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Identification
NameRemikiren
Accession NumberDB00212  (APRD00163)
TypeSmall Molecule
GroupsApproved
Description

Remikiren is an orally active, high specificity renin inhibitor.

Structure
Thumb
SynonymsNot Available
External Identifiers
  • Ro 42-5892
  • RO-42-5892
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIILC7FBL96A4
CAS number126222-34-2
WeightAverage: 630.838
Monoisotopic: 630.345106042
Chemical FormulaC33H50N4O6S
InChI KeyUXIGZRQVLGFTOU-VQXQMPIVSA-N
InChI
InChI=1S/C33H50N4O6S/c1-33(2,3)44(42,43)20-25(16-22-10-6-4-7-11-22)31(40)37-28(18-26-19-34-21-35-26)32(41)36-27(17-23-12-8-5-9-13-23)30(39)29(38)24-14-15-24/h4,6-7,10-11,19,21,23-25,27-30,38-39H,5,8-9,12-18,20H2,1-3H3,(H,34,35)(H,36,41)(H,37,40)/t25-,27+,28+,29+,30-/m1/s1
IUPAC Name
(2S)-2-{[(2S)-2-benzyl-1-hydroxy-3-(2-methylpropane-2-sulfonyl)propylidene]amino}-N-[(2S,3R,4S)-1-cyclohexyl-4-cyclopropyl-3,4-dihydroxybutan-2-yl]-3-(1H-imidazol-5-yl)propanimidic acid
SMILES
[H][C@@](CC1=CC=CC=C1)(CS(=O)(=O)C(C)(C)C)C(O)=N[C@@]([H])(CC1=CN=CN1)C(O)=N[C@@]([H])(CC1CCCCC1)[C@@]([H])(O)[C@@]([H])(O)C1CC1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzene and substituted derivatives. These are aromatic compounds containing one monocyclic ring system consisting of benzene.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassNot Available
Direct ParentBenzene and substituted derivatives
Alternative Parents
Substituents
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Sulfonyl
  • Sulfone
  • Imidazole
  • Azole
  • Secondary alcohol
  • 1,2-diol
  • Azacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidic acid derivative
  • Carboximidic acid
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Alcohol
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of hypertension and heart failure
PharmacodynamicsRemikiren is an orally available renin inhibitor with an established blood pressure-lowering effect in patients with essential hypertension. No data are available on the renal effects of remikiren in humans. In patients with essential hypertension, a single oral dose of remikiren can induce a renal vasodilation, without affecting the GFR and despite a significant decrease in blood pressure. This systemic and renal hemodynamic response is more pronounced in case of a more activated renin-angiotensin system.
Mechanism of actionSeveral in vivo experiments have shown that remikiren is specific for renin and does not decrease arterial pressure by an unrelated mechanism.
Related Articles
AbsorptionAbsorbed following oral administration.
Volume of distributionNot Available
Protein binding83%
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8744
Blood Brain Barrier-0.8746
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.7043
P-glycoprotein inhibitor INon-inhibitor0.6427
P-glycoprotein inhibitor IINon-inhibitor0.9732
Renal organic cation transporterNon-inhibitor0.8832
CYP450 2C9 substrateNon-substrate0.5243
CYP450 2D6 substrateNon-substrate0.7775
CYP450 3A4 substrateSubstrate0.5695
CYP450 1A2 substrateNon-inhibitor0.8245
CYP450 2C9 inhibitorNon-inhibitor0.6456
CYP450 2D6 inhibitorNon-inhibitor0.8548
CYP450 2C19 inhibitorNon-inhibitor0.6534
CYP450 3A4 inhibitorInhibitor0.8648
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6298
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.7601
BiodegradationNot ready biodegradable0.9754
Rat acute toxicity2.5600 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9958
hERG inhibition (predictor II)Non-inhibitor0.5881
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP3.9Not Available
Caco2 permeability-6.13ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.0128 mg/mLALOGPS
logP3.56ALOGPS
logP3.22ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)5.47ChemAxon
pKa (Strongest Basic)6.49ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area168.46 Å2ChemAxon
Rotatable Bond Count16ChemAxon
Refractivity170.64 m3·mol-1ChemAxon
Polarizability68.82 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Clozel JP, Fischli W: Discovery of remikiren as the first orally active renin inhibitor. Arzneimittelforschung. 1993 Feb;43(2A):260-2. [PubMed:8498974 ]
  2. Richter WF, Whitby BR, Chou RC: Distribution of remikiren, a potent orally active inhibitor of human renin, in laboratory animals. Xenobiotica. 1996 Mar;26(3):243-54. [PubMed:8730917 ]
External Links
ATC CodesC09XA01
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Receptor binding
Specific Function:
Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney.
Gene Name:
REN
Uniprot ID:
P00797
Molecular Weight:
45057.125 Da
References
  1. van Paassen P, Navis GJ, De Jong PE, De Zeeuw D: Pretreatment renal vascular tone predicts the effect of specific renin inhibition on natriuresis in essential hypertension. Eur J Clin Invest. 1999 Dec;29(12):1019-26. [PubMed:10583449 ]
  2. MacFadyen RJ, Jones CR, Doig JK, Birnbock H, Reid JL: Responses to an orally active renin inhibitor, remikiren (Ro 42-5892), after controlled salt depletion in humans. J Cardiovasc Pharmacol. 1995 Mar;25(3):347-53. [PubMed:7769797 ]
  3. Kiowski W, Beermann J, Rickenbacher P, Haemmerli R, Thomas M, Burkart F, Meinertz T: Angiotensinergic versus nonangiotensinergic hemodynamic effects of converting enzyme inhibition in patients with chronic heart failure. Assessment by acute renin and converting enzyme inhibition. Circulation. 1994 Dec;90(6):2748-56. [PubMed:7994817 ]
  4. Hilgers KF, Fischli W, Veelken R, Mann JF: Vascular renin in the guinea pig. Suppression by the renin inhibitor remikiren. Hypertension. 1994 Jun;23(6 Pt 2):861-4. [PubMed:8206619 ]
  5. Clozel JP, Fischli W: Comparative effects of three different potent renin inhibitors in primates. Hypertension. 1993 Jul;22(1):9-17. [PubMed:8319997 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23