162849-95-8

Basic information

• Product Name: (2S,3S,5S)-5-(tert-Butoxycarbonylamino)-2-(N-5-thiazolylmethoxycarbonyl)amino-1,6-diphenyl-3-hydroxyhexane
• Synonyms: (2S,3S,5S)-5-(tert-Butoxycarbonylamino)-2-(N-5-thiazolylmethoxycarbonyl)amino-1,6-diphenyl-3-hydroxyhexane;tert-Butyl (thiazol-5-ylmethyl) ((2S,3S,5S)-3-hydroxy-1,6-diphenylhexane-2,5-diyl)dicarbamate;N-[(1S,2S,4S)-4-[[(1,1-DiMethylethoxy)carbonyl]aMino]-2-hydroxy-5-phenyl-1-(phenylMethyl)pentyl]carbaMic Acid 5-ThiazolylMethyl Ester
• CAS NO: 162849-95-8
• Molecular Formula: C₂₈H₃₅N₃O₅S
• Molecular Weight: 526
• Mol File: 162849-95-8.mol

Chemical Properties

• Boiling Point: 722.3±60.0 °C(Predicted)
• Appearance: /
• Density: 1.219
• Storage Temp.: -20°C Freezer
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 11.48±0.46(Predicted)
• CAS DataBase Reference: (2S,3S,5S)-5-(tert-Butoxycarbonylamino)-2-(N-5-thiazolylmethoxycarbonyl)amino-1,6-diphenyl-3-hydroxyhexane(CAS DataBase Reference)
• NIST Chemistry Reference: (2S,3S,5S)-5-(tert-Butoxycarbonylamino)-2-(N-5-thiazolylmethoxycarbonyl)amino-1,6-diphenyl-3-hydroxyhexane(162849-95-8)
• EPA Substance Registry System: (2S,3S,5S)-5-(tert-Butoxycarbonylamino)-2-(N-5-thiazolylmethoxycarbonyl)amino-1,6-diphenyl-3-hydroxyhexane(162849-95-8)

Safety Data

• Hazardous Substances Data: 162849-95-8(Hazardous Substances Data)

Usage

Uses

1. Pharmaceutical Industry:
(2S,3S,5S)-5-(tert-Butoxycarbonylamino)-2-(N-5-thiazolylmethoxycarbonyl)amino-1,6-diphenyl-3-hydroxyhexane is used as an intermediate in the synthesis of Ritonavir (R535000), a selective HIV protease inhibitor. (2S,3S,5S)-5-(tert-Butoxycarbonylamino)-2-(N-5-thiazolylmethoxycarbonyl)amino-1,6-diphenyl-3-hydroxyhexane plays a crucial role in the development of medications for the treatment of HIV infections and AIDS. Ritonavir works by inhibiting the activity of the HIV protease enzyme, which is essential for the replication of the virus, thus helping to control the progression of the disease.
2. Chemical Research and Development:
Due to its unique structure and functional groups, (2S,3S,5S)-5-(tert-Butoxycarbonylamino)-2-(N-5-thiazolylmethoxycarbonyl)amino-1,6-diphenyl-3-hydroxyhexane may also be used in chemical research and development for the synthesis of other complex organic compounds, potentially leading to the discovery of new pharmaceuticals or materials with specific properties.

Upstream product

• 144163-97-3 ((5-thiazolyl)methyl)-(4-nitrophenyl)carbonate 
• 256328-84-4 (2S,3S,5S)-2-amino-3-hydroxy-5-tert-butoxycarbonylamino-1,6-diphenylhexane succinate 
• 154212-59-6 5-(p-nitrophenyloxycarbonyloxymethyl)thiazole hydrochloride 
• 144163-85-9 (2S,3S,5S)-2-amino-3-hydroxy-5-(t-butyloxycarbonylamino)-1,6-diphenylhexane 

Downstream Products

• 155213-67-5 ritonavir 
• 1448312-70-6 1,6-diphenyl-5(S)-tert-butoxycarbonylamino-2(S)-(5-thiazolemethoxy)carbonylamino-hexane 
• 1448312-69-3 3(S)-imidazolecarbothioic acid 1,6-diphenyl-5(S)-tert-butoxycarbonylamino-2(S)-(5-thiazolemethoxycarbonylamino)hexane, ester 
• 566939-06-8 (2S,3S,5S)-3-[O-[N-[N-methyl-N-[(2-isopropyl-4-thiazolyl)methyl]amino]carbonyl]-L-valyloxy]-5-[N-[(tert-butyloxy)carbonyl]amino]-2-[N-[(5-thiazolyl)methoxycarbonyl]amino]-1,6-diphenyl-3-hydroxyhexane 
• 144164-11-4 (2S,3S,5S)-5-Amino-2-(N-((5-thiazolyl)-methoxycarbonyl)amino)-3-hydroxy-1,6-diphenylhexane 

Relevant articles and documents

Design and synthesis of selenazole-substituted ritonavir analogs

With the help of Surflex-Dock calculation, two ritonavir analogs in which one thioazole unit was replaced by selenazole have been designed and synthesized. The key selenazole structure was constructed from β-azido diselenide through a cascade diselenide cleavage/selenocarbonylation/Staudinger reduction/aza-Wittig reaction and a following MnO2 oxidation. The accordingly prepared compounds exhibited good anti-HIV-1 (IIIB) activities comparable to that of the original ritonavir, as well as the positive SI values.

Ritonavir selenazole derivative with anti-HIV (Human Immunodeficiency Virus)-I activity and synthesis method

Certain Ritonavir selenazole analogues with good anti-HIV (Human Immunodeficiency Virus)-I activity are obtained by replacing a thiazole ring in a Ritonavir molecule with a selenazole ring and carrying out structure modification on a thiazole ring substit

METHODS AND INTERMEDIATES FOR PREPARING PHARMACEUTICAL AGENTS

Methods and intermediates useful for preparing a compound of formula I and salts thereof.

CYTOCHROME P450 OXIDASE INHIBITORS AND USES THEREOF

The present invention features compounds of formula I or pharmaceutically acceptable salts, solvates or prodrugs thereof, and methods of using the same to inhibit the metabolizing activities of CYP enzymes. The present invention also features methods of using these compounds, salts, solvates or prodrugs to improve the pharmacokinetics of drugs that are metabolized by CYP enzymes.

A PROCESS FOR THE SYNTHESIS OF 2-AMINO-5-PROTECTED AMINO-3-HYDROXY-1, 6-DIPHENYLHEXANE OR A SALT THEREOF - AN INTERMEDIATE FOR ANTIVIRAL DRUGS

The present invention relates to an improved process for preparing 2-amino-5-protected-amino-3-hydroxy-1,6-diphenylhexane compounds or acid addition salts thereof, which can be useful intermediates for preparing compounds with antiviral activity. The present invention further provides a process for preparing HIV protease inhibitors, lopinavir and ritonavir.

ACID ADDITION SALT OF 2-ISOPROPYL-4-(((N-METHYL)AMINO)METHYL)THIAZOLE AND ITS?USE IN THE PREPARATION OF RITONAVIR

The present invention relates to a novel acid addition salt of 2-Isopropyl-4-(((N-methyl)amino)methyl)thiazole of Formula (I) which is a useful intermediate for preparing HIV protease inhibitors. The present invention further provides a process for preparing ritonavir, a HIV protease inhibitor, using the compound of Formula (I).

RITONAVIR ANALOGOUS COMPOUND USEFUL AS RETROVIRAL PROTEASE INHIBITOR, PREPARATION OF THE RITONAVIR ANALOGOUS COMPOUND AND PHARMACEUTICAL COMPOSITION FOR THE RITONAVIR ANALOGOUS COMPOUND.

The present invention describes a new one ritonavir analogous compound that presents significantly superior activity in inhibition of HIV protease. There are also described the usage of the ritonavir analogous compound of the present invention or salt, ester or prodrug thereof as well as the usage of the compound and its pharmaceutical compositions in medicine, particularly, in the treatment of HIV infection, by itself or in combination with others anti-HIV drugs.

Retroviral protease inhibiting compounds

A compound comprising a substituent of the formula (II) is disclosed as an HIV protease inhibitor. Intermediates for making such compounds and processes for making such intermediates are also disclosed.

New water-soluble prodrugs of HIV protease inhibitors based on O→N intramolecular acyl migration

To improve the low water-solubility of HIV protease inhibitors, we synthesized water-soluble prodrugs of KNI-272 and KNI-279 which are potent HIV-1 protease inhibitors consisting of an Apns-Thz core structure (Apns; allophenylnorstatine, Thz; thiazolidine-4-carboxylic acid) as an inhibitory machinery. The prodrugs, which contained an O-acyl peptidomimetic structure with an ionized amino group leading to the increase of water-solubility, were designed to regenerate the corresponding parent drugs based on the O→N intramolecular acyl migration reaction at the α-hydroxy-β-amino acid residue, that is allophenylnorstatine. The synthetic prodrugs 3, 4, 6, and 7 improved the water-solubility (>300 mg/mL) more than 4000-fold in comparison with the parent compounds, which is the practically acceptable value as water-soluble drugs. These prodrugs were stable as an HCl salt and in a strongly acidic solution corresponding to gastric juice (pH 2.0), and could be converted to the parent compounds promptly in the aqueous condition from slightly acidic to basic pH at 37°C, with the suitable migration rate, via a five-membered ring intermediate. Using a similar method, we synthesized a prodrug (12) of ritonavir, a clinically useful HIV-1 protease inhibitor as an anti-AIDS drug. In contrast to the prodrugs 3, 4, 6, and 7, the prodrug 12 was very slowly converted to ritonavir probably through a six-membered ring intermediate, with the t1/2 value of 32 h that may not be suitable for practical use.

Pharmaceutical composition for inhibiting HIV protease

A pharmaceutical composition is disclosed which comprises a solution of an HIV protease inhibiting compound in a pharmaceutically acceptable organic solvent comprising a mixture of (1) (a) a solvent selected from propylene glycol and polyethylene glycol or (b) a solvent selected from polyoxyethyleneglycerol triricinoleate, polyethylene glycol 40 hydrogenated castor oil, fractionated coconut oil, polyoxyethylene (20) sorbitan monooleate and 2-(2-ethoxyethoxy)ethanol or (c) a mixture thereof and (2) ethanol or propylene glycol.