524 results about "Tetrahydroisoquinoline" patented technology

This invention provides the compounds of formula (I): or its a pharmaceutically acceptable ester or amide of such compound, or a pharmaceutically acceptable salt thereof, wherein X1 is NH; R1, R2, R4 through R6 and R7 through R11 are all hydrogen; R3 is hydroxy; X2 and X3 are methylene; X4 is a bond; and X5 is a carbon atom, and the like. These compounds have ORL1-receptor antagonist activity; and therefore, are useful to treat diseases or conditions such as pain, various CNS diseases etc.

The invention relates to melanocortin receptor ligands and methods of using the ligands to alter or regulate the activity of a melanocortin receptor. The invention further relates to tetrahydroisoquinoline aromatic amines that function as melanocortin receptor ligands and as agents for controlling cytokine-regulated physiologic processes and pathologies, and combinatorial libraries thereof.

The invention provides an imine coupled covalent organic framework material and a preparation method and application thereof and belongs to the technical field of porous materials. The structural formula of the imine coupled covalent organic framework material is shown in the description, and the material can be prepared by triazinyl aromatic polyamine A and alkoxy substituted aromatic aldehyde B through simple Schiff base condensation reaction. Under visible light excitation condition, the prepared imine coupled covalent organic framework material can catalyze multiple types of organic reactions, specifically for example reaction for photocatalysis of N-aryl tetrahydroisoquinoline and nucleophilic reagent. The prepared covalent organic framework material has very good chemical stability and heat stability, high specific surface area and high crystallinity, has strong visible light absorption properties, can serve as an excellent heterogeneous photocatalyst and has good industrial application prospect.

The invention discloses a synthetic method of a covalent organic framework (COF) material. The method comprises the following steps: after mixing 1,3,5-benzenetricarboxaldehyde with 2,5-di(N,N-dimethyl)amino-1,4-benzdihydrazide uniformly in an organic solvent, reacting in the presence of a catalyst acetic acid to obtain the COF material, wherein the mole ratio of 1,3,5-benzenetricarboxaldehyde to 2,5-di(N,N-dimethyl)amino-1,4-benzdihydrazide is 1:(0.5-3). The COF material obtained by adopting the method has relatively large specific surface area and regular open framework structure with adjustable diameter, thus being beneficial for mass transfer of reactants and products in photoabsorption and catalytic processes; the material can serve as a photocatalyst and can increase the yield of the dehydrogenative coupling reaction between 2-phenyl-1,2,3,4-tetrahydroisoquinoline and nitromethane from 39% in the absence of catalysts to 89%.

Certain tetrahydroisoquinoline compounds are histamine H3 receptor and serotonin transporter modulators useful in the treatment of histamine H3 receptor- and serotonin-mediated diseases.

The present invention relates to a method of treating disorders including cognition impairment, generalized anxiety disorder, acute stress disorder, social phobia, simple phobias, pre-menstrual dysphoric disorder, social anxiety disorder, major depressive disorder, eating disorders, obesity, anorexia nervosa, bulimia nervosa, binge eating disorder, substance abuse disorders, chemical dependencies, nicotine addiction, cocaine addiction, alcohol addiction, amphetamine addiction, Lesch-Nyhan syndrome, neurodegenerative diseases, late luteal phase syndrome, narcolepsy, psychiatric symptoms anger, rejection sensitivity, movement disorders, extrapyramidal syndrome, Tic disorder, restless leg syndrome, tardive dyskinesia, sleep related eating disorder, night eating syndrome, stress urinary incontinence, migraine, neuropathic pain, diabetic neuropathy, fibromyalgia syndrome, chronic fatigue syndrome, sexual dysfunction, premature ejaculation, and male impotence. This method involves administering to a patient in need of such treatment a therapeutically effective amount of a disclosed compound. Such compounds are 4-phenyl substituted tetrahydroisoquinolines having the Formula IA, IB, IIA, IIB, IIIA or IIIC as set forth herein.

Tetrhydroisoquinoline derivatives, pharmaceutical compositions comprising them and methods of treating disease are disclosed herein. The disclosed compounds are useful in the treatment and prevention of diseases mediated by chloride channel activity and / or protein trafficking, including, but not limited to, diseases associated with impaired mucociliary clearance such as cystic fibrosis, bronchitis, emphysema, and the like.

The compounds of the present invention are represented by the chemical structure found in Formula (I): wherein: the carbon atom designated * is in the R or S configuration; and X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined in R14; with R1, R2, R3, R4, R5, R6, R7, R8, and R14 defined herein.

The present invention relates to a method of treating disorders including cognition impairment, generalized anxiety disorder, acute stress disorder, social phobia, simple phobias, pre-menstrual dysphoric disorder, social anxiety disorder, major depressive disorder, eating disorders, obesity, anorexia nervosa, bulimia nervosa, binge eating disorder, substance abuse disorders, chemical dependencies, nicotine addiction, cocaine addiction, alcohol addiction, amphetamine addiction, Lesch-Nyhan syndrome, neurodegenerative diseases, late luteal phase syndrome, narcolepsy, psychiatric symptoms anger, rejection sensitivity, movement disorders, extrapyramidal syndrome, Tic disorder, restless leg syndrome, tardive dyskinesia, sleep related eating disorder, night eating syndrome, stress urinary incontinence, migraine, neuropathic pain, diabetic neuropathy, fibromyalgia syndrome, chronic fatigue syndrome, sexual dysfunction, premature ejaculation, and male impotence. This method involves administering to a patient in need of such treatment a therapeutically effective amount of a disclosed compound. Such compounds are 4-phenyl substituted tetrahydroisoquinolines having the Formula IA, IB, IIA, IIB, IIIA or IIIC as set forth herein.

Compounds are provided that, by way of their selective neurotransmitter binding useful for the treatment of various neurological and psychological disorders, e.g., ADHD. Such compounds are 4-phenyl substituted tetrahydroisoquinolines having the Formula IA, IB, IIA, IIB, IIIA or IIIC as set forth herein.

Described herein are compounds that are useful as caspase inhibitors having the formula: wherein Ring A is an optionally substituted piperidine, tetrahydroquinoline or tetrahydroisoquinoline ring; R1 is hydrogen, CN, CHN2, R, or CH2Y; R is an optionally substituted group selected from an aliphatic group, an aryl group, or an aralkyl group; Y is an electronegative leaving group; R2 is CO2H, CH2CO2H, or esters, amides or isosteres thereof; and R3 is hydrogen, an optionally substituted aryl group, an optionally substituted aralkyl group, or an optionally substituted C1-6 aliphatic group, R4 is an optionally substituted group selected from an aryl group or a heterocyclyl group, or R3 and R4 taken together with the nitrogen to which they are attached optionally form a substituted or unsubstituted monocyclic, bicyclic or tricyclic ring.

The compounds of the present invention are represented by the chemical structure found in Formula (I): wherein: the carbon atom designated * is in the R or S configuration; and X is a fused bicyclic carbocycle or heterocycle selected from the group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, benzoisoxazolyl, indazolyl, indolyl, isoindolyl, indolizinyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, benzotriazolyl, imidazo[1,2-a]pyridinyl, pyrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, thieno[2,3-b]pyridinyl, thieno[3,2-b]pyridinyl, 1H-pyrrolo[2,3-b]pyridinyl, indenyl, indanyl, dihydrobenzocycloheptenyl, tetrahydrobenzocycloheptenyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, indolinyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, 4H-quinolizinyl, 9aH-quinolizinyl, quinazolinyl, cinnolinyl, phthalazinyl, quinoxalinyl, benzo[1,2,3]triazinyl, benzo[1,2,4]triazinyl, 2H-chromenyl, 4H-chromenyl, and a fused bicyclic carbocycle or fused bicyclic heterocycle optionally substituted with substituents (1 to 4 in number) as defined in R14; with R1, R2, R3, R4, R5, R6, R7, R8, and R14 defined herein.

The present invention relates to a method of treating disorders by administering to a patient in need of such treatment a therapeutically effective amount of a compound of formula (I): wherein R1—R8 are as described herein, R4 being aryl or heteroaryl.

The present invention relates to a class of small molecule hydroxamic acid compounds capable of inhibiting histone deacetylases (HDACs). The present invention also relates to methods of preparation of hydroxamic acid HDAC inhibitor compounds of the invention, which are N-substituted-1,2,3,4-tetrahydroisoquinoline hydroxamic acid derivatives, and their incorporation into pharmaceutical compositions and methods of administration. The present invention also relates to N-substituted-1,2,3,4-tetrahydroisoquinoline hydroxamic acid derivatives, which may be prepared as a hydroxamic acid HDAC inhibitor compound library that can be utilized in screening methods known in the art.

The object of the present invention is to provide a differentiation inhibiting agent which allows culture of a stem cell or an embryonic stem cell in an undifferentiated state without use of any feeder cell, a method for culturing using the same, a cell culture liquid using the same, and a cell prepared by culturing using this differentiation inhibiting agent. The present invention provides a differentiation inhibiting agent which comprises a low molecular weight compound, especially a tetrahydroisoquinoline derivative, as an active ingredient; a method for safely culturing a stem cell in large scale in undifferentiated state in the absence of feeder cell which comprises culturing a stem cell by using a tetrahydroisoquinoline derivative; a culture liquid for stem cells comprising a tetrahydroisoquinoline derivative; and a cell which is obtained by culture using a tetrahydroisoquinoline derivative as a differentiation inhibiting agent.

Provided herein are compounds of the formula (I): wherein R1-R8 are as described herein, R4 being phthalazinyl, pyrazinyl, pyridazinyl, or quinoxalinyl. Such compounds are particularly useful in the treatment of a disorder which is created by or is dependent upon decreased availability of serotonin, norepinephrine, or dopamine.

Certain diaryl-substituted tetrahydroisoquinoline compounds are histamine H3 receptor and / or serotonin transporter modulators useful in the treatment of histamine H3 receptor- and / or serotonin-mediated diseases.

The invention discloses (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives, and a synthesis method and application thereof. The structural formula of the compounds is shown as a general formula I. Hexa hydro-pyrazino-pyridino-indoldione compounds are structurally modified by natural amino acid, the water solubility and in-vivo absorption are improved and the anti-thrombotic activity is improved. In-vitro and in-vivo anti-thrombotic activity experiments indicate that the compounds in the general formula I have excellent anti-thrombotic activity, and can be prepared into anti-thrombotic medicines.

This invention provides caspase inhibitors having the formula:wherein Ring A is an optionally substituted piperidine, tetrahydroquinoline or tetrahydroisoquinoline ring; R1 is hydrogen, CHN2, R, or —CH2Y; R is an optionally substituted group selected from an aliphatic group, an aryl group, an aralkyl group, a heterocyclic group, or an heterocyclylalkyl group; Y is an electronegative leaving group; R2 is CO2H, CH2CO2H, or esters, amides or isosteres thereof; Ar is an optionally substituted aryl group; and R3 is hydrogen, an optionally substituted C1-6 alkyl, F2, CN, aryl or R3 is attached to Ar to form an unsaturated or partially saturated five or six membered fused ring having 0–2 heteroatoms. The compounds are useful for treating caspase-mediated diseases in mammals.

The present invention discloses a synthesis method for a benzothiazole unit-based covalent organic framework material. The method comprises the following step of: in an organic solvent or an ionic liquid, performing a reaction on 2, 4, 6-trihydroxy benzenetricarboxaldehyde and 2, 6-diamino benzodithiazole to obtain the covalent organic framework material. The covalent organic framework material prepared by the method has a relatively large surface area and a regular channel structure, and is a good photocatalytic material; and the material can be used for cross-dehydrogenation coupling reaction for photocatalysis of N-aryl tetrahydroisoquinoline, and has good stability and an excellent catalytic effect.

The invention provides 15 6,7-dibydroxyl-1,1-dibydroxyl-tetrahydroisoquinoline-3-formyl amino acids of a general formula I. In the general formula I, AA is selected from L-Ala, Gly, L-Phe, L-Val, L-Leu, L-Ile, L-Trp, L-Ser, L-Thr, L-Tyr, L-Lys, L-Pro, L-Asp, L-Arg and L-Glu residues. The invention provides preparation methods of amino acids, and further provides the antithrombotic effect thereof on a rat carotid artery / jugular vein bypass intubation antithrombotic model. Therefore, the 15 6,7-dibydroxyl-1,1-dibydroxyl-tetrahydroisoquinoline-3-formyl amino acids of the general formula I has application prospect in clinical antithrombotic agents.

Certain diaryl-substituted tetrahydroisoquinoline compounds are histamine H3 receptor and / or serotonin transporter modulators useful in the treatment of histamine H3 receptor- and / or serotonin-mediated diseases.

The invention discloses a (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid kyrine conjugate, a preparation method and application thereof. The preparation method of the conjugate comprises the following steps of: preparing N-[(3S)-N-Boc-1,2,3,4- tetrahydroisoquinoline-3-formoxyl]-AA1-AA2-Arg (NO2)-OBzl by coupling N-[(3S)-N-Boc-1,2,3,4-tetrahydroisoquinoline-3-formoxyl]-AA1 and AA2-Arg (NO2)-OBzl; and detracting a protecting group, wherein AAl is selected from Gly, Asp or Gln, and AA2 is selected from Gly, Asp or Gln. The conjugate has excellent antithrombotic activity, can be clinically used as an antithrombotic agent, can be automatically assembled into nano particles in a water solution and is stable in the water solution; and the particle diameter is mostly from 200nm to 600nm.

A kind of tetrahydro isoquinoline derivatives (I), their preparation methods, medicine compositions and medicinal uses thereof, especially their uses as κ-opioid receptor excitant in pain relieving, which belongs to the medicine chemistry. The substituents R1, R2, R3, R4 of general formula (I) are defined as the description.