1000045-28-2

Basic information

• Product Name: (3S,5S)-5-[(1S)-1-azido-2-benzyloxyethyl]-3-isopropyldihydrofuran-2-one
• Synonyms: (3S,5S)-5-[(1S)-1-azido-2-benzyloxyethyl]-3-isopropyldihydrofuran-2-one
• CAS NO: 1000045-28-2
• Molecular Weight: 303.361
• Mol File: 1000045-28-2.mol
• Article Data: 7

Chemical Properties

• CAS DataBase Reference: (3S,5S)-5-[(1S)-1-azido-2-benzyloxyethyl]-3-isopropyldihydrofuran-2-one(CAS DataBase Reference)
• NIST Chemistry Reference: (3S,5S)-5-[(1S)-1-azido-2-benzyloxyethyl]-3-isopropyldihydrofuran-2-one(1000045-28-2)
• EPA Substance Registry System: (3S,5S)-5-[(1S)-1-azido-2-benzyloxyethyl]-3-isopropyldihydrofuran-2-one(1000045-28-2)

Safety Data

• Hazardous Substances Data: 1000045-28-2(Hazardous Substances Data)

Upstream product

• 1056674-54-4 (3S,5S)-5-[(1R)-2-(benzyloxy)-1-hydroxyethyl]-3-isopropyldihydrofuran-2(3H)-one 
• 112031-55-7 5,6-di-O-benzyl-3-deoxy-1,2-O-isopropylidene-α-D-glucofuranoside 
• 1056674-30-6 (2S,5S)-2-((R)-1,2-bis(benzyloxy)ethyl)-5-methoxytetrahydrofuran 
• 1056674-18-0 methyl 5,6-di-O-benzyl-3-deoxy-α-D-glucofuranoside 
• 100-39-0 benzyl bromide 
• 1067648-38-7 imidazole-1-carbothioic acid O-(5-(1,2-bisbenzyloxyethyl)-2-methoxytetrahydrofuran-3-yl) ester 
• 1056674-40-8 (3S,5S)-5-((R)-1,2-bis(benzyloxy)ethyl)-3-isopropyldihydrofuran-2(3H)-one 
• 1079398-63-2 methyl 5,6-di-O-benzyl-3-deoxy-D-glucofuranoside 
• 1056674-35-1 5,6-di-O-benzyl-2,3-dideoxy-D-glucono-1,4-lactone 
• 1067648-39-8 methyl 5,6-di-O-benzyl-2,3-dideoxy-D-glucofuranoside 
• 1056674-45-3 (3S,5S)-5-((R)-1,2-dihydroxyethyl)-3-isopropyldihydrofuran-2(3H)-one 
• 89358-30-5 benzyl (2E)-4-bromobut-2-en-1-yl ether 
• 1187941-31-6 C₂₆H₃₁NO₄ 
• 1000045-24-8 (2S,4E)-6-(benzyloxy)-2-isopropylhex-4-enoic acid 

Downstream Products

• 1067648-89-8 (2S,4S,5S)-5-azido-6-benzyloxy-4-hydroxy-2-isopropyl-hexanoic acid ((S)-1-benzylcarbamoyl-2-methyl-butyl)-amide 
• 1056674-63-5 (2S,4S,5S)-5-azido-6-benzyloxy-4-hydroxy-2-isopropyl-hexanoic acid ((S)-1-benzylcarbamoyl-2-methyl-propyl)amide 
• 1056676-15-3 (2S,4S,5S)-5-azido-6-benzyloxy-4-hydroxy-2-isopropyl-hexanoic acid ((1S,2S)-1-benzylcarbamoyl-2-methyl-butyl)-amide 
• 1056676-05-1 [(S)-2-benzyloxy-1-((2S,4S)-4-isopropyl-5-oxo-tetrahydro-furan-2-yl)-ethyl]-carbamic acid tert-butyl ester 
• 1056670-82-6 (2S,4S,5S)-5-amino-6-benzyloxy-4-hydroxy-2-isopropyl-hexanoic acid ((S)-1-benzylcarbamoyl-2-methyl-propyl)amide 
• 1067648-90-1 (2S,4S,5S)-5-amino-6-benzyloxy-4-hydroxy-2-isopropyl-hexanoic acid ((S)-1-benzylcarbamoyl-2-methyl-butyl)-amide 
• 1056670-83-7 (2S,4S,5S)-5-amino-6-benzyloxy-4-hydroxy-2-isopropyl-hexanoic acid ((S)-1-benzylcarbamoyl-2-methyl-propyl)amide trifluoroacetate 
• 1067648-25-2 methanesulphonic acid 3-[(1S,2S,4S)-4-((S)-1-benzylcarbamoyl-2-methyl-propylcarbamoyl)-1-benzyloxymethyl-2-hydroxy-5-methyl-hexylcarbamoyl]-5-((R)-1-phenyl-ethylcarbamoyl)-phenyl ester 
• 1067648-24-1 N-[(1S,2S,4S)-4-((S)-1-benzylcarbamoyl-2-methylpropylcarbamoyl)-1-benzyloxymethyl-2-hydroxy-5-methylhexyl]-5-(methanesulphonylmethylamino)-N'-((R)-1-phenylethyl)isophthalamide 
• 1067648-32-1 N-[(1S,2S,4S)-4-((S)-1-benzylcarbamoyl-2-methylpropylcarbamoyl)-1-benzyloxymethyl-2-hydroxy-5-methylhexyl]-5-(methanesulphonylmethylamino)-N-((S)-1-phenylethyl)isophthalamide 
• 1067648-28-5 N-[(1S,2S,4S)-4-((S)-1-benzylcarbamoyl-2-methyl-butylcarbamoyl)-1-benzyloxymethyl-2-hydroxy-5-methyl-hexyl]-5-(methanesulphonyl-methyl-amino)-N'-((R)-1-phenyl-ethyl)-isophthalamide 
• 1056674-78-2 acetic acid (1S,3S)-3-((S)-1-benzylcarbamoyl-2-methylpropylcarbamoyl)-1-((S)-1-tert-butoxycarbonylamino-2-hydroxy-ethyl)-4-methylpentyl ester 
• 1056674-68-0 [(1S,2S,4S)-4-((S)-1-benzylcarbamoyl-2-methylpropylcarbamoyl)-1-benzyloxymethyl-2-hydroxy-5-methylhexyl]-carbamic acid tert-butyl ester 
• 1056674-73-7 C₃₅H₅₁N₃O₇ 

Relevant articles and documents

Lead optimization of 5-amino-6-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)- 4-hydroxyhexanamides to reduce a cardiac safety issue: Discovery of DS-8108b, an orally active renin inhibitor

With the aim to address an undesired cardiac issue observed with our related compound in the recently disclosed novel series of renin inhibitors, further chemical modifications of this series were performed. Extensive structure-activity relationships studies as well as in vivo cardiac studies using the electrophysiology rat model led to the discovery of clinical candidate trans-adamantan-1-ol analogue 56 (DS-8108b) as a potent renin inhibitor with reduced potential cardiac risk. Oral administration of single doses of 3 and 10 mg/kg of 56 in cynomolgus monkeys pre-treated with furosemide led to significant reduction of mean arterial blood pressure for more than 12 h.

The P1 N-isopropyl motif bearing hydroxyethylene dipeptide isostere analogues of aliskiren are in vitro potent inhibitors of the human aspartyl protease renin

Novel nonpeptide small molecule renin inhibitors bearing an N-isopropyl P1 motif were designed based on initial lead structures 1 and aliskiren (2). (P3-P1)-Benzamide derivatives such as 9a and 34, as well as the corresponding P1 basic tertiary amine derivatives 10 and 35 were found to display low nanomolar inhibition against human renin in vitro.

ASPARTYL PROTEASE INHIBITORS

The invention provides compounds of the formula (I) wherein A is selected from the partial structures A1, A2 and A3; Ry and Ry' are both hydrogen, or Ry and Ry' together with the nitrogen atom to which they are attached form a cyclic amine such as morpholine, piperidine, piperazine or pyrrolidine; L is NHNH, CH2NH, O or S; Y is NH, NHNH, NHC(=O), S(=O)2NH, NHS(=O)2, CH2, CH2NH, O, S or S(=0)p; Q is aryl or heterocyclyl; Z is O, S, NRa or S(=0)p; m is O, 1 or 2; n is O, 1, 2 or 3; p is independently 1 or 2; q is 0 or 1; Ra is H or C1-C4alkyl; R1 is hydrogen, C1-C6alkyl, C3-C7cycloalkylC0-C3alkyl, arylC0-C3alkyl or heterocyclylC0-C3alkyl, R4'' is H or C1-C6alkyl; or R4' and R4'' together with the carbon atom to which they are attached define a C3-C6cycloalkyl; W is H, C1-C6alkyl, C3-C7ycycloalkyl, aryl or heterocyclyl; or a pharmaceutically acceptable salt, hydrate or N-oxide thereof. The compounds of the invention are inhibitors of aspartyl proteases such as renin and are among other things useful for the treatment of conditions associated with activities of the RAS, such as hypertension, heart failure and renal insufficiency.