308832-01-1

Basic information

• Product Name: 3-Thiophenecarboxylic acid, 2-[[(2,6-difluorophenyl)methyl](ethoxycarbonyl)amino]-4-[[(2-methoxyeth yl)methylamino]methyl]-5-(4-nitrophenyl)-, ethyl ester
• Synonyms: ethyl 2-[N-(2,6-difluorobenzyl)-N-ethoxycarbonylamino]-4-[N-(2-methoxyethyl)-N-methylaminomethyl]-5-(4-nitrophenyl)thiophene-3-carboxylate;ethyl 2-[N-(2,6-difluorobenzyl)-N-ethoxycarbonyl]amino-4-[N-(2-methoxyethyl)-N-methylaminomethyl]-5-(4-nitrophenyl)thiophene-3-carboxylate;2-[N-(2,6-difluorobenzyl)-N-ethoxycarbonyl]amino-4-[N-(2-methoxyethyl)-N-methylaminomethyl]-5-(4-nitrophenyl)thiophene-3-carboxylic acid ethyl ester
• CAS NO: 308832-01-1
• Molecular Formula: C28H31F2N3O7S
• Molecular Weight: 591.633
• Mol File: 308832-01-1.mol

Chemical Properties

• Boiling Point: 688.5±55.0 °C(Predicted)
• Density: 1.314±0.06 g/cm3(Predicted)
• CAS DataBase Reference: 3-Thiophenecarboxylic acid, 2-[[(2,6-difluorophenyl)methyl](ethoxycarbonyl)amino]-4-[[(2-methoxyeth yl)methylamino]methyl]-5-(4-nitrophenyl)-, ethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Thiophenecarboxylic acid, 2-[[(2,6-difluorophenyl)methyl](ethoxycarbonyl)amino]-4-[[(2-methoxyeth yl)methylamino]methyl]-5-(4-nitrophenyl)-, ethyl ester(308832-01-1)
• EPA Substance Registry System: 3-Thiophenecarboxylic acid, 2-[[(2,6-difluorophenyl)methyl](ethoxycarbonyl)amino]-4-[[(2-methoxyeth yl)methylamino]methyl]-5-(4-nitrophenyl)-, ethyl ester(308832-01-1)

Safety Data

• Hazardous Substances Data: 308832-01-1(Hazardous Substances Data)

Upstream product

• 308831-95-0 4-(bromomethyl)-2-((2,6-difluorobenzyl)(ethoxycarbonyl)amino)-5-(4-nitrophenyl)thiophene-3-carboxylic acid ethyl ester 
• 38256-93-8 N-methyl-N-(2-methoxyethyl)amine 
• 308831-93-8 2-((ethoxycarbonyl)amino)-4-methyl-5-(4-nitrophenyl)thiophene-3-carboxylic acid ethyl ester 
• 174072-89-0 2-Amino-4-methyl-5-(4-nitrophenyl)thiophene-3-carboxylic acid ethyl ester 
• 308831-94-9 2-((2,6-difluorobenzyl)(ethoxycarbonyl)amino)-4-methyl-5-(4-nitrophenyl)thiophene-3-carboxylic acid ethyl ester 

Downstream Products

• 577780-07-5 ethyl 5-(4-aminophenyl)-2-[(2,6-difluorobenzyl)(ethoxycarbonyl)amino]-4-{[(2-methoxyethyl)(methyl)amino]methyl}thiophene-3-carboxylate 
• 308832-02-2 1-(2,6-difluorobenzyl)-5-[N-(2-methoxyethyl)-N-methylaminomethyl]-3-(3,4-methylenedioxyphenyl)-6-(4-nitrophenyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione 
• 737789-92-3 ethyl 2-[(2,6-difluorobenzyl)(ethoxycarbonyl)amino]-5-{4-[(methoxycarbamoyl)amino]phenyl}-4-{[(2-methoxyethyl)(methyl)amino]methyl}thiophene-3-carboxylate 
• 737789-93-4 2-[(2,6-difluorobenzyl)(ethoxycarbonyl)amino]-5-{4-[(methoxycarbamoyl)amino]phenyl}-4-{[(2-methoxyethyl)(methyl)amino]methyl}thiophene-3-carboxylic acid 
• 737789-97-8 C₃₃H₃₆F₂N₆O₆S 
• 737790-70-4 1-{4-[1-(2,6-difluorobenzyl)-5-{[(2-methoxyethyl)(methyl)amino]methyl}-3-(6-methoxypyridin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl}-3-methoxyurea 

Relevant articles and documents

Discovery of 1-{4-[1-(2,6-difluorobenzyl)-5-[(dimethylamino)methyl]-3-(6- methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3- d ]pyrimidin-6-yl]phenyl}-3-methoxyurea (TAK-385) as a potent, orally active, non-peptide antagonist of the human gonadotropin-releasing hormone receptor

We previously discovered an orally active human gonadotropin-releasing hormone (GnRH) receptor antagonist, thieno[2,3-d]pyrimidine-2,4-dione derivative 1 (sufugolix). To reduce the cytochrome P450 (CYP) inhibitory activity and improve in vivo GnRH antagonistic activity, further optimization of this scaffold was carried out. We focused our synthetic efforts on chemical modification at the 5 and 3 positions of the thieno[2,3-d]pyrimidine-2,4-dione ring based on computational modeling, which resulted in the discovery of 1-{4-[1-(2,6-difluorobenzyl)-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3- yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl} -3-methoxyurea (16b) as a highly potent and orally active GnRH antagonist. Compound 16b showed potent in vitro GnRH antagonistic activity in the presence of fetal bovine serum (FBS) without CYP inhibition. Oral administration of 16b maintained the suppressive effect of the plasma luteinizing hormone levels in castrated cynomolgus monkeys at a 3 mg/kg dose for more than 24 h. Compound 16b is currently under clinical development with the code name of TAK-385.

Thienopyrimidine compounds, their production and use

A compound of the formula: wherein R1and R2each is hydrogen, hydroxy, C1-4alkoxy, C1-4alkoxy-carbonyl or C1-4alkyl which may be substituted; R3is hydrogen, halogen, hydroxy or C1-4alkoxy which may be substituted; or adjacent two R3may form C1-4alkylenedioxy; R4is hydrogen or C1-4alkyl; R6is C1-4alkyl which may be substituted or a group of the formula: wherein R5is hydrogen or R4and R5may form heterocycle; and n is 0-5, or a salt thereof, has an excellent GnRH-antagonizing activity, and is useful for preventing or treating sex hormone-dependent diseases.