4-[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbamoyl]benzoic acid

• ChemBase ID: 4401
• Molecular Formular: C22H25NO3
• Molecular Mass: 351.4388
• Monoisotopic Mass: 351.18344367
• SMILES: O=C(Nc1cc2C(CCC(c2cc1)(C)C)(C)C)c1ccc(cc1)C(=O)O
• Canonical SMILES: O=C(c1ccc(cc1)C(=O)O)Nc1ccc2c(c1)C(C)(C)CCC2(C)C
• InChI: InChI=1S/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)
• InChIKey: MUTNCGKQJGXKEM-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 4-[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbamoyl]benzoic acid
• IUPAC Traditional name: tamibarotene
• Brand Name: Amnoid; Tamibaro
• Synonyms: 4-((5,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthale n-2-yl)carbamoyl)benzoic acid; -((5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl)benzoic acid; 4-(((5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)amino)carbonyl)-benzoic acid; AM80; AMNOLAKE; Amnoid; N-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl)-2-naphthyl)terephthalamic acid; N-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)terephthalamic acid; NSC 608000; UNII-08V52GZ3H9; Tamibarotene; Am 80; retinobenzoic acid; Tamibarotene; Tamibarotene; 4-((5,5,8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbamoyl)benzoic acid; 4-[[(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)amino]carbonyl]benzoic Acid; Am 80 (pharmaceutical); Retinoid AM 80

Database IDs

• CAS Number: 94497-51-5
• MDL Number: MFCD00866188
• Beilstein Number: 3564473
• PubChem SID: 46509039; 160967833
• PubChem CID: 108143
• CHEMBL: 25202
• Chemspider ID: 97231
• DrugBank ID: DB04942
• Wikipedia Title: Tamibarotene

CALCULATED PROPERTIES

JChem

• Acid pKa: 3.693783
• H Acceptors: 3
• H Donor: 2
• LogD (pH = 5.5): 3.5442872
• LogD (pH = 7.4): 2.0411327
• Log P: 5.3491
• Molar Refractivity: 104.3773 cm^3
• Polarizability: 39.101734 Å^3
• Polar Surface Area: 66.4 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 4.99
• LOG S: -5.79
• Solubility (Water): 5.75e-04 g/l

PROPERTIES

Physical Property

• Solubility: DMSO: ≥10 mg/mL; Methanol
• Apperance: Off-White Solid; white to off-white powder
• Melting Point: 228-230°C

Safety Information

• Storage Condition: Refrigerator
• Storage Warning: IRRITANT
• German water hazard class: 3
• TSCA Listed: false
• Storage Temperature: room temp

Pharmacology Properties

• Target: Others

Product Information

• Purity: ≥98% (HPLC); 95+%
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C22H25NO3

DETAILS

DrugBank - DB04942

• Drug Groups: approved; investigational
• Description: Tamibarotene is a novel synthetic retinoid for acute promyelocytic leukaemia (APL). Tamibarotene is currently approved in Japan for treatment of recurrent APL, and is undergoing clinical trials in the United States.
• Indication: Investigated for use/treatment in leukemia (unspecified).
• Pharmacology: Tamibarotene is a new synthetic retinoid drug recently approved for relapsed or refractory acute promyelocytic leukemia (APL) in Japan. It is a specific agonist for retinoic acid receptor alpha/beta. Compared to all-trans retinoic acid (ATRA), a natural retinoid indicated for a first-line treatment of APL, tamibarotene is chemically more stable and several times more potent as an inducer of differentiation in promyelocytic leukemia cells. In contrast to ATRA, whose plasma concentration declines considerably during daily administration, tamibarotene sustains plasma level probably due to a lower affinity for cellular retinoic acid binding protein. Furthermore, adverse side effects were milder than those of ATRA in clinical trials.
• Affected Organisms: Humans and other mammals
• Protein Binding: Over 99%, predominantly to serum albumin.
• References: Miwako I, Kagechika H: Tamibarotene. Drugs Today (Barc). 2007 Aug;43(8):563-8. [Pubmed] ; Tamibarotene: AM 80, retinobenzoic acid, Tamibaro. Drugs R D. 2004;5(6):359-62. [Pubmed] ; Sanda T, Kuwano T, Nakao S, Iida S, Ishida T, Komatsu H, Shudo K, Kuwano M, Ono M, Ueda R: Antimyeloma effects of a novel synthetic retinoid Am80 (Tamibarotene) through inhibition of angiogenesis. Leukemia. 2005 Jun;19(6):901-9. [Pubmed] ; Takeuchi M: [Clinical experience with a new synthetic retinoid, tamibarotene (Am-80) for relapsed or refractory acute promyelocytic leukemia] Gan To Kagaku Ryoho. 2006 Mar;33(3):397-401. [Pubmed] ; Mizojiri K, Okabe H, Sugeno K, Misaki A, Ito M, Kominami G, Esumi Y, Takaichi M, Harada T, Seki H, Inaba A: Studies on the metabolism and disposition of the new retinoid 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid. 4th communication: absorption, metabolism, excretion and plasma protein binding in various animals and man. Arzneimittelforschung. 1997 Mar;47(3):259-69. [Pubmed]
• External Links: Wikipedia

Sigma Aldrich - T3205

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.

Toronto Research Chemicals - T005800

Synthetic retinoic acid receptor-α/β-selective retinoid. Antineoplastic.

REFERENCES

• Miwako I, Kagechika H: Tamibarotene. Drugs Today (Barc). 2007 Aug;43(8):563-8. Pubmed
• Tamibarotene: AM 80, retinobenzoic acid, Tamibaro. Drugs R D. 2004;5(6):359-62. Pubmed
• Takeuchi M: [Clinical experience with a new synthetic retinoid, tamibarotene (Am-80) for relapsed or refractory acute promyelocytic leukemia] Gan To Kagaku Ryoho. 2006 Mar;33(3):397-401. Pubmed
• Mizojiri K, Okabe H, Sugeno K, Misaki A, Ito M, Kominami G, Esumi Y, Takaichi M, Harada T, Seki H, Inaba A: Studies on the metabolism and disposition of the new retinoid 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid. 4th communication: absorption, metabolism, excretion and plasma protein binding in various animals and man. Arzneimittelforschung. 1997 Mar;47(3):259-69. Pubmed
• Sanda T, Kuwano T, Nakao S, Iida S, Ishida T, Komatsu H, Shudo K, Kuwano M, Ono M, Ueda R: Antimyeloma effects of a novel synthetic retinoid Am80 (Tamibarotene) through inhibition of angiogenesis. Leukemia. 2005 Jun;19(6):901-9. Pubmed
• Hashimoto, Y., et al.: Jpn. J. Cancer Res., 79, 473 (1988)
• Mizojiri, K., et al.: Arzneim.-Forsch., 47, 59 (1988)
• Shinjo, K., et al.: Int. J. Hematol., 72, 470 (1988)
• Sanda, T., et al.: Leukemia, 19, 901 (1988)