27 results about "Synthon" patented technology

An apparatus for improving a model for use in optimizing a multistep molecular reaction is provided. The apparatus includes an automated synthesis platform, and a computing system comprising one or more processors and memory addressable by the one or more processors. A plurality of instances of the molecular reaction is performed using synthons and normalized conditions. For each respective instance, at least a subset of the synthons is transformed using the molecular reaction, generating compounds. For each respective instance, a respective conversion value is obtained. A subset of instances is selected based on at least a threshold conversion value for the respective conversion value of each respective instance. The subset of instances is used to adjust one or more parameters in a plurality of parameters of the model, obtaining an updated plurality of parameters for the model. Using, subsequent to obtaining the updated plurality of parameters, the model to search for and identify an updated plurality of normalized conditions for the molecular reaction that collectively have an improved conversion value for the molecular reaction relative to the original plurality of normalized conditions.

Systems and methods for querying a combinatorial synthesis library comprising a plurality of compounds and representing a plurality of reaction types, where each reaction type maps to a plurality of reactants, and each reactant maps to a plurality of synthons, accepts a query in the form of a single graph into a molecular encoder model, thereby obtaining a query vector. The query vector is inputted into a reaction query generator model thereby obtaining a first reaction type and a first plurality of reactants. A synthon is determined for each reactant by inputting the reactant into a synthon query generator model. A set of synthons is therefore determined, each corresponding to a reactant in the first plurality of reactants. A molecular structure in the combinatorial synthesis library is identified that includes the set of synthons arranged in accordance with a synthesis rule associated with the first reaction type.

Embodiments of the present disclosure relate to modeling DEL data using factorized molecular representations (e.g., hierarchical single and double synthon building blocks), which leverages the hierarchical structure inherent to these molecules. Using factorized molecular representations, machine learning models are trained to learn the underlying binding affinity of compounds to targets and one or more covariates (e.g., loading / repeat noise). This results in machine learning models producing improved predictions in the form of higher enrichment scores that have good correlation with compound-target binding affinity.

The invention discloses a tetrazine probe synthon and a preparation method and application thereof.The preparation method comprises the following steps that under the inert atmosphere, diethyl cyanomethylphosphonate, 3-hydroxypropionitrile, 3-mercaptopropionic acid and hydrazine hydrate are mixed and then react at the room temperature, a sodium nitrite solution is added after the reaction is finished, then acid is continuously added till the reaction system reaches acidity, and a tetrazine probe synthon product is obtained; continuously reacting to obtain an intermediate; and dissolving the intermediate in a solvent in an inert atmosphere, adding triethylamine, slowly adding methanesulfonyl chloride, and reacting at room temperature to obtain the tetrazine probe synthon shown in the formula I. The invention further discloses a preparation method of the tetrazine probe synthon. The tetrazine probe synthon provided by the invention can perform series Heck reaction and HWE reaction, so that controllable combination of functional groups on two sides of a tetrazine coupling probe is realized under mild reaction conditions, and the functional groups on two sides are designed according to actual requirements to regulate and control photophysical properties of the probe. A brand new way is provided for developing a high-performance biological orthogonal fluorescent probe.

This invention discloses a fluorine-containing unsaturated hydroxyindole compound, its preparation method, and its applications. Using (E)-3-nitromethylene hydroxyindole as the key synthon, it is synthesized via S... N A series of novel hydroxyindole derivatives were designed and constructed using the V-reaction, and their antibacterial activities were explored. The method for constructing fluorinated unsaturated hydroxyindole compounds obtained by this invention is of positive significance for promoting the synthesis and widespread application research of hydroxyindole compounds.

The invention discloses a chiral phenol calix [4] aryl porous organic molecular cage material as well as a preparation method and application thereof. A chiral calix [4] arene raceme and an acyl chloride chiral auxiliary agent are used as initial raw materials to react to prepare a pair of diastereoisomers, gram-grade separation is achieved through silica gel column chromatography, then the chiral auxiliary agent is removed respectively, and the single enantiomer chiral phenol calix [4] arene compound with the ee value being 99.9% or above can be obtained. The preparation method comprises the following steps of: synthesizing tetraaldehyde chiral phenol calix [4] arene by introducing an aldehyde group unit on the tetraaldehyde chiral phenol calix [4] arene through Duff reaction, and assembling the tetraaldehyde chiral phenol calix [4] arene serving as a construction element with a polyamino organic synthesizer to prepare the chiral phenol calix [4] arene porous organic cage with a larger cavity. The preparation method of the chiral porous organic cage does not need a catalyst, the preparation process is simple, operation is easy and convenient, expansibility is good, the yield is high, and the prepared chiral molecular cage is large in cavity, large in specific surface area and good in repeatability and can be used for chiral recognition and gas adsorption.

Embodiments of the disclosure involve modeling DEL data using factorized molecular representations (e.g., hierarchical mono-synthon and di-synthon building blocks), which capitalizes on the inherent hierarchical structure of these molecules. Using the factorized molecular representations, machine learning models are trained to learn latent binding affinity of compounds for targets and one or more covariates (e.g., load / replicate noise). This leads to improved predictions by the machine learning models in the form of higher enrichment scores, which are well-correlated with compound-target binding affinity.

The present application relates to the technical field of organic synthesis, in particular to a synthesis method of polysubstituted pyrazole compounds, which comprises adding aryl diazonium salt 0.6 mmol, enone 0.9 mmol, 0.5 ml of acid and 0.3 mmol of electrolyte into a 10 ml three-necked bottle, and then adding 6 ml of solvent to dissolve; using a carbon rod as an anode and a platinum plate as a cathode, stirring the reaction, monitoring the reaction process by using thin layer chromatography, after the reaction is completed, extracting the mixture with ethyl acetate; drying the organic layer of the mixture with anhydrous sodium sulfate, rotary evaporating the solvent under reduced pressure, purifying the residue by column chromatography, and obtaining the target product; the method uses aryl diazonium salt as a double synthetic substrate under mild electrochemical conditions, continuously generates two free radicals by electrochemical reduction of aryl diazonium salt, directly synthesizes a series of polysubstituted pyrazole compounds, directly and orderly constructs polysubstituted pyrazole compounds without transition metal or external redox agent, is environment-friendly, efficient and high in atom economy.

Thioesters, thiocarbamates, thiocarbazates, semithiocarbazates, peptides, aza-amino acid conjugates, and azapeptides; and a chemoselective and site-specific functionalization protocol of protected thiocarbazates and semithiocarbazates are described. The protocol features the use of Mitsunobu reaction to alkylate specifically the nitrogen atom close to the acylthiol moiety with alcohols to produce protected mono-substituted thiocarbazates that can be stored for months, activated under mild conditions at low temperature using halonium reagents and integrated orthogonally to make substituted semicarbazides that can be used, e.g., as synthons in synthesis of aza-amino acid conjugates, azapeptides and other peptidomimetics. Methods for preparing and using ureases, carbazides, semicarbazides, beta-peptides, azapeptides, and other peptidomimetics and azapeptide conjugates, and uses of ureases, carbazides, semicarbazides, beta-peptides, azapeptides in drug discovery, diagnosis, inhibition, prevention and treatment of diseases are also described.

The application provides a reaction molecule prediction method, a training method, a device and an electronic device. The method comprises: performing feature extraction on a product molecule to obtain a feature of the product molecule; based on the feature of the product molecule, using a reverse reaction prediction model to predict a conversion path between the product molecule and a plurality of reaction molecules, to obtain a target path; and synthesizing a sub-path and completing a sub-path according to the target path to obtain a plurality of reaction molecules corresponding to the product molecule. The method provided by the application can not only reduce the prediction complexity of the reaction molecules and improve the generalization performance of the reaction molecule prediction, but also improve the prediction performance of the reaction molecules. The plurality of reaction molecules corresponding to the sub-path; the basic graph comprises a plurality of atoms or edges for connecting the atoms.

The invention discloses a method for synthesizing a gem-difluoroolefin compound through conversion of alkane under catalysis of acridine. The gem-difluoroolefin is a multifunctional fluorine-containing synthon and is a core unit structure for improving performance in the fields of medicines, pesticides and materials. According to the method, an alpha-trifluoroolefin compound and various alkanes are taken as raw materials, and gem-difluoroallylation is directly realized under the conditions of acridine, alkali and illumination. The method has the advantages of simple preparation operation and wide substrate applicability, and contains various electron-withdrawing or electron-donating groups and various cyclic heterocyclic or non-heterocyclic alkanes. The method is mild in reaction condition, relatively high in yield and simple in subsequent treatment, and is a green chemical synthesis method with a relatively good application prospect.

The application discloses an asymmetric catalytic synthesis method of chiral 3-amino piperidine and derivatives thereof, and relates to the technical field of asymmetric catalysis, which comprises the following steps: (1) a mixture containing compound 2 and iodine is reacted to obtain intermediate 3; (2) a mixture containing intermediate 3 and a sulfilimine compound is subjected to a free radical asymmetric cross-coupling reaction to obtain chiral compound 4; (3) chiral compound 4 is subjected to desulfilimine protection to obtain intermediate 5; and (4) intermediate 5 is subjected to deprotection to obtain 3-amino piperidine; the intermediate 5 is a 3-amino piperidine derivative. The application is aimed at important synthesizers such as chiral 3-amino piperidine and derivatives thereof, and the synthesizers are rapidly synthesized through a free radical asymmetric cross-coupling method; a free radical asymmetric cross-coupling reaction catalyzed by copper and a chiral anion ligand is utilized to construct chiral 3-amino piperidine and derivatives thereof under mild conditions.

Thioesters, thiocarbamates, thiocarbazates, semithiocarbazates, peptides, aza-amino acid conjugates, and azapeptides; and a chemoselective and site-specific functionalization protocol of protected thiocarbazates and semithiocarbazates are described. The protocol features the use of Mitsunobu reaction to alkylate specifically the nitrogen atom close to the acylthiol moiety with alcohols to produce protected mono-substituted thiocarbazates that can be stored for months, activated under mild conditions at low temperature using halonium reagents and integrated orthogonally to make substituted semicarbazides that can be used, e.g., as synthons in synthesis of aza-amino acid conjugates, azapeptides and other peptidomimetics. Methods for preparing and using ureases, carbazides, semicarbazides, beta-peptides, azapeptides, and other peptidomimetics and azapeptide conjugates, and uses of ureases, carbazides, semicarbazides, beta-peptides, azapeptides in drug discovery, diagnosis, inhibition, prevention and treatment of diseases are also described.

A method for training a model to estimate synthetic accessibility may be provided. A retrosynthesis-related synthetic accessibility model may be provided. A molecular structures database may be accessed. At least one molecular structure may be obtained from the molecular structures database with the model. The at least one molecular 5 structure may be virtually sliced into synthon-like fragments with the model. A frequency of the synthon-like fragments in natural molecules may be determined with the model. Molecular descriptors for the synthon-like fragments may be calculated with the model. An aggregated synthetic accessibility score for the synthon-like fragments may be determined with the model. The aggregated synthetic accessibility score for the synthon-10 like fragments may be stored in a database for the model.

The present invention relates to the field of asymmetric catalysis and organic synthesis, and specifically provides a general method for generating axial chirality by means of a chiral companion strategy. The features and concept of the method are: a chiral aromatic tertiary amine compound without a nitrogen chiral center is subjected to intramolecular chiral oxidation to induce the formation of a new aromatic tertiary amine N-oxide (NO) chiral center. Due to the structural rigidity of the chiral aromatic tertiary amine N-oxide compound, when the steric hindrance of different substituents Rb and Rs connected to ortho positions of an aromatic ring is relatively large, the rotation of the aromatic ring is hindered, and new rotation-hindered axial chirality is generated while an aromatic tertiary amine chiral N-oxide center is formed. By means of the method and by regulating the structural and functional characteristics of the different substituents Rb and Rs, various axial chiral ligands, chiral small-molecule catalysts, pharmaceutical and agrochemical intermediates, and chiral synthons can be prepared. The present invention has important scientific and application values for the design, synthesis, and application of chiral ligands, chiral catalysts, especially ligands and catalysts containing axial chirality, and chiral compounds having special functions.

The invention provides an active learning method for drug design that involves training surrogate models on synthon space – rather than molecule space or product space – to predict synthons that have a high probability of scoring favourably for a given objective function. Importantly, this means that combinatorial space is reduced by orders of magnitude prior to enumeration of molecules. In turn, this means that the total number of molecules that need to be scored via evaluation of an expensive scoring function is decreased drastically. The method achieves these benefits while also being then able to thereby identify optimised molecules – using the optimally identified synthons – in an enumerated molecule space.

The present disclosure relates to systems and methods for querying a combinatorial synthesis library comprising a plurality of compounds and representing a plurality of reaction types, wherein each reaction type maps to a plurality of reactants, and each reactant maps to a plurality of synthon, accepting a query to a molecular encoder model in the form of a single graph, thereby obtaining a query vector. The query vector is input into a reaction query generator model, thereby obtaining a first reaction type and a first plurality of reactants. Synthons for each reactant are determined by inputting the reactants into a synthon query generator model. A set of synthons is thus determined, each corresponding to a reactant in the first plurality of reactants. A molecular structure in a combinatorial synthesis library is identified, the combinatorial synthesis library comprising the set of synthons arranged according to synthesis rules related to the first reaction type.

A method for training a model to estimate synthetic accessibility may be provided. A retrosynthesis-related synthetic accessibility model may be provided. A molecular structures database may be accessed. At least one molecular structure may be obtained from the molecular structures database with the model. The at least one molecular structure may be virtually sliced into synthon-like fragments with the model. A frequency of the synthon-like fragments in natural molecules may be determined with the model. Molecular descriptors for the synthon-like fragments may be calculated with the model. An aggregated synthetic accessibility score for the synthon-like fragments may be determined with the model. The aggregated synthetic accessibility score for the synthon-like fragments may be stored in a database for the model.

The invention provides a novel chiral carbonyl imidazole derivative with structural formulas (III) and (IV) and a synthesis method of the novel chiral carbonyl imidazole derivative. The chiral carbonyl imidazole derivatives with the structural formulas (III) and (IV) are brand-new compounds, contain aryl conjugated trisubstituted olefin with a Z-type or E-type configuration and a carbonyl imidazole structure with a chiral center at a carbonyl alpha position, and can be used as important drug synthons and other functional molecule synthesis intermediates; according to the synthesis method, starting from an easily available Z / E mixed allyl methyl carbonate substrate, a prochiral carbonyl imidazole compound is taken as a nucleophilic reagent, and a compound with a structural formula as shown in a formula (III) or a formula (IV) is obtained in a Z / E convergence manner under a Pd / Ni bimetallic concerted catalysis system.

Systems and methods for improving molecular reaction conversion values for a set of synthons are provided. An initial conversion value for the synthons is obtained for an initial reaction instance that transforms the synthons into compounds under initial reaction conditions using an automated device. When the initial conversion value fails to satisfy a criterion, the synthons are optimized by performing test reaction instances using the synthons, each test instance comprising a corresponding set of normalized conditions. A test conversion value is determined for each test instance. Each test instance having a test conversion value that satisfies the criterion is selected. Systems and methods for selecting synthon sets for optimization of a molecular reaction are also provided. Further provided are systems and methods for determining synthons having target conversion values when transformed by a molecular reaction. Also provided are systems and methods for improving conversion values using multistep molecular reactions.

Synthesis of O-benzotriazole and O-imidazole synthons are described. Uses of synthons in synthesis of azapeptides and other peptidomimetics, azapeptides and other peptidomimetics synthesized from the synthons and uses of azapeptides and other peptidomimetics are also described.

The application discloses a trifluoromethyl alkynyl reaction containing photocatalysis 1,6-diene and application. 1,6-diene and alkynyl trifluoromethyl sulfone are used as raw materials, dimethyl benzoyl peroxide and sodium acetate additives are used, methyl tert-butyl ether is used as a reaction solvent, and a five-membered ring compound containing trifluoromethyl and alkynyl is obtained by reaction at room temperature. The synthesis method has the advantages of mild reaction condition, simple and safe operation, cheap and easily available raw material, and is an environment-friendly green synthesis method. Through the method, the trifluoromethyl alkynyl reaction of 1,6-diene can be successfully realized, and the obtained product can be used as an important organic synthon, and a series of molecular structures containing trifluoromethyl can be prepared through further oxidation or reduction reaction.

The invention discloses a synthesis method of a benzochromene compound, and belongs to the technical field of organic synthesis. According to the method, aryl diazonium salt serving as an aryl source and acetonitrile serving as a C1 synthon react with substituted binaphthol, and the benzochromene compound is synthesized through a three-component one-pot method under a certain temperature condition. The method has the advantages of simple operation, cheap and easily available raw materials, mild reaction conditions, green reaction, no catalyst, no additive, environmental friendliness and the like, and provides a new way for preparation of the benzochromene compound.

Site-selective conjugation to biomolecules via thiol-based chemistry is superior to the unselective modification of lysine residues, which produce a mixed product and can potentially interfere with binding affinity of the biomolecule. However, in physiological environments, the maleimide-thiol conjugation product which is the current gold-standard for site-selective thiol-conjugation can be susceptible to hydrolysis or a retro-Michael reaction via exchange with reactive thiols such as those in albumin or glutathione residues yet the degradation is relatively slow. Therefore, for in vivo studies, the maleimide-thiol conjugation proposes instability issues. The compositions and methods disclosed herein provide an alternative thiol-based linkage, one that overcomes the instability issues with conventional reagents and methods. The compositions and methods disclosed herein are useful in various contexts, for example, for 18F-labeling of peptides / proteins in the preparation of positron emission tomography (PET) probes.