- Synthesis of 6-cinnamoyl-2H-benzo[b][1,4]oxazin-3(4H)-ones and their effects on A549 lung cancer cell growth
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A series of novel 6-cinnamoyl-2H-benzo[b][1,4]oxazin-3(4H)-one derivatives was synthesized. The structures of compounds were characterized by 1H NMR, IR, and MS. Moreover, representative crystal structure was determined by X-ray diffraction ana
- Zhou, Xue-Wen,Ma, Han-Lin,Zhang, Xuan,Jing, Shi-Yao,Miao, Jun-Ying,Zhao, Bao-Xiang
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- Identification of benzoxazin-3-one derivatives as novel, potent, and selective nonsteroidal mineralocorticoid receptor antagonists
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Mineralocorticoid receptor (MR) blockade has come into focus as a promising approach for the treatment of cardiovascular diseases such as hypertension and congestive heart failure. In order to identify a novel class of nonsteroidal MR antagonists that exhibit significant potency and good selectivity over other steroidal hormone receptors, we designed a novel series of benzoxazin-3-one derivatives and synthesized them from 6-(7H-[1,2,4]triazolo[3,4-b][1,3,4] thiadiazin-6-yl)-2H-1,4-ben-zoxazin-3(4H)-one (1a), high-throughput screening (HTS) hit compound. Our design was based on a crystal structure of an MR/compound complex and a docking model. In the course of lead generation from 1a, a 1,2-diaryl framework was characterized as a key structure with high binding affinity. On the basis of scaffold hopping and optimization studies, benzoxazin-3-one derivatives possessing 1-phenyl-3-trifluoromethylpyrazol-5-yl moiety at the 6-position were identified as a novel series of potent and selective MR antagonists. Among these compounds, 6-[1-(4-fluoro-2-methylphenyl)- 3-(trifluoromethyl)-1H-pyrazol-5-yl]-2H-1,4-benzoxazin-3(4H)-one (14n) showed highly potent activity and good selectivity and also exhibited a significant antihypertensive effect in deoxycorticosterone acetate-salt hypertensive rats. On the basis of these results, compound 14n was progressed for further pharmacological evaluation. (Figure presented)
- Hasui, Tomoaki,Matsunaga, Nobuyuki,Ora, Taiichi,Ohyabu, Norio,Nishigaki, Nobuhiro,Imura, Yoshimi,Igata, Yumiko,Matsui, Hideki,Motoyaji, Takashi,Tanaka, Toshimasa,Habuka, Noriyuki,Sogabe, Satoshi,Ono, Midori,Siedem, Christopher S.,Tang, Tony P.,Gauthier, Cassandra,De Meese, Lisa A.,Boyd, Steven A.,Fukumoto, Shoji
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experimental part
p. 8616 - 8631
(2012/02/14)
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- FUSED HETEROCYCLIC COMPOUND AND USE THEREOF
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The present invention relates to wherein each symbol is as defined in the specification. The compound has a superior mineral corticoidreceptorantagonistic action and is useful as an agent for the prophylaxis or treatment of hypertension, cardiac failure and the like, a compound having a fused heterocycle, or a prodrug thereof, or a salt thereof; and an agent for the prophylaxis or treatment of hypertension, cardiac failure and the like.
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Page/Page column 248-249
(2008/06/13)
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- Synthesis of 6-(1,5-Benzothiazepinyl/pyridyl)-2H-[1,4]-benzoxazin-3[4H]- ones from 6-Acetyl-2H-[1,4]-benzoxazin-3(4H)-ones
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A series of 6-(2,3-dihydro-1,5-benzothiazepinyl/pyridyl)-2H-[1,4]- benzoxazin-3[4H]-ones (3a-d & 4a-h) have been synthesized from 1-(3-oxo-[1,4]-benzoxazin-6-yl) 3- arylpropen-1-ones (2a-d).
- Reddy, G. Jagath,Thirupathaiah,Rao, K. Srinivasa,Khalilullah
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