The present invention relates to an economical and feasible method for industrially producing a deuterated COVID-19 medicament key intermediate D. The method has low reaction line cost, and high conversion rate, selectivity, reaction yield, reaction efficiency, and deuterium abundance, and low energy consumption, convenience in post-treatment, and simple reaction operation, and thus is more suitable for industrial production. The intermediate D can be prepared at a high yield, the yield can reach about 95%, the product purity and the deuterium abundance both reach 99% or above, and a medicinal level is achieved.
C07D 207/267 - 2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atom
C07D 207/263 - 2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
The present invention relates to a method for industrially producing a deuterated pharmaceutical intermediate D by means of catalysis of solid-supported nickel. The conditions of the reaction route are mild, the conversion rate and selectivity are high, the reaction yield, reaction efficiency and deuterium abundance are high, the energy consumption is low, posttreatment is convenient, the reaction operation is simple, and the present invention is more suitable for industrial production. In the present invention, an intermediate D can be prepared at a high yield, the yield can reach about 90%, the product purity and the deuterium abundance both reach 99% or more, meeting pharmaceutical grade standards.
C07D 207/263 - 2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
3.
NOVEL DEUTERATED TRIAZINE COMPOUND, PREPARATION METHOD THEREFOR, COMPOSITION THEREOF AND USE THEREOF
Disclosed is a deuterated triazine compound represented by formula I or a pharmaceutically acceptable salt, isomer, prodrug or cocrystal thereof. Also disclosed are a preparation method for the deuterated compound, a composition of the deuterated compound and use of the deuterated compound. The compound, as a 3CL protease inhibitor, on the basis of having similar inhibitory activity against viruses, achieves better pharmacokinetic properties and therapeutic effects and better druggability. The structural formula of formula I is shown on the left.
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
A method for preparing a deuterated pharmaceutical intermediate D. The method has a mild reaction route condition, a high conversion rate and high selectivity, a high reaction yield, high reaction efficiency and high abundance of deuterium, low energy consumption, is convenient to perform a post-treatment thereon, has a simple reaction operation, and is more suitable for industrial production. In the method, the intermediate D can be prepared at a high yield, which can reach about 90%, and the purity and the deuterium abundance of the product can both reach 99% or more, thus achieving the pharmaceutical grade.
C07D 207/267 - 2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atom
5.
METHOD FOR PREPARING INTERMEDIATE FOR SYNTHESIZING NEW DEUTERATED CYANO COMPOUND
The present invention relates to a method for preparing a deuterated pharmaceutical intermediate D by means of using a boron-deuterium reducing agent. The method has a mild reaction route condition, high yield and abundance of deuterium, is convenient to perform post-treatment thereon, and is more suitable for industrial production. In the present invention, the deuterated pharmaceutical intermediate D can be prepared with high quality, the yield can reach 85% or more, and the deuterium abundance of the product can optimally reach 99%.
The present invention provides a pharmaceutical composition consisting of a novel deuterated cyano compound or an isomer thereof or a prodrug thereof or a solvate thereof or a pharmaceutically acceptable salt thereof, and ritonavir or an isomer thereof or a prodrug thereof or a solvate thereof or a pharmaceutically acceptable salt thereof, and an antiviral use of the pharmaceutical composition. Compared with other existing antiviral pharmaceutical compositions, the pharmaceutical composition of the present invention has better pharmacokinetic characteristics and a longer half-life period, can maintain a relatively high concentration in vivo, and has the advantages of high safety, reduced drug toxicity and side effects, reduced virus resistance and the like.
A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
A61K 31/4025 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
Disclosed is a new deuterated cyano compound as represented by formula I, or a pharmaceutically acceptable salt, an isomer or a prodrug thereof. Further disclosed are a method for preparing the deuterated compound, and a composition and the use thereof. The compound is used as a 3CL protease inhibitor, and achieves better pharmacokinetic properties and therapeutic effects and has better druggability on the basis of equivalent virus inhibition activity. The formula (I) is as shown below:
A61K 31/4015 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
A61K 31/4025 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
C07D 207/267 - 2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atom
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
Disclosed are a deuterated benzothiazole compound as represent by formula I, or a pharmaceutically acceptable salt, isomer, or prodrug thereof. Also disclosed are a preparation for and composition and application of the deuterated compound. The compound is used as a 3CL protease inhibitor, achieves better pharmacokinetic properties and therapeutic effects on the basis of comparable virus inhibitory activity, and has better druggability. Formula I is as shown as follows:
Disclosed is a novel cationic lipid compound represented by formula (A), or an isomer, an N-oxide, a pharmaceutically acceptable salt, or a prodrug thereof. Further disclosed are a preparation method, a composition and an application of the described novel cationic lipid compound. The compound, as a cationic lipid, is suitable for pharmaceutical compositions for nucleic acid delivery, and can achieve better stability, pKa value and intracellular drug delivery efficiency. Formula (A) is as follows:
C07C 235/10 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms not being part of nitro or nitroso groups
C07C 69/67 - Esters of carboxylic acids having esterified carboxyl groups bound to acyclic carbon atoms and having any of the groups OH, O-metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
C07C 231/02 - Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
C07C 67/08 - Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61P 43/00 - Drugs for specific purposes, not provided for in groups
10.
NEW TYPE PYRROLIDINE TYPE LIPID COMPOUND, PREPARATION METHOD THEREFOR, AND COMPOSITION AND USE THEREOF
Disclosed is a new type pyrrolidine type compound as represented by formula (A), or an isomer, an N-oxide, or a pharmaceutically acceptable salt and prodrug thereof. Also disclosed are a preparation method therefor, and a composition and the use thereof. The compound is used as a cationic lipid, is suitable for a pharmaceutical composition for nucleic acid delivery, and can achieve a better stability, pKa value and intracellular delivery efficiency of drugs. Formula A is as follows in the description.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A61K 47/22 - Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
A61K 47/28 - Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
A61K 47/24 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
The present invention relates to a novel PEG lipid compound, a preparation method therefor, and a composition and use thereof. Disclosed are a novel PEG lipid compound represented by formula A, or an isomer thereof, or a pharmaceutically acceptable salt thereof, or a prodrug thereof. Also disclosed are a preparation method for and a composition and use of the PEG lipid compound. As a functional PEG lipid, the compound is applicable to pharmaceutical compositions for nucleic acid delivery, and can achieve better stability and intracellular drug delivery efficiency. Formula A is as follows.
A pharmaceutical composition comprising a cytidine derivative having the structure of formula I or formula II or a pharmaceutically acceptable salt or physiologically acceptable salt thereof, wherein R1-R7 are combinations of "hydrogen" isotopes (comprising isotopes "deuterium" and "tritium"). The pharmaceutical composition can be used for treating or preventing viral infections, the viral infections being human coronavirus, novel coronavirus (SARS-CoV-2), SARS coronavirus, and MERS coronavirus infections.
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
A61K 9/00 - Medicinal preparations characterised by special physical form
The present invention relates to a lipid compound. The lipid compound can be used alone, or can be used in combination with other lipid components such as neutral lipids, spotted lipids, steroids and/or analogs thereof, and/or polymer-conjugated lipids, so as to form a lipid nanoparticle for delivering a therapeutic agent and/or a prophylactic agent.
C07C 217/46 - Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and unsaturated
C07D 317/24 - Radicals substituted by singly bound oxygen or sulfur atoms esterified
A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
C07C 217/28 - Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines
C07C 213/06 - Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton from hydroxy amines by reactions involving the etherification or esterification of hydroxy groups
C07C 213/10 - SeparationPurificationStabilisationUse of additives
C07B 59/00 - Introduction of isotopes of elements into organic compounds
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
C07C 219/06 - Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having the hydroxy groups esterified by carboxylic acids having the esterifying carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms of an acyclic saturated carbon skeleton
A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
122 as defined herein also provide a pharmaceutical composition comprising one or more compounds represented by the foregoing structural formula (I) and a therapeutic agent and/or preventive agent. In some embodiments, the pharmaceutical composition further comprises one or more components selected from among neutral lipids, charged lipids, steroids, and polymer conjugated lipids. The described compositions are useful for forming lipid nanoparticles for delivering a therapeutic agent and/or preventive agent. In other embodiments, the present invention provides a method for administering a therapeutic agent and/or preventive agent to a subject in need thereof. The method comprises preparing a pharmaceutical composition comprising lipid nanoparticles containing a compound represented by structural formula (I) and a therapeutic agent and/or preventive agent, and delivering the composition to a subject.
C07C 219/06 - Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having the hydroxy groups esterified by carboxylic acids having the esterifying carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms of an acyclic saturated carbon skeleton
A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
C07C 219/06 - Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having the hydroxy groups esterified by carboxylic acids having the esterifying carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms of an acyclic saturated carbon skeleton
A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
The present invention provides a lipid compound which can be used alone or in combination with other lipid components such as neutral lipids, charged lipids, steroids and/or analogs thereof, and/or polymer-conjugated lipids to form lipid nanoparticles for delivery of therapeutic and/or prophylactic agents. In some examples, lipid nanoparticles are used for delivering nucleic acids such as messenger RNAs and/or antisense RNAs. Also provided are a method for using such lipid nanoparticles to treat and/or prevent various diseases. In one embodiment, a compound having the structure of formula (I) below, or a salt, an isomer, or an N-oxide thereof is provided, wherein R1-R4 are as defined in the text. Also provided is a pharmaceutical composition comprising one or more of the described compounds of structural formula (I) and a therapeutic and/or prophylactic agent. In some embodiments, the pharmaceutical composition further comprises one or more components selected from neutral lipids, charged lipids, steroids, and polymer-conjugated lipids. Such a composition is useful for forming lipid nanoparticles for delivery of therapeutic and/or prophylactic agents. In other embodiments, the present invention provides a method of administering a therapeutic and/or prophylactic agent to a subject in need thereof, comprising preparing a pharmaceutical composition comprising lipid nanoparticles of the compound of structural formula (I) and a therapeutic and/or prophylactic agent, and delivering the composition to a subject.
C07D 295/13 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
The present invention relates to a lipid compound having the structure of formula (I), which can be used alone or in combination with other lipid components such as neutral lipids, band-point lipids, steroids and/or analogs thereof, and/or polymer-conjugated lipids to form lipid nanoparticles for delivery of therapeutic agents and/or prophylactic agents. In some examples, lipid nanoparticles are used for delivering nucleic acids such as messenger RNA and/or antisense RNA. Also provided are a method for using such lipid nanoparticles to treat and/or prevent various diseases, wherein the structure of formula (I) is as follows: or a salt or an isomer thereof or an N-oxide thereof, wherein R1 is as defined herein.
C07C 229/16 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids
A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
patents