Identification

Name
Rescinnamine
Accession Number
DB01180  (APRD00112)
Type
Small Molecule
Groups
Approved
Description

Rescinnamine is an angiotensin-converting enzyme inhibitor used as an antihypertensive drug. It is an alkaloid obtained from Rauwolfia serpentina and other species of Rauwolfia. [Wikipedia]

Structure
Thumb
Synonyms
  • 3,4,5-Trimethoxycinnamoyl methyl reserpate
  • Rescinnamine
  • Trimethoxy cinnamoyl reserpate de methyl
  • Tsuruselpi S
International/Other Brands
Tsuruselpi S
Categories
UNII
Q6W1F7DJ2D
CAS number
24815-24-5
Weight
Average: 634.716
Monoisotopic: 634.289030952
Chemical Formula
C35H42N2O9
InChI Key
SZLZWPPUNLXJEA-QEGASFHISA-N
InChI
InChI=1S/C35H42N2O9/c1-40-21-8-9-22-23-11-12-37-18-20-15-29(46-30(38)10-7-19-13-27(41-2)33(43-4)28(14-19)42-3)34(44-5)31(35(39)45-6)24(20)17-26(37)32(23)36-25(22)16-21/h7-10,13-14,16,20,24,26,29,31,34,36H,11-12,15,17-18H2,1-6H3/b10-7+/t20-,24+,26-,29-,31+,34+/m1/s1
IUPAC Name
methyl (1R,15S,17R,18R,19S,20S)-6,18-dimethoxy-17-{[3-(3,4,5-trimethoxyphenyl)prop-2-enoyl]oxy}-3,13-diazapentacyclo[11.8.0.0²,¹⁰.0⁴,⁹.0¹⁵,²⁰]henicosa-2(10),4(9),5,7-tetraene-19-carboxylate
SMILES
[H][C@]12C[C@@H](OC(=O)C=CC3=CC(OC)=C(OC)C(OC)=C3)[C@H](OC)[C@@H](C(=O)OC)[C@@]1([H])C[C@@]1([H])N(CCC3=C1NC1=C3C=CC(OC)=C1)C2

Pharmacology

Indication

For the treatment of hypertension.

Pharmacodynamics

Used to treat hypertension. Rescinnamine inhibits angiotensin-converting enzyme. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex and general vasoconstriction, both of which lead to increases vascular resistance. By inhibiting angiotensin II, aldosterone reabsorption is decreased as well as vasoconstriction. This combined effect serves to decrease blood pressure.

Mechanism of action

Rescinnamine Binds to and inhibits the angiotensin converting enzyme. Rescinnamine competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. Inhibition of ACE results in decreased plasma angiotensin II. As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin activity, lower concentrations result in a decrease in blood pressure and stimulation of baroreceptor reflex mechanisms, which leads to decreased vasopressor activity and to decreased aldosterone secretion.

TargetActionsOrganism
AAngiotensin-converting enzyme
inhibitor
Human
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
  • Humans and other mammals
Pathways
PathwayCategory
Rescinnamine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcebutololThe risk or severity of hyperkalemia can be increased when Rescinnamine is combined with Acebutolol.
AceclofenacThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Aceclofenac is combined with Rescinnamine.
AcemetacinThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Acemetacin is combined with Rescinnamine.
Acetylsalicylic acidThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Acetylsalicylic acid is combined with Rescinnamine.
AgmatineThe risk or severity of hyperkalemia can be increased when Rescinnamine is combined with Agmatine.
Agrostis gigantea pollenThe risk or severity of adverse effects can be increased when Rescinnamine is combined with Agrostis gigantea pollen.
Agrostis stolonifera pollenThe risk or severity of adverse effects can be increased when Rescinnamine is combined with Agrostis stolonifera pollen.
AlclofenacThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Alclofenac is combined with Rescinnamine.
AlfuzosinAlfuzosin may increase the hypotensive activities of Rescinnamine.
AliskirenThe risk or severity of hypotension, hyperkalemia, and nephrotoxicity can be increased when Aliskiren is combined with Rescinnamine.
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D00198
KEGG Compound
C06540
PubChem Compound
32681
PubChem Substance
46507786
ChemSpider
4444446
ChEBI
28572
ChEMBL
CHEMBL1668
Therapeutic Targets Database
DAP000910
PharmGKB
PA164768818
Wikipedia
Rescinnamine
ATC Codes
C02AA01 — RescinnamineC02LA02 — Rescinnamine and diureticsC02LA52 — Rescinnamine and diuretics, combinations with other drugs
MSDS
Download (52.7 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)238.5 °CPhysProp
logP3.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00349 mg/mLALOGPS
logP4.48ALOGPS
logP4.07ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)16.29ChemAxon
pKa (Strongest Basic)7.56ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area117.78 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity171.16 m3·mol-1ChemAxon
Polarizability69.65 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9604
Blood Brain Barrier+0.9248
Caco-2 permeable+0.6805
P-glycoprotein substrateSubstrate0.8163
P-glycoprotein inhibitor IInhibitor0.8826
P-glycoprotein inhibitor IINon-inhibitor0.6553
Renal organic cation transporterInhibitor0.5
CYP450 2C9 substrateNon-substrate0.8706
CYP450 2D6 substrateNon-substrate0.9064
CYP450 3A4 substrateSubstrate0.7223
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9144
CYP450 3A4 inhibitorNon-inhibitor0.8203
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7162
Ames testNon AMES toxic0.9208
CarcinogenicityNon-carcinogens0.9453
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.8345 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.697
hERG inhibition (predictor II)Non-inhibitor0.678
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (13.2 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as yohimbine alkaloids. These are alkaloids containing the pentacyclic yohimban skeleton. The Yohimbinoid alkaloids contain a carbocyclic ring E arising through C-17 to C-18 bond formation in a corynantheine precursor.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Yohimbine alkaloids
Sub Class
Not Available
Direct Parent
Yohimbine alkaloids
Alternative Parents
Corynanthean-type alkaloids / Beta carbolines / Cinnamic acid esters / Coumaric acids and derivatives / 3-alkylindoles / Styrenes / Phenoxy compounds / Anisoles / Methoxybenzenes / Alkyl aryl ethers
show 16 more
Substituents
Yohimbine / Corynanthean skeleton / Yohimbine alkaloid / Pyridoindole / Beta-carboline / Cinnamic acid or derivatives / Coumaric acid or derivatives / Cinnamic acid ester / 3-alkylindole / Indole or derivatives
show 38 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent...
Gene Name
ACE
Uniprot ID
P12821
Uniprot Name
Angiotensin-converting enzyme
Molecular Weight
149713.675 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Azhar I, Mazhar F, Manzar QN, Hussain I, Shamim S: Colorimetric determination of indolic drugs. Pak J Pharm Sci. 2005 Apr;18(2):48-51. [PubMed:16431399]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 04:57