176519-53-2

Basic information

• Product Name: Ethyl 2-(Methylethyl)-3-Oxo-4-Phenylbutyrate
• Synonyms: Ethyl 2-(Methylethyl)-3-Oxo-4-Phenylbutyrate;ETHYL 2-ISOPROPYL-3-OXO-4-PHENYLBUTANOATE
• CAS NO: 176519-53-2
• Molecular Formula: C₁₅H₂₀O₃
• Molecular Weight: 248.3175
• Mol File: 176519-53-2.mol

Chemical Properties

• Boiling Point: 328.2±17.0 °C(Predicted)
• Appearance: /
• Density: 1.038±0.06 g/cm3(Predicted)
• PKA: 12.08±0.46(Predicted)
• CAS DataBase Reference: Ethyl 2-(Methylethyl)-3-Oxo-4-Phenylbutyrate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl 2-(Methylethyl)-3-Oxo-4-Phenylbutyrate(176519-53-2)
• EPA Substance Registry System: Ethyl 2-(Methylethyl)-3-Oxo-4-Phenylbutyrate(176519-53-2)

Safety Data

• Hazardous Substances Data: 176519-53-2(Hazardous Substances Data)

Upstream product

• 718-08-1 ethyl 3-oxo-4-phenylbutyrate 
• 75-30-9 2-iodo-propane 
• 140-29-4 phenylacetonitrile 
• 75-26-3 isopropyl bromide 
• 103-80-0 phenylacetyl chloride 
• 609-12-1 ethyl 2-bromoisovalerate 

Downstream Products

• 176519-55-4 6-benzyl-5-isopropylpyrimidine-2,4(1H,3H)-dione 
• 175739-42-1 6-benzyl-1-[(benzyloxy)methyl]-5-isopropylpyrimidine-2,4(1H,3H)-dione 
• 1254831-85-0 3-amino-6-benzyl-1-(benzyloxymethyl)-5-isopropylpyrimidine-2,4(1H,3H)-dione 
• 1254831-86-1 6-benzyl-1-(ethoxymethyl)-3-hydroxy-5-isopropylpyrimidine-2,4(1H,3H)-dione 
• 1254831-82-7 6-benzyl-1-((4-fluorobenzyloxy)methyl)-3-hydroxy-5-isopropylpyrimidine-2,4(1H,3H)-dione 
• 1254831-80-5 6-benzyl-1-(benzyloxymethyl)-3-hydroxy-5-isopropylpyrimidine-2,4(1H,3H)-dione 
• 1254831-91-8 6-benzyl-1-(((4-fluorobenzyl)oxy)methyl)-5-isopropylpyrimidine-2,4(1H,3H)-dione 
• 149950-60-7 Emivirine 
• 199851-91-7 6-benzyl-5-isopropyl-2-thiouracil 

Relevant articles and documents

Synthesis and Antiviral Evaluation of 1-[(2-Phenoxyethyl)oxymethyl] and 6-(3,5-Dimethoxybenzyl) Analogues of HIV Drugs Emivirine and TNK-651

Novel emivirine analogues 6a, b were synthesized by reacting chloromethyl ethyl ether with 5-ethyl/isopropyl-6-(3,5-dimethoxybenzyl)uracils 5e, f. On the other hand, A series of new TNK-651 analogues 10a-f substituted at N-1 with phenoxyethoxymethyl moiety was prepared on treatment of the corresponding uracils 5a-f with bis(phenoxyethoxy)methane (9). The newly synthesized non-nucleosides were tested for antiviral activity against wild type HIV-1 IIIB as well as the resistant strains N119 (Y181C), A17 (K103N+Y181C), and the triple mutant EFVR (K103R+V179D+P225H) in MT-4 cells. Most of the tested compounds showed good activities. Among them 6-(3,5-dimethylbenzyl)-5-ethyl-1-[(2-phenoxyethyl)oxymethyl]uracil (10c) and 6-(3,5-dimethylbenzyl)-5-isopropyl-1-[(2-phenoxyethyl)oxymethyl]uracil (10d) that showed inhibitory potency higher than emivirine against both wild type HIV-1 and the tested mutant strains, as well as higher activity than efavirenz against EFVR.

New efficient and flexible synthetic route to Emivirine and its analogs

A revised synthetic route to Emivirine (MKC-442) via properly substituted β-keto ester converted from Meldrum's Acid was developed. This method could be applied to the synthesis of a variety of MKC-442 analogues and open the way for their systematic biological evaluation.

N-3 hydroxylation of pyrimidine-2,4-diones yields dual inhibitors of HIV reverse transcriptase and integrase

A new molecular scaffold featuring an N-hydroxyimide functionality and capable of inhibiting both reverse transcriptase (RT) and integrase (IN) of human immunodeficiency virus (HIV) was rationally designed based on 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) non-nucleoside RT inhibitors (NNRTIs). The design involves a minimal 3-N hydroxylation of the pyrimidine ring of HEPT compound to yield a chelating triad which, along with the existing benzyl group, appeared to satisfy major structural requirements for IN binding. In the mean time, this chemical modification did not severely compromise the compound's ability to inhibit RT. A preliminary structure-activity relationship (SAR) study reveals that this N-3 OH is essential for IN inhibition and that the benzyl group on N-1 side chain is more important for IN binding than the one on C-6.

Synthesis and anti-HIV-1 activity of S-dihydro(alkyloxy)benzyloxypyrimidine derivatives

Several 2-heteroaryl-, 2-heteroarylcarbonylmethyl-, 2-arylcarbonylmethyl, and 2-arylethyl derivatives of S-dihydro(alkyloxy)benzyloxypyrimidines have been synthesized and the anti-HIV activities of these compounds were tested in C8166 cell and against RT

Phenethyl-5-bromopyridylthiourea (PBT) and dihydroalkoxybenzyloxopyrimidine (DABO) derivatives exhibiting spermicidal activity

Novel phenethyl-5-bromopyridylthiourea (PBT) and dihydroalkoxybenzyloxopyrimidine (DABO) derivatives exhibiting spermicidal activity as well as anti-viral activity. These novel compounds can be incorporated within contraceptive compositions to provide for

Does the 2-methylthiomethyl substituent really confer high anti-HIV-1 activity to S-DABOs?

S-DABO derivatives containing the methylthiomethyl (MTM) group have been synthesized and tested for anti-HIV-1 activity in cell-based assay (MTT and p24 assays) and for their capability to target the HIV-1 reverse transcriptase in enzyme assays. Data of experiments lead to the conclusion that the introduction of a 2-MTM-thio side chain is not sufficient per se to significantly increase S-DABO's potency. Nevertheless, potent MTM-S-DABOs can be obtained by introducing a 2,6-difluorophenylmethyl moiety as a C-6 substituent.

5-alkyl-2-[(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-ones as potent non-nucleoside reverse transcriptase inhibitors of S-DABO series

Novel dihydroalkoxybenzyloxopyrimidine (S-DABO) derivatives targeting the non-nucleoside inhibitor (NNI) binding site of human immunodeficiency virus (IV) reverse transcriptase (RT) have been synthesized using a novel computer model for the NNI binding pocket and tested for their RT inhibitory activity in cell-free assays using purified recombinant HIV RT as well as for their anti-HIV activity in HTLVIIIB-infected peripheral blood mononuclear cells. Our computational approach allowed the identification of several ligand derivatization sites for the generation of more potent S-DABO derivatives. Our lead S-DABO derivative, 5-isopropyl-2- [(methylthiomethyl)thio]-6-(benzyl)-pyrimidin-4-(1H)-one (compound 3), elicited potent anti-HIV activity with an IC50 value of less than 1nM for inhibition of HIV replication without any evidence of cytotoxicity and an unprecedented selectivity index of > 100,000.

Structure-based design of novel dihydroalkoxybenzyloxopyrimidine derivatives as potent nonnucleoside inhibitors of the human immunodeficiency virus reverse transcriptase

Two highly potent dihydroalkoxybenzyloxopyrimidine (DABO) derivatives targeting the nonnucleoside inhibitor (NNI) binding site of human immunodeficiency virus (HIV) reverse transcriptase (RT) have been designed based on the structure of the NNI binding pocket and tested for anti-HIV activity. Our lead DABO derivative, 5-isopropyl-2-[(methylthiomethyl)thio]- 6-(benzyl)-pyrimidin-4-(1H)-one, elicited potent inhibitory activity against purified recombinant HIV RT and abrogated HIV replication in peripheral blood mononuclear cells at nanomolar concentrations (50% inhibitory concentration, 1 nM) but showed no detectable cytotoxicity at concentrations as high as 100 μM.

Synthesis and potent anti-HIV-1 activity of novel 6-benzyluracil analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine

Ethyl 2-alkyl-4-aryl-3-oxobutyrates were synthesized from the corresponding arylacetonitriles and 2-brome esters. Condensation of the butyrates with thiourea followed by treatment with chloroacetic acid afforded the 5-alkyl-6-(arylmethyl)uracils. Condensa