Tmic
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Record Information
Version1.0
Creation Date2014-10-15 22:04:45 UTC
Update Date2016-11-09 01:09:15 UTC
Accession NumberCHEM003950
Identification
Common Name22,23-dihydroavermectin b1b
ClassSmall Molecule
Description22,23-dihydroavermectin b1b is a component of Ivermectin, a broad-spectrum antiparasitic avermectin medicine. It is sold under brand names Sklice and Stromectol in the United States, Ivomec in Europe by Merial Animal Health, Mectizan in Canada by Merck and Ivexterm in Mexico by Valeant Pharmaceuticals International. In southeast Asian countries like Bangladesh, it is marketed by Delta Pharma Ltd. under the trade name Scabo 6. While in development, it was assigned the code MK-933 by Merck. It was first used against worms (except tapeworms), but in 2012 it was approved for the topical treatment of head lice infestations in patients 6 months of age and older. Ivermectin is mainly used in humans in the treatment of onchocerciasis, but is also effective against other worm infestations (such as strongyloidiasis, ascariasis, trichuriasis and enterobiasis).
Contaminant Sources
  • T3DB toxins
Contaminant Type
  • Antiparasitic Agent
  • Avermectin
  • Drug
  • Lachrymator
  • Metabolite
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
ValueSource
Avermectin H2b1bChEBI
Dihydroavermectin b1bChEBI
H2b1bChEBI
Ivermectin b1bChEBI
Ivermectin component b1bChEBI
H2b1b AvermectinMeSH
22,23-Dihydroavermectin b1(b)MeSH
22,23-Dihydroavermectin b(1)bMeSH
Chemical FormulaC47H72O14
Average Molecular Mass861.066 g/mol
Monoisotopic Mass860.492 g/mol
CAS Registry Number70209-81-3
IUPAC Name(1'R,2R,4'S,5S,6R,8'R,10'E,12'S,13'S,14'E,20'R,21'R,24'S)-21',24'-dihydroxy-12'-{[(2R,4S,5S,6S)-5-{[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy}-4-methoxy-6-methyloxan-2-yl]oxy}-5,11',13',22'-tetramethyl-6-(propan-2-yl)-3',7',19'-trioxaspiro[oxane-2,6'-tetracyclo[15.6.1.1⁴,⁸.0²⁰,²⁴]pentacosane]-10',14',16',22'-tetraen-2'-one
Traditional Name(1'R,2R,4'S,5S,6R,8'R,10'E,12'S,13'S,14'E,20'R,21'R,24'S)-21',24'-dihydroxy-12'-{[(2R,4S,5S,6S)-5-{[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy}-4-methoxy-6-methyloxan-2-yl]oxy}-6-isopropyl-5,11',13',22'-tetramethyl-3',7',19'-trioxaspiro[oxane-2,6'-tetracyclo[15.6.1.1⁴,⁸.0²⁰,²⁴]pentacosane]-10',14',16',22'-tetraen-2'-one
SMILES[H]\C1=C(C)/[C@@]([H])(O[C@@]2([H])C[C@]([H])(OC)[C@@]([H])(O[C@@]3([H])C[C@]([H])(OC)[C@@]([H])(O)[C@]([H])(C)O3)[C@]([H])(C)O2)[C@@]([H])(C)\C([H])=C(/[H])\C(\[H])=C2/CO[C@]3([H])[C@]([H])(O)C(C)=C[C@@]([H])(C(=O)O[C@@]4([H])C[C@@]([H])(C1)O[C@@]1(CC[C@]([H])(C)[C@]([H])(O1)C(C)C)C4)[C@]23O
InChI IdentifierInChI=1S/C47H72O14/c1-24(2)41-27(5)16-17-46(61-41)22-33-19-32(60-46)15-14-26(4)42(25(3)12-11-13-31-23-54-44-39(48)28(6)18-34(45(50)57-33)47(31,44)51)58-38-21-36(53-10)43(30(8)56-38)59-37-20-35(52-9)40(49)29(7)55-37/h11-14,18,24-25,27,29-30,32-44,48-49,51H,15-17,19-23H2,1-10H3/b12-11+,26-14+,31-13+/t25-,27-,29-,30-,32+,33-,34-,35-,36-,37-,38-,39+,40-,41+,42-,43-,44+,46+,47+/m0/s1
InChI KeyVARHUCVRRNANBD-PVVXTEPVSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as milbemycins. These are a group of macrolides with a structure containing a 16-membered lactone ring fused to a 1,7-dioxaspiroundecane ring system and to either a benzofuran (or hydrogenated derivative thereof). In some cases (e.g. Milbemycin E), the tetrahydrofuranyl ring is missing. Milbemycins can be o-glycosylated at C13 to form Avermectins. Milbemycins are produced by Streptomyces species.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassMacrolides and analogues
Sub ClassMilbemycins
Direct ParentMilbemycins
Alternative Parents
Substituents
  • Milbemycin
  • Disaccharide
  • Glycosyl compound
  • O-glycosyl compound
  • Ketal
  • Oxane
  • Tetrahydrofuran
  • Tertiary alcohol
  • Carboxylic acid ester
  • Lactone
  • Secondary alcohol
  • Acetal
  • Carboxylic acid derivative
  • Dialkyl ether
  • Ether
  • Oxacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Organic oxide
  • Carbonyl group
  • Hydrocarbon derivative
  • Alcohol
  • Organic oxygen compound
  • Organooxygen compound
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Apical Membrane
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder
Experimental Properties
PropertyValue
Melting Point155°C
Boiling PointNot Available
SolubilityInsoluble
Predicted Properties
PropertyValueSource
Water Solubility0.0078 g/LALOGPS
logP4.04ALOGPS
logP5.38ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)12.47ChemAxon
pKa (Strongest Basic)-3.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count13ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area170.06 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity225.73 m³·mol⁻¹ChemAxon
Polarizability94.71 ųChemAxon
Number of Rings7ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0cka-6700082390-1f206143ec8927597cd3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-05fs-6820091100-0c0f9d98e785ccca0947View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9240121010-8c24dab75acfbb7c53eaView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0bt9-1320031290-77c2925edeb47b909496View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-006y-1300091420-19d4a2fe68be388f9a95View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0h3s-7700493000-201a140113566e55552aView in MoNA
Toxicity Profile
Route of ExposureIvermectin is moderately well absorbed. Improved absorption with high fat meal. Ivermectin binds selectively and with high affinity to glutamate-gated chloride ion channels in invertebrate muscle and nerve cells of the microfilaria. This binding causes an increase in the permeability of the cell membrane to chloride ions and results in hyperpolarization of the cell, leading to paralysis and death of the parasite. Ivermectin also is believed to act as an agonist of the neurotransmitter gamma-aminobutyric acid (GABA), thereby disrupting GABA-mediated central nervous system (CNS) neurosynaptic transmission. Ivermectin may also impair normal intrauterine development of O. volvulus microfilariae and may inhibit their release from the uteri of gravid female worms. It has low solubility in water and extensive non-specific binding. It opens GABA-insensitive chloride channels, reducing membrane resistance and increasing conductance inward. (1) Primarily hepatic. Ivermectin and/or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1 % of the administered dose excreted in the urine. Route of Elimination: Ivermectin is metabolized in the liver, and ivermectin and/or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1% of the administered dose excreted in the urine. Half Life: 16 hours (also reported at 22-28 hours)
Mechanism of ToxicityIvermectin binds selectively and with high affinity to glutamate-gated chloride ion channels in invertebrate muscle and nerve cells of the microfilaria. This binding causes an increase in the permeability of the cell membrane to chloride ions and results in hyperpolarization of the cell, leading to paralysis and death of the parasite. Ivermectin also is believed to act as an agonist of the neurotransmitter gamma-aminobutyric acid (GABA), thereby disrupting GABA-mediated central nervous system (CNS) neurosynaptic transmission. Ivermectin may also impair normal intrauterine development of O. volvulus microfilariae and may inhibit their release from the uteri of gravid female worms. It has low solubility in water and extensive non-specific binding. It opens GABA-insensitive chloride channels, reducing membrane resistance and increasing conductance inward. (1)
MetabolismPrimarily hepatic. Ivermectin and/or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1 % of the administered dose excreted in the urine. Route of Elimination: Ivermectin is metabolized in the liver, and ivermectin and/or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1% of the administered dose excreted in the urine. Half Life: 16 hours (also reported at 22-28 hours)
Toxicity ValuesLD50 = 29.5 mg/kg (Mouse, oral); LD50 = 10 mg/kg (Rat, oral)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not listed by IARC.
Uses/SourcesFor the treatment of intestinal (i.e., nondisseminated) strongyloidiasis due to the nematode parasite Strongyloides stercoralis. Also for the treatment of onchocerciasis (river blindness) due to the nematode parasite Onchocerca volvulus. Can be used to treat scabies caused by Sarcoptes scabiei. Active ingredient in some commercial ant bait traps. (2)
Minimum Risk LevelNot Available
Health EffectsAvermectins are neurotoxic and have reproductive and developmental effects. (3)
SymptomsAvermectins cause irritation of skin and eyes, central nervous system depression (incoordination, tremors, lethargy, excitation, pupil dilation, coma), vomiting, convulsions and/or tremors, and respiratory failure at high doses. (3) Adverse effects include muscle or joint pain, dizziness, fever, headache, skin rash, fast heartbeat.
TreatmentNot Available
Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkNot Available
Chemspider IDNot Available
ChEBI ID63943
PubChem Compound IDNot Available
Kegg Compound IDNot Available
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

Shuet-Hing L. Chiu, Josephine R. Carlin, Rae Taub, “Ivermectin derivative compounds and process for preparing the same.” U.S. Patent US4963667, issued June, 1982.

MSDSLink
General References
1. https://www.ncbi.nlm.nih.gov/pubmed/?term=6125361
2. https://www.ncbi.nlm.nih.gov/pubmed/?term=6148214
3. https://www.ncbi.nlm.nih.gov/pubmed/?term=6895285
4. https://www.ncbi.nlm.nih.gov/pubmed/?term=6896121