94497-51-5 Usage
Description
Tamibarotene, also known as AM80, is an orally administered synthetic retinoid with the brand name Amnolake. It is a retinoic acid receptor agonist that is selective for RARα compared to RARβ and RARγ. Tamibarotene has potential anti-neoplastic activity against acute promyelocytic leukemia (APL) and can be used for the treatment of Alzheimer's disease, multiple myeloma, and Crohn's disease. It takes effect by acting as a specific agonist for retinoid acid receptor alpha/beta and potentially binding to the retinoid X receptors (RXR). Compared to all-trans retinoid acid (ATRA), Tamibarotene is chemically more stable and much more potent as an inducer of differentiation and apoptosis in promyelocytic leukemia cells.
Uses
Used in Pharmaceutical Industry:
Tamibarotene is used as an antineoplastic agent for the treatment of acute promyelocytic leukemia (APL). It is a selective agonist of the retinoic acid receptor and has been approved for the treatment of relapsed or refractory APL in Japan. It has shown high remission rates among patients who have recurrent disease after all-trans retinoic acid therapy.
Used in Alzheimer's Disease Treatment:
Tamibarotene is used as a potential treatment for Alzheimer's disease, as it has shown to have potential anti-neoplastic activity.
Used in Multiple Myeloma Treatment:
Tamibarotene is used as a potential treatment for multiple myeloma, a type of blood cancer.
Used in Crohn's Disease Treatment:
Tamibarotene is used as a potential treatment for Crohn's disease, a chronic inflammatory bowel disease.
References
https://en.wikipedia.org/wiki/Tamibarotene
https://www.drugbank.ca/drugs/DB04942
Originator
Toko Yakuhin Kogyo (Japan)
Biological Activity
Retinoic acid receptor α (RAR α ) agonist that induces differentiation (ED 50 = 0.79 nM) and apoptosis of HL-60 cells in vitro . Exhibits antiproliferative effects against a variety of human tumor cells lines (mean values of 35, 40 and 60% growth inhibition at 0.1, 1 and 10 μ M respectively) and displays anticancer activity against acute promyelocytic leukemia in vivo .
Biochem/physiol Actions
Tamibarotene (Am80) is a RAR α agonist. Tamibarotene was developed to overcome resistance to ATRA and is currently approved in Japan for treatment of recurrent acute promyelocytic leukemia (APL). The compound induces HL-60 cells differentiation and apoptosis. Similarly to TTNPB, the compound neither binds to nor transactivates the RXRs. In contrast to TTNPB (pan RAR agonist), Tamibarotene is rather specific toward RAR α. The compound is approximate 10 times more potent than ATRA.
Synthesis
Several synthesis of tamibarotene have been disclosed
in the literature including the process scale synthesis
as shown in the scheme. The synthesis started
with preparation of dichloride 134 in 82% yield from diol
133 by treating with concentrated HCL in DCM. Friedal
Crafts reaction of dichloride 134 with acetanilide in the presence
of aluminum chloride at -15°C for 2h provided
acetanilide derivative 136 in 78% yield. In a single pot, the
acetanilide was reacted with PCl5 and dimethylaniline at -25°C for 1.5h followed by quenching the reaction with
methanol for 2h after addition at -25°C. Addition of dimethylaniline
and terepthalic chloride mono-methylester at -30 - -
20°C for 1 hr provided the tamibarotene methyl easter 137 in
81% yield. Hydrolysis of the ester by heating with sodium
hydroxide in MeOH:water mixture for 1h followed isolation
and crystallization gave tamibarotene (XIX) in 92% yield.
Check Digit Verification of cas no
The CAS Registry Mumber 94497-51-5 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 9,4,4,9 and 7 respectively; the second part has 2 digits, 5 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 94497-51:
(7*9)+(6*4)+(5*4)+(4*9)+(3*7)+(2*5)+(1*1)=175
175 % 10 = 5
So 94497-51-5 is a valid CAS Registry Number.
InChI:InChI=1/C22H25NO3/c1-21(2)11-12-22(3,4)18-13-16(9-10-17(18)21)23-19(24)14-5-7-15(8-6-14)20(25)26/h5-10,13H,11-12H2,1-4H3,(H,23,24)(H,25,26)
94497-51-5Relevant articles and documents
Synthesis of Tamibarotene via Ullmann-Type Coupling
Bao, Xuefei,Qiao, Xuejun,Bao, Changshun,Liu, Yuting,Zhao, Xuan,Lu, Yi,Chen, Guoliang
, p. 748 - 753 (2017/05/29)
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 accepta
Highly efficient aminocarbonylation of iodoarenes at atmospheric pressure catalyzed by a robust acenaphthoimidazolyidene allylic palladium complex
Fang, Weiwei,Deng, Qinyue,Xu, Mizhi,Tu, Tao
supporting information, p. 3678 - 3681 (2013/08/23)
A robust allylic palladium-NHC complex was developed and exhibited extremely high catalytic activity toward aminocarbonylation of various (hetero)aryl iodides under atmospheric carbon monoxide pressure, in which a broad range of secondary and primary amines were well tolerated. In addition, the concise synthesis of an anticancer drug tamibarotene was accomplished even in a gram scale, further highlighting the practical applicability of the protocol.
Method of treating bone disease with pyridine, carboxamide and carboxylic derivatives
-
, (2008/06/13)
Treatment of osteopathic comprising administering as an active ingredient a compound represented by the following formula (I), (II) or (III): STR1
