| Identification | Back Directory | [Name]
OTAVA-BB 7070707015 | [CAS]
934593-90-5 | [Synonyms]
W6
LW6
LW8
CAY10585
HIF-1α inhibitor
OTAVA-BB 7070707015
CAY 10585;CAY-10585;CAY10585;LW6
Hypoxia inducible factor-1α inhibitor
LW 6 (This product is unavailable in the U.S.)
Methyl 3-[[[4-(adamantan-1-yl)phenoxy]acetyl]amino]-4-hydroxybenzoate
3-[[[4-(Adamantan-1-yl)phenoxy]acetyl]amino]-4-hydroxybenzoic Acid Methyl Ester
methyl 3-(2-(4-((1r,3r,5r,7r)-adamantan-2-yl)phenoxy)acetamido)-4-hydroxybenzoate
4-Hydroxy-3-[[2-(4-tricyclo[3.3.1.13,7]dec-1-ylphenoxy)acetyl]aMino]-benzoic Acid Methyl Ester
Benzoic acid, 4-hydroxy-3-[[2-(4-tricyclo[3.3.1.13,7]dec-1-ylphenoxy)acetyl]amino]-, methyl ester | [Molecular Formula]
C26H29NO5 | [MDL Number]
MFCD09907563 | [MOL File]
934593-90-5.mol | [Molecular Weight]
435.512 |
| Chemical Properties | Back Directory | [Boiling point ]
647.4±55.0 °C(Predicted) | [density ]
1.295±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:17.5(Max Conc. mg/mL);40.18(Max Conc. mM)
DMF:25.6(Max Conc. mg/mL);58.8(Max Conc. mM) | [form ]
powder to crystal | [pka]
7.59±0.48(Predicted) | [color ]
White to Light yellow to Light orange | [InChI]
1S/C26H29NO5/c1-31-25(30)19-2-7-23(28)22(11-19)27-24(29)15-32-21-5-3-20(4-6-21)26-12-16-8-17(13-26)10-18(9-16)14-26/h2-7,11,16-18,28H,8-10,12-15H2,1H3,(H,27,29) | [InChIKey]
BJRPPNOJYFZSLY-UHFFFAOYSA-N | [SMILES]
N(c5c(ccc(c5)C(=O)OC)O)C(=O)COc1ccc(cc1)C32CC4CC(C3)CC(C2)C4 |
| Hazard Information | Back Directory | [Description]
Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor composed of a HIF-1α subunit and HIF-1β subunit. Whereas the HIF-1β subunit is constitutively expressed, the HIF-1α subunit is regulated by cellular oxygen levels and therefore plays an important role in maintaining cellular oxygen homeostasis.1,2 Under normoxic conditions, HIF-1α is selectively hydroxylated on proline residues 402 and 577 and targeted for destruction by the ubiquitin-proteasome system. Under hypoxic conditions, HIF-1α accumulates and dimerizes with HIF-1β to promote the transcription of a number of genes involved in angiogenesis, glycolysis, growth factor signaling, tumor invasion, and metastasis. CAY10585 is a novel small molecule inhibitor of HIF-1α accumulation and gene transcriptional activity.3 In a gene reporter assay using human Hep3B and AGS cell lines, CAY10585 prevented HIF-1 transcriptional activity with IC50 values of 2.6 and 0.7 μM, respectively. It blocks HIF-1α accumulation in Hep3B cells in a concentration and time-dependent manner, with complete inhibition at a concentration of 30 μM within 12 hours. CAY10585 also significantly suppresses transcription of the HIF-1 target genes VEGF and erythropoietin at 10 μM.3 | [Uses]
CAY10585 is a class of hypoxia-inducible factor (HIF-1) responsible for radiation resistance and poor prognosis in cancer therapy. | [Synthesis]
Synthesis of methyl 3-[2-(4-adamantane-1-yl-phenoxy)-acetamido]-4-hydroxy-benzoate (Cas: 934593-90-5) from 2-(4-(1-adamantane)phenoxy)acetic acid (143.2 mg, 0.5 mmol) and methyl 3-amino-4-hydroxybenzoate (125.4 mg, 0.75 mmol) The general procedure was as follows: first, 2-(4-(1-adamantyl)phenoxy)acetic acid was dissolved in 5 mL of THF, oxalyl chloride (178.5 mg, 0.11 mL, 1.5 mmol) and a catalytic amount of DMF were added. the reaction mixture was stirred at room temperature for 1 h. The reaction mixture was then stirred at room temperature for 1 h. The reaction mixture was then stirred at room temperature for 1 h. The reaction mixture was then stirred at room temperature for 1 h. The reaction mixture was then stirred at room temperature for 1 h. Subsequently, methyl 3-amino-4-hydroxybenzoate and pyridine (0.05 mL) were added and the reaction continued at room temperature. Upon completion of the reaction, extraction was carried out with ethyl acetate and NaCl solution and the organic layer was dried and concentrated with anhydrous MgSO4. The residue was purified by silica gel column chromatography (n-hexane:EtOAc:MeOH = 6:3:1) to afford the target compound (183.2 mg, yield: 84.1%) as a white solid.1H-NMR (DMSO-d6, 300 MHz) δ: 11.10 (1H,s, OH), 9.24 (1H,s, NH), 8.69 (1H, m aromatic-H), 7.60-7.64 (1H, m, aromatic-H), 7.30 (2H, d, J = 8.4 Hz, aromatic-H), 6.94-6.99 (3H, m, aromatic-H), 4.74 (2H, s, CH2), 3.79 (3H, s, CH3), 2.04 (3H, m, adamantane-H), 1.83 (6H, m adamantane-H), 1.72 (6H, m, adamantane-H). | [in vivo]
LW6 (intraperitoneal injection; 10-20 mg/kg; 13 days) demonstrates strong anti-tumor efficacy in vivo and causes a decrease in HIF-1α expression in frozen-tissue immunohistochemical staining in mice carrying xenografts of human colon cancer HCT116 cells[2]. | [storage]
Store at -20°C | [References]
[1] Journal of Medicinal Chemistry, 2007, vol. 50, # 7, p. 1675 - 1684
[2] Patent: US2013/237542, 2013, A1. Location in patent: Paragraph 0216; 0217; 0218
[3] Patent: US2009/306078, 2009, A1. Location in patent: Page/Page column 26
[4] Journal of Organometallic Chemistry, 2013, vol. 747, p. 189 - 194
[5] Journal of Medicinal Chemistry, 2014, vol. 57, # 22, p. 9522 - 9538 |
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| Company Name: |
J & K SCIENTIFIC LTD.
|
| Telephone: |
18210857532 18210857532 |
| Website: |
https://www.jkchemical.com |
| Company Name: |
SPIRO PHARMA
|
| Telephone: |
|
| Website: |
www.spiropharma.com.cn |
| Company Name: |
Twochem Co.Ltd.
|
| Telephone: |
021-58111628 15800915896 |
| Website: |
cn.twochem.com |
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