31456-94-7Relevant articles and documents
AMINO PYRAZOLONE DERIVATIVE HAVING CONDENSED RING STRUCTURE
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Paragraph 0176; 0177; 0178, (2016/10/08)
PROBLEM TO BE SOLVED: To provide a compound that has excellent inhibitory action on ATPase activity of TIP48/TIP49 complex and is therefore useful for the treatment of tumor, or a pharmacologically acceptable salt thereof. SOLUTION: The present invention provides a compound having a structure represented by general formula (I), its pharmacologically acceptable salt, or a pharmaceutical composition comprising the compound (where R3, R4, R5, R6, R7, W, X, Y, and Z are as defined in the specifications). SELECTED DRAWING: None COPYRIGHT: (C)2016,JPOandINPIT
AMINOPYRAZOLONE DERIVATIVE
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Paragraph 0216, (2017/01/05)
The present invention is intended to provide a compound or a pharmacologically acceptable salt thereof which has an excellent inhibitory action on the ATPase activity of a TIP48/TIP49 complex and as such, is useful for the treatment of tumors. [Solution] The present invention provides a compound having a structure represented by the general formula (I) or a pharmacologically acceptable salt thereof, and a pharmaceutical composition comprising the compound. In the formula, R1, R2, R3, R4, R5, R6, R7, and W are as defined in the present specification.
Zatosetron, a Potent, Selective, and Long-Acting 5HT3 Receptor Antagonist: Synthesis and Structure-Activity Relationships
Robertson, David W.,Lacefield, William B.,Bloomquist, William,Pfeifer, William,Simon, Richard L.,Cohen, Marlene L.
, p. 310 - 319 (2007/10/02)
Antagonists of 5HT3 receptors are clinically effective in treating nausea and emesis associated with certain oncolytic drugs, including cisplatin.Moreover, these agents may be useful in pharmacological management of several central nervous system disorders, including anxiety, schizophrenia, dementia, and substance abuse.Our studies on aroyltropanamides led to the discovery that dihydrobenzofuranyl esters and amides are potent 5HT3 receptor antagonists.Simple benzoyl derivatives of tropine and 3α-aminotropane possessed weak 5HT3 receptor antagonist activity, as judged by blockade of bradycardia produced by iv injection of serotonin (5HT) to anesthetized rats.Within this series, use of benzofuran-7-carboxamide as the aroyl moiety led to a substantial increase of 5HT3 receptor affinity.The optimal 5HT3 receptor antagonist identified via extensive SAR studies was endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(8-methyl-8-azabicyclooct-3-yl)-7-benzofurancarboxamide (Z)-2-butenedioate (zatosetron maleate).The 7-carbamyl regiochemistry, dimethyl substitution, chloro substituent, and endo stereochemistry were all crucial elements of the SAR.Zatosetron maleate was a potent antagonist of 5HT-induced bradycardia in rats (ED50=0.86 μg/kg iv).Low oral doses of zatosetron (30 μg/kg) produced long-lasting antagonism of 5HT3 receptors, as evidenced by blockade of 5HT-induced bradycardia for longer than 6 h in rats.Moreover, this compound did not produce hemodynamic effects after iv administration to rats, nor did it block carbamylcholine-induced bradycardia in doses that markedly blocked 5HT3 receptors.Thus, zatosetron is a potent, selective, orally effective 5HT3 receptor antagonist with a long duration of action in rats.
