Syntheses of 3-acetoacetylaminobenzo[b]furan derivatives having cysteinyl leukotriene 2 receptor antagonistic activity

Ando, Kiyohiro; Tsuji, Emiko; Ando, Yoshio; Kuwata, Noriko; Kunitomo, Jun-ichi; Yamashita, Masayuki; Ohta, Shunsaku; Kohno, Shigekatsu; Ohishi, Yoshitaka

doi:10.1039/b312682j

Cited by 35 publications

(19 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SERMs are characterized by at least two common structural features, a phenolic hydroxyl group and a phenoxyethylamino group (phenyl-OCH 2 CH 2 N-). 14a,b,d We recently reported that the compound 4 15 prepared in our current studies displayed very potent anti-bone resorption activity in vitro and exhibits a potent anti-osteopenic effect in vivo. 14c It has also been suggested to influence the endometrial properties of SERMs in women by the antiestrogenic side chain.…”

Section: Introductionmentioning

confidence: 53%

“…16 Both the compound 4 15 and (E)-(8-bromo-(E)-2-aralkenylbenzo[b]furo[3,2d] [1,3]oxazin-4-ylidene)acetaldehydes (5) possess the phenoxyethenylamino moiety through the furan oxygen atom and the nitrogen atom. 16 Both the compound 4 15 and (E)-(8-bromo-(E)-2-aralkenylbenzo[b]furo[3,2d] [1,3]oxazin-4-ylidene)acetaldehydes (5) possess the phenoxyethenylamino moiety through the furan oxygen atom and the nitrogen atom.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Preparation of novel (Z)-4-ylidenebenzo[b]furo[3,2-d][1,3]oxazines and their biological activity

Tabuchi

Ando

Kanemura

et al. 2009

Bioorganic & Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

A reaction of 2-acetyl-3-acylaminobenzo[b]furans (9d-o) with Vilsmeier (VM) reagent afforded a mixture of (E)- and (Z)-{(E)-2-aralkenylbenzo[b]furo[3,2-d][1,3]oxazin-4-ylidene}acetaldehydes (5) with a characteristic exo-formylmethylene group on the oxazine ring. The Z-isomer was more stable than the E-isomer. The Z-isomers ((Z)-5) were reacted with phosphonate reagents under two different conditions to obtain various butadiene derivatives (12) containing benzo[b]furo[3,2-d][1,3]oxazine skeleton. Typical compounds (5 and 12) were evaluated for their anti-osteoclastic bone resorption activity, antagonistic activity for the cysLT1 receptor and growth inhibitory activity for MIA PaCa-2 and MCF-7. Compounds 12f and 12j showed potent anti-osteoclastic bone resorption activity comparable to E(2) (17beta-estradiol).

show abstract

Section: Introductionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Preparation of novel (Z)-4-ylidenebenzo[b]furo[3,2-d][1,3]oxazines and their biological activity

Tabuchi

Ando

Kanemura

et al. 2009

Bioorganic & Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…The two benzofurane and benzothiophene precursors ( 3 and 4 ) were obtained by methods previously described in the literature . Subsequently, 3‐amino‐2‐cyanobenzofurane 3 was prepared by treatment of 2‐hydroxybenzonitrile with bromoacetonitrile in dimethylformamide.…”

Section: Resultsmentioning

confidence: 99%

Efficient New Synthesis of N‐Arylbenzo[b]furo[3,2‐d]pyrimidin‐4‐amines and Their Benzo[b]thieno[3,2‐d]pyrimidin‐4‐amine Analogues via a Microwave‐Assisted Dimroth Rearrangement

Loidreau

Dubouilh-Benard

Marchand

et al. 2013

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

“…Biological Activity The benzo[b] furan compounds pre- Chart 2 pared in this work were evaluated for their cysLT1 and cysLT2 inhibitory activities by measuring their inhibition of agonist-induced calcium release according to the method reported by Nothacker. 11,12,32) Inhibitory activities of seven 2-thienylbenzo[b] furans (5b, d, 6a-e) were shown in Table 1. The 2-cyano-3-hydroxy-2-butenamide (6a) and the butyric acid 6b showed more than 40% inhibition of calcium mobilization in cysLT1 cells.…”

Section: Preparation Of 2-isoxazolylbenzo[b] Furans (9-12)mentioning

confidence: 99%

“…4) However, no selective cysLT2 antagonist has yet been developed for clinical applications. Recently, increased expression of cysLT2 receptor has been reported in colon cancer 9) and myocardial ischemia-reperfusion injury.10) The development of a dual antagonist and/or selective cysLT2 antagonist should be of great therapeutic value.In previous papers, we reported the preparation of sev-furan derivatives (A) and their cysLT1 and cysLT2 inhibitory activities 11,12) (Fig. 2).…”

mentioning

confidence: 99%

Preparation of Benzo[<i>b</i>]furans Having Five-Membered Heterocycles at the 2-Position and 2-(4-Alkylcarbamoylbuta-1,3-dienyl)benzo[<i>b</i>]furans, and Their Cysteinyl Leukotriene Receptor (cysLT1, cysLT2) Inhibitory Activity

Akai

Tabuchi

Ando

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

1-5) CysLTs mediate their effects through two different receptors, cysLT1 and cysLT2. 6) CysLT1 selective antagonists, such as pranlukast, montelukast and zafirlukast, have been shown to be clinically beneficial against chronic asthma. However, the synthesis of cysLT1 and/or cysLT2 antagonist still remains challenging. BAY u9773 was reported to be a dual cysLT1 and cysLT2 antagonist and a partial agonist of cysLT2.7,8) DUO-LT was also shown to be a dual antagonist (Fig. 1). 4) However, no selective cysLT2 antagonist has yet been developed for clinical applications. Recently, increased expression of cysLT2 receptor has been reported in colon cancer 9) and myocardial ischemia-reperfusion injury.10) The development of a dual antagonist and/or selective cysLT2 antagonist should be of great therapeutic value.In previous papers, we reported the preparation of sev-furan derivatives (A) and their cysLT1 and cysLT2 inhibitory activities 11,12) (Fig. 2). In our current work on leukotriene, we found that (E)-(2-diethylcarbamoyl-1-methylvinyl)-benzo [b] furans (B) showed potent leukotoriene B 4 (LTB 4 ) inhibitory activity, 13,14) and that compound (C) showed more potent LTB 4 inhibitory activity than compounds B. 15,16) In this time, in order to increase the inhibitory activity of the cycLTs receptor, acidic and amide moieties were introduced to the benzo [b] furan skeleton on the compound D on the basis of the structure of the compounds A and characteristic cysLTs molecular structures (Fig. 3). In addition, 2-(4-alkylcarbamoylbuta-1,3-dienyl) benzo [b] furans (E) having a wide range of conjugated systems were also prepared. In our design of compounds D and E, the structure of LTC 4 could be divided into the lipophilic, acidic and amide moieties. In the design of compound D, the benzo[b] furan ring having a fivemembered heterocyclic ring at the 2-position, the 4-oxypropanoic acid and the amide group on the heterocycle could be considered to correspond to the lipophilic, acidic and amide moieties in LTC 4 , respectively. Compound E was designed in the same manner as compound D, as shown in Fig. 3. Here Note * To whom correspondence should be addressed. e-mail: ikuo_k@mukogawa-u.ac.jp; nishide@mukogawa-u.ac.jp; ymohishi@kcc.zaq.ne.jp (1) 17,18) were treated with 2 eq of POCl 3 in N,N-dimethylformamide to give 2-(1-chloro-2-formylvinyl)-benzo [b] furans (2), 19,20) of which the stereochemistry of the (Z)-olefin is discussed below. Aldehydes (2) were converted to 2-(1-chloro-2-cyanovinyl) benzo [b] furans (3a, b) in two steps. 21)Cleavage of the methyl ether of 3b by treatment with BBr 3 afforded the 7-hydroxyl compound (3c) (Chart 1).Preparation of 2-Thienylbenzo[b] furans (4-6) Thiophene ring formation by treatment of 3 with ethyl thioglyco late proceeded smoothly to give 2-(3-amino-2-ethoxycarbonylthiophen-5-yl) benzo [b] furans (4a-c).21,22) The 7-hydroxyl compound (4c) was treated with several alkyl halides to afford the corresponding 7-alkyloxy-2-thienylbenzo[b]-furans (4d-e). Acylation of the 3-aminothiophene co...

show abstract

Syntheses of 3-acetoacetylaminobenzo[b]furan derivatives having cysteinyl leukotriene 2 receptor antagonistic activity

Cited by 35 publications

References 26 publications

Preparation of novel (Z)-4-ylidenebenzo[b]furo[3,2-d][1,3]oxazines and their biological activity

Preparation of novel (Z)-4-ylidenebenzo[b]furo[3,2-d][1,3]oxazines and their biological activity

Efficient New Synthesis of N‐Arylbenzo[b]furo[3,2‐d]pyrimidin‐4‐amines and Their Benzo[b]thieno[3,2‐d]pyrimidin‐4‐amine Analogues via a Microwave‐Assisted Dimroth Rearrangement

Preparation of Benzo[<i>b</i>]furans Having Five-Membered Heterocycles at the 2-Position and 2-(4-Alkylcarbamoylbuta-1,3-dienyl)benzo[<i>b</i>]furans, and Their Cysteinyl Leukotriene Receptor (cysLT1, cysLT2) Inhibitory Activity

Contact Info

Product

Resources

About