DR ANTHONY MELVIN CRASTO,WorldDrugTracker, helping millions, A 90 % paralysed man in action for you, I am suffering from transverse mylitis and bound to a wheel chair, With death on the horizon, this will not stop me, Only God and death can..........
DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai), INDIA, worlddrugtracker, 29Yrs Exp. in the feld of Organic Chemistry,Working for GLENMARK PHARMA at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.8 Million hits on google, world acclamation from industry, academia, drug authorities for websites, blogs and educational contributionn, सुकून उतना ही देना प्रभू, जितने से जिंदगी चल जाये।औकात बस इतनी देना,कि औरों का भला हो जाये।...........P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

Sunday, 13 March 2016

ODM-201


ODM-201.svg
ODM 201, BAY 1841788; ODM-201
N-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide
CAS 1297538-32-9
Chemical Formula: C19H19ClN6O2
Exact Mass: 398.1258
SYNTHESIS SEE BELOW
Phase III Prostate cancer
  • 12 Feb 2016 Bayer plans a phase I trial in healthy volunteers in Germany (NCT02671097)
  • 01 Nov 2015 Orion Corporation completes a phase II trial in Prostate cancer (late-stage disease, second-line or greater) in USA, Czech Republic, Estonia, France, Finland and United Kingdom (NCT01429064)
  • 16 Oct 2015 Phase-III clinical trials in Prostate cancer (Second-line therapy or greater) in Australia, Belarus, Canada, South Africa, South Korea, Russia, Spain, Taiwan and Ukraine (PO) 
  • Originator Orion
  • Developer Bayer HealthCare; Orion

  • Class Antineoplastics
  • Mechanism of Action Androgen receptor antagonists
ODM-201 (also known as BAY-1841788) is a non-steroidal antiandrogen, specifically, a full and high-affinity antagonist of the androgen receptor (AR), that is under development by Orion and Bayer HealthCare[1] for the treatment of advanced, castration-resistant prostate cancer (CRPC).[2][3]

Relative to enzalutamide (MDV3100 or Xtandi) and apalutamide (ARN-509), two other recent non-steroidal antiandrogens, ODM-201 shows some advantages.[3] ODM-201 appears to negligibly cross the blood-brain-barrier.[3] This is beneficial due to the reduced risk of seizures and other central side effects from off-target GABAA receptor inhibition that tends to occur in non-steroidal antiandrogens that are structurally similar to enzalutamide.[3] Moreover, in accordance with its lack of central penetration, ODM-201 does not seem to increase testosterone levels in mice or humans, unlike other non-steroidal antiandrogens.[3] Another advantage is that ODM-201 has been found to block the activity of all tested/well-known mutant ARs in prostate cancer, including the recently-identified clinically-relevant F876L mutation that produces resistance to enzalutamide and ARN-509.[3] Finally, ODM-201 shows higher affinity and inhibitory efficacy at the AR (Ki = 11 nM relative to 86 nM for enzalutamide and 93 nM for ARN-509; IC50 = 26 nM relative to 219 nM for enzalutamide and 200 nM for ARN-509) and greater potency/efficaciousness in non-clinical models of prostate cancer.[3]
ODM-201 has been studied in phase I and phase II clinical trials and has thus far been found to be effective and well-tolerated,[4] with the most commonly reported side effects including fatigue, nausea, and diarrhea.[5][6] No seizures have been observed.[6][7] As of July 2015, ODM-201 is in phase III trials for CRPC.[3]
ORM-15341 is the main active metabolite of ODM-201.[3] It, similarly, is a full antagonist of the AR, with an affinity (Ki) of 8 nM and an IC50 of 38 nM.[3]
ODM-201 is a new-generation, potent and selective androgen receptor (AR) inhibitor which is potential useful for treatment of castration-resistant prostate cancer (CRPC). ODM-201 is a full and high-affinity AR antagonist that, similar to second-generation antiandrogens enzalutamide and ARN-509, inhibits testosterone-induced nuclear translocation of AR. Importantly, ODM-201 also blocks the activity of the tested mutant ARs arising in response to antiandrogen therapies, including the F876L mutation that confers resistance to enzalutamide and ARN-509. In addition, ODM-201 reduces the growth of AR-overexpressing VCaP prostate cancer cells both in vitro and in a castration-resistant VCaP xenograft model. ODM-201 overcomes resistance to AR-targeted therapies by antagonizing both overexpressed and mutated ARs. ODM-201 is currently in a phase 3 trial in CRPC
Figure 1: The structures of ODM-201 (A) and its main metabolite ORM-15341 (B).
Figure 1
Representative binding affinities of ODM-201, ORM-15341, enzalutamide, and ARN-509 measured in competition with [3H]mibolerone using wtAR isolated from rat ventral prostates (C). All data points are means of quadruplicates ±SEM. Ki values are presented in parentheses. D. Antagonism to wtAR was determined using AR-HEK293 cells treated with ODM-201, ORM-15341, enzalutamide, or ARN-509 together with 0.45 nM testosterone in steroid-depleted medium for 24 hours before luciferase activity measurements. All data points are means of triplicates ±SEM. IC50 values are presented in parentheses.

 

WHIPPANY, N.J., Sept. 16, 2014 /PRNewswire/ -- Bayer HealthCare and Orion Corporation, a pharmaceutical company based in Espoo, Finland, have begun to enroll patients in a Phase III trial with ODM-201, an investigational oral androgen receptor inhibitor in clinical development. The study, called ARAMIS, evaluates ODM-201 in men with castration-resistant prostate cancer who have rising Prostate Specific Antigen (PSA) levels and no detectable metastases. The trial is designed to determine the effects of the treatment on metastasis-free survival (MFS).
"The field of treatment options for prostate cancer patients is evolving rapidly.  However, once prostate cancer becomes resistant to conventional anti-hormonal therapy, many patients will eventually develop metastatic disease," said Dr. Joerg Moeller, Member of the Bayer HealthCare Executive Committee and Head of Global Development. "The initiation of a Phase III clinical trial for ODM-201 marks the starting point for a potential new treatment option for patients whose cancer has not yet spread.  This is an important milestone for Bayer in our ongoing effort to meet the unmet needs of men affected by prostate cancer."
Earlier this year, Bayer and Orion entered into a global agreement under which the companies will jointly develop ODM-201, with Bayer contributing a major share of the costs of future development. Bayer will commercialize ODM-201 globally, and Orion has the option to co-promote ODM-201 in Europe. Orion will be responsible for the manufacturing of the product.
About the ARAMIS StudyThe ARAMIS trial is a randomized, Phase III, multicenter, double-blind, placebo-controlled trial evaluating the safety and efficacy of oral ODM-201 in patients with non-metastatic CRPC who are at high risk for developing metastatic disease. About 1,500 patients are planned to be randomized in a 2:1 ratio to receive 600 mg of ODM-201 twice a day or matching placebo. Randomisation will be stratified by PSA doubling time (PSADT less than or equal to 6 months vs. > 6 months) and use of osteoclast-targeted therapy (yes vs. no).
The primary endpoint of this study is metastasis-free survival (MFS), defined as time between randomization and evidence of metastasis or death from any cause. The secondary objectives of this study are overall survival (OS), time to first symptomatic skeletal event (SSE), time to initiation of first cytotoxic chemotherapy, time to pain progression, and characterization of the safety and tolerability of ODM-201.
About ODM-201ODM-201 is an investigational androgen receptor (AR) inhibitor that is thought to block the growth of prostate cancer cells. ODM-201 binds to the AR and inhibits receptor function by blocking its cellular function.
About Oncology at BayerBayer is committed to science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer now includes three oncology products and several other compounds in various stages of clinical development. Together, these products reflect the company's approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.
About Bayer HealthCare Pharmaceuticals Inc.Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals business of Bayer HealthCare LLC, a subsidiary of Bayer AG. Bayer HealthCare is one of the world's leading, innovative companies in the healthcare and medical products industry, and combines the activities of the Animal Health, Consumer Care, Medical Care, and Pharmaceuticals divisions. As a specialty pharmaceutical company, Bayer HealthCare provides products for General Medicine, Hematology, Neurology, Oncology and Women's Healthcare. The company's aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases.
Bayer® and the Bayer Cross® are registered trademarks of Bayer.

SYNTHESIS

str1
PATENT
US 2015203479

PATENT
WO 2012143599

References


Fenner A. Prostate cancer: ODM-201 tablets complete phase I. Nat Rev Urol. 2015 Dec;12(12):654. doi: 10.1038/nrurol.2015.268. Epub 2015 Nov 3. PubMed PMID: 26526759.
2: Massard C, Penttinen HM, Vjaters E, Bono P, Lietuvietis V, Tammela TL, Vuorela A, Nykänen P, Pohjanjousi P, Snapir A, Fizazi K. Pharmacokinetics, Antitumor Activity, and Safety of ODM-201 in Patients with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer: An Open-label Phase 1 Study. Eur Urol. 2015 Oct 10. pii: S0302-2838(15)00964-1. doi: 10.1016/j.eururo.2015.09.046. [Epub ahead of print] PubMed PMID: 26463318.
3: Fizazi K, Albiges L, Loriot Y, Massard C. ODM-201: a new-generation androgen receptor inhibitor in castration-resistant prostate cancer. Expert Rev Anticancer Ther. 2015;15(9):1007-17. doi: 10.1586/14737140.2015.1081566. PubMed PMID: 26313416; PubMed Central PMCID: PMC4673554.
4: Bambury RM, Rathkopf DE. Novel and next-generation androgen receptor-directed therapies for prostate cancer: Beyond abiraterone and enzalutamide. Urol Oncol. 2015 Jul 7. pii: S1078-1439(15)00269-0. doi: 10.1016/j.urolonc.2015.05.025. [Epub ahead of print] Review. PubMed PMID: 26162486.
5: Moilanen AM, Riikonen R, Oksala R, Ravanti L, Aho E, Wohlfahrt G, Nykänen PS, Törmäkangas OP, Palvimo JJ, Kallio PJ. Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies. Sci Rep. 2015 Jul 3;5:12007. doi: 10.1038/srep12007. PubMed PMID: 26137992; PubMed Central PMCID: PMC4490394.
6: Thibault C, Massard C. [New therapies in metastatic castration resistant prostate cancer]. Bull Cancer. 2015 Jun;102(6):501-8. doi: 10.1016/j.bulcan.2015.04.016. Epub 2015 May 26. Review. French. PubMed PMID: 26022286.
7: Bjartell A. Re: activity and safety of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (ARADES): an open-label phase 1 dose-escalation and randomised phase 2 dose expansion trial. Eur Urol. 2015 Feb;67(2):348-9. doi: 10.1016/j.eururo.2014.11.019. PubMed PMID: 25760250.
8: De Maeseneer DJ, Van Praet C, Lumen N, Rottey S. Battling resistance mechanisms in antihormonal prostate cancer treatment: Novel agents and combinations. Urol Oncol. 2015 Jul;33(7):310-21. doi: 10.1016/j.urolonc.2015.01.008. Epub 2015 Feb 21. Review. PubMed PMID: 25708954.
9: Boegemann M, Schrader AJ, Krabbe LM, Herrmann E. Present, Emerging and Possible Future Biomarkers in Castration Resistant Prostate Cancer (CRPC). Curr Cancer Drug Targets. 2015;15(3):243-55. PubMed PMID: 25654638.
10: ODM-201 is safe and active in metastatic castration-resistant prostate cancer. Cancer Discov. 2014 Sep;4(9):OF10. doi: 10.1158/2159-8290.CD-RW2014-150. Epub 2014 Jul 9. PubMed PMID: 25185192.
11: Fizazi K, Massard C, Bono P, Jones R, Kataja V, James N, Garcia JA, Protheroe A, Tammela TL, Elliott T, Mattila L, Aspegren J, Vuorela A, Langmuir P, Mustonen M; ARADES study group. Activity and safety of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (ARADES): an open-label phase 1 dose-escalation and randomised phase 2 dose expansion trial. Lancet Oncol. 2014 Aug;15(9):975-85. doi: 10.1016/S1470-2045(14)70240-2. Epub 2014 Jun 25. PubMed PMID: 24974051.
12: Agarwal N, Di Lorenzo G, Sonpavde G, Bellmunt J. New agents for prostate cancer. Ann Oncol. 2014 Sep;25(9):1700-9. doi: 10.1093/annonc/mdu038. Epub 2014 Mar 20. Review. PubMed PMID: 24658665.
13: Pinto Á. Beyond abiraterone: new hormonal therapies for metastatic castration-resistant prostate cancer. Cancer Biol Ther. 2014 Feb;15(2):149-55. doi: 10.4161/cbt.26724. Epub 2013 Nov 1. Review. PubMed PMID: 24100689; PubMed Central PMCID: PMC3928129.
14: Yin L, Hu Q, Hartmann RW. Recent progress in pharmaceutical therapies for castration-resistant prostate cancer. Int J Mol Sci. 2013 Jul 4;14(7):13958-78. doi: 10.3390/ijms140713958. Review. PubMed PMID: 23880851; PubMed Central PMCID: PMC3742227.
15: Leibowitz-Amit R, Joshua AM. Targeting the androgen receptor in the management of castration-resistant prostate cancer: rationale, progress, and future directions. Curr Oncol. 2012 Dec;19(Suppl 3):S22-31. doi: 10.3747/co.19.1281. PubMed PMID: 23355790; PubMed Central PMCID: PMC3553559.

ODM-201
ODM-201.svg
Systematic (IUPAC) name
N((R)-1-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide[1]
Identifiers
ChemSpider38772320
Chemical data
FormulaC19H19ClN6O2
Molar mass398.85 g·mol−1
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O=C(C1=NNC(C(O)C)=C1)N[C@@H](C)CN2N=C(C3=CC=C(C#N)C(Cl)=C3)C=C2
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GALETERONE



File:Galeterone.svg
Galeterone
SYNTHESIS SEE BELOW
A SARM potentially for the treatment of prostate cancer.
Research Code, TOK-001; VN; 124; 124-1; 1241
TOK-001; Galeterone; 851983-85-2; VN/124; UNII-WA33E149SW; VN/124-1;
CAS No. 851983-85-2(Galeterone)
(3S,8R,9S,10R,13S,14S)-17-(benzimidazol-1-yl)-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-ol
Fast track 2012 f
Molecular Formula:C26H32N2O
Molecular Weight:388.54508 g/mol


Galeterone (TOK-001 or VN/124-1) is a novel steroidal antiandrogen under development by Tokai Pharmaceuticals for the treatment of prostate cancer. It possesses a unique dual mechanism of action, acting as both an androgen receptor antagonist and an inhibitor of CYP17A1, an enzyme required for the biosynthesis of the androgens.[1] It shows selectivity for 17,20-lyase over 17-hydroxylase.[2]
As of 2016, galeterone is being compared to enzalutamide in a phase III clinical trial (ARMOR3-SV) for AR-V7-expressing metastatic castration-resistant prostate cancer.[3][4]
Specific Androgen Receptor Modulator CYP17 Inhibitor TOK-001 is an orally bioavailable small-molecule androgen receptor modulator and CYP17 lyase inhibitor with potential antiandrogen activity. Galeterone exhibits three distinct mechanisms of action: 1) as an androgen receptor antagonist, 2) as a CYP17 lyase inhibitor and 3) by decreasing overall androgen receptor levels in prostate cancer tumors, all of which may result in a decrease in androgen-dependent growth signaling. Localized to the endoplasmic reticulum (ER), the cytochrome P450 enzyme CYP17 (P450C17 or CYP17A1) exhibits both 17alpha-hydroxylase and 17,20-lyase activities, and plays a key role in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens.

About Galeterone

Tokai’s lead product candidate is galeterone, a highly-selective, oral small molecule with the potential to transform the treatment of prostate cancer. We are focusing our late-stage development of galeterone on the treatment of men with metastatic, castration-resistant prostate cancer, or CRPC, whose prostate tumor cells express the AR-V7 splice variant.
We are conducting ARMOR3-SV, a Phase 3 clinical trial of galeterone evaluating whether administration of galeterone results in a statistically significant increase in radiographic progression-free survival as compared to Xtandi® (enzalutamide), an oral therapy currently approved for the treatment of CRPC, in AR-V7 positive metastatic CRPC patients. ARMOR3-SV is the first pivotal trial in prostate cancer to employ a precision medicine approach for patient selection. For more information regarding ARMOR3-SV, click here.
Galeterone has been studied in over 250 subjects in Phase 1 and Phase 2 clinical trials, including in CRPC patients with and without the AR-V7 splice variant. In these trials, galeterone demonstrated good tolerability and showed clinically meaningful reductions in levels of prostate specific antigen, or PSA, a biochemincal marker used to evaluate prostate cancer patients for signs of response to therapy.
We are currently focusing our late-stage development of galeterone on AR-V7 positive metastatic CRPC patients because it represents an unmet need in prostate cancer and our precision medicine approach provides an efficient development path. Based on the data we and our collaborators have produced to date, we also believe there is rationale for the broader clinical exploration of galeterone in the future.
Galeterone acts by disrupting the androgen receptor signaling pathway. This pathway is activated by the binding of male hormones (also known as androgens), such as testosterone and dihydrotestosterone (DHT) to androgen receptors in prostate cancer cells.
Galeterone disrupts the activation of the androgen receptor pathway in three ways:
  • Androgen receptor degradation, which reduces the amount of androgen receptor protein in tumor cells. There are no currently marketed drugs whose mechanism of action entails degradation of the androgen receptor. Therefore, galeterone represents a potential first-in-class therapeutic opportunity.
  • CYP17 enzyme inhibition, which blocks the synthesis of testosterone. This mechanism has been validated clinically by Zytiga (abiraterone). Zytiga must be co-administered with the steroid prednisone in order to minimize the risk of a potentially fatal side effect called mineralocorticoid excess. Unlike Zytiga, galeterone has not been shown in clinical trials to cause mineralocorticoid excess and, as a result, does not require co-administration of steroids. As a result, we believe that galeterone may be easier to administer, provide convenience for patients and enhance patient compliance.
  • Androgen receptor inhibition, which blocks the binding of testosterone or DHT with the androgen receptor. This mechanism has been validated clinically by Xtandi® (enzalutamide), which is also currently approved for the treatment of CRPC. Xtandi™ has shown a risk of grand mal seizures in clinical trials. We have not had any reports of seizures in clinical trials of galeterone and, therefore, galeterone may have certain safety advantages over Xtandi.

Tokai retains global rights to galeterone. We intend to commercialize galeterone in the United States on our own, and to seek a partner to further develop and commercialize galeterone outside of the United States.
Galeterone has been granted Fast Track designation by U.S. Food and Drug Administration for the treatment of CRPC. Fast Track designation is designed to facilitate the development and expedite review of drugs intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.
Androgen receptor degradation, which reduces the amount of androgen receptor protein in the tumor cells.
Androgen receptor antagonism, which blocks the binding of testosterone or DHT with the androgen receptor.
Inhibition of the enzyme CYP17, which blocks the synthesis of testosterone.

Figure 3: The structures of abiraterone, orteronel and galeterone.

From CYP17 inhibitors—abiraterone, C17,20-lyase inhibitors and multi-targeting agents

Nature Reviews Urology 11,32–42 (2014)
doi:10.1038/nrurol.2013.274

 SYNTHESIS

http://www.google.com/patents/CN104098638A?cl=en
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CN 104098638
DETAILED DESCRIPTION
1J loss reaction.
  (1) raw material specifications to match.
acetate pregnancy dehydropregnenolone: ​​toluene + ethanol: Batch steep: hydrochloric acid amine light = 1: 3: 0 4: 0.213, which pregnenolone acetate pregnancy 160kg, toluene + ethanol 320kg + 160kg, approved Steep 64kg, hydrochloric acid amine light 34kg.
  (2) process operation.
  In the first input 1000L tank oximation with hydroxylamine hydrochloride in pyridine, and then pumped into a mixed solvent of toluene and ethanol, the reaction solution was stirred and heated to complete dissolution, pregnancy-dehydropregnenolone acetate was added and heated under reflux for 3 hours, cooling and crystallization, The Department conducted into the centrifuge centrifugal drying, apply a recovery from the mother liquor, rinse with warm water mixture to no foam, centrifugal drying, drying to a moisture at 0.2% or less, that acetic acid in pregnancy dehydropregnenolone oxime (oxime compounds) 163kg, content of 99%, a melting point of 202-204 ° C, a yield of about 102% (for pregnenolone acetate pregnancy weight ratio).
2, heavy drain hydrolysis reaction.
  (1) raw material specifications to match.
  acetate pregnancy dehydropregnenolone waning: Benzene: Batch steep: phosphorus oxychloride and toluene: HCl + water = 1: 6 5: 0 4: 1: 3.5, which acetate pregnancy alcohol one hand 163kg, benzene 1060kg, batch steep 64kg, phosphorus oxychloride and toluene 80kg + 80kg, hydrochloric acid + water 245kg + 325kg.
(2) process operation.
The first drying 2000L rearrangement reaction tank, then pumped to the reaction tank benzene, alcohol into acetate pregnancy oxime, pulls out into benzene, stirring heated to reflux until the reaction mixture is completely dissolved, cooling to 1 (TC When, pyridine, of the reaction liquid at temperatures down to 6 ° C, start dropping a mixed solution of previously prepared phosphorus oxychloride and toluene (1: 1 mass ratio), slowly dropping, dropping control, first After slow fast reaction when dropping liquid temperature control in 4-8 ° C, the addition was complete, the reaction solution at 9-12 ° C for 3 hours the first time under.
After incubation, a solution has been a mixed solution of hydrochloric acid and water, good preparation, while dropping the reaction liquid temperature is controlled at 15-25 ° C, the addition was complete, the reaction solution at 15-25 ° C under a second Insulation 1. 5-2 hours. After incubation, stand 40 minutes, then points to lower acidic water layer, the remaining upper layer was added 0.3 times the amount of 30-35 ° C in the brine and let stand 20 minutes, a second watershed, sub lower aqueous layer was then allowed to stand for 30 minutes, a third water diversion, to give the final weight of the upper layer reaction solution was drained.
  3, the red Dingding steam distillate process.
The rearrangement reaction liquid was pumped to punch distillate tank, conduct atmospheric distillate punch, has been rushed to the reaction mixture was distilled benzene mixed solvent only, at the start of the steam valve not to open too much, so as not to rush material, distillation after cooling discharge, centrifugal drying, washing with tap water to neutral, and then into the oven dried to a moisture in the square. 5% acetic acid in dehydroepiandrosterone (rearrangement thereof) The crude product is about 142kg, content of about 97.5%, a melting point of 160 ° C _165 ° C or so, yield about 88% (for acetate pregnancy dehydropregnenolone weight ratio).
  4, refining processes.
  The drying in acetic acid Dehydroepiandrosterone crude into refined tin, adding 8 times the weight of the crude methanol and 0.10 times the weight of activated carbon, heat, stirring to dissolve, reflux billion. 5 hours, filtered , concentrated, cooled to about 5 ° C, the discharge

str1

JMC 2005, 48, 2972-84
http://pubs.acs.org/doi/abs/10.1021/jm040202w
The most potent CYP17 inhibitors were 3β-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene (5, code named VN/124-1), 3β-hydroxy-17-(51-pyrimidyl)androsta-5,16-diene (15)

PAPER
JMC 1998 41, 902-12
http://pubs.acs.org/doi/abs/10.1021/jm970568r
The most potent compounds are 3β-hydroxy-17-(1H-imidazol-1-yl)androsta-5,16-diene (17), 3β-hydroxy-17-(1H-1,2,3-triazol-1-yl)androsta-5,16-diene (19), and 17-(1H-imidazol-1-yl)androsta-4,16-dien-3-one (28), with Ki values of 1.2, 1.4, and 1.9 nM, respectively,

Discovery and Development of Galeterone (TOK-001 or VN/124-1)
for the Treatment of All Stages of Prostate Cancer.......http://pubs.acs.org/doi/pdf/10.1021/jm501239f
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 CLICK ON PIC FOR CLEAR VIEW
http://www.google.com/patents/WO2014165815A2?cl=en
Patent IDDatePatent Title
US20110344282011-02-10Treatment of Prostate Cancer
US78755992011-01-25C-17-heteroaryl steroidal CYP17 inhibitors/antiandrogens, in vitro biological activities, pharmacokinetics and antitumor activity
US20101372692010-06-03Novel C-17-Heteroaryl Steroidal Cyp17 Inhibitors/Antiandrogens: Synehesis, In Vitro Biological Activities, Pharmacokinetics and Antitumor Activity
US20100489142010-02-25Novel C-17-Heteroaryl Steroidal Cyp17 Inhibitors/Antiandrogens, In Vitro Biological Activities, Pharmacokinetics and Antitumor Activity
US20100489132010-02-25Novel C-17-Heteroaryl Steroidal CYP17 Inhibitors/Antiandrogens Synthesis In Vitro Biological Activities, Pharmacokinetics and Antitumor Activity
US20100489122010-02-25Novel C-17-Heteroaryl Steroidal CYP17 Inhibitors/Antiandrogens, In Vitro Biological Activities, Pharmacokinetics and Antitumor Activity
US20100485242010-02-25Novel C-17-Heteroaryl Steroidal CYP17 Inhibitors/Antiandrogens Synthesis In Vitro Biological Activities, Pharmacokinetics and Antitumor Activity
US20100473382010-02-25Novel C-17-Heteroaryl Steroidal CYP17 Inhibitors/Antiandrogens, In Vitro Biological Activities, Pharmacokinetics and Antitumor Activity
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US20133369622013-12-19AZIRIDINE BISPHENOL ETHERS AND RELATED COMPOUNDS AND METHODS FOR THEIR USE

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CN101691392A *Sep 17, 2009Apr 7, 2010扬州市天平化工厂有限公司Method for preparing 3beta-acetoxyl group-5androstene-17ketone
CN102212099A *Apr 2, 2011Oct 12, 2011邵阳市科瑞化学品有限公司Synthesis method for dehydroepiandrosterone
CN102603839A *Jan 13, 2012Jul 25, 2012宜城市共同药业有限公司Preparation method of dehydroepiandrosterone
CN102746356A *Jul 17, 2012Oct 24, 2012湖北芳通药业股份有限公司Process for producing dehydroepiandrosterone acetate through homogeneous phase method
Reference
1 *石诚等: "5-雄甾烯-3β-醇-17-酮-3-醋酸酯的工艺研究", 《山东化工》, vol. 41, no. 1, 31 December 2012 (2012-12-31)
2 *石诚等: "醋酸妊娠双烯醇酮肟的工艺研究", 《广州化工》, vol. 39, no. 23, 31 December 2011 (2011-12-31), pages 78 - 79

References


Silberstein, John L.; Taylor, Maritza N.; Antonarakis, Emmanuel S. (2016-04-01). "Novel Insights into Molecular Indicators of Response and Resistance to Modern Androgen-Axis Therapies in Prostate Cancer". Current Urology Reports 17 (4): 29. doi:10.1007/s11934-016-0584-4. ISSN 1534-6285. PMID 26902623.

Galeterone
Galeterone.svg
Systematic (IUPAC) name
17-(1H-benzimidazol-1-yl)androsta-5,16-dien-3β-ol
Clinical data
Routes of
administration		Oral
Identifiers
CAS Number851983-85-2
PubChemCID 11188409
ChemSpider9363493
KEGGD10125 Yes
Chemical data
FormulaC26H32N2O
Molar mass388.25
///////
C[C@]12CC[C@@H](CC1=CC[C@@H]3[C@@H]2CC[C@]4([C@H]3CC=C4N5C=NC6=CC=CC=C65)C)O
CC12CCC(CC1=CCC3C2CCC4(C3CC=C4N5C=NC6=CC=CC=C65)C)O
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