575 results about "Selective inhibition" patented technology

A PI3Kα inhibitor and the use thereof. The inhibitor has a structure as shown in formula (I), has a good selective inhibitory activity on mutant PI3Kα, and can be used for preparing anti-tumor drugs.

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.

The invention belongs to the technical field of chemical synthesis, and particularly relates to a preparation method of N, N '-bis (2-bromine / chloroethyl) diamino phosphonic acid (1-methyl-4-nitro-1H-imidazole-2-cyanogen) methyl ester, 4-methylimidazole is used as a raw material, and (1-methyl-4-nitro-1H-imidazole-2-cyanogen) methanol is synthesized through nitration, methyl substitution, bromine substitution, bromomethyl substitution, hydrolysis and substitution; the preparation method comprises the following steps: reacting phosphorus oxychloride with ethyl amine salt to synthesize N, N '-bis (2-bromoethyl) diamino phosphonic acid and N, N'-bis (2-chloroethyl) diamino phosphonic acid, and finally condensing to obtain N, N '-bis (2-bromoethyl) diamino phosphonic acid (1-methyl-4-nitro-1H-imidazole-2-cyanogen) methyl ester and N, N'-bis (2-chloroethyl) diamino phosphonic acid (1-methyl-4-nitro-1H-imidazole-2-cyanogen) methyl ester. The compound can selectively inhibit ovarian cancer cell proliferation under a hypoxia condition.

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.

This application relates to a series of novel compounds that are selective inhibitors of phosphodiesterase type 9 ("PDE9") for the treatment of chronic heart failure. More particularly, the application relates to pyrazolo[3,4-d]pyrimidinone compounds for use in the treatment and prevention of chronic heart failure.

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.

The present invention relates to inhibitors of polo-like kinase 1 ("PLK1"). In particular, the present invention relates to compounds that selectively inhibit the activity of PLK1, pharmaceutical compositions comprising a therapeutically effective amount of the compounds, and methods of use therefor, such as methods for treating PLK1 -mediated diseases and disorders, such as cancer.

The present invention relates to a pharmaceutical composition for oral administration, for example in the form of a tablet or a powder suitable to be filled into a capsule shell, comprising 2-(isoindolin-2-ylmethyl)-5-((1-(methylsulfonyl)- piperidin-4-yl)methoxy)-4H-pyran-4-one (I) or a pharmaceutically acceptable salt thereof as an active ingredient. Compound (I) or a pharmaceutically acceptable salt thereof is a selective inhibitor of CYP11A1 enzyme and is useful in the treatment of hormonally regulated diseases such as cancer including prostate cancer and breast cancer.

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.

Cyclic compounds that selectively inhibit KRAS were found. Moreover, cyclic compounds were found to interact with an amino acid residue specific to KRAS.

The invention relates to the field of medicinal chemistry, in particular to a substituted thiazolidinedione compound and application thereof. Pharmacological test results show that when the concentration of the synthesized compound is 10 [mu] M, the inhibition rate of the synthesized compound on SphK1 is weaker than that of a positive control drug PF-543, but the inhibition rate of most of the synthesized compounds on SphK2 is superior to that of a positive control drug K145, and the synthesized compound shows an ideal selective inhibition effect on SphK2.

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 provides preparation and application of a novel MAO-B inhibitor containing a tetrahydronaphthalene-1-amine structure, and belongs to the field of medicine. The derivative is a compound as shown in a formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof. The compound disclosed by the invention can be used for inhibiting MAO (monoamine oxidase), and particularly can be used for selectively inhibiting MAO-B; the compound can be used for treating Parkinson's disease, Alzheimer's disease, emotional disorder and other diseases, and has a good application prospect.

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.

To provide 5- and 6-azaindole compounds for inhibition of BCR-ABL tyrosine kinases.SOLUTION: The present disclosure relates to compounds and compositions for inhibition of Bcr-Abl tyrosine kinases, methods of preparing the compounds and compositions, and their use in the treatment of various cancers, such as chronic myeloid leukemia (CML). Provided herein are compounds and compositions that selectively inhibit Bcr-Abl tyrosine kinases and that are useful for treating disorders mediated by Bcr-Abl tyrosine kinases.SELECTED DRAWING: None

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.

A compound can have a structure of Formula A, or derivative thereof, salt thereof, or stereoisomer thereof, or having any chirality at any chiral center, or tautomer, polymorph, solvate, or combination thereof:wherein ring A is a phenyl, indolyl, naphthyl, or benzothiazolyl; X is S, SO, or SO2; Y is a linker or bond; Z is CH, CR2, or N; Z1 is C or N to form an imidazopyridine; each Z2, Z3, or Z4 is independently CH, CR2, or N; each Z5 or Z6 is C or CH; each R1, R2, and R3 is independently a substituent, and at least one of R1, R2, or R3 is a substituent other than a hydrogen; m is 0, 1, 2, 3, or 4; and n is 0 or a positive integer. The compounds can have specific substituent patterns.

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.

The invention provides a compound as shown in a formula (I) and a racemate, a stereoisomer, a tautomer, an isotope label, nitrogen oxide, a solvate, a polymorphic substance, a metabolite, ester, a prodrug or pharmaceutically acceptable salt thereof. The compound has a good FGFR2 / 3 inhibition effect, can be used for treating or preventing FGFR2 / 3 mediated diseases and diseases, and can be used for preparing medicines for treating or preventing the diseases and diseases. # imgabs0 #

The present disclosure provides intermediates of 1-(1-oxo-1, 2-dihydrophthalazin-6-yl) cycloalkyl-1-carboxamide derivatives, and methods of synthesis thereof. The present invention relates to a 1-(1-oxo-1, 2-dihydrophthalazin-6-yl) cycloalkyl-1-carboxamide derivative compound, which can be used to selectively inhibit the synergistic activity of PRMT5 and MTA in a tumor carrying an MTAPDEL mutation, and a pharmaceutical composition comprising the compound as a therapeutic agent for various diseases, including cancer.

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".