Sufugolix

Base Information

• Chemical Name: Sufugolix
• CAS No.: 308831-61-0
• Deprecated CAS: 388563-81-3
• Molecular Formula: C36H31F2N5O4S
• Molecular Weight: 667.736
• UNII: 56S17Z6X9M
• DSSTox Substance ID: DTXSID40184893
• Wikipedia: Sufugolix
• Wikidata: Q21099001
• NCI Thesaurus Code: C97486
• Pharos Ligand ID: 2ZTKN3F9ALQB
• Metabolomics Workbench ID: 149806
• ChEMBL ID: CHEMBL22055
• Mol file: 308831-61-0.mol

Synonyms:5-(N-benzyl-N-methylaminomethyl)-1--(2,6-difluorobenzyl)-6-(4-(3-methoxyureido)phenyl)-3-phenylthieno(2,3-d)pyrimidine-2,4(1H,3H)-dione;TAK 013;TAK013

Chemical Property of Sufugolix

Chemical Property:

• PKA: 13.20±0.70(Predicted)
• PSA: 125.84000
• Density: 1.383g/cm3
• LogP: 6.98620
• XLogP3: 6.1
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 10
• Exact Mass: 667.20648198
• Heavy Atom Count: 48
• Complexity: 1090

Purity/Quality:

99% ^*data from raw suppliers

Sufugolix ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CN(CC1=CC=CC=C1)CC2=C(SC3=C2C(=O)N(C(=O)N3CC4=C(C=CC=C4F)F)C5=CC=CC=C5)C6=CC=C(C=C6)NC(=O)NOC
• Recent EU Clinical Trials: A Phase III, multi-center, randomized, double-blind study to evaluate the efficacy and safety of 50 mg and 100 mg of sufugolix (TAK-013) tablets administered twice daily versus placebo for 12 weeks in subjects with symptomatic endometriosis.
• Description: Sufugolix is a gonadotropin-releasing hormone (GnRH) receptor antagonist (IC50 = 0.1 nM). Sufugolix inhibits GnRH-induced arachidonic acid (Item Nos. 90010 | 90010.1 | 10006607) release in CHO cells expressing human recombinant or monkey recombinant GnRH (IC50s = 0.1 and 10 nM, respectively), but not the rat GnRH receptor. It inhibits luteinizing hormone (LH) release stimulated by GnRH in monkey pituitary cells ex vivo (IC50 = 36 nM). Sufugolix (10 and 30 mg/kg) reduces increases in plasma LH following castration in male cynomolgus monkeys and lowers serum LH, estradiol, and progesterone levels in female cynomolgus monkeys when administered at a dose of 90 mg/kg.

Technology Process of Sufugolix

There total 16 articles about Sufugolix which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 80.0%

N-methoxylamine hydrochloride (593-56-6) + 6-(4-aminophenyl)-5-(N-benzyl-N-methylaminomethyl)-1-(2,6-difluorobenzyl)-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (174072-63-0) → N-(4-(5-((benzyl(methyl)amino)methyl)-1-(2,6-difluorobenzyl)-1,2,3,4-tetrahydro-2,4-dioxo-3-phenylthieno[2,3-d]pyrimidin-6-yl)phenyl)-N'-methoxyurea (308831-61-0)

Guidance literature:

With triethylamine; 1,1'-carbonyldiimidazole; In dichloromethane;

Reference yield: 80.0%

N-methoxylamine hydrochloride (593-56-6) + 1,1'-carbonyldiimidazole (530-62-1) + 6-(4-aminophenyl)-5-(N-benzyl-N-methylaminomethyl)-1-(2,6-difluorobenzyl)-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (174072-63-0) → N-(4-(5-((benzyl(methyl)amino)methyl)-1-(2,6-difluorobenzyl)-1,2,3,4-tetrahydro-2,4-dioxo-3-phenylthieno[2,3-d]pyrimidin-6-yl)phenyl)-N'-methoxyurea (308831-61-0)

Guidance literature:

1,1'-carbonyldiimidazole; 6-(4-aminophenyl)-5-(N-benzyl-N-methylaminomethyl)-1-(2,6-difluorobenzyl)-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione; With triethylamine; In dichloromethane; at 20 ℃; for 42h;

N-methoxylamine hydrochloride; In dichloromethane; at 0 - 20 ℃; for 3h;

Reference yield:

2,6-difluorobenzyl chloride (697-73-4) → N-(4-(5-((benzyl(methyl)amino)methyl)-1-(2,6-difluorobenzyl)-1,2,3,4-tetrahydro-2,4-dioxo-3-phenylthieno[2,3-d]pyrimidin-6-yl)phenyl)-N'-methoxyurea (308831-61-0)

Guidance literature:

Multi-step reaction with 5 steps

1.1: 90 percent / KI; K₂CO₃ / dimethylformamide / 4 h / 20 °C

2.1: NBS; AIBN / chlorobenzene / 1.5 h / 90 °C

3.1: 33.0 g / i-Pr₂NEt / dimethylformamide / 2 h / 20 °C

4.1: 87 percent / HCl; HCO₂H / 10 percent Pd/C/water / diethyl ether / 3.5 h / 20 °C / atmospheric pressure

5.1: Et₃N / CH₂Cl₂ / 24 h / 20 °C

5.2: 71 percent / Et₃N / CH₂Cl₂ / 3 h / 20 °C

With hydrogenchloride; N-Bromosuccinimide; formic acid; 2,2'-azobis(isobutyronitrile); potassium carbonate; triethylamine; N-ethyl-N,N-diisopropylamine; potassium iodide; 10 percent Pd/C/water; In diethyl ether; dichloromethane; N,N-dimethyl-formamide; chlorobenzene;

DOI:10.1021/jm020180i

upstream raw materials:

N-methoxylamine hydrochloride

1,1'-carbonyldiimidazole

6-(4-aminophenyl)-5-(N-benzyl-N-methylaminomethyl)-1-(2,6-difluorobenzyl)-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

1-(4-nitrophenyl)propan-2-one

Downstream raw materials:

5-chloromethyl-1-(2,6-difluorobenzyl)-6-[4-(3-methoxyureido)phenyl]-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

1-{4-[1-(2,6-difluorobenzyl)-5-[(methylamino)methyl]-2,4-dioxo-3-phenyl-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl}-3-methoxyurea

N-{2-[{[1-(2,6-difluorobenzyl)-6-(4-{[(methoxyamino)carbonyl]amino}phenyl)-2,4-dioxo-3-phenyl-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-5-yl]methyl}(methyl)amino]ethyl}-N-methylmethanesulfonamide