A scalable synthesis of (R)-3-(2-aminopropyl)-7-benzyloxyindole via resolution

Fujii, Akihito; Fujima, Yoshito; Harada, Hiroshi; Ikunaka, Masaya; Inoue, Toru; Kato, Shiro; Matsuyama, Kiichi

doi:10.1016/s0957-4166(02)00004-6

Cited by 18 publications

(23 citation statements)

References 8 publications

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“…1, B and C) was synthesized using a combination of several published methods. The racemic tryptamine moiety (R,S-3) was synthesized and resolved into the desired individual enantiomer (R-3), according to a previous method (Fujii et al, 2001), and was then successfully converted to the free base (4) using a method described previously (Harada et al, 2004). Ring-opening of (R)-chlorostyrene oxide with the chiral amine, followed by treatment with aqueous NaOH, provided the compound TAK-677 as described previously by the Dainippon Pharmaceuticals Co. (Osaka, Japan) (Harada et al, 2005).…”

Section: Methodsmentioning

confidence: 99%

Effects of β₃-Adrenergic Receptor Activation on Rat Urinary Bladder Hyperactivity Induced by Ovariectomy

Kullmann¹,

Limberg²,

Artim³

et al. 2009

J Pharmacol Exp Ther

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Voiding dysfunctions, including increased voiding frequency, urgency, or incontinence, are prevalent in the postmenopausal population. ␤ 3 -Adrenergic receptor (␤ 3 AR) agonists, which relax bladder smooth muscle, are being developed to treat these conditions. We utilized the rat ovariectomy (OVX) model to investigate the effect of ovarian hormone depletion on bladder function and the potential for ␤ 3 AR agonists to treat bladder hyperactivity in this setting. OVX increased voiding frequency and decreased bladder capacity by ϳ25% in awake rats and induced irregular cystometrograms in urethane-anesthetized rats. Reverse transcription-polymerase chain reaction revealed three ␤ARs subtypes (␤ 1,2,3 ) in bladder tissue, and immunostaining indicated ␤ 3 AR localization in urothelium and detrusor. Receptor expression was not different in OVX and SHAM rats. ]amino]-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]oxy], ethyl ester, hydrochloride] was confirmed by examining the relative potency for elevation of cAMP in CHOK1 cells overexpressing the various rat ␤ARs. Intravenous injection of each of the ␤ 3 AR agonists (0.1-500 g/kg) in anesthetized rats decreased voiding frequency, bladder pressure, and amplitude of bladder contractions. In bladder strips, ␤ 3 AR agonists (10 Ϫ12-10 Ϫ4 M) decreased baseline tone and reduced spontaneous contractions. BRL37344 (5 mg/kg) and TAK-677 (5 mg/kg) injected intraperitoneally in awake rats decreased voiding frequency by 40 to 70%. These effects were not altered by OVX. The results indicate that OVX-induced bladder dysfunction, including decreased bladder capacity and increased voiding frequency, is not associated with changes in ␤ 3 AR expression or the bladder inhibitory effects of ␤ 3 AR agonists. This suggests that ␤ 3 AR agonists should prove effective for the treatment of overactive bladder symptoms in the postmenopausal population.Lower urinary tract (LUT) dysfunctions, including increased voiding frequency, urgency, incontinence and nocturia, increase in the elderly population and following menopause (Stewart et al., 2003). These dysfunctions could result from hormonally induced changes in bladder contractile and/or relaxing mechanisms. Bladder contractions are triggered by parasympathetic nerves, which release ACh that in turn activates postjunctional muscarinic receptors (mAChRs) in the detrusor. Bladder relaxation is induced by release of norepinephrine from sympathetic nerves, which activates ␤-adrenergic receptors (␤AR) (Fowler et al., 2008

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Section: Methodsmentioning

confidence: 99%

Effects of β₃-Adrenergic Receptor Activation on Rat Urinary Bladder Hyperactivity Induced by Ovariectomy

Kullmann¹,

Limberg²,

Artim³

et al. 2009

J Pharmacol Exp Ther

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“…Most of the synthetic routes for the preparation of carbolines involve ring -closure of their tryptamine precursors in PictetSpengler reactions. These tryptamine systems can be prepared by nitroaldol reactions/eliminations starting from indole carbaldehydes and nitroalkanes (Scheme 3.62 ) [124,125] . The obtained nitroalkenes can be completely reduced to the tryptamines by complex hydrides.…”

Section: Carbolines and Their Tryptamine Precursorsmentioning

confidence: 99%

Nitroalkenes as Amination Tools

Ballini

Marcantoni

Petrini

2007

Amino Group Chemistry

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“…The hydroxy-indole derivative is an important building block in the synthesis of pharmaceuticals, dye compounds, and chemicals (Fujii et al, 2001;Gartz, 1989). Gathergood and Scamel (2003), and Bartoli et al (1989) reported the synthesis of 4-hydroxy-tryptamine scaffold and 7-hydroxy-tryptamine, respectively.…”

Section: Introductionmentioning

confidence: 99%

Biotransformation of Indole Derivatives by Mycelial Cultures

Alarcón

Cid²,

Lillo³

et al. 2008

Zeitschrift Für Naturforschung C

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A scalable synthesis of (R)-3-(2-aminopropyl)-7-benzyloxyindole via resolution

Cited by 18 publications

References 8 publications

Effects of β₃-Adrenergic Receptor Activation on Rat Urinary Bladder Hyperactivity Induced by Ovariectomy

Effects of β₃-Adrenergic Receptor Activation on Rat Urinary Bladder Hyperactivity Induced by Ovariectomy

Nitroalkenes as Amination Tools

Biotransformation of Indole Derivatives by Mycelial Cultures

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A scalable synthesis of (R)-3-(2-aminopropyl)-7-benzyloxyindole via resolution

Cited by 18 publications

References 8 publications

Effects of β3-Adrenergic Receptor Activation on Rat Urinary Bladder Hyperactivity Induced by Ovariectomy

Effects of β3-Adrenergic Receptor Activation on Rat Urinary Bladder Hyperactivity Induced by Ovariectomy

Nitroalkenes as Amination Tools

Biotransformation of Indole Derivatives by Mycelial Cultures

Contact Info

Product

Resources

About

Effects of β₃-Adrenergic Receptor Activation on Rat Urinary Bladder Hyperactivity Induced by Ovariectomy

Effects of β₃-Adrenergic Receptor Activation on Rat Urinary Bladder Hyperactivity Induced by Ovariectomy