New Drug Approvals

Home » Posts tagged 'Tamibarotene'

Tag Archives: Tamibarotene

Advertisements
DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

Blog Stats

  • 2,573,502 hits

Flag and hits

Flag Counter

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

Join 2,385 other followers

Follow New Drug Approvals on WordPress.com

Categories

Flag Counter

ORGANIC SPECTROSCOPY

Read all about Organic Spectroscopy on ORGANIC SPECTROSCOPY INTERNATIONAL 

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

Join 2,385 other followers

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

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 GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 30 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, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, 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 30 year tenure till date Dec 2017, 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 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 50 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 19 lakh plus views on New Drug Approvals Blog in 216 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

Personal Links

Verified Services

View Full Profile →

Categories

Flag Counter
Advertisements

Tamibarotene, тамибаротен , تاميباروتان , 他米巴罗汀 ,


Tamibarotene2DACS.svg

Tamibarotene

тамибаротен تاميباروتان 他米巴罗汀 ,

94497-51-5  CAS

  • Molecular FormulaC22H25NO3
  • Average mass351.439 Da

4-(((5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)amino)carbonyl)benzoic Acid, Tamibarotene

4-[(5,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbamoyl]benzoic acid
Benzoic acid, 4-[[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)amino]carbonyl]-
Amnolake®
Amnoleuk
Benzoic acid, 4-(((5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)amino)carbonyl)-
BR-72889
C061133
DH6940000
MFCD00866188 [MDL number]
N-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl)-2-naphthyl)terephthalamic acid
QA-6963
retinobenzoic acid
  • Am 80
  • Am 80 (pharmaceutical)
  • Amnolake
  • NSC 608000
  • RR 110

Hisao Ekimoto, “TAMIBAROTENE CAPSULE PREPARATION.” U.S. Patent US20100048708, issued February 25, 2010.

US20100048708

Image result for Nippon Shinyaku

Tamibarotene , a small molecule retinoic acid receptor alpha (RARα) agonists developed by Nippon Shinyaku, was approved in Japan for the treatment of acute promyelocytic leukemia (APL) in 2005. Recently, the drug was in clinical development for the treatment of acute myeloid leukemia (AML), myelodysplasia, pediatric solid tumor, and steroid-refractory

Tamibarotene (brand name: Amnolake), also called retinobenzoic acid, is orally active, synthetic retinoid, developed to overcome all-trans retinoic acid (ATRA) resistance, with potential antineoplastic activity against acute promyelocytic leukaemia (APL) .[1] It is currently marketed only in Japan and early trials have demonstrated that it tends to be better tolerated than ATRA.[2] It has also been investigated as a possible treatment for Alzheimer’s disease, multiple myeloma and Crohn’s disease.[2][3]

Synthesis

The tetralin-based compound tamibarotene (7) has been tested as an agent for treating leukaemias.

Tamibarotene synth.png

Reaction of the diol (1) with hydrogen chloride affords the corresponding dichloro derivative (2). Aluminum chloride mediated Friedel–Crafts alkylation of acetanilide with the dichloride affords the tetralin (3). Basic hydrolysis leads to the primary amine (4). Acylation of the primary amino group with the half acid chloride half ester from terephthalic acid (5) leads to the amide (6). Basic hydrolysis of the ester grouping then affords (7).[4]

PAPER

Synthesis of Tamibarotene via Ullmann-Type Coupling

Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China
Org. Process Res. Dev., Article ASAP
Abstract Image

An effective process was developed for the preparation of tamibarotene via an Ullmann-type coupling in a nonpressurized l-proline/DMSO system. Notable features were the telescoping of reactions, avoiding environmentally hazardous materials, and an acceptable overall yield. The safe scalable process was validated on a 1 kg scale.

Mp 223–225 °C (lit.   SEE BELOW  mp 231–232 °C); 1H NMR (400 MHz, chloroform-d) δ 8.22 (d, J = 7.7 Hz, 2H), 7.97 (d, J = 7.7 Hz, 2H), 7.80 (s, 1H), 7.54 (s, 1H), 7.46 (d, J = 8.4 Hz, 1H), 7.33 (d, J = 8.3 Hz, 1H), 1.70 (s, 4H), 1.31 (s, 6H), 1.29 (s, 6H); MS (ESI) m/z: 350.0 [M – H]

Journal of Medicinal Chemistry (1988), 31 (11), 2182-92

PAPER

Journal of Medicinal Chemistry (1988), 31 (11), 2182-92

PAPER

Chem. Pharm. Bull. 61(8) 846–852 (2013)

https://www.jstage.jst.go.jp/article/cpb/61/8/61_c13-00356/_pdf

References

  1. Jump up^ “Tamibarotene: AM 80, retinobenzoic acid, Tamibaro”. Drugs in R&D. 5 (6): 359–62. 2004. doi:10.2165/00126839-200405060-00010. PMID 15563242.
  2. ^ Jump up to:a b Miwako, I; Kagechika, H (August 2007). “Tamibarotene”. Drugs Today (Barc). 43 (8): 563–568. doi:10.1358/dot.2007.43.8.1072615. PMID 17925887.
  3. Jump up^ Fukasawa, H; Nakagomi, M; Yamagata, N; Katsuki, H; Kawahara, K; Kitaoka, K; Miki, T; Shudo, K (2012). “Tamibarotene: a candidate retinoid drug for Alzheimer’s disease” (PDF). Biological & Pharmaceutical Bulletin. 35 (8): 1206–1212. doi:10.1248/bpb.b12-00314. PMID 22863914.
  4. Jump up^ Y. Hamada, I. Yamada, M. Uenaka, T. Sakata, U.S. Patent 5,214,202 (1993).
Tamibarotene
Tamibarotene2DACS.svg
Names
IUPAC name

4-[(1,1,4,4-tetramethyltetralin-6-yl)carbamoyl]benzoic acid
Identifiers
3D model (Jmol)
3564473
ChEBI
ChemSpider
DrugBank
UNII
Properties
C22H25NO3
Molar mass 351.45 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

////////////Tamibarotene, тамибаротен تاميباروتان 他米巴罗汀 

CC1(C)CCC(C)(C)C2=C1C=CC(NC(=O)C1=CC=C(C=C1)C(O)=O)=C2

Advertisements

CytRx Receives Recommendation from Data Safety Monitoring Committee to Complete Global Phase 2b Clinical Trial with Tamibarotene as First-Line Treatment for Non-Small-Cell Lung Cancer


4-[(1,1,4,4-tetramethyltetralin-6-yl)carbamoyl]benzoic acid, cas no  94497-51-5

“Tamibarotene is an orally available, rationally designed, synthetic retinoid compound that is 10-times more potent than all-trans retinoic acid (ATRA) and was designed to avoid several side effects of ATRA”

Tamibarotene, also called retinobenzoic acid, is orally active, synthetic retinoid, developed to overcome all-trans retinoic acid (ATRA) resistance, with potentialantineoplastic activity.

Tamibarotene synth.png

Y. Hamada, I. Yamada, M. Uenaka, T. Sakata, U.S. Patent 5,214,202 (1993).

  • “Tamibarotene: AM 80, retinobenzoic acid, Tamibaro”. Drugs in R&D 5 (6): 359–62. 2004. PMID 15563242.

January 31, 2013

CytRx Corporation(NASDAQ: CYTR), a biopharmaceutical research and development company specializing in oncology, announced that the Data Safety Monitoring Committee overseeing the Company’s global Phase 2b clinical trial with tamibarotene in combination with chemotherapeutical agents as a first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC) has recommended conducting the clinical trial through completion. Enrollment of at least 140 evaluable patients is expected in the first quarter of 2013.

“Tamibarotene is an orally available, rationally designed, synthetic retinoid compound that is 10-times more potent than all-trans retinoic acid (ATRA) and was designed to avoid several side effects of ATRA”

“The Committee’s recommendation indicates that no significant safety issues have been seen with tamibarotene in the international Phase 2b clinical trial as we near enrollment completion with tamibarotene’s use in combination with potent chemotherapy agents in patients with advanced NSCLC,” said CytRx CEO Steven A. Kriegsman. “We are one step closer to completing this important clinical trial and further assessing tamibarotene in a potential multibillion dollar market, which is a major priority for our Company and our shareholders.”

Subjects with stage IIIb or IV NSCLS who have not received prior non-adjuvant chemotherapy are being enrolled in the blinded, randomized clinical trial at sites in the U.S., Bulgaria, India, Mexico, Russia and Ukraine. Trial patients are treated with paclitaxel plus carboplatin and either tamibarotene or placebo. The primary objective of this trial is to determine the objective response rate (complete and partial responses) and progression-free survival. Secondarily, the trial will evaluate overall survival and quality-of-life in this population, among other measures. The Data Safety Monitoring Committee is an independent group of oncologists and biostatisticians who monitor the safety and efficacy of the Phase 2b trial.

“Tamibarotene is an orally available, rationally designed, synthetic retinoid compound that is 10-times more potent than all-trans retinoic acid (ATRA) and was designed to avoid several side effects of ATRA,” said Daniel Levitt, MD, Ph.D., CytRx’s Executive Vice President and Chief Medical Officer. “This event is significant due to favorable results from a single-center clinical trial in patients with advanced NSCLC that compared treatment with ATRA added to a regimen of paclitaxel plus cisplatin to a regimen of paclitaxel plus cisplatin alone. Patients who received the regimen with ATRA showed improved response rates of 55.8% versus 25.4%, increased progression-free survival of 8.9 months versus 6.0 months, and a 14-month median extension of life.”

CytRx holds the North American and European rights to certain tamibarotene intellectual property for the treatment of NSCLC, and retains an option to expand its licenses for the use of tamibarotene in other fields in oncology.

%d bloggers like this: