2-(2-(1-naphthoyl)-8-fluoro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid

Base Information

• Chemical Name: 2-(2-(1-naphthoyl)-8-fluoro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid
• CAS No.: 866460-33-5
• Molecular Formula: C₂₄H₁₉FN₂O₃
• Molecular Weight: 402.425
• Mol file: 866460-33-5.mol

Synonyms:2-(2-(1-naphthoyl)-8-fluoro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid;Setipiprant;ACT129968;2-[8-fluoro-2-(naphthalene-1-carbonyl)-3,4-dihydro-1H-pyrido[4,3-b]indol-5-yl]acetic acid;ACT-129968 (Setipiprant);8-Fluoro-1,2,3,4-tetrahydro-2-(1-naphthalenylcarbonyl)-5H-pyrido[4,3-b]indole-5-acetic acid

Chemical Property of 2-(2-(1-naphthoyl)-8-fluoro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid

Chemical Property:

• Appearance/Colour: Light yellow to yellow solid
• Boiling Point: 690.4±55.0 °C(Predicted)
• PKA: 4.24±0.10(Predicted)
• PSA: 62.54000
• Density: 1.37±0.1 g/cm3(Predicted)
• LogP: 4.15460

Purity/Quality:

99% ^*data from raw suppliers

Setipiprant(ACT129968) >98% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: Setipiprant is an orally bioavailable antagonist of the prostaglandin D2 (PGD2) receptor CRTH2/DP2 (IC50 = 6 nM for the human receptor). It is selective for CRTH2/DP2 over DP1 in a radioligand binding assay (IC50 = 1,290 nM) and the prostaglandin E2 (PGE2) receptor subtypes EP2 and EP4 in a β-arrestin assay (IC50s = 2,600 and >10,000 nM, respectively). Setipiprant inhibits PGD2-induced calcium flux in HEK293 cells expressing human CRTH2/DP2 (IC50 = 30 nM) and PGD2-induced shape change in human eosinophils (IC50 = 235 nM).
• Uses: Scalp hair loss Acting through DP2, PGD2 can inhibit hair growth, suggesting that this receptor is a potential target for bald treatment.[1] A phase 2A study to evaluate the safety, tolerability, and efficacy of oral setipiprant relative to a placebo in 18- to 49-year-old males with androgenetic alopecia was completed in May 2018 but no results have been published. Allergic conditions Setipiprant proved to be well tolerated and reasonably effective in reducing allergen-induced airway responses in asthmatic patient clinical trials. However, the drug, while supporting the concept that DP2 contributes to asthmatic disease, did not show sufficient advantage over existing drugs and was discontinued from further development for this application.
• Indications: Setipiprant (INN; developmental code names ACT-129968, KYTH-105) is an investigational drug developed for the treatment of asthma and scalp hair loss. It was originally developed by Actelion and acts as a selective, orally available antagonist of the prostaglandin D2 receptor 2 (DP2). The drug is being developed as a novel treatment for male pattern baldness by Allergan.

Technology Process of 2-(2-(1-naphthoyl)-8-fluoro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid

There total 9 articles about 2-(2-(1-naphthoyl)-8-fluoro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid 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: 93.2%

2-(1-naphthoyl)-8-fluoro-1.2.3.4-tetrahydropyrido[4,3,b]indole + chloroacetic acid (79-11-8) → setipiprant (866460-33-5)

Guidance literature:

With sodium hydroxide; In water; at 60 - 90 ℃; for 3h; Temperature;

Reference yield: 93.0%

ethyl 2-(2-(1-naphthoyl)-8-fluoro-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-5-yl)acetate (1443129-96-1) → setipiprant (866460-33-5)

Guidance literature:

With sodium hydroxide; In tetrahydrofuran; at 20 ℃; for 0.5h;

DOI:10.1021/jm400122f

Reference yield:

8-fluoro-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carboxylic acid tert-butyl ester (870471-42-4) → setipiprant (866460-33-5)

Guidance literature:

Multi-step reaction with 4 steps

1: caesium carbonate / acetone / 20 °C

2: hydrogenchloride / dichloromethane; 1,4-dioxane / 3 h / 20 °C

3: N-ethyl-N,N-diisopropylamine / dichloromethane / 1 h / 0 - 20 °C

4: sodium hydroxide / tetrahydrofuran / 0.5 h / 20 °C

With hydrogenchloride; caesium carbonate; N-ethyl-N,N-diisopropylamine; sodium hydroxide; In tetrahydrofuran; 1,4-dioxane; dichloromethane; acetone;

DOI:10.1021/jm400122f

upstream raw materials:

Ethyl 2-(8-Fluoro-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-5-yl)acetate hydrochloride

naphthalene-1-carbonic acid chloride

8-fluoro-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carboxylic acid tert-butyl ester

tert-butyl 5-(2-ethoxy-2-oxoethyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate