197067-27-9

Basic information

• Product Name: 3,3-difluoro-1,3-dihydro-2H-Indol-2-one
• Synonyms: 3,3-difluoro-1,3-dihydro-2H-Indol-2-one;3,3-Difluoroindolin-2-one
• CAS NO: 197067-27-9
• Molecular Formula: C₈H₅F₂NO
• Molecular Weight: 169.1282064
• Mol File: 197067-27-9.mol

Chemical Properties

• Boiling Point: 251.0±40.0 °C(Predicted)
• Appearance: /
• Density: 1.41±0.1 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• PKA: 10.24±0.40(Predicted)
• CAS DataBase Reference: 3,3-difluoro-1,3-dihydro-2H-Indol-2-one(CAS DataBase Reference)
• NIST Chemistry Reference: 3,3-difluoro-1,3-dihydro-2H-Indol-2-one(197067-27-9)
• EPA Substance Registry System: 3,3-difluoro-1,3-dihydro-2H-Indol-2-one(197067-27-9)

Safety Data

• Hazardous Substances Data: 197067-27-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Research:
3,3-difluoro-1,3-dihydro-2H-Indol-2-one is used as a precursor in the synthesis of various pharmaceutical compounds. Its unique chemical structure and properties contribute to the development of new medicinal drugs, particularly those targeting mental health and cancer treatment.
Used in Medicinal Drug Development:
In the field of medicinal drug development, 3,3-difluoro-1,3-dihydro-2H-Indol-2-one is utilized for its potential antipsychotic and antitumor properties. Its incorporation into new drug formulations aims to address unmet needs in the treatment of psychiatric disorders and various types of cancer.

Upstream product

• 667-27-6 Ethyl bromodifluoroacetate 
• 62-53-3 aniline 
• 221665-91-4 1-benzyl-3,3-difluoroindolin-2-one 
• 91-56-5 indole-2,3-dione 
• 2365-44-8 3-hydrazonoindolin-2-one 

Downstream Products

• 1521271-20-4 3,3-difluoro-3H-indol-2-yl 3,4,6-tri-O-acetyl-2-O-benzyl-β-D-glucopyranoside 
• 1521271-22-6 3,3-difluoro-3H-indol-2-yl 3,4,6-tri-O-acetyl-2-O-benzyl-α-D-glucopyranoside 
• 1521271-26-0 3,3-difluoro-3H-indol-2-yl 2,3,4,6-tetra-O-benzoyl-α-D-glucopyranoside 
• 1521271-28-2 3,3-difluoro-3H-indol-2-yl 2,3,4,6-tetra-O-benzoyl-α-D-mannopyranoside 
• 1521271-14-6 3,3-difluoro-3H-indol-2-yl 2,3,4,6-tetra-O-benzyl-α-D-glucopyranoside 
• 1521271-16-8 3,3-difluoro-3H-indol-2-yl 2,3,4,6-tetra-O-benzyl-β-D-glucopyranoside 
• 1521271-18-0 3,3-difluoro-3H-indol-2-yl 2,3,4,6-tetra-O-benzyl-α-D-mannopyranoside 
• 1521271-27-1 3,3-difluoro-3H-indol-2-yl 2,3,4,6-tetra-O-benzoyl-β-D-galactopyranoside 
• 1352949-53-1 tert-butyl 3-((8-(3-(3,3-difluoro-2-oxoindolin-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate 

Relevant articles and documents

Solvent Effects: Syntheses of 3,3-Difluorooxindoles and 3-Fluorooxindoles from Hydrazonoindolin-2-one by Selectfluor

Efficient syntheses of 3,3-difluorooxindoles and 3-fluorooxindoles via fluorination of hydrazonoindolin-2-one with Selectfluor are reported. Under different solvent conditions, this method produced 3,3-difluorooxindoles and 3-fluorooxindoles selectively. The broad substrate scope and mild reaction conditions make this transformation a valuable method in drug discovery and development.

New Imatinib Derivatives with Antiproliferative Activity against A549 and K562 Cancer Cells

Tyrosine kinase enzymes are among the primary molecular targets for the treatment of some human neoplasms, such as those in lung cancer and chronic myeloid leukemia. Mutations in the enzyme domain can cause resistance and new inhibitors capable of circumventing these mutations are highly desired. The objective of this work was to synthesize and evaluate the antiproliferative ability of ten new analogs that contain isatins and the phenylamino-pyrimidine pyridine (PAPP) skeleton, the main pharmacophore group of imatinib. The 1,2,3-triazole core was used as a spacer in the derivatives through a click chemistry reaction and gave good yields. All the analogs were tested against A549 and K562 cells, lung cancer and chronic myeloid leukemia (CML) cell lines, respectively. In A549 cells, the 3,3-difluorinated compound (3a), the 5-chloro-3,3-difluorinated compound (3c) and the 5-bromo-3,3-difluorinated compound (3d) showed IC50 values of 7.2, 6.4, and 7.3 μM, respectively, and were all more potent than imatinib (IC50 of 65.4 μM). In K562 cells, the 3,3-difluoro-5-methylated compound (3b) decreased cell viability to 57.5% and, at 10 μM, showed an IC50 value of 35.8 μM (imatinib, IC50 = 0.08 μM). The results suggest that 3a, 3c, and 3d can be used as prototypes for the development of more potent and selective derivatives against lung cancer.

INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE

Disclosed herein are compounds which inhibit RIPK1, pharmaceutical compositions, and methods of treatment of RIPK1-mediated diseases, such as neurodegenerative disorders, inflammatory disorders, and cancer.

ISATIN-DERIVED COMPOUNDS, USE OF THE COMPOUNDS FOR THE TREATMENT OF AIDS AND METHOD OF TREATMENT USING THESE COMPOUNDS

This invention relates to HIV-inhibiting compounds consisting of other Formulae I, II or III isatin derivatives, as shown below (Formulae I, II and III), whereby in Formulae I, II and III, R1 is selected from H, CH3 or Cl; R2 is selected from one of the following radicals: zidovudine, amprenavir or an acyclic phosphonate chain, as shown below. This invention also relates to the use and treatment method using the Formulae I, II and III compounds. According to this invention, these compounds are also used for the treatment of infections caused by HBV or co-infection caused by HIV and HBV.

PHARMACEUTICAL COMPOUNDS

Benzimidazole derivatives of formula (I): (Formula (I)) wherein: R1is -(CH2)m-R7, (Formula (II)) or (Formula (III)); R2 is H, halo, -(CH2)m-NH2, -(CH2)n-C(=NH)-NH2 or -(CH2)n-NH-(CH2)m-NHR9; R3 is H, F or Cl; each of R4, R5 and R6 is independently H or F; R7 is C1-C6 alkyl, CF3, -SO2R11, -NH-(CH2)2-(NH)r-R8, -NH-CH(R8R9) or a group of the following formula (A): (Formula (A)): W is -(CH2)m-, -CH2-O-CH2-, -CH2-S-CH2-, -(CH2)r-S(O)2-CH2-or -(CH2)r-NR8-CH2-; m is an integer of 1 to 3; n is 1 or 2; p is 1 and V is CH; or p is 0 and V is N; q is 0 or 1; r is 0 or 1; R8 is H, -SO2R11,-SO2CF3, -COR11, -C(O)OR11, -CON(R9)2 or -(CH2)nSO2R11; R9 is H or C1-C6 alkyl, each R9 being the same or different when two are present; R10 is -SO2R11, -SO2CF3, -COR11, -CON(R9)2 or -(CH2)nSO2R11; and R11 is C1-C6 alkyl; and the pharmaceutically acceptable salts thereof are inhibitors of RSV and can therefore be used to treat or prevent an RSV infection.

Selective fluorination method for isatin hydrazones compounds

The invention discloses a selective fluorination method for an isatin hydrazones compound. The method comprises the steps that one pot reaction is carried out on isatin hydrazone, 1-chloromethyl-4-fluorine-1,4-diazabicyclo [2.2.2] octane bis (tetrafluoroborate) salt and alkali compounds, corresponding 3,3-difluoro indolone and fluorooxindole fluorination products are selectively synthesized; the method fills up technical gaps in the prior art that isatin hydrazones compound is selectively synthesized by using a three-position single fluorination or double fluorination technology starting fromisatin, the operation is simple, the process is short, the product yield is high, and industrial production requirements are met.

Copper/B2pin2-catalyzed C-H difluoroacetylation-cycloamidation of anilines leading to the formation of 3,3-difluoro-2-oxindoles

An original and efficient synthesis of 3,3-difluoro-2-oxindole derivatives has been developed via copper/B2pin2-catalyzed difluoroacetylation of aniline via C-H activation followed by intramolecular amidation. In this method, amino groups in primary, secondary or tertiary anilines act as directing groups, providing ortho-difluoroacetylated products regioselectively. And in the first two cases, further intramolecular amidation affords 3,3-difluoro-2-oxindole derivatives via a one-pot strategy. This method facilitates the synthesis of compound A as a potent and selective EP3 receptor antagonist in only five steps in 13% yield instead of the previously reported nine steps in overall 4% yield.

Visible-Light-Promoted Tandem Difluoroalkylation-Amidation: Access to Difluorooxindoles from Free Anilines

An efficient and synthetically convenient method for the synthesis of 3,3-difluoro-2-oxindole through a visible-light-induced photoredox difluoromethylation-amidation is described. The process can generate a broad range of difluorooxindoles using bromodifluoroacetate and broadly available free anilines. The wide range of substrate tolerance and mild reaction conditions make this transformation a highly valuable method in applications for drug discovery and development.

Phenyl Benzenesulfonylhydrazides Exhibit Selective Indoleamine 2,3-Dioxygenase Inhibition with Potent in Vivo Pharmacodynamic Activity and Antitumor Efficacy

Tryptophan metabolism has been recognized as an important mechanism in immune tolerance. Indoleamine 2,3-dioxygenase plays a key role in local tryptophan metabolism via the kynurenine pathway and has emerged as a therapeutic target for cancer immunotherapy. Our prior study identified phenyl benzenesulfonyl hydrazide 2 as a potent in vitro (though not in vivo) inhibitor of indoleamine 2,3-dioxygenase. Further lead optimization to improve in vitro potencies and pharmacokinetic profiles resulted in N′-(4-bromophenyl)-2-oxo-2,3-dihydro-1H-indole-5-sulfonyl hydrazide 40, which demonstrated 59% oral bioavailability and 73% of tumor growth delay without apparent body weight loss in the murine CT26 syngeneic model, after oral administration of 400 mg/kg. Accordingly, 40, is proposed as a potential drug lead worthy of advanced preclinical evaluation.

Regenerative glycosylation under nucleophilic catalysis

This article describes 3,3-difluoroxindole (HOFox)-mediated glycosylation. The uniqueness of this approach is that both the in situ synthesis of 3,3-difluoro-3H-indol-2-yl (OFox) glycosyl donors and activation thereof can be conducted in a regenerative fashion as is a typical reaction performed under nucleophilic catalysis. Only a catalytic amount of the OFox imidate donor and a Lewis acid activator are present in the reaction medium. The OFox imidate donor is constantly regenerated upon its consumption until glycosyl acceptor has reacted.