77603-39-5

Upstream product

• 825-40-1 2-bromo-p-chloroacetophenone 
• 28144-70-9 anthranilic acid amide 
• 6341-92-0 6-chloroisatin 
• 118-48-9 isatoic anhydride 

Relevant academic research and scientific papers

Synthesis of substituted tryptanthrin via aryl halides and amines as antitumor and anti-MRSA agents

The natural alkaloid, tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione), and its analogues are found to exhibit potent antitumor and anti-MRSA activities. An efficient and convenient method has been developed for the synthesis of tryptanthrin D-ring derivatives through the reaction of substituted tryptanthrins and secondary amines in moderate to good yields. Some of the new compounds exhibited antitumor activities against the human tumor cell lines A549, HCT116 and MDA-MB-231, with mean IC50 values at low micromolar levels. In addition, some of the compounds showed excellent anti-MRSA activities and were more effective than vancomycin, with MIC values of 0.31–1.25 μg/mL for Mu50,RN4220, and Newman strains.

Method for synthesizing tryptanthrin alkaloids through one-pot series reaction

The invention discloses a method for synthesizing tryptanthrin alkaloids through one-pot series reaction, belonging to the technical field of organic synthesis. According to key points of the technical scheme of the invention, the method comprises the following steps: (1) putting an o-bromoacetophenone compound, dimethyl sulfoxide and an iodine simple substance in a reaction vessel, and heating, stirring and reacting at the temperature of 110 DEG C; (2) cooling to room temperature, adding an anthranilamide compound, copper salt and alkali, stirring and reacting at room temperature, then heating up to 100 DEG C, stirring and reacting until TLC tracking monitoring reaction is complete, and finally obtaining the tryptanthrin alkaloids. The method disclosed by the invention overcomes the defects that raw material types are fewer, substrate application range is narrow, reaction conditions are harsh and a strong acid reagent sensitive to water is used in an existing synthesis method of the tryptanthrin alkaloids, is an efficient tryptanthrin alkaloid one-pot series synthesis method and has the advantages of simple and easily available starting materials, mild reaction conditions, simplicity in operation and the like.

Design, synthesis, and structure-activity relationship studies of tryptanthrins as antitubercular agents

The natural product tryptanthrin (1a) represents a potential lead for new tuberculosis (TB) drugs since tryptanthrin and its synthetic analogues possess potent in vitro activity against Mycobacterium tuberculosis (Mtb). However, in spite of their in vitro activity, none of these agents have been shown to be efficacious in vivo against animal models of TB. Described herein are syntheses of new tryptanthrin analogues together with a systematic investigation of their in vitro antitubercular activity and ADME properties followed by pharmacokinetic characterization in rodents for the most promising compounds. Those with the best potency and oral bioavailability were progressed to evaluations of efficacy against acute murine TB. The work aimed to prove the concept that this compound class can limit growth of Mtb during infection as well as to establish the SAR for in vitro activity against Mtb and the range of in vitro ADME parameters for this class of natural products. Novel C-11-deoxy (5b) and A-ring-saturated (6) tryptanthrin analogues were discovered that maintained activity against Mtb and showed improved solubility compared to tryptanthrin as well as evidence of oral bioavailability in rodents. However, neither 5b nor 6 demonstrated efficacy against acute murine TB following administration at doses up to 400 mg/kg daily for 4 weeks. Although 5b and 6 failed to inhibit replication or kill Mtb in vivo, they illuminate a path to new structural variations of the tryptanthrin scaffold that may maximize the potential of this class of compounds against TB.

Discovery of tryptanthrin derivatives as potent inhibitors of indoleamine 2,3-dioxygenase with therapeutic activity in lewis lung cancer (LLC) tumor-bearing mice

Indoleamine 2,3-dioxygenase (IDO-1) is emerging as an important new therapeutic target for the treatment of cancer, neurological disorders, and other diseases that are characterized by pathological tryptophan metabolism. However, only a few structural classes are known to be IDO-1 inhibitors. In this study, a natural compound tryptanthrin was discovered to be a novel potent IDO-1 inhibitor by screening of indole-based structures. Three series of 13 tryptanthrin derivatives were synthesized, and the structure-activity analysis was undertaken. The optimization led to the identification of 5c, which exhibited the inhibitory activity at a nanomolar level. In vitro 5c dramatically augmented the proliferation of T cells. When administered to Lewis lung cancer (LLC) tumor-bearing mice, 5c significantly inhibited IDO-1 activity and suppressed tumor growth. In addition, 5c reduced the numbers of Foxp3 + regulatory T cells (Tregs), which are known to prevent the development of efficient antitumor immune responses.

Indolo[2,1-biquinazoline-6,12-dione antibacterial compounds and methods of use thereof

Methods, compounds and compositions are provided form inhibiting the growth of pathogenic mycobacteria in vitro and of treatment of pathogenic mycobacterial infections in vivo using indolo[2,1-b]quinazoline-6,12-dione compounds of the formula (I): STR1 wherein A, B, C, D, E, F, G and H are independently selected from carbon and nitrogen, or A and B or C and D can be taken together to be nitrogen or sulfur, and the pharmaceutically acceptable salts thereof. The methods, compounds and compositons are particularly useful for inhibiting the growth of Mycobacterium tuberculosis, and may be used alone, or in combination with other anti-Mycobacterium tuberculosis agents, such as isoniazid, rifampin, pyrazinamide, rifabutin, streptomycin and ciprofloxacin, to provide new agents for the treatment of tuberculosis, including multidrug-resistant tuberculosis (MDRTB).

ANTIMICROBIAL AGENTS FROM HIGHER PLANTS. NEW SYNTHESIS AND BIOACTIVITY OF TRYPTANTHRIN (INDOLO--QUINAZOLIN-6,12-DIONE) AND ITS ANALOGUES.

Base-catalyzed condensation of substituted isatins and substituted isatoic anhydrides provides a convenient, one-step flexible synthesis of indolo--quinazolin-6,12-diones, including the antifungal natural product tryptanthrin.This new process provides the basis for a systematic exploration of the relationship between structure and antimicrobial activity.Preliminary findings demonstrate that non-symmetrically substituted analogues are easily prepared and the method tolerates the presence of a variety of ring substituents.