25 results about "Bioisostere" patented technology

Disclosed herein are methods of synthesizing compounds of the formula (I) wherein the variables are defined herein. Also provided are compounds produced using these methods. In some aspects, the methods provided herein may be used to install aryl bioisosteres.

The invention discloses a derivative of a rice bran extract as well as a preparation method and application of the derivative. A C-3 benzoate prodrug system is constructed, the transmembrane absorption efficiency is remarkably improved by optimizing the oil-water partition coefficient, fixed-point slow release of active ingredients is achieved through inflammatory tissue esterase, and high bioavailability and low irritation are both considered. Meanwhile, C-25 fluorine atoms are introduced to serve as biological electron isosteres, and target affinity is enhanced by means of the unique electronic effect and polar hydrophobicity of the C-25 fluorine atoms; spatial conformation is locked through side chain saturation, so that the compound shows anti-inflammatory and tissue repair activity which is obviously superior to that of natural cycloartanol under the same dosage.

Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for predicting toxicity of molecules. In one aspect, a method comprises: obtaining data identifying: (i) an input molecule, and (ii) a target molecule fragment; determining, for each candidate molecule fragment in a database of candidate molecule fragments, a respective similarity measure between: (i) an embedding of the target molecule fragment, and (ii) an embedding of the candidate molecule fragment; selecting a plurality of candidate molecule fragments for inclusion in a set of alternative molecule fragments based on the similarity measures; and generating data defining a plurality of modified molecules, wherein each modified molecule is a modified version of the input molecule where the target molecule fragment is replaced by a respective alternative molecule fragment from the set of alternative molecule fragments; and generating a respective toxicity prediction for each of the plurality of modified molecules.

The application discloses a data processing method based on a bioisostere search platform, comprising the following steps: S1, obtaining a target functional group input by a user; S2, generating SMILES coding of the target functional group; S3, inquiring whether the bioisostere containing the target functional group is contained in a database storing bioisosteres according to the SMILES coding, if yes, entering step S8, otherwise, entering step S4; S4, processing the SMILES coding to obtain a ligand of the target functional group; S5, generating a bioisostere of the target functional group according to the ligand of the target functional group; S6, optimizing the bioisostere to obtain an optimal bioisostere; S7, taking the bioisostere of the target functional group as the optimal bioisostere; and S8, outputting the optimal bioisostere as a data processing result in a visualized manner. The application can reduce the time and cost of drug research and development.

The invention discloses a 2-azabicyclo [3.1. 1] heptene derivative as well as a synthesis method and application of the 2-azabicyclo [3.1. 1] heptene derivative. The 2-azabicyclo [3.1. 1] heptene derivative provided by the invention is obtained by exciting a rhodium complex by visible light to catalyze bicyclo [1.1. 0] butane to perform cycloaddition reaction. The 2-azabicyclo [3.1. 1] heptene derivative constructed by the method can be applied to the aspects of simulating bioisosteres and the like, is expected to obtain more innovative achievements in the field of organic synthesis methodology, and also can provide a brand new thought and a structural basis for developing novel drug molecules; and the medicine with better curative effect and less side effect can be designed.

Described are compositions comprising a compound of formula I: in which R represents H, or optionally substituted C1-15 alkyl, C1-15 alkenyl or C1-15 alkynyl; or a pharmaceutically acceptable salt, solvate, metabolite, prodrug, bioisostere, or protected form thereof, for use in the treatment or prevention of a sleep disorder, together with methods of treating or preventing a sleep disorder in a subject or of treating or preventing a symptom or co-morbidity associated with a sleep disorder.

Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for predicting toxicity of molecules. In one aspect, a method comprises: obtaining data identifying: (i) an input molecule, and (ii) a target molecule fragment; determining, for each candidate molecule fragment in a database of candidate molecule fragments, a respective similarity measure between: (i) an embedding of the target molecule fragment, and (ii) an embedding of the candidate molecule fragment; selecting a plurality of candidate molecule fragments for inclusion in a set of alternative molecule fragments based on the similarity measures; and generating data defining a plurality of modified molecules, wherein each modified molecule is a modified version of the input molecule where the target molecule fragment is replaced by a respective alternative molecule fragment from the set of alternative molecule fragments; and generating a respective toxicity prediction for each of the plurality of modified molecules.

Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for predicting toxicity of molecules. In one aspect, a method comprises: obtaining data identifying: (i) an input molecule, and (ii) a target molecule fragment; determining, for each candidate molecule fragment in a database of candidate molecule fragments, a respective similarity measure between: (i) an embedding of the target molecule fragment, and (ii) an embedding of the candidate molecule fragment; selecting a plurality of candidate molecule fragments for inclusion in a set of alternative molecule fragments based on the similarity measures; and generating data defining a plurality of modified molecules, wherein each modified molecule is a modified version of the input molecule where the target molecule fragment is replaced by a respective alternative molecule fragment from the set of alternative molecule fragments; and generating a respective toxicity prediction for each of the plurality of modified molecules.

The invention relates to the technical field of preparation of anti-cancer drugs, in particular to a Schiff base gold (III) compound and a preparation method and application thereof.The series of symmetric or asymmetric Schiff base gold (III) compounds are synthesized on the basis of the bioisostere principle in combination with a Schiff base ligand, the cyclohexanediamine structure and the NNOO coordination mode of oxaliplatin are reserved, platinum (II) is replaced with gold (III), and the Schiff base gold (III) compound is synthesized. Meanwhile, the invention relates to application of the Schiff base gold (III) compound in preparation of anti-hepatoma drugs, the defects that oxaliplatin is strong in side effect and the like are overcome, in-vivo and in-vitro experiment results of the Schiff base gold (III) compound provided by the invention show that the compounds Au3 and Au7 are remarkable in anti-hepatoma activity and can target thioredoxin reductase (TrxR) and mitochondrial DNA (mtDNA) at the same time, and the Schiff base gold (III) compound can be used for preparing anti-hepatoma drugs. The further mechanism research shows that the compound can promote the generation of reactive oxygen species (ROS) to cause endoplasmic reticulum stress (ERS) and mitochondrial injury and finally induce pyroptosis and immunogenic cell death, and has great application potential.

The invention provides a teisabatine derivative and a preparation method and application thereof.The teisabatine derivative has the structure shown in the formula I. On the basis of a derivative Leu10-Teixobactin and on the basis of the bioisostere theory, relevant amido bonds on a main peptide chain are subjected to sulfo modification, amide is replaced with sulfo amide, and the teisabatine derivative is obtained. According to the present invention, with the application of the Teixobactin derivative, the antibacterial effect of the obtained Teixobactin derivative is equivalent to or even stronger than the antibacterial effect of Leu10-Teixobactin, and the enzymatic hydrolysis resistance is stronger;

This invention discloses a method for synthesizing 4,6-bis(trifluoromethyl)-1,3,5-triazabicyclo[3.1.0]hex-2-ene compounds. Using nitrile compounds and diacaridine as raw materials, the method utilizes photo-induced decomposition of diacaridine to efficiently construct the target azabicyclo skeleton. This method features mild reaction conditions and a simple synthetic route. Furthermore, it exhibits broad functional tolerance, mild reaction conditions, high yield, and simple post-processing, making it a promising green chemical synthesis method. The novel skeleton can serve as a novel bioisostere, overcoming the bottlenecks of limited existing skeleton structures and high synthetic difficulty, providing technical support for drug molecule optimization and new drug development.

The compounds represented by formula (I) or (II) are provided herein, or a pharmaceutically acceptable salt, or a prodrug or bioisostere thereof; where R1, R2a, R2b, R2c, R3, R4, R5, R6a, R6b, R2a', R2b', R2c', R3', R4', R5', R6a', R6b', Y, Y', and the subscripts mn are defined herein.

The present invention relates to a compound of Formula (I): (I) or a pharmaceutically acceptable salt, stereoisomer, hydrate, solvate, prodrug, polymorph, N-oxide, or bioisostere thereof; wherein: "R1, R2, and R3", "ring A", and "Het" are as defined in the specification, which can be used as a medicament or therapeutic agent in the prevention or treatment of a condition or a disease or a disorder where there is an advantage in inhibiting S. aureus or other Gram-positive bacteria.

The invention discloses a preparation method of a cyclic 1, 2-oxaacid ester derivative, and belongs to the technical field of organic synthesis. It is found for the first time that NaHMDS serving as alkali can promote activation of a borohydride reagent, trans-addition of propargyl alcohol is achieved, and five-membered ring 1, 2-oxaboric acid can be constructed in one step. The method has the advantages of mild reaction conditions, wide substrate range, strong functional group tolerance and specific regioselectivity. In addition, the cyclic 1, 2-oxaboric acid is also a bioisostere of a butenolactone structure, and is expected to have considerable biological activity.

Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for predicting toxicity of molecules. In one aspect, a method comprises: obtaining data identifying: (i) an input molecule, and (ii) a target molecule fragment; determining, for each candidate molecule fragment in a database of candidate molecule fragments, a respective similarity measure between: (i) an embedding of the target molecule fragment, and (ii) an embedding of the candidate molecule fragment; selecting a plurality of candidate molecule fragments for inclusion in a set of alternative molecule fragments based on the similarity measures; and generating data defining a plurality of modified molecules, wherein each modified molecule is a modified version of the input molecule where the target molecule fragment is replaced by a respective alternative molecule fragment from the set of alternative molecule fragments; and generating a respective toxicity prediction for each of the plurality of modified molecules.

The present invention relates to novel dihydroorotate dehydrogenase (DHODH) inhibitors of formula (I) having carboxylic acid, carboxamide or bioisostere moieties and optionally deuterated, pharmaceutical formulations comprising them, their process of preparation and their use as a medicament, alone or in combination with one or more other agents, for the treatment of various diseases in which inhibition of DHODH is desired, such as SARS-CoV-2 or IDH mutant cancers.

The application relates to the technical field of chemical synthesis, and particularly discloses a synthesis method of a triplet carbene-mediated C2-substituted bicyclo[1.1.1]pentane derivative, which successfully opens up a synthesis path of C2-substituted bicyclo[1.1.1]pentane (BCP) by inserting bicyclo[1.1.0]butane (BCB) under photosensitive conditions; the 1,4-dibasic radical species generated by the triplet carbene has a faster recombination rate; the method not only lays a solid foundation for the application of bicyclo[1.1.1]pentane in medicinal chemistry, but also overcomes the limitation of traditional benzene rings in metabolic stability and water solubility by replacing a bioisostere and using a three-dimensional bridged ring structure. In addition, the synthesized derivatives exhibit excellent biological activity, and experimental data prove that the derivatives have significant fungal inhibition activity in tests such as botrytis cinerea, thereby providing important technical support for the design and development of new drugs.

Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for predicting toxicity of molecules. In one aspect, a method comprises: obtaining data identifying: (i) an input molecule, and (ii) a target molecule fragment; determining, for each candidate molecule fragment in a database of candidate molecule fragments, a respective similarity measure between: (i) an embedding of the target molecule fragment, and (ii) an embedding of the candidate molecule fragment; selecting a plurality of candidate molecule fragments for inclusion in a set of alternative molecule fragments based on the similarity measures; and generating data defining a plurality of modified molecules, wherein each modified molecule is a modified version of the input molecule where the target molecule fragment is replaced by a respective alternative molecule fragment from the set of alternative molecule fragments; and generating a respective toxicity prediction for each of the plurality of modified molecules.

The invention belongs to the technical field of organic synthesis, and discloses a method for preparing polysubstituted 4-hydroxy-2-thiabicyclo [3.1. 1] heptane through cycloaddition reaction catalyzed by lewis acid. The method comprises the following steps: by taking polysubstituted bicyclo [1.1. 0] butane and 2, 5-dihydroxy-1, 4-dithiane as raw materials, in the presence of a Lewis acid catalyst and an organic solvent, obtaining a cyclization product as shown in a formula I; and removing R1 from the cyclization product as shown in the formula I to obtain a molecule as shown in a formula II. In addition, an asymmetric catalysis method is developed to realize enantioselective synthesis of the cyclization product as shown in the formula I. Compared with a traditional method, the preparation method has the advantages that the raw materials and the catalyst are simple and easy to obtain, the synthesis route is short, the atom economy is high, and the substrate universality is wide; the reaction product can be used as a potential bioisostere of drug active molecules containing ortho-position, meta-position or 1, 2, 4-trisubstituted aromatic hydrocarbon, such as diflunisal; the 4-hydroxy-2-thiabicyclo [3.1. 1] heptane product is subjected to pharmacokinetics and other activity tests, and shows a good application prospect.

The invention belongs to the technical field of preparation of medical compounds, and particularly relates to a 5-(1H-indol-6-yl)-1, 3, 4-oxadiazole-2-formylhydrazine derivative as well as a preparation method and application thereof. The 5-(1H-indol-6-yl)-1, 3, 4-oxadiazole-2-formylhydrazine with a new structure is designed and synthesized by taking a quinoline compound and a hydrazide compound as a research basis and utilizing a molecular heterozygosis method and a bioisostere design thought, the derivative is low in reaction cost and high in yield, the reaction process is simple and easy to control, and the method is suitable for industrial production. And the derivatives have certain anti-prostatic cancer activity, and can be used for preparing anti-prostatic cancer drugs and researching the structure-function relationship of the compounds.

Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for predicting toxicity of molecules. In one aspect, a method comprises: obtaining data identifying: (i) an input molecule, and (ii) a target molecule fragment; determining, for each candidate molecule fragment in a database of candidate molecule fragments, a respective similarity measure between: (i) an embedding of the target molecule fragment, and (ii) an embedding of the candidate molecule fragment; selecting a plurality of candidate molecule fragments for inclusion in a set of alternative molecule fragments based on the similarity measures; and generating data defining a plurality of modified molecules, wherein each modified molecule is a modified version of the input molecule where the target molecule fragment is replaced by a respective alternative molecule fragment from the set of alternative molecule fragments; and generating a respective toxicity prediction for each of the plurality of modified molecules.

The invention relates to the technical field of organic chemistry, and particularly discloses a chiral azabicyclo [2.1. 1] hexane derivative intermediate and a preparation method thereof.The chiral azabicyclo [2.1. 1] hexane derivative (BCH) can be used for synthesizing a chiral bicyclo [1.1. 1] pentane (BCP) derivative, the yield and chiral conversion rate of the preparation method are high, and the method is suitable for industrial production. According to the method for synthesizing the bicyclo [1.1. 1] pentane through a nitrogen atom insertion and deletion strategy, the reaction path has good stereoselectivity, the chirality is maintained, and the synthesized chiral bicyclo [1.1. 1] pentane (BCP) derivative is a bicyclic hydrocarbon substituted aromatic ring rich in C (sp3), is called as bioisostere substitution, has wide application research in modern medicine function research, and has broad application prospects. In a plurality of literatures, the chiral bicyclo [1.1. 1] pentane (BCP) can be coupled with a plurality of drugs, and the drug effect, the pharmacokinetic property and the water solubility can be remarkably improved.

Provided in the present invention are a novel ionizable lipid, a preparation method therefor, and the use thereof. The structural formula of the novel ionizable lipid is as shown in formula (I). An ionizable lipid compound of the present invention contains structures of urea and a bioisostere thereof. By virtue of hydrogen bonds which squaramide, urea, and thiourea structures form with nucleic acid, the encapsulation effect of the ionizable lipid is enhanced and the immunogenicity of the ionizable lipid is reduced. Nanoparticles prepared using the ionizable lipid of the present invention have a high encapsulation efficiency, a low PDI, and a broadly adaptable and stable process.

The invention discloses a synthesis method of a diaryl ketone biological electron isostere. The method comprises the following steps: adding a heteroaryl halide, aromatic aldehyde, an additive, a photocatalyst and inorganic alkali into a reaction container, adding a reaction solvent and [1.1. 1] propeller alkane in an argon atmosphere, reacting for 24 hours under blue light irradiation, adding water for quenching, extracting the obtained mixture with ethyl acetate, and purifying to obtain the target product. And washing with a saturated saline solution, and separating to obtain a corresponding 3-heteroaryl bicyclo [1.1. 1] pentanone product. The method has the advantages of high reaction efficiency, low cost, simplicity and convenience in operation and the like.

The invention belongs to the technical field of organic synthesis, and discloses a synthesis method and application of an oxa-aza bridged ring compound shown as a formula (I). In the reaction, the selection of a substrate oxidant, the equivalent weight of the oxidant, the temperature and the concentration of a solvent are optimized. Development of the method aims to construct a rigid bridged ring molecule rich in C (sp) as a potential bioisostere of pyridine to improve drug solubility and metabolic stability. The reaction adopts a water phase condition and uses a classical oxidation halogenation method, so that not only is the green chemical concept manifested, but also the method has high atom economy, and is beneficial to energy conservation and environment protection. In addition, the product successfully generates a disubstituted oxa-aza bridged ring compound under the action of alkali, and multiple functional groups easy to modify and convert are introduced; the hematopoietic prostaglandin D synthetase inhibitor analogue is successfully synthesized, and preliminary biological activity tests show that the hematopoietic prostaglandin D synthetase inhibitor analogue has application value in the aspect of treating asthma.