737789-87-6

Basic information

• Product Name: TAK-385
• Synonyms: TAK-385;Relugolix;Altropane;TKA-385 Relugolix;1-[4-[1-[(2,6-difluorophenyl)methyl]-5-(dimethylaminomethyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-6-thieno[4,5-e]pyrimidinyl]phenyl]-3-methoxyurea;Relugolix TAK-385;TAK-385,Relugolix
• CAS NO: 737789-87-6
• Molecular Formula: C29H27F2N7O5S
• Molecular Weight: 623.6303864
• Product Categories: API
• Mol File: 737789-87-6.mol
• Article Data: 13

Chemical Properties

• Melting Point: 228 °C (decomp)(Solv: ethyl acetate (141-78-6); tetrahydrofuran (109-99-9))
• Appearance: /
• Density: 1.442±0.06 g/cm3(Predicted)
• PKA: 13.17±0.70(Predicted)
• CAS DataBase Reference: TAK-385(CAS DataBase Reference)
• NIST Chemistry Reference: TAK-385(737789-87-6)
• EPA Substance Registry System: TAK-385(737789-87-6)

Safety Data

• Hazardous Substances Data: 737789-87-6(Hazardous Substances Data)

Usage

Description

Relugolix (TAK-385)?is a potent, orally active, nonpeptidic?gonadotropin-releasing hormone (GnRH)?antagonist. It possesses high affinity and potent antagonistic activity for human receptor (binding?IC50=0.33 nM) and monkey receptor (IC50=0.32 nM) compared with TAK-013 (HY-100209). Relugolix is used for the study of sex-hormone-dependent diseases, such as including endometriosis, uterine fibroids and prostate cancer et al.

Uses

Relugolix is a highly selective, oral, nonpeptide GnRH antagonist being investigated as a possible prostate cancer treatment

Mechanism of action

The mechanism of action of relugolix is as a?Gonadotropin Releasing Hormone?Receptor Antagonist, and Cytochrome P450 3A Inducer, and Cytochrome P450 2B6 Inducer, and Breast Cancer Resistance Protein Inhibitor, and P-Glycoprotein Inhibitor. The physiologic effect of relugolix is by means of Decreased?GnRH?Secretion.

Pharmacokinetics

Relugolix is a?selective?antagonist?of the?gonadotropin-releasing hormone receptor?(GnRHR) (IC50?= 0.12?nM).A single oral administration of relugolix at a dose of 3?mg/kg has been found to suppress?luteinizing hormone?(LH) levels for more than 24?hours in?castrated?cynomolgus monkeys, indicating a long?duration of action. The drug (80–160?mg/day) has been found to reduce?testosterone?levels to sustained?castrate?levels in men with once-daily administration.[8]?Lower dosages (10–40?mg/day) are being studied in the treatment of endometriosis and uterine fibroids to achieve partial?sex hormone?suppression.? The reasoning behind partial suppression for these conditions is to reduce the incidence and severity of?menopausal?symptoms such as?hot flushes?and to avoid?bone mineral density?changes caused by?estrogen deficiency?that can eventually lead to?osteoporosis.

Clinical Use

Relugolix was first approved in Japan in 2019, under the brand name Relumina, for the symptomatic treatment of uterine fibroids, and more recently by the United States' FDA in 2020, under the brand name Orgovyx, for the treatment of advanced prostate cancer. Relugolix has also been studied in the symptomatic treatment of endometriosis.

Upstream product

• 5332-96-7 1-(4-nitrophenyl)propan-2-one 
• 697-73-4 2,6-difluorobenzyl chloride 
• 1589503-93-4 1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxypyridazin-3-yl)-6-(4-aminophenyl)thiophene[2,3-d]pyrimidine-2,4(1H,3H)-dione 
• 593-56-6 N-methoxylamine hydrochloride 
• 530-62-1 1,1'-carbonyldiimidazole 
• 174072-89-0 2-Amino-4-methyl-5-(4-nitrophenyl)thiophene-3-carboxylic acid ethyl ester 
• 124-40-3 dimethyl amine 
• 737789-93-4 2-[(2,6-difluorobenzyl)(ethoxycarbonyl)amino]-5-{4-[(methoxycarbamoyl)amino]phenyl}-4-{[(2-methoxyethyl)(methyl)amino]methyl}thiophene-3-carboxylic acid 
• 737789-92-3 ethyl 2-[(2,6-difluorobenzyl)(ethoxycarbonyl)amino]-5-{4-[(methoxycarbamoyl)amino]phenyl}-4-{[(2-methoxyethyl)(methyl)amino]methyl}thiophene-3-carboxylate 
• 577780-07-5 ethyl 5-(4-aminophenyl)-2-[(2,6-difluorobenzyl)(ethoxycarbonyl)amino]-4-{[(2-methoxyethyl)(methyl)amino]methyl}thiophene-3-carboxylate 
• 308832-01-1 ethyl 2-[(2,6-difluorobenzyl)(ethoxycarbonyl)amino]-4-{[(2-methoxyethyl)(methyl)amino]methyl}-5-(4-nitrophenyl)thiophene-3-carboxylate 
• 1589503-95-6 2-((2,6-difluorobenzyl)(ethoxycarbonyl)amino)-4-((dimethylamino)methyl)-5-(4-nitrophenyl)thiophene-3-carboxylic acid 
• 1589503-97-8 ethyl 2-((2,6-difluorobenzyl)(ethoxycarbonyl)amino)-4-((dimethylamino)methyl)-5-(4-nitrophenyl)thiophene-3-carboxylate 

Relevant articles and documents

Synthetic method of Relugolix

The invention provides a synthesis method of Relugolix, and belongs to the field of medicine synthesis. The method comprises the following steps: (i) subjecting a compound 8 and a halogenating reagent to a halogenating reaction to obtain a compound 9, wherein in the compound 9, X is halogen; and (ii) carrying out a reaction on the compound 9 and N,N-diisopropyl ethyl amine to obtain Relugolix. The method provided by the invention is simple to operate, mild in reaction condition, few in side reaction, high in yield and purity, easy to purify the product, and suitable for commercial large-scale production.

Preparation method of Relugolix

The invention provides a preparation method of the Relugolix, intermediates of the Relugolix, namely, a compound shown as a formula (VI), a compound shown as a formula (V) and a compound shown as a formula (III) defined in the description, and a preparation method of the intermediates of the Relugolix. The method is simple to operate, safe, efficient, high in reaction purity and yield and relatively low in process cost, and is a preparation method which conforms to a green chemical principle and is suitable for large-scale production.

Rayleigh intermediate and preparation method thereof

The invention discloses an intermediate and a preparation method thereof. The preparation method of the compound F comprises the following steps: carrying out cyclization reaction on the compound E in the presence of an organic solvent and/or water as a s