- Tolvaptan-Type Vasopressin Receptor Ligands: Important Role of Axial Chirality in the Active Form
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The anti and syn isomers of tolvaptan-type compounds, N-benzoyl-5-hydroxy-1-benzazepines (5a-c), were prepared in a stereocontrolled manner by biasing the conformation with a methyl group at C9 and C6, respectively, and the enantiomeric forms were separat
- Tabata, Hidetsugu,Yoneda, Tetsuya,Oshitari, Tetsuta,Takahashi, Hideyo,Natsugari, Hideaki
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p. 4503 - 4509
(2017/06/05)
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- Preparation method of conivaptan hydrochloride
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The invention discloses a preparation method of conivaptan hydrochloride. The preparation method includes: taking aniline (compound I) as a raw material which is subjected to amidation, alkylation, friedel-crafts acylation, nitro reduction, amidation, alpha-chloro, cyclization and salt-forming reaction to obtain the conivaptan hydrochloride. With the method, the aniline is taken as the raw material easy to obtain, and toxic substances of acyl chloride and the like are avoided during amidation. The entire synthesis process is small in pollution and easy to process with the brand new synthesis theory, and reaction conditions of procedures are moderate; the preparation method is moderate in reaction condition of each procedure, simple in operation, high in yield and purity, environment friendly, low in production cost and suitable in industrial production.
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- Practical Synthesis of N-{4-[(2-Methyl-4,5-dihydroimidazo[4,5-d][1] benzazepin-6(1H)-yl)carbonyl]phenyl}biphenyl-2-carboxamide Monohydrochloride: An Arginine Vasopressin Antagonist
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A novel, reliable, and cost-effective synthetic route to N-{4-[(2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl)carbonyl] -phenyl}biphenyl-2-carboxamide monohydrochloride (1, YM087), a potent Arginine vasopressin antagonist, has been developed. Using moisture-controlled potassium carbonate, imidazole formation from α-bromoketone furnished imidazobenzazepine, avoiding potential oxazole-ring formation. Catalytic reduction of nitro imidazobenzazepine afforded the corresponding amine in high yields. Treatment of the imidazole-containing amine directly, with a carbonyl chloride, afforded the target amide circumventing protection of the imidazole.
- Tsunoda, Takashi,Yamazaki, Atsuki,Iwamoto, Hidenori,Sakamoto, Shuichi
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p. 883 - 887
(2013/09/05)
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- Condensed benzazepine derivative and pharmaceutical composition thereof
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This invention relates to nitrogen-containing aromatic 5-membered ring-condensed benzazepine derivatives represented by the general formula (I) STR1 (symbols in the formula have the following meanings; ring B: a nitrogen-containing aromatic 5-membered ring having at least 1 nitrogen atom and optionally one oxygen or sulfur atom, which may optionally have substituent(s), R1 and R2 : these may be the same or different from each other and each represents a hydrogen atom, a halogen atom, a lower alkyl group, an amino group which may optionally be substituted by lower alkyl group(s), or a lower alkoxy group, A: a single bond; a group represented by the formula n: 0 or an integer of from 1 to 3, R3 and R4 : these may be the same or different from each other and each represents a hydrogen atom, a lower alkyl group (provided that R3 and R4 may together form a lower alkylene group having 2 to 7 carbon atoms), and ring C: a benzene ring which may optionally have substituent(s)) and salts thereof; to pharmaceutical compositions which contain these compounds as an active ingredient and to intermediates which are useful in synthesizing these compounds. The compounds of this invention are useful as arginine vasopressin antagonists.
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- BENZOHETEROCYCLIC COMPOUNDS
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Novel benzoheterocyclic compounds of the formula: STR1 wherein R. sup.1 is H, halogen, alkyl, optionally substituted amino, alkoxy; R 2 is H, halogen, alkoxy, phenyialkoxy, OH, alkyl, optionally substituted amino, carbamoyl-alkoxy, optionally substituted
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- Orally active, nonpeptide vasopressin V2 receptor antagonists: A novel series of 1-[4-(benzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepines and related compounds
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This paper describes a novel series of nonpeptide vasopressin V2 receptor antagonists. It has been demonstrated that the 1-[4- (benzoylamino)benzoyl]-2,3,4,5-1H-benzazepines and 1-[4- (benzoylamino)benzoyl]-2,3,4,5-1H-1,5-benzodiazepines show a high affinity for V2 (and V(1a)) receptors. Among the 1-[4-(benzoylamino)benzoyl]-2,3,4,5- 1H-benzazepine series, compounds with an alkylamino group on the benzazepine ring have been shown to have oral activity. A lipophilic group at the ortho position on the terminal benzoyl ring is important for both high V2 receptor affinity and oral activity. On the basis of these favorable properties, clinical testing of 31b has begun for use as an oral and iv aquaretic agent.
- Ogawa, Hidenori,Yamashita, Hiroshi,Kondo, Kazumi,Yamamura, Yoshitaka,Miyamoto, Hisashi,Kan, Keizo,Kitano, Kazuyoshi,Tanaka, Michinori,Nakaya, Kenji,Nakamura, Shigeki,Mori, Toyoki,Tominaga, Michiaki,Yabuuchi, Youichi
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p. 3547 - 3555
(2007/10/03)
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