Abstract: The present invention relates to the field of pharmaceutical technology, and specifically to substituted pyridotriazole compounds and the preparation method and use thereof. The present description discloses substituted pyridotriazole compounds having an inhibitory effect on RIPK1 and/or MLK, or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof. The compound is represented by formula (I), wherein the definitions of respective groups in the formula are detailed in the description. In addition, the present invention further discloses a pharmaceutical composition comprising the compound, and use thereof in the preparation of a medicine for treating RIPK1-related diseases or disorders.

Abstract: The present invention relates to the field of chemical medicines. Disclosed are a 1H-pyrrole-2-amide derivative and a use thereof. In order to obtain a specific inhibitor for an m6A-modified RNA reader protein YTHDC1 of AML, the present invention provides a 1H-pyrrole-2-amide derivative as shown in formula I, wherein said derivative has high inhibitory activity against YTHDC1. In-vitro experiments prove that said derivative can effectively inhibit the proliferation of acute myeloid leukemia cells, significantly arrest a cell cycle of the acute myeloid leukemia cells in the G0/G1 phase, and induce differentiation and apoptosis of the acute myeloid leukemia cells. A compound and a salt thereof or a pharmaceutical composition of the 1H-pyrrole-2-amide derivative of the present invention provide new options for anti-tumor drug development targeting YTHDC1 in the art, and have good application prospects.

Abstract: The present application is directed to PDGF-D prodomain or its mutant or fusion. The present application is also directed to a process or use of the PDGF-D prodomain or its mutant or fusion for inhibiting PDGFR phosphorylation, for inhibiting cell proliferation stimulated by PDGF, or for preventing and/or treating diseases associated therewith.

Abstract: A phenothiazine ferroptosis inhibitor, a preparation method therefor and an application thereof. Specifically provided is a compound represented by formula I, or a salt thereof, or a stereoisomer thereof. The synthesized phenothiazine compound has a good inhibitory effect on ferroptosis and has good drug safety. Moreover, the compound can be used to prepare a ferroptosis inhibitor, and can also be used to prepare a drug for treating diseases related to ferroptosis, such as neurodegenerative diseases, tumors, tissue ischemia reperfusion injury, stroke, cardiovascular diseases, renal failure, and diabetic complications.

Abstract: A class of ketoamide derivatives and pharmaceutical uses thereof are provided. Specifically provided are the compound represented by formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or an optical isomer thereof, or a deuterated compound thereof. The compound can effectively inhibit the activity of SARS-CoV-2 Mpro, and can be used in the manufacturer of SARS-CoV-2 Mpro inhibitors, blocking the replication and transcription of SARS-CoV-2 virus in patients. The compound can be used in preparing SARS-CoV-2 Mpro inhibitors, anti-SARS-CoV-2 medicaments, as well as the medicaments for preventing and/or treating Corona Virus Disease 2019 (COVID-19).

Abstract: A method for digital twin virtual-reality synchronization mapping of a mechanical arm comprises acquiring a virtual mechanical arm model built based on an actual mechanical arm in a virtual environment, where the virtual mechanical arm model is configured to map the actual mechanical arm; acquiring real motion information collected when the actual mechanical arm moves; constructing a training set and a test set based on the real motion information; training a target multilayer perceptron model based on the training set, and testing the target multilayer perceptron model based on the test set, where the target multilayer perceptron model is configured to predict a motion of the virtual mechanical arm model in the virtual environment; and deploying the target multilayer perceptron model on the actual mechanical arm when the target multilayer perceptron model meets a preset condition. According to this method, operation accuracy and efficiency of the mechanical arm are improved.

Abstract: A method for intelligently controlling a mechanical arm includes building a twin model of a mechanical arm, and extracting a state parameter and an action parameter corresponding to task characteristics from the twin model; determining a reward function corresponding to the task characteristics; training a twin delayed deep deterministic policy gradient (TD3) reinforcement learning model; simulating in the twin model based on a physical state parameter of the mechanical arm by using the TD3 reinforcement learning model, to obtain a controllable parameter; and controlling the mechanical arm to execute a corresponding task by using the controllable parameter. The TD3 reinforcement learning model is built based on the state parameter and the action parameter corresponding to the task characteristics and the reward function corresponding to the task characteristics, which can adapt to a dynamically changing environment and requirements for multiple tasks.

Abstract: Provided are a 5-substituted indole 3-amide derivative, a preparation method and a use thereof, belonging to the field of medicine. A compound represented by formula I or a pharmaceutically acceptable salt thereof is provided. This type of compound can significantly inhibit the activity of RIPK1 kinase, has high selectivity and excellent safety, serves as a RIPK1 kinase inhibitor, and can be used as a potential therapeutic drug for inflammation, immune diseases, tumors and neurodegenerative diseases. TNF?-induced SIRS model experiments proved that the compound can inhibit a RIPK1 kinase in vivo. Pharmacokinetic results showed that this series of compounds has excellent pharmacokinetic properties, thus providing a novel strategy and means for disease treatments targeting RIPK1.

Abstract: Provided in the present invention are a salt of an arylaminopurine derivative represented by Formula (2), a preparation method therefor and the use thereof. The salt obtained in the present invention has good crystallinity and significantly improved solubility relative to that in the free form, and the preferred salt and crystal form have low hygroscopicity and can exist stably. Therefore, compared with the free form of arylaminopurine derivatives or other salts, it is easier to prepare same into a medicine.

Abstract: A phenothiazine ferroptosis inhibitor, a preparation method therefor and an application thereof. Specifically provided is a compound represented by formula I, or a salt thereof, or a stereoisomer thereof. The synthesized phenothiazine compound has a good inhibitory effect on ferroptosis and has good drug safety. Moreover, the compound can be used to prepare a ferroptosis inhibitor, and can also be used to prepare a drug for treating diseases related to ferroptosis, such as neurodegenerative diseases, tumors, tissue ischemia reperfusion injury, stroke, cardiovascular diseases, renal failure, and diabetic complications.

Abstract: 10H-phenothiazine derivatives capable of inhibiting ferroptosis has structural formula (I). The derivatives, pharmaceutically acceptable salts thereof, crystal forms thereof, or solvates thereof exhibit inhibitory effect on ferroptosis, and therapeutic effect on a rat model of focal cerebral ischemia and thus can be used as a main active ingredient in the preparation of ferroptosis inhibitors. The compounds and the inhibitors prepared by the compounds have good medicinal potential and are expected to be used as drug candidates for the treatment of stroke.

Abstract: The present invention discloses a compound shown in formula I or a stereoisomer, pharmaceutically acceptable salt, crystal form, solvate or isotopologue thereof. The compound of the present invention shows excellent inhibition activity against histone deacetylases, has remarkable inhibition effects on cancer cells, and provides a new choice of drugs used for the clinic treatment and diseases related to the abnormal activity of histone deacetylases.

Abstract: 10H-phenothiazine derivatives capable of inhibiting ferroptosis has structural formula (I). The derivatives, pharmaceutically acceptable salts thereof, crystal forms thereof, or solvates thereof exhibit inhibitory effect on ferroptosis, and therapeutic effect on a rat model of focal cerebral ischemia and thus can be used as a main active ingredient in the preparation of ferroptosis inhibitors. The compounds and the inhibitors prepared by the compounds have good medicinal potential and are expected to be used as drug candidates for the treatment of stroke.

Abstract: The present invention discloses a compound shown in formula I or a stereoisomer, pharmaceutically acceptable salt, crystal form, solvate or isotopologue thereof. The compound of the present invention shows excellent inhibition activity against histone deacetylases, has remarkable inhibition effects on cancer cells, and provides a new choice of drugs used for the clinic treatment and diseases related to the abnormal activity of histone deacetylases.