4692-98-2Relevant academic research and scientific papers
Discovery of phthalazino[1,2-b]-quinazolinone derivatives as multi-target HDAC inhibitors for the treatment of hepatocellular carcinoma via activating the p53 signal pathway
Liu, Qingqing,Zhang, Bin,Wang, Yuanjiang,Wang, Xinyi,Gou, Shaohua
, (2021/12/30)
In view of histone deacetylases (HDACs) as a promising target for cancer therapy, a series of phthalazino[1,2-b]-quinazolinone units were hybrided with ortho-aminoanilide or hydroxamic acid to serve as multi-target HDAC inhibitors for the treatment of solid tumors. Among the target compounds, 8h possessed nano-molar IC50 values toward the tested cancer cells and HDAC subtypes, which was more potent than the HDAC inhibitor SAHA (vorinostat). Mechanism study revealed that compound 8h could suppress the HepG2 cell proliferation via prompting the acetylation of histone 3 (H3) and α-tubulin, and activating the p53 signal pathway as designed. In addition, compound 8h exhibited much stronger in vivo antitumor efficacy than SAHA in the HepG2 xenograft tumor model with negligible toxicity. As a novel multi-target HDAC inhibitor, compound 8h deserves further development as a potential anticancer agent.
Multi-target anti-tumor small molecules and their derivatives, preparation methods, pharmaceutical compositions and applications
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Paragraph 0039-0043, (2022/01/05)
The present invention discloses a class of multi-target anti-tumor small molecules and derivatives thereof, preparation methods, pharmaceutical compositions and applications. The chemical structure of such small molecules as shown in formula I, the derivative of which relates to a pharmaceutically acceptable salt of the small molecule. This class of small molecules and their derivatives has a highly efficient tumor suppressor effect in vivo and abroad, low toxicity to cells and organisms, no genotoxicity; anti-tumor activity is achieved through multi-target action, with pan-HDAC inhibitory activity, and can also effectively activate the p53 pathway, inhibit topoisomerase activity, can be used to prepare anti-tumor drugs; the preparation method is simple and easy to operate.
Total synthesis of acronycine and noracronycine: An aryne amination approach
Xu, Yuan-Ze,Wen, Qi-Ling,Sha, Feng,Li, Qiong,Wu, Xin-Yan
, (2021/06/28)
Acronycine and noracronycine are chromene-containing alkaloids with significant biological activity. We have accomplished a concise total synthesis of acronycine and noracronycine. The key step, regioselective nucleophilic addition of anthranilate to chromene-type arynes under mild and transition-metal-free conditions was achieved. In addition, further modifications of nucleophilic addition products, such as hydrogenation, O-functionalization and palladium-catalyzed coupling reactions have also been developed, providing a concise procedure for these alkaloids and their derivatives.
Benzimidazoquinazolines as new potent anti-TB chemotypes: Design, synthesis, and biological evaluation
Chakraborti, Asit K.,Dhameliya, Tejas M.,Jadhavar, Pradeep S.,Krishna, Vagolu Siva,Patel, Kshitij I.,Saha, Nirjhar,Sriram, Dharmarajan,Vaja, Maulikkumar D.
, (2020/03/31)
In search for new molecular entities as anti-TB agents, the benzimidazoquinazoline polyheterocyclic scaffold has been designed adopting the scaffold hopping strategy. Thirty-two compounds have been synthesized through an improved tandem decarboxylative nucleophilic addition cyclocondensation reaction of o-phenylenediamine with isatoic anhydride followed by further cyclocondensation of the intermediately formed 2-(o-aminoaryl)benzimidazole with trialkyl orthoformate/acetate. The resultant benzimidazoquinazolines were evaluated in vitro for anti-TB activity against M. tuberculosis H37Rv (ATCC27294 strain). Fourteen compounds exhibiting MIC values in the range of 0.4–6.25 μg/mL were subjected to cell viability test against RAW 264.7 cell lines and were found to be non-toxic (30% inhibition at 50 μg/mL). The active compounds were further evaluated against INH resistant Mtb strains. The most active compound 6x [MIC (H37Rv) of 0.4 μg/mL] and the compound 6d [MIC (H37Rv) of 0.78 μg/mL] were also found to be active against INH resistant Mtb strain with MIC values of 12.5 and 0.78 μg/mL, respectively.
Synthesis of novel tryptanthrin derivatives as dual inhibitors of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase
Cui, Menghan,Kuang, Chunxiang,Li, Yuanyuan,Liu, Wei,Wang, Rong,Yang, Qing,Zhang, Shengnan
supporting information, (2020/04/10)
Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are promising drug development targets due to their implications in pathologies such as cancer and neurodegenerative diseases. The search for IDO1 inhibitor has been intensely pursued but there is a paucity of potent TDO and IDO1/TDO dual inhibitors. Natural product tryptanthrin has been confirmed to bear IDO1 and/or TDO inhibitory activities. Herein, twelve novel tryptanthrin derivatives were synthesized and evaluated for the IDO1 and TDO inhibitory potency. All of the compounds were found to be IDO1/TDO dual inhibitors, in particular, compound 9a and 9b bore IDO1 inhibitory activity similar to that of INCB024360, and compound 5a and 9b had remarkable TDO inhibitory activity superior to that of the well-known TDO inhibitor LM10. This work enriches the collection of IDO1/TDO dual inhibitors and provides chemical molecules for potential development into drugs.
APPLICATION OF N-BENZYL TRYPTANTHRIN DERIVATIVE AS TRYPTOPHAN DIOXYGENASE (TDO) INHIBITOR
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Paragraph 0102; 0104, (2020/04/24)
The present invention provides an application of N-benzyl tryptanthrin derivative as tryptophan dioxygenase (TDO) inhibitor, and more specifically an application of N-benzyl tryptanthrin derivative or a pharmaceutically acceptable salt thereof. Said derivative has a structural general formula as represented by formula 1, wherein each group is defined as in the specification. The derivative of the present invention has a good TDO inhibiting activity and can be used to prepare a treatment for diseases associated with TDO activity and expression.
Target protein degradation inducing compound, preparation method thereof and pharmaceutical composition for preventing or treating targeted protein related diseases containing the same as an active ingredient
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Paragraph 0609; 0611-0613, (2020/05/01)
The present invention relates to a degraducer for inducing the decomposition of target protein, a producing method thereof, and a pharmaceutical composition for preventing or treating target protein-related diseases by containing the degraducer as an active ingredient. A novel compound represented by chemical formula 1, ULB-L-PTM, by the present invention, as a degraducer compound inducing the decomposition of target protein using cereblon E3 ubiquitin ligase, is able to significantly achieve a target protein degradation-inducing activity with an excellent binding activity of a cereblon E3 ubiquitin ligase binder thereby, being able to achieve an excellent protein degradation activity by targeting protein or polypeptide related to various diseases. The bromodomain-containing pharmaceutical composition for preventing or treating protein-related diseases or conditions contains the novel compound represented by chemical formula 1 as an active ingredient and has a useful effect of providing a health functional food composition for prevention or improvement.(AA) Example 22 (nM, 24h)COPYRIGHT KIPO 2020
NOVEL PIPERIDINE-2,6-DIONE DERIVATIVE AND USE THEREOF
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Paragraph 0146-0148, (2020/03/09)
The present disclosure relates to a novel piperidine-2,6-dione derivative and a use thereof and, more specifically, to a piperidine-2,6-dione derivative compound having a structure of a thalidomide analog. A compound of chemical formula 1 according to the present disclosure specifically binds with CRBN protein, and is involved in functions thereof. Therefore, the compound of the present disclosure can be favorably used in the prevention or treatment of leprosy, chronic graft versus host disease, an inflammatory disease, or cancer, which are caused by actions of CRBN protein.
Protein arginine methyltransferase 5 (PRMT5) inhibitor, pharmaceutical products thereof, and methods thereof
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Paragraph 0334-0338, (2020/11/05)
The present invention provides a PRMT5 inhibitor of formula (I); R1 is a non-hydrogen monovalent group; W is a direct bond or-NH-; T, U and V are independently from each other selected from C and N; R2 is H or halogen; m is 1 or 2; X is carbon, nitrogen or oxygen; Y is C or N; Z is a direct bond or carbon; R3 is H, a non-hydrogen monovalent group, an oxo group, a divalent spiro-forming group or adivalent bridge-forming group; and n is 1 or 2, and represents a single or double bond. The present invention also provides pharmaceutical products comprising the PRMT5 inhibitor and use thereof in the treatment of proliferative disorders such as cancer, metabolic disorders, hematological disorders, autoimmune diseases and inflammatory diseases.
Carbene-Catalyzed Enantioselective Decarboxylative Annulations to Access Dihydrobenzoxazinones and Quinolones
Lee, Ansoo,Zhu, Joshua L.,Feoktistova, Taisiia,Brueckner, Alexander C.,Cheong, Paul H.-Y.,Scheidt, Karl A.
supporting information, p. 5941 - 5945 (2019/04/03)
A direct decarboxylative strategy for the generation of aza-o-quinone methides (aza-o-QMs) by N-heterocyclic carbene (NHC) catalysis has been discovered and explored. This process requires no stoichiometric additives in contrast with current approaches. Aza-o-QMs react with trifluoromethyl ketones through a formal [4+2] manifold to access highly enantioenriched dihydrobenzoxazin-4-one products, which can be converted to dihydroquinolones through an interesting stereoretentive aza-Petasis–Ferrier rearrangement sequence. Complementary dispersion-corrected density functional theory (DFT) studies provided an accurate prediction of the reaction enantioselectivity and lend further insight to the origins of stereocontrol. Additionally, a computed potential energy surface around the major transition structure suggests a concerted asynchronous mechanism for the formal annulation.
