153587-14-5

Basic information

• Product Name: 3-Cyclopentyloxy-4-difluoromethoxy-benzaldehyde
• Synonyms: Benzaldehyde, 3-(cyclopentyloxy)-4-(difluoromethoxy)-
• CAS NO: 153587-14-5
• Molecular Formula: C₁₃H₁₄F₂O₃
• Molecular Weight: 256.25
• Mol File: 153587-14-5.mol

Chemical Properties

• Boiling Point: 348.4±37.0 °C(Predicted)
• Appearance: /
• Density: 1.249±0.06 g/cm3(Predicted)
• CAS DataBase Reference: 3-Cyclopentyloxy-4-difluoromethoxy-benzaldehyde(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Cyclopentyloxy-4-difluoromethoxy-benzaldehyde(153587-14-5)
• EPA Substance Registry System: 3-Cyclopentyloxy-4-difluoromethoxy-benzaldehyde(153587-14-5)

Safety Data

• Hazardous Substances Data: 153587-14-5(Hazardous Substances Data)

Upstream product

• 151103-08-1 4-difluoromethoxy-3-hydroxybenzaldehyde 
• 139-85-5 3,4-dihydroxybenzaldehyde 
• 75-45-6 Chlorodifluoromethane 
• 137-43-9 Cyclopentyl bromide 
• 930-28-9 cyclopentyl chloride 

Downstream Products

• 775350-89-5 (4-chloro-phenyl)-(3-cyclopentyloxy-4-difluoromethoxy-phenyl)-methanol 
• 153587-51-0 4-difluoromethoxy-3-(cyclopentyloxy)phenylmethanol 
• 159783-08-1 3-(cyclopentyloxy)-4-(difluoromethoxy)benzoic acid 
• 1093411-89-2 1-(3-cyclopentyloxy-4-difluoromethoxyphenyl)-3-methylbutan-1-ol 
• 159783-09-2 3-cyclopentyloxy-4-difluoromethoxybenzoyl chloride 

Relevant articles and documents

New hybrid pyrazole and imidazopyrazole antinflammatory agents able to reduce ROS production in different biological targets

Several anti-inflammatory agents based on pyrazole and imidazopyrazole scaffolds and a large library of substituted catechol PDE4D inhibitors were reported by us in the recent past. To obtain new molecules potentially able to act on different targets involved in inflammation onset we designed and synthesized a series of hybrid compounds by linking pyrazole and imidazo-pyrazole scaffolds to differently decorated catechol moieties through an acylhydrazone chain. Some compounds showed antioxidant activity, inhibiting reactive oxygen species (ROS) elevation in neutrophils, and a good inhibition of phosphodiesterases type 4D and, particularly, type 4B, the isoform most involved in inflammation. In addition, most compounds inhibited ROS production also in platelets, confirming their ability to exert an antiinflammatory response by two independent mechanism. Structure–activity relationship (SAR) analyses evidenced that both heterocyclic scaffolds (pyrazole and imidazopyrazole) and the substituted catechol moiety were determinant for the pharmacodynamic properties, even if hybrid molecules bearing to the pyrazole series were more active than the imidazopyrazole ones. In addition, the pivotal role of the catechol substituents has been analyzed. In conclusion the hybridization approach gave a new serie of multitarget antiinflammatory compounds, characterized by a strong antioxidant activity in different biological targets.

Insight into GEBR-32a: Chiral resolution, absolute configuration and enantiopreference in PDE4D inhibition

Alzheimer's disease is the most common type of dementia, affecting millions of people worldwide. One of its main consequences is memory loss, which is related to downstream effectors of cyclic adenosine monophosphate (cAMP). A well-established strategy to avoid cAMP degradation is the inhibition of phosphodiesterase (PDE). In recent years, GEBR-32a has been shown to possess selective inhibitory properties against PDE type 4 family members, resulting in an improvement in spatial memory processes without the typical side effects that are usually correlated with this mechanism of action. In this work, we performed the HPLC chiral resolution and absolute configuration assignment of GEBR-32a. We developed an efficient analytical and semipreparative chromatographic method exploiting an amylose-based stationary phase, we studied the chiroptical properties of both enantiomers and we assigned their absolute configuration by 1H-NMR (nuclear magnetic resonance). Lastly, we measured the IC50 values of both enantiomers against both the PDE4D catalytic domain and the long PDE4D3 isoform. Results strongly support the notion that GEBR-32a inhibits the PDE4D enzyme by interacting with both the catalytic pocket and the regulatory domains.

Synthesis, biological activities and pharmacokinetic properties of new fluorinated derivatives of selective PDE4D inhibitors

Abstract A new series of selective PDE4D inhibitors has been designed and synthesized by replacing 3-methoxy group with 3-difluoromethoxy isoster moiety in our previously reported cathecolic structures. All compounds showed a good PDE4D3 inhibitory activity, most of them being inactive toward other PDE4 isoforms (PDE4A4, PDE4B2 and PDE4C2). Compound 3b, chosen among the synthesized compounds as the most promising in terms of inhibitory activity, selectivity and safety, showed an improved pharmacokinetic profile compared to its non fluorinated analogue. Spontaneous locomotor activity, assessed in an open field apparatus, showed that, differently from rolipram and diazepam, selective PDE4D inhibitors, such as compounds 3b, 5b and 7b, did not affect locomotion, whereas compound 1b showed a tendency to reduce the distance traveled and to prolong the immobility period, possibly due to a poor selectivity.

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.

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.

NEW HETEROCYCLIC AMIDE COMPOUNDS USEFUL FOR THE TREATMENT OF INFLAMMATORY AND ALLERGIC DISORDERS: PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

The present invention relates to novel heterocyclic compounds that inhibit phosphodiesterase type 4 (PDE 4). The compounds are useful for treating inflammatory conditions, diseases of the central nervous systems and insulin resistant diabetes.

CONDENSED HETEROCYCLIC COMPOUNDS AS PDE-IV INHIBITORS FOR THE TREATMENT OF INFLAMMATORY AND ALLERGIC DISORDERS

The present invention relates to novel heterocyclic compounds that inhibit phosphodiesterase type 4 (PDE4). The compounds are useful for treating inflammatory conditions, diseases of the central nervous system and insulin resistant diabetes , (formula I)

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.

COMPOUNDS CONTAINING PHENYL LINKED TO ARYL OR HETEROARYL BY AN ALIPHATIC- OR HETEROATOM-CONTAINING LINKING GROUP

This invention is directed to the pharmaceutical use of phenyl compounds, which are linked to an aryl moiety by various linkages, for inhibiting tumor necrosis factor. The invention is also directed to the compounds, their preparation and pharmaceutical compositions containing these compounds. Furthermore, this invention is directed to the pharmaceutical use of the compounds for inhibiting cyclic AMP phosphodiesterase

FLUOROALKOXY-SUBSTITUTED BENZAMIDES AND THEIR USE AS CYCLIC NUCLEOTIDE PHOSPHODIESTERASE INHIBITORS

Compounds of formula (I), in which one of the substituents R1 or R2 stands for hydrogen, 1-6C-alkoxy, 3-7C-cycloalkoxy, 3-7C-cycloalkylmethoxy, benzyloxy or totally or partially fluorine-substituted 1-4C-alkoxy, and the other stands for totally or partially fluorine-substituted 1-4C-alkoxy, and R3 stands for phenyl, pyridyl, R31, R32 and R33-substituted phenyl or R34, R35, R36 and R37-substituted pyridyl, in which R31 stands for hydroxy, halogen, cyano, carboxyl, trifluoromethyl 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyl, 1-4C-alkylcarbonyloxy, amino, mono- or di-1-4C-atkylamino or 1-4C-alkylcarbonylamino; R32 stands for hydrogen, hydroxy, halogen, amino, trifluoromethyl, 1-4C-alkyl or 1-4C-alkoxy; R33 stands for hydrogen, halogen, 1-4C-alkyl or 1-4C-alkoxy; R34 stands for hydroxy, halogen, cyano, carboxyl, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl or amino; R35 stands for hydrogen, halogen, amino or 1-4C-alkyl; R36 stands for hydrogen or halogen; and R37 stands for hydrogen or halogen. These compounds constitute new effective bronchotherapeutic drugs