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 50 Target ID: CHEMBL226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9443164	Antagonist 2778	156.0 µM [Ki]
Adenosine A2a receptor 30 Target ID: CHEMBL251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9443164	Antagonist 2778	32.0 µM [Ki]
Adenosine A2b receptor 22 Target ID: CHEMBL255 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9443164	Antagonist 2778	7.0 µM [Ki]
Adenosine A3 receptor 24 Target ID: CHEMBL256 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9443164	Antagonist 2778	65.0 µM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Asthma 241 Sources: http://pharmacycode.com/Enprofylline.html	Palliative	Not Provided 504	Unknown Approved Use Unknown
Chronic obstructive pulmonary disease 174 Sources: http://pharmacycode.com/Enprofylline.html	Palliative	Not Provided 504	Unknown Approved Use Unknown
Cerebrovascular insufficiency 15 Sources: http://pharmacycode.com/Enprofylline.html	Palliative	Not Provided 504	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Effects of enprofylline, a xanthine lacking adenosine receptor antagonism, in patients with chronic obstructive lung disease.	1982	6288396
Continuous treatment of asthmatic patients with enprofylline and theophylline.	1984 Oct	6386511
Enprofylline and theophylline slow-eroding tablets in the treatment of asthma: a comparison.	1986	3523664
Additive bronchodilator effects of terbutaline and enprofylline in asthma.	1987	3582466
Comparative assessment of enprofylline and theophylline for chronic obstructive airways disease in the elderly.	1990 May	2218006
Sleep disturbances in asthma: theophylline versus enprofylline.	1991	1776216
Proliferation, migration, and ERK activation in human retinal endothelial cells through A(2B) adenosine receptor stimulation.	2001 Aug	11481274
Adenosine receptor antagonists and retinal neovascularization in vivo.	2001 Dec	11726639
Alkylxanthine-induced recovery of respiratory function following cervical spinal cord injury in adult rats.	2001 Mar	11170727
Adenosine A(2A) and A(2B) receptor activation of erythropoietin production.	2001 Nov	11592940
Inhibition of human mast cell activation with the novel selective adenosine A(2B) receptor antagonist 3-isobutyl-8-pyrrolidinoxanthine (IPDX)(2).	2001 Nov 1	11705449
Antioxidant and radical scavenging properties of 8-oxo derivatives of xanthine drugs pentoxifylline and lisofylline.	2001 Nov 16	11700041
Adenosine-mediated hypotension in in vivo guinea-pig: receptors involved and role of NO.	2001 Oct	11606314
Pharmacological characterization of adenosine receptors in PGT-beta mouse pineal gland tumour cells.	2001 Sep	11522605
Structure-activity relationships at human and rat A2B adenosine receptors of xanthine derivatives substituted at the 1-, 3-, 7-, and 8-positions.	2002 May 23	12014951
Direct effects of caffeine and theophylline on p110 delta and other phosphoinositide 3-kinases. Differential effects on lipid kinase and protein kinase activities.	2002 Oct 4	12145276
Regional differences in the adenosine A(2) receptor-mediated modulation of contractions in rat vas deferens.	2003 Jan 24	12559381
Characterization of adenosine receptor(s) involved in adenosine-induced bronchoconstriction in an allergic mouse model.	2003 Jun	12533441
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 Jul	15107462
Long-term hypothermic lung preservation: does adenosine A1 receptor antagonism have a role in ischemic preconditioning protection?	2004 Mar	17670210
Enprofylline protects motor neurons from in vitro excitotoxic challenge.	2005	16909021
The Quintiles Prize Lecture 2004. The identification of the adenosine A2B receptor as a novel therapeutic target in asthma.	2005 Aug	15980878
Adenosine A2A receptor stimulation increases angiogenesis by down-regulating production of the antiangiogenic matrix protein thrombospondin 1.	2005 May	15673602
Purinergic substances promote murine keratinocyte proliferation and enhance impaired wound healing in mice.	2006 Mar-Apr	16630104
P1 receptors and cytokine secretion.	2007 Mar	18404415
Possible involvement of organic anion and cation transporters in renal excretion of xanthine derivatives, 3-methylxanthine and enprofylline.	2007 Sep 22	17897683
Comparative diffusion of drugs through bronchial tissue.	2008 Jun 5	18295419
Theophylline inhibits the differentiation of human monocyte into dendritic cell potentially via adenosine receptor antagonism.	2009 Dec	20085598
Progress in the discovery of selective, high affinity A(2B) adenosine receptor antagonists as clinical candidates.	2009 Mar	18568423
Allergen-induced airway inflammation and its therapeutic intervention.	2009 Oct	20224664
Contraction-induced secretion of VEGF from skeletal muscle cells is mediated by adenosine.	2010 Sep	20543089

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

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

Systematic Name

English

D 4028

Code

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