223673-36-7Relevant articles and documents
Systematic Investigation into the Formation of Significant Amounts of Unknown Impurity during Scale-up of NaBH4-I2 Mediated Reduction of Nitro-Amide Intermediate of Mirabegron No.
Bangal, Mukund N.,Deshmukh, Dattatray G.,Kalawade, Kaustubh A.,Mathad, Vijayavitthal T.
, p. 286 - 293 (2020/03/10)
After successful development of a manufacturing process for the Mirabegron (1) at the laboratory scale, a muddled situation was aroused during the scale-up batches, wherein sodium borohydride-iodine (NaBH4-I2) mediated reduction of nitro-amide 4 ended up with substantial amounts (～10%) of unspecified impurity in the nitro-amine intermediate 5. On the basis of the structure elucidation and meticulous investigation, a reaction path for its genesis during the process was identified and an efficient mechanism proposed to arrest its formation. In-situ generated nickel boride (Ni2B) due to reaction of NiI2 (corrosion product) with NaBH4 followed by electrophilic attack of THF (solvent) was found to be the reason for the formation of impurity (8a). Execution of subsequent batches with proper controls arrested this impurity and successfully provided the Mirabegron with the desired quality.
Aryl or heteroaryl substituted pyrrolidine amide derivatives and application thereof
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Paragraph 0230-0232, (2019/05/22)
The invention discloses aryl or heteroaryl substituted pyrrolidine amide derivatives and an application thereof, in particular to a novel aryl or heteroaryl substituted pyrrolidine amide derivative and a pharmaceutical composition containing the same, which can be used for activating beta3-adrenergic receptor. The invention also relates to a method for preparing the compounds and pharmaceutical compositions, as well as an application thereof in preparing drugs for treating diseases or symptoms mediated by beta3-adrenergic receptor, and especially for treating the overactive bladder.
Amide substituted pyrrolidine amide derivatives and use thereof (by machine translation)
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Paragraph 0233; 0245; 0246, (2019/06/07)
The invention discloses amide substituted pyrrolidine amide derivatives and their use, in particular, the invention relates to a novel class of amide substituted pyrrolidine amide derivatives containing such compounds and pharmaceutical composition, can be used to activate β 3 - adrenergic receptor. The invention also relates to processes for preparing such compounds and pharmaceutical compositions, and in the preparation of the treatment by the β 3 - adrenergic receptor activation mediated diseases or conditions, in particular the overactive bladder of the use of the medicament. (by machine translation)
Acyl-substituted pyrrolidine amide derivative and application thereof
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Paragraph 0234; 0246; 0247, (2019/06/12)
The invention discloses an acyl-substituted pyrrolidine amide derivative and application thereof. Specifically, the invention relates to a novel acyl-substituted pyrrolidine amide derivative and a pharmaceutical composition containing the compound, which can be used for activation of beta3-adrenoceptor. The invention also relates to a method for preparing the compound and the pharmaceutical composition and their application in the preparation of beta3-adrenoceptor activation-mediated diseases or symptoms, especially overactive bladder.
Nitrogen heterocyclic ring group substituted amide derivative and application thereof
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Paragraph 0213; 0231-0233, (2019/06/05)
The invention discloses a nitrogen heterocyclic ring group substituted amide derivative and application thereof, particularly relates to a novel nitrogen heterocyclic ring group substituted amide derivative and a drug composition comprising the compound, and further relates to methods for preparing the compound and the drug composition, and application of the compound and the drug composition to preparation of drugs for treating diseases or symptoms, particularly overactive bladder, excited and mediated by beta 3-adrenergic receptors. The compound and the drug composition can be used for activating the beta 3-adrenergic receptors.
Synthesis and evaluation of novel phenylethanolamine derivatives containing acetanilides as potent and selective b 3-adrenergic receptor agonists
Maruyama, Tatsuya,Onda, Kenichi,Hayakawa, Masahiko,Suzuki, Takayuki,Kimizuka, Tetsuya,Matsui, Tetsuo,Takasu, Toshiyuki,Nagase, Itsuro,Hamada, Noritaka,Ohta, Mitsuaki
experimental part, p. 533 - 545 (2010/09/06)
In the search for potent and selective human β3-adrenergic receptor (AR) agonists as potential pharmacotherapies for the treatment of obesity and non-insulin dependent (type II) diabetes, we prepared a novel series of phenylethanolamine derivatives containing acetanilides and evaluated their biological activities at the human β3-, β2-, and β1-ARs. Among these compounds, the 6-amino-2-pyridylacetanilide (36b), 2-amino-5- methylthiazol- 4-ylacetanilide (36g), and 5-amino-1,2,4-thiadiazol-3- ylacetanilide (36h) derivatives showed potent agonistic activity at the β3-AR with functional selectivity over the β1- and β2-ARs. In addition, these compounds exhibited significant hypoglycemic activity in a rodent diabetic model.
Amide derivatives or salts thereof
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Page column 13, (2008/06/13)
Amide derivatives represented by general formula (I) or salts thereof wherein each symbol has the following meaning: ring B: an optionally substituted heteroaryl optionally fused with a benzene ring; X: a bond, lower alkylene or lower alkenylene optionally substituted by hydroxy or lower alkyl, carbonyl, or a group represented by —NH— (when X is lower alkylene optionally substituted by lower alkyl which may be bonded to the hydrogen atom bonded to a constituent carbon atom of ring B to form lower alkylene to thereby form a ring); A: a lower alkylene or a group represented by -(lower alkylene)—O—; R1a and R1b: the same or different and each hydrogen or lower alkyl; R2: hydrogen or halogeno; and Z: nitrogen or a group represented by =CH—. The compounds are useful as a diabetes remedy which not only functions to both accelerate the secretion of insulin and enhance insulin sensitivity but has an antiobestic action and an antihyperlipemic action based on its selective stimulative action on a β3 receptor.
Azolidines as beta-3 adrenergic receptor agonists
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, (2008/06/13)
This invention provides compounds of Formula I having the structure wherein, A, X, Y, Z, W, R1, R2, R3, R4, R5, and R6 are as defined hereinbefore or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenetic inflammation, glaucoma, ocular hypertension and frequent urination; and are particularly useful in the treatment or inhibition of type II diabetes.
Potent, selective aminothiazolidinediones agonists of the human β3 Adrenergic receptor
Malamas,Largis,Gunawan,Li,Tillett,Han,Mulvey
, p. 164 - 177 (2007/10/03)
A cloned human β3 adrenergic receptor assay was used to identify potent and selective β3 agonists. The thiazolidinedione moiety has been identified as a new pharmacophore for the human β3 adrenergic receptor. The versatility of the thiazolidinedione pharmacophore was demonstrated in both the arylethanolamine and phenylpropanolamine families of β3 agonists, where potent and selective compounds have been synthesized. Thiazolidinedione 20, a potent and selective human β3 agonist, increased thermogenesis and lowered plasma glucose levels in the db/db mice.
