34 results about "Pazopanib" patented technology

The present invention provides a method for treating a proliferative disease in a patient. The method comprises administering to a patient in need thereof: a) a vascular disrupting agent and (b) at least one hypoxia targeting agent. Preferred combinations are BNC105 and Pazopanib and BNC 105 and Bortezomib.

The present invention provides diagnostic methods, therapeutic methods, and compositions for the treatment of cancer (e.g., kidney cancer (e.g., renal cell carcinoma (RCC)), lung cancer (e.g., non-small cell lung cancer (NSCLC)), bladder cancer (e.g., urothelial bladder cancer (UBC)), liver cancer (e.g., hepatocellular carcinoma (HCC)), ovarian cancer, or breast cancer (e.g., triple-negative breast cancer (TNBC))). The invention is based, at least in part, on the discovery that expression levels of one or more biomarkers described herein in a sample from an individual having cancer can be used in methods of predicting the therapeutic efficacy of treatment with a VEGF antagonist (e.g., an anti-VEGF antibody, (e.g., bevacizumab) or a VEGFR inhibitor (e.g., a multi-targeted tyrosine kinase inhibitor (e.g., sunitinib, axitinib, pazopanib, or cabozantinib))) and a PD-L1 axis binding antagonist (e.g., a PD-L1 binding antagonist (e.g., anti-PD-L1 antibody, e.g., atezolizumab (MPDL3280A)) or a PD-1 binding antagonist (e.g., anti-PD-1 antibody)), or with an angiogenesis inhibitor (e.g., a VEGF antagonist (e.g., a VEGFR inhibitor, (e.g., a multi-targeted tyrosine kinase inhibitor (e.g., sunitinib, axitinib, pazopanib, or cabozantinib)))).

The present disclosure relates to stable formulations of receptor tyrosine kinase inhibitors (TKI), e.g., pazopanib; methods of preparation thereof; and use of the disclosed formulations in sustained delivery of the active agent to a target site. The disclosure further relates to methods of converting one polymorphic Form of a TKI to another polymorphic Form and / or an amorphous form.

The invention belongs to the technical field of pharmaceutical chemistry synthesis and particularly relates to a green preparation method of pazopanib hydrochloride. The method comprises the steps ofallowing o-toluidine and N-chlorosuccinimide to give a chlorination reaction to form 2-methyl-5-chlorine-aniline, allowing 2-methyl-5-chlorine-aniline to react with a nitrous acid compound to form 6-chlorine-2H-indole hydrochloride, performing N methylation reaction to form N-methyl-6-chlorine-2H-indole, performing 3-delta carbon alkylation reaction in the presence of dimethyl sulfoxide to form 2,3-dimethyl-6-chlorine-2H-indazole, allowing 2,3-dimethyl-6-chlorine-2H-indazole to react with 2-chlorine-4-amino-pyrimidine and methyl iodide to form N-(2-chloropyrimidine-4)-N-methyl-2,3-dimethyl-2H-indazole-6-amine, and at last, allowing N-(2-chloropyrimidine-4)-N-methyl-2,3-dimethyl-2H-indazole-6-amine to react with 3-sulfamate-4-methyl-aniline to form pazopanib hydrochloride. The method is lowin raw material price, simple to operate and low in operational risk, and avoids generation of waste acid; and a reaction yield and purity are high.

The invention discloses application of pazopanib, a pharmaceutical composition, an injection, a preparation method and application. The pharmaceutical composition comprises the following components: pazopanib, a cyclodextrin solubilizer and a solvent, wherein the mass ratio of pazopanib to the cyclodextrin solubilizer is 1: (13-100); and based on 1mL of the pharmaceutical composition, the concentration of the cyclodextrin solubilizer in the pharmaceutical composition is 6-330mg / mL. The pharmaceutical composition prepared by the invention can be used for treating diseases such as acute lung injury, pulmonary fibrosis and acute respiratory distress syndrome, and the treatment aim can be achieved by using a small amount of pazopanib; and moreover, the pharmaceutical composition is high in bioavailability, high in stability and low in impurity content, and the phenomenon of drug accumulation is avoided.

The present invention relates to a pazopanib-based HDAC and VEGFR double-target inhibitor, a preparation method therefor and an application thereof. Said compound has a structure as presented in formula I, II or III. The present invention also relates to a preparation method for this type of compound and the application thereof in preparing drugs for treating or preventing oncological diseases.

A method for preventing, treating and / or improving a prostatic disease or disorder associated with epithelial hyperplasia and / or fibrosis, comprising: administering an effective amount of a multikinase inhibitor to a subject in need thereof, wherein the multikinase inhibitor has a certain spectrum of kinase inhibitory activity. The multikinase inhibitor is sunitinib, regorafenib, ponatinib, pazopanib, nintedanib and / or lenvatinib. The prostatic disease or disorder is selected from the group consisting of benign prostate hyperplasia and its associated lower urinary tract symptoms, fibrosis of ureters and renal pelvis, prostate adenoma, and prostatic intraepithelial neoplasia in animals and humans.

The present invention provides methods and compositions for treating and preventing lung injuries due to or associated with coronavirus infections that cause Severe Acute Respiratory Syndrome, including COVID-19. More specifically the present invention provides methods for treating or preventing the lung injuries associated with SARS-CoV-2 infections, such as acute lung injury (ALI), lung fibrosis, and acute respiratory distress syndrome (ARDS). The methods comprise administering a therapeutically effective amount of a pharmaceutical composition comprising a protein kinase inhibitor compound having MAP3K2 / MAP3K3 inhibition activity, such as pazopanib or nintedanib, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, to a patient in need thereof. The present invention also provides devices for administering the compositions.

The invention discloses a preparation method and an intermediate of Pazopanib. The preparation method comprises the steps of carrying out two-step condensation reaction on 2,4-dichloro-5-nitropyrimidine so as to obtain a compound of a formula 5 (shown in the description), and carrying out reduction on the compound of the formula 5, so as to obtain Pazopanib. The preparation method has the beneficial effects that the yield of Pazopanib is increased, reaction conditions are mild, column chromatography purification is not required, and the preparation method is applicable to industrial production.

The present invention provides diagnostic methods, therapeutic methods, and compositions for the treatment of cancer (e.g., kidney cancer (e.g., renal cell carcinoma (RCC)), lung cancer (e.g., non-small cell lung cancer (NSCLC)), bladder cancer (e.g., urothelial bladder cancer (UBC)), liver cancer (e.g., hepatocellular carcinoma (HCC)), ovarian cancer, or breast cancer (e.g., triple-negative breast cancer (TNBC))). The invention is based, at least in part, on the discovery that expression levels of one or more biomarkers described herein in a sample from an individual having cancer can be used in methods of predicting the therapeutic efficacy of treatment with a VEGF antagonist (e.g., an anti-VEGF antibody, (e.g., bevacizumab) or a VEGFR inhibitor (e.g., a multi-targeted tyrosine kinase inhibitor (e.g., sunitinib, axitinib, pazopanib, or cabozantinib))) and a PD-L1 axis binding antagonist (e.g., a PD-L1 binding antagonist (e.g., anti-PD-L1 antibody, e.g., atezolizumab (MPDL3280A)) or a PD-1 binding antagonist (e.g., anti-PD-1 antibody)), or with an angiogenesis inhibitor (e.g., a VEGF antagonist (e.g., a VEGFR inhibitor, (e.g., a multi-targeted tyrosine kinase inhibitor (e.g., sunitinib, axitinib, pazopanib, or cabozantinib)))).

A pharmaceutical composition for prevention or treatment of a disease or disorder characterized by chronic inflammation, associated with angiogenesis and fibrosis. The pharmaceutical composition includes a multi-target inhibitor, multi-phase modulator, or multi-kinase inhibitor, such as axitinib, nintedanib, pirfenidone, riociguat, sorafenib, sunitinib, lenvatinib, regorafenib, ponatinib, or pazopanib.

The present invention provides methods of treating solid cancer by co-administering an inhibitor of cyclin-dependent kinase 4 / 6 (CDK 4 / 6) and multi-targeted receptor tyrosine kinase inhibitor (mt RTKI). Particular examples of CDK 4 / 6 inhibitor are palbociclib, abemaciclib and ribociclib and of mt RTKI are sunitinib, sorafenib and pazopanib. Administration of the combination may confer a synergic effect in treatment solid tumors. In particular synergic combinations of palbociclib with sunitinib or sorafenib are provided that synergically inhibit progression of a plurality of solid cancer types. The invention also provides pharmaceutical compositions comprising combinations of CDK 4 / 6 inhibitors and mt RTKIs and their use in treating solid cancer.

The invention provides a synthesis method of a trimer impurity of a pazopanib hydrochloride bulk drug. The synthesis method comprises following steps: taking a compound (I) as the raw material, carrying out condensation reactions between the compound (I) and 2-methyl-5-nitrobenzene sulfonyl chloride to obtain a compound (II); reacting the compound (II) with tert-butyl carbamate to generate a compound (III); reacting the compound (III) with hydrochloric acid to obtain a compound (IV); and finally carrying out condensation reactions between the compound (IV) and N-(2-chloropyrimidine-4-yl)-N-methyl-2,3-dimethyl-2H-indazole-6-amine to obtain the trimer impurity (V). The yield of the synthesis method is high; and the prepared impurity can be used as a reference substance in quality analysis ofpazopanib hydrochloride.

The invention discloses a method for detecting the drug concentration of pazopanib in human plasma through LC-MS / MS combination, and belongs to the technical field of drug concentration analysis. Themethod comprises the following steps: respectively mixing a series of pazopanib working solutions with human blank plasma, performing pre-treating, injecting the mixture into LC-MS / MS for analysis, adding an internal standard working solution mainly prepared from pazopanib-d6 into human plasma to be detected, performing pre-treating, injecting the mixture into LC-MS / MS for analysis, drawing a standard curve by taking the chromatographic peak area ratio of pazopanib to internal standard pazopanib-d6 as an ordinate and the concentration of pazopanib in human blank plasma as an abscissa, and calculating the concentration of pazopanib in the human plasma sample to be detected according to the standard curve, wherein a protein precipitation method is adopted to pretreat a human plasma sample, an electrospray ion source is adopted as an ionization technology, and the detection method is simple and convenient to operate, high in sensitivity, good in reproducibility, high in selectivity, shortin analysis time and suitable for large-batch detection of clinical samples.

The present invention is relates to an improved process for the preparation of pazopanib or a pharmaceutically acceptable salts thereof. The present invention also relates to novel polymorphic Forms of pazopanib hydrochloride, and its intermediates thereof.

The invention belongs to the field of medicinal chemistry, and in particular relates to a preparation method of related substances of pazopanib. Using the compound shown in formula I as a raw material, reacting with the compound of formula II to prepare the compound shown in formula III, and then reacting with aniline to prepare the compound shown in formula IV or its acid addition salt, the compound shown in formula IV and benzophenone imine reaction, and then react with the compound shown in formula VIII to prepare the compound shown in formula V, and then prepare the compound shown in formula VII, the related substance of pazopanib, through nitro reduction and condensation reaction.

The present disclosure relates to stable formulations of receptor tyrosine kinase inhibitors (TKI), e.g., pazopanib; methods of preparation thereof; and use of the disclosed formulations in sustained delivery of the active agent to a target site. The disclosure further relates to methods of converting one polymorphic Form of a TKI to another polymorphic Form and / or an amorphous form.