- Molecular design, synthesis and in vitro biological evaluation of thienopyrimidine–hydroxamic acids as chimeric kinase HDAC inhibitors: a challenging approach to combat cancer
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A series of thieno[2,3-d]pyrimidine-based hydroxamic acid hybrids was designed and synthesised as multitarget anti-cancer agents, through incorporating the pharmacophore of EGFR, VEGFR2 into the inhibitory functionality of HDAC6. Three compounds (12c, 15b and 20b) were promising hits, whereas (12c) exhibited potent VEGFR2 inhibition (IC50=185 nM), potent EGFR inhibition (IC50=1.14 μM), and mild HDAC6 inhibition (23% inhibition). Moreover, compound (15c) was the most potent dual inhibitor among all the synthesised compounds, as it exhibited potent EGFR and VEGFR2 inhibition (IC50=19 nM) and (IC50=5.58 μM), respectively. While compounds (20d) and (7c) displayed nanomolar selective kinase inhibition with EGFR IC50= 68 nM and VEGFR2 IC50= 191 nM, respectively. All of the synthesised compounds were screened in vitro for their cytotoxic effect on 60 human NCI tumour cell lines. Additionally, molecular docking studies and ADMET studies were carried out to gain further insight into their binding mode and predict the pharmacokinetic properties of all the synthesised inhibitors.
- Abdel-Atty, Mona M.,Farag, Nahla A.,Serya, Rabah A. T.,Abouzid, Khaled A. M.,Mowafy, Samar
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p. 1290 - 1312
(2021/07/09)
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- COMPOUNDS, COMPOSITIONS, AND METHODS FOR MODULATING ANDROGEN RECEPTOR ACTIVITY
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Inhibitors of androgen receptors that are thienopyrimidine derivatives corresponding to formula (I), and salts thereof, and associated compositions and methods of treatment:
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Page/Page column 13; 14; 46; 47
(2020/07/15)
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- SUBSTITUTED CONDENSED THIOPHENES AS MODULATORS OF STING
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A compound of formula (I), wherein: R1 is selected from (i) H, (ii) C3-6cycloalkyl, (iii) C3-7heterocyclyl optionally substituted with a group selected from: methyl and ester, and (iv) linear or branched C1-4alkyl optionally substituted with a group selected from: alkoxy, amino, amido, acylamido, acyloxy, alkyl carboxyl ester, alkyl carbamoyl, alkyl carbamoyl ester, phenyl, phosphonate ester, C3-7heterocyclyl optionally substituted with a group selected from methyl and oxo, and a naturally occurring amino acid, optionally N-substituted with a group selected from methyl, acetyl and boc; A1 is CRA or N; A2 is CRB or N; A3 is CRC or N; A4 is CRD or N; where no more than two of A1, A2, A3, and A4 may be N; one or two of RA, RB, RC, and RD, (if present) are selected from H, F, Cl, Br, Me, CF3, cyclopropyl, cyano, OMe, OEt, CH2OH, CH2OMe and CH2NMe2; the remainder of RA, RB, RC, and RD, (if present) are H; Y is O, NH or CH2; RY is selected from: (RYA) and (RYB).
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Page/Page column 113
(2019/12/04)
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- Hetero-aromatic compound and its use in medicine
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The invention provides a hetero-aromatic compound or a stereisomer, geometric isomer, tautomer, despinner, nitrogen oxide, hydrate, solvate, metabolite, metabolism precursor and pharmaceutically acceptable salt or prodrug thereof, which is used for treating proliferative diseases. The invention also discloses a pharmaceutical composition containing the compound and an application of the compound or pharmaceutical composition thereof in preparation of a medicine for treating proliferative diseases.
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Paragraph 1416; 1422-1424
(2019/07/04)
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- Design, synthesis, neuroprotective, antibacterial activities and docking studies of novel thieno[2,3-d]pyrimidine-alkyne Mannich base and oxadiazole hybrids
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A series of thieno[2,3-d]pyrimidine alkyne Mannich base derivatives (7a-e, 8a-e) and thieno[2,3-d]pyrimidine 1,3,4-oxadiazole derivatives (9a-e, 10a-e) have been synthesized and evaluated for their neuroprotective and neurotoxicity activities where 9a, 10d displayed good neuroprotection 10.6 and 11.88 μg/mL respectively against the H2O2 induced cell death at the EC50 values and 9b, 9d showed respective toxic effects on PC12 cells at CC50 86.12 and 94.16 μg/mL. Compounds 9a, 9e, 10a and 10b showed strong antibacterial activity against two gram positive (S. aureus, B. subtilis) and two gram-negative strains (E. coli, P. aeruginosa) and showed good binding affinities with C(30) carotenoid dehydrosqualene synthase, Gyrase A and LpxC. This is the first report for the demonstration of thieno[2,3-d] pyrimidine derivatives as promising neuroprotective agents against H2O2 induced neurotoxicity on PC12 cells.
- Triloknadh, Settypalli,Venkata Rao, Chunduri,Nagaraju, Kerru,Hari Krishna, Nallapaneni,Venkata Ramaiah, Chintha,Rajendra, Wudayagiri,Trinath, Daggupati,Suneetha, Yeguvapalli
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supporting information
p. 1663 - 1669
(2018/03/29)
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- Design and synthesis of novel protein kinase CK2 inhibitors on the base of 4-aminothieno[2,3-d]pyrimidines
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An extension of our previous research work has resulted in a number of new ATP-competitive CK2 inhibitors that have been identified among 4-aminothieno[2,3-d]pyrimidine derivatives. The most active compounds obtained in the course of the research are 3-(5-p-tolyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5e (NHTP23, IC50 = 0.01 μM), 3-(5-phenyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5g (NHTP25, IC50 = 0.065 μM) and 3-(6-methyl-5-phenyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5n (NHTP33, IC50 = 0.008 μM). Structure-activity relationships of the tested 4-aminothieno[2,3-d]pyrimidine derivatives have been studied and their binding mode with ATP-acceptor site of CK2 has been proposed. A negative effect of intramolecular hydrogen bonding in the compounds' structure is discussed.
- Ostrynska, Olga V.,Balanda, Anatoliy O.,Bdzhola, Volodymyr G.,Golub, Andriy G.,Kotey, Igor M.,Kukharenko, Olexander P.,Gryshchenko, Andrii A.,Briukhovetska, Nadiia V.,Yarmoluk, Sergiy M.
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p. 148 - 160
(2016/04/05)
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- COMPOUNDS FOR ERADICATING OR INHIBITING PROLIFERATION OF CANCER STEM CELLS
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The present invention provides compounds of formula (I), compositions, uses thereof and methods for eradicating or inhibiting proliferation of cancer stem cells which includes killing; and/or inducing apoptosis in cancer stem cells. Included within the sc
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Page/Page column 36; 38
(2015/10/05)
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- CANCER STEM CELL TARGETING COMPOUNDS
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The present invention provides compounds of formula (I), compositions, uses thereof and methods for inhibiting proliferation or obliterating cancer stem cells which includes killing; and/or inducing apoptosis in cancer stem cells. Included within the scope of such compounds, compositions, uses thereof and methods are those in which proliferation of cancer stem cells are selectively eradicated or inhibited.
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Page/Page column 34
(2015/10/05)
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- Design, synthesis & evaluation of condensed 2H-4-arylaminopyrimidines as novel antifungal agents
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A small, focussed library of condensed 2H-4-arylaminopyrimidines, with 3-diversity points, based on an initial design by molecular docking study of this scaffold at the active site of the fungal enzyme of cytochrome P 450 family, lanosterol 14α
- Jain, Kishor S.,Khedkar, Vijay M.,Arya, Nikhilesh,Rane, Prasad V.,Chaskar, Pratip K.,Coutinho, Evans C.
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p. 166 - 175
(2014/04/03)
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- Novel dual use of formamide-POCl3 mixture for the efficient, one-pot synthesis of condensed 2 H-pyrimidin-4-amine libraries under microwave irradiation
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The novel dual use of formamide-POCl3 mixture for the incorporation of a C-N fragment to form the pyrimidine nucleus and its subsequent chlorination in an efficient, one-pot synthesis of potentially bioactive condensed 2H-pyrimidin-4-amine libraries under
- Jain, Kishore S.,Kathiravan, Muthu K.,Bariwal, Jitender B.,Chaskar, Pratip K.,Tompe, Santosh S.,Arya, Nikhilesh
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p. 719 - 727
(2013/01/15)
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- PHENYL-ANILINE SUBSTITUTED BICYCLIC COMPOUNDS USEFUL AS KINASE INHIBITORS
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Compounds having the formula (I), and pharmaceutically acceptable salts, prodrugs, and solvates thereof, are useful as kinase inhibitors, wherein R, R1 , R2, R5, R6a, R6b, J, K, X and Z are as described in the specification.
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Page/Page column 57
(2010/02/11)
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- New thieno compounds. Part 14: Synthesis of 4 amino-substituted thieno[2,3-d]pyrimidine-6-carboxylic acid derivatives
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The combination of a basic and a carboxylic ester group in the thieno[2,3-d]pyrimidine structure could give interesting biological activities. Starting from the diester of 2-amino-4-methylthiophene-3,5-diacid the ethylesters of 3,4-dihydro-5-methyl-4-oxot
- Baumgartner,Pech,Bohm
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p. 192 - 194
(2007/10/02)
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- TRANSFORMATIONS OF 5-METHYL-6-CARBETHOXY-3,4-DIHYDROTHIENOPYRIMIDINE FOR SYNTHESIS OF 4-METHOXY-, 4-ALKYLAMINO-, AND OTHER DERIVATIVES OF THIENOPYRIMIDINE
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4-Chloro derivatives of thienopyrimidine are formed by the action of phosphorus oxychloride on 5-methyl- and 5-methyl-6-carbethoxythienopyrimidin-4-ones.Action of nucleophilic reagents (methanol, sodium methylate, primary and secondary amines) on these chloro derivatives gave 4-methoxy-, 4-alkylamino-, and 4-dialkylamino substituted thienopyrimidines.It was found that 4-methoxy derivatives of thienopyrimidines undergo a thermal rearrangement into 3-methyl-substituted thienopyrimid-4-ones.In the bromination of 5-methyl-4-chloro- and 5-methyl-4-methoxy-substituted thienopyrimidines by N-bromosuccinimide, 5-bromomethyl derivatives of thienopyrimidine are formed, from which, by the action of primary and secondary amines, 5-aminomethyl-substituted thienopyrimidines were obtained.A synthesis of 1,2,3,4-tetrahydro-1,3-diazepinothienopyrimidines was also carried out.
- Grinev, A. N.,Kaplina, N. V.
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p. 767 - 770
(2007/10/02)
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