672883-68-0

Usage

Uses

Used in Organic Synthesis:
3-(cyclopropylMethoxy)-4-(difluoroMethoxy)benzoyl chloride is used as a reagent for the introduction of the benzoyl group in organic synthesis. Its unique functional groups allow for the creation of a variety of chemical structures.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 3-(cyclopropylMethoxy)-4-(difluoroMethoxy)benzoyl chloride is used as an intermediate for the preparation of various pharmaceutical compounds. Its specific functional groups contribute to the development of new drugs with potential therapeutic applications.
Used in Agrochemical Industry:
3-(cyclopropylMethoxy)-4-(difluoroMethoxy)benzoyl chloride is also utilized in the agrochemical industry as a precursor for the synthesis of agrochemical compounds. Its properties enable the production of effective pesticides and other agricultural chemicals.

InChI:InChI=1/C12H11ClF2O3/c13-11(16)8-3-4-9(18-12(14)15)10(5-8)17-6-7-1-2-7/h3-5,7,12H,1-2,6H2

Upstream product

• 162401-62-9 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzoic acid 
• 151103-08-1 4-difluoromethoxy-3-hydroxybenzaldehyde 
• 151103-09-2 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzaldehyde 
• 139-85-5 3,4-dihydroxybenzaldehyde 
• 4049-39-2 4-benzyloxy-3-hydroxy-benzaldehyde 
• 1381886-14-1 4-(benzyloxy)-3-(cyclopropylmethoxy)benzaldehyde 
• 25934-52-5 3-(cyclopropylmethoxy)-4-hydroxybenzaldehyde 

Downstream Products

• 672883-67-9 (3S)-3-(3-cyclopropylmethyloxy-4-difluoromethoxyphenylcarboxamido)-2,6-dioxo-hexahydropyridine 
• 672883-84-0 (3S)-3-(3-cyclopropylmethyloxy-4-difluoromethoxyphenylcarboxamido)-2-oxohexahydro-pyridine 
• 672883-90-8 (3S)-3-(3-cyclopropylmethyloxy-4-difluoromethoxyphenylcarboxamido)-2-oxo-1-phenyl-hexahydropyridine 
• 672883-96-4 (3S)-3-(3-cyclopropylmethyloxy-4-difluoromethoxyphenylcarboxamido)-6-oxo-hexahydropyridine 
• 672884-01-4 (3S)-3-(3-cyclopropylmethyloxy-4-difluoromethoxyphenylcarboxamido)-6-oxo-1-phenyl-hexahydropyridine 
• 1001909-97-2 1-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3,5-dichloro-1-pyridin-4-yl)ethanone 

Relevant academic research and scientific papers

Synthesis and evaluation of clioquinol-rolipram/roflumilast hybrids as multitarget-directed ligands for the treatment of Alzheimer's disease

Considering the importance of PDE4D inhibition and the modulation of biometals in Alzheimer's disease (AD) therapeutics, we have designed, synthesized and evaluated a series of new clioquinol-rolipram/roflumilast hybrids as multitarget-directed ligands fo

A Direct Approach to Decoration of Bioactive Compounds via C-H Amination Reaction

The development of new methods to achieve the direct synthesis of bioactive organic molecules is always an important topic in organic synthesis. We hereby demonstrate that N-methoxyamide is an excellent amino source in the iridium-catalyzed intermolecular C-H amination reaction. The linkage of two bioactive organic molecules can be well achieved with this new protocol. More than 20 examples of decorated bioactive compounds were reported, which can facilitate the discovery of new bioactive molecules.

A method for preparing raw material for roflumilast and detection method

The invention discloses a preparation method and a detection method of a roflumilast material. The preparation method comprises the following steps: mixing 3-cyclopropyl methoxy group-4-difluoro methoxy group benzoic acid SM-1, thionyl chloride, dimethyl formamide with toluene, and carrying out an acylating chlorination reaction to obtain a midbody 1; mixing 3,5-dichloro-4-aminopyridine SM-2, tetrahydrofuran with potassium tert-butoxide and carrying out a salt forming reaction to obtain tetrahydrofuran solution of a midbody 2; and then mixing the midbody 1 and the midbody 2 with tetrahydrofuran, carrying out amidation to obtain a crude product of roflumilast, and refining the crude product of roflumilast to prepare the roflumilast material. Aiming to overcome the shortage of the prior art, the preparation process of the roflumilast material is optimized, so that the curative effect for treating diseases such as chronic obstructive pulmonary disease (COPD) is more remarkable; and besides, a systematic, complete and effective composition identifying and content measuring method is provided, so that the quality of the medicine can be effectively controlled, and the clinical effect is ensured.

Synthesis and molecular docking of new roflumilast analogues as preferential-selective potent PDE-4B inhibitors with improved pharmacokinetic profile

In the present work, we designed and synthesized new roflumilast analogues with preferential-selective PDE-4B inhibition activity and improved pharmacokinetic properties. The unsubstituted benzo[d]thiazol-2-yl and -6-yl benzamide derivatives (4a and 6a) showed both good potency and preferential selectivity for PDE-4B. More remarkably, 6c revealed 6 times preferential PDE-4B/4D selectivity with a significant increase of in vitro cAMP and good % inhibition of TNF-α concentration. In addition, the in vitro pharmacokinetics of 6c showed good metabolic stability with in vitro CLint (5.67 mL/min/kg) and moderate % plasma protein binding (53.71%). This was reflected onto increased in vivo exposure with a half-life greater than roflumilast by 3 folds (21 h) and a Cmax value of 113.958 ng/mL. Molecular docking attributed its good activity to its key binding interactions in PDE-4B active site with additional hydrogen bonding with amino acids lining the metal pocket. Summing up, 6c can be considered as suitable candidate for further investigation for the treatment of COPD.

Discovery of N-Alkyl Catecholamides as Selective Phosphodiesterase-4 Inhibitors with Anti-neuroinflammation Potential Exhibiting Antidepressant-like Effects at Non-emetic Doses

Depression involving neuroinflammation is one of the most common disabling and life-threatening psychiatric disorders. Phosphodiesterase 4 (PDE4) inhibitors produce potent antidepressant-like and cognition-enhancing effects. However, their clinical utilit

Novel 3-cyclopropylmethoxy-4-alkoxybenzamide PDE (phosphodiesterase) 4 inhibitors

The invention discloses novel 3-cyclopropylmethoxy-4-alkoxybenzamide PDE (phosphodiesterase) 4 inhibitors. The inhibitors are compounds represented in a general formula I or a general formula II, prodrugs thereof, pharmaceutically usable salts thereof or solvates thereof, wherein R is independent methyl (Me-) or difluoromethyl (CF2H-); R is independent H, Me or Et; R is independent H, MeO or Cl; CnH(2n+2) is alkyl, and N is larger than or equal to 2; a substance shown in the specification is a substituted benzene ring or pyridine ring; X is C or N; Y is C or N. The novel 3-cyclopropylmethoxy-4-alkoxybenzamide PDE 4 inhibitors have the advantages of high in-vitro enzyme inhibition activity, capability of selective application to PDE4 and good anti-inflammation effect and anti-depression effect.

Development of highly potent phosphodiesterase 4 inhibitors with anti-neuroinflammation potential: Design, synthesis, and structure-activity relationship study of catecholamides bearing aromatic rings

In this study, catecholamides (7a–l) bearing different aromatic rings (such as pyridine-2-yl, pyridine-3-yl, phenyl, and 2-chlorophenyl groups) were synthesized as potent phosphodiesterase (PDE) 4 inhibitors. The inhibitory activities of these compounds w

Catecholic amides as potential selective phosphodiesterase 4D inhibitors: Design, synthesis, pharmacological evaluation and structure-activity relationships

In this study, a series of catechol-based amides (8a-n) with different amide linkers linking the catecholic moiety to the terminal phenyl ring was designed and synthesized as potent phosphodiesterase (PDE) 4D inhibitors. The inhibitory activities of these compounds were evaluated against the core catalytic domains of human PDE4 (PDE4CAT), full-length PDE4B1 and PDE4D7 enzymes, and other PDE family members. The results indicated the majority of compounds 8a-n displayed moderate to good inhibitory activities against PDE4CAT. Among these compounds, compound 8j with a short amide linker (-CONHCH2-) displayed comparable PDE4CAT inhibitory activity (IC50 = 410 nM) with rolipram. More interestingly, compound 8g, a potent and selective PDE4D inhibitor (IC50 = 94 nM), exhibited a 10-fold selectivity over the PDE4B subtypes and an over 1000-fold selectivity against other PDE family members. Docking simulations suggested that 8g forms three extra H-bonds with the N-H of residue Asn487 and two water molecules.

HETEROAROMATIC DERIVATIVES AND PHARMACEUTICAL APPLICATIONS THEREOF

Provided herein are novel heteroaromatic derivatives, or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a prodrug, a pharmaceutically acceptable salt or a prodrug thereof, and pharmaceutical compositions containing such compounds. Also provided herein are uses of such compounds or pharmaceutical compositions thereof in the manufacture of a medicament for treating respiratory diseases, especially chronic obstructive pulmonary disease (COPD).

Novel class of benzoic acid ester derivatives as potent PDE4 inhibitors for inhaled administration in the treatment of respiratory diseases

The first steps in the selection process of a new anti-inflammatory drug for the inhaled treatment of asthma and chronic obstructive pulmonary disease are herein described. A series of novel ester derivatives of 1-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3,5-dichloropyridin-4- yl) ethanol have been synthesized and evaluated for inhibitory activity toward cAMP-specific phosphodiesterase-4 (PDE4). In particular, esters of variously substituted benzoic acids were extensively explored, and structural modification of the alcoholic and benzoic moieties were performed to maximize the inhibitory potency. Several compounds with high activity in cell-free and cell-based assays were obtained. Through the evaluation of opportune in vitro ADME properties, a potential candidate suitable for inhaled administration in respiratory diseases was identified and tested in an in vivo model of pulmonary inflammation, proving its efficacy.