72338results about "Organic chemistry" patented technology

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 present invention relates to a compound of formula (I), or a stereoisomer, a tautomer, a deuterated compound or a pharmaceutically acceptable salt thereof, a preparation method therefor, a pharmaceutical composition comprising the compound, and the use thereof as a drug for treating and / or preventing KRAS-mediated diseases.

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).

Provided herein are KRAS proteolysis targeting chimeras (PROTACs), compositions comprising the KRAS PROTACs, and methods of making and using the KRAS PROTACs, e.g., to promote degradation of KRAS and / or treat KRAS-associated cancers. In an embodiment, the KRAS PROTAC has the structural formula (I) or a pharmaceutically acceptable salt thereof, wherein values for the variables are as described herein.

The disclosure provides compounds, e.g., compounds of Formulae (I)-(III), 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.

The application relates to modulators of RAS-PI3K of formula (I) or (la) useful for the treatment of cancer and immunological diseases.

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.

The present disclosure relates to PROTAC (proteolysis targeting chimera) compounds that bind to Keapl ubiquitin ligase and can promote ubiquitination and degradation of a target protein, particularly Kirsten rat sarcoma (KRAS) and androgen receptor (AR). Also disclosed herein are pharmaceutical compositions that can include a compound of Formula (I), the use and preparation thereof.

A CDK inhibitor having a structure of formula (I), a pharmaceutical composition thereof, the use thereof as a CDK inhibitor, and the use thereof in the preparation of a drug for treating cancers or tumors at least partially associated with CDK. The various substituents in formula (I) are as defined in the description.

An organic molecule is disclosed comprising:a first chemical moiety with a structure of formula I,andtwo second chemical moieties, each at each occurrence independently from another consisting of a structure of formula II,wherein the first chemical moiety is linked to each of the two second chemical moieties via a single bond.

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.

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 provides KRAS inhibitors of formula (I). Methods of treating cancers using the compounds are also provided.

The present disclosure provides quinazoline- and azaquinazoline-based compounds and pharmaceutically acceptable salts thereof, and methods of using the same as modifiers of mutant Ras protein. 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.

Provided herein are compounds of Formula (I), or a pharmaceutically acceptable form thereof, and pharmaceutical compositions comprising the same. Also provided herein methods of modulating the activity of cellular targets by administering to a subject a compound of Formula (I), or a pharmaceutically acceptable form thereof. Further provided herein are methods of treating cancer, fibrotic diseases, and inflammatory diseases by administering to a subject a compound of or a pharmaceutically acceptable form thereof.

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.

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

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 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.