127842-54-0

Basic information

• Product Name: 3,4-BIS-DIFLUOROMETHOXY-BENZALDEHYDE
• Synonyms: 3,4-BIS-DIFLUOROMETHOXY-BENZALDEHYDE;Benzaldehyde, 3,4-bis(difluoroMethoxy)-;Roflumilast Impurity K
• CAS NO: 127842-54-0
• Molecular Formula: C₉H₆F₄O₃
• Molecular Weight: 238.1357528
• EINECS: 1312995-182-4
• Product Categories: Aromatics;Intermediates;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 127842-54-0.mol

Chemical Properties

• Boiling Point: 265.8±35.0℃ (760 Torr)
• Flash Point: 111.1±20.8℃
• Appearance: /
• Density: 1.387±0.06 g/cm3 (20 ºC 760 Torr)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• CAS DataBase Reference: 3,4-BIS-DIFLUOROMETHOXY-BENZALDEHYDE(CAS DataBase Reference)
• NIST Chemistry Reference: 3,4-BIS-DIFLUOROMETHOXY-BENZALDEHYDE(127842-54-0)
• EPA Substance Registry System: 3,4-BIS-DIFLUOROMETHOXY-BENZALDEHYDE(127842-54-0)

Safety Data

• Hazardous Substances Data: 127842-54-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
3,4-Bis(difluoromethoxy)benzaldehyde is used as an intermediate compound for the development of PDE4 inhibitors, which are crucial in the treatment of various medical conditions such as cancer, CNS disorders, and inflammatory disorders. Its role in the synthesis of these compounds contributes to the advancement of therapeutic options for patients suffering from these conditions.
Used in Antiasthmatic Drug Production:
In the pharmaceutical industry, 3,4-Bis(difluoromethoxy)benzaldehyde is used as an impurity in the production of Roflumilast (R639700), an antiasthmatic drug. Its presence, despite being an impurity, is significant in the overall synthesis and effectiveness of the drug in treating asthma-related symptoms.
Used in Chemical Research:
3,4-Bis(difluoromethoxy)benzaldehyde's unique chemical properties make it a valuable compound for research purposes. It can be used in the study of various chemical reactions and mechanisms, contributing to the broader understanding of organic chemistry and its applications in the development of new drugs and materials.

Upstream product

• 1514-87-0 metyhyl chlorodifluoroacetate 
• 139-85-5 3,4-dihydroxybenzaldehyde 
• 1895-39-2 sodium chlorodifluoroacetate 
• 75-45-6 Chlorodifluoromethane 
• 151103-08-1 4-difluoromethoxy-3-hydroxybenzaldehyde 

Downstream Products

• 1164145-18-9 (E)-3-[3,4-bis(difluoromethoxy)phenyl]-2-propenoic acid 
• 192767-14-9 3-(3,4-bis-difluoromethoxy-phenyl)-2-pyridin-4-yl-3-{4-[2,2,2-trifluoro-1-trifluoromethyl-1-(2-trimethylsilanyl-ethoxymethoxy)-ethyl]-phenyl}-propionic acid ethyl ester 
• 192767-15-0 4-(2-(3,4-bis-difluoromethoxy-phenyl)-2-{4-[2,2,2-trifluoro-1-trifluoromethyl-1-(2-trimethylsilanyl-ethoxymethoxy)-ethyl]-phenyl}-ethyl)-pyridine 
• 192767-01-4 L 791943 
• 474499-55-3 {4-[1-(3,4-bis-difluoromethoxy-phenyl)-2-pyridin-4-yl-ethyl]-phenyl}-acetic acid 3-hydroxy-2-hydroxymethyl-2-methyl-propyl ester 
• 192767-00-3 2-{4-[1-(3,4-bis-difluoromethoxy-phenyl)-2-pyridin-4-yl-ethyl]-phenyl}-1,1,1,3,3,3-hexafluoro-propan-2-ol 

Relevant articles and documents

3′,4′-Bis-difluoromethoxycinnamoylanthranilate (FT061): An orally-active antifibrotic agent that reduces albuminuria in a rat model of progressive diabetic nephropathy

Cinnamoylanthranilates including tranilast have been identified as promising antifibrotics that can reduce fibrosis occurring in the kidney during diabetes, thereby delaying and/or preventing kidney dysfunction. Structure-activity relationships aimed at improving potency and metabolic stability have led to the discovery of FT061. This compound, which bears a bis-difluoromethoxy catechol, attenuates TGF-β-stimulated production of collagen in cultured renal mesangial cells (approx 50% at 3 μM). When dosed orally at 20 mg/kg to male Sprague Dawley rats, FT061 exhibited a high bioavailability (73%), Cmax of 200 μM and Tmax of 150 min, and a half-life of 5.4 h. FT061 reduced albuminuria when orally dosed in rats at 200 mg kg/day in a late intervention study of a rat model of progressive diabetic nephropathy.

TRIPYRIDYL CARBOXAMIDE OREXIN RECEPTOR ANTAGONISTS

The present invention is directed to tripyridyl carboxamide compounds which are antagonists of orexin receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

HALOGENATED ANALOGUES OF ANTI-FIBROTIC AGENTS

The present invention relates to halogenated compounds of formula (I) with the substituents as described within the specification. The compounds may be useful as anti-fibrqtic agents. The present invention also relates to methods for their preparation.

PYRIDINE CARBOXAMIDE OREXIN RECEPTOR ANTAGONISTS

The present invention is directed to pyridyl carboxamide compounds which are antagonists of orexin receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved

Design, synthesis, and structure - Activity relationship, molecular modeling, and NMR studies of a series of phenyl alkyl ketones as highly potent and selective phosphodiesterase-4 inhibitors

Phosphodiesterase 4 catalyzes the hydrolysis of cyclic AMP and is a target for the development of anti-inflammatory agents. We have designed and synthesized a series of phenyl alkyl ketones as PDE4 inhibitors. Among them, 13 compounds were identified as having submicromolar IC50 values. The most potent compounds have IC50 values of in the mid- to low-nanomolar range. Compound 5v also showed preference for PDE4 with selectivity of >2000-fold over PDE7, PDE9, PDE2, and PDE5. Docking of 5v, 5zf, and 5za into the binding pocket of the PDE4 catalytic domain revealed a similar binding profile to PDE4 with rolipram except that the fluorine atoms of the difluoromethyl groups of 5v, 5za, and 5zf are within a reasonable range for hydrogen bond formation with the amide hydrogen of Thr 333 and the long alkyl chain bears additional van der Waals interactions with His 160, Asp 318, and Tyr 159.

PHENYLGLYCINAMIDE DERIVATIVES USEFUL AS ANTICOAGULANTS

The present invention relates generally to phenylglycinamide derivatives that inhibit serine proteases. In particular it is directed to novel phenylglycinamide derivatives, and analogues thereof, which are useful as selective inhibitors of serine protease enzymes of the coagulation cascade; for example thrombin, factor VIIa, factor Xa, factor XIa, factor IXa, and/or plasma kallikrein. In particular, it relates to compounds that are factor VIIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of using the same.

INHIBITORS OF PHOSPHODIESTERASE TYPE-IV

The present invention relates to isoxazoline derivatives, which can be used as selective inhibitors of phosphodiesterase (PDE) type IV. In particular, compounds disclosed herein can be useful in the treatment of AIDS, asthma, arthritis, bronchitis, chronic obstructive pulmonary disease (COPD), psoriasis, allergic rhinitis, shock, atopic dermatitis, Crohn's disease, adult respiratory distress syndrome (ARDS), eosinophilic granuloma, allergic conjunctivitis, osteoarthritis, ulcerative colitis and other inflammatory diseases in a patient, particularly in humans. The present invention also relates to processes for the preparation of disclosed compounds, as well as pharmaceutical compositions thereof, and their use as phosphodiesterase (PDE) type IV inhibitors.

NOVEL OXABISPIDINE COMPOUNDS AND THEIR USE IN THE TREATMENT OF CARDIAC ARRHYTHMIAS

There is provided compounds of formula (I), wherein R1, R2, R3, R4, R 41 to R46, A, B and G have meanings given in the description, which are useful in the prophylaxis and in the treatment of arrhythmias, in particular atrial and ventricular arrhythmias.

Improving metabolic stability of phosphodiesterase-4 inhibitors containing a substituted catechol: Prevention of reactive intermediate formation and covalent binding

A detailed study directed towards metabolic stability optimization of the alkoxy substituents on the catechol moiety of CDP-840 is reported. Replacement of the methoxy and cyclopentyloxy substituents by cyclobutyloxy and/or difluromethoxy groups resulted in the discovery of potent and selective PDE4 inhibitors where the formation of reactive metabolites that could covalently bind to microsomal protein was significantly reduced or eliminated.

Discovery of L-791,943: a potent, selective, non emetic and orally active phosphodiesterase-4 inhibitor.

Structure-activity relationship studies directed toward improving the potency and metabolic stability of CDP-840 (3) resulted in the discovery of L-791,943 (11n) as a potent (HWB TNF-alpha = 0.67 microM) and orally active phosphodiesterase type 4 (PDE4) inhibitor. This compound, which bears a stable bis-difluoromethoxy catechol and a pendant hexafluorocarbinol, exhibited a long half-life in rat and in squirrel monkey. It is well tolerated in ferret with an emetic threshold greater than 30 mg/kg (po) and was found to be active in the ovalbumin-induced bronchoconstriction model in guinea pig and in the ascaris-induced bronchoconstriction models in sheep and squirrel monkey.