Identification

Name
Tanaproget
Accession Number
DB04787
Type
Small Molecule
Groups
Investigational
Description

Tanaproget (NSP-989) is an investigational non-steroidal progestin. It is a high affinity, high efficacy, and very selective agonist of the progesterone receptor (PR). Due to its much more selective binding profile relative to most conventional, steroidal progestins, tanaproget may prove to produce fewer side effects in comparison. It is currently in the process of being developed for clinical use as a contraceptive by Ligand Pharmaceuticals. An analog of tanaproget, 4-fluoropropyltanaproget (18F), has been developed as a radiotracer for imaging of the PR in positron emission tomography.

Structure
Thumb
Synonyms
Not Available
External IDs
NSP-989
Categories
UNII
W9F9H8GXWR
CAS number
304853-42-7
Weight
Average: 297.375
Monoisotopic: 297.093582807
Chemical Formula
C16H15N3OS
InChI Key
PYVFWTPEBMRKSR-UHFFFAOYSA-N
InChI
InChI=1S/C16H15N3OS/c1-16(2)12-8-10(4-6-13(12)18-15(21)20-16)14-7-5-11(9-17)19(14)3/h4-8H,1-3H3,(H,18,21)
IUPAC Name
5-(4,4-dimethyl-2-sulfanylidene-2,4-dihydro-1H-3,1-benzoxazin-6-yl)-1-methyl-1H-pyrrole-2-carbonitrile
SMILES
CN1C(=CC=C1C1=CC=C2NC(=S)OC(C)(C)C2=C1)C#N

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
AProgesterone receptor
agonist
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
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference

Arwinder Nagi, Ramarao Chatlapalli, Shamim Hasan, Mohamed Ghorab, Dhaval Gaglani, "Micronized tanaproget, compositions, and methods of preparing the same." U.S. Patent US20060246135, issued November 02, 2006.

US20060246135
General References
  1. Zhang Z, Olland AM, Zhu Y, Cohen J, Berrodin T, Chippari S, Appavu C, Li S, Wilhem J, Chopra R, Fensome A, Zhang P, Wrobel J, Unwalla RJ, Lyttle CR, Winneker RC: Molecular and pharmacological properties of a potent and selective novel nonsteroidal progesterone receptor agonist tanaproget. J Biol Chem. 2005 Aug 5;280(31):28468-75. Epub 2005 Jun 3. [PubMed:15937332]
  2. Bapst JL, Ermer JC, Ferron GM, Foss D, Orczyk GP: Pharmacokinetics and safety of tanaproget, a nonsteroidal progesterone receptor agonist, in healthy women. Contraception. 2006 Nov;74(5):414-8. Epub 2006 Sep 15. [PubMed:17046384]
  3. Bayes M, Rabasseda X, Prous JR: Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2005 Sep;27(7):505-22. [PubMed:16258596]
External Links
PubChem Compound
4369524
PubChem Substance
46509047
ChemSpider
3572060
BindingDB
50375821
ChEMBL
CHEMBL539163
Therapeutic Targets Database
DPR000116
HET
T98
Wikipedia
Tanaproget
PDB Entries
1zuc

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
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0311 mg/mLALOGPS
logP3.72ALOGPS
logP3.82ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)10.79ChemAxon
pKa (Strongest Basic)-2.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area49.98 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity88.42 m3·mol-1ChemAxon
Polarizability32.33 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9867
Blood Brain Barrier+0.8806
Caco-2 permeable+0.5421
P-glycoprotein substrateNon-substrate0.7957
P-glycoprotein inhibitor IInhibitor0.8716
P-glycoprotein inhibitor IIInhibitor0.7057
Renal organic cation transporterNon-inhibitor0.8453
CYP450 2C9 substrateNon-substrate0.839
CYP450 2D6 substrateNon-substrate0.7643
CYP450 3A4 substrateSubstrate0.6161
CYP450 1A2 substrateInhibitor0.7139
CYP450 2C9 inhibitorInhibitor0.7003
CYP450 2D6 inhibitorNon-inhibitor0.8663
CYP450 2C19 inhibitorInhibitor0.708
CYP450 3A4 inhibitorNon-inhibitor0.5155
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8987
Ames testNon AMES toxic0.558
CarcinogenicityNon-carcinogens0.8121
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4870 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9733
hERG inhibition (predictor II)Inhibitor0.643
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
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 benzoxazines. These are organic compounds containing a benzene fused to an oxazine ring (a six-membered aliphatic ring with four carbon atoms, one oxygen atom, and one nitrogen atom).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzoxazines
Sub Class
Not Available
Direct Parent
Benzoxazines
Alternative Parents
N-methylpyrroles / Benzenoids / Thiocarbamic acid esters / Heteroaromatic compounds / Oxacyclic compounds / Nitriles / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Hydrocarbon derivatives
Substituents
Benzoxazine / N-methylpyrrole / Substituted pyrrole / Benzenoid / Pyrrole / Heteroaromatic compound / Thiocarbamic acid ester / Thiocarbamic acid derivative / Oxacycle / Nitrile
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Details
1. Progesterone receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor ...
Gene Name
PGR
Uniprot ID
P06401
Uniprot Name
Progesterone receptor
Molecular Weight
98979.96 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
  2. Zhang Z, Olland AM, Zhu Y, Cohen J, Berrodin T, Chippari S, Appavu C, Li S, Wilhem J, Chopra R, Fensome A, Zhang P, Wrobel J, Unwalla RJ, Lyttle CR, Winneker RC: Molecular and pharmacological properties of a potent and selective novel nonsteroidal progesterone receptor agonist tanaproget. J Biol Chem. 2005 Aug 5;280(31):28468-75. Epub 2005 Jun 3. [PubMed:15937332]

Drug created on September 11, 2007 11:49 / Updated on December 01, 2017 15:32