Abstract: Provided are a solid form of a Rho-associated protein kinase inhibitor (6-(4-(4-(1H-pyrazol-4-yl)phenylamino)pyrimidin-2-yl)-1-methyl-1H-indol-2-yl)(3,3-difluoroazetidin-1-yl)methanone or a solvate thereof, a method for preparing the solid form, a pharmaceutical composition comprising the solid form, and a use of the solid form as a Rho-associated protein kinase (ROCK) inhibitor, preferably a selective ROCK2 inhibitor.

Abstract: The disclosure discloses a linker compound, a polyethylene glycol-linker conjugate and a derivative thereof, and a polyethylene glycol-linker-drug conjugate. The linker compound as well as the conjugate thereof with the polyethylene glycol and the derivative thereof may be used for modifying a drug, and a modification reaction is simple and easy to carry out. Moreover, a reaction yield is high, and an application range of the modified drug is wide. The modified drugs gradually degrade from a chain of the conjugate in vivo, and may stay in a lesion (such as a cancer site) for a longer period of time, achieving purposes of sustained and controlled release, reducing an administration frequency, and greatly improving a bioavailability of the drug and a patient compliance.

Abstract: The disclosure provides a multi-arm multi-claw polyethylene glycol derivative suitable for click chemistry reactions of general formula I, wherein R is a polyethylene glycol residue having a linear-chain structure, a Y-type structure or a multi-branched structure, R1, R2 and R3 are linking groups, P is an terminal group of non-azido non-alkynyl group, D is —N3 or —C?CH, l is selected from an integer of 1 to 20, and m is selected from an integer of 0 to 19.

Abstract: The present invention relates to a salt of (6-(4-((4-(1H-pyrazol-4-yl)phenypamino)pyrimidin-2 -yl)-1-methyl-1H-indo1-2-yl)(3,3-difluoroazetidine-1-yl)methanone (hereinafter referred to as “compound A”), a solid form of the salt, a method for preparing the solid form, a pharmaceutical composition comprising the solid form, and uses of the solid form as a Rho-associated protein kinase (ROCK) inhibitor, preferably a selective ROCK2 inhibitor.

Abstract: A preparation method for a novel Rho-related protein kinase inhibitor having the structure of formula A and an intermediate in the preparation method.

Abstract: A PEG linker as represented by formula (I), wherein n and m are respectively an integer from 1 to 7, providing the PEG linker with 1 to 49 linking sites. A ligand drug conjugate as represented by formula (II). The conjugate uses the PEG linker to increase a drug loading capacity and drug loading diversity, thereby improving pharmaceutical efficacy.

Abstract: The invention discloses use of a conjugate of polyethylene glycol and a local anesthetic in non-anesthetic analgesia. A local anesthetic is prepared into a prodrug or a sustained release preparation, wherein a high molecular polymer such as polyethylene glycol in the prodrug is covalently bonded with a local anesthetic, and auxiliary materials with a sustained release effect in the sustained release preparation are non-covalently bonded to the local anesthetic. After administration, there is no anesthesia and analgesic effect before the release of the free local anesthetic. After the free local anesthetic is released, an analgesic effect is achieved.

Abstract: The present invention discloses a conjugate of PEG (polyethylene glycol) and rapamycin and use thereof, in particular use in preparation of a medicament for reducing immune response, wherein conjugate of PEG and rapamycin can remarkably lower the generation rate of an antibody directed to foreign immunogen, and reduce excessive immune responses caused by use thereof. The conjugate of PEG and rapamycin has beneficial effects of ensuring and even improving the treatment effect of a therapeutic agent, improving the own immunity of a subject, reducing and even eliminating graft rejection, and is advantageous in a relatively simple preparation process thereof, low cost, easy industrial production, and a high application value.

Abstract: The present invention provides a multi-drug-loading site and high drug-loading capacity ligand-drug conjugate. The ligand-drug conjugate has a structure of general formula (I). The ligand-drug conjugate has the characteristics of high loading capacity, high drug efficacy, low toxicity, and low risks. The ligand-drug conjugate can be used particularly to connect to a low toxicity chemical molecule, thereby extending a therapeutic window. Furthermore, the present invention provides an antibody-drug conjugate molecule. The antibody-drug conjugate molecule has the characteristics of multiple drug-loading ability and high drug-loading capacity, such that the antibody-drug conjugate can carry a large amount of a low toxicity chemical molecule and achieve a therapeutic effect without depending on antibody targeting or high toxicity chemicals.

Abstract: A new compound of general formula (X) inhibiting and inducing degradation of an EGFR and ALK, and a pharmaceutical composition containing said compound. The compound and the pharmaceutical composition can be used for treating diseases related to the EGFR and the ALK kinase, such as cancer. The present invention further provides the preparation and use of the compound.

Abstract: The present invention relates to a solid form of 5-((2-ethynyl-5-isopropylpyridin-4-yl)oxy)pyrimidine-2,4-diamine or a hydrate thereof, a method for preparing the solid form, a pharmaceutical composition comprising the solid form, and a use of the solid form for the prevention or treatment of a disease modulated by P2X3 and/or P2X2/3 receptor antagonists.

Abstract: The present invention relates to a salt of 5-((2-ethynyl-5-isopropylpyridin-4-yl)oxy)pyrimidine-2,4-diamine and a solid form thereof, a method for preparing the solid form and a pharmaceutical composition comprising the solid form, as well as a use of the solid form for preventing or treating diseases modulated by P2X3 and/or P2X2/3 receptor antagonists.

Abstract: The present invention discloses a conjugate of PEG (polyethylene glycol) and rapamycin and use thereof, in particular use in preparation of a medicament for reducing immune response, wherein conjugate of PEG and rapamycin can remarkably lower the generation rate of an antibody directed to foreign immunogen, and reduce excessive immune responses caused by use thereof. The conjugate of PEG and rapamycin has beneficial effects of ensuring and even improving the treatment effect of a therapeutic agent, improving the own immunity of a subject, reducing and even eliminating graft rejection, and is advantageous in a relatively simple preparation process thereof, low cost, easy industrial production, and a high application value.

Abstract: The disclosure discloses a linker compound, a polyethylene glycol-linker conjugate and a derivative thereof, and a polyethylene glycol-linker-drug conjugate. The linker compound as well as the conjugate thereof with the polyethylene glycol and the derivative thereof may be used for modifying a drug, and a modification reaction is simple and easy to carry out. Moreover, a reaction yield is high, and an application range of the modified drug is wide. The modified drugs gradually degrade from a chain of the conjugate in vivo, and may stay in a lesion (such as a cancer site) for a longer period of time, achieving purposes of sustained and controlled release, reducing an administration frequency, and greatly improving a bioavailability of the drug and a patient compliance.

Abstract: The invention discloses use of a conjugate of polyethylene glycol and a local anesthetic in non-anesthetic analgesia. A local anesthetic is prepared into a prodrug or a sustained release preparation, wherein a high molecular polymer such as polyethylene glycol in the prodrug is covalently bonded with a local anesthetic, and auxiliary materials with a sustained release effect in the sustained release preparation are non-covalently bonded to the local anesthetic. After administration, there is no anesthesia and analgesic effect before the release of the free local anesthetic. After the free local anesthetic is released, an analgesic effect is achieved.

Abstract: The disclosure provides a multi-arm multi-claw polyethylene glycol derivative suitable for click chemistry reactions of general formula I, wherein R is a polyethylene glycol residue having a linear-chain structure, a Y-type structure or a multi-branched structure, R1, R2 and R3 are linking groups, P is an terminal group of non-azido non-alkynyl group, D is —N3 or —C?CH, l is selected from an integer of 1 to 20, and m is selected from an integer of 0 to 19.

Abstract: The present invention relates to the technical field of medicine, in particular to a conjugate of dezocine and polyethylene glycol and a pharmaceutical composition thereof. The conjugate of dezocine and water-soluble oligomer provided by the present invention has better pharmacokinetic properties and a high drug absorption degree, may reduce the side effects of the drug, and achieve a smaller administration dosage and a more diverse mode of administration, such as oral administration, in clinic. Compared with dezocine, the conjugate of the present invention has a stronger analgesic effect and a longer analgesic duration, may reduce the frequency of drug administration, improve patient compliance, and has advantages in effectiveness and safety of the drug, as well as drug tolerance, etc.

Abstract: The present invention provides a multi-drug-loading site and high drug-loading capacity ligand-drug conjugate. The ligand-drug conjugate has a structure of general formula (I). The ligand-drug conjugate has the characteristics of high loading capacity, high drug efficacy, low toxicity, and low risks. The ligand-drug conjugate can be used particularly to connect to a low toxicity chemical molecule, thereby extending a therapeutic window. Furthermore, the present invention provides an antibody-drug conjugate molecule. The antibody-drug conjugate molecule has the characteristics of multiple drug-loading ability and high drug-loading capacity, such that the antibody-drug conjugate can carry a large amount of a low toxicity chemical molecule and achieve a therapeutic effect without depending on antibody targeting or high toxicity chemicals.

Abstract: A conjugate represented by general formula (I), wherein R0 is a C1-6 alkyl, B is an anesthetic, and A is a linking group, and a quaternary ammonium salt is formed at the linking position between B and R0. The conjugate has a prolonged analgesic effect, and can be used in postoperative analgesia or treatment for chronic pain.

Abstract: The present invention relates to the technical field of medicine, in particular to a conjugate of dezocine and polyethylene glycol and a pharmaceutical composition thereof. The conjugate of dezocine and water-soluble oligomer provided by the present invention has better pharmacokinetic properties and a high drug absorption degree, may reduce the side effects of the drug, and achieve a smaller administration dosage and a more diverse mode of administration, such as oral administration, in clinic. Compared with dezocine, the conjugate of the present invention has a stronger analgesic effect and a longer analgesic duration, may reduce the frequency of drug administration, improve patient compliance, and has advantages in effectiveness and safety of the drug, as well as drug tolerance, etc.