- Discovery of the programmed cell death-1/programmed cell death-ligand 1 interaction inhibitors bearing an indoline scaffold
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Inhibiting the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway is an attractive strategy for tumor immunotherapy. Here, a novel series of indoline-containing compounds were developed, among which, A13 was identified as the most promising PD-1/PD-L1 pathway inhibitor. At the biochemical level, A13 demonstrated strong inhibition of the PD-1/PD-L1 interaction, with an IC50 of 132.8 nM. Notably, it exhibited outstanding immunoregulatory activity, and significantly elevated interferon-γ secretion in a Hep3B/OS-8/hPD-L1 and CD3 T cell co-culture model, without significant toxic effect. Therefore, A13 could be employed as a suitable lead compound for further design of non-peptide inhibitors targeting the PD-1/PD-L1 interaction. In addition, the preliminary structure-activity relationships of these new indoline compounds were investigated in this study, providing valuable information for future drug development.
- Qin, Mingze,Cao, Qi,Wu, Xia,Liu, Chunyang,Zheng, Shuaishuai,Xie, Hongbo,Tian, Ye,Xie, Jun,Zhao, Yanfang,Hou, Yunlei,Zhang, Xian,Xu, Boxuan,Zhang, Haotian,Wang, Xiaobo
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Read Online
- Regioselective Formation of Substituted Indoles: Formal Synthesis of Lysergic Acid
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A Diels–Alder reaction-based strategy for the synthesis of indoles and related heterocycles is reported. An intramolecular cycloaddition of alkyne-tethered 3-aminopyrones gives 4-substituted indolines in good yield and with complete regioselectivity. Additional substitution is readily tolerated in the transformation, allowing synthesis of complex and non-canonical substitution patterns. Oxidative conditions give the corresponding indoles. The strategy also allows the synthesis of carbazoles. The method was showcased in a formal synthesis of lysergic acid.
- Beaudry, Christopher M.,Points, Gary L.,Stout, Kenneth T.
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supporting information
p. 16655 - 16658
(2020/12/01)
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- Indoline compounds and preparing method and application thereof
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The invention belongs to the technical field of medicines, and discloses indoline compounds having a general formula I in which substitutes R1, R2, R3, R4 and R5 are defined in the specification and apreparing method and application thereof. The indoline
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- Indoline compounds used as immunomodulator, and preparation method thereof
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The invention relates to the technical field of medicines, and relates to indoline compounds used as an immunomodulator, stereoisomers and pharmaceutically acceptable salts thereof, a preparation method thereof, and a medicinal composition containing the
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- Ring-fused compound, preparation method thereof and application of compound
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The invention relates to a ring-fused compound or pharmaceutically acceptable salt thereof, ester, a steric isomer, a tautomer, a polymorphic substance, a solvate, a hydrate, a metabolite or prodrug or mixture of the materials, a medicine composition and medicine box product comprising the compound, a preparation method of the compound and an application of the compound to preparation of medicinesfor preventing or treating PD-1/PD-L1 related diseases.
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Paragraph 0191; 0192; 0193; 0194; 0195
(2019/05/02)
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- HETEROCYCLIC COMPOUNDS AS IMMUNOMODULATORS
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Disclosed are compounds of Formula (I′), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds inhibit PD-1/PD-L1 interaction and are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.
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Paragraph 0693-0694
(2018/07/15)
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- CYANOPYRROLIDINES AS DUB INHIBITORS FOR THE TREATMENT OF CANCER
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The present invention relates to novel compounds and method for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C- terminal hydrolase L1 (UCHL1) and ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30). The invention further relates to the use of DUB inhibitors in the treatment of cancer and conditions involving mitochondrial dysfunction. Compounds of the invention include compounds having the formula (I) or a pharmaceutically acceptable salt thereof, wherein R1,R2,R3,R4,R5,R6,R7,R8 and R9 are as defined herein.
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- NOVEL COMPOUNDS
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The present invention relates to novel compounds of formula (I) and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 or ubiquitin spec
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- NOVEL PYRIMIDINE DERIVATIVES, PREPARATION THEREOF, AND PHARMACEUTICAL USE THEREOF AS AKT(PKB) PHOSPHORYLATION INHIBITORS
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The present invention relates to novel chemical compounds derived from pyrimidines, to the method for preparing same, to the novel intermediates obtained, to the use thereof as drugs, to the pharmaceutical compositions containing same, and to the therapeutic use thereof as AKT inhibitors.
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Paragraph 3029-3033
(2013/10/22)
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- Phenylaminopropanol derivatives and methods of their use
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The present invention is directed to phenylaminopropanol derivatives of formulae I, II, and III: [image] or a pharmaceutically acceptable salt thereof, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromyalgia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, schizophrenia, and combinations thereof.
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Page/Page column 48
(2010/11/26)
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- Heteroatom- and carbon-linked biphenyl analogs of Brequinar as immunosuppressive agents
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Structure-activity relationships were explored for some analogs of Brequinar having a linking atom between the 2-biphenyl substituent and the quinoline ring. Activities as inhibitors of dihydroorotate dehydrogenase and the mixed lymphocyte reaction were related to the overall shape and lipophilicity of the 2-substituent.
- Batt, Douglas G.,Petraitis, Joseph J.,Sherk, Susan R.,Copeland, Robert A.,Dowling, Randine L.,Taylor, Tracy L.,Jones, Elizabeth A.,Magolda, Ronald L.,Jaffee, Bruce D.
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p. 1745 - 1750
(2007/10/03)
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- 2-carbocyclic and 2-heterocyclic quinoline-4-carboxylic acids and salts thereof useful as immunosuppressive agents
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This invention relates to 2-carbocyclic and 2-heterocyclic quinoline-4-carbocyclic acid compounds, and salts thereof, to pharmaceutical compositions comprising such compounds, and to methods of using such compounds for the treatment and/or prevention of o
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