866460-33-5 Usage
Description
2-(2-(1-naphthoyl)-8-fluoro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid is a complex organic compound with a unique molecular structure. It is characterized by its naphthoic acid moiety, fluorine substitution, and tetrahydropyridoindole core. This molecule has potential applications in various fields due to its specific chemical properties and interactions with biological targets.
Uses
Used in Pharmaceutical Industry:
2-(2-(1-naphthoyl)-8-fluoro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid is used as a potential therapeutic agent for treating scalp hair loss. Acting through the DP2 receptor, it can inhibit hair growth by modulating the effects of PGD2, making it a promising candidate for baldness treatment.
Used in Allergy Treatment:
In the field of allergy treatment, 2-(2-(1-naphthoyl)-8-fluoro-1,2,3,4-tetrahydropyrido[4,3-b]indol-5-yl)acetic acid has demonstrated its potential as an antagonist of the prostaglandin D2 (PGD2) receptor CRTH2/DP2. It has been shown to be well-tolerated and reasonably effective in reducing allergen-induced airway responses in asthmatic patients, suggesting its use as a possible treatment for allergic conditions.
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.
Biological Activity
A potent and selective CRTh2 antagonist. CRTh2 is a G-protein-coupled receptor for prostaglandin D2 (PGD2), a key mediator in inflammatory disorders.
Mechanism of action
Setipiprant binds to the DP2 receptor with a dissociation constant of 6 nM, representing potent antagonism of the receptor.The DP2 receptor, also called the CRTh2 receptor, is a G-protein-coupled receptor (GPCR) that is expressed on certain inflammatory cells, such as eosinophils, basophils, and certain lymphocytes. For its mechanism of action in the treatment of allergic conditions, setipiprant's DP2 antagonism prevents the action of prostaglandin D2 (PGD2) on these receptors. The DP2 receptor mediates the activation of type 2 helper T (Th2) cells, eosinophils, and basophils in the lungs, which are white blood cells implicated in producing the inflammatory response the characterizes allergic conditions. Activation of DP2 on Th2 cells by PGD2 induces the secretion of inflammatory cytokines (interleukin (IL) 4, IL-5, and IL-13), which cause an increase of eosinophils in the blood, remodeling of lung tissue, and hypersensitivity of lung tissue to allergens.Setipiprant does not antagonize the thromboxane receptor (TP). The bronchoconstricting properties of PGD2 are not inhibited by setipiprant, since these are mediated by the TP receptor. As a point of contrast, ramatroban is a selective TP antagonist and DP2 receptor antagonist.Setipiprant does not appreciably inhibit the activity of the enzyme cyclooxygenase 1 (COX-1), which is responsible for the synthesis of prostaglandins (including PGD2).Scalp hair lossProstaglandin D2 synthase (PTGDS) is an enzyme that produces PGD2. In men with androgenic alopecia, the enzyme PTGDS is elevated in the bald scalp tissue, as well as its product PGD2. PGD2 inhibits the growth of hair follicles through its activity on the DP2 receptor, but not the DP1 receptor. Theoretically, setipiprant's DP2 receptor antagonism may counteract the activity of PGD2 in hair follicles, thereby stimulating hair growth.
Pharmacokinetics
The oal hicalailityof setipiorartis44% in rts and % in dog, wichsugestistht itshoud beoall ioalale in humanst . theha ltfscf setprnt in humans is bot 11 hours.The
maximum concentration in plasma(Cmax is 6.04 and 6.44 mcgrml for setipiprant tablets and capule respectively with an area under the curve of 31.88 and 31.5l mcg hours/ml for setipiprantbles.
and capsules respectively.8BCmay was reached between 1.8-4 hours after oral administration.8.The tablet and capsul formulations are bioequivalent.
Side effects
Data from phase II and III clinical trials did not detect any severe adverse effects to setipiprant. The authors were unable to identify any pattern of adverse effects that differ from placebo, including subjective reporting of symptoms and objective laboratory monitoring.
Check Digit Verification of cas no
The CAS Registry Mumber 866460-33-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,6,6,4,6 and 0 respectively; the second part has 2 digits, 3 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 866460-33:
(8*8)+(7*6)+(6*6)+(5*4)+(4*6)+(3*0)+(2*3)+(1*3)=195
195 % 10 = 5
So 866460-33-5 is a valid CAS Registry Number.
866460-33-5Relevant articles and documents
Method for preparing tetrahydropyridine diindyl compounds
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, (2018/12/05)
The invention relates to a method for preparing tetrahydropyridine diindyl compounds. The method includes carrying out condensation on 4-fluorine-2-nitrotoluene and N-(2-cyano group) ethyl-1-naphthamide under the effects of alkali catalysts to generate an intermediate N-[4-(4-fluorine-2-nitrobenzophenone)-3-imido butyl]-1-naphthamide; directly carrying out catalytic hydrogenation and cyclization on a product mixed liquid to obtain N-(1-naphthoyl)-2-(2-amine) ethyl-6-fluoroindole; carrying out cyclization on the N-(1-naphthoyl)-2-(2-amine) ethyl-6-fluoroindole and formaldehyde; then carrying out condensation on cyclization products and chloroacetate in the presence of alkali to obtain Setipiprant. The method has the advantages that raw materials for the tetrahydropyridine diindyl compoundsare low in cost and are easily available, and the method includes short technological processes, is easy and convenient to operate and is green and environmentally friendly; the method is good in reaction selectivity, and the tetrahydropyridine diindyl compounds which are products are high in yield and purity.
TETRAHYDROPYRIDOINDOLE DERIVATIVES
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Page/Page column 55, (2008/06/13)
The invention relates to tetrahydropyridoindole derivatives and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharma
