191591-55-6Relevant academic research and scientific papers
Pyrroloazepine compounds
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, (2008/06/13)
Disclosed are pyrroloazepine compounds and their salts. These pyrroloazepine compounds are represented by formula (I) wherein the dashed line indicates the presence or absence of a bond; and, when the bond is present, Z2is not present and Z1is H but, when the bond is absent, Z1and Z2are both Hs; Z1is H and Z2is OH; Z1and Z2are both SR5s in which R5is alkyl, aralkyl or aryl; or Z1and Z2are combined together to represent O, NOR6in which R6is H, alkyl, aralkyl or aryl, or C2-C3alkylenedithio; R is H, alkyl, cycloalkyl, cycloalkyl alkyl or aralkyl; and the ring P is a specific pyrrole ring. These pyrroloazepine compounds and salts are effective as preventives or therapeutics for general circulatory diseases such as hypertension, heart failure, ischemic hear diseases, cerebrovascular disturbances and peripheral circulatory disturbances. Their production processes are also disclosed
Pyrroloazepine derivatives
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, (2008/06/13)
A method for treating a circulatory disease or condition in a mammal, which entails administering to the mammal an effective amount of a compound of the formula (I) or a pharmaceutically acceptable salt thereof: wherein the ring P represented by ?is a pyrrole ring having the following structure: wherein R1represents C1-C8alkyl, C3-C8cycloalkyl, C4-C8cycloalkyl-alkyl, C6-C14aryl or C7-C22aralkyl, which are optionally substituted; and R2represents H or C1-C8alkyl, which is optionally substituted; the dashed line indicates the presence or absence of a bond; and, when the bond is present, Z2is not present and Z1represents H, but, when the bond is absent, Z1and Z2are both H; Z1represents H and Z2represents a group OR3, in which R3represents H, C1-C8alkyl, or C7-C22aralkyl, which are optionally substituted; Z1and Z2both represent groups SR4, in which R4represents C1-C8alkyl or C7-C22aralkyl, which are optionally substituted; or Z1and Z2are combined together to represent O, a group NOR5, in which R5represents H, or C1-C8alkyl or C2-C3alkylenedithio, which are optionally substituted; A represents alkylene, alkenylene or alkynylene; and Y represents a group in which W is CH, C═ or N, m is for 0 or 1, n is for 1, 2 or 3, G is O, S, C═O, sulfinyl, sulfonyl, alkylene, alkenylene or acetal; E1and E2is H or C1-C8alkyl; and D represents an aromatic hydrocarbon or an aromatic heterocyclic ring. The compound (I) has strong serotonin-2 receptor antagonistic action and low toxicity and less side effects, and is therapeutically useful in the treatment of circulatory diseases and/or conditions related thereto.
Synthesis and serotonin 2 (5-HT2) receptor antagonist activity of 5- aminoalkyl-substituted pyrrolo [3,2-c]azepines and related compounds
Mizuno, Akira,Ogata, Atsuto,Kamei, Tomoe,Shibata, Makoto,Shimamoto, Tetsuo,Hayashi, Yasuhiro,Nakanishi, Kyoko,Takiguchi, Chikako,Oka, Naomi,Inomata, Norio
, p. 623 - 635 (2007/10/03)
A series of 5-aminoalkylpyrrolo[3,2,c]azepine derivatives was synthesized and their serotonin 2 (5-HT2) receptor antagonist and antiplatelet aggregation activities were evaluated. 5-HT2 receptor antagonist activity was largely determined by the nature of the substituent at the 8-position as well as the aminoalkyl group at the 5-position of the pyrrolo[3,2-c]azepine ring. Compound 18a, 5-[3-[4-(4-(4- fluorophenyl)piperazin-1-yl]propyl]-8-hydroxy-1-methyl-1,4,5,6,7,8- hexahydropyrrolo[3,2-c]azepin-4-one, was recognized as having potent 5-HT2 receptor antagonist activity with weak α1 adrenoceptor blocking activity and no significant D2 receptor binding affinity, while the corresponding isomeric pyrrolo[3,4-c]azepine derivative (22) displayed only weak 5-HT2 receptor antagonist activity. After racemic 18a was resolved directly via diastereomeric salt formation, each enantiomer was evaluated precisely. The 5-HT2 receptor antagonist activity of 18a was found to reside primarily in (-)-18a (which was about 14-fold more potent than (+)-18a in isolated guinea pig arteries). Consequently, (S)-(-)-18a (SUN C5174)displayed the overall best profile with potent 5-HT2 receptor antagonist activity (pA2 = 8.98 ± 0.06) and high selectivity versus other receptors. SUN C5174 showed a marked inhibitory effect on the platelet aggregation induced by serotonin in combination with collagen and adenosine diphosphate (ADP) in canine or human platelet-rich plasma (IC50 = 6.5 to 16 nM). Moreover, this compound significantly inhibited the mortality rate in mouse acute pulmonary thromboembolitic death induced by collagen and serotonin at oral doses of 0.3 mg/kg or higher. SUN C5174 is currently undergoing clinical evaluation.
Pyrroloazepine derivatives
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, (2008/06/13)
A pyrroloazepine compound having the following formula (I): wherein the ring P represented by STR1 is a pyrrole ring having the following structure: STR2 wherein R1 represents C1 -C8 alkyl, C3 -C8 cycloalkyl, C4 -C8 cycloalkyl-alkyl, C6 -C14 aryl or C7 -C22 aralkyl, which are optionally substituted; and R2 represents H or C1 -C8 alkyl, which is optionally substituted; the dashed line indicates the presence or absence of a bond; and, when the bond is present, Z2 is not present and Z1 represents H, but, when the bond is absent, Z1 and Z2 are both H; Z1 represents H and Z2 represents a group OR3, in which R3 represents H, C1 -C8 alkyl, or C7 -C22 aralkyl, which are optionally substituted; Z1 and Z2 both represent groups SR4, in which R4 represents C1 -C8 alkyl or C7 -C22 aralkyl, which are optionally substituted; or Z1 and Z2 are combined together to represent O, a group NOR5, in which R5 represents H, or C1 -C8 alkyl or C2 -C3 alkylenedithio, which are optionally substituted; A represents alkylene, alkenylene or alkynylene; and Y represents a group in which W is CH, C= or N, m is for 0 or 1, n is for 1, 2 or 3, G is O, S, C=O, sulfinyl, sulfonyl, alkylene, alkenylene or acetal; E1 and E2 is H or C1 -C8 alkyl; and D represents an aromatic hydrocarbon or an aromatic heterocyclic ring. The compound (I) has strong serotonin-2 receptor antagonistic action and low toxicity and less side effects, and is therapeutically useful in the treatment of circulatory diseases and/or conditions related thereto.
