- Chemoselective and Kilogram-Scale Synthesis of Acetanilide β3-Adrenergic Receptor Agonist
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We describe an alternative route for the synthesis of β3-adrenergic receptor agonist (S)-2-(2-phenylamino-1,3- thiazol-4-yl)-4′-{2-[(2-hydroxy-3-phenoxypropyl)amino]ethyl}acetanilide (1). The key intermediate (S)-1-{[2-(4-aminophenyl)ethyl]amin
- Kawazoe, Souichirou,Suzuki, Takayuki,Nakamura, Hirofumi,Sugimori, Toshiyuki,Onda, Kenichi,Maruyama, Tatsuya,Okada, Minoru
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- Synthesis and evaluation of novel phenoxypropanolamine derivatives containing acetanilides as potent and selective β3-adrenergic receptor agonists
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In the search for potent and selective human β3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, a novel series of phenoxypropanolamine derivatives containing acetanilides were prepared and their biological activities were evaluated at the human β3-, β2-, and β1-ARs. Several of the analogues (21a, 21b, and 27a) exhibited potent agonistic activity at the β3-AR. Among the compounds described herein, the N-methyl-1-benzylimidazol-2-ylacetanilide derivative (21b) was found to be the most potent and selective β3-AR agonist, with an EC50 value of 0.28 μM and no agonistic activity for either the β1- or β2-AR. In addition, 21b showed significant hypoglycemic activity in a rodent diabetic model.
- Maruyama, Tatsuya,Onda, Kenichi,Hayakawa, Masahiko,Seki, Norio,Takahashi, Takumi,Moritomo, Hiroyuki,Suzuki, Takayuki,Matsui, Tetsuo,Takasu, Toshiyuki,Nagase, Itsuro,Ohta, Mitsuaki
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experimental part
p. 3283 - 3294
(2009/09/08)
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- Azolidines as beta-3 adrenergic receptor agonists
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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.
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- Amide derivatives and medicinal compositions thereof
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PCT No. PCT/JP98/00237 Sec. 371 Date May 7, 1999 Sec. 102(e) Date May 7, 1999 PCT Filed Jan. 22, 1998 PCT Pub. No. WO98/32742 PCT Pub. Date Jul. 30, 1998An amide derivative represented by the following general formula (I) or a salt thereof and a pharmaceutical composition containing the amide derivative and a pharmaceutically acceptable vehicle. (The symbols in the formula have the following meanings. (wherein A: heteroarylene; X: bond, O, S, -NR5-, -NR5CO-, -NR5CONH-, -NR5SO2- or -NR5C(=NH)NH-; R1: -H, -optionally substituted lower alkyl, -optionally substituted aryl, -optionally substituted heteroaryl or -optionally substituted cycloalkyl; R2a, R2b: -H or -lower alkyl, which may be the same or different; R3: -H or -lower alkyl; R4a, R4b: -H or -OH, which may be the same different, or R4a and R4b are taken together to form =O or =N DIFFERENCE O-lower alkyl; and R5: -H or -lower alkyl.
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