Details
Stereochemistry | UNKNOWN |
Molecular Formula | C28H31N3O4S |
Molecular Weight | 505.628 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@]12CCN(C)C[C@@]1([H])C3=C(C=C(OC)C(OC)=C3)C(=N2)C4=CC=C(NS(=O)(=O)C5=CC=C(C)C=C5)C=C4
InChI
InChIKey=FVZJIAUYFDQQKJ-DQEYMECFSA-N
InChI=1S/C28H31N3O4S/c1-18-5-11-21(12-6-18)36(32,33)30-20-9-7-19(8-10-20)28-23-16-27(35-4)26(34-3)15-22(23)24-17-31(2)14-13-25(24)29-28/h5-12,15-16,24-25,30H,13-14,17H2,1-4H3/t24-,25-/m0/s1
Tolafentrine is phosphodiesterase 3/4 (PDE3/4) inhibitor. Treatment of endothelial cells with tolafentrine significantly decreased asymmetrical dimethylarginine-induced apoptosis via a cAMP/PKA-dependent pathway by induction of dimethylarginine dimethylaminohydrolase 2 (DDAH2). Chronic nebulization of PDE3/4 inhibitor significantly attenuated monocrotaline-induced hemodynamic, gas exchange abnormalities, vascular remodeling, and right heart hypertrophy. When chronically nebulized from day 28 to 42 (12 daily aerosol maneuvers), after full establishment of severe pulmonary hypertension, tolafentrine reversed about 60% of all hemodynamic abnormalities in rats, right heart hypertrophy and monocrotaline-induced structural lung vascular changes, including the proportion of pulmonary artery muscularization. Tolafentrine was developed as therapeutic agent for the treatment of asthma. However, this development was discontinued.
Originator
Approval Year
PubMed
Title | Date | PubMed |
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In vitro differentiation of human monocytes to macrophages: change of PDE profile and its relationship to suppression of tumour necrosis factor-alpha release by PDE inhibitors. | 1997 May |
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Coaerosolization of phosphodiesterase inhibitors markedly enhances the pulmonary vasodilatory response to inhaled iloprost in experimental pulmonary hypertension. Maintenance of lung selectivity. | 2001 Nov 1 |
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Amplification of the pulmonary vasodilatory response to inhaled iloprost by subthreshold phosphodiesterase types 3 and 4 inhibition in severe pulmonary hypertension. | 2002 Nov |
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Antiremodeling effects of iloprost and the dual-selective phosphodiesterase 3/4 inhibitor tolafentrine in chronic experimental pulmonary hypertension. | 2004 Apr 30 |
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cAMP phosphodiesterase inhibitors increases nitric oxide production by modulating dimethylarginine dimethylaminohydrolases. | 2011 Mar 22 |
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NCI_THESAURUS |
C744
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C152677
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CHEMBL2104505
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100000077730
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SUB11145MIG
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65990
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7113
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139308-65-9
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DTXSID20161006
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11U7K6T56X
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C094030
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ACTIVE MOIETY