- Anti-HIV agents. Part 55: 3′R,4′R-Di-O-(-)-camphanoyl-2′,2′- dimethyldihydropyrano[2,3-f]chromone (DCP), a novel anti-HIV agent
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3′R,4′R-Di-O-(-)-camphanoyl-2′,2′- dimethyldihydropyrano[2,3-f]chromone (DCP) (2) was designed and synthesized on the basis of a structure-activity relationship study of 3′R,4′R-di-O-(-)-camphanoyl-(+)-cis-khellactone DCK (1) and its analogues. DCP (2), a pyranochromone, and DCK (1), a pyranocoumarin, have different skeletons. Compound 2 showed potent in vitro inhibition of HIV-1 replication in H9 lymphocyte cells with an EC50 of 6.78×10-4 μM and TI of 14,500. These values are comparable with those for DCK (1) and better than those of AZT in the same assay.
- Yu, Donglei,Brossi, Arnold,Kilgore, Nicole,Wild, Carl,Allaway, Graham,Lee, Kuo-Hsiung
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Read Online
- Asymmetric Synthesis of Sakuranetin-Relevant Flavanones for the Identification of New Chiral Antifungal Leads
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Discovery and efficient synthesis of new promising leads have a central role in agrochemical science. Reported herein is the sakuranetin-directed synergistic exploration of an asymmetric synthesis and an antifungal evaluation of chiral flavanones. A new palladium catalytic system with CarOx-type ligands was successfully identified for the highly enantioselective addition of arylboronic acids to chromones. This enabled the facile and programmable construction of a constellation of chiral flavanones (up to 98% yield and 97% ee), in which (R)-pinostrobin was efficiently constructed without laborious protecting/deprotecting operations. Its good performance in asymmetric induction and functional tolerance expanded the chemical space of pharmaceutically important flavanones. The chiral differentiation of flavanones based on antifungal activity and a concise structure-activity relationship model was disclosed and summarized. This synergistic project culminated with acquisition of the naturally unprecedented flavanones with better antifungal potentials than sakuranetin, in which the R-enantiomer of flavanone 54 (EC50 = 0.8 μM) demonstrated better performance than boscalid against Rhizoctonia solani. The novel scaffold and predicted new target compared with the commercial fungicides in the FRAC reinforce the value of further exploration.
- Yang, Juan,Lai, Jixing,Kong, Wenlong,Li, Shengkun
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p. 3409 - 3419
(2022/03/31)
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- Design, synthesis and biological evaluation of novel benzoxaborole derivatives as potent PDE4 inhibitors for topical treatment of atopic dermatitis
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In this work, a series of structurally novel benzoxaborole derivatives were designed, synthesized and biologically evaluated as PDE4 inhibitors for battling atopic dermatitis (AD). Among them, the majority exhibited superior PDE4B inhibitory activities to that of the lead compound Crisaborole, an approved PDE4 inhibitor. In particular, 72, the most potent PDE4B inhibitor throughout this series, displayed 136-fold improved enzymatic activity (IC50 = 0.42 nM) as compared to Crisaborole (IC50 = 57.20 nM), along with favorable isoform specificity. In the phorbol ester (PMA)-induced mouse ear oedema model, 72 exerted remarkably greater efficacy than Crisaborole at the same dosage (P 0.05). Moreover, the ointment of 72 exerted dramatically enhanced therapeutic potency than the ointment of Crisaborole (P 0.05) in the calcipotriol-induced mouse AD model. In addition to the potent in vitro and in vivo activity, 72 displayed favorable safety in the repeated oral dose toxicity study and did not exhibit phototoxicity. With the above attractive biological performance, 72 is worthy of further functional investigation as a novel anti-AD therapeutic agent.
- Chu, Zhaoxing,Xu, Qinlong,Zhu, Qihua,Ma, Xiaodong,Mo, Jiajia,Lin, Gaofeng,Zhao, Yan,Gu, Yuanfeng,Bian, Lincui,Shao, Li,Guo, Jing,Ye, Wenfeng,Li, Jiaming,He, Guangwei,Xu, Yungen
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- Synthesis and evaluation of trypanocidal activity of chromane-type compounds and acetophenones
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American trypanosomiasis (Chagas disease) caused by the Trypanosoma cruzi parasite, is a severe health problem in different regions of Latin America and is currently reported to be spreading to Europe, North America, Japan, and Australia, due to the migration of populations from South and Central America. At present, there is no vaccine available and chemotherapeutic options are reduced to nifurtimox and benznidazole. Therefore, the discovery of new molecules is urgently needed to initiate the drug development process. Some acetophenones and chalcones, as well as chromane-type substances, such as chromones and flavones, are natural products that have been studied as trypanocides, but the relationships between structure and activity are not yet fully understood. In this work, 26 compounds were synthesized to determine the effect of hydroxyl and isoprenyl substituents on trypanocide activity. One of the compounds showed interesting activity against a resistant strain of T. cruzi, with a half effective concentration of 18.3 μM ± 1.1 and an index of selectivity > 10.9.
- Escobar, Gustavo,González, Luis A.,Qui?ones, Wiston,Robledo, Sara,Upegui, Yulieth
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- Chromone derivatives bearing pyridinium moiety as multi-target-directed ligands against Alzheimer's disease
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A new serise of 7-hydroxy-chromone derivatives bearing pyridine moiety were synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). Most of the compounds were good AChE inhibitors (IC50 = 9.8–0.71 μM) and showed remarkable BuChE inhibition activity (IC50 = 1.9–0.006 μM) compared with donepezil as the standard drug (IC50 = 0.023 and 3.4 μM). Compounds 14 and 10 showed the best inhibitory activity toward AChE (IC50 = 0.71 μM) and BuChE (IC50 = 0.006 μM), respectively. The ligand–protein docking simulations and kinetic studies revealed that compound 14 and 10 could bind effectively to the peripheral anionic binding site (PAS) of the AChE and BuChE through mixed-type inhibition. In addition, the most potent compounds showed acceptable neuroprotective activity on H2O2- and Aβ-induced.neurotoxicity in PC12 cells, more than standard drugs. The compounds could block effectively self- and AChE-induced Aβ aggregation. All the results suggest that compounds 14 and 10 could be considered as promising multi-target-directed ligands against AD.
- Abdpour, Shahin,Jalili-Baleh, Leili,Nadri, Hamid,Forootanfar, Hamid,Bukhari, Syed Nasir Abbas,Ramazani, Ali,Ebrahimi, Seyed Esmaeil Sadat,Foroumadi, Alireza,Khoobi, Mehdi
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- Discovery of 4 H-Chromen-4-one Derivatives as a New Class of Selective Rho Kinase (ROCK) Inhibitors, which Showed Potent Activity in ex Vivo Diabetic Retinopathy Models
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Diabetic retinopathy (DR) is a major cause of blindness, and there is a lack of effective treatment at present. Rho-associated coiled-coil containing serine/threonine protein kinases (ROCKs) have recently been suggested as potential targets for the DR treatment. We herein report the discovery of 4H-chromen-4-one derivatives as a new class of ROCK inhibitors. Structure-activity relationship analyses led to the identification of the most active compound, 4-(dimethylamino)-N-(3-{2-[(4-oxo-4H-chromen-7-yl)oxy]acetamido}phenyl) (12j). This compound showed excellent kinase selectivity for ROCK I and ROCK II against 387 other kinases. In retinal explants, compound 12j protected retinal neurons from high glucose-induced oxidative stress and apoptosis-mediated cell death. Furthermore, 12j administration suppressed the improper proliferation of Müller cells and promoted the regression of vascular vessels in retinal explants cultured in a high glucose microenvironment. Collectively, our data suggest that 12j could be a potential lead compound for the treatment of DR, hence deserving further in-depth studies.
- Zhao, Lanying,Li, Yueshan,Wang, Yujiao,Qiao, Zeen,Miao, Zhuang,Yang, Jiao,Huang, Luyi,Tian, Chenyu,Li, Linli,Chen, Danian,Yang, Shengyong
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p. 10691 - 10710
(2019/11/28)
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- Flavonoid derivative with ROCK kinase inhibiting effect
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The invention relates to a flavonoid derivative with a ROCK kinase inhibiting effect, belongs to the technical field of organic synthetic medicines, and solves the technical problems that the existingglaucoma treating medicines are poor in effect, especially effective therapeutic medicines for treating glaucoma with normal intraocular pressure lack, and medicines for treating diabetic retinopathy, such as conbercept and ranibizumab, can only be applied to the later stage of a disease, are ineffective for the early stage of the disease and destroy the protective effect of VEGF on a normal retinal tissue after long-term use. A technical scheme for solving the problems is achieved by providing a compound shown as a formula I. Experimental results show that the compound has the significant ROCK kinase inhibiting effect, can effectively reduce the intraocular pressure, protect retinal ganglion cells, reduce the retinal reactive oxygen level and inhibit retinal angiogenesis, and provides anovel medication choice for clinical treatment of the glaucoma and the diabetic retinopathy.
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Paragraph 0103; 0104; 0105-0107
(2018/10/19)
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- SUBSTITUTED CHROMANES AND METHOD OF USE
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The invention provides for compounds of formula (I), wherein R1, X, Y, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, m, and R" have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions mediated and modulated by CFTR, including cystic fibrosis, Sj?gren's syndrome, pancreatic insufficiency, chronic obstructive lung disease, and chronic obstructive airway disease. Also provided are pharmaceutical compositions comprised of one or more compounds of formula (I).
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Page/Page column 146-147
(2016/05/19)
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- Synthesis, antiproliferative, and c-Src kinase inhibitory activities of 4-oxo-4H-1-benzopyran derivatives
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A new class of 4-oxo-4H-1-benzopyran derivatives were synthesized and their antiproliferative activity examined against a panel of three human cancer cell lines, that is, breast carcinoma (MDA-MB-468), ovarian adenocarcinoma (SK-OV-3), and colorectal adenocarcinoma (HT-29). Two compounds, that is, 3-hexyl-7,8-dihydroxy-4-oxo-4H-1-benzopyran and (E)-ethyl 3-(7-methoxy-4-oxo-4H-1-benzopyran-3-yl)acrylate were found to be potent against all three cancer cell lines studied at 50 μM concentration. Also, the inhibitory potency of the compounds was evaluated against active Src kinase. A few of these compounds exhibited modest Src kinase inhibitory activity (IC50 = 52-57 μM). Structure-activity relationship studies with respect to the nature and position of substituents on the lead compounds could be further exploited for the design and development of more potent antiproliferative agents and/or Src kinase inhibitors.
- Chand, Karam,Tiwari, Rakesh K.,Kumar, Sumit,Shirazi, Amir Nasrolahi,Sharma, Sweta,Van Der Eycken, Erik V.,Parmar, Virinder S.,Parang, Keykavous,Sharma, Sunil K.
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p. 562 - 572
(2015/03/30)
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- Development of 3-alkyl-6-methoxy-7-hydroxy-chromones (AMHCs) from natural isoflavones, a new class of fluorescent scaffolds for biological imaging
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Starting from 7-hydroxyisoflavones, we developed a new class of fluorescent scaffolds, 3-alkyl-6-methoxy-7-hydroxy-chromones (AMHCs, MW ～ 205.19, λab ～ 350 nm, λem ～ 450 nm) via a trial and error process. AMHCs have the advantages of being a small molecular moiety, having strong fluorescence in basic buffers, reasonable solubility and stability, non-toxicity, and are conveniently linked to pharmacophores. AMHCs were successfully used in fluorescence microscopy imaging of cells and tissues. This journal is
- Miao, Jianzhuang,Cui, Huaqing,Jin, Jing,Lai, Fangfang,Wen, Hui,Zhang, Xiang,Ruda, Gian Filippo,Chen, Xiaoguang,Yin, Dali
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supporting information
p. 881 - 884
(2015/02/19)
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- Multifunctional tacrine-flavonoid hybrids with cholinergic, β-amyloid-reducing, and metal chelating properties for the treatment of Alzheimer's disease
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A new series of tacrine-flavonoid hybrids (13a-u) had been designed, synthesized, and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of the molecules exhibited a significant ability to inhibit ChE and self-induced amyloid-β (Aβ1-42) aggregation. Kinetic and molecular modeling studies also indicated compounds were mixed-type inhibitors, binding simultaneously to active, peripheral and mid-gorge sites of AChE. Particularly, compound 13k was found to be highly potent and showed a balanced inhibitory profile against ChE and self-induced Aβ1-42 aggregation. Moreover, it also showed excellent metal chelating property and low cell toxicity. These results suggested that 13k might be an excellent multifunctional agent for AD treatment.
- Li, Su-Yi,Wang, Xiao-Bing,Xie, Sai-Sai,Jiang, Neng,Wang, Kelvin D.G.,Yao, He-Quan,Sun, Hong-Bin,Kong, Ling-Yi
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p. 632 - 646
(2013/10/22)
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- FURO[3,2-G]CHROMENE COMPOUNDS AND USES THEREOF
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Disclosed are furo[3,2-g]chromene derivatives represented by formula (I), stereoisomers, pharmaceutically acceptable salts, and pharmaceutical compositions thereof, as well as uses thereof as estrogen receptor modulators.
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Paragraph 0040
(2013/04/24)
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- Palladium-catalyzed asymmetric conjugate addition of arylboronic acids to heterocyclic acceptors
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Flava Flavanone: Asymmetric conjugate additions to chromones and 4-quinolones are reported utilizing a single catalyst system formed in situ from Pd(OCOCF3)2 and (S)-tBuPyOX. Notably, these reactions are performed in wet solvent under ambient atmosphere, and employ readily available arylboronic acids as the nucleophile, thus providing ready access to these asymmetric heterocycles (see scheme).
- Holder, Jeffrey C.,Marziale, Alexander N.,Gatti, Michele,Mao, Bin,Stoltz, Brian M.
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supporting information
p. 74 - 77
(2013/02/25)
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- A mild and efficient protocol to synthesize chromones, isoflavones, and homoisoflavones using the complex 2,4,6-trichloro-1,3,5-triazine/ dimethylformamide
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A mild and efficient one-flask method has been developed for the synthesis of chromones, isoflavones, and homoisoflavones from 2-hydroxyacetophenones, deoxybenzoins, and dihydrochalcones, respectively, via one-carbon extension using the complex 2,4,6-trichloro-1,3,5-triazine/dimethylformamide. Deoxybenzoins and dihydrochalcones were prepared in situ by the reaction of readily available substituted phenols with phenylacetic acids and 3-phenylpropanoic acids, respectively. This method allows the synthesis of a wide range of compounds with multiple phenolic hydroxyls and other substituents. The methodology has been applied to the synthesis of three naturally occurring isoflavones such as formononetin (9c), daidzein (9d), and retusin (9h).
- Basha, G. Mahaboob,Yadav, S. Kumar,Srinuvasarao,Prasanthi,Ramu,Mangarao,Siddaiah
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p. 763 - 768
(2013/08/23)
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- Convenient synthesis of novel geiparvarin analogs with potential anti-cancer activity via click chemistry
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Based on the advantages of natural products in new anti-cancer drug development, we synthesized a series of novel benzopyran-4-one derivatives and evaluated their in vitro anti-cancer activities. The bioassays showed that the majority of the resultant compounds exerted anti-tumor effect against six human cancer cell lines to various extents, which supported the rationale of the design. Compound 5s exhibited highest potency of all the synthesized compounds.
- Zhang, Yikai,Lv, Zhiliang,Zhong, Hanyu,Geng, Dongping,Zhang, Mingfeng,Zhang, Tao,Li, Yongmei,Li, Ke
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scheme or table
p. 356 - 363
(2012/08/08)
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- The heck reaction of protected hydroxychromones: On route to natural products
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The Heck reaction has been successfully extended to the bromochromones with an adjacent protected phenolic hydroxy group which offers a new methodology to various naturally occurring derivatives including tricyclic O-heterocycles. Phosphine-free coupling conditions are found to be effective. Surprisingly, the methoxymethyl protecting group is unstable in several cases but benzyl proved to be an ideal protecting group which could be selectively cleaved by boron trihalides in good yields. CSIRO 2011.
- Vasas, Attila,Patonay, Tamas,Konya, Krisztina,Silva, Artur M. S.,Cavaleiro, Jose A. S.
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scheme or table
p. 647 - 657
(2011/12/16)
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- Synthesis, characterization, crystal structure and cytotoxicities of 2-aroyl-3-aryl-5H-furo[3,2-g]chromene derivatives
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Five 2-aroyl-3-aryl-5H-furo[3,2-g]chromene derivatives have been synthesized, and their structures were characterized by IR, NMR, ESI-MS and elemental analysis. The crystal structure for 2-benzoyl-3-(4-methoxyphenyl)-6,7- dihydro-5H-furo[3,2-g]chromene has been determined by single-crystal X-ray diffraction. X-ray analysis reveals that the pyran ring adopts a half-chair conformation, while the fused furo[3,2-g]chromene ring is approximately coplanar with a slight distortion. The preliminary pharmacological test showed all target compounds exhibit cytotoxicities against the U2OS-EGFP-4F12G cell line. ARKAT USA, Inc.
- Wang, Shi-Hui,Wang, Yan,Zhu, Yu-Ying,Han, Jian,Zhou, Yi-Fan,Koirala, Diwa,Li, Da-Wei,Hu, Chun
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experimental part
p. 204 - 214
(2010/12/19)
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- CHROMEN-4-ONE DERIVATIVES AS SELF-TANNING SUBSTANCE
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The invention relates to the use of compounds of the formula (I), where R1 and R2 may be identical or different and stand for H, OH, OCH3, CH3, CH2OH or CH2OCH3, R3 stands for H or straight-chain or branched C1- to C20-alkyl groups, R4 stands for H or OR8, R5 and R6 may be identical or different and are selected from —H, —OH, straight-chain or branched C1 to C20-alkyl groups, straight-chain or branched C3- to C20-alkenyl groups, straight-chain or branched C1- to C20-hydroxyalkyl groups, where the hydroxyl group may be bonded to a primary or secondary carbon atom of the chain, and furthermore the allyl chain may also be interrupted by oxygen, and R8 stands for H or straight-chain or branched C1- to C20-alkyl groups, with the proviso that R2 does not denote H if R1 denotes CH3, as self-tanning agents, and to compounds and the preparation thereof.
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- Anti-AIDS agents. 60. Substituted 3′R,4′R-di-O-(-)-camphanoyl- 2′,2′-dimethyldihydropyrano[2,3-f]chromone (DCP) analogues as potent anti-HIV agents
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Synthesis of positional isomers is a commonly used technique in drug design. Accordingly, based on prior SAR studies of 3′R,4′R-di-O-(S)- camphanoyl-(+)-cis-khellactone (DCK, 1) analogues, a series of mono- and disubstituted chromone derivatives of 3′R,4′R-di-O-(-)camphanoyl- 2′,2′-dimethyldihydropyrano[2,3-f]chromone (DCP, 4) were designed and synthesized. Together with 1 and 4-methyl DCK (2), all newly synthesized DCP analogues (4-21) were screened for anti-HIV-1 activity against a non-drug-resistant strain in H9 lymphocytes and a multiple reverse transcriptase (RT) inhibitor-resistant strain in the MT4 cell line. Several DCP analogues (4, 5, 7, 8, 13, and 17) exhibited extremely high anti-HIV activity in the nondrug-resistant strain assay, with EC50 values ranging from 0.00032 to 0.0057 μM and remarkable therapeutic indexes (TI) ranging from 5.6 × 103 to 1.16 × 105, which were similar to those of 2 (EC50 0.0059 μM, TI > 6.6 × 103) and better than those of 1 (EC50 0.049 μM, TI > 328). Even more promisingly, some DCP analogues also showed activity against a multi-RT inhibitor-resistant strain, HIV-1 RTMDR1, whereas most DCK analogues did not. The most significant compound was 8, with an EC50 value of 0.06 μM and TI of 718 against the multi-RT inhibitor-resistant HIV-1 strain. Compounds 9 and 10 also showed good activity with an EC50 value of 0.14 μM, and TIs of 272 and >111, respectively. 2-Ethyl DCP (8) exhibited the best anti-HIV activity in both assays. Further development of 8-related compounds as clinical trial candidates is warranted.
- Yu, Donglei,Chen, Chin-Ho,Brossi, Arnold,Lee, Kuo-Hsiung
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p. 4072 - 4082
(2007/10/03)
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- Behaviour of o-hydroxyacetophenones towards action of POCl3/DMF (Vilsmeier reagent) in presence of BF3.Et2O: A novel observation in the synthesis of chromones
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The influence of the presence of BF3.Et2O on the Vilsmeier reactions of o-hydroxyacetophenones and related naphthophenones has been examined. A significant and novel feature of this study is the development of new and facile procedure for the synthesis of some chromones. The reaction offers a first example of monoformylation of o-hydroxyacetophenones.
- Prakash, Om,Kumar, Ravi,Sharma, Deepak,Bhardwaj, Vikas
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p. 888 - 890
(2007/10/03)
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- Benzopyran and benzo-fused compounds, their preparation and their use as leukotriene B4 (LTB4 ) antagonists
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This invention relates to novel benzopyran and other benzo-fused leukotriene B4 (LTB4) antagonists and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions containing such compounds, and to a method of using such compounds as LTB4 antagonists. The compounds of this invention inhibit the action of LTB4 and are therefore useful in the treatment of LTB4 induced illnesses such as inflammatory disorders including rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, psoriasis and other skin disorders such as eczema, erythema, pruritus and acne, stroke and other forms of reperfusion injury, graft rejection, autoimmune diseases, asthma, and other conditions where marked neutrophil infiltration occurs.
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- Benzopyran and benzo-fused compounds, their preparation and their use as leukotriene B4 (LTB4) antagonists
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PCT No. PCT/IB95/00401 Sec. 371 Date Apr. 9, 1997 Sec. 102(e) Date Apr. 9, 1997 PCT Filed May 26, 1995 PCT Pub. No. WO96/11920 PCT Pub. Date Apr. 25, 1996This invention relates to novel benzopyran and other benzo-fused leukotriene B4 (LTB4) antagonists and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions containing such compounds or a pharmaceutically acceptable salt thereof, and to methods of using such compounds as LTB4 antagonists. The compounds and the pharmaceutically acceptable salts of this invention inhibit the action of LTB4 and are therefore useful in the treatment of LTB4 induced illnesses such as inflammatory disorders including rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, psoriasis and other skin disorders such as eczema, erythema, pruritus and acne, stroke and other forms of reperfuslon injury, graft rejection, autoimmune diseases, asthma, and other conditions where marked neutrophil infiltration occurs.
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- Tetrahydronaphthalene and tetrahydroquinoline compounds, their preparation and their use as leukotriene B4(LTB4) antagonists
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This invention relates to novel benzopyran and other benzo-fused leukotriene B4 (LTB4) antagonists and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions containing such compounds or a pharmaceutically acceptable salt thereof, and to methods of using such compounds as LTB4 antagonists. The compounds and the pharmaceutically acceptable salts of this invention inhibit the action of LTB4 and are therefore useful in the treatment of LTB4 induced illnesses such as inflammatory disorders including rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, psoriasis and other skin disorders such as eczema, erythema, pruritus and acne, stroke and other forms of reperfusion injury, graft rejection, autoimmune diseases, asthma, and other conditions where marked neutrophil infiltration occurs.
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- BENZOPYRAN AND BENZO-FUSED COMPOUNDS, THEIR PREPARATION AND THEIR USE AS LEUKOTRIENE B4' (LTB4) ANTAGONISTS
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The invention relates to novel benzopyran and other benzo-fused leukotriene B 4 (LTB 4) antagonists of formula I and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions containing such compounds, and to a method of using such compounds as LBT. sub.4 antagonists. The compounds of the invention inhibit the action of LTB 4 and are therefore useful in the treatment of LTB 4 induced illnesses such as inflammatory disorders including rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, psoriasis and other skin disorders such as eczema, erythema, pruitus and acne, stroke and other forms of reperfusion injury, graft rejection, autoimmune diseases, asthma and other conditions where marked neutrophil infiltration occurs. STR1
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- Method of preventing allograft rejection
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Use of a compound for formula I, or a pharmaceutically acceptable acid addition salt thereof, in the preparation of a medicament for suppressing the rejection of allogeneic transplants in a mammal; wherein n, A, B, R1and R2are as defined above, or the pharmaceutically acceptable salt thereof, in combination therapy with cyclosporin A or FK506.
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- Use of benzopyranes for preventing allograft rejection
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A method for suppressing the rejection of allogeneic transplants in a mammal, including a human comprising administering to said mammal an effective amount of the compound of the formula wherein n, A, B, R1and R2are as defined above, or the pharmaceutically acceptable salt thereof.
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- Method of preventing allograft rejection
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A method for suppressing the rejection of allogeneic transplants in a mammal, including a human, comprising administering to said mammal an effective amount of the compound of the formula wherein n, A, B, R1and R2are as defined above, or the pharmaceutically acceptable salt thereof.
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- 7-[3-(1-piperidinyl)propoxy]chromenones as potential atypical antipsychotics. 2. Pharmacological profile of 7-[3-[4-(6-fluoro-1,2- benzisoxazol-3-yl)piperidin-1-yl] propoxy]-3-(hydroxymethyl)chromen-4-one (abaperidone, FI-8602)
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A series of novel 7-[3-(1-piperidinyl)propoxy]chromenones was synthesized and tested as potential antipsychotics in several in vitro and in vive assays. The compounds possessed good affinity for D2 receptors, together with a greater affinity for 5-HT2 receptors, a profile which has been proposed as a model for atypical antipsychotics. Several agents also displayed a high potency in the climbing mice assay on oral administration, suggesting a potent antipsychotic effect as compared to reference standards. Compound 23 was selected for further pharmacological evaluation. Induction of catalepsy and inhibition of stereotypies weaker than standards, along with a lower increase in serum prolactin levels, were indicative of a potential atypical profile for this compound. From these results, 7-[3-[4-(6-fluoro- 1,2-benzisoxazol-3-yl)piperidin1-yl]propoxy]-3-(hydroxymethyl)chromen-4-one (23, abaperidone) has been proposed for clinical evaluation in humans as a potential atypical antipsychotic.
- Bolós, Jordi,Anglada, Lluís,Gubert, Santiago,Planas, Josep M.,Agut, Julián,Príncep, Marta,De La Fuente, àngels,Sacristán, Aurelio,Ortiz, José A.
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p. 5402 - 5409
(2007/10/03)
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- BENZOPYRAN AND RELATED LTB4 ANTAGONISTS
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The invention relates to benzopyran leukotriene B 4 (LTB. sub.4) antagonists and pharmaceutical compositions containing the compounds. The compounds inhibit the action of LTB 4 and are therefore useful in the treatment of LTB 4 induced illnesses such as inflammatory disorders.
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- BENZOPYRAN AND RELATED LTB ANTAGONISTS
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Benzopyran and other benzo-fused leukotriene B 4 antagonists have the formula STR1 wherein R 1 is a phenyl or substituted phenyl group, and A, n, R 2 and R 3 are as defined herein.
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- Potent Inhibitors of Acyl-CoA:Cholesterol Acyltransferase. Structure-Activity Relationships of Novel N-(4-Oxochroman-8-yl)amides
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Novel N-(4-oxochroman-8-yl)amide derivatives 1 were synthesized and tested for their ability to inhibit rabbit small intestinal ACAT (acyl-CoA:cholesterol acyltransferase) in vitro and to lower serum total cholesterol in cholesterol-fed rats in vivo.Among the synthesized compounds, N-(7-alkoxy-4-oxochroman-8-yl)amide derivatives showed potent ACAT inhibitory activity both in vitro and in vivo.The structure-activity relationships of these N-(4-oxochroman-8-yl)amides and related compounds are discussed on the basis of these two assays.The carbonyl group at position 4 of the 4-chromanone was essential for potent ACAT inhibitory activity.N-(Chromon-8-yl) derivatives were less potent than N-(4-oxochroman-8-yl) derivatives.An alkoxy group at position 7 of the 4-chromanone moiety was important for potent ACAT inhibitory activity.In the N-(7-alkoxy-4-oxochroman-8-yl)amide derivatives, another necessary factor to elicit the potent ACAT inhibitory activity was lipophilicity of the molecules.The highly lipophilic acid amides N-(7-methoxy-4-oxochroman-8-yl)-2,2-dimethyldodecanamide (35) and 4-oxy>-N-(7-methoxy-4-oxochroman-8-yl)benzamide (63) showed potent activity.Introduction of a highly lipophilic alkoxy group at position 7 of the 4-chromanone moiety instead of methoxy group also resulted in potent activity.In this case, highest inhibitory activity was obtained by N--2,2-dimethylpropanamide (65).The most potent compound, N-(7-methoxy-4-oxochroman-8-yl)-2,2-dimethyldodecanamide (35, TEI-6522), showed significant ACAT inhibitory activity (rabbit small intestine IC50 = 13 nM, rabbit liver IC50 = 16 nM), foam cell formation inhibitory activity (rat peritoneal macrophage IC50 = 160 nM), and extremely potent serum cholesterol-lowering activity in cholesterol-fed rats (61percent at a dose of 0.1 mg/kg/day po).
- Kataoka, Ken-ichiro,Shiota, Tatsuki,Takeyasu, Takumi,Mochizuki, Tsutomu,Taneda, Keiko,et al.
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p. 3174 - 3186
(2007/10/02)
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- Flavonoids, 45 . A General and Efficient Synthesis of Hydroxyflavones and -chromones
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An efficient and versatile method for the synthesis of flavones hydroxylated in either ring A or B and of chromones hydroxylated in is described.This approach is based on the acidic resin-promoted cyclodehydration and simultaneous deprotection of methoxymethoxylated 1-(2-hydroxyphenyl)propane-1,3-diones easily available by either the Baker-Venkataraman rearrangement or the Claisen condensation. - Key words: Amberlyst 15 / Baker-Venkataraman rearrangement / Claisen condensation / hydroxychromone / hydroxyflavone / methoxymethyl protection
- Patonay, Tamas,Molnar, Denes,Muranyi, Zoltan
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p. 233 - 242
(2007/10/02)
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- Dopamine autoreceptor agonists as potential antipsychotics. 2. (Aminoalkoxy)-4H-1-benzopyran-4-ones
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The synthesis and pharmacological properties of a novel type of [(arylpiperazinyl)alkoxy]-4H-1-benzopyran-4-ones with dopaminergic activity are described. The nature of the arylpiperazine (AP) moiety determines the dopamine (DA) agonist/antagonist character of this series of compounds; when the aryl portion of the AP is unsubstituted the compounds appear to be DA autoreceptor agonists while substituted aryl groups seem to impart DA antagonist activity. A heterocyclic piperazine, 7-[3-[4-(2-pyridinyl)-1-piperazinyl]propoxy]-4H-1-benzopyran-4-one (31, PD 119819) has been identified as an extremely selective DA autoreceptor agonist in tests that include [3H]haloperiodol binding, inhibition of spontaneous locomotor activity, inhibition of brain DA synthesis, inhibition of brain DA neuronal firing, stereotypy assessment, and reversal of 6-hydroxydopamine (6-OHDA) induced akinesia in rats. In addition, 31 possesses good oral activity in the Sidman avoidance test in squirrel monkeys, a predictor of clinical antipsychotic efficacy. In another primate model, 31 has been found to lack the liability for extrapyramidal side effects observed with currently available antipsychotic drugs.
- Jaen,Wise,Heffner,Pugsley,Meltzer
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p. 248 - 256
(2007/10/02)
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