phenazine. Dibenzoquinoline iridium (III). The preparation method comprises the following steps: reacting 8hydroxyquinoline with hydrochloric acid and NaClO3; adding anhydrous potassium carbonate; adding 2-aminopyridine; adding o-phenylenediamine; obtaining a compound 3a; reacting 7,8-benzoquinoline with iridium trichloride hydrate to obtain a compound 4; and reacting the compound 3a with the compound 4 to obtain the mixed quinoline derivative iridium (III) complex. The in-vitro anti-tumor activity of the compound on a human ovarian cancer drug-resistant strain SK-OV-3 / DDP is greater than that of an 8-hydroxyquinoline derivative ligand and a metal-based anti-cancer drug cis-platinum; the toxicity to normal cells HL-7702 is very low, and a good effect of targeted inhibition of human ovarian cancer proliferation is reflected.

The invention discloses a human ovarian cancer cell inhibitor as well as a preparation method and application thereof, and belongs to the field of medicines. The chemical name of the compound is hexafluorophosphorylate.2,12,13-trimethylpyrido[3, 2-a]pyrido[1',2':1,2]imidazo[4, 5-c]phenazine.bis-benzoquinolineiridium (III). The preparation method comprises the following steps: reacting 8-hydroxyquinoline with hydrochloric acid and NaClO3; adding anhydrous potassium carbonate; adding 2-amino-5-methyl pyridine; adding 4,5-dimethyl o-phenylenediamine to prepare a compound (3a); reacting 7,8-benzoquinoline with iridium trichloride hydrate to obtain a compound 4; and reacting the compound 3a with a compound 4 to obtain the human ovarian cancer cell inhibitor. The in-vitro anti-tumor activity of the compound on a human ovarian cancer drug-resistant strain SK-OV-3 / DDP is greater than that of an 8hydroxyquinoline derivative ligand and a metal-based anti-cancer drug cis-platinum; the toxicity to normal cells HL-7702 is very low, and a good effect of targeted inhibition of human ovarian cancer proliferation is reflected.

The present invention relates to a new process for manufacturing (6aR,10aR)-7-propyl-6,6a,7,8,9,10,10a,11-octahydro-[1,3]dioxolo[4′,5′:5,6]benzo[1,2-g]quinoline with formula (Ib) below, (4aR,10aR)-1-Propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[g]quinoline-6,7-diol with formula (I) below and salts thereof.Both compounds are for use in the treatment of neurodegenerative diseases and disorders such as Parkinson's Disease. The invention also relates to new intermediate compounds of said process.

The present invention relates to a process for manufacturing (2S,3S,4S,5R,6S)-3,4,5- trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a- octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid with the formula (Id) below and pharmaceutically acceptable salts thereof. The compound of formula (Id) is a prodrug of a catecholamine for use in treatment of neurodegenerative diseases and disorders such as Parkinson's Disease. The invention also relates to a new intermediate of said process.

The instant invention relates to novel prodrugs of optically pure benzoquinolizine-2-carboxylic acid and pharmaceutical compositions that include the prodrugs. In particular, the present invention relates to the sulfonic acid salts of L-alanine and L-valine prodrugs of S-(−)-9-fluoro-6,7-dihydro-8-(4-hydroxypiperidin-1-yl)-5-methyl-1-oxo-1H,5H-benzo[i,j]quinolizine-2-carboxylic acid. The compounds and compositions of the invention can be used to treat bacterial Gram-positive, Gram-negative and anaerobic infections, especially infections caused by resistant Gram-positive organism and Gram-negative organism, mycobacterial infections and emerging nosocomial pathogen infections.

The present invention relates to a novel hexahydrodibenzo[a,g]quinoline compound represented by general formula (I) and its derivatives, enantiomer, diastereoisomer, raceme and mixtures thereof, as well as pharmaceutically acceptable salts thereof. The present invention further relates to a method for preparing the compound, and the compound has good prevention and treatment effect on neurological diseases, especially diseases associated with dopamine receptor and 5-hydroxytryptamine receptor. The bioactivity experiment demonstrates that, the compound is expected to be developed into a novel and potent chemical entity for treating diseases associated with dopamine receptor and 5-hydroxytryptamine receptor, especially schizophrenia, Parkinson's disease, drug addiction, migraine and so on.

The invention discloses a substituted aza [5] helicene derivative and a preparation method and application thereof, the aza [5] helicene derivative has the following structural general formula: wherein the substitution site of R1 is any one of 1-7, the substitution site of R2 is any one of 8-11, and the substitution site of R3 is any one of 12-15; r1 is selected from one of hydrogen, C1-C5 alkyl, halogen, phenyl, substituted phenyl, naphthyl, thienyl, dibenzothienyl, furyl and N-phenyl carbazolyl, and R2 and R3 are respectively and independently selected from one of hydrogen and C1-C5 alkyl. The aza [5] helicene derivative is obtained by reacting benzo [h] quinoline and a diaryl cyclic high-iodine reagent in the presence of a metal palladium catalyst and alkali, the preparation method is simple and efficient, raw materials are easy to obtain, a substrate is easy to modify, and the aza [5] helicene derivative conforms to the green chemistry concept; in addition, the prepared aza [5] helicene derivative has potential application value in the fields of photoelectric materials, organic small molecule catalysis and the like.

The invention discloses an iridium complex and its synthesis method and application. The synthesis method of the complex is: taking 5-chloro-8-hydroxyquinoline and 7,8-benzoquinoline iridium dimer in an organic In a solvent, react under heating or without heating to obtain the target compound; wherein, the organic solvent is ethanol, or ethanol mixed with water, acetone, dichloromethane, chloroform, dimethyl sulfoxide and One or a combination of two or more of N,N-dimethylformamides. The applicant's test results show that the complex has significant biological activity (activity significantly higher than cisplatin) to cervical cancer and ovarian cancer cells, and it has minimal toxicity to normal human liver cells (IC 50 >80μM).

The present invention includes in one aspect substituted 2-oxo-1,2,5,6-tetrahydrobenzo[h]quinoline-3-carboxylic acids, analogues thereof, and compositions comprising the same, which can be used to treat and / or prevent hepatitis B virus (HBV) infection and / or hepatitis D virus (HDV) in a patient. In certain embodiments, the invention provides a compound of formula (I), or a salt, solvate, geometric isomer, stereoisomer, tautomer, and any mixtures thereof: