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

• ChemBase编号: 4401
• 分子式: C22H25NO3
• 平均质量: 351.4388
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: 4-[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbamoyl]benzoic acid
• IUPAC传统名: tamibarotene
• 商标名: Amnoid; Tamibaro
• 别名: 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

登记号

• CAS号: 94497-51-5
• MDL号: MFCD00866188
• Beilstein号: 3564473
• PubChem SID: 46509039; 160967833
• PubChem CID: 108143
• CHEMBL: 25202
• Chemspider ID: 97231
• DrugBank ID: DB04942
• 维基百科标题: Tamibarotene

理论计算性质

JChem

• Acid pKa: 3.693783
• 质子受体: 3
• 质子供体: 2
• LogD (pH = 5.5): 3.5442872
• LogD (pH = 7.4): 2.0411327
• Log P: 5.3491
• 摩尔折射率: 104.3773 cm^3
• 极化性: 39.101734 Å^3
• 极化表面积: 66.4 Å^2
• 可自由旋转的化学键: 3
• 里宾斯基五规则: false

ALOGPS 2.1

• Log P: 4.99
• LOG S: -5.79
• 溶解度: 5.75e-04 g/l

分子性质

理化性质

• 溶解度: DMSO: ≥10 mg/mL; Methanol
• 外观: Off-White Solid; white to off-white powder
• 熔点: 228-230°C

安全信息

• 保存条件: Refrigerator
• 保存注意事项: IRRITANT
• 德国WGK号: 3
• TSCA收录: false
• 保存温度: room temp

药理学性质

• 作用靶点: Others

产品相关信息

• 纯度: ≥98% (HPLC); 95+%
• 成盐信息: Free Base
• Empirical Formula (Hill Notation): C22H25NO3

详细说明

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.

参考文献

• 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)