CHF-6001 - CAS 1239278-59-1
Catalog number: 1239278-59-1
Category: Inhibitor
Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Molecular Formula:
C30H30Cl2F2N2O8S
Molecular Weight:
687.53
COA:
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Targets:
Phosphodiesterase (PDE)
Description:
This active molecular is a Type 4 cyclic nucleotide phosphodiesterase (PDE4) inhibitor originated by Chiesi Farmaceutici with IC50 value of 0.026 ± 0.006 nM. CHF6001 inhibited PDE4 isoforms A to D with equal potency, showed an elevated ratio of high-affinity rolipram binding site versus low-affinity rolipram binding site and displayed >20,000-fold selectivity versus PDE4 compared with a panel of PDEs. In May 2016, Chiesi completed a phase I trial in Chronic Obstructive Pulmonary Disease (In volunteers) in United Kingdom (Inhalation). In Oct 2016, Phase-II clinical trials in Chronic obstructive pulmonary disease (Adjunctive treatment) in Hungary (Inhalation) was on-going.
Purity:
98%
Appearance:
Powder
Synonyms:
CHF-6001; CHF 6001; CHF6001. UNII-0984EU6E2F; 0984EU6E2F; CHEMBL3113974; SCHEMBL12096092; CHF6001; VCFBPAOSTLMYIV-SANMLTNESA-N;[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)ethyl] 3-(cyclopropylmethoxy)-4-(methanesulfonamido)benzoate
Solubility:
Soluble in DMSO
Storage:
-20°C Freezer
MSDS:
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Application:
Allergic asthma; Chronic obstructive pulmonary disease
Quality Standard:
In-house standard
Shelf Life:
2 month in rt, long time
Quantity:
Milligrams-Grams
InChIKey:
VCFBPAOSTLMYIV-SANMLTNESA-N
InChI:
InChI=1S/C30H30Cl2F2N2O8S/c1-45(39,40)35-24-8-6-20(11-27(24)41-15-17-2-3-17)29(37)43-26(12-21-22(31)13-36(38)14-23(21)32)19-7-9-25(44-30(33)34)28(10-19)42-16-18-4-5-18/h6-11,13-14,17-18,26,30,35H,2-5,12,15-16H2,1H3/t26-/m0/s1
Canonical SMILES:
CS(=O)(=O)NC1=C(C=C(C=C1)C(=O)OC(CC2=C(C=[N+](C=C2Cl)[O-])Cl)C3=CC(=C(C=C3)OC(F)F)OCC4CC4)OCC5CC5
Current Developer:
Originator: Chiesi Farmaceutici
1.CHF6001 II: a novel phosphodiesterase 4 inhibitor, suitable for topical pulmonary administration--in vivo preclinical pharmacology profile defines a potent anti-inflammatory compound with a wide therapeutic window.
Villetti G;Carnini C;Battipaglia L;Preynat L;Bolzoni PT;Bassani F;Caruso P;Bergamaschi M;Pisano AR;Puviani V;Stellari FF;Cenacchi V;Volta R;Bertacche V;Mileo V;Bagnacani V;Moretti E;Puccini P;Catinella S;Facchinetti F;Sala A;Civelli M J Pharmacol Exp Ther. 2015 Mar;352(3):568-78. doi: 10.1124/jpet.114.220558. Epub 2015 Jan 9.
CHF6001 [(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoyloxy)ethyl)pyridine 1-oxide] is a novel phosphodiesterase 4 (PDE4) inhibitor designed for use in pulmonary diseases by inhaled administration. Intratracheal administration of CHF6001 to ovalbumin-sensitized Brown-Norway rats suppressed the antigen-induced decline of lung functions (ED50 = 0.1 µmol/kg) and antigen-induced eosinophilia (ED50 = 0.03 µmol/kg) when administered (0.09 μmol/kg) up to 24 hours before antigen challenge, in agreement with CHF6001-sustained lung concentrations up to 72 hours after intratracheal treatment (mean residence time 26 hours). Intranasal, once daily administration of CHF6001 inhibited neutrophil infiltration observed after 11 days of tobacco smoke exposure in mice, both upon prophylactic (0.15-0.45 µmol/kg per day) or interventional (0.045-0.45 µmol/kg per day) treatment. CHF6001 was ineffective in reversing ketamine/xylazine-induced anesthesia (a surrogate of emesis in rat) up to 5 µmol/kg administered intratracheally, a dose 50- to 150-fold higher than anti-inflammatory ED50 observed in rats. When given topically to ferrets, no emesis and nausea were evident up to 10 to 20 µmol/kg, respectively, whereas the PDE4 inhibitor GSK-256066 (6-[3-(dimethylcarbamoyl)phenyl]sulfonyl-4-(3-methoxyanilino)-8-methylquinoline-3-carboxamide) induced nausea at 1 µmol/kg intratracheally.
2.CHF6001 I: a novel highly potent and selective phosphodiesterase 4 inhibitor with robust anti-inflammatory activity and suitable for topical pulmonary administration.
Moretto N;Caruso P;Bosco R;Marchini G;Pastore F;Armani E;Amari G;Rizzi A;Ghidini E;De Fanti R;Capaldi C;Carzaniga L;Hirsch E;Buccellati C;Sala A;Carnini C;Patacchini R;Delcanale M;Civelli M;Villetti G;Facchinetti F J Pharmacol Exp Ther. 2015 Mar;352(3):559-67. doi: 10.1124/jpet.114.220541. Epub 2015 Jan 9.
This study examined the pharmacologic characterization of CHF6001 [(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoyloxy)ethyl)pyridine 1-oxide], a novel phosphodiesterase (PDE)4 inhibitor designed for treating pulmonary inflammatory diseases via inhaled administration. CHF6001 was 7- and 923-fold more potent than roflumilast and cilomilast, respectively, in inhibiting PDE4 enzymatic activity (IC50 = 0.026 ± 0.006 nM). CHF6001 inhibited PDE4 isoforms A-D with equal potency, showed an elevated ratio of high-affinity rolipram binding site versus low-affinity rolipram binding site (i.e., >40) and displayed >20,000-fold selectivity versus PDE4 compared with a panel of PDEs. CHF6001 effectively inhibited (subnanomolar IC50 values) the release of tumor necrosis factor-α from human peripheral blood mononuclear cells, human acute monocytic leukemia cell line macrophages (THP-1), and rodent macrophages (RAW264.7 and NR8383). Moreover, CHF6001 potently inhibited the activation of oxidative burst in neutrophils and eosinophils, neutrophil chemotaxis, and the release of interferon-γ from CD4(+) T cells. In all these functional assays, CHF6001 was more potent than previously described PDE4 inhibitors, including roflumilast, UK-500,001 [2-(3,4-difluorophenoxy)-5-fluoro-N-((1S,4S)-4-(2-hydroxy-5-methylbenzamido)cyclohexyl)nicotinamide], and cilomilast, and it was comparable to GSK256066 [6-((3-(dimethylcarbamoyl)phenyl)sulfonyl)-4-((3-methoxyphenyl)amino)-8-methylquinoline-3-carboxamide].
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