Apalutamide

A summary of the most common chemical descriptors (InChI Key and SMILES codes) for Apalutamide are summarized together with 3D and 2D structures and relevant physico-chemical properties.

What is the Apalutamide?

The molecule Apalutamide presents a molecular formula of C21H15F4N5O2S and its IUPAC name is 4-[7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide.

Apalutamide (trade name Erleada) is a nonsteroidal antiandrogen (NSAA) of the androgen receptor (AR) antagonist type that is used in the treatment of prostate cancer. It was approved in the United States in 2018, and in the European Union in 2019..

Apalutamide is a prodrug of the active metabolite N-desethyl apalutamide, which is also an AR antagonist. In addition to its AR antagonist activity, apalutamide has agonist activity at the estrogen receptor (ER) and the progesterone receptor (PR), and antagonist activity at the androgen receptor (AR)..

Apalutamide has shown efficacy in the treatment of metastatic castration-resistant prostate cancer (mCRPC) in two Phase III clinical trials, SPARTAN and TITAN. In the SPARTAN trial, 1,207 men with mCRPC were randomized to receive either apalutamide (n=605) or placebo (n=602). The primary endpoint was radiographic progression-free survival (rPFS), and the secondary endpoint was overall survival (OS)..

At the time of the primary analysis, the median rPFS was not reached in the apalutamide group and was 18.4 months in the placebo group (HR=0.41, 95% CI: 0.34-0.50, p<0.0001). The median OS was not reached in the apalutamide group and was 35.3 months in the placebo group (HR=0.63, 95% CI: 0.50-0.79, p<0.0001)..

In the TITAN trial, 1,052 men with mCRPC were randomized to receive either apalutamide (n=526) or placebo (n=526). The primary endpoint was rPFS, and the secondary endpoint was OS..

At the time of the primary analysis, the median rPFS was not reached in the apalutamide group and was 16.6 months in the placebo group (HR=0.46, 95% CI: 0.37-0.57, p<0.0001). The median OS was not reached in the apalutamide group and was 33.3 months in the placebo group (HR=0.68, 95% CI: 0.54-0.85, p<0.0001)..

The most common adverse reactions (>=10%) in the apalutamide group were fatigue, hypertension, diarrhea, nausea, weight loss, arthralgia, hot flush, convulsion, and decreased appetite..

Apalutamide is a novel androgen receptor inhibitor with a unique mechanism of action. It is the first and only AR inhibitor to demonstrate efficacy in the treatment of mCRPC in two Phase III clinical trials..

3D structure

Cartesian coordinates

Geometry of Apalutamide in x, y and z coordinates (Å units) to copy/paste elsewhere. Generated with Open Babel software.

2D drawing

 

Apalutamide HJBWBFZLDZWPHF-UHFFFAOYSA-N chemical compound 2D structure molecule svg
Apalutamide

 

Molecule descriptors

 
IUPAC name4-[7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide
InChI codeInChI=1S/C21H15F4N5O2S/c1-27-17(31)13-4-3-11(8-15(13)22)30-19(33)29(18(32)20(30)5-2-6-20)12-7-14(21(23,24)25)16(9-26)28-10-12/h3-4,7-8,10H,2,5-6H2,1H3,(H,27,31)
InChI KeyHJBWBFZLDZWPHF-UHFFFAOYSA-N
SMILESCNC(=O)c1ccc(N2C(=S)N(c3cnc(C#N)c(C(F)(F)F)c3)C(=O)C23CCC3)cc1F

Other names (synonyms)

IUPAC nomenclature provides a standardized method for naming chemical compounds. Although this system is widely used in chemistry, many chemical compounds have also other names commonly used in different contexts. These synonyms can come from a variety of sources and are used for a variety of purposes.

One common source of synonyms for chemical compounds is the common or trivial names, assigned on the basis of appearance, properties, or origin of the molecule.

Another source of synonyms are historical or obsolete names employed in the past, however replaced nowadays by more modern or standardized names.

In addition to common and historical names, chemical compounds may also have synonyms that are specific to a particular field or industry.

  • 24872560, Erleada, C21H15F4N5O2S
  • 4-(7-(6-CYANO-5-(TRIFLUOROMETHYL)PYRIDIN-3-YL)-8-OXO-6-THIOXO-5,7-DIAZASPIRO[3.4]OCTAN-5-YL)-2-FLUORO-N-METHYLBENZAMIDE
  • 4-(7-(6-Cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro(3.4)octan-5-yl)-2-fluoro-N-methylbenzamide
  • 4-[7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide
  • 4-{7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl}-2-fluoro-N-methylbenzamide
  • 4T36H88UA7
  • 956104-40-8
  • 956104-40-8 (free base)
  • AC-27403
  • AMY24182
  • AR509
  • AR509/AR-509
  • ARN 509
  • ARN-509
  • ARN509
  • AS-35181
  • Apalutamide
  • Apalutamide (ARN-509)
  • Apalutamide (JAN/INN)
  • ApalutamideARN509
  • BCP05829
  • BDBM50094975
  • BENZAMIDE, 4-(7-(6-CYANO-5-(TRIFLUOROMETHYL)-3-PYRIDINYL)-8-OXO-6-THIOXO-5,7-DIAZASPIRO(3.4)OCT-5-YL)-2-FLUORO-N-METHYL-
  • CCG-264760
  • CS-0885
  • D11040
  • DB11901
  • EX-A089
  • Erleada
  • GTPL9043
  • HMS3656N12
  • HY-16060
  • J-519596
  • JNJ 56021927
  • JNJ-56021927
  • MFCD22380626
  • MLS006011109
  • NCGC00346725-01
  • NCGC00346725-02
  • NCGC00346725-06
  • NSC-771649
  • NSC-794776
  • NSC771649
  • NSC794776
  • PB27306
  • Q21098975
  • SMR004702891
  • SW220300-1
  • apalutamide
  • s2840

Reference codes for other databases

There exist several different chemical codes commonly used in orded to identify molecules:
  • ZINC43174901
  • UNII-4T36H88UA7
  • AKOS025401932
  • DTXSID40241899
  • CHEMBL3183409
  • SCHEMBL909297

Physico-Chemical properties

IUPAC name4-[7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide
Molecular formulaC21H15F4N5O2S
Molecular weight477.435
Melting point (ºC)
Boiling point (ºC)
Density (g/cm3)
Molar refractivity118.94
LogP4.1
Topological polar surface area121.4

LogP and topological polar surface area (TPSA) values were estimated using Open Babel software.

The n-octanol/water partition coeficient (Kow) data is applied in toxicology and drug research. Kow values are used, to guess the environmental fate of persistent organic pollutants. High partition coefficients values, tend to accumulate in the fatty tissue of organisms. Molecules with a log(Kow) (or LogP) greater than 5 are considered to bioaccumulate.

TPSA values are the sum of the surface area over all polar atoms or molecules, mainly oxygen and nitrogen, also including hydrogen atoms.

In medicinal chemistry, TPSA is used to assess the ability of a drug to permeabilise cells.

For molecules to penetrate the blood-brain barrier (and act on receptors in the central nervous system), TPSA values below 90 Å2 are required. Thus, molecules with a polar surface area greater than 140 Å2 tend to be poorly permeable to cell membranes.