公开(公告)号：EP4378936A1

公开(公告)日：2024-06-05

申请号：EP22848701.3

申请日：2022-07-29

申请人： Hinova Pharmaceuticals Inc.

发明人： DU, Wu ,  LI, Xinhai ,  WEN, Kun ,  QIN, Dekun ,  ZHANG, Shaohua ,  CHEN, Song ,  DUAN, Jingyi ,  LV, Haibin ,  LI, Haibo ,  LI, Yu ,  HE, Jinyun ,  CHEN, Muyang ,  LIU, Shijuan ,  FU, Yiwei ,  GUAN, Yikai ,  TU, Zhilin

IPC分类号： C07D401/04 ,  C07D401/14 ,  A61K31/496 ,  A61K31/4439 ,  A61P35/00

CPC分类号： A61K31/454 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K31/53 ,  A61K31/5377 ,  A61K31/519 ,  A61P11/00 ,  A61P17/10 ,  A61P17/14 ,  A61P31/14 ,  A61P35/00 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/10 ,  C07D471/04 ,  C07D487/04 ,  C07D487/08 ,  C07D487/10 ,  C07D491/107 ,  C07D498/04 ,  C07D519/00 ,  C07D401/04 ,  A61K31/4439

摘要： A compound as shown in formula I, or an optical isomer thereof, a solvate thereof, a pharmaceutically acceptable salt thereof, a prodrug thereof, a tautomer thereof, a mesomer thereof, a racemate thereof, an enantiomer thereof, a diastereomer thereof, a mixture form thereof, a metabolite thereof, a metabolic precursor thereof, or an isotope substitute form thereof. TB is a target recognition/binding portion, L is a linking portion, and U is a ubiquitin protease recognition/binding portion, the three portions being connected by means of chemical bonds. The compound can significantly down-regulate mutated androgen receptor (AR) proteins, and has good inhibitory activity on prostate cancer cell lines. The compound of formula I can be used for preparation of a protein degradation targeted chimera for targeted regulation of androgen receptors, and a drug for treating diseases correlated with regulation by androgen receptors, and has particularly good application prospects in drugs for treating prostate cancers and breast cancers.

公开(公告)号：EP3778538A1

公开(公告)日：2021-02-17

申请号：EP19785608.1

申请日：2019-04-12

申请人： Hinova Pharmaceuticals Inc.

发明人： DU, Wu ,  WEN, Kun ,  HE, Jinyun ,  LI, Haibo ,  QIN, Dekun ,  LI, Xinghai ,  CHEN, Yuanwei

IPC分类号： C07B43/06 ,  C07D233/86 ,  C07D401/04 ,  C07D401/06 ,  C07C231/10 ,  C07C233/65 ,  C07C233/58 ,  C07C233/11 ,  C07C233/05

摘要： Disclosed is a novel method for synthesizing deuterated amides and deuterated sulfonamides, the steps being as follows: (1) adding a compound M, DMAP, R 3 -X to a solvent to obtain a compound N after a reaction is complete; (2) adding the compound N, R 4 -NH-R 5 , or a salt and base thereof to a solvent, and purifying after a reaction is complete to obtain a compound I. The method has mild reaction conditions and a short synthesis route, and a product may be obtained in only two steps; the method may be applied to raw materials which are not suitable for existing methods, and may increase synthesis efficiency; the method may be suitable for many amide compounds, has strong universality, and provides a novel option for the preparation of deuterated amide and sulfonamide compounds.

公开(公告)号：EP3971176A1

公开(公告)日：2022-03-23

申请号：EP20809358.3

申请日：2020-05-15

申请人： Hinova Pharmaceuticals Inc.

发明人： DU, Wu ,  LV, Haibin ,  LI, Haibo ,  QIN, Dekun ,  AI, Chaowu ,  LI, Yu ,  DUAN, Jingyi ,  TU, Zhilin ,  ZHANG, Chengzhi ,  CHEN, Yuanwei ,  LI, Xinghai

IPC分类号： C07D401/04 ,  C07D307/52 ,  C07D235/06 ,  C07D207/16 ,  A61K31/4025 ,  A61P35/00

摘要： An aromatic amine androgen receptor (AR) and BET targeting protein degradation chimera compound and its use. Specifically provided is a compound represented by formula I. Experimental results show that the compound can target and degrade both AR and BRD4, and down-regulate the expression of AR and BRD4 proteins; the compound can inhibit the proliferation of a variety of prostate cancer cells; the compound can inhibit the proliferation of a prostate cancer cell line LNCaP/AR, which overexpresses the AR, and can achieve a good inhibition effect on a prostate cancer cell line 22RV1, which is resistant to a marketed prostate cancer drug (enzalutamide); the compound also shows good metabolic stability, and has a good application prospect in the preparation of an AR and/or BET protein degradation targeting chimera, and a drug for the treatment of related diseases regulated by the AR and BET.

公开(公告)号：EP3957633A1

公开(公告)日：2022-02-23

申请号：EP20791055.5

申请日：2020-04-16

申请人： Hinova Pharmaceuticals Inc.

发明人： DU, Wu ,  WEN, Kun ,  FU, Yiwei ,  LV, Haibin ,  HE, Jinyun ,  QIN, Dekun ,  LI, Yu ,  DUAN, Jingyi ,  LI, Yong ,  AI, Chaowu ,  TU, Zhilin ,  CHEN, Yuanwei ,  LI, Xinghai ,  LI, Haibo

IPC分类号： C07D403/12 ,  C07D401/14 ,  C07D239/42 ,  C07D411/12 ,  A61K31/4439 ,  A61P35/00

摘要： The present invention relates to a class of bifunctional chimeric heterocyclic compounds for targeted degradation of androgen receptors and use thereof, and specifically provides a compound of formula (I), or an isotopic compound thereof, or an optical isomer thereof, or a tautomer thereof, or a pharmacologically acceptable salt thereof, or a prodrug thereof, or a solvate thereof, wherein ARB is an androgen receptor recognition/binding part, L is a link part, and U is a ubiquitin protease recognition/binding part; and the three parts are connected by means of chemical bonds. The compound can perform the targeted degradation on androgen receptors in prostate cancer cells, and suppress the proliferation of the prostate cancer cells, and also show good metabolic stability and pharmacokinetic properties. The compound has good application prospect in the preparation of targeted chimeras for protein degradation of androgen receptors and in the preparation of drugs for treating the related diseases regulated by the androgen receptors.

公开(公告)号：EP3950678A1

公开(公告)日：2022-02-09

申请号：EP20784231.1

申请日：2020-03-31

申请人： Hinova Pharmaceuticals Inc.

发明人： DU, Wu ,  LV, Haibin ,  QIN, Dekun ,  LI, Haibo ,  LI, Yu ,  TU, Zhilin ,  CHEN, Yuanwei ,  LI, Xinghai

IPC分类号： C07D231/12 ,  C07D261/08 ,  C07D413/04 ,  C07D413/12 ,  C07D413/14 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D417/12 ,  C07D498/04 ,  A61K31/4155 ,  A61K31/422 ,  A61K31/423 ,  A61K31/427 ,  A61K31/4439 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K31/4355 ,  A61P35/00

摘要： Provided are an aromatic amine compound and a use thereof in the preparation of AR and BRD4 dual inhibitors and regulators. Specificially provided is the the compound shown in formula I, said compound having dual inhibitory effects on AR and BRD4. The compound is not only capable of inhibiting the proliferation of androgen receptor AR multi-expressed prostate cancer cell line LNCAP/AR, but also shows good inhibitory effects on prostate cancer lines VCaP and RRRV1 which are resistant to prostate cancer drugs (enzalutamide) on the market. The compound is itself a compound capable of simultaneously identifying AR and BRD4 dual targets and can be used as a dual AR/BRD4 inhibitor, and is also capable of being used for preparing proteolysistargeting chimeras (PROTACs) for inducing the degradation of AR/BRD4 dual targets, and has good propects for application in the preparation of drugs for the treatment of AR and BRD4-related diseases.

公开(公告)号：EP3730484A1

公开(公告)日：2020-10-28

申请号：EP18890728.1

申请日：2018-12-20

申请人： Hinova Pharmaceuticals Inc.

发明人： DU, Wu ,  AI, Chaowu ,  LI, Yu ,  WEN, Kun ,  LV, Haibin ,  REN, Wen ,  HE, Jinyun ,  QIN, Dekun ,  LI, Xinghai ,  CHEN, Yuanwei

IPC分类号： C07D271/08 ,  C07D413/12 ,  A61P27/12 ,  A61P25/00 ,  A61P37/02 ,  A61K31/4245 ,  A61P35/00

摘要： Provided is a compound represented by formula (I). Also provided are a pharmaceutical composition containing the compound of formula (I) and use of the compound in preparing indoleamine-2,3-dioxygenase (IDO) inhibitor drugs. The compound or the pharmaceutical composition thereof can be used for preparing drugs for preventing and/or treating diseases having pathological features of IDO-mediated tryptophan metabolic pathways.