New Drug Approvals

Home » Preclinical drugs » Enzalutamide




Read all about Organic Spectroscopy on ORGANIC SPECTROSCOPY INTERNATIONAL 


Blog Stats

  • 4,301,185 hits

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 2,821 other subscribers

add to any





Drug Name:
Research Code:
Trade Name:
Androgen receptor inhibitor
Prostate cancer
Medivation (Originator) , Astellas
$2,100.8 Million (Y2015); 
$1,247.3 Million (Y2014);
$546 Million (Y2013);
$148.8 Million (Y2012);
ATC Code:
Approved Countries or AreaUpdate Date:2015-07-29

Approval Date Approval Type Trade Name Indication Dosage Form Strength Company Review Classification
2012-08-31 Marketing approval Xtandi Prostate cancer Capsule, Liquid filled 40 mg Astellas Priority
Approval Date Approval Type Trade Name Indication Dosage Form Strength Company Review Classification
2013-06-21 Marketing approval Xtandi Prostate cancer Capsule 40 mg Astellas
Approval Date Approval Type Trade Name Indication Dosage Form Strength Company Review Classification
2014-03-24 Marketing approval Xtandi Prostate cancer Capsule 40 mg Astellas


Enzalutamide was approved by the U.S. Food and Drug Administration (FDA) on August 31, 2012, then approved by European Medicine Agency (EMA) on June 21, 2013, and approved by Pharmaceuticals and Medical Devices Agency of Japan (PMDA) on March 24, 2014. It was developed by Medivation and Astellas and marketed as Xtandi® by Astellas.

Enzalutamide is an androgen receptor inhibitor that decreases proliferation and induces death of prostate cancer cells. It is indicated for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel.

Xtandi® is available as capsule for oral use, containing 40 mg of free Enzalutamide, and the recommended doe is 160 mg once daily.

Prostate cancer, one of the most malignant tumors worldwide, is the second leading cause of cancer deaths among men in America . Although androgen deprivation therapy (ADT) has been proved to be effective initially, the tumor will eventually progress and develop into the lethal castration resistant prostate cancer (CRPC) . The androgen receptor (AR) is a ligand-dependent transcription factor belonging to the nuclear receptor superfamily and plays a critical role in the progression of normal prostate cells. However, overexpression of AR was found in most CRPC, which is essential for CRPC to adapt to the low levels of androgens. As AR contributes significantly to the resistance to castration, it has been recognized as an attractive target for the treatment of CRPC

Reagents and conditions: (i) HNO3 , H2SO4 , -5 oC, 3 h; (ii) SOCl2 , MeOH, reflux, 12 h; (iii) H2 , Pd/C, MeOH, rt, 12 h; (iv) (CH3CO)2O, TEA, 50 oC, 6 h; (v) H2 , Pd/C, MeOH, rt, 12 h; (vi) acetone, HCl (6 mol/L), -10 oC, 0.5 h, NaNO2 , H2O, -10 oC, 1 h, CuCl/CuBr/KI, 0 oC, 3 h; (vii) HCl, 50 oC, 3 h; (viii) SOCl2 , MeOH, reflux, 12 h; (ix) 2, DMF, TEA, 60 oC, 1 h.

4-(6-chloro-1-oxo-3-thioxo-9,9a-dihydro-1H-imidazo[1,5-a]indol-2(3H)-yl)-2-(trifluoromethyl)-benzonitrile (48c). It was obtained as a yellow solid

m.p. 220-222 oC;

1H-NMR (300 MHz,DMSO-d6): δ 8.40 (d, J = 8.1 Hz, 1H, Ar-H), 8.19 (s, 1H, Ar-H), 8.02-7.92 (m, 2H, Ar-H), 7.49-7.46 (m, 1H, Ar-H), 7.34-7.32 (m, 1H, Ar-H), 5.56 (t, J = 9.6 Hz, 1H, -CH-), 3.58 (d, J = 9.6 Hz, 2H, -CH2-) ppm;

13C-NMR (75 MHz, DMSO-d6): δ 184.1, 172.1, 142.3, 138.5, 136.8, 134.7, 131.9, 131.5, 128.0, 126.1 (q, J = 267.9 Hz, CF3), 117.2, 115.4, 66.9, 39.9 ppm;

IR (KBr): 3094, 2232, 1763, 1607, 1499, 1270, 1136, 1052, 998, 786 cm-1;

HRMS (ESI): m/z, calculated for C18H9ClF3N3OS 408.0180 (M + H)+ , found 408.0173.


A series of indoline thiohydantoin derivatives were synthesized and evaluated in vitro.The most potent compound 48c shows comparable ability with enzalutamide in proliferation inhibition of LNCaP cells.Compound 48c has less cytotoxic to AR-negative cells compared with Enzalutamide.

The bicalutamide-resistant mechanism was clarified and overcome by compound 48c.


A novel scaffold of indoline thiohydantoin was discovered as potent androgen receptor (AR) antagonist through rational drug designation. Several compounds showed good biological profiles in AR binding and higher selective toxicity than enzalutamide toward LNCaP cells (AR-rich) versus DU145 cells (AR-deficient). In addition, the docking studies supported the rationalization of the biological evaluation. Among these compounds, the representative compound 48c exhibited the strongest inhibitory effect on LNCaP growth and also acted as a competitive AR antagonist. Further preliminary mechanism study confirmed that 48c exerted its AR antagonistic activity through impairing AR nuclear translocation. All these results indicated that the novel scaffold compounds demonstrated AR antagonistic behaviour and promising candidates for future development were identified.

Graphical abstract

Image 1

Available online 22 October 2016

Design and synthesis of indoline thiohydantoin derivatives based on enzalutamide as antiproliferative agents against prostate cancer
  • Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China


Chinese Chemical Letters

Volume 28, Issue 2, February 2017, Pages 426-430
An improved and practical route for the synthesis of enzalutamide and potential impurities study
An improved and practical route for the synthesis of enzalutamide and  potential impurities study - ScienceDirect
An improved and practical route for the synthesis of enzalutamide and  potential impurities study - ScienceDirect


. WO2006124118A1.

2. WO2007127010A2 / US8110594B2.

3. J. Med. Chem. 201053, 2779-2796.

4. WO2013087004A1 / US20140371284A1.


WO2011106570A1 / US20130190507A1.

2. WO2014041487A2.

3. CN103980141A.

4. CN104016924A.


WO2011106570A1 / US20130190507A1.



2. Fine Chem. Intermed. 201242, 34-36.


////////Prostate cancer, Androgen receptor, Antagonist, Indoline thiohydantoin derivatives, indoline thiohydantoin derivatives, enzalutamide, antiproliferative agents, prostate cancer


Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.


Follow New Drug Approvals on

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 2,821 other subscribers


DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with AFRICURE PHARMA, ROW2TECH, NIPER-G, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Govt. of India as ADVISOR, earlier assignment was with GLENMARK LIFE SCIENCES LTD, as CONSUlTANT, Retired from GLENMARK in Jan2022 Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 32 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 32 PLUS year tenure till date Feb 2023, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 100 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 100 Lakh plus views on dozen plus blogs, 227 countries, 7 continents, He makes himself available to all, contact him on +91 9323115463, email, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 38 lakh plus views on New Drug Approvals Blog in 227 countries...... , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc He has total of 32 International and Indian awards

Personal Links

View Full Profile →


Follow my blog with Bloglovin The title of your home page You could put your verification ID in a comment Or, in its own meta tag Or, as one of your keywords Your content is here. The verification ID will NOT be detected if you put it here.
%d bloggers like this: