Rolofylline - DrugBank

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name

Rolofylline

Accession Number

DB12670 (DB05360)

Type

Small Molecule

Groups

Investigational

Description

Rolofylline is under clinical development by pharmaceutical company NovaCardia for the treatment of congestive heart failure.

Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

Not Available

External IDs

KW 3902 / KW-3902 / MK-7418

Product Ingredients

Not Available

Products

Not Available

International Brands

Not Available

Brand mixtures

Not Available

Categories

UNII

7805S5HIHX

CAS number

136199-02-5

Weight

Average: 356.47
Monoisotopic: 356.221226158

Chemical Formula

C₂₀H₂₈N₄O₂

InChI Key

PJBFVWGQFLYWCB-QUYAXPHCSA-N

InChI

InChI=1S/C20H28N4O2/c1-3-5-23-16-15(17(25)24(6-4-2)19(23)26)21-18(22-16)20-10-12-7-13(11-20)9-14(20)8-12/h12-14H,3-11H2,1-2H3,(H,21,22)/t12-,13+,14?,20?

IUPAC Name

1,3-dipropyl-8-[(1R,5S)-tricyclo[3.3.1.0^{3,7}]nonan-3-yl]-2,3,6,7-tetrahydro-1H-purine-2,6-dione

SMILES

CCCN1C2=C(NC(=N2)C23C[C@@H]4CC2C[[email protected]](C3)C4)C(=O)N(CCC)C1=O

Pharmacology

Indication

Not Available

Structured Indications

Not Available

Pharmacodynamics

Not Available

Mechanism of action

Rolofylline is an adenosine A1-receptor antagonist. Plasma adenosine levels are elevated in patients with heart failure and adenosine A1 receptors in the kidney mediate vasoconstriction of afferent arterioles, reabsorption of sodium and water in proximal tubules, and tubuloglomerular feedback in the juxtaglomerular apparatus. Accordingly, inhibition of these receptors would be expected to increase renal blood flow and enhance diuresis. The effects of Rolofylline on renal function are consistent with those obtained with another adenosine A1-receptor antagonist in both experimental and human heart failure.

Target	Kind	Pharmacological action	Actions	Organism	UniProt ID
Adenosine receptor A1	Protein	unknown	Not Available	Human	P30542	details

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

Not Available

Half life

Not Available

Clearance

Not Available

Toxicity

Not Available

Affected organisms

Not Available

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction	Drug group
Alfentanil	The risk or severity of adverse effects can be increased when Alfentanil is combined with Rolofylline.	Approved, Illicit
Alphacetylmethadol	The risk or severity of adverse effects can be increased when Alphacetylmethadol is combined with Rolofylline.	Experimental, Illicit
Bezitramide	The risk or severity of adverse effects can be increased when Bezitramide is combined with Rolofylline.	Experimental, Illicit, Withdrawn
Buprenorphine	The risk or severity of adverse effects can be increased when Buprenorphine is combined with Rolofylline.	Approved, Illicit, Investigational, Vet Approved
Butorphanol	The risk or severity of adverse effects can be increased when Butorphanol is combined with Rolofylline.	Approved, Illicit, Vet Approved
Carfentanil	The risk or severity of adverse effects can be increased when Carfentanil is combined with Rolofylline.	Illicit, Vet Approved
Codeine	The risk or severity of adverse effects can be increased when Codeine is combined with Rolofylline.	Approved, Illicit
Dextromoramide	The risk or severity of adverse effects can be increased when Dextromoramide is combined with Rolofylline.	Experimental, Illicit
Dextropropoxyphene	The risk or severity of adverse effects can be increased when Dextropropoxyphene is combined with Rolofylline.	Approved, Illicit, Withdrawn
Dezocine	The risk or severity of adverse effects can be increased when Dezocine is combined with Rolofylline.	Approved
Dihydrocodeine	The risk or severity of adverse effects can be increased when Dihydrocodeine is combined with Rolofylline.	Approved, Illicit
Dihydroetorphine	The risk or severity of adverse effects can be increased when Dihydroetorphine is combined with Rolofylline.	Experimental, Illicit
Dihydromorphine	The risk or severity of adverse effects can be increased when Dihydromorphine is combined with Rolofylline.	Experimental, Illicit
Diphenoxylate	The risk or severity of adverse effects can be increased when Diphenoxylate is combined with Rolofylline.	Approved, Illicit
Ethylmorphine	The risk or severity of adverse effects can be increased when Ethylmorphine is combined with Rolofylline.	Approved, Illicit
Etorphine	The risk or severity of adverse effects can be increased when Etorphine is combined with Rolofylline.	Illicit, Vet Approved
Fentanyl	The risk or severity of adverse effects can be increased when Fentanyl is combined with Rolofylline.	Approved, Illicit, Investigational, Vet Approved
Heroin	The risk or severity of adverse effects can be increased when Heroin is combined with Rolofylline.	Approved, Illicit
Hydrocodone	The risk or severity of adverse effects can be increased when Hydrocodone is combined with Rolofylline.	Approved, Illicit
Hydromorphone	The risk or severity of adverse effects can be increased when Hydromorphone is combined with Rolofylline.	Approved, Illicit
Ketobemidone	The risk or severity of adverse effects can be increased when Ketobemidone is combined with Rolofylline.	Approved
Levomethadyl Acetate	The risk or severity of adverse effects can be increased when Levomethadyl Acetate is combined with Rolofylline.	Approved
Levorphanol	The risk or severity of adverse effects can be increased when Levorphanol is combined with Rolofylline.	Approved
Lofentanil	The risk or severity of adverse effects can be increased when Lofentanil is combined with Rolofylline.	Illicit
Methadone	The risk or severity of adverse effects can be increased when Methadone is combined with Rolofylline.	Approved
Methadyl Acetate	The risk or severity of adverse effects can be increased when Methadyl Acetate is combined with Rolofylline.	Approved, Illicit
Morphine	The risk or severity of adverse effects can be increased when Morphine is combined with Rolofylline.	Approved, Investigational
Nalbuphine	The risk or severity of adverse effects can be increased when Nalbuphine is combined with Rolofylline.	Approved
Normethadone	The risk or severity of adverse effects can be increased when Normethadone is combined with Rolofylline.	Approved, Illicit
Opium	The risk or severity of adverse effects can be increased when Opium is combined with Rolofylline.	Approved, Illicit
Oxycodone	The risk or severity of adverse effects can be increased when Oxycodone is combined with Rolofylline.	Approved, Illicit, Investigational
Oxymorphone	The risk or severity of adverse effects can be increased when Oxymorphone is combined with Rolofylline.	Approved, Investigational, Vet Approved
Pentazocine	The risk or severity of adverse effects can be increased when Pentazocine is combined with Rolofylline.	Approved, Vet Approved
Pethidine	The risk or severity of adverse effects can be increased when Pethidine is combined with Rolofylline.	Approved
Piritramide	The risk or severity of adverse effects can be increased when Piritramide is combined with Rolofylline.	Investigational
Remifentanil	The risk or severity of adverse effects can be increased when Remifentanil is combined with Rolofylline.	Approved
Sufentanil	The risk or severity of adverse effects can be increased when Sufentanil is combined with Rolofylline.	Approved, Investigational
Tapentadol	The risk or severity of adverse effects can be increased when Tapentadol is combined with Rolofylline.	Approved
Tramadol	The risk or severity of adverse effects can be increased when Tramadol is combined with Rolofylline.	Approved, Investigational

Food Interactions

Not Available

References

Synthesis Reference

Not Available

General References

Not Available

External Links

Resource	Link
ChemSpider	10122604

ATC Codes

Not Available

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Clinical Trials

Phase	Status	Purpose	Conditions	Count
2	Completed	Treatment	Heart Failure, Unspecified	1
3	Completed	Treatment	Congestive Heart Failure (CHF)	3

Properties

State

Not Available

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.125 mg/mL	ALOGPS
logP	4.11	ALOGPS
logP	3.27	ChemAxon
logS	-3.5	ALOGPS
pKa (Strongest Acidic)	7.83	ChemAxon
pKa (Strongest Basic)	-0.72	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	69.3 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	99.06 m³·mol^-1	ChemAxon
Polarizability	40.66 Å³	ChemAxon
Number of Rings	5	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Not Available

Taxonomy

Description

This compound belongs to the class of organic compounds known as xanthines. These are purine derivatives with a ketone group conjugated at carbons 2 and 6 of the purine moiety.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Imidazopyrimidines

Sub Class

Purines and purine derivatives

Direct Parent

Xanthines

Alternative Parents

6-oxopurines / Alkaloids and derivatives / Pyrimidones / Vinylogous amides / Imidazoles / Heteroaromatic compounds / Ureas / Lactams / Azacyclic compounds / Organooxygen compounds

Substituents

Xanthine / 6-oxopurine / Purinone / Alkaloid or derivatives / Pyrimidone / Pyrimidine / Azole / Imidazole / Heteroaromatic compound / Vinylogous amide

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Targets

Details

1. Adenosine receptor A1

Kind: Protein
Organism: Human
Pharmacological action: unknown

General Function:: Purine nucleoside binding
Specific Function:: Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:: ADORA1
Uniprot ID:: P30542
Uniprot Name:: Adenosine receptor A1
Molecular Weight:: 36511.325 Da

Drug created on October 20, 2016 17:33 / Updated on June 11, 2017 21:36

Structure for DB12670 (Rolofylline)

Targets