346 results about "Pharmacophore" patented technology

A system for analyzing a vast amount of data representative of chemical structure and activity information and concisely providing conclusions about structure-to-activity relationships. A computer may adaptively learn new substructure descriptors based on its analysis of the input data. The computer may then apply each substructure descriptor as a filter to establish new groups of molecules that match the descriptor. From each new group of molecules, the computer may in turn generate one or more additional new groups of molecules. A result of the analysis in an exemplary arrangement is a tree structure that reflects pharmacophoric information and efficiently establishes through lineage what effect on activity various chemical substructures are likely to have. The tree structure can then be applied as a multi-domain classifier, to help a chemist classify test compounds into structural subclasses.

The present invention provides methods for treating or preventing cancer or neoplastic disease comprising administering to a patient a compound having the features of a pharmacophore for human anti-apotptotic Bcl protein inhibitors or identified by the in vitro methods for identifying anti-apotptotic-Bcl protein inhibitors. Also disclosed are methods for inhibiting the growth of a cancer cell or a neoplastic cell, comprising contacting the cancer cell or neoplastic cell with a compound having the features of a pharmacophore for human anti-apoptotic-Bcl protein inhibitors.

Pharmacophore models to be used in drug design and discovery are provided. An in silico protocol and in vitro assays are presented. Compounds and their pharmaceutically acceptable salts with HIV-1 integrase inhibitory and anti-HIV activity and use thereof in the treatment of HIV / AIDS and related infections either alone or in combination with all the known antiretroviral therapeutics are described.

The invention discloses a cyclopropylfluoroquinolone C-3 s-triazole thioether ketone thiosemicarbazone compound and a preparation method and application thereof. The chemical general structure of the compound is shown in formula I, in which R is at least one of H, ether group, hydroxyl, methyl, halogeno-group and nitro. According to the cyclopropylfluoroquinolone C-3 s-triazole thioether ketone thiosemicarbazone compound disclosed by the invention, a fluoroquinolone framework is actively overlaid or structurally complemented with three different pharmacophores such as a s-triazole heterocyclic ring, thiosemicarbazone and the like, so that the anti-tumor activity of the novel compound is increased, the toxic and side effects of normal cells are reduced, and the compound can serve as an anti-tumor activity matter to develop an anti-tumor drug of a novel structure.

The invention discloses a construction and prediction method of an integrated drug target prediction system. The method comprises the following steps of: analyzing a protein crystal structure database; selecting the protein bound with the drug-like ligand small molecule or the protein with the small molecule ligand binding potential as a target point, and building a crystal structure database of targets; for these targets, collecting the information of the targets related to diseases, the biology type and the active small molecule ligand information, and integrating a comprehensive target screening database composed of an active site database, a pharmacophore database, a small molecular compound database and a target basic information database. Based on the comprehensive target screening database, the construction of the integrated drug target prediction system is realized through a script program or a PipelinePilot flow, and the probability of target prediction accuracy of the method is provided. The method provided by the invention exerts the three above technical advantages to provide the probability of target prediction, thereby providing effective basis for further experimental verification.

The invention discloses a method for preparing a DNA coding compound library containing two or more pharmacophores. A novel initial head fragment used by the method has two or more chemically-modifiedlinking groups and comprises a nucleotide chain, 5' and 3' of the nucleotide chain respectively have a group R1 and a group R2 capable of performing chemical reaction, n connecting heads are arrangedon the nucleotide chain, each of the connecting heads is a long chain extended after a nucleotide monomer on the nucleotide chain is modified, and the long chain has a site G capable of performing chemical reaction. The site G of the initial head fragment respectively reacts with a fragment compound to generate a fragment compound residue B connecting the site G with the fragment compound together, a DNA coding compound is formed, and finally, the DNA coding compound library containing the two or more pharmacophores can be obtained. Through the method disclosed by the invention and the initial head fragment, the DNA coding compound library containing the two or more pharmacophores can be efficiently, simply and quickly obtained.

The invention discloses a method for measuring the combustion heat value of boron powder. The method comprises the following steps of: mixing SQ-2 powder and the boron powder and weighing; spraying standard acetone onto mixed powder for bonding into a pharmacophore; drying the pharmacophore in the air, weighing once again and cutting the dried pharmacophore into a plurality of sample medicament strips; winding the medicament strips on an ignition thread and connecting the ignition thread to an ignition electrode in an oxygen bullet; observing the sealing status of the oxygen bullet and recording initial temperature data; igniting the medicament strips to observe the variation curve of the temperature data; and integrating, cooling, correcting and processing the temperature data of inner and outer barrels by a cooling and correcting method so as to finally obtain the combustion heat value of a boron powder sample. The method ensures full combustion of the boron powder.

HPLC methods are provided to separate and detect morphinone, morphine, and dihydromorphine in the presence of hydromorphone. The isocratic HPLC methods employ ion-pair solute-solute ion-exchange mobile phase techniques in reversed phase chromatography. Method conditions in the disclosure provide separation and quantification of opioid pharmacophores in accordance with federal guidelines for obtaining resolution between analytes R≧2.0; tailing factor T≦2.0, capacity factor 2<k′≦50, and theoretical plate number N≧2000 for each opioid analyte peak.

The present invention is a one-step method for efficiently converting carbon-hydrogen bonds into carbon-carbon bonds using a combination of aryl halides, a substrate, and a copper salt as catalyst. This method allows faster introduction of complex molecular entities, a process that would otherwise require many more steps. This invention is particularly relevant for the organic synthesis of complex molecules such as, but not limited to, pharmacophores and explosives.

The invention provides a brand new drug molecule construction method based on a pharmacophore model which relates to the medicine development assisted by computers. A pharmacodynamic characteristic segment is selected, folded and placed in an appropriate position in the pharmacophore model. The connection of the pharmacodynamic characteristic segment is controlled by a genetic algorithm to construct a new molecule completely fitting for the pharmacophore model. The method thereof comprises the following steps: the pharmacophore model is input; a sub-database of the pharmacodynamic characteristic segment and the connection is built; the pharmacodynamic characteristic segment is reasonably placed in the framework of the pharmacophore model, and the population is initialized; a judgment is made on whether the pharmacodynamic characteristic segment is directly connected or a linker is added; the produced molecule is judged on pharmacophore characteristic, space steric hindrance limitation and pharmacodynamic property; the individual fitness degree is calculated; with the operation of hybridization and mutation, and a new population is generated; a compositionality appreciation is carried out on a new compound produced. The method achieves the beginning design of the molecule under the condition that the three dimensional structure of the Danpabai is unknown, and the constructed molecule completely meets the requirement of the pharmacodynamic characteristic. The method is novel and has significant meaning.

A compound of formula (I) is provided which is able to interact with beta-catenin / TCF-4 binding site, having a structure essentially equivalent to a pharmacophore (IA), as herein described.

Compounds of the current invention relate to rifamycin derivatives having antimicrobial activities, including activities against drug-resistant microorganisms. More specifically, compounds of the current invention relate to C-25 carbamate derivatives of rifamycin having another functional group or pharmacophore covalently attached to this position through a carbamate linkage. The resulting compounds exert their antimicrobial activity through a dual-function mechanism and therefore exhibit reduced frequency of resistance.

Disclosed are pharmacophores for developing and screening compounds having G-protein-coupled receptor antagonist activity, including LPA1, LPA2, LPA3 and S1P antagonists. These compositions have therapeutic benefit in the fields of cancer chemotherapy, cardiovascular disease prevention, and fertility protective agents during radiation and chemotherapy.

The invention discloses a 3,3'-methene-difluoroquinolone derivative of a chiral oxazine quinoline ring as well as a preparation method and application of the 3,3'-methene-difluoroquinolone derivative. The 3,3'-methene-difluoroquinolone derivative has a chemical general structural formula I shown in the specification, wherein R represents cyclopropyl or ethyl or fluoroethyl; R1 represents a hydrogen atom or methyl or ethyl; R2 represents a hydrogen atom or methyl; X represents a nitrogen atom or a hydrocarbon (CH) group or a fluoro-substituted carbon atom (F-C) or a methoxyl-substituted carbon atom (CH3O-C). The 3,3'-methene-difluoroquinolone derivative of the chiral oxazine quinoline ring, disclosed by the invention, can be used for realizing the superposition of a difluoroquinolone framework and alpha, beta-unsaturated ketone pharmacophores, so that the antitumor activity of a new compound is improved, the toxic and side effects on normal cells can be reduced, and the 3,3'-methene-difluoroquinolone derivative can be used as an antitumor active substance for developing an antitumor drug of a totally new structure.

The invention provides a symmetrical difunctional coupling agent compound (I), i.e. N-fluorenylmethyloxycarbonyl-L-beta-glutamate-di-N-succinimide (Fmoc-beta-Glu(OSu)-OSu), and a production method thereof. Based on the compound, a series of novel coupling compounds which respectively contain a symmetrical difunctional coupling base, i.e. beta-Glu (beta-glutamate) are prepared through being coupled to ligand molecules; the structural formula of the series of coupling compounds is shown as (II), wherein M1 is a -NH2-contained ligand of a target molecule T1, M2 is a -NH2-contained ligand of a target molecule T2, L is a linking group, and S is a report signal group. The compound (1) provided by the invention has been used in coupling a targeted integrin alphavbeta3 receptor ligands, gastrin-releasing peptide receptor ligands, telomerase inhibitor pharmacophores and epidermal growth factor receptor ligands, and thus, a plurality of coupled bi-ligand molecular imaging agents and coupled tri-ligand molecular imaging agents are synthesized. The invention further relates to the use of the compound (I) and the series of novel coupling compounds (II) in the preparation of imaging agent drugs.

The invention discloses a fluoroquinolone-methyl thiazolyl tetrazolium heterozygous derivative as shown in formula I. The derivate is characterized in that pharmacophores of fluoroquinolone and methylthiazolyl tetrazolium type medicines are interconnected through proper connection structures; the bioactivity experiment verifies that the compound has bacteria and fungus inhibiting activity and hasgood application prospect.

The invention discloses a chirality 7-(piperazine-substituted pyrazol aldehyde condensation isoniazide) fluoroquinolone carboxylic acid derivative as well as a preparation method and application thereof. The chirality 7-(piperazine-substituted pyrazol aldehyde condensation isoniazide) fluoroquinolone carboxylic acid derivative is a compound with the general structural formula (I), wherein R1 is H, methyl or ethyl, and R2 is H or methyl. According to the chirality 7-(piperazine-substituted pyrazol aldehyde condensation isoniazide) fluoroquinolone carboxylic acid derivative provided by the invention, fluoroquinolone, isoniazide and pyrazole aldehyde hydrazone are effectively combined to form a compound with a new structure; superposition and cooperation of activity are achieved; superposition of the three pharmacophores of fluoroquinolone, isoniazide and pyrazole aldehyde hydrazone is realized, the antituberculosis activity is improved, the toxic and side effects of fluoroquinolone and isoniazide to normal cells are decreased, and meanwhile, the probability that mycobacterium tuberculosis resists such drugs can be lowered; the chirality 7-(piperazine-substituted pyrazol aldehyde condensation isoniazide) fluoroquinolone carboxylic acid derivative can serve as an antituberculous active substance used for development of an antituberculous drug with a new structure.

Provided herein are compounds having anti-proliferative effect. Also provided are compounds that can modulate the activity of multi-domain proteins comprising a dimerization arm and interdomain tether, such as EGFR, where an untethered, extended conformation is the active state and a tethered conformation is the inactive state, resulting in an autoinhibited configuration. Also provided are methods and pharmacophores for identifying such compounds. Other aspects provide methods or therapeutic treatment for proliferative diseases, disorders, or conditions, such as those associated with EGFR.

The invention comprises for methods of identifying pharmacophores based on the spleen tyrosine kinase (SYK) protein or fragment thereof. The invention further provides methods of identifying SYK inhibitors using pharmacophores that are identified from co-crystals of SYK and its ligands. Further, the invention comprises methods of inhibiting SYK comprising contacting the residues lining the binding site with an inhibitor compound identified from pharmacophores.

The present invention relates to FGFR pharmacophores, and in particular to compounds which are capable of binding to FGFR with greater affinity than their binding to VEGFR and methods of identifying such compounds using the pharmacophore. The present invention further relates to compositions, methods and uses of the compounds and the pharmacophores disclosed herein.

The invention discloses a 1,8-anhydride naphthalene derivative with the side chain containing isoquinoline and synthesis and application thereof, and belongs to the field of biological organic synthesis. According to the 1,8-anhydride naphthalene derivative with the side chain containing isoquinoline, 1,2,3,4-tetrahydro naphthalene is introduced into one end of naphthalimide through an alkyl chain to serve as pharmacophore, a different cyclammonium side chain is introduced into the other end of naphthalimide, the purpose is to introduce isoquinoline pharmacophore with the antitumor activity to increase the conjugate area and improve biological activity of molecules, and therefore the antitumor effect is improved.

The current invention provides a series of bicyclic nitroimidazole- substituted phenyl oxazolidinones in which a bicyclic nitroimidazole pharmacophore is covalently bonded to a phenyl oxazolidinone, their pharmaceutical compositions, and the method of use of the compositions for prevention and treatment of bacterial infections. The bicyclic nitroimidazole-substituted phenyl oxazolidinones possess surprising antibacterial activity against wild- type and resistant strains of pathogens, and are therefore useful for the prevention, control and treatment of a number of human and veterinary bacterial infections caused by these pathogens, such as Mycobacterium tuberculosis.

A computational method of determining a set of proposed pharmacophore features describing interactions between a known biological target and known training ligands that show activity towards the biological target.

An assay for Alzheimer's disease (AD) pathology in a living patient is disclosed wherein an amount of α7nAChR or TLR4 in a FLNA-captured protein complex or α7nAChR in an Aβ-captured protein complex or α7nAChR-FLNA, or TLR4-FLNA and / or α7nAChR-Aβ42 complex present as a protein-protein complex in a sample is compared to the amount in a standard sample from a person free of AD pathology. An amount greater than in the standard sample indicates AD pathology. Also disclosed is an assay predictive of prognosis for treatment with a medicament in which the amount of an above protein or protein complex is compared to an amount in the presence of a medicament that binds to a FLNA pentapeptide and contains at least four pharmacophores of FIGS. 7-12. An amount of protein or protein complex determined in the presence of medicament that is less than the first amount indicates a favorable treatment prognosis.

The present invention provides a compound of formula: wherein X is a group comprising one or more amino acid residues, Y is a spacer, and Z comprises a fluorescent molecule, and compositions and methods of identifying δ- and μ-opioid receptors.

The invention discloses 3-trifluoromethyl-5-tert-butoxycarbonyl-2,5-diheterobicyclo[2.2.1]heptane and a preparation method thereof. The invention mainly solves the technical problems that when a methyl derivative is introduced to the 3-site of the 2,5-diheterobicyclo[2.2.1]heptane compound, the synthesis steps are complicated, the water solubility is poor and the total yield is low. The structural formula of the compounds is shown as below, wherein R is NH or O; when R is NH, the compound is 3-trifluoromethyl-5-tert-butoxycarbonyl-2,5-diazabicyclo[2.2.1]heptane; and when R is O, the compound is 3-trifluoromethyl-5-tert-butoxycarbonyl-2-oxa-5-azabicyclo[2.2.1]heptane. The obtained compounds are mainly used to effectively connect the pharmacophore unit.

The invention relates to a novel nicotinic acid derivative and an application thereof and further relates to the application of the nicotinic acid derivative in preparation of medicine and pharmaceutic preparation for disease prevention or treatment, especially for prevention or treatment of stroke diseases. Experiments prove that the nicotinic acid derivative has a direct protection function on neurons on a cell model and substantially reduces the hindbrain infarct volume of a mouse with ischemic stroke in an animal model. Therefore, the application of the nicotinic acid derivative with the novel chemical structural formula in preparation of the medicine for prevention or treatment of the stroke diseases is provided. The nicotinic acid derivative contains a nicotinic acid pharmacophore as well as pharmacophores aiming at other pathogenic mechanisms, and the nicotinic acid derivative has better stroke disease prevention or / and treatment effect than the prototype drug nicotinic acid.

The present invention provides TLR agonist conjugates (compounds) and compositions, as well as methods of using them. The compounds of the invention are broad-spectrum, long-lasting, and non-toxic combination of synthetic immunostimulatory agents, which are useful for activating the immune system of a mammal, preferably a human and can help direct the pharmacophore to the receptor within the endosomes of target cells and enhance the signal transduction induced by the pharmacophore.

The embodiment of the invention discloses a molecule generation method and device, a computer readable storage medium and terminal equipment, and is applied to the technical field of information processing of artificial intelligence. The molecule generation device can determine activity information of generated molecules formed after the seed molecules are subjected to shape change, so that the combination stability of the generated molecules and a receptor is considered; meanwhile, the molecule generation device can compare the first pharmacophore characteristics of the generation molecules with higher activity with the second pharmacophore characteristics of the seed molecules to obtain the generation molecules with the similarity in a preset range as new seed molecules, and then the newgeneration molecules are formed. When the similarity of the pharmacophore characteristics is small, the skeleton difference between the generated molecules and the seed molecules is large, such thatthe generated molecules with characteristics of rich skeleton and high activity can be obtained when the new generated molecules are formed through the new seed molecules so as to accelerate the discovery of the new drug.

The invention relates to quinazolinyl-aryl urea derivatives with antitumor function disclosed as general formula (II) and application thereof. The substituent group in the general formula (II) is defined in the specification. By using sorafenib and gefitinib as lead compounds, the pharmacophore-uramido group of the sorafenib is retained; and meanwhile, the quinazoline rings in the gefitinib and other EGFR-TKIs are retained to synthesize a series of quinazolinyl-aryl urea derivatives. The in-vitro activity test proves that parts of the compounds have excellent antitumor activity, and the compounds have higher research and practical values. (II).