Synthesis and evaluation of 1-arylsulfonyl-3-piperazinone derivatives as factor Xa inhibitors(1-6) VI. A series of new derivatives containing N,S- and N,SO2-spiro acetal scaffolds.
In the course of development of factor Xa (FXa) inhibitors, we have found unique compounds containing an N,O- and an N,N-spiro acetal structure. It appeared that the difference in overall conformation due to the N,X-spiro acetal structure might be important for FXa inhibitory activity. Therefore, other N,X-spiro acetal structures, an N,S- and an N,SO2-spiro acetal, were developed as analogues of the N,X-spiro acetal structure. Compound 7b (N,S-spiro acetal structure) was found to have the strongest activity in these series of N,X-spiro acetal compounds, which had ever been synthesized.(4,5)).
Saitoh
Fumihiko
F
Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan. fsaitoh@mochida.co.jp
Nishida
Hidemitsu
H
Mukaihira
Takafumi
T
Kosuga
Naoto
N
Ohkouchi
Munetaka
M
Matsusue
Tomokazu
T
Shiromizu
Ikuya
I
Hosaka
Yoshitaka
Y
Matsumoto
Miwa
M
Yamamoto
Ichiro
I
D000080:Acetals / Q000737:chemistry*; D000925:Anticoagulants / Q000494:pharmacology; D000990:Antithrombin III / Q000138:chemical synthesis* / Q000494:pharmacology; D008968:Molecular Conformation; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry*; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology
D000080:Acetals; D000925:Anticoagulants; D010880:Piperidines; D015842:Serine Proteinase Inhibitors; D013141:Spiro Compounds; D000990:Antithrombin III; D009584:Nitrogen; D010100:Oxygen