37 results about "Neratinib" patented technology

The invention provides a preparation method of antineoplastic drug maleic acid neratinib. The defects in the prior art are overcome. The preparation method comprises the steps that the formula II and the formula III are coupled to form the formula IV under the effect of a catalyst; a nitro-compound IV is reduced under the effect of a reduction system to form a formula V; an amino compound V and a formula VI are condensed to obtain neratinib VII, and then the neratinib VII and maleic acid form a salt to obtain the maleic acid neratinib I. By the adoption of the technical route, the preparation method has the advantages that the synthetic route is short, reaction conditions are mild, the yield is high, raw materials are wide in source, and environmental protection is achieved.

Amorphous neratinib is characterized in that no characteristic peak of neratinib exists in an X-ray powder diffraction spectrum. Amorphous neratinib maleate is characterized in that no characteristic peak of neratinib maleate exists in an X-ray powder diffraction spectrum. The invention further discloses a preparation method of an amorphous state of the amorphous neratinib or pharmaceutically acceptable salt thereof, as well as a solid dispersion prepared from the amorphous neratinib or the pharmaceutically acceptable salt thereof and medicinal auxiliary materials and a preparation method thereof, wherein the neratinib or the pharmaceutically acceptable salt thereof are amorphous. The solid dispersion prepared from the neratinib or the pharmaceutically acceptable salt thereof and the medicinal auxiliary materials is good in stability and dispersion, so that the dissolution of the neratinib or the salt thereof is improved and thus the improvement on the bioavailability of a medicinal preparation and medicine absorption of a body is more facilitated; under an accelerated test condition, the solid dispersion keeps good physical and chemical stability. The preparation method of the amorphous solid dispersion is easy to operate, low in cost, good in reproducibility and easy to implement, and is suitable for industrial production.

An extended regimen for treatment of HER-2/neu overexpressed/amplified cancer is described, with involves delivering a course of neratinib therapy to HER-2/neu overexpressed/amplified cancer patients following the completion of surgical and adjuvant therapy. The neratinib regimen may be continued for upwards of twelve months to five years. Also provided are pharmaceutical kits designed to facilitate compliance with the regimen.

The invention relates to a preparation method of a medicinal composition of neratinib or a medicinal salt of the neratinib. A medicinal preparation with good stability can be prepared through keeping the maximum water content of a granule in the granulation period to be 10% or less or/and controlling the water content of a final granule or the medicinal composition to be 2% or less in the preparation process of the neratinib granule, and the medicinal preparation has good dissolving property.

The invention relates to a method for purifying neratinib. The method provided by the invention is capable of effectively reducing the content of impurities in neratinib and preparing high-purity neratinib, and moreover is simple in operation, high in yield and very applicable to industrial production.

This invention relates to the treatment of breast cancer in a subject, for example a female subject. Including methods of: treating metastatic breast cancer; refractory breast cancer; AR-positive breast cancer; AR-positive refractory breast cancer; AR-positive metastatic breast cancer; AR-positive and ER-positive breast cancer; triple negative breast cancer; advanced breast cancer; breast cancer that has failed selective estrogen receptor modulator (SERM) (tamoxifen, toremifene, raloxifene), gonadotropin-releasing hormone (GnRH) agonist (goserelin), aromatase inhibitor (AI) (letrozole, anastrozole, exemestane), cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor (palbociclib (Ibrance), ribociclib (Kisqali), abemaciclib (Vorzenio)), mTOR inhibitor (everolimus), trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), lapatinib, neratinib (Nerlynx), olaparib (Lynparza) (an inhibitor of the enzyme poly ADP ribose polymerase (PARP)), bevacizumab (Avastin), and/or fulvestrant treatments; metastasis in a subject suffering from breast cancer; HER2-positive; and/or treating a subject suffering from ER mutant expressing breast cancer, comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound.

The invention belongs to the technical field of medicine, and specifically relates to neratinib and a preparation method thereof. The new crystal form of neratinib obtained in the invention has the advantages of high purity, the largest impurity is less than 0.5‰, good stability, and heavy method. The reproducibility is good, and the purity and crystal form can be well reproduced when it is scaled up to the pilot scale.

The invention relates to the field of chemical synthesis, and specifically relates to a preparation method of a Neratinib intermediate. A compound (I) is taken as the raw material, and through a series of reactions, the intermediate compound (VIII) of a novel antitumor drug Neratinib is obtained. A high efficient synthesis route is provided and has the characteristics of low cost, few byproducts, high yield, and little environmental pollution.

The invention relates to a crystal form of neratinib dimaleate. Compared with the prior art, the crystal form of neratinib dimaleate in the invention has better solubility in water. The invention alsorelates to a preparation method for the crystal form of neratinib dimaleate, a pharmaceutical composition of neratinib dimaleate and application of neratinib dimaleate to preparation of drugs used for treating, inhibiting and/or preventing cancers.

The invention relates to a neratinib hydrochloride new crystal form I and a preparation method thereof, and belongs to the technical field of medicines. An X-ray powder diffraction pattern of the neratinib hydrochloride crystal form I has characteristic absorption peaks when the reflection angle, namely 2*theta is 4.0+/-0.2 degrees, 8.8+/-0.2 degrees, 11.1+/-0.2 degrees, 15.7+/-0.2 degrees, 17.6+/-0.2 degrees, 20.2+/-0.2 degrees, 23.8+/-0.2 degrees, 26.6+/-0.2 degrees, 27.1+/-0.2 degrees and 28.9+/-0.2 degrees, and the crystal form I has the excellent stability and purity; and additionally, the preparation method of the crystal form I is simple, easy to operate, mild in reaction condition, small in type and using quantity of organic solvents and environmentally friendly, and facilitates industrialization innovation.

The invention discloses a preparation method of a Neratinib intermediate. The preparation method comprises the following steps: by taking a compound A and POCl3 as raw materials, and a nitrogenous compound as a catalyst, allowing the compound A and POCl3 to react with the nitrogenous compound to obtain the Neratinib intermediate, wherein the compound A is (E)-N-(4-((2-cyano-3-morpholino-3-oxopropionic-1-alky-1-base)amino)-2-ethoxy phenyl) acetamide. According to the method, the nitrogenous compound is used as the catalyst, high temperature is not needed in the reaction, the reaction can be performed at the temperature of 65 to 75 DEG C, compared with the traditional method requiring the high temperature of 200 to 250 DEG C, the reaction temperature is greatly reduced, the high-temperature reaction is avoided, operation safety is ensured, the reaction yield is also increased to 45 to 57 percent, and the yield is obviously increased.

The invention relates to crystal forms and a preparation method of neratinib free alkali. Specifically, the invention discloses new crystal forms of a compound shown in a formula (I) or a solvate thereof, namely a crystal form III, a crystal form IV, a crystal form V and a crystal form VI respectively. The new crystal forms disclosed by the invention are beneficial to separation and purification of a compound free alkali shown in the formula (I), and process efficiency and chemical quality of a product are greatly improved. (The formula (I) is as shown in the description.).

The invention aims to provide a new route for preparing neratinib key intermediate 3-cyano-4-oxo-6-nitro-7-ethoxy-1, 4-dihydroquinoline, and the route takes 2-halo-4-fluoro-5-nitrobenzoic acid as a starting material, and the synthesis of the target intermediate is conveniently realized through four steps of reactions.

The invention relates to neratinib dimaleate crystal forms and a preparation method thereof. Particularly, the invention discloses three crystal forms of neratinib dimaleate, i.e., crystal forms IV, Vand VI respectively, which are all anhydrous substances of the neratinib dimaleate, wherein the crystal forms IV and V have better solubility than a known crystal form II, the crystal form V has lower hygroscopicity, and the crystal forms cannot be transformed by a relative moisture change. The invention further discloses proper medicine research of the three crystal forms and the preparation method in industrial production.

The invention relates to a preparation method for neratinib. Specifically, N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-2-diethyl phosphate-acetamide reacts with 2,2-diethoxy-N,N-dimethylethylamine or 2-(dimethylamino)acetaldehyde in the presence of a lithium salt and an alkali to produce neratinib. The method provided by the invention has the advantages of high yield, mild reaction conditions, usage of common and commercially available reagents, a low price, suitability for industrial production and good economic prospects.

This invention relates to the treatment of breast cancer in a subject, and the subject can be either a male or female subject. Including methods of: treating metastatic breast cancer; refractory breast cancer; AR-positive breast cancer; AR-positive refractory breast cancer; AR-positive metastatic breast cancer; AR-positive and ER-positive breast cancer; triple negative breast cancer; advanced breast cancer; breast cancer that has failed selective estrogen receptor modulator (SERM) (tamoxifen, toremifene, raloxifene), gonadotropin-releasing hormone (GnRH) agonist (goserelin), aromatase inhibitor (AI) (letrozole, anastrozole, exemestane), cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor (palbociclib (Ibrance), ribociclib (Kisqali), lerociclib, abemaciclib (Vorzenio), trilaciclib, lerociclib), mTOR inhibitor (everolimus), trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), alpelisib (Piqray) (an inhibitor of phosphatidylinositol-3-kinase subunit alpha (PI3Kα)), lapatinib, neratinib (Nerlynx), olaparib (Lynparza) (an inhibitor of the enzyme poly ADP ribose polymerase (PARP)), bevacizumab (Avastin), and/or fulvestrant treatments; metastasis in a subject suffering from breast cancer; HER2 -positive; treating a subject suffering from ER mutant expressing breast cancer and/or treating breast cancer in a subject, by first determining the ¹⁸F-16β-fluoro-5α-dihydrotestosterone (¹⁸F-DHT) tumor uptake and identifying said subject as having AR-positive breast cancer based on ¹⁸F-DHT tumor uptake, comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound and a cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor.