52190-18-8

From an aqueous decoction of the traditional Chinese medicine “ban lan gen” (the Isatis indigotica root), an antiviral natural product CI - 39 was isolated as an NNRTI (non-nucleoside reverse transcriptase inhibitor) (EC50 = 3.40 μM). Its novel structure was determined as methyl (1-methoxy-1H-indol-3-yl)acetamidobenzoate by spectroscopic data and confirmed by single crystal X-ray diffraction. Through synthesis and structure-activity relationship (SAR) investigation of CI - 39 and 57 new derivatives (24 with EC50 values of 0.06–8.55 μM), two optimized derivatives 10f and 10i (EC50: 0.06 μM and 0.06 μM) having activity comparable to that of NVP (EC50 = 0.03 μM) were obtained. Further evaluation verified that 10f and 10i were RT DNA polymerase inhibitors and exhibited better activities and drug resistance folds compared to NVP against seven NNRTI-resistant strains carrying different mutations. Especially, 10i (EC50 = 0.43 μM) was more active to the L100I/K103N double-mutant strain as compared to both NVP (EC50 = 0.76 μM) and EFV (EC50 = 1.08 μM). The molecular docking demonstrated a possible binding pattern between 10i and RT and revealed activity mechanism of 10i against the NNRTI-resistant strains.

Sulphate modified multiwalled carbon nanotubes (S-MWCNT) and Mesoporous carbon (S-MC) catalysts were prepared by wet impregnation method. These materials were characterized by different analytical techniques such as Powder-XRD, BET surface area analysis, SEM-EDS and TEM analysis to evaluate their bulk and surface properties. Surface acidity of the catalyst was measured by TPD-NH3 technique, as well as n-butyl amine titration. The estimated surface acidity of S-MWCNT and S-MC using n-butyl amine titration was found to be 0.82 and 1.75 mmol/g respectively. The catalytic activity of these materials was investigated in the synthesis of acetamide derivatives using aromatic acids with substituted aromatic amines in a liquid phase reaction. The reaction conditions were optimized to achieve good % yield of the products. In general S-MC catalyst exhibited good catalytic activity and gave higher % yield of the respective acetamides than S-MWCNT. This is attributed to higher surface acidity of S-MC, however the catalyst was found to be non-recyclable. S-MWCNT exhibited moderate % yield and 100% selectivity towards the formation of products. S-MWCNT catalyst was recycled up to 5 times with a consistent % yield of the respective acetamide derivatives. The synthesized acetamide derivatives were analyzed by M.P, 1HNMR techniques.

The invention discloses an application of indole compounds extracted from radix isatidis and represented by general formula (I), and derivatives and pharmaceutically acceptable salts thereof in the preparation of anti-influenza virus medicines or healthcare products, and discloses a preparation method of the compounds, and an application of medicinal compositions containing the compounds in the preparation of the anti-influenza virus medicines or healthcare products.

The invention discloses an indole compound extracted from radix isatidis shown in a general formula (I) and a derivative of the indole compound, as well as a salt acceptable on pharmacy, a preparation method of the compound, and a medicinal composite. The compound has apparent HIV-resisting activity and influenza virus-resisting activity, and can be used for preparing drugs or healthcare products for resisting HIV or influenza viruses. (The formula is shown in the description.).

The invention relates to the field of pharmaceutical chemistry and discloses an indolylcarboxylic acid compound represented by a formula (I) shown in the description and an application thereof in the preparation of antitumor drugs. The indolylcarboxylic a

The present patent discloses a novel one pot two-step process for the synthesis of ivacaftor and related compounds of [Formula (I)], wherein R1, R2, R3, R4, R5, R6, R7 and Ar1 are as described above; its tautomers or pharmaceutically acceptable salts thereof starting from indole acetic acid amides.

A series of novel indole derivatives as CDK4 inhibitors were designed and synthesized though the condensation reaction between the indolic acid and the corresponding substituted amine. The key step of our synthetic process is the efficient condensation reaction conducted by two different methods. The MTT and kinase assays were conducted used to assess the antitumor activity and cyclin-dependent kinases (CDKs) inhibitory activity. The most active compound 8b has an IC50 of 10-25 μM for the inhibition of four different tumor cells and CDK4. The higher activities of 8b were influenced by more conformational freedom resulted form the non-planar structure and by the stronger hydrogen bonding capability. Thus, the strategy we adapt to design potent, non-toxic CDK4 inhibitors is successful.

A simple and convenient method to access 4-quinolone-3-carboxylic acid amides from indole-3-acetic acid amides through one-pot oxidative cleavage of the indole ring followed by condensation (Witkop-Winterfeldt type oxidation) was explored. The scope of the method was confirmed with more than 20 examples and was successfully applied to the synthesis of the drug Ivacaftor, the most expensive drug on the market.

A series of 7,12-dihydroindolo[3,2-d][1]benzazepine-6(5H)-ones (paullones) substituted at C9/C10 (Br) and C2 (Me, CF3, CO2Me) have been synthesized by a one-pot Suzuki-Miyaura cross-coupling of an o-aminoarylboronic acid and methyl 2-iodoindoleacetate followed by intramolecular amide formation. Other approaches to the paullone scaffold based on Pd-catalyzed C-H activation were unsuccessful. In vitro enzymatic assay with recombinant human SIRT-1 indicated a strong inhibitory profile for the series, in particular the analogue with a methoxycarbonyl group at C2 and a bromine at C9. These compounds are, in general, inducers of granulocyte differentiation of the U937 acute leukemia cell line and cause a marked increase in pre-G1 of the cell cycle.

Structure-activity relationships within the indole-3-glyoxylamide series of antiprion agents have been explored further, resulting in discovery of several new compounds demonstrating excellent activity in a cell line model of prion disease (EC50 10 nM). After examining a range of substituents at the para-position of the N-phenylglyoxylamide moiety, five-membered heterocycles containing at least two heteroatoms were found to be optimal for the antiprion effect. A number of modifications were made to probe the importance of the glyoxylamide substructure, although none were well tolerated. The most potent compounds did, however, prove largely stable towards microsomal metabolism, and the most active library member cured scrapie-infected cells indefinitely on administration of a single treatment. The present results thereby confirm the indole-3-glyoxylamides as a promising lead series for continuing in vitro and in vivo evaluation against prion disease.Making mad cows a myth! The indole-3-glyoxylamide series of antiprion agents has been further optimised, and characteristics contributing to their activity have been identified by computational studies. Varying the glyoxylamide motif or introducing substitution at N-1 gave analogues with lower efficacy.

The short total synthesis of paullone (1) and dimethyl paullone (2) via a novel palladium-catalyzed intramolecular coupling using the o-bromo- and o-iodo anilides of indoles (3 and 3a) and N-methyl indole 4 is described.

The acylation of benzo[b]furan-, benzo[b]thiophene, and indolyl-3-acetic acid arylamides using acetic anhydride in the presence of 70% perchloric acid occurs at the α-position of the heterocycle to give 2-acetylbenzo[b]furan- , 2-acetylbenzo[b]thiophene,