107619results about "Organic active ingredients" patented technology

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

The present disclosure provides compounds and pharmaceutically acceptable salts thereof, and methods of using the same. The compounds and methods have a range of utilities as therapeutics, diagnostics, and research tools. In particular, the subject compositions and methods are useful for reducing signaling output of oncogenic protein.

Compounds of Formulae (I)-(VII) or their pharmaceutically acceptable salts can inhibit the G12C, G12D, G12V, and / or G13D mutants of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formulae (I)-(VII) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

The present disclosure relates to a fused heteroaryl compound, a preparation method therefor, and a use thereof in medicine. Specifically, the present disclosure relates to a fused heteroaryl compound represented by general formula (I'), a preparation method therefor, a pharmaceutical composition containing said compound, and a use thereof as a therapeutic agent, especially a use thereof in the preparation of a medicament for inhibiting KRAS amplification and / or mutant activity. Each group in general formula (I') is as defined in the description.

The disclosure provides compounds, e.g., compounds of Formula I, and their use in treating medical diseases or disorders, such as cancer. Pharmaceutical compositions and methods of making various indene compounds are provided. The compounds are contemplated to be modulators of Ras (e.g., K-Ras).

This disclosure provides compounds of Formula (l-c) or pharmaceutically acceptable salts thereof, that inhibit a KRas protein. In some embodiments, the KRas protein has a dysregulation (e.g., the KRas protein is mutated or amplified). These compounds are useful, for example, for treating a disease, disorder, or condition in which increased and / or sustained (e.g., excessive) KRas activation, for example, KRas activation associated with a mutant KRas protein, contributes to the pathology and / or symptoms and / or progression of the disease, disorder, or condition (e.g., cancer) in a subject (e.g., a human). This disclosure also provides compositions containing compounds of Formula (A) (e.g., Formula (I) (e.g., Formula (l-a), (I- b), (l-c), (l-d), (l-c2), (l-c3), (l-c4), (l-d), or (l-e))) or Formula (B), or pharmaceutically acceptable salts thereof, as well as methods of using and making the same.

Compounds of formula (I) useful as cancer treatment, the preparation method thereof, pharmaceutical compositions comprising the compounds, and the pharmaceutical uses for the treatment of certain diseases or disorders are disclosed.

A fused ring compound, a pharmaceutical composition comprising same, and the use thereof. The compound has a structure as represented by formula (I), or is a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer or a mixture form thereof, a metabolite, a metabolic precursor, an isotope-substituted form, a pharmaceutically acceptable salt, a hydrate, a solvate, a polymorph or a co-crystal thereof. The compound can be used for treating one or more cancers caused by KRAS mutation.

Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting KRAS activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with KRAS activity such as cancer.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Disclosed in the present invention are a macrocyclic compound having a structure represented by formula I, a preparation method therefor and a use thereof. The compound has significant inhibitory effects on KRAS and PI3K protein activity, can be used as a KRAS and / or PI3K protein inhibitor, and is used for preparing a drug for treating diseases such as KRAS and / or PI3K protein-mediated cancers. Moreover, the compound of the present invention has an extremely strong inhibitory effect on KRAS G12D inhibitor drug-resistant cancer cells, and has a wide application prospect.

Provided is the use of a PARP inhibitor in the treatment of a cancer, and in particular to the use of a PARP inhibitor in the maintenance therapy of ovarian cancer. More specifically, provided is a maintenance therapy for a patient with ovarian cancer, which includes administering an effective amount of 5-fluoro-1- (4-fluoro-3- (4- (pyrimidin-2-yl)piperazine-1-carbonyl) benzyl) quinazoline-2, 4 (1H, 3H) -dione, a hydrate or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing 5-fluoro-1- (4-fluoro-3- (4-(pyrimidin-2-yl) piperazine-1-carbonyl) benzyl) quinazoline-2, 4 (1H, 3H) -dione, the hydrate or the pharmaceutically acceptable salt thereof or a medicament containing the pharmaceutical composition to a patient with ovarian cancer who have received a first-line platinum-containing therapeutic regimen and achieved complete response or partial response.

The present invention provides substituted tricyclic compound of formula (I), which are therapeutically useful as KRAS degraders. These compounds are useful in the treatment and / or prevention of diseases or disorders dependent upon KRAS. The present invention also provides pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt or a stereoisomer or a tautomer thereof thereof.

A fused ring compound, a pharmaceutical composition comprising same, and a use. The compound has a structure represented by formula (I) or a tautomer, mesomere, racemate, enantiomer, diastereomer or mixture thereof, metabolite, metabolic precursor, isotope substitution form, pharmaceutically acceptable salt, hydrate, solvate, polymorph or eutectic thereof. The compound can be used for treating a cancer caused by KRAS mutations, and said cancer is selected from one or more cancers caused by KRAS G12C, KRAS G12V, KRAS G12A and G12D mutations. In particular, the compound can serve as a G12D inhibitor and has relatively high inhibitory activity.

The present disclosure relates to methods of co-administering PROTAC (proteolysis targeting chimera) compounds that can promote ubiquitination and degradation of a target protein. The present disclosure also relates to antibody drug conjugates of PROTAC compounds Also disclosed herein are pharmaceutical compositions that can include a compound of Formula (V), the use and preparation thereof.

The compositions and methods provided herein include a pharmaceutical formulation for oral administration comprising a daily dose of a modified release formulation of minoxidil or a pharmaceutically acceptable salt thereof. Also provided herein are pharmaceutical formulations for oral administration comprising a daily dose of a modified release formulation of minoxidil or a pharmaceutically acceptable salt thereof and one or more additional active agents. Also provided herein are methods of treating hair loss by administering to a subject in need thereof a daily dose of a modified release formulation of minoxidil or a pharmaceutically acceptable salt thereof. Further provided herein is a kit including a slow modified release vehicle comprising oral minoxidil or a pharmaceutically acceptable salt thereof.

Provided herein are methods of treating cancer by administering a combination therapy comprising a KRAS G12D inhibitor and a PD-1 inhibitor or a PD-L1 inhibitor.

The present invention is directed to the compounds of Formula (A) inhibitors of KRAS(G12D). The inhibitors described herein can be useful in the treatment of diseases or disorders associated with KRAS(G12D), such as Lung cancer, Pancreatic cancer, Colorectal cancer et al. In particular, the invention is concerned with compounds and pharmaceutical compositions inhibiting KRAS(G12D), methods of treating diseases or disorders associated with KRAS(G12D), and methods of synthesizing these compounds.

Provided herein are methods of treating cancer by administering a combination therapy comprising a KRAS G12D inhibitor and an EGFR inhibitor.

The Application describes new SOS1 inhibitors for use in the treatment of pain and cancer.

Provided herein are methods of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a combination of a RTK-MAPK pathway inhibitor and a compound of Formula (I).

The present invention belongs to the technical field of pharmaceutical chemistry, and relates to a benzylamino-substituted tricyclic heterocyclic compound as represented by formula I, a composition thereof, a preparation thereof and the use thereof. Specifically, the general formula of the tricyclic heterocyclic ring has a structure as represented by formula I. The compound of the present invention has excellent in-vitro inhibitory activity against SOS1, and has good in-vivo inhibitory activity against an NCI-H358 subcutaneous xenograft tumor. In addition, the compound of the present invention has characteristics such as relatively low plasma clearance, relatively long drug half-life, relatively good exposure and relatively high bioavailability, has good pharmacokinetic properties, does not show strong inhibition against various CYP enzyme subtypes, is high in terms of levels of safety, has in-vivo anti-tumor activity, and is relatively low in terms of levels of toxicity.

The present application relates to the technical field of medicines, and relates to a macrocyclic compound containing amide substitution, in particular to a compound as shown in formula (I) or a pharmaceutically acceptable salt thereof, and a preparation method therefor, a pharmaceutical composition containing the compound, and a use thereof in the treatment of disease.

The present invention relates to four specific macrocyclic compounds for use as inhibitors of KRAS mutant for the treatment of cancer. Example (1): 1-[4-(dimethylamino)-4-methyl-pent-2-ynoyl]-N-[(1S)-1-[[(6S,8S,14S)-22-ethyl-25-fluoro-(21M)-21-[2-[(1S)-1-methoxyethyl]-3-pyridyl]-18,18-dimethyl-9,15-dioxo-5,16-dioxa-2,10,22,28-tetrazapentacyclo[18.5.2.12,6.110,14.023,27]nonacosa-1(26),20,23(27),24-tetraen-8-yl]carbamoyl]-2-methyl-propyl]-4-fluoro-N-methyl-piperidine-4-carboxamide.

The invention relates to the field of antitumor drugs, in particular to a pharmaceutical composition of a KRAS G12C inhibitor and mitoxantrone and application of the pharmaceutical composition. The mitoxantrone hydrochloride and the KRAS G12C inhibitor are combined to play a synergistic effect, a DNA damage repair pathway is inhibited, a better inhibition effect is generated on tumor cells containing KRAS G12C mutation, the dosage required for achieving the same anti-tumor effect is greatly reduced, and the medication safety is improved.

The present application belongs to the field of medical chemistry, and relates to a fused tricyclic compound and the medical use thereof. The compound has a structure as represented by formula (I). Particularly, the present application further relates to a method for preparing the compound, a pharmaceutical composition of the compound and the use of the compound in the treatment of diseases.

The present disclosure provides novel compounds useful as inhibitors of KRAS, in particular KRAS G12D and / or other KRAS G12 mutants, as well as pharmaceutical compositions comprising these compounds and methods of treatment by administration of these compounds or the pharmaceutical compositions.