- Piperazine compounds
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A compound selected from those of formula (I): wherein: R1, R2, R3 and R4, which may be the same or different, each represent an atom or group selected from hydrogen, halogen, alkyl, alkoxy, phenyl and cyano, X represents a bond, an oxygen atom or a group selected from —(CH2)m—, —OCH2— and —NR5—, wherein m represents 1 or 2, and R5 is as defined in the description, Y represents an oxygen atom or a group selected from NR7 and CHR8, wherein R7 and R8 are as defined in the description, Z represents a nitrogen atom or a CH group, n represents 1 or 2, Ak represents an alkylene chain, Ar represents an aryl or heteroaryl group, its optical isomers, and addition salts thereof with a pharmaceutically acceptable acid. Medical products containing the same which are useful in the treatment of conditions requiring a serotonin reuptake inhibitor and/or NK1 antagonist.
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Page/Page column 10
(2008/06/13)
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- Practical and environmentally friendly epoxidation of olefins using Oxone
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A practical and efficient epoxidation of aromatic olefins using Oxone in a two-phase system (ethyl acetate - water) is described. The reported method is suitable for large-scale synthesis and does not require phase transfer catalyst (PTC) or pH control.
- Hashimoto, Norio,Kanda, Atsushi
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p. 405 - 406
(2013/09/06)
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- New platelet fibrinogen receptor glycoprotein IIb-IIIa antagonists: Orally active series of N-alkylated amidines with a 6,6-bicyclic template
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The design, synthesis, and pharmacological evaluation of (S)-(-)-ethyl [6-[4-(morpholino-formimidoyl)benzamido]-3,4-dihydro-2H-1-benzopyran-3- yl]acetate hydrochloride ((S)-4·HCl, MS-180), an orally active glycoprotein IIb-IIIa (GPIIb-IIIa) antagonist, are reported. Pharmacophore mapping of amidino and carboxyl groups of already known GPIIb-IIIa antagonists led to the synthesis of nine amidino acids containing 6,6-bicyclic ring skeletons (10a-i). Among them, the compounds 10a,c,e having an amide bond and 1,2,3,4- tetrahydronaphthalene or 3,4-dihydro-2H-1-benzopyran skeleton showed marked inhibitions with IC50 values of 46-57 nM in human platelet aggregation assay in vitro, but low oral activities. N-Alkylation of the amidino group coupled with the ester prodrug approach afforded MS-180 ((S)-4·HCl), which generates in vivo the corresponding carboxylic acid (S)-3 as an active species. In vitro, (S)-3 inhibited ADP-induced aggregation of guinea pig, dog, and human platelets (IC50 = 110, 253, and 35 nM, respectively) and inhibited the binding of fibrinogen to immobilized GPIIb-IIIa of human platelets (IC50 = 0.12 nM). After oral administration of MS-180 ((S)4·HCl) to fasted beagle dog, ex vivo inhibition of platelet aggregation was observed. The maximal inhibitions were observed 2-4 h after dosing with dose dependency (60% inhibition at a dose of 1 mg/kg, 85% at 3 mg/kg, and 100% at 10 mg/kg, respectively) and the extent of the inhibitions paralleled the plasma concentration of the active species (S)-3. On the basis of these studies, we selected MS-180 ((S)-4·HCl) as a candidate for clinical evaluation as a drug for the treatment and prevention of thrombosis in patients.
- Okumura, Kunio,Shimazaki, Toshiyuki,Aoki, Yoji,Yamashita, Hiroyuki,Tanaka, Eishi,Banba, Shinichi,Yazawa, Kouhei,Kibayashi, Kenji,Banno, Hitoshi
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p. 4036 - 4052
(2007/10/03)
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- Synthesis and Dopaminergic Activity of 2-Substituted Octahydrobenzoquinolines
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A series of 2-substituted octahydrobenzoquinolines has been synthesized and assayed for dopamine agonist activity.Only the compounds corresponding to the β-rotameric conformation of dopamine showed biphasic activity in competition binding studies with the radioligand spiroperidol.These findings suggest that the congeners possessing the β-rotamer conformation show receptor-binding characteristics that resemble those of the ergolines more closely than do those of the corresponding α-rotamer congeners.
- Craig, J. Cymerman,Torkelson, Steven M.,Findell, Paul R.,Weiner, Richard I.
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p. 961 - 968
(2007/10/02)
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