753498-25-8 Usage
Chemical Properties
White Solid
Uses
A long-acting β2 adrenoreceptor agonist and bronchodilator, for the treatment of asthma and chronic obstructive pulmonary disease.
Definition
ChEBI: A maleate salt obtained by reaction of indacaterol with one equivalent of maleic acid. Used for treatment of chronic obstructive pulmonary disease.
Clinical Use
Indacaterol is a b-adrenoceptor agonist currently approved in
Europe as Onbrez, and is marketed by Novartis. It needs to be
taken only once a day, unlike competitors formoterol and salmeterol.
These drugs are used in the treatment of chronic obstructive
pulmonary disease (COPD) and asthma. Onbrez is administered via
an aerosol formulation through a dry powder inhaler. A Phase III
trial published in July 2010 suggested that indacaterol is significantly
more effective than twice-daily formoterol in improving
FEV1 and reduces the need for rescue medication.
Synthesis
The synthesis
of indacaterol relies on the union of the dihydroindeneamine
region and the quinolinol region of the molecule. Preparation of
the dihydroindene unit of indacaterol was reported by researchers
at Novartis in 2006 and is summarized in the scheme.
2,3-Dihydro-1H-inden-2-amine (59) was protected as its trifluoroacetamide
61 and was followed by Friedel–Crafts alkylation with
acetylchloride to give 62. Hydrogenative carbonyl reduction of this
unsymmetrical dihydroindene provided amide 63. An iterative Friedel–Crafts acylation/hydrogenation sequence was used to install
the second ethyl group, giving rise to trifluoroacetamide 64.
Basic hydrolysis to remove the trifluoroacetamide functionality,
followed by salt formation by means of gaseous HCl furnished
the dihydroindene amine 65. The synthesis of the remaining
portion of the molecule starts from 8-hydroxyquinoline (66).
Friedel–Crafts alkylation with acetylchloride and trichloroaluminum
installed the acetophenone functionality at the 5-position of
the quinoline frame followed by benzyl protection of the hydroxyl
group to give ether 67. Oxidation of quinoline 67 with mCPBA and
acylation of the resulting N-oxide with acetic anhydride and thermal
rearrangement produced quinolone 68. Bromination of the
methyl ketone and subsequent asymmetric reduction provided
(R)-alcohol 69. Bromohydrin 69 was then converted to the epoxide
using potassium carbonate prior to amination of the epoxide with
dihydroindene intermediate 65 to furnish the indacaterol skeleton
70. Hydrogenolytic debenzylation and maleate salt formation
provided indacaterol maleate (XI).
Check Digit Verification of cas no
The CAS Registry Mumber 753498-25-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 7,5,3,4,9 and 8 respectively; the second part has 2 digits, 2 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 753498-25:
(8*7)+(7*5)+(6*3)+(5*4)+(4*9)+(3*8)+(2*2)+(1*5)=198
198 % 10 = 8
So 753498-25-8 is a valid CAS Registry Number.
753498-25-8Relevant articles and documents
INHALABLE FORMULATION OF A SOLUTION CONTAINING INDACATEROL MALEATE AND GLYCOPYRRONIUM BROMIDE
-
Paragraph 0078-0080, (2020/12/13)
The present invention discloses a liquid, propellant-free pharmaceutical preparation and a method for administering a pharmaceutical preparation by nebulizing the pharmaceutical preparation in an inhaler. The propellant-free pharmaceutical preparation comprising: (a) active substances selected from glycopyrronium bromide and indacaterol maleate; (b) a solvent; and (c) a pharmacologically acceptable preservative, optionally including a pharmacologically acceptable stabilizer, a pharmacologically acceptable solubilizing agent, a pharmacologically acceptable co-solvent, or other pharmacologically acceptable additives.
Preparation method of indacaterol and salt thereof
-
, (2020/11/01)
The invention relates to a preparation method of indacaterol and a salt thereof. The preparation method comprises the following steps: in a solvent, reacting a mixture containing a compound as shown in a formula I with m-chlorobenzoic acid to obtain a com
Preparation method for indacaterol or salt thereof
-
Paragraph 0046; 0047; 0048; 0052, (2018/06/26)
The invention relates to a preparation method for indacaterol or a salt thereof. According to the method, hydrogen diluted by inert gas is selected and used as a hydride source, and high-purity indacaterol maleate is prepared under metal catalysis conditions.
