Month: October 2022

Zhao, Yujun; Bai, Longchuan; Liu, Liu; McEachern, Donna; Stuckey, Jeanne A.; Meagher, Jennifer L.; Yang, Chao-Yie; Ran, Xu; Zhou, Bing; Hu, Yang; Li, Xiaoqin; Wen, Bo; Zhao, Ting; Li, Siwei; Sun, Duxin; Wang, Shaomeng published the artcile< Structure-Based Discovery of 4-(6-Methoxy-2-methyl-4-(quinolin-4-yl)-9H-pyrimido[4,5-b]indol-7-yl)-3,5-dimethylisoxazole (CD161) as a Potent and Orally Bioavailable BET Bromodomain Inhibitor>, Safety of Isoquinolin-8-ylboronic acid, the main research area is quinolinyl pyrimidoindolyl dimethylisoxazole preparation oral BET bromodomain inhibitor.

A series of 9H-pyrimido[4,5-b]indole-containing compounds was designed and synthesized to obtain potent and orally bioavailable BET inhibitors. By incorporation of an indole or a quinoline moiety to the 9H-pyrimido[4,5-b]indole core, we identified a series of small mols. showing high binding affinities to BET proteins and low nanomolar potencies in inhibition of cell growth in acute leukemia cell lines. One such compound, 4-(6-methoxy-2-methyl-4-(quinolin-4-yl)-9H-pyrimido[4,5-b]indol-7-yl)-3,5-dimethylisoxazole (I) has excellent microsomal stability and good oral pharmacokinetics in rats and mice. Orally administered, I achieves significant antitumor activity in the MV4;11 leukemia and MDA-MB-231 triple-neg. breast cancer xenograft models in mice. Determination of the cocrystal structure of I with BRD4 BD2 provides a structural basis for its high binding affinity to BET proteins. Testing its binding affinities against other bromodomain-containing proteins shows that I is a highly selective inhibitor of BET proteins. These data show that I is a potent, selective, and orally active BET inhibitor.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 721401-43-0 belongs to class isoquinoline, and the molecular formula is C9H8BNO2, Safety of Isoquinolin-8-ylboronic acid.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Hu, Yijie; Ye, Liufeiyang; Chen, Jie; Zhang, Hui; Deng, Hongmei; Lin, Jin-Hong; Cao, Weiguo published the artcile< An Efficient Construction of CF3-Substituted Spirooxindole-Fused Benzo[a]quinolizidines by a Three-Component Cyclization>, Recommanded Product: 5-Methoxyisoquinoline, the main research area is isoquinoline perfluoroalkylpropiolate oxoindolinylidene propanedinitrile three component cyclization; perfluoroalkyl dicyano spirooxindoline benzoquinolizidine carboxylate preparation.

A convenient three-component cyclization was described for the efficient construction of CF3-substituted spirooxindole-fused benzo[a]quinolizidines by using CF3-propiolate as a building block. This attractive protocol may find great synthetic utility since CF3-containing complex structures were installed by a one-step cyclization under mild conditions.

European Journal of Organic Chemistry published new progress about Alkynes, fluoro Role: RCT (Reactant), RACT (Reactant or Reagent). 90806-58-9 belongs to class isoquinoline, and the molecular formula is C10H9NO, Recommanded Product: 5-Methoxyisoquinoline.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Pumuye, Paul P.; Evison, Benny J.; Konda, Shyam K.; Collins, J. Grant; Kelso, Celine; Medan, Jelena; Sleebs, Brad E.; Watson, Keith; Phillips, Don R.; Cutts, Suzanne M. published the artcile< Formaldehyde-activated WEHI-150 induces DNA interstrand crosslinks with unique structural features>, Computed Properties of 144511-13-7, the main research area is formaldehyde WEHI150 DNA interstrand crosslink; Anthracenediones; Cancer chemotherapy; DNA sequence specificity; Drug-DNA adducts; Mitoxantrone analogues.

Mitoxantrone is an anticancer anthracenedione that can be activated by formaldehyde to generate covalent drug-DNA adducts. Despite their covalent nature, these DNA lesions are relatively labile. It was recently established that analogs of mitoxantrone featuring extended side-chains terminating in primary amino groups typically yielded high levels of stable DNA adducts following their activation by formaldehyde. In this study we describe the DNA sequence-specific binding properties of the mitoxantrone analog WEHI-150 which is the first anthracenedione to form apparent DNA crosslinks mediated by formaldehyde. The utility of this compound lies in the versatility of the covalent binding modes displayed. Unlike other anthracenediones described to date, WEHI-150 can mediate covalent adducts that are independent of interactions with the N-2 of guanine and is capable of adduct formation at novel DNA sequences. Moreover, these covalent adducts incorporate more than one formaldehyde-mediated bond with DNA, thus facilitating the formation of highly lethal DNA crosslinks. The versatility of binding observed is anticipated to allow the next generation of anthracenediones to interact with a broader spectrum of nucleic acid species than previously demonstrated by the parent compounds, thus allowing for more diverse biol. activities.

Bioorganic & Medicinal Chemistry published new progress about Crosslinking agents. 144511-13-7 belongs to class isoquinoline, and the molecular formula is C13H5F2NO2, Computed Properties of 144511-13-7.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Cheng, Yunfeng; Ni, Nanting; Yang, Wenqian; Wang, Binghe published the artcile< A New Class of Fluorescent Boronic Acids That Have Extraordinarily High Affinities for Diols in Aqueous Solution at Physiological pH>, Application of C9H8BNO2, the main research area is fluorescent boronate high affinity diol aqueous solution physiol pH.

The boronic acid group is an important recognition moiety for sensor design. Herein, the authors report a series of isoquinolinylboronic acids that have extraordinarily high affinities for diol-containing compounds at physiol. pH. In addition, 5- and 8-isoquinolinylboronic acids also showed fairly high binding affinities towards D-glucose (Ka=42 and 46 M-1, resp.). For the first time, weak but encouraging binding of cis-cyclohexanediol was found for these boronic acids. Such binding was coupled with significant fluorescence changes. Furthermore, 4- and 6-isoquinolinylboronic acids also showed the ability to complex Me α-D-glucopyranose (Ka=3 and 2 M-1, resp.).

Chemistry – A European Journal published new progress about Affinity. 721401-43-0 belongs to class isoquinoline, and the molecular formula is C9H8BNO2, Application of C9H8BNO2.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Liao, Lan-Shan; Tan, Lin-Jie; Chen, Yin; Yang, Qi-Yuan; Choudhary, Muhammad Iqbal; Pan, Ying-Ming; Tang, Hai-Tao; Su, Gui-Fa; Liang, Hong; Chen, Zhen-Feng published the artcile< One-pot synthesis of oxoaporphines as potent antitumor agents and investigation of their mechanisms of actions>, Reference of 721401-43-0, the main research area is oxoporphine derivative preparation antitumor agents; Antitumor activity; Apoptosis; Cell cycle; Oxoaporphine.

An efficient one-pot reaction for the synthesis of oxoaporphine alkaloids has been developed. Twenty-three compounds of oxoaporphine alkaloids were prepared and assessed for their antitumor activities. Most compounds inhibited the growth of T-24 tumor cells in vitro. Particularly, I displayed the most potent activity with an IC50 value of 0.5μM, which was 19-fold more potent than the parent compound 4. The substitution at C3-position of oxoaporphine core by -NO2 significantly enhanced the anticancer activity. Mechanism studies indicated that II and I induced cell cycle arrest at G2/M phase; in contrast, III induced cell cycle arrest at the S phase. Increase of mitochondrial ROS/Ca2+ and decrease of MMP, accompanied by activation of caspase-3/9, were observed in T-24 cells after exposure to compounds I, II and III, suggesting that the mitochondrial pathway was involved in the induced apoptosis. Moreover, compound I effectively inhibited tumor growth in a mouse xenograft model bearing T-24.

European Journal of Medicinal Chemistry published new progress about Alkaloids Role: PAC (Pharmacological Activity), SPN (Synthetic Preparation), BIOL (Biological Study), PREP (Preparation). 721401-43-0 belongs to class isoquinoline, and the molecular formula is C9H8BNO2, Reference of 721401-43-0.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Hartung, Ryan E.; Wall, Mark C.; Lebreton, Sylvain; Smrcina, Martin; Patek, Marcel published the artcile< Selectivity of N- versus O-alkylation in Mitsunobu reactions with various quinolinols and isoquinolinols>, Quality Control of 3336-49-0, the main research area is quinolinol alc chemoselective Mitsunobu alkylation; isoquinolinol alc chemoselective Mitsunobu alkylation.

Reacting quinolinols and isoquinolinols under Mitsunobu conditions could give rise to N-alkylated products in addition to the normally desired O-alkylated structures. An in-depth study of how the solvent, reagent equivalent, position of the quinoline/isoquinoline nitrogen and type of reacting aliphatic alc. employed affected the ratio of N- vs. O-alkylation was described.

Heterocycles published new progress about Aliphatic alcohols Role: RCT (Reactant), RACT (Reactant or Reagent). 3336-49-0 belongs to class isoquinoline, and the molecular formula is C9H7NO, Quality Control of 3336-49-0.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Xiong, Qian; Dong, Shunxi; Chen, Yushuang; Liu, Xiaohua; Feng, Xiaoming published the artcile< Asymmetric synthesis of tetrazole and dihydroisoquinoline derivatives by isocyanide-based multicomponent reactions>, Formula: C10H9NO, the main research area is alkylidene malonate diastereoselective enantioselective annulation isoquinoline isocyanide; imino dihydro pyrroloisoquinoline dicarboxylate enantioselective diastereoselective preparation; isocyanide trimethylsilyl azide alkylidene malonate enantioselective heterocyclization; tetrazole diester enantioselective preparation.

Herein, several isocyanide-based multicomponent reactions based on enantioselective addition of simple isocyanides to C=C bonds were realized in the presence of a chiral Mg(II)-N,N’-dioxide catalyst. Three- or four-component reactions of an isocyanide, TMSN3, and an (alkylidene)malonate could be precisely controlled by modulating reaction conditions to afford two types of enantioenriched tetrazole derivatives in moderate to high yields. Possible catalytic cycles via a key zwitterionic intermediate, and the vital roles of H2O or excess ligand are provided based on control experiments Moreover, taking advantage of this zwitterionic intermediate as a 1,3-dipole, an enantioselective dearomative [3+2] annulation reaction of nonactivated isoquinolines is achieved, furnishing chiral dihydropyrrolo[2,1-a]isoquinolines in good to excellent results.

Nature Communications published new progress about Diastereoselective synthesis. 90806-58-9 belongs to class isoquinoline, and the molecular formula is C10H9NO, Formula: C10H9NO.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Xie, Hongling; Yang, Zhenkun; Tang, Luning; Han, Zhengyu; Sun, Jianwei; Huang, Hai published the artcile< Construction of nine-membered N,N,O-heterocycles via Pd-catalyzed [6+3] dipolar cycloaddition>, SDS of cas: 90806-58-9, the main research area is vinyl oxetane iminoisoquinolinium ylide palladium catalyst dipolar cycloaddition; tetrahydrooxadiazoninoisoquinoline preparation.

A new approach for the synthesis of 9-membered N,N,O-heterocycles by Pd-catalyzed [6+3] dipolar cycloaddition of N-iminoisoquinolinium ylides and 2-vinyl oxetanes was developed. The scope of this cycloaddition was demonstrated with 28 examples. This was another important synthetic strategy for medium-sized rings by employing N-iminoisoquinolinium ylides as ternary synthons.

Chemical Communications (Cambridge, United Kingdom) published new progress about Allylic alcohols Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 90806-58-9 belongs to class isoquinoline, and the molecular formula is C10H9NO, SDS of cas: 90806-58-9.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Huang, Cheng; Wang, Jing-Hao; Qiao, Jia; Fan, Xiu-Wei; Chen, Bin; Tung, Chen-Ho; Wu, Li-Zhu published the artcile< Direct Arylation of Unactivated Alkanes with Heteroarenes by Visible-Light Catalysis>, Synthetic Route of 90806-58-9, the main research area is alkane heteroarene arylation iridium visible light; alkylheteroarene preparation; iridium visible light arylation catalyst.

The functionalization of aliphatic C-H bonds is both a major challenge and a desirable goal in organic synthesis. Here, a successful arylation of unactivated alkanes with heteroarenes by using iridium polypyridyl complexes as the photocatalyst and persulfate as the HAT catalyst precursor under visible-light irradiation, is described. This reaction features good functional group tolerance and broad scope with regard to both alkane and heteroarene substrates (37 examples), which allows direct access to alkyl-substituted N-heteroarenes, a key structural motif in natural products and bioactive mols.

Journal of Organic Chemistry published new progress about Alkanes Role: RCT (Reactant), RACT (Reactant or Reagent). 90806-58-9 belongs to class isoquinoline, and the molecular formula is C10H9NO, Synthetic Route of 90806-58-9.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Zhou, Wei; Liu, Hao; Guo, Yongyi; Gu, Yiting; Han, Jing; Chen, Jie; Deng, Hongmei; Shao, Min; Zhang, Hui; Cao, Weiguo published the artcile< Base-promoted [3+2] cycloaddition/aromatization cascade reaction under air: An approach to access perfluoroalkylated pyrrolo[2,1-a]isoquinolines>, Synthetic Route of 90806-58-9, the main research area is isoquinoline bromomethyl aryl ketone perfluoroalkynoate dipolar cycloaddition aromatization cascade; pyrroloisoquinoline perfluoroalkylated preparation.

A facile [3 + 2] cycloaddition / aromatization cascade reaction with broad substrate scopes in up to 94% isolated yield was disclosed herein. This tandem approach was accomplished by employing isoquinolines and bromoacetyl derivatives with Me perfluoroalk-2-ynoates as readily available starting materials. In the presence of base, this method provides an efficient access to synthesize perfluoroalkylated pyrrolo[2,1-a]isoquinolines with ambient air as a terminal oxidant at room temperature in one-pot.

Journal of Fluorine Chemistry published new progress about 1,3-Dipolar cycloaddition reaction. 90806-58-9 belongs to class isoquinoline, and the molecular formula is C10H9NO, Synthetic Route of 90806-58-9.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem