206 results about "Dihydropyridine" patented technology

Provided herein are compounds of Formula (IV-b), or pharmaceutically acceptable salts thereof, that inhibit a KRas protein (e.g., a dysregulated KRas protein (e.g., a mutated or amplified KRas protein)). This disclosure also provides compositions containing the compounds as provided herein, or pharmaceutically acceptable salts thereof, as well as methods of using and making the same.

The present invention relates to crystalline forms of salts of the KRas G12C inhibitor 2-[(2b)-4- [7-(8-chloro-1-naphthyl)-2-[[(25)-1-methylpyrrolidin-2-yl]methoxy]-6,8-dihydro-5H -pyrido [3,4- d]pyrimidin-4-yl]-1-(2-fluoroprop-2-enoyl)piperazin-2-yl]acetonitrile, pharmaceutical compositions comprising the crystalline forms, processes for preparing the crystalline forms and methods of use thereof.

The invention relates to a method for synthesizing 1, 2-allene ketone, and discloses a method for synthesizing 1, 2-allene ketone by taking eneyne, 1, 4-dihydropyridine and benzoyl fluoride as substrates, 2, 4, 5, 6-tetra (diphenylamino)-isophthalonitrile as a photocatalyst, 5, 6, 7, 8-tetrahydro-3-(2, 6-diisopropyl phenyl)-4H-cycloheptyl thiazole perchlorate as N-heterocyclic carbene, cesium carbonate as alkali and acetonitrile as a solvent through a one-pot method. And reacting at room temperature for 4 hours under visible light of 12W and 460nm LED blue light to obtain allene ketone. The reaction conditions are mild, and the method has good functional group tolerance.

The invention discloses an isoquinolinone dihydropyridine-[1, 2-alpha] indole spiro compound as well as a preparation method and application thereof, and belongs to the technical field of synthesis of organic compounds. An N-indole connected o-alkynyl nitrone compound is used as a raw material, a two-step one-pot method is adopted, and the isoquinolinone dihydropyridine-[1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, 2, 4] triazolo [1, the invention relates to a novel method for synthesizing a spiro [1, 2-alpha] indole. The method disclosed by the invention has the advantages of simplicity in operation, low catalyst loading capacity, wide reaction substrate range, single stereoselectivity, high yield and the like. The isoquinolinone dihydropyridine-[1, 2-alpha] indole spiro compound prepared by the invention has a certain inhibition effect on phytopathogen, and can be potentially applied to prevention and treatment of tomato gray mold, wheat scab and rhizoctonia solani.

The invention provides a lysine artificial operon and application thereof. The gene sequence of the artificial operon comprises a promoter, a lysC gene for coding aspartate kinase, an asd gene for coding aspartate semialdehyde dehydrogenase, a dapA gene for coding dihydropicolinic acid synthetase and a dapB gene for coding dihydropicolinic acid reductase, the ddh gene is used for coding diaminopimelate dehydrogenase; the lysA gene is used for coding diaminopimelate decarboxylase; except for the first lysC gene, sequences of RBS ribose binding sites of other genes are RBS ribose binding sites translated after gene transcription by intercepting 20-26nt DNA sequences at the upstream of a coding region ATG (adenosine triphosphate); the RBS ribose binding site is connected in front of the corresponding gene.

The invention discloses a trifluoromethyl alkyl quinoline compound, a synthesis method and anti-tumor application thereof in the field of organic synthesis and medicinal chemistry. Trifluoropropene quinoline or N-benzoyl pyrrole (A) and oxidation-reduction active ester (B) are used as raw materials, dimethyl sulfoxide is used as a solvent, dihydropyridine is used as an electron donor, and the trifluoromethyl alkyl quinoline compound is prepared through a one-step reaction. The trifluoromethyl alkyl quinoline and the analogue (C) thereof are synthesized at high yield under the irradiation of visible light. The specific reaction formula is as follows: # imgabs0. The compound provided by the invention has excellent anti-tumor activity and shows low toxicity to normal cells, so that the compound has an application prospect in preparation of anti-tumor drugs.

The invention relates to the technical field of synthesis of photosensitive organic compounds, and discloses a novel hydroxyl-containing dihydropyridine photosensitizer and a preparation method and application thereof.The method comprises the steps that 5-hydroxy-2-nitrobenzaldehyde serves as an initial raw material and reacts with 3-aminocrotonic acid methyl benzoate under the catalytic action of trifluoroformic acid, and a reaction product is obtained; precipitating, filtering and recrystallizing the product to obtain a photosensitive dihydropyridine monomer; the preparation method comprises the following steps: by taking 3, 5-dibromophenol as an initial raw material, introducing halogenated straight-chain alkyl of which the tail end is halogen into a hydroxyl position on the 3, 5-dibromophenol; dissolving a photosensitive dihydropyridine monomer and the intermediate A, and carrying out substitution reaction under the action of alkali to prepare an intermediate B; and carrying out Suzuki coupling reaction on the intermediate B and 4-hydroxymethyl phenylboronic acid to finally obtain the novel dihydropyridine photosensitizer containing hydroxyl. The novel hydroxyl-containing dihydropyridine photosensitizer (DHPDO) is good in compound stability, the preparation process is simple and convenient, the stability of an intermediate product is high, and after-treatment purification is low in toxicity and harmless.

The invention relates to an application of a dihydropyridine compound or a salt thereof in preparation of a medicine for preventing and / or treating HPV infection, and belongs to the technical field of medicines and medicinal preparations. The invention provides application of a dihydropyridine compound or a salt thereof in preparation of a medicine for preventing and / or treating HPV (human papillomavirus) infection. The dihydropyridine compound is selected from one or more of nifedipine, amlodipine, lercanidipine, nimodipine, nitrendipine, nisoldipine, felodipine, benidipine, lacidipine and azelnidipine. According to the scheme, the application of the dihydropyridine compound or the salt thereof in prevention and / or treatment of HPV is reported for the first time, and an in-vitro cell experiment is carried out through azelnidipine in the dihydropyridine compound; furthermore, the inhibition effect on the HPV virus is verified through mouse intradermal vaccination virus model drug delivery and mouse vaginal vaccination virus model drug delivery.

The present invention relates to the synthesis of 3-[(1S,2S)-1-[5-[(4S)-2,2-dimethyloxan-4-yl]-2-[(4S)-2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(4-fluoro-1-methylindazol-5-yl)-2-oxoimidazol-1-yl]-4-methyl-6,7-dihydro-4H-pyrazolo [4,3-c] pyridine-5-carbonyl] indol-1-yl]-2-methylcyclopropyl]-4H-1,2,4-oxadiazol-5-one, or a salt thereof, and related synthetic intermediate compounds.

The present invention addresses the problem of providing a low-alcohol beer-taste beverage that suppresses burnt and soybean odors and has an excellent fermented feel and beer-like beverage quality. A low-alcohol beer-taste beverage according to the present invention has an alcohol concentration of less than 1 v / v%, a 2-acetyltetrahydropyridine compound concentration of at least one of 2-acetyl-3,4,5,6-tetrahydropyridine and the tautomer 2-acetyl-1,4,5,6-tetrahydropyridine of more than 1 ppb but no more than 30 ppb, and a propyl acetate concentration of 0.2–50 ppm.

The invention relates to a synthetic method of a finelrenone racemate, which comprises the following steps: carrying out Knoevenagel condensation, Hantzsch dihydropyridine synthesis, O-ethylation and deprotection four-step reaction, selecting a compound shown as a formula (2) and a compound shown as a formula (3) as initial raw materials, and carrying out Knoevenagel condensation reaction under the combined action of organic alkali and organic acid to synthesize a compound shown as a formula (4); carrying out Hantzsch reaction on the compound in the formula (4) and a compound in a formula (5) to synthesize a compound in a formula (6); carrying out O-ethylation reaction on the compound shown in the formula (6) and an ethylation reagent under the catalysis of acid to synthesize a compound shown in a formula (7); finally, 2, 4-dimethoxybenzyl is removed from the compound shown in the formula (7) under the promotion of acid to synthesize the finerenone racemate, the method is high in selectivity and simple in post-treatment, the yield and purity of the product are high, the HPLC purity can reach 99% or above, a new synthesis route and method are developed for synthesizing the finerenone racemate, and the method has good application potential and research value.

The invention relates to the technical field of optical encryption, and discloses a photosensitive polyurethane film with a surface relief grating pattern and a preparation method and application thereof.The method comprises the steps that in an ice bath and inert atmosphere, toluene diisocynate and a dihydropyridine photosensitizer monomer are added into N, N-dimethylformamide, and a mixture is obtained; the preparation method comprises the following steps: adding the raw materials into a mixed solvent of N, N-diethyl formamide and dimethyl sulfoxide, and then dropwise adding 1, 4-dibutanol; removing the ice bath, and reacting at the temperature of room temperature to 60 DEG C to obtain a photosensitive polyurethane solution; spin-coating the photosensitive polyurethane solution on a substrate, and drying to obtain a photosensitive polyurethane film; and exposing the designed mask plate on the surface of the photosensitive polyurethane film. According to the invention, the non-covalent interaction difference of the polymer-dihydropyridine / pyridine part can be constructed to realize effective surface patterning, and the generation of a two-dimensional ordered grating-shaped wrinkle structure with a sinusoidal phase is realized on the surface of the polyurethane film in a wrinkling manner in combination with an optical anti-counterfeiting technology, so that pattern anti-counterfeiting is realized.

The invention relates to the field of chemical pharmacy, and in particular to a synthesis process of apixaban, comprising the following steps: using 3-chloro-1-(4-(2-oxopiperidin-1-yl)phenyl-5,6-dihydropyridine-2(1H)-one (intermediate A) to react with oxalyl chloride monoester to obtain compound B, then reacting with p-methoxyphenylhydrazine hydrochloride to form a ring through condensation and coupling to obtain compound D, and finally preparing apixaban through amine ester exchange of compound D. Compared with the prior art, the invention has the advantages of: 1. The synthesis process is more efficient and mild, the operation is simple, and the raw materials are easy to obtain; 2. It avoids the use of expensive or toxic and irritating reagents; 3. The total yield is high and is suitable for industrial production.

The invention provides an additive containing amino acid complexed potassium and magnesium as well as a preparation method and application of the additive, and relates to the technical field of feed additives. The additive containing amino acid complexed potassium magnesium is prepared from the following raw materials in parts by weight: 45-55 parts of amino acid complexed potassium magnesium, 15-25 parts of sorbitol, 5-15 parts of sodium citrate, 2-4 parts of guanidinoacetic acid, 2-4 parts of dihydropyridine and 10-20 parts of glucose, wherein the amino acid complexed potassium magnesium is prepared from amino acid, potassium hydroxide and magnesium chloride. The prepared additive containing amino acid complexed potassium and magnesium can improve the anti-stress capability of chickens, can reduce the feed conversion ratio and the death rate when being used in chicken feed, reduces the damage to the chickens caused by stress reaction, and also can reduce the expression of inflammatory factors and improve the expression of anti-inflammatory cytokines, thereby improving the immunity of the organism.

The invention discloses an anti-tumor compound, a preparation method, a pharmaceutical composition containing the compound and application, and belongs to the technical field of biological medicine. The compound disclosed by the invention has a remarkable effect in an in-vitro anti-tumor activity test. In the design process, the N3-((4, 6-dimethyl-2-oxo-1, 2-dihydropyridine-3-yl) methyl)-N3 '-(R)-[1, 1'-biphenyl]-3, 3 '-dicarboxamide compound is designed and synthesized, the anti-tumor effect is improved, and it is found that the N3-((4, 6-dimethyl-2-oxo-1, 2-dihydropyridine-3-yl) methyl)-N3'-(R)-[1, 1 '-biphenyl]-3, 3'-dicarboxamide compound has good anti-proliferation capacity on human melanoma cells A375. In the synthesis process, the synthesis steps are optimized, and possibility is provided for future industrial production.

The invention provides a polyvinyl alcohol derivative as well as a preparation method and application thereof. The polyvinyl alcohol derivative comprises a structural unit of 1, 4-dihydropyridine, a structural unit of vinyl alcohol and a structural unit of vinyl acetate. The preparation method comprises the following steps: dissolving polyvinyl alcohol in an anhydrous organic solvent, adding an acetoacetic acid reagent for reaction to obtain a polyvinyl alcohol derivative containing beta-diketone, and in the presence of a catalyst, reacting an aldehyde compound containing an aggregation-induced emission structure, an ammonia source compound and 1, 2-diketone to obtain the beta-diketone-containing polyvinyl alcohol derivative. And adding a 1, 3-diketone compound into the obtained polyvinyl alcohol derivative containing beta-diketone, and carrying out Hantzsch reaction, so as to obtain the antioxidant aggregation-induced emission polyvinyl alcohol derivative containing the 1, 4-dihydropyridine structure. The polyvinyl alcohol derivative disclosed by the invention has excellent oxidation resistance and aggregation-induced emission performance, and can be applied to the fields of food packaging, biological medicine, health care and the like.

The application belongs to the field of organic synthesis, and particularly relates to a synthesis method of 2-(3,3-dimethylbutyl)pyridine. 2-vinylpyridine, brominated tertiary butane, a mixed solution of dimethyl ether and isopropyl ether as a reaction system solvent, nickel iodide as a nickel salt, bipyridine as a ligand, dicyclohexylmethylamine as a base in the system, 2,6-dimethyl-3,5-diethyl-1,4-dihydropyridine as a reducing agent, a photocatalyst 2,4,5,6-tetrakis(9 ‑ Carbazole) - m-phenylenedinitrile, under the condition of room temperature and nitrogen atmosphere, a reduction cross-coupling reaction is used to synthesize 2-(3,3-dimethylbutyl)pyridine. The application uses inexpensive nickel metal as a catalyst, constructs a cross-coupling reaction of carbon-carbon bond, and has the advantages of mild reaction condition, high economy and the like.

In one aspect, the use of compounds as active agents for the treatment and prevention of hearing impairment, and methods of using the compositions for the treatment and / or prevention of hearing impairment or disorder, are disclosed. In zebrafish and mice, the (E)-1-(3-(3, 4, 5-trimethoxyphenyl) acryloyl)-S, 6-dihydropyridine-2 (1H)-ketone and the derivative have an excellent protective effect on hearing loss induced by antibiotics, and the application of the (E)-1-(3-(3, 4, 5-trimethoxyphenyl) acryloyl)-S, 6-dihydropyridine-2 (1H)-ketone and the derivative has a good application prospect. In one aspect, (E)-1-(3-(3, 4, 5-trimethoxyphenyl) acryloyl)-S, 6-dihydropyridine-2 (1H)-one and derivatives are useful as therapies for the treatment and / or prevention of hearing loss. This abstract is intended as a scanning tool for purposes of retrieval in the particular art and is not intended to be limiting of the present invention.

The present invention relates to a pharmaceutical composition for treating myopia, preventing myopia and / or suppressing myopia progression, comprising (+)-11-[2-[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one or a salt thereof as an active ingredient, wherein the pharmaceutical composition is substantially free of (−)-11-[2-[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one or a salt thereof.

The purpose of the present invention is to provide an industrially preferred method for producing a p-toluenesulfonate of 7-(2,3-difluoro-4-(2-((2-methoxyethyl)(methyl)amino)ethoxy)benzyl)-10-hydroxy-6-methyl-N-(4-methyl-2-(6-methylpyrimidin-4-yl)phenyl)-8-oxo-6,7-diazaspiro[4,5]dec-9-ene-9-carboxamide, which enables a target product to be obtained more inexpensively and easily as compared to conventional methods.The present invention has attained a method which enables a target product to be efficiently obtained by a step of preparing wet powder of a p-toluenesulfonate of 7-(2,3-difluoro-4-(2-((2-methoxyethyl)(methyl)amino)ethoxy)benzyl)-10-hydroxy-6-methyl-N-(4-methyl-2-(6-methylpyrimidin-4-yl)phenyl)-8-oxo-6,7- diazaspiro[4,5]dec-9-ene-9-carboxamide, and a step of drying the wet powder.

The invention belongs to the technical field of chemical synthesis, and particularly relates to a synthesis method of 1-(tert-butyl)-3-ethyl-4-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborane-2-yl)-5, 6-dihydropyridine-1, 3 (2H)-dicarboxylate. According to the invention, 1-(tert-butyl)-3-ethyl-4-oxopiperidine-1, 3-diformate, namely the compound A, is taken as a base material, two-step reaction is carried out, the reaction conditions are relatively mild, the product yield is high, and the operation is easy.

The present invention relates to the technical field of A01P13 / 00, and more specifically, the present invention relates to a dispersible oil-based suspension concentrate containing 3-(2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidine-1(2H)-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ethyl ester and a preparation method therefor. The dispersible oil-based suspension concentrate containing 3-(2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidine-1(2H)-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ethyl ester comprises the following components in parts by weight: 22-44 parts of glyphosate ammonium salt, 0.5-1.5 parts of 3-(2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidine-1(2H)-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ethyl ester, 3-8 parts of a wetting dispersant, 10-15 parts of an emulsifier, 1-2 parts of a structure modifier, and the balance of a solvent till 100 parts. In the present application, the dispersible oil-based suspension concentrate solves the problem in the prior art of decomposition of 3-(2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidine-1(2H)-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ethyl ester, and the dispersible oil-based suspension concentrate does not have the problem of creaming, has good high and low temperature resistance, and has good dilution stability, lasting foamability and suspensibility.

The invention belongs to the field of medicine synthesis, and particularly relates to a method for preparing fenerenone by recycling a fenerenone enantiomer. A brand new reaction route is designed, an enantiomer is subjected to photochemical catalysis to obtain an aromatization product, then in the presence of a specific catalyst, the aromatization product is subjected to dihydropyridine reduction to obtain a finelrenone racemate, and the finelrenone racemate is subjected to resolution, dissociation and recrystallization to obtain the finelrenone. Compared with the prior art, the method has the advantages that the fennerenone enantiomer is recycled, the recycled fennerenone enantiomer is used for preparing the fennerenone, compared with the prior art, photochemical catalysis is realized under the action of the specific catalyst, the reaction condition is mild, the operation is simple, the requirement on equipment is low, and the method is suitable for industrial production. According to the method, the recycling of the enantiomer of the fenerenone can be realized for industrial production of the fenerenone, the commercialization cost of the fenerenone is reduced, large-scale industrial production can be carried out, repeated recycling is realized, and a direction is provided for process improvement of the fenerenone.

The application discloses a trifluoromethyl alkyl quinoline compound, a synthesis method and anti-tumor application in the field of organic synthesis and medicinal chemistry, which is synthesized from trifluoropropylene quinoline or N-benzoyl pyrrole (A) and redox active ester (B) as raw materials, dimethyl sulfoxide as a solvent, dihydropyridine as an electron donor, and under visible light irradiation, a trifluoromethyl alkyl quinoline and analogues (C) are synthesized at a high yield. The specific reaction formula is as follows: The compounds provided by the application all have excellent anti-tumor activity and low toxicity to normal cells, and therefore have application prospects for preparing anti-tumor drugs.

The invention discloses a method and a device for preparing triacetonamine, and the method comprises the following steps: (a) introducing acetone and ammonia into a first reactor, and forming acetonine in the presence of a first acidic catalyst; (b) introducing the acetoneine and water into a second reactor to form triacetonamine and a by-product in the presence of a second acidic catalyst, the by-product being diacetone alcohol, diacetonamine, isopropylidene acetone, 2, 2, 4, 6-tetramethyl-2, 3-dihydropyridine, or a combination of the diacetone alcohol, the diacetonamine, the isopropylidene acetone, the 2, 2, 4, 6-tetramethyl-2, 3-dihydropyridine and the diacetonamine, the 2, 2, 4, 6-tetramethyl-2, 3-dihydropyridine; (c) separating triacetonamine from byproducts by reduced pressure distillation; (d) introducing the by-product and water into a third reactor, and heating and cracking the by-product in the presence of an amphiphilic catalyst to form acetone; and (e) conducting the acetone of step (d) back to the first reactor.

The invention relates to a synthesis method of 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-1, 4-dihydro-2, 8-dimethyl-1, 6-naphthyridine-3-formamide, which comprises the following four steps: carrying out a Knoevenagel condensation reaction, carrying out a Hantzsch dihydropyridine synthesis method, carrying out an O-ethylation reaction and carrying out a deprotection reaction to synthesize the 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-1, 4-dihydro-2, 8-dimethyl-1, 6-naphthyridine-3-formamide, and carrying out a reaction to obtain the 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-1, 4-dihydro-2, 8-dimethyl-1, 6-naphthyridine-3-formamide. The preparation method of the 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-1, 4-dihydro-2, 8-dimethyl-1, 6-naphthyridine-3-formamide has the advantages that the selectivity is high, the post-treatment is simple, the yield and the purity of the product are high, a new synthesis route and method are developed for synthesizing the 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-1, 4-dihydro-2, 8-dimethyl-1, 6-naphthyridine-3-formamide, the amplified production is conveniently realized, and the method is suitable for industrial production. The method has good application potential and research value.

The present disclosure provides compounds of Formula I that are inhibitors of the histone methyltransferase polycomb repressive complex 2 (PRC2) and its subunits, including embryonic ectoderm development (EED) proteins, and are therefore useful for treating diseases treatable by inhibiting dysregulation of PRC2 and EED, such as cancer. Pharmaceutical compositions containing such compounds and methods for preparing such compounds are also provided. In certain embodiments, the subject matter described herein is directed to compounds of Formula I, including all of the subformulas of Formula I, or pharmaceutically acceptable salts or solvates thereof. JPEG2026504602000095.jpg5157

To provide methods for treating diseases or disorders responsive to inhibition of EZH2.SOLUTION: The present disclosure relates to a crystalline form 1 of 7-chloro-2-(4-(3-methoxyazetidin-1-yl)cyclohexyl)-2,4-dimethyl-N-((6-methyl-4-(methylthio)-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzo[d][1,3]dioxole-5-carboxamide, which is useful as a modulator for the activity of histone methyl modifying enzymes.SELECTED DRAWING: None

Provided herein is (R)-7-chloro-2-((1r,4R)-4-(3-methoxyaetidin-1-yl)cyclohexyl)-2,4-dimethyl-N-((6-methyl-4-(methylthio)-2-oxo-1,2-dihydropyridin-3-yl)methyl)benzo[d][1,3]dioxole-5-carboxamide, or a pharmaceutically acceptable salt thereof for use in methods of treating certain cancers having at least one BAP1 mutation.

The present application provides a method for preparing a high-purity key intermediate M2 of dicardipine drugs, belonging to the technical field of drug intermediate preparation. A dehydrating agent is added during the preparation of the intermediate M2, and the dehydrating agent is an orthoester dehydrating agent. Using the method provided in the present application, the yield of the intermediate M2 is 84.3%, the HPLC purity is 99.63%, M2Z3: 0.17%; M2Z4: 0.15%; other impurities <0.10%, and the content of impurities P0Z4 (i.e., M2Z3) and P0Z5 in the further prepared nicardipine is determined to be: P0Z5 <0.02%, P0Z4 <0.02%.