- Preparation method of tetrahydroisoquinoline derivative
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The invention discloses a preparation method of a tetrahydroisoquinoline derivative which is N-Fmoc-1,2,3,4-tetrahydroisoquinoline-5-alcohol. The preparation method comprises the following steps: taking isoquinoline as a starting raw material, loading sulfonic acid groups, hydrolyzing, hydrogenating and carrying out Fmoc protection to obtain a target product. The compound is used as an important medical intermediate.
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Paragraph 0021; 0022
(2018/03/24)
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- ISOQUINOLINESULFONYL DERIVATIVE AS RHO KINASE INHIBITOR
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The present invention discloses a class of isoquinolinesulfonyl derivatives as RHO kinase inhibitors, and pharmaceutical compositions thereof, and relates to pharmaceutically acceptable uses thereof. Specifically, the present invention relates to a compound as represented by formula (I), or a pharmaceutically acceptable salt thereof.
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Paragraph 0064-0067
(2017/06/12)
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- Exploration of N-(2-aminoethyl)piperidine-4-carboxamide as a potential scaffold for development of VEGFR-2, ERK-2 and Abl-1 multikinase inhibitor
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VEGFR, ERK and Abl had been respectively identified as good drug targets, and their crosstalk also had been well elaborated. Multitarget drugs were more advantageous for cancer treatment, however, no inhibitors simultaneously acting on the three proteins were developed due to their structural diversities. Herein, N-(4-((2-(2-(naphthaen-1-yl)acetamido)ethyl)carbamoyl)piperidin-4-yl)-6- (trifluoromethyl)nicotinamide (NEPT, 6a) was discovered as an active scaffold against VEGFR-2, ERK-2 and Abl-1 kinases through the combination of support vector machine, similarity searching and molecular docking. NEPT and its derivatives were synthesized by convenient routine, their in vitro anti-proliferative abilities against human liver cancer cell line HepG2 were preliminarily evaluated. A representative compound 6b showed an IC50 value of 11.3 μM and induced significant HepG2 cells apoptosis. Besides, these compounds displayed better anti-proliferative abilities against K562 cells (a cell line with typical hyperactivity of the above multikinases), for example compound 6b exhibited an IC50 value of 4.5 μM. Based on hepatotoxicity case reports of Abl inhibitors, cytotoxicity of synthetic compounds against normal liver cell lines (QSG7701 and HL7702) was studied, 6b had a similar toxic effect with positive control imatinib, and most compounds showed less than 35% inhibition activities at 100 μM. Molecular docking study disclosed interactions of 6b with VEGFR-2, ERK-2 and Abl-1 kinases, respectively. Our data suggested the biological activities of 6b may derived from collaborative effects of VEGFR-2, ERK-2 and Abl-1 inhibition.
- Jin, Feng,Gao, Dan,Wu, Qin,Liu, Feng,Chen, Yuzong,Tan, Chunyan,Jiang, Yuyang
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p. 5694 - 5706
(2013/09/12)
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- De novo design and synthesis of HIV-1 integrase inhibitors
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Existing AIDS therapies are out of reach for most HIV-infected people in developing countries and, where available, they are limited by their toxicity and their cost. New anti-HIV agents are needed urgently to combat emerging viral resistance and reduce the side effects associated with currently available drugs. Toward this end, LeapFrog, a de novo drug design program was used to design novel, potent, and selective inhibitors of HIV-1 integrase. The designed compounds were synthesized and tested for in vitro inhibition of HIV-1 integrase. Out of the 25 compounds that were designed, and synthesized, four molecules (compounds 23, 26, 43, and 59) showed moderate to low inhibition of HIV-1 integrase for 3′-processing and 3′- strand transfer activities. Nonetheless, these compounds possess structural features not seen in known HIV-1 integrase inhibitors and thus can serve as excellent leads for further optimization of anti-HIV-1 integrase activity.
- Makhija, Mahindra T.,Kasliwal, Rajesh T.,Kulkarni, Vithal M.,Neamati, Nouri
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p. 2317 - 2333
(2007/10/03)
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- SYNTHESIS OF POTENTIAL &β-BLOCKERS DERIVED FROM 5-HYDROXYISOQUINOLINE
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The synthesis of N-substituted amides 5-hydroxyisoquinaldate is described.Keywords: 5-hydroxyisoquinoline derivatives, synthesis, elemental and spectral analysis.
- Walczynski, Krzysztof,Glinka, Ryszard
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p. 479 - 482
(2007/10/02)
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