![1-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropyl)ethanone](/Databaselist/images/loading.webp)
862574-88-7Relevant academic research and scientific papers
Pharmaceutical compositions for the treatment of cystic fibrosis transmembrane conductance regulator mediated diseases
-
, (2021/04/21)
The present invention features compositions comprising a plurality of therapeutic agents wherein the presence of one therapeutic agent enhances the properties of at least one other therapeutic agent. In one embodiment, the therapeutic agents are cystic fibrosis transmembrane conductance regulators (CFTR) such as a CFTR corrector or CFTR potentiator for the treatment of CFTR mediated diseases such as cystic fibrosis. Methods and kits thereof are also disclosed.
METHODS OF TREATMENT FOR CYSTIC FIBROSIS
-
, (2020/06/05)
This application describes methods of treating cystic fibrosis or a CFTR mediated disease comprising administering Compound I or a pharmaceutically acceptable salt thereof. (I) The application also describes pharmaceutical compositions comprising Compound I or a pharmaceutically acceptable salt thereof and optionally comprising one or more additional CFTR modulating agents.
METHODS OF TREATMENT FOR CYSTIC FIBROSIS
-
, (2019/02/06)
Compound I of the formula (I) and/or pharmaceutically acceptable salt(s) of Compound I comprised in a pharmaceutical composition and methods of using the same to treat cystic fibrosis.
Oxidative Ring Contraction of Cyclobutenes: General Approach to Cyclopropylketones including Mechanistic Insights
Baumann, Andreas N.,Schüppel, Franziska,Eisold, Michael,Kreppel, Andrea,De Vivie-Riedle, Regina,Didier, Dorian
, p. 4905 - 4921 (2018/05/17)
An original oxidative ring contraction of easily accessible cyclobutene derivatives for the selective formation of cyclopropylketones (CPKs) under atmospheric conditions is reported. Comprehensive mechanistic studies are proposed to support this novel, yet unusual, rearrangement. Insights into the mechanism ultimately led to simplification and generalization of the ring contraction of cyclobutenes using mCPBA as an oxidant. This unique and functional group tolerant transformation proceeds under mild conditions at room temperature, providing access to a new library of polyfunctionalized motifs. With CPKs being attractive and privileged pharmacophores, the elaboration of such a simple and straightforward strategy represents a highly valuable tool for drug discovery and medicinal chemistry. Additionally, the described method was employed to generate a pool of bioactive substances and key precursors in a minimum number of steps.
MODULATOR OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR, PHARMACEUTICAL COMPOSITIONS, METHODS OF TREATMENT, AND PROCESS FOR MAKING THE MODULATOR
-
, (2018/06/30)
Compounds of Formula (I) pharmaceutically acceptable salts thereof, deuterated derivatives of any of the foregoing, and metabolites of any of the foregoing are disclosed. Pharmaceutical compositions comprising the same, methods of treating cystic fibrosis using the same, and methods for making the same are also disclosed. Also disclosed are solid state forms of Compound 1 and salts and solvates thereof.
Synthetic method of key intermediate of lumacaftor
-
, (2018/04/26)
The invention relates to a synthetic method of the key intermediate 1-(2, 2-difluorobenzo[D][1, 3]dioxole-5) cyclopropanecarboxylic acid of lumacaftor. 2, 2-difluoro-1, 3-benzodioxole is used as a starting material, and the Friedel-Crafts reaction, the Grignard reaction, dehydration, catalytic hydrogenation, a substitution reaction, a cyclization reaction and a hydrolysis reaction are carried outto obtain 1-(2, 2-difluorobenzo[D][1, 3]dioxole-5) cyclopropanecarboxylic acid. The method has no demanding reaction conditions, the method is simple and easy to operate, used reagents are easy to obtain, use of the hypertoxic material sodium cyanide is avoided, the reaction yield is improved, and the method is suitable for industrial production.
1 - (2, 2 - Difluorobenzene and [d] [1, 3] dioxo heterocyclic pentene - 5 - yl) cyclopropanecarboxylic acid synthetic method and intermediate
-
, (2018/04/02)
The invention belongs to the field of chemical synthesis of drugs, particularly relates to a synthetic method of 1-(2,2-difluoro-benzo[d][1,3]) dioxole-5-yl) cyclopropanecarboxylic acid and an intermediate and aims to provide a synthesis method of a compound (1). The method comprises steps as follows: a, a compound (4) and boron tribromide react, and a compound (3) is synthesized; b, the compound (3) and difluorodibromomethane have a ring closing reaction in the presence of a phase-transfer catalyst, and a compound (2) is synthesized; c, the compound (2) is hydrolyzed, and the compound (1) is synthesized. According to the synthetic method and the intermediate, one novel compound (4) is provided, one novel preparation method of the compound (1) is obtained, with the adoption of the method, not only can the overall yield of the reaction be increased, but also expensive reaction raw materials can be avoided, and the reaction cost is reduced to the great extent; besides, according to the method, utilization of a palladium catalyst and a dangerous sodium cyanide reagent can further be avoided, the safety of pharmaceutical production is guaranteed, and the method is applicable to industrial production.
Synthesis and biological evaluation of novel thiazole- VX-809 hybrid derivatives as F508del correctors by QSAR-based filtering tools
Liessi, Nara,Cichero, Elena,Pesce, Emanuela,Arkel, Maria,Salis, Annalisa,Tomati, Valeria,Paccagnella, Matteo,Damonte, Gianluca,Tasso, Bruno,Galietta, Luis J.V.,Pedemonte, Nicoletta,Fossa, Paola,Millo, Enrico
, p. 179 - 200 (2017/12/28)
The most common CF mutation, F508del, impairs the processing and gating of CFTR protein. This deletion results in the improper folding of the protein and its degradation before it reaches the plasma membrane of epithelial cells. Present correctors, like VX809 only induce a partial rescue of the mutant protein. Our previous studies reported a class of compounds, called aminoarylthiazoles (AATs), featuring an interesting activity as correctors. Some of them show additive effect with VX809 indicating a different mechanism of action. In an attempt to construct more interesting molecules, it was thought to generate chemically hybrid compounds, blending a portion of VX809 merged to the thiazole scaffold. This approach was guided by the development of QSAR analyses, which were performed based on the F508del correctors so far disclosed in the literature. This strategy was aimed at exploring the key requirements turning in the corrector ability of the collected derivatives and allowed us to derive a predictive model guiding for the synthesis of novel hybrids as promising correctors. The new molecules were tested in functional and biochemical assays on bronchial CFBE41o-cells expressing F508del-CFTR showing a promising corrector activity.
PHARMACEUTICAL COMPOSITIONS OF 3-(6-(1-(2,2-DIFLUOROBENZO[D][1,3]DIOXOL-5-YL)CYCLOPROPANECARBOXAMIDO)-3-METHYLPYRIDIN-2-YL)BENZOIC ACID AND ADMINISTRATION THEREOF
-
, (2019/03/09)
A pharmaceutical composition comprising Compound 1,(3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid), and at least one excipient selected from: a filler, a diluent, a disintegrant, a surfactant, a binder, a glidant and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Methods for treating a patient in need thereof include administering an oral pharmaceutical formulation of Compound 1 to the patient.
Method for preparing benzo[1,3-d] dioxole and intermediate of benzo[1,3-d] dioxole
-
Paragraph 0056; 0057; 0058, (2017/08/29)
The invention relates to the field of medicinal chemical synthesis, and discloses a method for preparing benzo[1,3-d] dioxole and an intermediate of benzo[1,3-d] dioxole. The method comprises the following steps: performing three steps of reactions of chloro-substitution, fluorination and deprotection on a compound of formula (4) as shown in the specification so as to prepare a compound of formula (1) as shown in the specification, and in the formulae, R is a carboxyl protection group. By adopting the method, the problems that in the prior art, the yield of benzo[1,3-d] dioxole is low and the reaction operation is not safe can be solved, the compound of the formula (4) is adopted as a raw material which is directly introduced into a three-membered ring structure, so that a dangerous sodium cyanide reagent is not used, and moreover, a reaction route is shortened, the overall yield of the reaction can be greatly increased, and the method is applicable to industrial production.
