224results about How to "Good pharmacokinetic properties" patented technology

Described herein are compounds that are useful as caspase inhibitors having the formula: wherein Ring A is an optionally substituted piperidine, tetrahydroquinoline or tetrahydroisoquinoline ring; R1 is hydrogen, CN, CHN2, R, or CH2Y; R is an optionally substituted group selected from an aliphatic group, an aryl group, or an aralkyl group; Y is an electronegative leaving group; R2 is CO2H, CH2CO2H, or esters, amides or isosteres thereof; and R3 is hydrogen, an optionally substituted aryl group, an optionally substituted aralkyl group, or an optionally substituted C1-6 aliphatic group, R4 is an optionally substituted group selected from an aryl group or a heterocyclyl group, or R3 and R4 taken together with the nitrogen to which they are attached optionally form a substituted or unsubstituted monocyclic, bicyclic or tricyclic ring.

Compounds comprising peptides capable of binding C3 protein and inhibiting complement activation are disclosed. The compounds comprise compstatin analogs in which the N-terminus contains an added or substituted component that improves (1) the peptide's binding affinity to C3 or its fragments, (2) the peptide's solubility in aqueous liquids, (3) the peptide's plasma stability, (4) the peptide's in vivo retention and/or (5) the peptide's bioavailability, as compared with an unmodified compstatin peptide under equivalent conditions. Pharmaceutical compositions and methods of using the compounds are also disclosed.

The present invention discloses an antibody drug conjugate of a CLDN 18.2-resistant antibody. The structure of the antibody drug conjugate (ADC) is shown as Ab-[(L2)n-L1-D]y in a formula I, wherein Dis a small-molecule cytotoxic drug, L1 and L2 are connected to the drug and the antibody separately, and n is 0 or 1; y represents the average number of D which is coupled to Ab, 0 < y <= 10, and Ab is an antibody which can be specifically bound to human CLDN 18.2, and includes a light-chain variable region (VL) and/or a heavy-chain variable region (VH); and the CLDN 18.2-resistant antibody correspondingly contains at least one specific complementary determining region (CDR) sequence or a mutant sequence of the specific complementary determining region (CDR) sequence in the light-chain variable region (VL) and/or a heavy-chain variable region (VH), and binding of the antibody to CLDN 18.2 is maintained or improved through the mutation. The invention also discloses a ADC-containing pharmaceutical composition and a preparation method and application of ADC. The antibody drug conjugate of the antibody has a large security window and low toxic and side effects, and provides more specific,more effective and better treatment option for tumor patients.

This invention provides caspase inhibitors of formula I:

wherein Z is oxygen or sulfur; R¹is hydrogen, —CHN₂, R, CH₂OR, CH₂SR, or —CH₂Y; Y is an electronegative leaving group; R² is CO₂H, CH₂CO₂H, or esters, amides or isosteres thereof; R³ is a group capable of fitting into the S2 subsite of a caspase enzyme; R⁴ and R⁵ are taken together with the intervening nitrogen to form heterocyclic ring and R is as described in the specification. The compounds are effective inhibitors of apoptosis and IL-1β secretion.

The invention provides an RGD polypeptide coordination complex of a radioactive nuclide label. According to the structure of the coordination complex, the radioactive nuclide is selected from 64Cu, 68Ga, 111In, 62Cu, 67Cu, 67Ga, 86Y, 89Zr or 18F; the ligand is a ligand compound containing an RGD structure, which is shown in a formula (I). The coordination complex has stronger ligand stability and high target/non-target ratio, and the appetency of the ligand with integrin AlphavBeta3 is stronger. The invention further provides a preparation method of the coordination complex, and an application of the coordination complex in preparing tumor developers.

The invention discloses a fused cyanopyridine compound shown as a general formula I-1 or I-2, or a pharmaceutically acceptable salt thereof, or an enantiomer, a diastereoisomer, a tautomer, a torsional isomer, a solvate, a polymorphic substance or a prodrug thereof, and a preparation method and a pharmaceutical application of the fused cyanopyridine compound, wherein the definition of each group is shown in the specification.

The invention discloses a novel Tepotinib derivative and a preparation method thereof and an application of the derivative in an antitumor drug. According to the invention, a chiral structure is introduced in molecules, a hydrogen isotope deuterium is introduced in an easily metabolical part in the molecules, and atoms of sulfur, selenium and sulfoxide or groups are introduced in the molecules. The antineoplastic active experiments (having c-Met-expressed tumor cells) on a cell level proves that the compound has excellent antineoplastic activity, and the stability of the antineoplastic compound is obviously increased.

This invention provides caspase inhibitors having the formula:

wherein R¹ is CO₂H, CH₂CO₂H, or esters, amides or isosteres thereof; R² and R³ are each independently selected from hydrogen or an optionally substituted C₁–C₆ aliphatic group; and R⁴ and R⁵ are each independently selected from hydrogen, an optionally substituted C₁–C₆ aliphatic group, or R⁴ and R⁵ taken together with the ring to which they are attached form an optionally substituted bicyclic ring. The caspase inhibitors are useful for treating a number of diseases such as cancer, acute inflammatory and autoimmune disorders, ischemic diseases and certain neurodegenerative disorders.

The invention discloses a pyrazolo[1, 5-a]pyridine compound with the structure characteristic shown in the formula (I) or its pharmaceutically acceptable salt, stereoisomer or prodrug molecule and a use thereof. The compound has good in-vitro anti-tubercle bacillus activity, has the minimal inhibitory concentration (MIC) less than 0.1 micrograms per milliliter and partial MIC of 0.01 micrograms per milliliter and has strong inhibition effects on a clinically sorted multi-drug-resistant tuberculosis (MDR-TB) strain. In an in-vivo experiment, at a dosage of 20mg/kg/d, the pyrazolo[1, 5-a]pyridine compound can effectively eliminate H37Ra infection in a mouse and is a novel anti-tuberculosis compound.

The invention belongs to the technical field of medicines and particularly relates to a CDK kinase inhibitor represented as the general formula (I), pharmaceutically-accepatable salt, ester and solvate thereof, and stereisomers thereof. The R1, R2, R3, R4, A1, A2, A3 and n are defined as the specification. The invention also relates to a preparation method of the compounds, a medicine preparation and a medicine composition comprising the compounds, and an application of the compounds, the pharmaceutically accepatable salt, ester and solvate thereof, and the stereisomers thereof in preparation of a medicine for treating and/or preventing cancer-related diseases induced by the CDK kinase.

The present invention relates to deuterated nucleoside derivative, particularly to a compound having a structure represented by a formula I or a pharmaceutically acceptable salt thereof. According to the present invention, the compound represented by the formula I has excellent pharmacokinetic properties and is expected to reduce the clinical dose so as to reduce the treatment and benefit more patients. The formula I is defined in the specification.

The invention belongs to the technical field of medicines, and particularly relates to a compound as shown in the formula (I), and pharmaceutically acceptable salt and ester or a stereisomer thereof.R1, R2, R3, M1, M2, m, n, Q, L, ring A, ring B and ring C are as defined in the specification. The invention further relates to a preparation method of the compounds, and application in preparing medicines for treating and/or preventing related diseases such as non-alcoholic fatty liver disease, primary biliary cirrhosis, lipid metabolism disorders, diabetic complication and malignant tumors mediated by an FXR. The formula (I) is shown in the description.

The present invention relates to ansamycin analogues that are useful, e.g. in the treatment of cancer, B-cell malignancies, malaria, fungal infection, diseases of the central nervous system and neurodegenerative diseases, diseases dependent on angiogenesis, autoimmune diseases or a prophylactic pretreatment for cancer. The present invention also provides methods for the production of these compounds and their use in medicine.

The invention relates to a compound used as a CDK7 kinase inhibitor and application thereof. Specifically, the compound disclosed by the invention has a structure shown as a formula I, and the definitions of all groups and substituents are as described in the specification. The compounds of the present invention are useful as inhibitors of cyclin-dependent kinase 7 (CDK7) for the treatment or prevention of proliferative diseases such as cancer, especially for modulating and treating diseases associated with abnormal activity of cyclin-dependent kinase 7 (CDK7).

There is provided a compound of formula (I) wherein R<1>, R<2a>, R<2b>, R<3a>, R<3b>, R<4>, R<5>, R<6>, A, G and L have meanings given in the description, which compounds are useful as, or are useful as prodrugs of, competetive inhibitors of trypsin-like proteases, such as trombin, and thus, in particular, in the treatment of conditions where inhibition of thrombin is beneficial (e,g. conditions, such as thrombo-embolisms, where inhibition of trombin is required or desired, and/or conditions wherea anticoagulant thererapy is indicated).

The invention relates to the technical field of medicine, in particular to a ketohexokinase (KHK) inhibitor compound, pharmaceutically acceptable salts of the compound, esters of the compound or stereoisomers of the compound, a pharmaceutical composition and preparation containing the compound, the pharmaceutically acceptable salts of the compound, the esters of the compound or the stereoisomers of the compound, and application of the compound, the pharmaceutically acceptable salts of the compound, the esters of the compound or the stereoisomers of the compound to preparation of drugs for treating and/or preventing KHK-mediated diseases and related diseases.