Aliskiren

Base Information

• Chemical Name: Aliskiren
• CAS No.: 173334-57-1
• Deprecated CAS: 401809-63-0,957114-21-5
• Molecular Formula: C30H53 N3 O6
• Molecular Weight: 551.767
• UNII: 502FWN4Q32
• DSSTox Substance ID: DTXSID40891494
• Nikkaji Number: J1.947.312K
• Wikipedia: Aliskiren
• Wikidata: Q414904
• NCI Thesaurus Code: C65222
• RXCUI: 325646
• Pharos Ligand ID: 1XBWHQAWBVC1
• Metabolomics Workbench ID: 43464
• ChEMBL ID: CHEMBL1639
• Mol file: 173334-57-1.mol

Synonyms:2(S),4(S),5(S),7(S)-N-(2-carbamoyl-2-methylpropyl)-5-amino-4-hydroxy-2,7-diisopropyl-8-(4-methoxy-3-(3-methoxypropoxy)phenyl)octanamid hemifumarate;aliskiren;CGP 060536B;CGP-060536B;CGP060536B;rasilez;SPP100;Tekturna

Chemical Property of Aliskiren

Chemical Property:

• Vapor Pressure: 1.12E-24mmHg at 25°C
• Melting Point: 98-99 °C
• Boiling Point: 748.4 °C at 760 mmHg
• PKA: 9.49(at 25℃)
• Flash Point: 406.4 °C
• PSA: 146.13000
• Density: 1.067 g/cm³
• LogP: 5.08500
• Storage Temp.: Inert atmosphere,Store in freezer, under -20°C
• XLogP3: 3.5
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 19
• Exact Mass: 551.39343642
• Heavy Atom Count: 39
• Complexity: 717

Purity/Quality:

98%min, ^*data from raw suppliers

Aliskiren 99% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antihypertensive Agents
• 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
• 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
• Recent ClinicalTrials: Evaluation of a Renin Inhibitor, Aliskiren, Compared to Enalapril, in C3 Glomerulopathy
• Recent EU Clinical Trials: A randomized, double-blind, parallel group, active-controlled study to compare the systolic blood pressure lowering efficacy of aliskiren, ramipril and a combination of aliskiren and amlodipine, with an initial 8-week evaluation, followed by a 2-3 year follow-up to compare long-term safety of an aliskiren-based regimen to a ramipril-based regimen in hypertensive patients ? 65 years of age.
• Recent NIPH Clinical Trials: Efficacy of Aliskiren in hypertensive patients with diabetes mellitus or obesity
• Description: Aliskiren is a first-in-class antihypertensive drug that acts by direct inhibition of renin. It is indicated for oral administration either as monotherapy or in combination with other antihypertensive agents. Renin catalyzes the cleavage of angiotensin to form angiotensin I, the first and the rate-limiting step of the RAAS. The inhibition of renin by aliskiren results in reduced levels of angiotensin I, angiotensin II, and aldosterone, all of which contribute to the antihypertensive effect. RAAS modulators are among some of the most commonly prescribed antihypertensive agents to date.The most common side effect of aliskiren is diarrhea, particularly with doses higher than 300mg daily. Unlike ACE inhibition, direct inhibition of renin does not increase bradykinin levels. Elevated bradykinin levels are thought to be responsible for the angioderma and cough that occur commonly during treatment with ACE inhibitors. .
• Uses: An orally active, synthetic nonpeptide renin inhibitor. Antihypertensive

Technology Process of Aliskiren

There total 165 articles about Aliskiren 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: 87.0%

C37H59N3O6 → (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)

Guidance literature:

With hydrogen; ethanolamine; 10% palladium on activated carbon; In methanol; at 20 ℃; for 3h; under 760.051 Torr;

Reference yield: 68.0%

aminopivalinamide (324763-51-1) + C29H49NO6S → (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)

Guidance literature:

With 2-hydroxypyridin; hydrogenchloride; triethylamine; In methanol; at 80 ℃;

Reference yield: 40.0%

3-amino-2,2-dimethylpropionamide ammonium chloride + 1,1-dimethylethyl[(1S,3S)-3-[{4-methoxy-3-(3-methoxypropoxy)phenyl}methyl]-4-methyl-1-[tetrahydro-4-(1-methylethyl)-5-oxo-2-furanyl]pentyl]carbamate → (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)

Guidance literature:

3-amino-2,2-dimethylpropionamide ammonium chloride; 1,1-dimethylethyl[(1S,3S)-3-[{4-methoxy-3-(3-methoxypropoxy)phenyl}methyl]-4-methyl-1-[tetrahydro-4-(1-methylethyl)-5-oxo-2-furanyl]pentyl]carbamate; sodium 2-ethylhexanoic acid; at 120 ℃; for 1h;

With amine HCl;

With NaA; Product distribution / selectivity;

upstream raw materials:

(2S,4S,5S,7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-azido-4-hydroxy-2-isopropyl-7-(4-methoxy-3-(methoxypropoxy)benzyl)-8-methylnonanamide

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

(2-carbamoyl-2-methylpropyl)carbamic acid benzyl ester

(1S,3S)-{1-formyl-3-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester

Downstream raw materials:

(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

(2S),(4S),(5S),(7S)-N-(3-amino-2,2-dimethyl-3-oxopropyl)-2,7-di(1-methylethyl)-4-hydroxy-5-amino-8-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-octanamide L-malate

aliskiren glycolic acid salt

aliskiren D-mandelic acid salt

Refernces

• 1、 Barbaras, Damien,Brozio, Joerg,Johannsen, Ib,Allmendinger, Thomas. "Removal of heavy metals from organic reaction mixtures: Preparation and application of functionalized resins". . p. 1068 - 1079. Retrieved 2009.
• 2、 Cini, Elena,Banfi, Luca,Barreca, Giuseppe,Carcone, Luca,Malpezzi, Luciana,Manetti, Fabrizio,Marras, Giovanni,Rasparini, Marcello,Riva, Renata,Roseblade, Stephen,Russo, Adele,Taddei, Maurizio,Vitale, Romina,Zanotti-Gerosa, Antonio. "Convergent Synthesis of the Renin Inhibitor Aliskiren Based on C5-C6 Disconnection and CO2H-NH2 Equivalence". . p. 270 - 283. Retrieved 2016/03/04.
• 3、 -. "PROCESS FOR PREPARING 8-ARYLOCTANOIC ACIDS". Page/Page column 32; 33. . Retrieved 2015/02/02.