98818-45-2

Basic information

• Product Name: 5(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-phenylmethylhexanoic acid
• Synonyms: 5(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-phenylmethylhexanoic acid
• CAS NO: 98818-45-2
• Molecular Weight: 413.514
• Mol File: 98818-45-2.mol

Chemical Properties

• CAS DataBase Reference: 5(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-phenylmethylhexanoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 5(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-phenylmethylhexanoic acid(98818-45-2)
• EPA Substance Registry System: 5(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-phenylmethylhexanoic acid(98818-45-2)

Safety Data

• Hazardous Substances Data: 98818-45-2(Hazardous Substances Data)

Upstream product

• 143337-98-8 (5S,1'S)-5-(1'-(dibenzylamino)-2'-phenylethyl)dihydrofuran-2(3H)-one 
• 98818-41-8 (3R,5S)-3-benzyl-5-{(1S)-1-[(tert-butoxycarbonyl)amino]-2-phenylethyl}dihydrofuran-2-(3H)-one 
• 100-39-0 benzyl bromide 
• 193338-94-2 (5S,1'S)-carbetoxy-5-<1-<<(1',1-dimethylothoxy)carbonyl>amino>-2-phenylmethyl>dihydrofuran-2(3H)-one 
• 63516-03-0 α-bromo-p-toluidine 
• 154160-21-1 (2S,3S)-2-Dibenzylamino-5-[1,3]dioxan-2-yl-1-phenyl-pentan-3-ol 
• 154160-19-7 (2S,3S)-2-Dibenzylamino-5-[1,3]dioxolan-2-yl-1-phenyl-pentan-3-ol 
• 154160-17-5 (S)-2-Dibenzylamino-5-[1,3]dioxan-2-yl-1-phenyl-pentan-3-one 
• 154160-16-4 (S)-2-Dibenzylamino-5-[1,3]dioxolan-2-yl-1-phenyl-pentan-3-one 
• 131150-35-1 (S)-2-(dibenzylamino)-N'-methoxy-N'-methyl-3-phenylpropane amide 
• 95437-43-7 (S)-2-(N,N-dibenzylamino)-3-phenylpropanoic acid 
• 24424-99-5 di-tert-butyl dicarbonate 
• 133333-27-4 tert-butyl (1S)-1-[(2S)-5-oxotetrahydrofuran-2-yl]-2-phenylethylcarbamate 
• 207222-78-4 (S)-5-tert-Butoxycarbonylamino-4-hydroxy-6-phenyl-hexanoic acid ethyl ester 

Downstream Products

• 126409-25-4 (2R,4S,5S)-N,2-dibenzyl-5-[(tert-butoxycarbonyl)amino]-4-hydroxy-6-phenylhexanamide 
• 98818-74-7 L-364,505 
• 132565-30-1 ((S)-1-{(1S,2S,4R)-1-Benzyl-4-[(S)-1-((S)-1-carbamoyl-2-phenyl-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-2-hydroxy-5-phenyl-pentylcarbamoyl}-2-phenyl-ethyl)-carbamic acid tert-butyl ester 
• 126410-69-3 [(1S,2S,4R)-4-{(S)-1-[(1H-Benzoimidazol-2-ylmethyl)-carbamoyl]-2-methyl-butylcarbamoyl}-1-benzyl-2-(tert-butyl-dimethyl-silanyloxy)-5-phenyl-pentyl]-carbamic acid tert-butyl ester 
• 126409-81-2 N'-(2-benzimidazolylmethyl)-N-<5(S)-<(tert-butoxycarbonyl)amino>-4(S)-hydroxy-6-phenyl-2(R)-(phenylmethyl)hexanoyl>isoleucine amide 
• 98818-75-8 [(1S,2S,4R)-1-Benzyl-4-((S)-1-benzylcarbamoyl-3-methyl-butylcarbamoyl)-2-(tert-butyl-dimethyl-silanyloxy)-5-phenyl-pentyl]-carbamic acid tert-butyl ester 
• 129252-98-8 [(1S,2S,4R)-1-Benzyl-4-((S)-1-benzylcarbamoyl-2-methyl-butylcarbamoyl)-2-(tert-butyl-dimethyl-silanyloxy)-5-phenyl-pentyl]-carbamic acid tert-butyl ester 
• 132565-31-2 [(1S,2S,4R)-1-Benzyl-2-hydroxy-4-((S)-3-methyl-1-phenethylcarbamoyl-butylcarbamoyl)-5-phenyl-pentyl]-carbamic acid tert-butyl ester 
• 98818-68-9 [(1S,2S,4R)-1-Benzyl-4-((S)-1-benzylcarbamoyl-3-methyl-butylcarbamoyl)-2-hydroxy-5-phenyl-pentyl]-carbamic acid tert-butyl ester 
• 126409-47-0 [(1S,2S,4R)-1-Benzyl-4-((S)-1-benzylcarbamoyl-2-methyl-butylcarbamoyl)-2-hydroxy-5-phenyl-pentyl]-carbamic acid tert-butyl ester 
• 126409-66-3 {(1S,2S,4R)-1-Benzyl-4-[(S)-1-(2,3-dihydroxy-propylcarbamoyl)-2-methyl-butylcarbamoyl]-2-hydroxy-5-phenyl-pentyl}-carbamic acid tert-butyl ester 
• 129252-92-2 (2R,4S,5S)-5-Amino-2-benzyl-4-hydroxy-6-phenyl-hexanoic acid [(S)-1-((S)-1-carbamoyl-2-phenyl-ethylcarbamoyl)-3-methyl-butyl]-amide 
• 1027975-83-2 ((1S,2S,4R)-1-Benzyl-2-(tert-butyl-dimethyl-silanyloxy)-4-{[(1H-indol-2-yl)-phenyl-methyl]-carbamoyl}-5-phenyl-pentyl)-carbamic acid tert-butyl ester 
• 1026657-06-6 (2R,4S,5S)-5-Amino-2-benzyl-4-hydroxy-6-phenyl-hexanoic acid [(1H-indol-2-yl)-phenyl-methyl]-amide 

Relevant articles and documents

Design and synthesis of HIV-1 protease inhibitors for a long-acting injectable drug application

The design and synthesis of novel HIV-1 protease inhibitors (PIs) (1-22), which display high potency against HIV-1 wild-type and multi-PI-resistant HIV-mutant clinical isolates, is described. Lead optimization was initiated from compound 1, a Phe-Phe hydroxyethylene peptidomimetic PI, and was directed towards the discovery of new PIs suitable for a long-acting (LA) injectable drug application. Introducing a heterocyclic 6-methoxy-3-pyridinyl or a 6-(dimethylamino)-3-pyridinyl moiety (R3) at the para-position of the P1′ benzyl fragment generated compounds with antiviral potency in the low single digit nanomolar range. Halogenation or alkylation of the metabolic hot spots on the various aromatic rings resulted in PIs with high stability against degradation in human liver microsomes and low plasma clearance in rats. Replacing the chromanolamine moiety (R1) in the P2 protease binding site by a cyclopentanolamine or a cyclohexanolamine derivative provided a series of high clearance PIs (16-22) with EC50s on wild-type HIV-1 in the range of 0.8-1.8 nM. PIs 18 and 22, formulated as nanosuspensions, showed gradual but sustained and complete release from the injection site over two months in rats, and were therefore identified as interesting candidates for a LA injectable drug application for treating HIV/AIDS.

Protease inhibitors that overcome drug resistance

HIV protease inhibitors are among the most powerful drugs in suppressing HIV in human patients. However, HIV developed resistance to all protease inhibitor drugs so far marketed or used in clinical trials. HIV generates resistance by mutating its protease. The strains of HIV containing mutant proteases less vulnerable to inhibitor drug are able to replicate better and maintain the infection. No effective principle exists for the design of resistance-proof HIV protease inhibitors (HIVPr). A new inhibitor has been developed based on a new concept for designing resistance invulnerable HIVPr inhibitors. In vitro data have shown that this inhibitor is effective against many known HIVPr mutants resistant to other HIVPr inhibitor drugs. The new concept is, therefore, generally applicable for the design of other resistance invulnerable HIVPr inhibitor drugs.

Allyltrichlorostannane additions to α-amino aldehydes: Application to the total synthesis of the aspartyl protease inhibitors L-682,679, L-684,414, L-685,434, and L-685,458

The hydroxyethylene dipeptide isosteres L-682,679, L-684,414, L-685,434, and L-685,458 were synthesized in a few steps by a sequence involving an allyltrichlorostannane coupling with an α-amino aldehyde, followed by hydroboration of the corresponding 1,2-

Short total synthesis of aspartyl protease inhibitors L-685,434, L-682,679 and L-685,458

Hydroxyethylene dipeptide isosteres L-685,434, L-682,679 and L-685,458 were synthesized in a few steps by a sequence involving an allyltrichlorostannane coupling with an α-aminoaldehyde followed by hydroboration of the corresponding 1,2-syn and 1,2-anti a

Peptide inhibitors of aspartic proteinases with hydroxyethylene isostere replacement of peptide bond. I. Preparation of four diastereoisomeric (2R or 2S, 4R or 4S, 5S)-2-benzyl-5-[(tert-butoxycarbonyl)amino]-4-hydroxy-6-phenylhexanoic acids

By two separate routes were prepared four diastereoisomers of (2R or 2S,5R or 5S)-3-benzyl-5-{(1S)-[(tert-butoxycarbonyl)amino]-2-phenylethyl}tetrahydrofuran- 2-ones (11, 12, 17 and 18). Since the furanones were derived from (S)-phenylalanine, absolute co

ANTIVIRAL ETHERS OF ASPARTATE PROTEASE SUBSTRATE ISOSTERES

Antiretroviral compounds (which are effective, for example, against HIV) of the formula I STR1 in which R 1 is an acyl radical lower-alkoxyl-lower-alkanoyl whose lower alkoxy radical is unsubstituted or is substituted by halogen, phenyl, lower alkoxy or a heterocyclic radical selected from piperidinyl, pyrrolidinyl, tetrahydropyranyl, tetrahydrofuranyl, thiazolidinyl, thiazolyl, indolyl or 4H-1-benzopyranyl which is unsubstituted or substituted by oxo, hydroxyl, amine, lower alkyl, lower-alkoxycarbonyl and/or phenyl-lower-alkoxycarbonyl; lower alkanoyl which is unsubstituted or is substituted by one of the said unsubstituted or substituted heterocyclic radicals; arylcarbonyl or heterocyclylcarbonyl which are substituted by heterocyclyl or heterocyclyl-lower-alkyl; phenyl-lower-alkanoyl which is substituted by hydroxyl and lower alkyl; or arylsulfonyl;or the residue of an amino acid which is defined in accordance with the description (and which may be acylated on the amino nitrogen by one of the abovementioned acyl radicals);R 2 and R 3 are in each case cyclohexyl, cyclohexenyl, phenyl, naphthyl or tetrahydronaphthyl which are unsubstituted or substituted by lower alkyl, phenyl, cyanophenyl, phenyl-lower-alkyl, halogen, halo-lower-alkyl, cyano, hydroxyl, lower alkoxy, phenyl-lower-alkoxyl, pyridyl-lower-alkoxy, lower-alkoxy-lower-alkoxy, lower-alkoxycarbonyl-lower-alkoxy, carboxyl-lower-alkoxy, hydroxyl-lower-alkoxy, carbamoyl-lower-alkoxy, cyano-lower-alkoxy, and phenyl-lower-alkanesulfonyl which is unsubstituted or substituted by halogen;R 4 is lower alkyl, cyclohexyl or phenyl; and R 5 is lower alkyl; and n is 1 or 2, or salts thereof, are novel.

Crystal-structure-based design and synthesis of novel C-terminal inhibitors of HIV protease

The X-ray crystal-structure-based design, synthesis, computational evaluation, and activity of a novel class of HIV protease inhibitors are described. The initial lead compounds 2 and 3 were designed by modeling replacement groups for the C-terminal Val-V

Stereoselective Synthesis of a Hydroxyethylene Dipeptide Isostere

A stereoselective synthesis of a hydroxyethylene dipeptide isostere for Phe-Gly, (4S, 5S)-4-hydroxy-5-amino-6-phenylhexanoic acid, is described.The use of dibenzyl protecting groups on ketoamine 5 accounts for the selectivity on reduction.Also, the dibenzyl group plays a role in directing the introduction of a third chiral center.

HIV-1 protease inhibitors based on hydroxyethylene dipeptide isosteres: An investigation into the role of the P1' side chain on structure-activity

A systematic investigation was undertaken to determine the role of the P1' sidechain in a series of hydroxyethylene isostere based inhibitors of HIV-1 protease. Substitution and homologation of the benzyl P1' side chain of the Phe-Phe isostere based pseudo peptides 1 (L-682,679) and 2 (L-685,434) with various heteroalkyl groups leads to a series of extremely potent inhibitors of the enzyme. Several examples of the most potent inhibitors were very effective in an ex vivo cell based viral spread assay using human H9 T- lymphocytes and the IIIb isolate of HIV-1. Compound 19 is 120 times more potent than 1 and 16 times more potent than 2 in inhibiting the spread of infection in this assay.