119 results about "Tetrahydroisoquinoline derivatives" patented technology

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 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.

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.

The invention discloses a method for synthesizing a chiraltetrahydro naphthalenederivate through asymmetric hydrogenation on isoquinoline by means of an iridium catalyst. A catalysis system applied in the method is a chiral bi-phosphine complex of metal iridium. The reaction is carried out under the conditions that the temperature is 25-60 DEG C; the volume ratio of tetrahydrofuran to dichloromethane in a solvent, namely a mixed solvent of tetrahydrofuran and dichloromethane is 1:1; the pressure is 13-50 Mpa; the ratio of a substrate to a catalyst is 50:1; the catalyst is a coordination compound of a (1,5-cyclooctadiene) iridium chloridedipolymer and a chiral bi-phosphine ligand. The corresponding chiral 1-position or 3-position substituted tetrahydro naphthalenederivate through hydrogenation on isoquinoline, and the enantiomeric excess of the derivate can reach 96%. The method is simple and practical in operation, raw materials are easy to obtain, the enantioselectivity is high, the yield is high, the reaction has atom economy, and the environment is friendly.

The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, Inhibitors of Apoptosis Proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation / inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

PPAR alpha activators, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and / or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases, in mammals, including humans.

Disclosed are compounds of formula (I) which inhibit the activity of anti-apoptotic Bcl-xL proteins, compositions containing the compounds and methods of treating diseases during which Bcl-xL proteins are expressed, eg cancer. X is heteroaryl; Y1 is phenylene or heteroarylene; L1 is a linker; Y2 is cycloalkyi, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl; Z1 is C(O)OR9, C(O)NR10R11, C(O)R11, NR10C(O)R11, etc.

The invention discloses 1,2,3,4-tetrahydroisoquinoline derivatives, and a preparation method and application thereof. The invention particularly relates to 1,2,3,4-tetrahydroisoquinoline derivatives having the structure of formula (I) shown in the specification, and a preparation method and application thereof, wherein substituents in the formula (I) are as defined in the specification. Such series of compounds are active for treating, preventing or relieving neuropathy or neuropathic pain, are applicable to the development of drugs for treating primary neuropathy, secondary neuropathy, peripheral neuropathy, neuropathy due to mechanical nerve injury or biochemical nerve injury, painful diabetic neuropathy (PDN) or related neuropathic diseases, and have a promising application prospect.

The invention relates to novel tetrahydroisoquinoline derivatives, namely compounds shown as a general formula (I) and pharmaceutically acceptable salts thereof. The invention also provides application of the novel tetrahydroisoquinoline derivatives, and in particular relates to application to the reversion of multi-medicine resistance of tumors. The derivatives are used for improving the curative effects of anti-tumor medicines.

The present invention is directed to a process for the synthesis of substituted-1,2,3,4-tetrahydroisoquinoline derivatives, useful as intermediates in the synthesis of pharmaceutical agents.

Provided are 7-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline derivatives and synthesis methods thereof. The compounds significantly inhibit the production of nitrogen monoxide (NO) and superoxide in an activated microglial cell and expressions of TNF-alpha, IL- 1beta inducive NO synthase and cyclooxygenase-2 genes. They also prevent NF-kB shift to a nucleus, decrease reactive oxygen species (ROS), inhibit expression of GTP cyclohydrolase I gene and over-production of tetrahydrobiopterin (BH 4 ), and protect dopaminergic neurons from injury due to activated microglial cells. Consequently, the compounds are effective in treating inflammatory and neurodegenerative diseases.

The present invention belongs to the field of medicine synthesis technology, and is especially 1- (3-indolyl)- 6, 7-methylene dioxy-1, 2, 3, 4-tetrahydro isoquinoine compounds and analogs in the general expression as shown and with substituted hydroxyl radical or acyl radical in the 2nd position, and their preparation process and medical application. Initial pharmacodynamic research of extracorporeal rice blast mold resisting experiment and extracorporeal antitumor experiment shows that these compounds has excellent activity, so that they may be developed into antifungal medicine and antitumor medicine.

The present disclosure relates to new enantiomers of tetrahydroisoquinoline derivatives and pharmaceutically acceptable salts thereof, their formulations and pharmaceutical compositions. Enantiomers of tetrahydroisoquinoline derivatives are provided for heart rate stimulating and blood pressure lowering activity, inhibitory activity on platelet aggregation, and inhibition of inducible NO synthase activity. The enantiomers of tetrahydroisoquinoline derivatives and their pharmaceutically acceptable salts are useful in the treatment of congestive heart failure, hypertension, thrombosis, inflammation, sepsis, cardiac insufficiency, and disseminated intravascular coagulation.

The invention relates to a novel tetrahydroisoquinoline derivative which is a compound with the general formula (I), and pharmaceutically acceptable salts thereof. The invention also provides the application of the novel tetrahydroisoquinoline derivative, particularly the application for reversing the multidrug resistance of tumors. The novel tetrahydroisoquinoline derivative and the pharmaceutically acceptable salts thereof can be used for improving the treatment effect of antineoplastic drug.

The invention discloses a C3-substituted tetrahydroisoquinoline derivative. A structure formula of the derivative is shown in formula I or formula II, wherein an R1 group is hydrogen, a naphthenic group, an alkyl group, a phenyl group or a substituted phenyl group; an R2 group is hydrogen or an alkyl group; a R3 group is an alkyl group; the substituted group is an alkyl group with 1 to 3 carbon atoms. The invention also provides a preparation method of the derivative and application in preparing phosphodiesterase II inhibitors. The preparation method comprises the following steps of using vanilline as raw material, and sequentially performing substituting reaction, addition and elimination reaction, reduction reaction, condensation reaction, Bischler-Napieralski reaction, acylation reaction, hydrolysis reaction and amidation reaction, so as to obtain the derivative. The derivative has stronger inhibition function on phosphodiesterase II, and has potential preventing and treatment effect on asthma and chronic pulmonary thromboembolism diseases.

PPAR alpha activators, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and / or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases, in mammals, including humans.

The invention discloses a preparation method of a 1,2,3,4-tetrahydroisoquinoline derivative. Aromatic iodide, aziridine compounds and olefin compounds are used as initial materials and stirred to react at 30-120 DEG C under the action of a catalyst, a ligand, a norbornene derivative and alkali, separation and purification are performed after the reaction, and the 1,2,3,4-tetrahydroisoquinoline derivative can be obtained. The 1,2,3,4-tetrahydroisoquinoline derivative can be synthesized efficiently, economically and greenly with the method. The method is mild in condition, good in substrate universality and high in yield, and the prepared 1,2,3,4-tetrahydroisoquinoline derivative can be widely applied to the fields of medicinal chemistry and organic chemistry.

The invention relates to a tetrahydroisoquinoline derivative, and a preparation method and medical application thereof. Particularly, the invention relates to the tetrahydroisoquinoline derivative asshown in a general formula (I), the preparation method of the tetrahydroisoquinoline derivative, a pharmaceutical composition containing the tetrahydroisoquinoline derivative, the application of the tetrahydroisoquinoline derivative as an estrogen receptor modulator, and the application of the tetrahydroisoquinoline derivative in preparation of drugs for treating estrogen receptor mediated or dependent diseases or symptoms. Each substituent in the general formula (I) is as defined in the specification.

The invention relates to the use of tetrahydroisoquinoline derivatives and relates to the use of compounds of a general formula (1) and salts thereof in the preparation of medicaments, in particular to the use in the preparation of novel anti-inflammatory and analgesic medicaments. The tetrahydroisoquinoline derivatives have the same or higher activity than ibuprofen and avoid gastrointestinal tract side effects of common nonsteroidal anti-inflammatory medicaments.

The present invention relates to the field of medicinal chemistry, and specifically relates to a category of novel tetrahydrocannabinol isoquinoline compounds (I), the preparation method, the pharmaceutical preparations containing the compounds and the application as tumor multi-drug and drug-resistant reversal agents. Wherein, the R 1 , R 2 and X are defined in the specification.

The invention belongs to the field of synthesis of medicaments, and relates to a 6,7-methylene-dioxy-1,2,3,4-tetrahydroisoquinoline derivative and a preparation method and application thereof, in particular to a 6,7-methylene-dioxy-1,2,3,4-tetrahydroisoquinoline derivative of which sites 1 and 2 are provided with N-substituted indole and the preparation method and application thereof. The general formula of the derivative is shown as the formula (I) in the specification. In-vitro antitumor experiments show that the compound provided by the invention has high activity and high biological activity and can be further researched and developed to be a novel antitumor medicament which is shown as the formula (I) in the specification.

1, 2, 3, 4-tetrahydroisoquinoline derivatives and synthetic method and uses thereof, the present invention belongs to medicine synthesis technique field, relating to general formula (1) is: X=(CH[2]) [n], n=1-15 or X=CO (CH[2]) [n-1], n=1-15; R[1], R[3], R[4], R[5], R[6] are 1, 2, 3, 4-tetrahydroisoquinoline compounds with different substituents and salt thereof, method thereof and application if medicine. The present invention discloses chemical structure and synthetic method and vitro acetylcholine esterase repress activity of the chemical compounds, which can be developed into new patern medicine for treating alzheimer's disease in further.

The invention discloses an application of a dibenzyl tetrahydroisoquinoline derivative in preparation of an anti-coronavirus drug. The structure of the bibenzyl tetrahydroisoquinoline derivative is shown as a formula I, and the bibenzyl tetrahydroisoquinoline derivative can effectively inhibit the infection ability of various coronaviruses to cells, and especially has excellent inhibitory activityto SARS-CoV-2 (S-D614), SARS-CoV-2 (S-G614), SARS-CoV, MERS-CoV coronavirus infection. The bibenzyl tetrahydroisoquinoline derivative disclosed by the invention has a good application prospect in preparation of anti-coronavirus medicines and medicines for preventing and / or treating diseases caused by coronavirus infection.

Provided are a tetrahydroisoquinoline derivative and an application thereof. The invention relates to a compound represented by the formula (V) and a preparation method and an application thereof in medicines. In particular, the invention relates to the derivative of the compound represented by the general formula (V) and a preparation method and the application thereof as a therapeutic agent in prevention and treatment of hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hepatic steatosis, type-II diabetes, hyperglycemia, obesity or insulin resistance syndromes and metabolic syndromes. The compound disclosed by the invention also can reduce total cholesterol, LDL-cholesterol and triglycerides, and increases the expression of hepatic LDL receptors and inhibits the expression of PCSK9.

The present invention relates to a compound or a pharmacologically acceptable salt thereof having an excellent DGAT inhibitory effect and feeding suppressant effect. The present invention provides a compound represented by the general formula (I), or pharmacologically acceptable salt thereof:[wherein,R1 represents a phenylaminocarbonyl group that may be substituted with 1 to 5 group(s) independently selected from Substituent Group A, a benzoxazol-2-yl group that may be substituted with 1 to 3 group(s) independently selected from Substituent Group A, or the like; R2 independently represents a C1-C6 alkyl group; R3 represents a group represented by the formula —C(═O)—O—R4 or the like; R4 represents a hydrogen atom, a C1-C6 alkyl group that may be substituted with 1 to 3 group(s) independently selected from Substituent Group B, or the like; X represents an oxygen atom, a methylene group, or a group represented by the formula —NH—, or the like; L represents a single bond, a methylene group, or the like; . . . represents a single bond or a double bond; m represents 1 or 2; n represents an integer of 0 to 5; Substituent Group A represents a halogen atom, a C1-C6 alkyl group, a C1-C6 halogenated alkyl group, a C1-C6 alkoxy group, or the like; and Substituent Group B represents a C3-C6 cycloalkyl group, a phenyl group, a carboxyl group, or the like].

1,2,3,4-Tetrahydroisoquinoline derivatives and their synthesis method and application, the invention belongs to the technical field of drug synthesis, and relates to the general formula (I): X=(CH2)n, n=1-15 Or X=CO(CH2)n-1, n=1-15; R1, R2, R3, R4, R5, R6 are 1,2,3,4-tetrahydroisoquinoline compounds and their salts with different substituents , its preparation method and application in medicine. The invention discloses the chemical structure, synthesis method and in vitro acetylcholinesterase inhibitory activity of these compounds, which can be further developed as novel drugs for treating Alzheimer's disease.

The invention provides a type of novel 1,2,3,4-tetrahydroisoquinoline derivatives with a structure of formula (I):wherein R1 represents propargyl or cyclopropylmethyl; wherein R2 represents N-ethyl-N-methylamino, 1-Pyrrolidyl, 1-Piperidinyl, or 1-Morpholinyl. The invention provides further a process for preparing said derivatives and a pharmaceutical composition containing the same. Said derivatives can be used to modulate the proteolytic process of amyloid precursor proteins (APP), and provides further novel compounds useful for treating Alzheimer's disease (AD).