Day: November 17, 2022

Chen, Jiong J. published the artcileSynthesis and Antiviral Evaluation of Trisubstituted Indole N-Nucleosides as Analogues of 2,5,6-Trichloro-1-(β-D-ribofuranosyl)benzimidazole (TCRB), Related Products of indole-building-block, the main research area is ribofuranosyl chloroindole analog stereochem preparation antiviral cytomegalovirus inhibition; indole nucleoside preparation cytotoxicity virucide structure activity.

2,5,6-Trichloro-1-(β-D-ribofuranosyl)benzimidazole (TCRB) and 2-bromo-5,6-dichloro-1-(β-D-ribofuranosyl)benzimidazole (BDCRB) are nucleosides that exhibit strong and selective activity against human cytomegalovirus (HCMV). Selected polyhalogenated indole nucleosides have now been synthesized as 3-deaza analogs of the benzimidazole nucleosides using the sodium salt glycosylation method. 2-Benzylthio-1-[2-deoxy-3,5-bis-O-(4-methylbenzoyl)-β-D-erythro-pentofuranosyl]-5,6-dichloroindole was prepared stereoselectively via the coupling of a 2-deoxyribofuranosyl α-chloride derivative with the sodium salt of 2-benzylthio-5,6-dichloroindole. This compound was then elaborated into the targeted 2-benzylthio-1-(β-D-ribofuranosyl)-5,6-dichloroindole in five steps. 2,5,6-Trichloro-(1-β-D-ribofuranosyl)indole was prepared using the same synthetic route with 2,5,6-trichloroindole as the starting material. The authors were subsequently able to prepare 2,5,6-trichloro-1-(β-D-ribofuranosyl)indole in three steps using a modification of the sodium salt glycosylation method. 2-Bromo-5,6-dichloro-1-(β-D-ribofuranosyl)indole was also prepared using the same procedures. Target compounds were tested for activity against HCMV, herpes simplex virus type 1 (HSV-1), and human herpes virus six (HHV-6) and for cytotoxicity. All of the compounds were less active against HCMV than TCRB and weakly active or inactive against HSV-1 and HHV-6.

Journal of Medicinal Chemistry published new progress about Antiviral agents. 71293-59-9 belongs to class indole-building-block, name is 5,6-Dichloroindolin-2-one, and the molecular formula is C8H5Cl2NO, Related Products of indole-building-block.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Certal, Victor published the artcilePreparation and optimization of new 4-(2-(indolin-1-yl)-2-oxoethyl)-2-morpholinothiazole-5-carboxylic acid and amide derivatives as potent and selective PI3Kβ inhibitors, COA of Formula: C8H8ClN, the main research area is indolinyloxoethylmorpholinothiazole carboxylic acid amide derivative phosphatidylinositol kinase inhibitor antitumor; PI3Kβ; PTEN; Thiazole; pAKT.

In the authors’ continuous efforts to identify and develop novel targeted cancer treatments, a new morpholino-thiazole scaffold active against PI3Kβ was identified. This Letter reports the optimization of this compound class to develop PI3Kβ isoform-selective inhibitors with suitable pharmacol. properties.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 41910-64-9 belongs to class indole-building-block, name is 4-Chloroindoline, and the molecular formula is C8H8ClN, COA of Formula: C8H8ClN.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Iwaki, Yuzo published the artcileONO-8430506: A Novel Autotaxin Inhibitor That Enhances the Antitumor Effect of Paclitaxel in a Breast Cancer Model, Safety of N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, the main research area is ONO 8430506 autotaxin inhibitor preparation paclitaxel breast cancer.

Lysophosphatidic acid (LPA) is a bioactive lipid mediator that elicits a number of biol. functions, including smooth muscle contraction, cell motility, proliferation, and morphol. change. LPA is endogenously produced by autotaxin (ATX) from extracellular lysophosphatidylcholine (LPC) in plasma. Herein, we report our medicinal chem. effort to identify a novel and highly potent ATX inhibitor, ONO-8430506 (20), with good oral availability. To enhance the enzymic ATX inhibitory activity, we designed several compounds by structurally comparing our hit compound with the endogenous ligand LPC. Further optimization to improve the pharmacokinetic profile and enhance the ATX inhibitory activity in human plasma resulted in the identification of ONO-8430506 (20), which enhanced the antitumor effect of paclitaxel in a breast cancer model.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents. 5654-92-2 belongs to class indole-building-block, name is N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, and the molecular formula is C10H13N3, Safety of N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Certal, Victor published the artcileDiscovery and Optimization of Pyrimidone Indoline Amide PI3Kβ Inhibitors for the Treatment of Phosphatase and Tensin Homologue (PTEN)-Deficient Cancers, Recommanded Product: 4-Chloroindoline, the main research area is PI3Kbeta phosphatase tensin homolog PTEN neoplasm structure activity preparation.

Compelling mol. biol. publications have reported the implication of phosphoinositide kinase PI3Kβ in PTEN-deficient cell line growth and proliferation. These findings supported a scientific rationale for the development of PI3Kβ-specific inhibitors for the treatment of PTEN-deficient cancers. This paper describes the discovery of 2-[2-(2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one and the optimization of this new series of active and selective pyrimidone indoline amide PI3Kβ inhibitors. 2-[2-(2-Methyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one (I), identified following a carefully designed Me scan, displayed improved physicochem. and in vitro pharmacokinetic properties. Structural biol. efforts enabled the acquisition of the first x-ray cocrystal structure of p110β with the selective inhibitor compound I bound to the ATP site. The nonplanar binding mode described herein is consistent with observed structure-activity relationship for the series. Compound I demonstrated significant in vivo activity in a UACC-62 xenograft model in mice, warranting further preclin. investigation. Following successful development, compound 28 entered phase I/Ib clin. trial in patients with advanced cancer.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 41910-64-9 belongs to class indole-building-block, name is 4-Chloroindoline, and the molecular formula is C8H8ClN, Recommanded Product: 4-Chloroindoline.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Parrino, Barbara published the artcileSynthesis of the new ring system bispyrido[4′,3′:4,5]pyrrolo[1,2-a:1′,2′-d]pyrazine and its deaza analogue, Quality Control of 800401-68-7, the main research area is pyrrolopyridinecarboxylic acid preparation; bispyridopyrrolopyrazine dione preparation antineoplastic mol docking; pyridopyrrolopyrazino indole dione antineoplastic mol docking.

A series of bispyridopyrrolopyrazine diones I [R1 = R4 = H, Cl, OMe; R2 = R3 = H, OMe] and their deaza analogs pyridopyrrolopyrazinoindole diones II [R1 = R2 = H, Cl, OMe] was synthesized and evaluated for their antineoplastic activities and mol. docking studies. Among the synthesized compounds I [R1 = R2 = R4 = H; R3 = OMe] and II [R1 = R2 = H; R1 = OMe, R2 = H; R1 = H, R2 = OMe] exhibited modest activity against MCF7 (a breast cancer cell line) and/or UO-31 (a renal cancer cell line).

Molecules published new progress about Antitumor agents. 800401-68-7 belongs to class indole-building-block, name is 5-Chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid, and the molecular formula is C8H5ClN2O2, Quality Control of 800401-68-7.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Kemnitzer, William published the artcileDiscovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high throughput screening assay. Structure-activity relationships of N-alkyl substituted pyrrole fused at the 7,8-positions, Application of 4-(Benzyloxy)-1-methyl-1H-indole, the main research area is aryl chromene preparation structure antitumor neoplasm.

In the continuing effort to discover and develop apoptosis inducing 4-aryl-4H-chromenes as novel anticancer agents, the authors explored the structure-activity relationship (SAR) of alkyl substituted pyrrole fused at the 7,8-positions. A Me group substituted at the nitrogen in the 7-position of the pyrrole ring led to a series of potent apoptosis inducers with potency in the low nanomolar range. These compounds were also found to be low nanomolar or subnanomolar inhibitors of cell growth, and they inhibited tubulin polymerization, indicating that methylation of the 7-position nitrogen does not change the mechanism of action of these chromenes. Compound 2 d was identified as a highly potent apoptosis inducer with an EC50 value of 2 nM and a highly potent inhibitor of cell growth with a GI50 value of 0.3 nM in T47D cells.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 13523-93-8 belongs to class indole-building-block, name is 4-(Benzyloxy)-1-methyl-1H-indole, and the molecular formula is C16H15NO, Application of 4-(Benzyloxy)-1-methyl-1H-indole.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Nimbarte, Vijaykumar D. published the artcileSynthesis and in Vitro Evaluation of Novel 5-Nitroindole Derivatives as c-Myc G-Quadruplex Binders with Anticancer Activity, Quality Control of 5654-92-2, the main research area is human cervical cancer anticancer cMyc; G-quadruplex binders; c-Myc; nitroindoles; oncogene promoters, reactive oxygen species, structure-activity relationships.

Lead-optimization strategies for compounds targeting c-Myc G-quadruplex (G4) DNA are being pursued to develop anticancer drugs. Here, we investigate the structure-activity- relationship (SAR) of a newly synthesized series of mols. based on the pyrrolidine-substituted 5-nitro indole scaffold to target G4 DNA. Our synthesized series allows modulation of flexible elements with a structurally preserved scaffold. Biol. and biophys. analyses illustrate that substituted 5-nitroindole scaffolds bind to the c-Myc promoter G-quadruplex. These compounds downregulate c-Myc expression and induce cell-cycle arrest in the sub-G1/G1 phase in cancer cells. They further increase the concentration of intracellular reactive oxygen species. NMR spectra show that three of the newly synthesized compounds interact with the terminal G-quartets (5′- and 3-ends) in a 2 : 1 stoichiometry.

ChemMedChem published new progress about Antitumor agents. 5654-92-2 belongs to class indole-building-block, name is N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, and the molecular formula is C10H13N3, Quality Control of 5654-92-2.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Cho, Er-Chieh published the artcileRing size changes in the development of class I HDAC inhibitors, Application of Methyl 2-methyl-1H-indole-5-carboxylate, the main research area is thienylbenzamide anticancer SAR HDAC inhibitor docking; HDAC; Thienylbenzamides; colon cancer; ring transformation.

Five pathways involving different ring structures led to generation of fourteen thienylbenzamides which display the structure-activity relationships of class I HDAC inhibitors. All the synthesized compounds inhibit HDAC1 and HDAC2 selectively over other isoforms and many inhibit DLD1 and HCT116 cells more effectively than a parent compound Compounds and inhibit HCT116 cells by activation of the apoptosis pathway.

Journal of Enzyme Inhibition and Medicinal Chemistry published new progress about Antitumor agents. 57663-18-0 belongs to class indole-building-block, name is Methyl 2-methyl-1H-indole-5-carboxylate, and the molecular formula is C11H11NO2, Application of Methyl 2-methyl-1H-indole-5-carboxylate.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Sirisoma, Nilantha published the artcileDiscovery of substituted N’-(2-oxoindolin-3-ylidene)benzohydrazides as new apoptosis inducers using a cell- and caspase-based HTS assay, Computed Properties of 1677-47-0, the main research area is antitumor oxoindolinylidenebenzohydrazide preparation apoptosis neoplasm.

The discovery of a series of substituted N’-(2-oxoindolin-3-ylidene)benzohydrazides as inducers of apoptosis using a proprietary cell- and caspase-based ASAP HTS assay is reported. Through SAR studies, N’-(4-bromo-5-methyl-2-oxoindolin-3-ylidene)-3,4,5-trimethoxybenzohydrazide (3g) was identified as a potent apoptosis inducer with an EC50 value of 0.24 μM in human colorectal carcinoma HCT116 cells, more than a 40-fold increase in potency from the initial screening hit N’-(5-bromo-2-oxoindolin-3-ylidene)-3,4,5-trimethoxybenzohydrazide (2a). Compound 3g also was found to be highly active in a growth inhibition assay with a GI50 value of 0.056 μM in HCT116 cells. A group of potentially more aqueous soluble analogs were prepared and found to be highly active. Among them, compound 4e incorporating a Me piperazine moiety was found to have EC50 values of 0.17, 0.088 and 0.14 μM in human colorectal carcinoma cells HCT116, hepatocellular carcinoma cancer SNU398 cells and human colon cancer RKO cells, resp. Compounds 3g and 4e were found to function as inhibitors of tubulin polymerization

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 1677-47-0 belongs to class indole-building-block, name is 4,5-Dichloroisatin, and the molecular formula is C8H3Cl2NO2, Computed Properties of 1677-47-0.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Li, Xiang published the artcileAerobic Transition-Metal-Free Visible-Light Photoredox Indole C-3 Formylation Reaction, Quality Control of 13523-93-8, the main research area is indole TMEDA oxygen Rose Bengal visible light photoredox formylation; formyl indole regioselective preparation.

An aerobic visible-light-promoted indole C-3 formylation reaction catalyzed by Rose Bengal has been developed. This transition-metal-free process employs mol. oxygen as the terminal oxidant and uses TMEDA as the one-carbon source through C-N bond cleavage. The reaction is compatible with a variety of functional groups.

ACS Catalysis published new progress about C-N bond cleavage. 13523-93-8 belongs to class indole-building-block, name is 4-(Benzyloxy)-1-methyl-1H-indole, and the molecular formula is C16H15NO, Quality Control of 13523-93-8.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles