(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,35R)-12-[(2R)-1-[(1S,3R)-4-dimethylphosphoryloxy-3-methoxycyclohexyl]propan-2-yl]-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone

Base Information

• Chemical Name: (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,35R)-12-[(2R)-1-[(1S,3R)-4-dimethylphosphoryloxy-3-methoxycyclohexyl]propan-2-yl]-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone
• CAS No.: 572924-54-0
• Molecular Formula: C53H84NO14P
• Molecular Weight: 990.222
• European Community (EC) Number: 682-462-9
• Wikipedia: Ridaforolimus
• Mol file: 572924-54-0.mol

Synonyms:AP-23573;AP23573;deforolimus;MK 8669;MK-8669;MK8669;ridaforolimus

Chemical Property of (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,35R)-12-[(2R)-1-[(1S,3R)-4-dimethylphosphoryloxy-3-methoxycyclohexyl]propan-2-yl]-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone

Chemical Property:

• Appearance/Colour: Off-white solid
• Melting Point: 95-98 °C
• Refractive Index: 1.539
• Boiling Point: 996.16 °C at 760 mmHg
• PKA: 10.40±0.70(Predicted)
• Flash Point: 556.257 °C
• PSA: 211.31000
• Density: 1.18 g/cm³
• LogP: 7.68050
• Storage Temp.: Hygroscopic, -20?C Freezer, Under Inert Atmosphere
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• XLogP3: 5.9
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 14
• Rotatable Bond Count: 8
• Exact Mass: 989.56294335
• Heavy Atom Count: 69
• Complexity: 1940

Purity/Quality:

98%,99%, ^*data from raw suppliers

Ridaforolimus ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1CCC2CC(C(=CC=CC=CC(CC(C(=O)C(C(C(=CC(C(=O)CC(OC(=O)C3CCCCN3C(=O)C(=O)C1(O2)O)C(C)CC4CCC(C(C4)OC)OP(=O)(C)C)C)C)O)OC)C)C)C)OC
• Isomeric SMILES: C[C@@H]1CCC2C[C@@H](/C(=C/C=C/C=C/[C@H](C[C@H](C(=O)[C@@H]([C@@H](/C(=C/[C@H](C(=O)C[C@H](OC(=O)[C@@H]3CCCCN3C(=O)C(=O)[C@@]1(O2)O)[C@H](C)C[C@@H]4CCC([C@@H](C4)OC)OP(=O)(C)C)C)/C)O)OC)C)C)/C)OC
• Recent EU Clinical Trials: A Phase 2 Randomized Trial of the Combination of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in High Proliferation, Estrogen Receptor Positive Breast Cancer Patients
• Description: Ridaforolimus (Deforolimus, MK-8669, AP23573) is a selective mTOR inhibitor with IC50 of 0.2 nM in HT-1080 cell line; while not classified as a prodrug, mTOR inhibition and FKBP12 binding is similar to rapamycin. Phase 3. MK-8669 is a rapamycin analog that selectively inhibits mTOR (IC50 = 0.2 nM). Like rapamycin, MK-8669 binds FKBP12 to form a complex that associates with the FKBP-rapamycin binding domain on mTOR and allosterically inhibits mTORC1 kinase activity. MK-8669 is more water soluble than rapamycin and is amenable to oral or intravenous administration. Formulations containing rapalogs, including MK-8669, have promise against a subset of cancers, including advanced kidney cancer. MK-8669 is also being examined for effectiveness against cancers when used in combination with other chemotherapeutic compounds.
• Uses: An immunosupressant and is currently being investigated for use in cancer treatments. Ridaforolimus may act as a regulator of protein synthesis, cell proliferation, cell cycle progression and cell survival. Ridaforolimus, was formerly known as Deforolimus. Ridaforolimus is a semisynthetic macrocyclic lactone prepared from rapamycin by selective alkylation of the 42-hydroxy group with a dimethylphosphinate moiety. Like all tacrolimus analogues, ridaforolimus binds to receptor protein, FKBP12. The complex then binds to mTOR preventing its interaction with target proteins. Ridaforolimus is extensively cited in the literature with over 70 citations. An immunosupressant and is currently being investigated for use in cancer treatments. Ridaforolimus may act as a regulator of protein synthesis, cell proliferation, cell cycle progression and cell survival. Ridaforolimus, was formerly known as Deforolimus. Potent mTORC1 inhibitor.

Technology Process of (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,35R)-12-[(2R)-1-[(1S,3R)-4-dimethylphosphoryloxy-3-methoxycyclohexyl]propan-2-yl]-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone

There total 8 articles about (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,35R)-12-[(2R)-1-[(1S,3R)-4-dimethylphosphoryloxy-3-methoxycyclohexyl]propan-2-yl]-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield:

sirolimus (53123-88-9) + dimethylphosphinic acid chloride (1111-92-8) → Ridaforolimus (572924-54-0)

Guidance literature:

With 2,6-di-tert-butyl-4-methylpyridine; In dichloromethane; at 0 ℃; for 3.5h;

Reference yield:

42-(dimethylphosphinate)-(31-triethylsilylether)rapamycin (1568833-30-6) → Ridaforolimus (572924-54-0)

Guidance literature:

With sulfuric acid; water; In tetrahydrofuran; at -5 - 0 ℃;

Reference yield:

31-(trimethylsilylether)rapamycin (331810-10-7) + dimethylphosphinic acid chloride (1111-92-8) → Ridaforolimus (572924-54-0) + sirolimus (53123-88-9)

Guidance literature:

31-(trimethylsilylether)rapamycin; With 3,5-Lutidine; In dichloromethane; at 0 - 5 ℃; for 1.08333h; Inert atmosphere;

dimethylphosphinic acid chloride; In dichloromethane; at 0 - 5 ℃; for 1h; Inert atmosphere;

upstream raw materials:

sirolimus

dimethylphosphinic acid chloride

31-(triethylsilylether)rapamycin

31-(trimethylsilylether)rapamycin

Refernces

• 1、 -. "Phosphorus-containing compounds and uses thereof". Page 38. . Retrieved 2010/02/06.