336 results about "Pharmacophore" patented technology

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.

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.

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.

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 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.

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 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).

Methods and systems for generating pharmacophore models are characterized both by molecular features that are present in the model and features that are defined as absent. Thus, models can be developed that take into account features such as steric bulk that inhibit activity for a specified target as well as features such as functional groups that promote activity. Features that inhibit activity can be identified by comparing known active molecules with known inactive molecules. Features that are present in the inactive molecules but absent in the active molecules can be defined in a pharmacophore model.

The present invention is directed to a monomer useful in preparing therapeutic compounds. The monomer includes one or more pharmacophores which potentially binds to a target molecule with a dissociation constant of less than 300 μM and a linker element connected to the pharmacophore. The linker element has a molecular weight less than 500 daltons, is connected, directly or indirectly through a connector, to the pharmacophore.

The present invention relates to processes for producing an optimized pharmacophore for a target protein. The present invention also relates to processes for identifying compounds having an affinity to a target protein. The present invention also relates to processes for designing a ligand for a target protein using the optimized pharmacophore of the present invention. The present invention also provides a computer for use in designing a ligand for a target protein using the optimized pharmacophore of the present invention.