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

TAK-385, also known as Relugolix, is a potent, orally active, nonpeptidic gonadotropin-releasing hormone (GnRH) antagonist. It exhibits high affinity and potent antagonistic activity for human and monkey receptors, making it a promising pharmaceutical candidate for the study and treatment of sex-hormone-dependent diseases.
Used in Pharmaceutical Industry:
TAK-385 is used as a therapeutic agent for the treatment of sex-hormone-dependent diseases such as endometriosis, uterine fibroids, and prostate cancer. Its high selectivity and potent antagonistic activity make it a promising candidate for these applications.
Used in Prostate Cancer Treatment:
TAK-385 is used as a highly selective, oral, nonpeptide GnRH antagonist for the treatment of prostate cancer. Its ability to modulate the hormonal pathways involved in the growth and progression of prostate cancer makes it a potential treatment option for patients suffering from this condition.

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

• 308831-93-8 2-((ethoxycarbonyl)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 
• 308831-95-0 4-(bromomethyl)-2-((2,6-difluorobenzyl)(ethoxycarbonyl)amino)-5-(4-nitrophenyl)thiophene-3-carboxylic acid ethyl ester 
• 308832-01-1 ethyl 2-[(2,6-difluorobenzyl)(ethoxycarbonyl)amino]-4-{[(2-methoxyethyl)(methyl)amino]methyl}-5-(4-nitrophenyl)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 
• 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 
• 124-40-3 dimethyl amine 
• 174072-89-0 2-Amino-4-methyl-5-(4-nitrophenyl)thiophene-3-carboxylic acid ethyl ester 
• 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 
• 697-73-4 2,6-difluorobenzyl chloride 
• 5332-96-7 1-(4-nitrophenyl)propan-2-one 

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.

Intermediate compound for preparing relugolix, preparation method of intermediate compound and preparation method of relugolix

The invention relates to the technical field of medicine synthesis, in particular to an intermediate compound for preparing relugolix, a preparation method of the intermediate compound and a preparation method of relugolix. The intermediate compound for preparing the relugolix is any one of compounds shown in the following structural formula, wherein R is a leaving group. The embodiment of the invention provides a novel intermediate for preparing the relugolix, and provides a novel method for synthesizing the relugolix, so that the yield can be increased, and the impurity content can be reduced.

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