TOLAFENTRINE

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

Structure Search

SMILES

COC1=C(OC)C=C2C(=C1)[C@@H]3CN(C)CC[C@@H]3N=C2C4=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

HIDE SMILES / InChI

Molecular Formula	C28H31N3O4S
Molecular Weight	505.628
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16262900 | https://www.ncbi.nlm.nih.gov/pubmed/21382892

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

Targets

Primary Target	Pharmacology	Condition	Potency
Phosphodiesterase 4 54 Target ID: CHEMBL2093863 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12441759 \| https://www.scbt.com/scbt/product/tolafentrine-139308-65-9	Inhibitor 8504
Phosphodiesterase 3 61 Target ID: CHEMBL2094125 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12441759 \| https://www.scbt.com/scbt/product/tolafentrine-139308-65-9	Inhibitor 8504

PubMed

Title	Date	PubMed
Targeting dimethylarginine dimethylaminohydrolases in pulmonary arterial hypertension: a new approach to improve vascular dysfunction?	2011-03-22	21382895
cAMP phosphodiesterase inhibitors increases nitric oxide production by modulating dimethylarginine dimethylaminohydrolases.	2011-03-22	21382892
Inhaled tolafentrine reverses pulmonary vascular remodeling via inhibition of smooth muscle cell migration.	2005-11-01	16262900
Antiremodeling effects of iloprost and the dual-selective phosphodiesterase 3/4 inhibitor tolafentrine in chronic experimental pulmonary hypertension.	2004-04-30	15031263
Cyclic AMP increases endogenous granulocyte colony-stimulating factor formation in monocytes and THP-1 macrophages despite attenuated TNF-alpha formation.	2003-08	12884304
Amplification of the pulmonary vasodilatory response to inhaled iloprost by subthreshold phosphodiesterase types 3 and 4 inhibition in severe pulmonary hypertension.	2002-11	12441759
Coaerosolization of phosphodiesterase inhibitors markedly enhances the pulmonary vasodilatory response to inhaled iloprost in experimental pulmonary hypertension. Maintenance of lung selectivity.	2001-11-01	11719312
Subthreshold doses of specific phosphodiesterase type 3 and 4 inhibitors enhance the pulmonary vasodilatory response to nebulized prostacyclin with improvement in gas exchange.	2000-02	10640287
Low-dose systemic phosphodiesterase inhibitors amplify the pulmonary vasodilatory response to inhaled prostacyclin in experimental pulmonary hypertension.	1999-11	10556112
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.	1997-05	9154331
Differential effects of non-selective and selective phosphodiesterase inhibitors on human eosinophil functions.	1995-02	7539697

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:37:12 GMT 2025` Edited by `admin` on `Mon Mar 31 18:37:12 GMT 2025`
Record UNII	11U7K6T56X
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

B-9004070

Preferred Name

English

TOLAFENTRINE

Official Name

English

Tolafentrine [WHO-DD]

Common Name

English

(-)-4'-(CIS-1,2,3,4,4A,10B-HEXAHYDRO-8,9-DIMETHOXY-2-METHYLBENZO(C)(1,6)NAPHTHYRIDIN-6-YL)-P-TOLUENESULFONANILIDE

Common Name

English

BENZENESULFONAMIDE, N-(4-(1,2,3,4,4A,10B-HEXAHYDRO-8,9-DIMETHOXY-2-METHYLBENZO(C)(1,6)NAPHTHYRIDIN-6-YL)PHENYL)-4-METHYL-, CIS-(-)

Systematic Name

English

BENZENESULFONAMIDE, N-(4-((4AR,10BS)-1,2,3,4,4A,10B-HEXAHYDRO-8,9-DIMETHOXY-2-METHYLBENZO(C)(1,6)NAPHTHYRIDIN-6-YL)PHENYL)-4-METHYL-, REL-(-)-

Systematic Name

English

BY-4070

Code

English

tolafentrine [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C744