103177-37-3

Basic information

• Product Name: Pranlukast
• Synonyms: PRANLUKAST;4-oxo-8-(4-(4-phenylbutoxy)benzoylamino)-2-(tetrazol-5-yl)-4h-1-benzopyranh;benzamide,n-(4-oxo-2-(1h-tetrazol-5-yl)-4h-1-benzopyran-8-yl)-4-(4-phenylbutox;emihydrate;ONO-RS-411;ONO-RS-411-01;N-[4-keto-2-(2H-tetrazol-5-yl)chromen-7-yl]-4-(4-phenylbutoxy)benzamide;N-[4-oxo-2-(2H-1,2,3,4-tetrazol-5-yl)chromen-7-yl]-4-(4-phenylbutoxy)benzamide
• CAS NO: 103177-37-3
• Molecular Formula: C₂₇H₂₃N₅O₄
• Molecular Weight: 481.5
• EINECS: 201-616-4
• Product Categories: Aromatics;Heterocycles;API;Antiasthmatic;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 103177-37-3.mol

Chemical Properties

• Melting Point: 236-238°C
• Appearance: off-white solid
• Density: 1.374 g/cm³
• Refractive Index: 1.68
• Storage Temp.: Store at +4°C
• Solubility: Soluble in DMSO (up to 25 mg/ml)
• PKA: 4.96±0.10(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.
• Merck: 14,7710
• CAS DataBase Reference: Pranlukast(CAS DataBase Reference)
• NIST Chemistry Reference: Pranlukast(103177-37-3)
• EPA Substance Registry System: Pranlukast(103177-37-3)

Safety Data

• Hazard Codes: F,C
• Statements: 11-34
• Safety Statements: 16-26-36/37/39-45
• RTECS: CV5647500
• Hazardous Substances Data: 103177-37-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Pranlukast is used as an antiasthmatic agent for the treatment of bronchial asthma and allergic diseases. It acts as a leukotriene receptor-1 antagonist, helping to reduce inflammation and improve respiratory function in patients with asthma.
Used in Clinical Research:
Pranlukast is being evaluated clinically for the treatment of perennial allergic rhinitis, pediatric asthma, and cutaneous pruritus in dialysis patients. Its therapeutic potential in managing irritable bowel syndrome has also been suggested.
Chemical Properties:
Pranlukast is an off-white solid.

Asthma drugs

Pranlukast is a common respiratory drug, it belongs to asthma drugs , it is the cysteinyl leukotrienes (LTs) receptor antagonist and it can bind to LTC4, LTD4, LTE4 receptors selectively to antagonize their effect . Roles and application are similar to zafirlukast. It is clinically used for the prevention of bronchial asthma. Oral 225mg once, 2 times one day, morning and evening after meal. After taking ,there may be gastrointestinal reactions,or there may be nausea, vomiting, abdominal pain, diarrhea or constipation, sometimes , fever, rash, pruritus and liver function abnormalities such as serum aminotransferase or bilirubin increase are visible . Pregnant women should use with caution , the elderly should take appropriate reductions. This product can not alleviate the onset of asthma. At present, three leukotriene receptor antagonists are used for the following purposes: 1, zafirlukast :it is effective for mild to moderate asthma ,it can cause improvement in dose-dependent lung function, and reduce the amount of β agonists. Absorption of the product is affected by food, it should not be taken together with food. Oral each 20mg, 2 times/d. 2, montelukast: it is valid for intermittent or persistent asthma in adults and children. This product is approved by the FDA for the treatment of children aged 6 to 12. Absorption of the product is not affected by food, it can be taken with food . Oral each 10mg, once/d. 3, pranlukast :it is used for mild to moderate asthma, pranlukast can increase patients maximum expiratory flow,and improve asthma symptoms, it can be used as a daily treatment of chronic asthma. Each oral 450mg, 2 times/d. The above information is edited by the lookchem of Tian Ye.

Originator

Ono (Japan)

Biological Activity

Selective cysteinyl leukotriene receptor 1 (CysLT 1 ) antagonist (IC 50 values are ~ 4-7 and 3620 nM for CysLT 1 and CysLT 2 respectively). Inhibits contraction of airway smooth muscle, microvascular leakage into airways and eosinophil infiltration. Can decrease symptoms of bronchial asthma.

References

1) Nakai?et al. (1988),?New Potent Antagonists of Leukotrienes C4 and D4. 1. Synthesis and Structure-Activity Relationships; J. Med. Chem.?31?84 2) Taniguchi?et al.?(1993),?The effect of an oral leukotriene antagonist, ONO-1078, on allergen-induced immediate bronchoconstriction in asthmatic subjects; J. Allergy Clin. Immunol.?92?507 3) Ciana?et al.?(2006),?The orphan receptor GPR17 identified as a new dual uracil nucleotides/cysteinyl-leukotrienes receptor; EMBO J.?25?4615 4) Hennen?et al. (2013),?Decoding Signaling and Function of the Orphan G Protein-Coupled Receptor GPR17 with a Small-Molecule Agonist; Sci. Signal.?6?ra93

InChI:InChI=1/C27H23N5O4/c33-23-17-24(26-29-31-32-30-26)36-25-21(23)10-6-11-22(25)28-27(34)19-12-14-20(15-13-19)35-16-5-4-9-18-7-2-1-3-8-18/h1-3,6-8,10-15,17H,4-5,9,16H2,(H,28,34)(H,29,30,31,32)

Upstream product

• 55408-10-1 1H-tetrazole-5-carboxylic acid ethyl ester 
• 136450-06-1 3-[4-(4-phenyl-1-butoxy)benzoyl]amino-2-hydroxyacetophenone 
• 108807-05-2 4-(4-phenyl-1-butoxy)benzoyl chloride 
• 110683-23-3 8-amino-4-oxo-2-tetrazol-5-yl-4H-1-benzopyran hydrochloride 
• 1229412-35-4 N-(4-oxo-2-(1-trityl-1H-tetrazol-5-yl)-4H-chromen-8-yl)-4-(phenylbutoxy)benzamide 
• 586-76-5 4-Bromobenzoic acid 
• 3360-41-6 4-phenyl-butan-1-ol 
• 586-75-4 4-chlorobenzoyl chloride 
• 136450-11-8 8-[4-(4-phenyl-1-butoxy)-benzoyl]amino-2-cyano-4-oxo-4H-benzopyran 
• 30131-16-9 4-(4-phenyl-1-butoxy)benzoic acid 
• 70977-72-9 3'-Amino-2'-hydroxyacetophenone 
• 125620-28-2 Pd-C 
• 144-55-8 sodium hydrogencarbonate 
• 174403-16-8 [8-[4-(4-phenylbutoxy)benzoyl]-amino-4-oxo-4H-benzopyran-2-yl]amidrazone 

Relevant articles and documents

A direct and high yielding route to 2-(5-tetrazolyl) substituted benzopyran-4-ones: Synthesis of pranlukast

A direct and high yielding route to 2-(5-tetrazolyl)benzopyran-4-ones 1, including pranlukast 1a is described. This involves the Claisen condensation reaction between the relevant hydroxyacetophenone 2 and the ethyl ester of tetrazole-2-carboxylic acid 5 to give the 1,3-diketone 6, which is then cyclised to give the desired benzopyran-4-ones 1.

Industrial preparation method of anti-asthma drug pranlukast intermediate

The invention discloses a preparation method of a pranlukast intermediate N-(2-cyano-4-oxo-4H-chromene-8-yl)-4-(4-butoxyphenyl)benzamide (short for formula I), specifically a method for preparing N-(2-cyano-4-oxo-4H-chromene-8-yl)-4-(4-butoxyphenyl)benzamide by carrying out a dewatering reaction on 4-oxo-8-[4-(4-butoxyphenyl)benzamide]-4H-chromene-2-formamide (short for formula II). The preparation method of the pranlukast intermediate represented by the formula I is high in yield, good in product color, high in product purity and beneficial to industrial production.

Preparation method for pranlukast

The invention belongs to the field of medicines and especially relates to a preparation method for pranlukast. The method comprises the following steps: A) adding 4-bromobenzoic acid and thionyl chloride into a solvent and reacting, thereby acquiring 4-bromo-benzoyl chloride; B) adding the 4-bromo-benzoyl chloride acquired in the step A), alkali and 3-amino-2-ethyl iodobenzoate into the solvent and reacting, thereby acquiring 2-iodine-3-(4-bromobenzamide) ethyl benzoate; C) adding the 2-iodine-3-(4-bromobenzamide) ethyl benzoate acquired in the step B), alkali and 1-(1H-tetrazole-5-group) aceton into the solvent and reacting, thereby acquiring 4-bromine-N-(4-oxo-2-(1H-tetrazole-5-group)-4H-benzopyrone-8-group) benzamide; D) adding the 4-bromine-N-(4-oxo-2-(1H-tetrazole-5-group)-4H-benzopyrone-8-group) benzamide acquired in the step C), catalyst and alkali into the solvent and reacting, thereby acquiring the product. The method provided by the invention is simple and practicable in process, low in production cost and high in yield.

Novel method for preparing high-purity asthma treatment drug pranlukast

The invention discloses a novel method for preparing a high-purity asthma treatment drug pranlukast, and relates to the technical field of organic synthesis of drugs. The method comprises the following steps: carrying out neutralization and a salt forming reaction on a reaction raw material 8-amino-4-oxo-2-tetrazole-5-yl-4H-1-benzopyran hydrochloride and an alkaline substance to generate an intermediate, and carrying out an amidation reaction on the obtained intermediate and p-phenylbutoxybenzoyl chloride in a non-polar solvent to prepare the pranlukast. The whole process of the method is simple and clean, is easy to control, allows the purity of the obtained crude product to reach 99% or above, and allows the purity of a one-time purified product to reach 99.9% or more.

New preparation method of Pranlukast

The invention provides a new preparation method of drug Pranlukast for treating asthma. The new preparation method includes the specific steps that with 2-aminophenol-4-sulfonic acid as a starting material, a key intermediate 3-amino-2-hydroxyacetophenone is prepared by means of acylation, Fries rearrangement and deprotection, then reacts with 4-(phenylbutoxy)benzoic acid, and then is subjected to condensation with ethyl 1H-tetrazole-5-acetate, and finally preparation is achieved through ring closing under the acidic condition. Compared with the prior art, the raw material used for the new preparation method is low in price and easy to obtain, industrialization of a process can be achieved easily, and the obtained final product is high in purity; and no dangerous process exists, equipment is simple, and the route is novel.

METHOD OF REMOVING THE TRIPHENYLMETHANE PROTECTION GROUP

The present invention relates to a method of removing triphenylmethane protection group. The method for preparing biphenyl benzoic acid derivatives of the present invention is economically advantageous and very excellent in the aspect of improving process in that: process safety is secured by using acidic ion exchange resin in the presence of organic solvent instead of using highly corrosive acid; the reaction takes much less time than do the conventional reactions which use only anhydrous methanol and few sub-reaction does occur; and the ion-exchange resin of the present invention is excellent for mass-processing because the resin can be collected and recycled only by filtration after being used.

METHODS FOR PREPARING AMIDE DERIVATIVES

The present invention provides a novel method for preparing an amide derivative. The method of the present invention enables to economically prepare various amide derivatives containing pranlukart by reacting a carboxylic acid derivative 5 and an amine derivative through a brief procedure compared with a conventional technology, and permits to obtain a final product at a high yield rate because it is feasible to eliminate by-products after termination of reactions. Accordingly, the present method is to be quite suitable for massive production.

PROCESS FOR PREPARING SUBSTITUTED BENZOPYRAN COMPOUNDS

The present invention relates to a novel method of synthesizing substituted benzopyran compounds, their novel intermediates and a method of their preparation thereof.

Process for the production of tetrazolylbenzopyrans

PCT No. PCT/EP97/07341 Sec. 371 Date Jul. 6, 1999 Sec. 102(e) Date Jul. 6, 1999 PCT Filed Dec. 30, 1997 PCT Pub. No. WO98/30559 PCT Pub. Date Jul. 16, 1998A process for preparing certain substituted benzopyran compounds of formula (I) is disclosed.

Production process and intermediate of tetrazole compound

There are disclosed an industrially favorable process for producing a tetrazole compound of general formula (1): STR1 characterized in that a nitrile of general formula (2): is reacted with hydrazine or a salt thereof in the presence of a catalyst, followed by reaction with a nitrous acid compound of general formula (3): or a nitrile of general formula (2) is reacted with hydrogen sulfide, followed by reaction with an alkyl halide of general formula (4): with hydrazine or a salt thereof, and then with a nitrous acid compound of general formula (3); and an intermediate of general formula (5): which is useful for the production of the tetrazole compound (in which R1 to R6, A and J in the above formulas are as defined in the specification).