- Synthesis and evaluation of tetrahydroisoquinoline derivatives against Trypanosoma brucei rhodesiense
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Human African Trypanosomiasis (HAT) is a neglected tropical disease caused by the parasitic protozoan Trypanosoma brucei (T. b.), and affects communities in sub-Saharan Africa. Previously, analogues of a tetrahydroisoquinoline scaffold were reported as having in vitro activity (IC50 = 0.25–70.5 μM) against T. b. rhodesiense. In this study the synthesis and antitrypanosomal activity of 80 compounds based around a core tetrahydroisoquinoline scaffold are reported. A detailed structure activity relationship was revealed, and five derivatives (two of which have been previously reported) with inhibition of T. b. rhodesiense growth in the sub-micromolar range were identified. Four of these (3c, 12b, 17b and 26a) were also found to have good selectivity over mammalian cells (SI > 50). Calculated logD values and preliminary ADME studies predict that these compounds are likely to have good absorption and metabolic stability, with the ability to passively permeate the blood brain barrier. This makes them excellent leads for a blood-brain barrier permeable antitrypanosomal scaffold.
- Cullen, Danica R.,Gallagher, Ashlee,Duncan, Caitlin L.,Pengon, Jutharat,Rattanajak, Roonglawan,Chaplin, Jason,Gunosewoyo, Hendra,Kamchonwongpaisan, Sumalee,Payne, Alan,Mocerino, Mauro
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- Hi-JAK-ing the ubiquitin system: The design and physicochemical optimisation of JAK PROTACs
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PROTACs have recently emerged as a novel paradigm in drug discovery. They can hijack existing biological machinery to selectively degrade proteins of interest, in a catalytic fashion. Here we describe the design, optimisation and biological activity of a
- Bartholomew, Michelle A.,Coe, Diane M.,Evans, John P.,Menon, Malini,Mihut, Andrei,Murphy, John A.,Redmond, Joanna M.,Shah, Rishi R.
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supporting information
(2020/01/31)
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- Novel linker compound and Site-Specific compounds of Antibody-Drug Conjugate Comprising the Same
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The present invention relates to a novel linker compound, and relates to a site-specific antibody-drug conjugate (ADC) compound comprising the same, a method for manufacturing the same, and an anticancer composition comprising the same as an active component. The linker compound produces a uniform ADC compound with excellent site specificity in manufacturing an ADC compound, and the ADC compound comprising the same exhibits an excellent anticancer effect.COPYRIGHT KIPO 2020
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- Substituted xanthine compound and its preparation and use (by machine translation)
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The invention discloses substituted xanthine compounds, a preparation method and applications thereof, and specifically relates to compounds represented by the formula (I), stereo isomers and pharmaceutically acceptable salts thereof, wherein the R1 and R2 are defined in the description. The invention also relates to a pharmaceutical composition containing the compounds, an application of the pharmaceutical composition in preparation of drugs for treating diseases or symptoms caused by high activity of DPP-IV or overexpression of DPP-IV, and a method using the pharmaceutical composition to treat related diseases. The provided compounds can effectively inhibit the activity of DPP-IV.
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Paragraph 0191; 0192; 0193
(2018/09/26)
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- Design, synthesis and biological evaluation of novel podophyllotoxin derivatives bearing 4β-disulfide/trisulfide bond as cytotoxic agents
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A novel series of C-4β-disulfide/trisulfide-containing podophyllotoxin derivatives were designed, synthesized, and biologically evaluated for their cytotoxic activities against human cancer cell lines, including KB (Mouth Epidermal Carcinoma Cells) and KB/VCR (Vincristine-resistant Mouth Epidermal Carcinoma Cells). Most of these compounds exhibited promising moderate to good cytotoxic activities. In particular, some of them displayed even superior activities to that of etoposide, especially for KB/VCR cell lines, indicating that introduction of the disulfide/trisulfide moiety would be beneficial for overcoming the multi-drug resistant limitation of etoposide. Moreover, the metabolic evaluation of the most promising compound was further performed to reveal that disulfide bond can be stable in human plasma over 8 hours, indicating good potential of these compounds for in vivo anti-cancer activities.
- Zhu, Shi-Jun,Ying, Hua-Zhou,Wu, Yan,Qiu, Ni,Liu, Tao,Yang, Bo,Dong, Xiao-Wu,Hu, Yong-Zhou
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p. 103172 - 103183
(2015/12/23)
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- NOVEL CYCLOSPORIN DERIVATIVES AND USES THEREOF
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The present invention relates to a compound of the Formula (I)): or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification; a pharmaceutical composition comprising the same, a method for treating or preventing viral infections, inflammation, dry eye, central nervous disorders, cardiovascular diseases, cancer, obesity, diabetes, muscular dystrophy, and hair loss.
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- NEW Na-SUBSTITUTED CARBOLINE COMPOUNDS USABLE FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
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The present invention relates to a compound according to Formula (III) or a pharmaceutically acceptable salt, solvate, clathrate, hydrate or polymorph thereof and its use.
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Page/Page column 13; 16
(2015/01/16)
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- CARBOLINE COMPOUNDS USABLE IN THE TREATMENT OF NEURODEGENERATIVE DISEASES
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The present invention relates to a compound according to Formula (A) or a pharmaceutically acceptable salt, solvate, clathrate, hydrate or polymorph thereof, and its use.
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Page/Page column 19; 21
(2015/01/16)
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- RADIOLABELED COMPOUNDS AND METHODS THEREOF
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The present invention relates to radiodiagnostic compounds, methods of making those compounds, and methods of use thereof as imaging agents for preferably a HA serotonin 5-HT1A receptor for use in PET or SPECT, preferably PET. Compositions comprising an imaging-effective amount of radiolabeled compounds are also disclosed. The present invention also relates to non-radiolabeled compounds, methods of making those compounds, and methods of use thereof to treat various neurological and/or psychiatric disorders.
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Page/Page column 66; 68
(2011/12/14)
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- IMAGING PROBES
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The present invention relates to molecular probes of the formula (I) {L1 -R1 -L}n-A-CO-NH-R2-L2 (I) as defined herein that allow for the observation of the catalytic activity of a selected cathepsin in in vitro assays, in cells or in multicellu
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Page/Page column 85
(2008/12/07)
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- CHEMICAL COMPOUNDS
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The present invention provides novel compounds that demonstrate protective effects on target cells from HIV infection in a manner as to bind specifically to the chemokine receptor, and which affect the binding of the natural ligand or chemokine to a receptor such as CXCR4 and/or CCR5 of a target cell.
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Page/Page column 67
(2010/10/20)
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- 3- Or 4-monosubstituted phenol derivatives useful as H3 ligands
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The invention relates to 3- or 4-monosubstituted phenol derivatives and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such derivatives. Said 3- or 4-monosubstituted phenol derivatives are H3 ligands and are useful in numerous diseases, disorders and conditions, in particular inflammatory, allergic and respiratory diseases, disorders and conditions.
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Page/Page column 79
(2010/02/14)
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- Synthesis and structure-activity relationships of pyrazine-pyridine biheteroaryls as novel, potent, and selective vascular endothelial growth factor receptor-2 inhibitors
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There is much evidence that direct inhibition of the kinase activity of vascular endothelial growth factor receptor-2 (VEGFR-2) will result in the reduction of angiogenesis and the suppression of tumor growth. Palladium-catalyzed C-C bond, C-N bond formation reactions were used to assemble various pyrazine-pyridine biheteroaryls as potent VEGFR-2 inhibitors. Among them, 4-{5-[6-(3-chloro-phenylamino)-pyrazin-2-yl]-pyridin-3-ylamino}-butan-1-ol (39) and N-{5-[6-(3-chloro-phenylamino)-pyrazin-2-yl]-pyridin-3-yl}-N′, N′-dimethyl-ethane-1,2-diamine (41) exhibited the highest kinase selectivity against fibroblast growth factor receptor kinase, platelet-derived growth factor receptor kinase, and glycogen synthase kinase-3. All of these compounds showed good cellular potency to inhibit VEGF-stimulated proliferation of human umbilical vein endothelial cells (HUVEC) but with modest effects on the unstimulated growth of HUVEC. The low inhibition of these compounds to the growth of tumor cell lines, such as HeLa, HCT-116, and A375 further confirms that these VEGFR-2 inhibitors are not cytotoxic agents. The in vivo antitumor activity of 39 and 41 were demonstrated in the A375 human melanoma xenograft nude mice model. Molecular modeling (QSAR analysis) was conducted in an attempt to rationalize the observed structure-activity relationship.
- Kuo, Gee-Hong,Prouty, Catherine,Wang, Aihua,Emanuel, Stuart,DeAngelis, Alan,Zhang, Yan,Song, Fengbin,Beall, Lawrence,Connolly, Peter J.,Karnachi, Prahba,Chen, Xin,Gruninger, Robert H.,Sechler, Jan,Fuentes-Pesquera, Angel,Middleton, Steven A.,Jolliffe, Linda,Murray, William V.
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p. 4892 - 4909
(2007/10/03)
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- CYCLOOXYGENASE-2 INHIBITORS
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Use of compounds of formula (I) or salts thereof for the preparation of COX-2 inhibitor drugs: R-T1-B-Cc0-N(O)s (formula I), for the treatment and/or prophylaxis of inflammatory processes.
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