cas 320345-99-1, Aclidinium bromide | Articles data

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A PROCESS FOR PREPARING ACLIDINIUM BROMIDE AND INTERMEDIATES THEREOF
Provided herein is a process for synthesis of aclidinium bromide and intermediates thereof, wherein the process for the preparation of aclidinium bromide increases the % yield of aclidinium bromide by about 70% to 90%.
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(2018/09/12)

Choline M receptor anti-caking agent re-crystallization method
The invention provides a choline M receptor anti-caking agent re-crystallization method, which comprises: (1) heating an aclidinium bromide crude product and DMF to a temperature of 90-130 DEG C, stirring, dissolving, and clarifying; (2) cooling the solut
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Page/Page column 7-15

(2018/10/11)

Novel method for synthesis and purification of aclidinium bromide
The invention discloses a novel method for synthesis and purification of aclidinium bromide. According to the method, tetrahydrofuran is used, haloalkane is used as an initiator, and a finished product is obtained through solvent extraction and recrystall
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Page/Page column 6-9

(2018/12/05)

High-purity high-yield aclidinium bromide preparation method suitable for industrial production
The invention discloses a high-purity high-yield aclidinium bromide preparation method suitable for industrial production. The preparation method comprises the following steps: 1) adding methyl 2,2-di(2-thienyl)-2-hydroxyacetate and TBDMSCl into solvent,
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(2017/07/21)

Discovery of Novel Potent Muscarinic M3 Receptor Antagonists with Proper Plasma Stability by Structural Recombination of Marketed M3 Antagonists
The marketed long-acting M3 antagonists for treatment of chronic obstructive pulmonary disease have inappropriate plasma stability (either overstable or excessively unstable), which causes substantial systemic exposure or poor patient compliance. To discover novel M3 antagonists with proper plasma stability, we synthesized and biologically evaluated a series of chiral quaternary ammonium salts of pyrrolidinol esters, which were designed by structural recombination of the marketed M3 antagonists. As a result, two novel potent M3 antagonists, (R/S)-3-[2-hydroxy-2,2-di(thiophen-2-yl)acetoxy]-1,1-dimethylpyrrolidinium bromides (1 a: Ki=0.16 nm, IC50=0.38 nm, t1/2=9.34 min; 1 b: Ki=0.32 nm, IC50=1.01 nm, t1/2=19.2 min) with proper plasma stability were identified, which (particularly 1 a) hold great promise as clinical drug candidates to overcome the drawbacks caused by the inappropriate stability of the currently marketed M3 antagonists. In addition, structure–activity relationship studies revealed that the R configuration of the pyrrolidinyl C3 atom was clearly better than the S configuration.
Xiang, Zuojuan,Liu, Jun,Sun, Hongbin,Wen, Xiaoan
p. 1173 - 1182
(2017/08/15)

AN ADVANTAGEOUS PROCESS FOR PREPARING 1-AZONIABICYCLO[2.2.2]OCTANE,3-[(HYDROXYDI-2-THIENYLACETYL)OXY]-1-(3?PHENOXYPROPYL)-, BROMIDE, (3R)- AND ITS NOVEL CRYSTALLINE FORM-I
The present invention discloses the process for preparation of 1- ?Azoniabicyclo[2.2.2]octane,3-[(hydroxydi-2-thienylacety1)oxy]-1-(3?iphenoxypropy1)-, bromide, (3R)- and its novel crystalline form-I
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Page/Page column 19

(2016/10/31)

Choline M receptor antagonist aclidinium bromide and preparation method thereof
The invention relates to choline M receptor antagonist aclidinium bromide and a preparation method thereof. According to the preparation method, 2,2-di(2-thienyl)-2-methyl glycolate reacts with 3-quinuclidinol to obtain 2-hydroxy-2,2-di(2-thienyl) acetic
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(2016/10/17)

PROCESS FOR THE PREPARATION OF ACLIDINIUM BROMIDE
A process for preparing (3R)-3-[2-Hydroxy(di-2-thienyl)acetoxy]-1-(3-phenoxypropyl)-1- azoniabicyclo[2.2.2]octane bromide (aclidinium bromide) comprises reacting 2-hydroxy-2,2- dithien-2-ylacetic acid 1-azabicyclo[2.2.2]oct-3(R) yl methyl ester and 3-phen
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Page/Page column 9

(2016/12/12)

A choline M receptor antagonists arab League bromine ammonium and its preparation method
The invention relates to choline M receptor antagonist aclidinium bromide and a preparation method thereof. The chemical structural formula of the choline M receptor antagonist aclidinium bromide is as shown in the specification. The preparation method comprises the following steps: mixing R-quinine-3 alcohol, alkali and an organic solvent, dripping methyl oxalyl chloride, after the methyl oxalyl chloride is completely dripped, heating, performing heating reflux for 1-20 hours, and separating and purifying, thereby obtaining a substance A; adding iodine into a tetrahydrofuran solution of 2-bromothiophene and magnesium powder to initiate reaction for 1-5 hours, thereby preparing a Grignard reagent of 2-bromothiophene, adding the substance A, stirring to react for 10-30 minutes at the room temperature, performing heating reflux for 4-6 hours, separating and purifying, thereby preparing 2,2-dithienyl-2-glycolic acid-R-quinine-3-base ester, and performing quaterisation reaction with 3-phenoxypropyl bromine, thereby obtaining aclidinium bromide. The aclidinium bromide provided by the invention is simple in reaction operation, high in yield, low in price, short in reaction route, small in waste generation and easy in industrialization production.
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(2016/12/22)

NOVEL QUINUCLIDINE DERIVATIVES AND MEDICINAL COMPOSITIONS CONTAINING THE SAME
A compound according to formula (I) wherein z? is a phenyl ring, a C4 to C9 heteroaromatic compound containing one or more heteroatoms, or a naphthalenyl, 5,6,7,8-tetrahydronaphthalenyl or biphenyl group; R1, R2 and R3 each independently represent a hydrogen or halogen atom, or a hydroxy group, or a phenyl, —OR4, —SR4, —NR4R5, —NHCOR4, —CONR4R5, —CN, —NO2, —COOR4 or —CF3 group, or a straight or branched lower alkyl group which may optionally be substituted, for example, with a hydroxy or alcoxy group, wherein R4 and R5 each independently represent a hydrogen atom, straight or branched lower alkyl group, or together form an alicyclic ring; or R1 and R2 together form an aromatic, alicyclic or heterocyclic ring; n is an integer from 0 to 4; A represents a —CH2—, —CH═CR6, —CR6═CH—, —CR6122—, —CO—, —O—, —S—, —S(O)—, SO2 or NR6— group, wherein R6 and R2 each independently represent a hydrogen atom, straight or branched lower alkyl group, or R6 and 122 together form an alicyclic ring; m is an integer from 0 to 8; provided that when m=0, A is not —CH2—; p is an integer from 1 to 2 and the substitution in the azoniabicyclic ring may be in the 2,3 or 4 position including all possible configurations of the asymmetric carbons; B represents a group of formula (i) or (ii), wherein R10 represents a hydrogen atom, a hydroxy or methyl group; and R8 and R9 each independently represents formulae (a), (b), (c), (d) and wherein R11 represents a hydrogen or halogen atom, or a straight or branched lower alkyl group and Q represents a single bond, —CH2—, —CH2—CH2, —O—, —O—CH2—, —S—, —S—CH2— or —CH═CH—, and when (i) or (ii) contain a chiral centre they may represent either configuration; X represents a pharmaceutically acceptable anion of a mono or polyvalent acid, which shows high affinity for muscarinic M3 receptors (Hm3).
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Paragraph 0088; 0212

(2015/10/05)

PROCESS FOR THE PREPARATION OF ACLIDINIUM BROMIDE
The present invention relates to process for the preparation of aclidiunium or intermediates thereof. More particularly, it relates to the preparation of aclidinium bromide.
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Page/Page column 18; 19

(2015/06/03)

AN INDUSTRIALLY APPLICABLE PROCESS FOR PREPARING HIGH PURITY ACLIDINIUM BROMIDE
An efficient and industrially applicable process for preparing aclidinium bromide of formula I, comprising the following steps a) preparation of the quinuclidinyl ester by transestenfication of methyl di(2-thienly)giycolate with R-(-)-3-quinuclidinol in t
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Page/Page column 12; 23

(2015/05/19)

Discovery of novel quaternary ammonium derivatives of (3R)-quinuclidinol esters as potent and long-acting muscarinic antagonists with potential for minimal systemic exposure after inhaled administration: Identification of (3R)-3-{[hydroxy(di-2-thienyl)acetyl]oxy}-1-(3-phenoxypropyl)-1-azoniabicyclo[2. 2.2]octane bromide (aclidinium bromide)
The objective of this work was to discover a novel, long-acting muscarinicM3 antagonist for the inhaled treatment of chronic obstructive pulmonary disease (COPD), with a potentially improved risk-benefit profile compared with current antimuscarinic agents. A series of novel quaternary ammonium derivatives of (3R)-quinuclidinol esters were synthesized and evaluated. On the basis of its overall profile, (3R)-3-{[hydroxy(di-2-thienyl) acetyl]oxy}-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide (aclidiniumbromide) emerged as a candidate for once-daily maintenance treatment of COPD. This compound is a potent muscarinic antagonist, with long duration of action in vivo, and was found to have a rapid hydrolysis in human plasma, minimizing the potential to induce class-related systemic side effects. Aclidinium bromide is currently in phase III development for maintenance treatment of patients with COPD.
Prat, María,Fernández, Dolors,Buil, M. Antonia,Crespo, María I.,Casals, Gaspar,Ferrer, Manuel,Tort, Laia,Castro, Jordi,Monleón, Juan M.,Gavaldà, Amadeu,Miralpeix, Montserrat,Ramos, Israel,Doménech, Teresa,Vilella, Dolors,Antón, Francisca,Huerta, Josep M.,Espinosa, Sonia,López, Manuel,Sentellas, Sonia,González, Marisa,Albertí, Joan,Segarra, Victor,Cárdenas, Alvaro,Beleta, Jorge,Ryder, Hamish
experimental part
p. 5076 - 5092
(2010/03/01)

PROCESS FOR MANUFACTURING 3(R)-(2-HYDROXY-2,2-DITHIEN-2-YLACETOXY)-1-(3- PHENOXYPROPYL)-1 -AZONIABICYCLO[2.2.2]OCTANE BROMIDE
This invention is directed to a process for manufacturing 3(R)-(2-hydroxy-2,2- dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide by reacting 2-hydroxy-2,2-dithien-2-ylacetic acid 1 -azabicyclo[2.2.2]oct-3(R)yl ester and 3-pheno
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Page/Page column 3-4

(2008/06/13)