- Design, synthesis and biological evaluation of novel tetrahydroisoquinoline derivatives as potential PDE4 inhibitors
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The design, synthesis, and biological evaluation of new phosphodiesterase type 4 (PDE4) inhibitors, which possessed 7-(cyclopentyloxy)-6-methoxy 1,2,3,4-tetrahydroisoquinoline ring, were described. Compound 8 [(7-cyclopentyloxy)-6-methoxy-3,4-dihydroisoqu
- Song, Gaopeng,Zhao, Dongsheng,Hu, Dekun,Li, Yasheng,Jin, Hongwei,Cui, Zining
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Read Online
- Rational design of conformationally constrained oxazolidinone-fused 1,2,3,4-tetrahydroisoquinoline derivatives as potential PDE4 inhibitors
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Improvement of subtype selectivity of an inhibitor's binding activity using the conformational restriction approach has become an effective strategy in drug discovery. In this study, we applied this approach to PDE4 inhibitors and designed a series of nov
- Song, Gaopeng,Zhu, Xiang,Li, Junhua,Hu, Dekun,Zhao, Dongsheng,Liao, Yixian,Lin, Juntong,Zhang, Lian-Hui,Cui, Zi-Ning
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Read Online
- Cyclopentyl: A novel protective group for phenols
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We have discovered cyclopentyl as a novel group for the protection of hydroxyl functionality of phenols. The key steps involved are cyclopentylation and decyclopentylation. Copyright Taylor & Francis Group, LLC.
- Gajera, Jitendra M.,Gharat, Laxmikant A.,Farande, Aniket V.
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Read Online
- Cyclopentyl: A novel protective group for phenols
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We have discovered cyclopentyl as a novel group for the protection of hydroxyl functionality of phenols. The key steps involved are cyclopentylation and decyclopentylation. Copyright Taylor & Francis Group, LLC.
- Gajera, Jitendra M.,Gharat, Laxmikant A.,Farande, Aniket V.
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Read Online
- TETRAHYDROISOQUINOLINE COMPOUND, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION CONTAINING SAME, AND USE THEREOF
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Disclosed are a novel tetrahydroisoquinoline compound, a method for preparing intermediates thereof, a pharmaceutical composition thereof and the use thereof. The tetrahydroisoquinoline compound of the present invention has a good inhibitory effect on phosphodiesterase (PDE4), and can be used in the prevention, treatment or auxiliary treatment of multiple diseases associated with the activity or expression of phosphodiesterase, especially PDE4-associated immune and inflammatory diseases, such as psoriasis and arthritis. (I)
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Paragraph 0077-0078
(2020/12/22)
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- Tetrahydroisoquinoline and carbamate containing compound, preparation method therefor and application of compound
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The invention discloses a tetrahydroisoquinoline and carbamate containing compound. The tetrahydroisoquinoline and carbamate containing compound has a structure represented by a formula I shown in the description, wherein R1 is H, cycloalkyl, alkyl or sub
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Paragraph 0053; 0055; 0056
(2017/05/19)
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- C3-substituted tetrahydroisoquinoline derivative and preparation method and application thereof
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The invention discloses a C3-substituted tetrahydroisoquinoline derivative. A structure formula of the derivative is shown in formula I or formula II, wherein an R1 group is hydrogen, a naphthenic group, an alkyl group, a phenyl group or a substituted phe
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Paragraph 0066; 0067; 0068; 0069; 0070; 0071
(2017/08/29)
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- BICYCLIC FUSED PYRAZOLE DERIVATIVES FOR THE TREATMENT OF RSV
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Disclosed herein are compounds and compositions for treating or inhibiting RSV and related members of the pneumovirus and paramyxovirus families such as human metapneumovirus, mumps virus, human parainfluenzaviruses, and Nipah and hendra virus, and method
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Page/Page column 87
(2017/12/05)
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- Chemical assembly systems: Layered control for divergent, continuous, multistep syntheses of active pharmaceutical ingredients
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While continuous chemical processes have attracted both academic and industrial interest, virtually all active pharmaceutical ingredients (APIs) are still produced by using multiple distinct batch processes. To date, methods for the divergent multistep continuous production of customizable small molecules are not available. A chemical assembly system was developed, in which flow-reaction modules are linked together in an interchangeable fashion to give access to a wide breadth of chemical space. Control at three different levels - choice of starting material, reagent, or order of reaction modules - enables the synthesis of five APIs that represent three different structural classes (γ-amino acids, γ-lactams, β-amino acids), including the blockbuster drugs Lyrica and Gabapentin, in good overall yields (49-75%).
- Ghislieri, Diego,Gilmore, Kerry,Seeberger, Peter H.
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supporting information
p. 678 - 682
(2015/03/04)
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- Imidazole derivatives show anticancer potential by inducing apoptosis and cellular senescence
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Imidazole-based compounds are attractive targets in the design of novel chemical structures for the discovery of new drugs. In the current study, we have synthesized a series of new 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles by multicomponent reaction (MCR). Vanillin and isovanillin derivatives were reacted with benzil/pyridil and diverse amines and ammonium acetate in acetic acid at 50-110 °C for 24 h to afford respective imidazoles in 55-70% yields. The series of molecules were evaluated for anti-cancer potential against the National Cancer Institute's 60 human cancer cell line panel. Preliminary screening highlighted the anticancer potential of 2,2′-(2-(3-(cyclopentyloxy)-4-methoxyphenyl)-1-isobutyl-1H-imidazole-4,5-diyl)dipyridine (NSC 771432) against different cancer cell types. A549 cells were treated in vitro to determine the mode of action of NSC 771432 on growth of these cells. This compound inhibits anchorage independent growth and cell migration, and induces cell cycle arrest in the G2/M phase. Also, the exposure of A549 cells to NSC 771432 leads to cellular senescence. This journal is
- Sharma, Gangavaram V. M.,Ramesh, Adepu,Singh, Ashita,Srikanth, Gourishetty,Jayaram, Vankudoth,Duscharla, Divya,Jun, Jung Ho,Ummanni, Ramesh,Malhotra, Sanjay V.
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p. 1751 - 1760
(2014/12/11)
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- Synthesis of 8-(cyclopentyloxy)phenyl substituted xanthine derivatives as adenosine A2A ligands
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The present paper describes the synthesis of a series of 8-(cyclopentyloxy)phenyl-xanthines and their evaluation for affinity for A 1 and A2 adenosine receptors using radioligand binding assays. The effects of moving the cyclopentyloxy substituent with or without an ortho methoxy group on the various positions of the 8-phenyl ring have been studied. The vanilloid based xanthines 8-[4-(cyclopentyloxy)-3-methoxyphenyl]-1, 3-dimethylxanthine (6a) (Ki = 100 nM) and 8-[(4-cyclopentyloxy)-3- methoxyphenyl]-3-methyl-1-propylxanthine (12) (Ki = 150 nM) displayed the highest affinity at A2A receptors as well as over 1000 fold selectivity over the A1 adenosine receptor subtype. ECV · Editio Cantor Verlag, Aulendorf (Germany).
- Bansal, Ranju,Kumar, Gulshan,Gandhi, Deepika,Yadav, Rakesh,Young, Louise C.,Harvey, Alan L.
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experimental part
p. 131 - 136
(2011/07/30)
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- Evaluation and optimization of antifibrotic activity of cinnamoyl anthranilates
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Tranilast is an anti-inflammatory drug in use for asthma and atopic dermatitis. In studies over the last decade it has been revealed that tranilast can reduce fibrosis occurring in the kidney during diabetes, thereby delaying and/or preventing kidney dysfunction. We report a structure-activity study aimed at optimizing the antifibrotic activity of tranilast. A series of cinnamoyl anthranilates were prepared and assessed for their ability to prevent TGF-β-stimulated production of collagen in cultured renal mesangial cells. We reveal derivatives with improved potency and reduced cellular toxicity relative to tranilast. 3-Methoxy-4-propargyloxycinnamoyl anthranilate reduces albuminuria in a rat model of progressive diabetes, and thus has potential as an innovative treatment for diabetic nephropathy.
- Zammit, Steven C.,Cox, Alison J.,Gow, Renae M.,Zhang, Yuan,Gilbert, Richard E.,Krum, Henry,Kelly, Darren J.,Williams, Spencer J.
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supporting information; experimental part
p. 7003 - 7006
(2010/07/08)
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- THERAPEUTIC COMPOUNDS
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Substituted cinnamoyl anthranilate compounds exhibiting anti-fibrotic activity; or derivatives thereof, analogues thereof, pharmaceutically acceptable salts thereof, and metabolites thereof; with the proviso that the compound is not Tranilast.
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Page/Page column 64
(2008/06/13)
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- Tetrafluoroboric acid adsorbed on silica gel as a reusable heterogeneous dual-purpose catalyst for conversion of aldehydes/ketones into acetals/ketals and back again
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Aldehydes and ketones can be protected as acetals and ketals by treatment with trimethyl orthoformate (TMOF) or triethyl orthoformate (TEOF) under the catalytic influence of tetrafluoroboric acid adsorbed on silica gel (HBF 4-SiO2). In the case of aldehydes or ketones with highly electrophilic carbonyl group, the reactions are carried out under solvent-free conditions. Aryl alkyl ketones, aryl styryl ketones, aldehydes with weakly electrophilic carbonyl groups, and aldehydes with substituents that can coordinate with the catalyst require the presence of the corresponding alcohol as solvent. For substrates that can be converted into acetals under neat conditions, the acetal formation takes place at a faster rate when the alcohol is used as the solvent. The catalyst can be recovered and reused/recycled four times (after reactivation after each use) without any significant decrease in its catalytic efficiency. The parent aldehydes/ketones are regenerated from the corresponding acetals/ketals in high yields by the treatment with water-alcohol in the presence of HBF4-SiO2 at room temperature for short times. Excellent selectivity was observed during inter- and intramolecular competition studies involving carbonyl substrates with varying electronic and steric environments. Selective acetal formation of benzaldehyde takes place in the presence of 4-(dimethylamino)benzaldehyde, thiophene-2-carboxaldehyde, 1-naphthaldehyde, 9-anthraldehyde, or acetophenone, but 3-nitrobenzaldehyde undergoes selective acetal formation in preference to benzaldehyde. In the case of 4-acetylbenzaldehyde, exclusive acetal formation of the aldehyde carbonyl group occurs. Georg Thieme Verlag Stuttgart.
- Kumar, Dinesh,Kumar, Raj,Chakraborti, Asit K.
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p. 1249 - 1256
(2008/12/22)
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- Perchloric acid adsorbed on silica gel (HClO4-SiO2) as an inexpensive, extremely efficient, and reusable dual catalyst system for acetal/ketal formation and their deprotection to aldehydes/ketones
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Perchloric acid adsorbed on silica gel (HClO4-SiO2) is reported as extremely efficient, inexpensive, and reusable catalyst for dual role for protection of aldehydes/ketones (with trialkyl orthoformates) as acetals/ketals and deprotection (with water-alcohol) to regenerate the carbonyl compounds in high yields at room temperature and in short times. Acetalization/ketalization of electrophilic aldehydes/ketones was carried out under solvent-free conditions. Weakly electrophilic aldehydes/ketones and aldehydes having a substituent that can coordinate with the catalyst, required the corresponding alcohol as solvent. Georg Thieme Verlag Stuttgart.
- Kumar, Raj,Kumar, Dinesh,Chakraborti, Asit K.
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p. 299 - 303
(2007/10/03)
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- Benzazine derivatives phosphodiesterase 4 inhibitors
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Compounds of formula (I) wherein A is an orthocondensed heterocycle optionally substituted by certain substituents and necessarily substituted by a —B—Cy group where the variables are as defined in the specification and the N→O derivatives and pharmaceutically acceptable salts thereof are phosphodiesterase-4 inhibitors.
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- Butadiene derivatives and process for preparing thereof
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A novel butadiene derivative of the formula: wherein Ring A is heterocycle, or benzene being optionally substituted by lower alkyl, alkoxy, nitro, hydroxy, substituted or unsubstituted amino or halogen, Ring B is heterocycle, or benzene being optionally substituted by lower alkoxy, lower alkylenedioxy or di-lower alkylamino, R1and R2are each H or lower alkyl, one of —COR32and —COR42is carboxyl, and the other is carboxyl being optionally esterified, or the corresponding amide or pyrrolidine derivatives, or a pharmaceutically acceptable salt thereof. Said compounds show excellent PAI-1 inhibitory activity and are useful in the prophylaxis or treatment of various thromboses such as myocardial infarction, intra-atrial thrombus in atrial fibrillation, cerebral infarction, angina pectoris, stroke, pulmonary infarction, deep venous thrombus (DVT), disseminated intravascular coagulation syndrome (DIC), diabetic complications, restenosis after percutaneous transluminal coronary angioplasty (PTCA), etc.
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