- Discovery of a novel bicyclic compound, DS54360155, as an orally potent analgesic without mu-opioid receptor agonist activity
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We synthesized derivatives of a natural alkaloid, conolidine, and evaluated these derivatives in the acetic acid-induced writhing test and formalin test in ddY mice after oral administration. As a result, we identified (5S)-6-methyl-1,3,4,5,6,8-hexahydro-7H-2,5-methano[1,5]diazonino[7,8-b]indol-7-one sulfate salt, 15a (DS54360155), with a unique and original bicyclic skeleton, as an analgesic more potent than conolidine. Moreover, 15a did not exhibit mu-opioid receptor agonist activity.
- Arita, Tsuyoshi,Asano, Masayoshi,Kubota, Kazufumi,Domon, Yuki,Machinaga, Nobuo,Shimada, Kousei
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supporting information
(2019/11/11)
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- METHOD FOR PRODUCTION OF OPTICALLY ACTIVE 3-AMINO-NITROGENATED COMPOUND
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Aiming at production of an optically active 3-amino nitrogen-containing compound which is useful as an intermediate in synthesis of medicines and pesticides, in particular, an optically active 1-protected-3-aminopyrrolidine derivative, from an inexpensive and readily available raw material by a process which is efficient and can be practiced industrially, an optically active 3-amino nitrogen-containing compound is produced by performing a reaction of an optically active 3-substituted nitrogen-containing compound with ammonia, methylamine, ethylamine or dimethylamine in the presence of water. In addition, a 1-protected-3-aminopyrrolidine derivative is produced by performing a reaction of an optically active 1-protected-3-(sulfonyloxy)pyrrolidine derivative with ammonia, methylamine, ethylamine, or dimethylamine in the presence of methanol, ethanol, n-propanol, or isopropanol under a pressure of less than 30 barr.
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Page/Page column 20
(2009/05/29)
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- Azetidine, pyrrolidine and piperidine derivatives as 5-HT receptor agonists
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PCT No. PCT/GB97/01137 Sec. 371 Date Oct. 14, 1998 Sec. 102(e) Date Oct. 14, 1998 PCT Filed Apr. 24, 1997 PCT Pub. No. WO97/42189 PCT Pub. Date Nov. 13, 1997A class of compounds of formula (I) wherein Z, E, Q, T, U, V, W, M, R1, R7 and R8 are as defined herein; are selective agonists of 5-HT1-like receptors, being potent agonists of the human 5-HT1D alpha receptor subtype whilst possessing at least a 10-fold selective affinity for the 5-HT1D alpha receptor subtype relative to the 5-HT1D beta subtype; they are therefore useful in the treatment and/or prevention of clinical conditions, in particular migraine and associated disorders, for which a subtype-selective agonist of 5-HT1D receptors is indicated, whilst eliciting fewer side-effects, notably adverse cardiovascular events, than those associated with non-subtype-selective 5-HT1D receptor agonists.
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