- MODIFIED PROTEINS AND PROTEIN DEGRADERS
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Provided herein are compounds, pharmaceutical compositions, and methods for binding or degrading target proteins. Further provided herein are compounds having a DNA damage-binding protein 1 (DDB1) binding moiety. Some such embodiments include a linker. Some such embodiments include a target protein binding moiety. Further provided herein are ligand-DDB1 complexes. Further provided herein are in vivo modified DDB1 proteins.
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Paragraph 00663-00665
(2021/12/08)
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- Discovery and Pre-Clinical Characterization of Third-Generation 4-H Heteroaryldihydropyrimidine (HAP) Analogues as Hepatitis B Virus (HBV) Capsid Inhibitors
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Described herein are the discovery and structure-activity relationship (SAR) studies of the third-generation 4-H heteroaryldihydropyrimidines (4-H HAPs) featuring the introduction of a C6 carboxyl group as novel HBV capsid inhibitors. This new series of 4-H HAPs showed improved anti-HBV activity and better drug-like properties compared to the first- and second-generation 4-H HAPs. X-ray crystallographic study of analogue 12 (HAP_R01) with Cp149 Y132A mutant hexamer clearly elucidated the role of C6 carboxyl group played for the increased binding affinity, which formed strong hydrogen bonding interactions with capsid protein and coordinated waters. The representative analogue 10 (HAP_R10) was extensively characterized in vitro (ADMET) and in vivo (mouse PK and PD) and subsequently selected for further development as oral anti-HBV infection agent.
- Qiu, Zongxing,Lin, Xianfeng,Zhang, Weixing,Zhou, Mingwei,Guo, Lei,Kocer, Buelent,Wu, Guolong,Zhang, Zhisen,Liu, Haixia,Shi, Houguang,Kou, Buyu,Hu, Taishan,Hu, Yimin,Huang, Mengwei,Yan, S. Frank,Xu, Zhiheng,Zhou, Zheng,Qin, Ning,Wang, Yue Fen,Ren, Shuang,Qiu, Hongxia,Zhang, Yuxia,Zhang, Yi,Wu, Xiaoyue,Sun, Kai,Zhong, Sheng,Xie, Jianxun,Ottaviani, Giorgio,Zhou, Yuan,Zhu, Lina,Tian, Xiaojun,Shi, Liping,Shen, Fang,Mao, Yi,Zhou, Xue,Gao, Lu,Young, John A. T.,Wu, Jim Zhen,Yang, Guang,Mayweg, Alexander V.,Shen, Hong C.,Tang, Guozhi,Zhu, Wei
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supporting information
p. 3352 - 3371
(2017/05/05)
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- Imidazole [2, 1-b] thiazole derivative as well as preparation method and application thereof
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The invention belongs to the field of chemical pharmaceuticals, and particularly relates to an imidazole [2, 1-b] thiazole derivative as well as a preparation method and an application thereof. The structure of the imidazole [2, 1-b] thiazole derivative i
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Paragraph 0144; 0145; 0146; 0156; 0157
(2017/01/02)
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- Discovery of imidazo[2,1- b ]thiazole HCV NS4B inhibitors exhibiting synergistic effect with other direct-acting antiviral agents
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The design, synthesis, and SAR studies of novel inhibitors of HCV NS4B based on the imidazo[2,1-b]thiazole scaffold were described. Optimization of potency with respect to genotype 1b resulted in the discovery of two potent leads 26f (EC50 = 16
- Wang, Ning-Yu,Xu, Ying,Zuo, Wei-Qiong,Xiao, Kun-Jie,Liu, Li,Zeng, Xiu-Xiu,You, Xin-Yu,Zhang, Li-Dan,Gao, Chao,Liu, Zhi-Hao,Ye, Ting-Hong,Xia, Yong,Xiong, Ying,Song, Xue-Jiao,Lei, Qian,Peng, Cui-Ting,Tang, Hong,Yang, Sheng-Yong,Wei, Yu-Quan,Yu, Luo-Ting
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p. 2764 - 2778
(2015/04/14)
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- Novel 6-amino acid heteroaryldihydropyrimidines for the treatment and prophylaxis of hepatitis B virus infection
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The invention provides novel compounds having the general formula: wherein R1, R2, R3, R4 and A are as described herein, compositions including the compounds and methods of using the compounds.
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Paragraph 0333; 0334
(2015/02/19)
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- 6-AMINO ACID HETEROARYLDIHYDROPYRIMIDINES FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION
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The invention provides novel compounds having the general formula:, wherein R1, R2, R3, R4 and A are as described herein, compositions including the compounds and methods of using the compounds.
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Page/Page column 98; 99
(2014/03/26)
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- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS AND USES THEREOF
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The present invention relates to compounds of formula (I), or pharmaceutically acceptable salts, prodrugs, salts of prodrugs, or combinations thereof, wherein R1, R2, R3, R4, and L2, are defined in th
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Page/Page column 127
(2008/06/13)
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- QUINAZOLINE DERIVATIVES
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The invention concerns quinazoline derivatives of Formula (I) or a pharmaceutically-acceptable salt, solvate or pro-drug thereof, wherein each of X1, p, R1, q, R2, R3, R4, R5, Ring A, r and R6 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders or in the treatment of disease states associated with angiogenesis and/or vascular permeability.
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Page/Page column 163-164
(2008/06/13)
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- Thiazole-4-carboxyamide derivatives
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The present invention is concerned with novel thiazole 4-carboxyamide derivatives of the general formula (I) and with methods for the preparation thereof, which compounds are useful as metabotropic glutamate receptor antagonists: wherein R1 to R4 are as defined in the specification.
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Page/Page column 56
(2008/06/13)
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- Pyridine-2-carboxyamide derivatives
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The invention relates to compounds of formula I: wherein R1 to R3 are as defined in the specification, to processes for their preparation, to pharmaceutical compositions containing them, and to methods for treating CNS disorders.
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Page/Page column 25
(2008/06/13)
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- ARYL SULFONES AND USES RELATED THERETO
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Aryl sulfone compounds of formula (I) and (II) are described and have therapeutic utility, particularly in the treatment of diabetes, obesity and related conditions and disorders.
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Page/Page column 95
(2010/02/14)
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