ENPROFYLLINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C8H10N4O2
Molecular Weight	194.1906
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCN1C2=C(N=CN2)C(=O)NC1=O

InChI

InChIKey=SIQPXVQCUCHWDI-UHFFFAOYSA-N

InChI=1S/C8H10N4O2/c1-2-3-12-6-5(9-4-10-6)7(13)11-8(12)14/h4H,2-3H2,1H3,(H,9,10)(H,11,13,14)

HIDE SMILES / InChI

Description
Sources: http://www.hmdb.ca/metabolites/HMDB14962 | https://www.ncbi.nlm.nih.gov/pubmed/7956392 | https://www.ncbi.nlm.nih.gov/pubmed/9443164

Enprofylline is a xanthine derivative that shares theophylline's bronchodilator properties. It can be considered a relatively selective, though not potent adenosine A2B receptors antagonist. Enprofylline is used in asthma, chronic obstructive pulmonary disease, and in the management of cerebrovascular insufficiency, sickle cell disease, and diabetic neuropathy. Long-term enprofylline administration may be associated with the elevation in liver enzyme levels and unpredictable blood levels.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Adenosine A1 receptor 54 Target ID: CHEMBL226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9443164	Antagonist 2849	156.0 µM [Ki]
Adenosine A2a receptor 31 Target ID: CHEMBL251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9443164	Antagonist 2849	32.0 µM [Ki]
Adenosine A2b receptor 22 Target ID: CHEMBL255 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9443164	Antagonist 2849	7.0 µM [Ki]
Adenosine A3 receptor 24 Target ID: CHEMBL256 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9443164	Antagonist 2849	65.0 µM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Asthma 244 Sources: http://pharmacycode.com/Enprofylline.html	Palliative	Not Provided 511	Unknown Approved Use Unknown
Chronic obstructive pulmonary disease 175 Sources: http://pharmacycode.com/Enprofylline.html	Palliative	Not Provided 511	Unknown Approved Use Unknown
Cerebrovascular insufficiency 15 Sources: http://pharmacycode.com/Enprofylline.html	Palliative	Not Provided 511	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Contraction-induced secretion of VEGF from skeletal muscle cells is mediated by adenosine.	2010-09	20543089
Theophylline inhibits the differentiation of human monocyte into dendritic cell potentially via adenosine receptor antagonism.	2009-12	20085598
Allergen-induced airway inflammation and its therapeutic intervention.	2009-10	20224664
Progress in the discovery of selective, high affinity A(2B) adenosine receptor antagonists as clinical candidates.	2009-03	18568423
Comparative diffusion of drugs through bronchial tissue.	2008-06-05	18295419
Possible involvement of organic anion and cation transporters in renal excretion of xanthine derivatives, 3-methylxanthine and enprofylline.	2007-09-22	17897683
P1 receptors and cytokine secretion.	2007-03	18404415
Purinergic substances promote murine keratinocyte proliferation and enhance impaired wound healing in mice.	2006-04-25	16630104
The Quintiles Prize Lecture 2004. The identification of the adenosine A2B receptor as a novel therapeutic target in asthma.	2005-08	15980878
Adenosine A2A receptor stimulation increases angiogenesis by down-regulating production of the antiangiogenic matrix protein thrombospondin 1.	2005-05	15673602
Enprofylline protects motor neurons from in vitro excitotoxic challenge.	2005	16909021
A putative osmoreceptor system that controls neutrophil function through the release of ATP, its conversion to adenosine, and activation of A2 adenosine and P2 receptors.	2004-07	15107462
Long-term hypothermic lung preservation: does adenosine A1 receptor antagonism have a role in ischemic preconditioning protection?	2004-03	17670210
Characterization of adenosine receptor(s) involved in adenosine-induced bronchoconstriction in an allergic mouse model.	2003-06	12533441
Regional differences in the adenosine A(2) receptor-mediated modulation of contractions in rat vas deferens.	2003-01-24	12559381
Direct effects of caffeine and theophylline on p110 delta and other phosphoinositide 3-kinases. Differential effects on lipid kinase and protein kinase activities.	2002-10-04	12145276
Structure-activity relationships at human and rat A2B adenosine receptors of xanthine derivatives substituted at the 1-, 3-, 7-, and 8-positions.	2002-05-23	12014951
Adenosine receptor antagonists and retinal neovascularization in vivo.	2001-12	11726639
Antioxidant and radical scavenging properties of 8-oxo derivatives of xanthine drugs pentoxifylline and lisofylline.	2001-11-16	11700041
Inhibition of human mast cell activation with the novel selective adenosine A(2B) receptor antagonist 3-isobutyl-8-pyrrolidinoxanthine (IPDX)(2).	2001-11-01	11705449
Adenosine A(2A) and A(2B) receptor activation of erythropoietin production.	2001-11	11592940
Adenosine-mediated hypotension in in vivo guinea-pig: receptors involved and role of NO.	2001-10	11606314
Pharmacological characterization of adenosine receptors in PGT-beta mouse pineal gland tumour cells.	2001-09	11522605
Proliferation, migration, and ERK activation in human retinal endothelial cells through A(2B) adenosine receptor stimulation.	2001-08	11481274
Alkylxanthine-induced recovery of respiratory function following cervical spinal cord injury in adult rats.	2001-03	11170727
Sleep disturbances in asthma: theophylline versus enprofylline.	1991	1776216
Comparative assessment of enprofylline and theophylline for chronic obstructive airways disease in the elderly.	1990-05	2218006
Additive bronchodilator effects of terbutaline and enprofylline in asthma.	1987	3582466
Enprofylline and theophylline slow-eroding tablets in the treatment of asthma: a comparison.	1986	3523664
Continuous treatment of asthmatic patients with enprofylline and theophylline.	1984-10	6386511
Effects of enprofylline, a xanthine lacking adenosine receptor antagonism, in patients with chronic obstructive lung disease.	1982	6288396

Patents

Sample Use Guides

In Vivo Use Guide

The dosage of enprofylline was incremented from 150 mg twice daily at initiation to 300 and later 450 mg twice daily depending on the patient's tolerance.

Route of Administration: Oral

In Vitro Use Guide

Enprofylline antagonized the 5'-N-ethylcarboxamidoadenosine (NECA)-induced stimulation of platelet adenylate cyclase activity with a Kb of 130 microM. In human platelets, enprofylline did not antagonize but potentiated the NECA-induced inhibition of aggregation. This potentiation was abolished in the presence of the phosphodiesterase inhibitor papaverine. An adenosine antagonistic effect of enprofylline could not be evaluated on A2 receptors of the guinea-pig lung because the xanthine enhanced basal and NECA-stimulated cyclic AMP accumulation. Enprofylline antagonized the N6-R-(-)-phenylisopropyladenosine (R-PIA)-induced inhibition of rat fat cell adenylate cyclase with a Kb of 32 microM. The Ki value for inhibition of [3H]PIA binding to rat fat cell membranes was 45 microM. Enprofylline inhibited cyclic AMP phosphodiesterase activity of human platelets, guinea-pig lung and rat fat cells with Ki values of 15, 130 and 110 microM, respectively.

Name

Type

Language

ENPROFYLLINE

Official Name

English

D 4028

Preferred Name

English

1H-PURINE-2,6-DIONE, 3,7-DIHYDRO-3-PROPYL-

Systematic Name

English

ENPROFYLLINE [USAN]

Common Name

English

ENPROFYLLINE [MART.]

Common Name

English

3-Propylxanthine

Systematic Name

English

D-4028

Code

English

Enprofylline [WHO-DD]

Common Name

English

enprofylline [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C257