450 results about "Selective inhibition" patented technology

The invention relates to compounds of formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a PROTAC molecule thereof that selectively inhibit the activity of K-Ras G12D protein, compositions comprising the same, the methods of using the same and related intermediates.

The present invention discloses a series of fluorine-substituted heterocyclic compounds, specifically, compounds represented by formula (XII) and pharmaceutically acceptable salts thereof. 【Chemical 1】 JPEG2025516367000403.jpg44170

Disclosed are RAS(ON) multi-selective inhibitor compositions and methods of treating RAS protein-related diseases or disorders using an intermittent dosing regimen. RAS(ON) multi-selective inhibitors having tight binding to cyclophilin A (CypA) result in high exposure levels, prolonged tissue retention, and / or slow clearance rates, thereby increasing the risk of inhibition of wild-type RAS in normal tissues. Accordingly, provided herein are methods for the safe and effective dosing of low KD1 RAS(ON) multi-selective inhibitors using an intermittent dosing regimen. Also provided are methods of selecting or identifying such RAS(ON) multi-selective inhibitors suitable for intermittent administration.

Provided herein are compounds that selectively inhibit HDAC6, a protein whose activity is associated with a variety of diseases (e.g., cancer, neurological disorders). Also provided are pharmaceutical compositions and kits comprising the compounds, and methods of treating HDAC6-related diseases and disorders (e.g., Alzheimer's disease, cancer) with the compounds in a subject, by administering the compounds and / or compositions described herein.

The present invention relates to a voltage-gated sodium channel Nav1.8 selective inhibitor and the use thereof in the preparation of a related drug. The drug is used for treating diseases responsive to the inhibition of voltage-gated sodium channel NaV1.8, such as chronic pain, enterodynia, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, post-operative pain, visceral pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough or arrhythmia. Specifically, the present invention relates to a compound as shown in formula (X), and an isomer, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug thereof.

Disclosed herein are monoclonal antibodies and antigen-binding fragments thereof capable of selectively inhibiting TGFβ1 with high potency. Related compositions, methods and therapeutic use are also disclosed.

The present provides a method of treating ovarian cancer, breast cancer, gastrointestinal cancer, lung cancer, cancer of the brain or prostate cancer in a subject in need thereof, comprising administering to the subject a first amount of a selective PARP1 inhibitor or a pharmaceutically acceptable salt thereof, and a second amount of an ATR inhibitor or a pharmaceutically acceptable salt thereof. Also disclosed are compositions and kits comprising a PARP inhibitor and ATR inhibitor.

The invention can provide compounds, analogs of blebbistatin, effective and selective inhibitors of nonmuscle myosin II relative to cardiac myosin II. Compounds can be used in the method of treating a disease, disorder, or medical condition in a patient, comprising modulating myosin II ATPase, such as treatment of substance abuse relapse disorder, or of renal disease, cancer and metastasis, benign prostate hyperplasia, hemostasis or thrombosis, nerve injury including retinal damage, lung fibrosis, liver fibrosis, arthrofibrosis, wound healing, spinal cord injury, periodontitis, glaucoma and immune-related diseases including multiple sclerosis; or wherein the disease, disorder, or medical condition comprises addiction including abuse of or addiction to anything classified as a Substance-Related or Addictive Disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM), such as, but not limited to, cocaine, opioids, amphetamines, ethanol, cannabis / marijuana, nicotine, and activities including gambling.Compounds are of general formulawith substituents as defined herein.

The invention provides a fluorite flotation composite inhibitor and a preparation method and application thereof.The composite inhibitor can be used for flotation of phosphorus-containing high-calcium low-grade fluorite mine and comprises, by mass, 1-5 parts of sodium hexametaphosphate, 8-40 parts of sodium humate, 2.8-14 parts of tannin extract, 5-40 parts of water glass and 0.2-1 part of sodium acrylate. The preparation method comprises the following steps: S1, dissolving sodium hexametaphosphate, water glass and sodium acrylate in water to obtain a mixed solution; and S2, adding the tannin extract and the sodium humate into the mixed solution, and uniformly mixing the tannin extract and the sodium humate. The fluorite flotation composite inhibitor is high in selective inhibition performance, small in influence on floatability of fluorite while inhibiting calcite and apatite, better in selective inhibition effect compared with a single traditional inhibitor such as water glass and the like, capable of achieving efficient separation of calcite, apatite and other calcium-containing gangue minerals and fluorite and capable of achieving efficient flotation of fluorite. And high-quality and high-recovery-rate fluorite concentrate is obtained, and the comprehensive benefits of the flotation process are greatly improved.

The invention discloses application of quaternary ammonium cation modified cellulose as a talc inhibitor, and belongs to the technical field of mineral separation. The quaternary ammonium cation modified cellulose has the following molecular structural formula: # imgabs0 #, R1, R2 and R3 are independently selected from hydrogen or quaternary ammonium salt groups, and at least one of R1, R2 and R3 is a quaternary ammonium salt group; and m / (m + n) is equal to 0.18-0.90. The talc flotation inhibitor has a good selective inhibition effect on talc flotation, and is particularly suitable for efficient flotation separation of metal sulfide ores (such as molybdenite, galena and sphalerite) and talc.

The present invention provides a compound of Formula Iand pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age related macular edema, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

The present invention relates to a substituted pyrimidine-fused ring inhibitor, a method for preparing same, and use thereof. Specifically, the compound of the present invention has a structure represented by formula (I). Further disclosed are a method for preparing the compound, and use of the compound as a KRAS mutation inhibitor. The compound has a good selective inhibition effect on KRAS mutation and has better pharmacodynamic and pharmacokinetic performance and lower toxic and side effects.

Provided herein are compounds that selectively inhibit HDAC6, a protein whose activity is associated with a variety of diseases (e.g., cancer, neurological disorders). Also provided are pharmaceutical compositions and kits comprising the compounds, and methods of treating HDAC6-related diseases and disorders (e.g., Alzheimer's disease, cancer) with the compounds in a subject, by administering the compounds and / or compositions described herein.

The invention relates to a 5, 9-di-tert-butyl naphtho-indolizine phenothiazine compound as well as a preparation method and medical application thereof. The compound is efficiently synthesized through Ullmann coupling and palladium-catalyzed intramolecular arylation reaction. In-vitro anti-tumor activity research shows that the compound has remarkable selective inhibitory activity on various human tumor cell lines, and particularly, the inhibitory effect on non-small cell lung cancer A549 cells (IC50 = 0.21 mu M) is improved by two orders of magnitude compared with that of cis-platinum; iC50 (half maximal inhibitory concentration) of other cell lines are as follows: 1.26 mu M of prostate cancer PC-3 cells, 6.78 mu M of liver cancer HepG2 cells, 7.99 mu M of cervical cancer Hela cells and 25.46 mu M of breast cancer MCF-7 cells. Preliminary toxicity experiments prove that the compound has the characteristic of low cytotoxicity. The compound can be used as a novel high-efficiency low-toxicity anti-tumor lead compound, and provides an important structural basis for the development of anti-cancer drugs.

The present invention relates to the technical field of thyroid cancer drugs, and specifically relates to the application of honeysuckle polysaccharide in the preparation of drugs for treating thyroid cancer. Based on the isolation and purification of honeysuckle polysaccharide with good homogeneity, it is found that it has no toxic effect on normal thyroid follicular cells, but selectively inhibits the proliferation of recurrent and metastatic papillary thyroid cancer cells, and has an inhibitory effect on the xenograft tumors of nude mice inoculated with recurrent and metastatic papillary thyroid cancer cell lines. The honeysuckle polysaccharide of this scheme has good homogeneity, a molecular weight of 23 ± 4 kDa, and is mainly composed of five monosaccharides, mainly connected by α-(1→4)-D-GalpA to form the main chain. While the polysaccharide effectively inhibits the cell viability of IHH-4, it has no toxic effect on normal thyroid cells. This technical scheme can solve the technical problem in the prior art of lacking drugs with small side effects and high specificity for treating recurrent and metastatic papillary thyroid cancer, and has an ideal application prospect.

This disclosure features structurally-stabilized and / or cysteine-reactive peptide inhibitors for selective targeting of BFL-1, or dual targeting of BFL-1 and MCL-1. Also disclosed are methods of using such structurally-stabilized and cysteine-reactive peptides in the treatment of BFL-1- and / or MCL-1-expressing or -dependent cancers or diseases of cellular excess (e.g., autoimmune or inflammatory conditions). Also provided are combination therapies comprising such structurally-stabilized and / or cysteine-reactive peptides and inhibitors of the DNA damage response pathway, such as an ATM kinase inhibitor, ATR kinase inhibitor, CHK1 / 2 inhibitor, or PARP inhibitor; or an inhibitor of MCL-1, or a selective inhibitor of BCL-2, or an inhibitor of BCL-2 / BCL-XL, for the treatment of BFL-1-expressing or -dependent cancers (e.g., AML), BFL-1 and MCL-1-expressing or -dependent cancers, or diseases of cellular excess (e.g., autoimmune or inflammatory conditions).

The present application relates to the technical field of medicine, in particular to the application of gansix triol A in the preparation of a drug for treating gastric cancer and / or non-small cell lung cancer, gansix triol A plays an anti-gastric cancer role by selectively inhibiting the proliferation of gastric cancer MGC-803 cells and inhibiting angiogenesis, the mechanism involves inhibiting the VEGF / VEGFR2 signal pathway and inducing cell apoptosis; the mechanism of gansix triol A in inhibiting the VEGF / VEGFR2 signal pathway is similar to that of bevacizumab; gansix triol A plays an anti-non-small cell lung cancer role by selectively inhibiting the proliferation of non-small cell lung cancer A549 cells, the mechanism involves inhibiting the MAPK / ERK signal pathway and inducing cell apoptosis. The present application finds that the cytotoxic activity of gansix triol A on MGC-803 cells and A549 cells is significantly stronger than that of tanshinone IIA; gansix triol A has an anti-tumor effect of "one drug with double targets, double inhibition" and "high efficiency and low toxicity".

The invention discloses a phenyl-substituted pyrazolopyridine compound as well as a preparation method and application thereof, and belongs to the technical field of medicinal chemistry. The structure of the compound is as follows: # imgabs 0 #, wherein R1 is any one of the following structures: # imgabs 1 #; and R2 is any one of the following structures: # imgabs2. The compound has the beneficial effects that the compound has a proliferation inhibition effect on various tumor cells and can selectively inhibit proliferation of triple negative breast cancer cells MDA-MB-468, the half inhibitory concentration IC50 of the compound 8 is 2.500 M, the selection index SI is 8.428, and the compound 8 can be deeply developed as a lead compound for resisting triple negative breast cancer.

The present invention relates to a substituted pyrimidine-fused ring inhibitor, a method for preparing same, and use thereof. Specifically, the compound of the present invention has a structure represented by formula (I). Further disclosed are a method for preparing the compound, and use of the compound as a KRAS mutation inhibitor. The compound has a good selective inhibition effect on KRAS mutation and has better pharmacodynamic and pharmacokinetic performance and lower toxic and side effects.

Myotonic Dystrophy type 1 (DM1) is an inherited disease characterized by multi-systemic symptoms, particularly in skeletal muscles (progressive weakness and atrophy, myotonia). The inventors screened 7 500 bioactive compounds for their ability to improve the myogenic fusion and reduce the molecular hallmarks of DM1 skeletal muscle cells. The inventors found that five compounds, all inhibiting HDAC6, a cytoplasmic histone deacetylase, were effective at the micromolar range in normalizing the myogenic fusion, reducing the number of nuclear foci of mutant DMPK mRNA, decreasing the expression level of DMPK mRNA, restoring the splicing of several genes, and increasing the acetylation of SMAD3, a transcription factor involved in muscle development. The effects of HDAC6 inhibitors were observed both in immortalized and hiPSC-derived skeletal muscle cells from DM1 patients, and in different stages of differentiation. Thus, the present invention relates to the use of selective HDAC6 inhibitors for the treatment of DM1.

The invention relates to the technical field of medicines, in particular to fused tricyclic substituted isoxazolidinyl urea derivatives, pharmaceutically acceptable salts, stereoisomers, pharmaceutical compositions and application thereof. The structure of the fused tricyclic substituted isoxazolidinyl urea derivative is as shown in a formula (I). The fused tricyclic substituted isoxazolidinyl urea derivative disclosed by the invention has obvious TrkA kinase and cell inhibition activity and selective inhibition activity.

Provided are a series of 5,6-dihydrothieno[3,4-h]quinazoline compounds as represented by formula (P) and pharmaceutically acceptable salts thereof, and the use of the compounds or pharmaceutically acceptable salts thereof in the preparation of solid tumor drugs, such as solid tumor drugs associated with selective PLK1 inhibitors.

The present application discloses a TYK2 selective inhibitor and its use, specifically relates to a compound of formula (I) or its tautomer, mesomer, racemate, enantiomer, diastereoisomer or pharmaceutically acceptable salt thereof, and its use for preparing a drug for treating a disease mediated by TYK2.

A substituted pyrazolo[1,5-a]pyrimidine-7-amine derivative having a structure as shown in formula (I) or a pharmaceutically acceptable salt, solvate, stereoisomer, prodrug, or pharmaceutical composition thereof. The derivative has significant CDK9 selective inhibitory activity. #imgabs0#

The invention discloses a heterocyclic-substituted five-and six-membered heteroaryl derivative. The structure of the heterocyclic-substituted five-and six-membered heteroaryl derivative is shown as a formula (I). In addition, the invention also discloses pharmaceutically acceptable salts, stereoisomers, pharmaceutical compositions and applications of the derivatives. The compound provided by the invention has remarkable AAK1 selective inhibitory activity, lower hERG inhibitory effect and more excellent central nervous system permeability, and has very practical value. # imgabs0 #

The present invention relates to pyrazolo[1,5-a][1,3,5]triazine derivatives and pyrazolo[1,5-a]pyrimidine derivatives and / or pharmaceutically acceptable salts thereof, and the use of these derivatives as pharmaceutically active agents, particularly for the prevention and / or treatment of cell proliferative diseases, inflammatory diseases, immunological diseases, cardiovascular diseases, and infectious diseases. Furthermore, the present invention relates to pharmaceutical compositions comprising at least one of the pyrazolo[1,5-a][1,3,5]triazine derivatives and pyrazolo[1,5-a]pyrimidine derivatives and / or pharmaceutically acceptable salts thereof.

The invention relates to the field of antitumor drugs, in particular to a benzimidazole spleen tyrosine kinase inhibitor as well as a preparation method and application thereof. The inhibitor has a molecular structure as shown in a formula 1, in the formula 1, an R0 group is an R1 group containing an amide group, the R1 group is selected from at least one of the following groups, and an R3 group is selected from at least one of the following groups: H, F, Cl and Br; according to the benzimidazole inhibitor, the structure of the benzimidazole inhibitor can be optimized by introducing the R1 group of acylamino and the R2 group of multiple cyclic structures, so that efficient selective inhibition on spleen tyrosine kinase (Syk) is realized.

Mcl-1 selective inhibitors, Bcl-2 selective inhibitors, and Mcl-1 / Bcl-2 dual inhibitors and methods of using the same for the treatment of disease are disclosed.

The present disclosure relates to the field of pharmaceutical chemistry, and specifically relates to a crystal form of a selective PARP-1 inhibitor, i.e. a crystal form of a compound represented by formula (I), a preparation method therefor and the use thereof. The crystal form of the compound represented by formula (I) provided by the present disclosure has at least one of the following excellent characteristics: good stability, high purity, good solubility, good dissolution, high bioavailability, low hygroscopicity, good fluidity, good mechanical stress stability, good processability, such as good compressibility, good crystal morphology, good pressure resistance, capability of stable storage, capability of avoiding crystal transformation of a drug during development and storage processes, a simple and reliable preparation method and high development value.

The present invention provides an amide derivative shown as in formula (I) or a tautomer, stereoisomer or pharmaceutically acceptable salt thereof, and a use thereof. In-vitro experimental results show that the compound in the present invention has relatively high MAO-B selective inhibition activity. In-vivo experimental results show that the compound in the present invention can remarkably reduce the weight of a mouse under the condition that the feeding amount is not affected.