Aliskiren fumarate

Base Information

• Chemical Name: Aliskiren fumarate
• CAS No.: 173334-58-2
• Molecular Formula: 2(C30H53N3O6)^.C4H4O4
• Molecular Weight: 609.804
• NSC Number: 759185
• ChEMBL ID: CHEMBL1667
• Mol file: 173334-58-2.mol

Synonyms:Aliskiren fumarate;1196835-68-3;Aliskiren (fumarate);ALISKIRENFUMARATE;(2E)-but-2-enedioic acid;bis((2S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2,2-dimethylethyl)-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide);5-amino-N-(3-amino-2,2-dimethyl-3-oxopropyl)-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnonanamide fumarate;CHEMBL1667;MLS006010401;HMS3264I19;Pharmakon1600-01505710;HY-12176B;MFCD10566724;MFCD27756642;NSC759185;AKOS025149418;AKOS037643745;CCG-213555;Aliskiren hemifumarate, >=95% (HPLC);(2S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2,2-dimethylethyl)-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide;but-2-enedioic acid;AS-35076;SMR004701404;CS-0134304;EN300-150155;SR-05000001949;SR-05000001949-1;5-Amino-N-(3-amino-2,2-diMe-3-oxoprop)-4-OH-2-isoprop-7-[4-MeO-3-(3-MeO-propoxy)benzyl]-8-methylnonanamide hemifumarate;Benzeneoctanamide, delta-amino-N-(3-amino-2,2-dimethyl-3-oxopropyl)-gamma-hydroxy-4-methoxy-3-(3-methoxypropoxy)-alpha,zeta-bis(1-methylethyl)-, (alphaS,gammaS,deltaS,zetaS)-, (2E)-2-butenedioate (2:1)

Chemical Property of Aliskiren fumarate

Chemical Property:

• Appearance/Colour: white powder
• Vapor Pressure: 1.59E-23mmHg at 25°C
• Melting Point: 72-75?C
• Boiling Point: 748.4 °C at 760 mmHg
• Flash Point: 406.4 °C
• PSA: 366.86000
• LogP: 9.88180
• Storage Temp.: Hygroscopic, -20°C Freezer, Under Inert Atmosphere
• Solubility.: Methanol (Slightly), Water (Slightly)
• Hydrogen Bond Donor Count: 6
• Hydrogen Bond Acceptor Count: 11
• Rotatable Bond Count: 21
• Exact Mass: 667.40439502
• Heavy Atom Count: 47
• Complexity: 836

Purity/Quality:

98.0-102.0% ^*data from raw suppliers

Aliskiren hemifumarate ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)C(CC1=CC(=C(C=C1)OC)OCCCOC)CC(C(CC(C(C)C)C(=O)NCC(C)(C)C(=O)N)O)N.C(=CC(=O)O)C(=O)O
• Isomeric SMILES: CC(C)[C@@H](CC1=CC(=C(C=C1)OC)OCCCOC)C[C@@H]([C@H](C[C@@H](C(C)C)C(=O)NCC(C)(C)C(=O)N)O)N.C(=C/C(=O)O)\C(=O)O
• Recent NIPH Clinical Trials: The comparative study between direct renin inhibitor and angiotensin II receptor antagonist in hypertensive patients with chronic kidney disease
• Description: Aliskiren hemifumarate (Tekturna(R)) was the first renin inhibitor approved by FDA in March 2007, and genomic analysis validated that Pgx-based dosing guidelines are not required for this drug. The once-daily, oral, direct renin inhibitor received FDA approval for treatment of high blood pressure as mono therapy or in combination with other antihypertensive medications. Furthermore, aliskiren demonstrated increased efficacy when used in combination with other commonly used blood pressure-lowering medications. Novartis is conducting a large outcome trial program to evaluate the long-term effects of aliskiren and of direct renin inhibition in general.
• Uses: Aliskiren hemifumarate is a potent renin inhibitor (IC50 = 0.6 and 80 nM for human and rat respectively). It has antihypertensive activity, decreasing plasma renin activity and inhibiting the conversion of angiotensinogen to Angiotensin I by binding to the S3 sub-pocket of renin. Exhibits selectivity for renin over a range of other aspartic proteinases (>5000 nM). Lowers blood pressure in a hypertensive rodent model. Orally active.Aliskiren hemifumarate (ALS) has been used to treat hypertension, alone or with other antihypertensive medications. It is suitable for oral administration. ALS regulates baseline systolic and diastolic blood pressure by blocking the catalytic activity of renin system at its rate-limiting step. An orally active, synthetic nonpeptide renin inhibitor. Antihypertensive.
• Clinical Use: Renin inhibitor: Hypertension
• Drug interactions: Potentially hazardous interactions with other drugs Other antihypertensive agents: enhanced antihypertensive effect; concentration possibly reduced by irbesartan; increased risk of hyperkalaemia and hypotension with ACE-Is and ARBs. Antifungals: concentration increased by itraconazole and ketoconazole, avoid with itraconazole. Ciclosporin: concentration of aliskiren increased - avoid. Diuretics: may reduce concentration of furosemide; hyperkalaemia with potassium-sparing diuretics. Grapefruit juice: concentration of aliskiren reduced - avoid. Heparins: increased risk of hyperkalaemia. Potassium salts: increased risk of hyperkalaemia.

Technology Process of Aliskiren fumarate

There total 11 articles about Aliskiren fumarate 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: 100.0%

(1S,2S,4S)-4-(2-carbamoyl-2-methylpropyl-carbamoyl)-2-hydroxy-1-{(S)-2-[4-methoxy-3-(3-methoxypropoxy)-benzyl]-3-methylbutyl}-5-methylhexyl-carbamic acid benzyl ester (1236549-06-6) + (2E)-but-2-enedioic acid (110-17-8,26099-09-2) → (2S,4S,5S,7S)-5-amino-N-(3-amino-2,2-dimethyl-3-oxypropyl)-4-hydroxy-7-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-8-methyl-(2-propan-2-yl)nonanamide hemifumarate (173334-58-2)

Guidance literature:

(1S,2S,4S)-4-(2-carbamoyl-2-methylpropyl-carbamoyl)-2-hydroxy-1-{(S)-2-[4-methoxy-3-(3-methoxypropoxy)-benzyl]-3-methylbutyl}-5-methylhexyl-carbamic acid benzyl ester; With palladium 10% on activated carbon; hydrogen; In isopropyl alcohol; at 20 ℃; under 760.051 Torr;

(2E)-but-2-enedioic acid; In ethanol;

Reference yield: 85.0%

tert-butyl (3S,5S,6S,8S)-8-(3-amino-2,2-dimethyl-3-oxopropylcarbamoyl)-6-hydroxy-3-(4-methoxy-3-(3-methoxypropoxy)benzyl)-2,9-dimethyldecan-5-ylcarbamate (173338-07-3) + (2E)-but-2-enedioic acid (110-17-8,26099-09-2) → (2S,4S,5S,7S)-5-amino-N-(3-amino-2,2-dimethyl-3-oxypropyl)-4-hydroxy-7-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-8-methyl-(2-propan-2-yl)nonanamide hemifumarate (173334-58-2)

Guidance literature:

tert-butyl (3S,5S,6S,8S)-8-(3-amino-2,2-dimethyl-3-oxopropylcarbamoyl)-6-hydroxy-3-(4-methoxy-3-(3-methoxypropoxy)benzyl)-2,9-dimethyldecan-5-ylcarbamate; With hydrogenchloride; In dichloromethane; at 0 ℃; for 3h;

(2E)-but-2-enedioic acid; In ethanol;

Reference yield: 81.5%

(2E)-but-2-enedioic acid (110-17-8,26099-09-2) + (2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide (173334-57-1) → (2S,4S,5S,7S)-5-amino-N-(3-amino-2,2-dimethyl-3-oxypropyl)-4-hydroxy-7-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-8-methyl-(2-propan-2-yl)nonanamide hemifumarate (173334-58-2)

Guidance literature:

In methanol; Solvent; Concentration; Time; Temperature;

upstream raw materials:

aliskiren

(2E)-but-2-enedioic acid

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

aminopivalinamide

Downstream raw materials:

(2S,4S,5S,7S)-5-Amino-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-8-methyl-nonanoic acid (2-carbamoyl-2-methyl-propyl)-amide

Refernces

• 1、 -. "A new crystalline forms of lueck logical sequence half fumaric acid salt and its preparation and use". Paragraph 0032; 0033. . Retrieved 2017/04/04.
• 2、 -. "PROCESS FOR THE PREPARATION OF ALISKIREN". Page/Page column 11. . Retrieved 2013/10/21.