Structure-based design and optimization of pyrimidine- and 1,2,4-triazolo[4,3-a]pyrimidine-based matrix metalloproteinase-10/13 inhibitors via Dimroth rearrangement towards targeted polypharmacology
[Display omitted] •Novel hydrazones 6–10 were cyclized to isomeric triazolo[4,3-a]pyrimidines 12–19.•5-Oxo-1,2,4-triazolo[4,3-a]pyrimidines exhibited higher MMP-10/13 inhibition than their regioisomers.•Inactive triazolopyrimidines were rearranged to the potent Dimroth products.•The most active MMP-...
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Published in | Bioorganic chemistry Vol. 96; p. 103616 |
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Main Authors | , , , , , |
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Language | English |
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Abstract | [Display omitted]
•Novel hydrazones 6–10 were cyclized to isomeric triazolo[4,3-a]pyrimidines 12–19.•5-Oxo-1,2,4-triazolo[4,3-a]pyrimidines exhibited higher MMP-10/13 inhibition than their regioisomers.•Inactive triazolopyrimidines were rearranged to the potent Dimroth products.•The most active MMP-10 inhibitor 16 (IC50 = 24 nM) was selective over MMP-13,-9 and-7.•MMP-10/13 inhibitors 16 and 18 exhibited anticancer activities superior to quercetin.
Recently, interest in matrix metalloproteinases (MMPs) -10 and -13 has been revitalized with the growing knowledge on their relevance within the MMPs network and significance of their inhibition for treatment of various diseases like arthritis, cancer, atherosclerosis and Alzheimer. Within this approach, dual MMP-10/13 inhibition was disclosed as new approach for targeted polypharmacology. While several efficient MMP-13 inhibitors are known, very few potent and selective MMP-10 inhibitors were reported. This study describes the design, synthesis and optimization of novel MMP-10/13 inhibitors with enhanced MMP-10 potency and selectivity towards polypharmacology. Starting with a lead fused pyrimidine-based MMP-13 inhibitor with weak MMP-10 inhibition, a structure-based design of pyrimidine and fused pyrimidine scaffolds was rationalized to enhance activity against MMP-10 in parallel with MMP-13. Firstly, a series of 6-methyl pyrimidin-4-one hydrazones 6–10 was synthesized via conventional and ultrasonic-assisted methods, then evaluated for MMP-10/13 inhibition. The most active derivative 9 exhibited acceptable dual potency with 7-fold selectivity for MMP-10 (IC50 = 53 nM) over MMP-13. Such hydrazones were then cyclized to the corresponding isomeric 1,2,4-triazolo[4,3-a]pyrimidines 12–19. Their MMP-10/13 inhibition assay revealed, in most cases, superior dual activities with general MMP-10 selectivity compared to the corresponding precursors 6–10. In addition, a clear structure activity relationship trend was deduced within the identified regioisomers, where the 5-oxo-1,2,4-triazolo[4,3-a]pyrimidine derivatives 15 and 16 were far more active against MMP-10/13 than their regioisomers 12 and 13. Remarkably, the p-bromophenyl derivative 16 exhibited the highest MMP-10 inhibition (IC50 = 24 nM), whereas the p-methoxy derivative 18 was the most potent MMP-13 inhibitor (IC50 = 294 nM). Moreover, 16 exhibited 19-fold selectivity for MMP-10 over MMP-13, 10-fold over MMP-9, and 29-fold over MMP-7. Docking studies were performed to provide reasonable explanation for structure-activity relationships and isoform selectivity. 16 and 18 were then evaluated for their anticancer activities against three human cancers to assess their therapeutic potential at cellular level via MTT assay. Both compounds exhibited superior anticancer activities compared to quercetin. Their in silico ligand efficiency metrics, physicochemical properties and ADME parameters were drug-like. Guided by such findings that point to 16 as the most promising compound in this study, further structure optimization was carried out via photoirradiation-mediated Dimroth rearrangement of the inactive triazolopyrimidine 13 to its potent regioisomer 16. |
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AbstractList | [Display omitted]
•Novel hydrazones 6–10 were cyclized to isomeric triazolo[4,3-a]pyrimidines 12–19.•5-Oxo-1,2,4-triazolo[4,3-a]pyrimidines exhibited higher MMP-10/13 inhibition than their regioisomers.•Inactive triazolopyrimidines were rearranged to the potent Dimroth products.•The most active MMP-10 inhibitor 16 (IC50 = 24 nM) was selective over MMP-13,-9 and-7.•MMP-10/13 inhibitors 16 and 18 exhibited anticancer activities superior to quercetin.
Recently, interest in matrix metalloproteinases (MMPs) -10 and -13 has been revitalized with the growing knowledge on their relevance within the MMPs network and significance of their inhibition for treatment of various diseases like arthritis, cancer, atherosclerosis and Alzheimer. Within this approach, dual MMP-10/13 inhibition was disclosed as new approach for targeted polypharmacology. While several efficient MMP-13 inhibitors are known, very few potent and selective MMP-10 inhibitors were reported. This study describes the design, synthesis and optimization of novel MMP-10/13 inhibitors with enhanced MMP-10 potency and selectivity towards polypharmacology. Starting with a lead fused pyrimidine-based MMP-13 inhibitor with weak MMP-10 inhibition, a structure-based design of pyrimidine and fused pyrimidine scaffolds was rationalized to enhance activity against MMP-10 in parallel with MMP-13. Firstly, a series of 6-methyl pyrimidin-4-one hydrazones 6–10 was synthesized via conventional and ultrasonic-assisted methods, then evaluated for MMP-10/13 inhibition. The most active derivative 9 exhibited acceptable dual potency with 7-fold selectivity for MMP-10 (IC50 = 53 nM) over MMP-13. Such hydrazones were then cyclized to the corresponding isomeric 1,2,4-triazolo[4,3-a]pyrimidines 12–19. Their MMP-10/13 inhibition assay revealed, in most cases, superior dual activities with general MMP-10 selectivity compared to the corresponding precursors 6–10. In addition, a clear structure activity relationship trend was deduced within the identified regioisomers, where the 5-oxo-1,2,4-triazolo[4,3-a]pyrimidine derivatives 15 and 16 were far more active against MMP-10/13 than their regioisomers 12 and 13. Remarkably, the p-bromophenyl derivative 16 exhibited the highest MMP-10 inhibition (IC50 = 24 nM), whereas the p-methoxy derivative 18 was the most potent MMP-13 inhibitor (IC50 = 294 nM). Moreover, 16 exhibited 19-fold selectivity for MMP-10 over MMP-13, 10-fold over MMP-9, and 29-fold over MMP-7. Docking studies were performed to provide reasonable explanation for structure-activity relationships and isoform selectivity. 16 and 18 were then evaluated for their anticancer activities against three human cancers to assess their therapeutic potential at cellular level via MTT assay. Both compounds exhibited superior anticancer activities compared to quercetin. Their in silico ligand efficiency metrics, physicochemical properties and ADME parameters were drug-like. Guided by such findings that point to 16 as the most promising compound in this study, further structure optimization was carried out via photoirradiation-mediated Dimroth rearrangement of the inactive triazolopyrimidine 13 to its potent regioisomer 16. Recently, interest in matrix metalloproteinases (MMPs) -10 and -13 has been revitalized with the growing knowledge on their relevance within the MMPs network and significance of their inhibition for treatment of various diseases like arthritis, cancer, atherosclerosis and Alzheimer. Within this approach, dual MMP-10/13 inhibition was disclosed as new approach for targeted polypharmacology. While several efficient MMP-13 inhibitors are known, very few potent and selective MMP-10 inhibitors were reported. This study describes the design, synthesis and optimization of novel MMP-10/13 inhibitors with enhanced MMP-10 potency and selectivity towards polypharmacology. Starting with a lead fused pyrimidine-based MMP-13 inhibitor with weak MMP-10 inhibition, a structure-based design of pyrimidine and fused pyrimidine scaffolds was rationalized to enhance activity against MMP-10 in parallel with MMP-13. Firstly, a series of 6-methyl pyrimidin-4-one hydrazones 6-10 was synthesized via conventional and ultrasonic-assisted methods, then evaluated for MMP-10/13 inhibition. The most active derivative 9 exhibited acceptable dual potency with 7-fold selectivity for MMP-10 (IC = 53 nM) over MMP-13. Such hydrazones were then cyclized to the corresponding isomeric 1,2,4-triazolo[4,3-a]pyrimidines 12-19. Their MMP-10/13 inhibition assay revealed, in most cases, superior dual activities with general MMP-10 selectivity compared to the corresponding precursors 6-10. In addition, a clear structure activity relationship trend was deduced within the identified regioisomers, where the 5-oxo-1,2,4-triazolo[4,3-a]pyrimidine derivatives 15 and 16 were far more active against MMP-10/13 than their regioisomers 12 and 13. Remarkably, the p-bromophenyl derivative 16 exhibited the highest MMP-10 inhibition (IC = 24 nM), whereas the p-methoxy derivative 18 was the most potent MMP-13 inhibitor (IC = 294 nM). Moreover, 16 exhibited 19-fold selectivity for MMP-10 over MMP-13, 10-fold over MMP-9, and 29-fold over MMP-7. Docking studies were performed to provide reasonable explanation for structure-activity relationships and isoform selectivity. 16 and 18 were then evaluated for their anticancer activities against three human cancers to assess their therapeutic potential at cellular level via MTT assay. Both compounds exhibited superior anticancer activities compared to quercetin. Their in silico ligand efficiency metrics, physicochemical properties and ADME parameters were drug-like. Guided by such findings that point to 16 as the most promising compound in this study, further structure optimization was carried out via photoirradiation-mediated Dimroth rearrangement of the inactive triazolopyrimidine 13 to its potent regioisomer 16. |
ArticleNumber | 103616 |
Author | El Ashry, El Sayed Helmy Abu-Serie, Marwa M. Abd Al Moaty, Mohamed Nabil Awad, Laila Fathy Teleb, Mohamed Ibrahim, Nihal Ahmed |
Author_xml | – sequence: 1 givenname: El Sayed Helmy surname: El Ashry fullname: El Ashry, El Sayed Helmy email: eelashry60@hotmail.com organization: Chemistry Department, Faculty of Science, Alexandria University, Alexandria 21321, Egypt – sequence: 2 givenname: Laila Fathy surname: Awad fullname: Awad, Laila Fathy organization: Chemistry Department, Faculty of Science, Alexandria University, Alexandria 21321, Egypt – sequence: 3 givenname: Mohamed surname: Teleb fullname: Teleb, Mohamed organization: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt – sequence: 4 givenname: Nihal Ahmed surname: Ibrahim fullname: Ibrahim, Nihal Ahmed organization: Chemistry Department, Faculty of Science, Alexandria University, Alexandria 21321, Egypt – sequence: 5 givenname: Marwa M. surname: Abu-Serie fullname: Abu-Serie, Marwa M. organization: Medical Biotechnology Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Egypt – sequence: 6 givenname: Mohamed Nabil surname: Abd Al Moaty fullname: Abd Al Moaty, Mohamed Nabil email: mohamednabil_sc_chem@yahoo.com organization: Chemistry Department, Faculty of Science, Alexandria University, Alexandria 21321, Egypt |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32032847$$D View this record in MEDLINE/PubMed |
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Cites_doi | 10.1586/ecp.12.74 10.1021/acs.jmedchem.7b01001 10.1016/B978-012744481-9/50014-3 10.1021/cr9804543 10.1021/acs.jmedchem.7b00514 10.1593/neo.04283 10.2174/092986711794940905 10.3184/030823408X327875 10.1071/CH9772515 10.3109/s10165-004-0292-7 10.1002/art.22167 10.1016/j.tetlet.2008.06.104 10.1161/01.RES.0000070112.80711.3D 10.1023/A:1020444330011 10.1021/cn100007x 10.1023/A:1012102522787 10.1038/nrm2125 10.1016/S0361-090X(02)00035-1 10.1016/j.gendis.2019.02.004 10.1146/annurev.cellbio.17.1.463 10.1002/cmdc.200700290 10.1200/JCO.2009.23.5556 10.1007/s11172-006-0579-2 10.1016/B978-0-12-417205-0.00015-8 10.1111/j.1745-7254.2005.00068.x 10.1016/j.jmb.2003.12.033 10.4236/ijoc.2017.71002 10.1016/j.chembiol.2004.11.014 10.1016/S0040-4020(01)81656-2 10.1021/jm201705f 10.1021/js9803205 10.1002/open.201600158 10.3390/ijms17030314 10.1161/ATVBAHA.111.231563 10.1023/A:1024926507658 10.4049/jimmunol.173.6.3605 10.1016/j.bmc.2008.03.004 10.1016/j.bioorg.2018.10.054 10.1021/jm020017n 10.1016/j.ejmech.2019.02.051 10.1021/jm701255b 10.1186/1471-2407-9-188 10.1002/cmdc.201700349 10.1016/j.tet.2010.03.009 10.1074/jbc.274.31.21491 10.1016/j.molstruc.2017.11.066 10.1016/S0928-0987(00)00076-2 10.1016/j.cardiores.2005.12.002 10.1016/j.addr.2012.09.019 10.1038/6657 10.1080/10426509208031548 10.1371/journal.pone.0025438 10.1038/nrd4390 10.1038/nrd2796 10.2174/138161207781039706 10.1016/j.biochi.2004.11.019 10.1186/s12885-016-2515-7 10.1016/j.bmc.2014.07.025 10.1016/j.ejmech.2019.111875 10.1021/jm000942e 10.1080/10409230290771483 10.1021/jm500981k 10.1023/B:RUGC.0000030401.30369.4d 10.1021/acs.jmedchem.6b01007 10.1023/A:1011930411574 |
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Keywords | MMP-10/13 Triazolopyrimidine Dimroth rearrangement Polypharmacology Anticancer Pyrimidine |
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References | Molinspiration cheminformatics Nara, Sato, Naito, Mototani, Oki, Yamamoto, Kuno, Santou, Kanzaki, Terauchi, Uchikawa (b0115) 2014; 57 Rizk, El-Naggar, El-Badawy (b0260) 2018; 1155 Whittaker, Floyd, Brown, Gearing (b0025) 1999; 99 Polinsky, Shaw (b0325) 2003 Li, Shi, Tang, Wang, Song, Qian, Qian, Duan (b0095) 2011; 18 Agrawal, Romero-Perez, Jacobsen, Villarreal, Cohen (b0375) 2008; 3 Fischer, Riedl (b0135) 2016; 17 Molsoft L.L.C.: Drug-Likeness and molecular property prediction Leeman, Curran, Murray (b0070) 2002; 37 Salah Ayoup, Wahby, Abdel-Hamid, Ramadan, Teleb, Abu-Serie, Noby (b0385) 2019; 168 Wager, Chandrasekaran, Hou, Troutman, Verhoest, Villalobos, Will (b0295) 2010; 1 Lipinski, Lombardo, Dominy, Feeney (b0300) 2012; 64 El Ashry, Nadeem, Shah, El Kilany (b0175) 2010; vol. 101 Abdel-Fattah, Negm, Gaafar (b0230) 1992; 72 Nagase, Visse, Murphy (b0010) 2006; 69 Fischer, Riedl (b0130) 2013; 8 C. Andrianjara, D.F. Ortwine, A.G. Pavlovsky, W.H. Roark, Matrix metalloproteinase inhibitors, 2002, Patent WO2002064080. (accessed August 1, 2019). Xie, Wan, Liu (b0145) 2017; 12 Nara, Kaieda, Sato, Naito, Mototani, Oki, Yamamoto, Kuno, Santou, Kanzaki, Terauchi (b0170) 2017; 60 Erkin, Krutikov, Pavlovich (b0380) 2003; 73 Page-McCaw, Ewald, Werb (b0005) 2007; 8 Ferlay, Colombet, Soerjomataram (b0205) 2018 Reynolds, Tounge, Bembenek (b0275) 2008; 51 Lauer-Fields, Minond, Chase, Baillargeon, Saldanha, Stawikowska, Hodder, Fields (b0165) 2009; 17 Mathew, Khanna, Kumar, Mathur, Shukla, Ralhan (b0075) 2002; 26 Vandenbroucke, Libert (b0055) 2014; 13 Zhao, Abraham, Lee, Hersey, Luscombe, Beck, Sherborne, Cooper (b0315) 2002; 19 Deraz, Kudo, Yoshida, Obayashi, Tsunematsu, Tani, Siriwardena, Kiekhaee, Qi, Iizuka, Ogawa, Campisi, Muzio, Abiko, Kikuchi, Takata (b0065) 2011; 6 Köhrmann, Kammerer, Kapp, Dietl, Anacker (b0215) 2009; 9 . P. Nagy, I. Grobe, V. Pany, L. Fodor, Rom 63 (1978) 828; C.A 92, 41980n (1980). Choi, Fuerst, Knapinska, Taylor, Smith, Cao, Hart, Fields, Roush (b0140) 2017; 60 Lovejoy, Welch, Carr, Luong, Broka, Hendricks, Campbell, Walker, Martin, Van Wart, Browner (b0225) 1999; 6 Sternlicht, Werb (b0015) 2001; 17 Brown, Nagamatsu (b0190) 1977; 30 Lauria, Abbate, Patella, Gambino, Silvestri, Barone, Almerico (b0265) 2008; 49 Reiter, Bongo, Dyortsok (b0245) 1987; 43 Ertl, Rohde, Selzer (b0330) 2000; 43 Roy, Yang, Moses (b0050) 2009; 27 Arnott, Kumar, Planey (b0285) 2013; 1 Paumier, Thinakaran (b0105) 2019; 1, 6(1) Klupp, Neumann, Kahlert, Diers, Halama, Franz, Schmidt, Koch, Weitz, Schneider, Ulrich (b0210) 2016; 16 Chernyshev, Astakhov, Starikova (b0255) 2010; 66 Irvine, Takahashi, Lockhart, Cheong, Tolan, Selick, Grove (b0340) 1999; 88 H. Chen, O. Engkvist, T. Kogej, Compound Properties and their Influence on Drug Quality. In: Pract. Med. Chem., fourth ed., Elsevier, 2015, pp. 379–393 (Chapter 15). Veber, Johnson, Cheng, Smith, Ward, Kopple (b0310) 2002; 45 Van Themsche, Alain, Kossakowska, Urbanski, Potworowski, St-Pierre (b0080) 2004; 173 Yazdanian, Glynn, Wright, Hawi (b0345) 1998; 15 Nagase, Woessner (b0035) 1999; 274 Maskos (b0045) 2005; 87 Keserü, Makara (b0280) 2009; 8 Reddy, Zhang (b0160) 2013; 6 Yee (b0350) 1997; 14 Vorobev, Kletskii, Krasnikov, Mezheritskii, Steglenko (b0195) 2006; 55 (accessed January 13, 2019). Ayoup, Fouad, Abdel-Hamid, Abu-Serie, Noby, Teleb (b0200) 2020,; 186 Teleb, Rizk, Zhang, Fronczek, Zamponi, Fahmy (b0320) 2019; 83 Nara, Sato, Naito, Mototani, Oki, Yamamoto, Kuno, Santou, Kanzaki, Terauchi, Uchikawa, Kori (b0120) 2014; 22 Yamashita, Furubayashi, Kataoka, Sakane, Sezaki, Tokuda (b0335) 2000; 10 Gill, Kirwan, Seargent, Martin, Tijani, Anikin, Mearns, Bibby, Anthoney, Loadman (b0060) 2004; 6 Quillard, Tesmenitsky, Croce, Travers, Shvartz, Koskinas, Sukhova, Aikawa, Aikawa, Libby (b0100) 2011; 31 Erkin, Krutikov, Chubraev (b0235) 2004; 74 Molecular Operating Environment (MOE), Chemical Computing Group, Montreal, Canada Barksby, Milner, Patterson, Peake, Hui, Robson, Lakey, Middleton, Cawston, Richards, Rowan (b0090) 2006; 54 Jabeen, Pleban, Rinner, Chiba, Ecker (b0290) 2012; 55 PreADMET Tardif, Reboul, Pelletier, Martel-Pelletier (b0085) 2004; 14 Visse, Nagase (b0020) 2003; 92 Hamed, El Ashry, Zeid, Badr (b0185) 2008; 6 Jacobsen, Jourden, Miller, Cohen (b0370) 2010; 1803 Senn, Ott, Lanz, Riedl (b0110) 2017; 13 Nuti, Tuccinardi, Rossello (b0030) 2007; 13 Engel, Pirard, Schimanski, Kirsch, Habermann, Klingler, Schlotte, Weithmann, Wendt (b0150) 2005; 12 ElAshry, El Kilany, Rashed, Assafir (b0180) 1999; vol. 75 Mohamed, Abu-Alola, Al-Zaidi, Saad (b0250) 2016; 7 Bertini, Calderone, Fragai, Luchinat, Mangani, Terni (b0040) 2004; 336 Fischer, Riedl (b0125) 2017; 6 Ma, Chen, Yang (b0355) 2005; 26 Brown (10.1016/j.bioorg.2020.103616_b0190) 1977; 30 Keserü (10.1016/j.bioorg.2020.103616_b0280) 2009; 8 Li (10.1016/j.bioorg.2020.103616_b0095) 2011; 18 Yee (10.1016/j.bioorg.2020.103616_b0350) 1997; 14 Xie (10.1016/j.bioorg.2020.103616_b0145) 2017; 12 Deraz (10.1016/j.bioorg.2020.103616_b0065) 2011; 6 10.1016/j.bioorg.2020.103616_b0365 Gill (10.1016/j.bioorg.2020.103616_b0060) 2004; 6 Salah Ayoup (10.1016/j.bioorg.2020.103616_b0385) 2019; 168 10.1016/j.bioorg.2020.103616_b0240 Lovejoy (10.1016/j.bioorg.2020.103616_b0225) 1999; 6 Lipinski (10.1016/j.bioorg.2020.103616_b0300) 2012; 64 Fischer (10.1016/j.bioorg.2020.103616_b0135) 2016; 17 10.1016/j.bioorg.2020.103616_b0360 Nagase (10.1016/j.bioorg.2020.103616_b0010) 2006; 69 Tardif (10.1016/j.bioorg.2020.103616_b0085) 2004; 14 Page-McCaw (10.1016/j.bioorg.2020.103616_b0005) 2007; 8 Nuti (10.1016/j.bioorg.2020.103616_b0030) 2007; 13 Klupp (10.1016/j.bioorg.2020.103616_b0210) 2016; 16 Vandenbroucke (10.1016/j.bioorg.2020.103616_b0055) 2014; 13 Fischer (10.1016/j.bioorg.2020.103616_b0125) 2017; 6 Barksby (10.1016/j.bioorg.2020.103616_b0090) 2006; 54 Erkin (10.1016/j.bioorg.2020.103616_b0235) 2004; 74 Erkin (10.1016/j.bioorg.2020.103616_b0380) 2003; 73 Zhao (10.1016/j.bioorg.2020.103616_b0315) 2002; 19 Sternlicht (10.1016/j.bioorg.2020.103616_b0015) 2001; 17 Abdel-Fattah (10.1016/j.bioorg.2020.103616_b0230) 1992; 72 Reynolds (10.1016/j.bioorg.2020.103616_b0275) 2008; 51 Ertl (10.1016/j.bioorg.2020.103616_b0330) 2000; 43 Leeman (10.1016/j.bioorg.2020.103616_b0070) 2002; 37 Choi (10.1016/j.bioorg.2020.103616_b0140) 2017; 60 Bertini (10.1016/j.bioorg.2020.103616_b0040) 2004; 336 Lauria (10.1016/j.bioorg.2020.103616_b0265) 2008; 49 Teleb (10.1016/j.bioorg.2020.103616_b0320) 2019; 83 Visse (10.1016/j.bioorg.2020.103616_b0020) 2003; 92 Reiter (10.1016/j.bioorg.2020.103616_b0245) 1987; 43 ElAshry (10.1016/j.bioorg.2020.103616_b0180) 1999; vol. 75 Roy (10.1016/j.bioorg.2020.103616_b0050) 2009; 27 Nagase (10.1016/j.bioorg.2020.103616_b0035) 1999; 274 Agrawal (10.1016/j.bioorg.2020.103616_b0375) 2008; 3 Quillard (10.1016/j.bioorg.2020.103616_b0100) 2011; 31 Veber (10.1016/j.bioorg.2020.103616_b0310) 2002; 45 Ferlay (10.1016/j.bioorg.2020.103616_b0205) 2018 Yazdanian (10.1016/j.bioorg.2020.103616_b0345) 1998; 15 Jabeen (10.1016/j.bioorg.2020.103616_b0290) 2012; 55 10.1016/j.bioorg.2020.103616_b0305 Nara (10.1016/j.bioorg.2020.103616_b0120) 2014; 22 Ayoup (10.1016/j.bioorg.2020.103616_b0200) 2020; 186 Whittaker (10.1016/j.bioorg.2020.103616_b0025) 1999; 99 Lauer-Fields (10.1016/j.bioorg.2020.103616_b0165) 2009; 17 Mathew (10.1016/j.bioorg.2020.103616_b0075) 2002; 26 Wager (10.1016/j.bioorg.2020.103616_b0295) 2010; 1 Arnott (10.1016/j.bioorg.2020.103616_b0285) 2013; 1 10.1016/j.bioorg.2020.103616_b0220 Irvine (10.1016/j.bioorg.2020.103616_b0340) 1999; 88 Reddy (10.1016/j.bioorg.2020.103616_b0160) 2013; 6 Yamashita (10.1016/j.bioorg.2020.103616_b0335) 2000; 10 Polinsky (10.1016/j.bioorg.2020.103616_b0325) 2003 Senn (10.1016/j.bioorg.2020.103616_b0110) 2017; 13 Hamed (10.1016/j.bioorg.2020.103616_b0185) 2008; 6 Ma (10.1016/j.bioorg.2020.103616_b0355) 2005; 26 Engel (10.1016/j.bioorg.2020.103616_b0150) 2005; 12 Paumier (10.1016/j.bioorg.2020.103616_b0105) 2019; 1, 6(1) Jacobsen (10.1016/j.bioorg.2020.103616_b0370) 2010; 1803 Mohamed (10.1016/j.bioorg.2020.103616_b0250) 2016; 7 Maskos (10.1016/j.bioorg.2020.103616_b0045) 2005; 87 Nara (10.1016/j.bioorg.2020.103616_b0170) 2017; 60 Rizk (10.1016/j.bioorg.2020.103616_b0260) 2018; 1155 Fischer (10.1016/j.bioorg.2020.103616_b0130) 2013; 8 Köhrmann (10.1016/j.bioorg.2020.103616_b0215) 2009; 9 Chernyshev (10.1016/j.bioorg.2020.103616_b0255) 2010; 66 10.1016/j.bioorg.2020.103616_b0155 10.1016/j.bioorg.2020.103616_b0270 El Ashry (10.1016/j.bioorg.2020.103616_b0175) 2010; vol. 101 Van Themsche (10.1016/j.bioorg.2020.103616_b0080) 2004; 173 Nara (10.1016/j.bioorg.2020.103616_b0115) 2014; 57 Vorobev (10.1016/j.bioorg.2020.103616_b0195) 2006; 55 |
References_xml | – volume: 8 start-page: 203 year: 2009 end-page: 212 ident: b0280 article-title: The influence of lead discovery strategies on the properties of drug candidates publication-title: Nat. Rev. Drug Discov. contributor: fullname: Makara – volume: 6 start-page: 41 year: 2013 end-page: 47 ident: b0160 article-title: Polypharmacology: drug discovery for the future publication-title: Expert Rev. Clin. Phar. contributor: fullname: Zhang – volume: 45 start-page: 2615 year: 2002 end-page: 2623 ident: b0310 article-title: Molecular properties that influence the oral bioavailability of drug candidates publication-title: J. Med. Chem. contributor: fullname: Kopple – volume: 6 year: 2011 ident: b0065 article-title: MMP-10/stromelysin-2 promotes invasion of head and neck cancer publication-title: PLoS ONE contributor: fullname: Takata – volume: 6 start-page: 217 year: 1999 end-page: 221 ident: b0225 article-title: Crystal structures of MMP-1 and -13 reveal the structural basis for selectivity of collagenase inhibitors publication-title: Nat. Struct. Biol. contributor: fullname: Browner – volume: 31 start-page: 2464 year: 2011 end-page: 2472 ident: b0100 article-title: Selective inhibition of matrix metalloproteinase-13 increases collagen content of established mouse atherosclerosis publication-title: Arterioscler. Thromb. Vasc. Biol. contributor: fullname: Libby – volume: 274 start-page: 21491 year: 1999 end-page: 21494 ident: b0035 article-title: Matrix metalloproteinases publication-title: J. Biol. Chem. contributor: fullname: Woessner – volume: 14 start-page: 763 year: 1997 end-page: 766 ident: b0350 article-title: permeability across Caco-2 cells (colonic) can predict in vivo (small intestinal) absorption in man-fact or myth publication-title: Pharm. Res. contributor: fullname: Yee – volume: 37 start-page: 149 year: 2002 end-page: 166 ident: b0070 article-title: The structure, regulation, and function of human matrix metalloproteinase-13 publication-title: Crit. Rev. Biochem. Mol. Biol. contributor: fullname: Murray – volume: 6 start-page: 334 year: 2008 end-page: 339 ident: b0185 article-title: The Dimroth rearrangement: synthesis and interconversion of isomeric triazolothienopyrimidines publication-title: J. Chem. Res. contributor: fullname: Badr – volume: 22 start-page: 5487 year: 2014 end-page: 5505 ident: b0120 article-title: Thieno[2,3-d]Pyrimidine-2-Carboxamides Bearing a Carboxyben- zene Group at 5-Position: Highly Potent, Selective, and Orally Available MMP-13 Inhibitors Interacting with the S1″ Binding Site publication-title: Bioorg. Med. Chem. contributor: fullname: Kori – volume: 1 start-page: 31 year: 2013 end-page: 36 ident: b0285 article-title: Lipophilicity indices for drug development publication-title: J. Appl. Biopharm. Pharmacokinet. contributor: fullname: Planey – volume: 336 start-page: 707 year: 2004 end-page: 716 ident: b0040 article-title: Crystal structure of the catalytic domain of human matrix metalloproteinase 10 publication-title: J. Mol. Biol. contributor: fullname: Terni – volume: 6 start-page: 192 year: 2017 end-page: 195 ident: b0125 article-title: Targeted fluoro positioning for the discovery of a potent and highly selective matrix metalloproteinase inhibitor publication-title: ChemistryOpen contributor: fullname: Riedl – volume: 99 start-page: 2735 year: 1999 end-page: 2776 ident: b0025 article-title: Design and therapeutic application of matrix metalloproteinase inhibitors publication-title: Chem. Rev. contributor: fullname: Gearing – volume: 72 start-page: 145 year: 1992 end-page: 156 ident: b0230 article-title: Reactions with 6-methyl-2-thiouracil synthesis of dipyrimidino[ 2,1-b: 1',2'-c]thiazine. A new ring system publication-title: Phosphorus, Sulfur Silicon Relat. Elem. contributor: fullname: Gaafar – volume: 8 start-page: 221 year: 2007 end-page: 233 ident: b0005 article-title: Matrix metalloproteinases and the regulation of tissue remodelling publication-title: Nat. Rev. Mol. Cell Biol. contributor: fullname: Werb – volume: 26 start-page: 222 year: 2002 end-page: 228 ident: b0075 article-title: Stromelysin-2 overexpression in human esophageal squamous cell carcinoma: potential clinical implications publication-title: Cancer Detect. Prev. contributor: fullname: Ralhan – volume: 1 start-page: 420 year: 2010 end-page: 434 ident: b0295 article-title: Defining desirable cental nervous system drug space through the alignment of molecular properties, invitro ADME, safety attributes publication-title: ACS Chem. Neurosci. contributor: fullname: Will – volume: 6 start-page: 777 year: 2004 end-page: 785 ident: b0060 article-title: MMP-10 is overexpressed, proteolytically active, and a potential target for therapeutic intervention in human lung carcinomas publication-title: Neoplasia contributor: fullname: Loadman – volume: 13 start-page: 9585 year: 2017 end-page: 9598 ident: b0110 article-title: Targeted polypharmacology: discovery of a highly potent non-hydroxamate dual matrix metalloproteinase (MMP)-10/-13 inhibitor publication-title: J. Med. Chem. contributor: fullname: Riedl – volume: 12 start-page: 181 year: 2005 end-page: 189 ident: b0150 article-title: Structural basis for the highly selective inhibition of MMP-13 publication-title: Chem. Biol. contributor: fullname: Wendt – volume: 12 start-page: 1157 year: 2017 end-page: 1168 ident: b0145 article-title: Recent research advances in selective matrix metalloproteinase-13 inhibitors as anti-osteoarthritis agents publication-title: ChemMedChem contributor: fullname: Liu – volume: 43 start-page: 3714 year: 2000 end-page: 3717 ident: b0330 article-title: Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties publication-title: J. Med. Chem. contributor: fullname: Selzer – volume: 9 start-page: 188 year: 2009 ident: b0215 article-title: Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: New findings and review of the literature publication-title: BMC Cancer contributor: fullname: Anacker – volume: 1155 start-page: 720 year: 2018 end-page: 733 ident: b0260 article-title: Synthesis, spectroscopic characterization and computational chemical study of 5-cyano-2-thiouracil derivatives as potential antimicrobial agents publication-title: J. Mol. Struct. contributor: fullname: El-Badawy – volume: 55 start-page: 3261 year: 2012 end-page: 3273 ident: b0290 article-title: Structure-activity relationships, ligand efficiency, and lipophilic efficiency profiles of benzophenone-type inhibitors of the multidrug transporter P-glycoprotein publication-title: J. Med. Chem. contributor: fullname: Ecker – start-page: 147 year: 2003 end-page: 157 ident: b0325 article-title: High-speed chemistry libraries: assessment of druglikeness publication-title: Pract. Med. Chem. contributor: fullname: Shaw – volume: 64 start-page: 4 year: 2012 end-page: 17 ident: b0300 article-title: Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings publication-title: Adv. Drug Deliv. Rev. contributor: fullname: Feeney – volume: 10 start-page: 195 year: 2000 end-page: 204 ident: b0335 article-title: Optimized conditions for prediction of intestinal drug permeability using Caco-2 cells publication-title: Eur. J. Pharm. Sci. contributor: fullname: Tokuda – volume: 54 start-page: 3244 year: 2006 end-page: 3253 ident: b0090 article-title: MatrixMetalloproteinase 10 promotion of collagenolysis via procollagenase activation: implications for cartilage degradation in arthritis publication-title: Arthritis Rheum. contributor: fullname: Rowan – volume: 83 start-page: 354 year: 2019 end-page: 366 ident: b0320 article-title: Design, synthesis and pharmacological evaluation of some substituted dihydropyrimidines with L-/T-type calcium channel blocking activities publication-title: Bioorg. Chem. contributor: fullname: Fahmy – year: 2018 ident: b0205 article-title: Global and regional estimates of the incidence and mortality for 38 cancers: GLOBOCAN 2018 contributor: fullname: Soerjomataram – volume: 26 start-page: 500 year: 2005 ident: b0355 article-title: Predictive model of blood-brain barrier penetration of organic compounds publication-title: Acta Pharmacol. Sin. contributor: fullname: Yang – volume: 168 start-page: 340 year: 2019 end-page: 356 ident: b0385 article-title: Design, synthesis and biological evaluation of novel α-acyloxy carboxamides publication-title: Eur. J. Med. Chem. contributor: fullname: Noby – volume: 69 start-page: 562 year: 2006 end-page: 573 ident: b0010 article-title: Structure and function of matrix metalloproteinases and TIMPs publication-title: Cardiovasc. Res. contributor: fullname: Murphy – volume: vol. 75 start-page: 79 year: 1999 ident: b0180 article-title: Dimroth Rearrangement. Translocation of heteroatoms in heterocyclic rings and its role in ring transformations of heterocycles publication-title: Advances in Heterocyclic Chemistry contributor: fullname: Assafir – volume: 3 start-page: 812 year: 2008 end-page: 820 ident: b0375 article-title: Zinc-binding groups modulate selective inhibition of MMPs publication-title: ChemMedChem: Chem. Enabling Drug Discov. contributor: fullname: Cohen – volume: 60 start-page: 5816 year: 2017 end-page: 5825 ident: b0140 article-title: Structure-based design and synthesis of potent and selective matrix metalloproteinase 13 inhibitors publication-title: J. Med. Chem. contributor: fullname: Roush – volume: 92 start-page: 827 year: 2003 end-page: 839 ident: b0020 article-title: Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry publication-title: Circ. Res. contributor: fullname: Nagase – volume: 19 start-page: 1446 year: 2002 end-page: 1457 ident: b0315 article-title: Rate-limited steps of human oral absorption and QSAR studies publication-title: Pharm. Res. contributor: fullname: Cooper – volume: 13 start-page: 2087 year: 2007 end-page: 2100 ident: b0030 article-title: Matrix metalloproteinase inhibitors: new challenges in the era of post broad-spectrum inhibitors publication-title: Curr. Pharm. Des. contributor: fullname: Rossello – volume: 66 start-page: 3301 year: 2010 end-page: 3313 ident: b0255 article-title: Reaction of 1-substituted 3, 5-diamino-1, 2, 4-triazoles with β-keto esters: synthesis and new rearrangement of mesoionic 3-amino-2H-[1,2,4] triazolo-[4,3- publication-title: Tetrahedron contributor: fullname: Starikova – volume: 14 start-page: 197 year: 2004 end-page: 204 ident: b0085 article-title: Ten years in the life of an enzyme: the story of the human MMP-13 (Collagenase-3) publication-title: Mod. Rheumatol. contributor: fullname: Martel-Pelletier – volume: 60 start-page: 608 year: 2017 end-page: 626 ident: b0170 article-title: Discovery of novel, highly potent, and selective matrix metalloproteinase (MMP)-13 inhibitors with a 1, 2, 4-triazol-3-yl moiety as a zinc binding group using a structure-based design approach publication-title: J. Med. Chem. contributor: fullname: Terauchi – volume: 88 start-page: 28 year: 1999 end-page: 33 ident: b0340 article-title: MDCK (Madin–Darby canine kidney) cells: a tool for membrane permeability screening publication-title: J. Pharm. Sci. contributor: fullname: Grove – volume: 1, 6(1) start-page: 1 year: 2019 end-page: 2 ident: b0105 article-title: Matrix metalloproteinase 13, a new target for therapy in Alzheimer's disease publication-title: Genes Diseases. contributor: fullname: Thinakaran – volume: 87 start-page: 249 year: 2005 end-page: 263 ident: b0045 article-title: Crystal structures of MMPs in complex with physiological and pharmacological inhibitors publication-title: Biochimie contributor: fullname: Maskos – volume: vol. 101 start-page: 162 year: 2010 ident: b0175 article-title: Recent advances in Dimroth rearrangement. A valuable tool for synthesis of heterocycles publication-title: Advances in Heterocylic Chemistry contributor: fullname: El Kilany – volume: 57 start-page: 8886 year: 2014 end-page: 8902 ident: b0115 article-title: Discovery of novel, highly potent, and selective quinazoline-2-carboxamide-based matrix metalloproteinase (MMP)-13 inhibitors without a zinc binding group using a structure-based design approach publication-title: J. Med. Chem. contributor: fullname: Uchikawa – volume: 18 start-page: 977 year: 2011 end-page: 1001 ident: b0095 article-title: New hope for the treatment of osteoarthritis through selective inhibition of MMP-13 publication-title: Curr. Med. Chem. contributor: fullname: Duan – volume: 173 start-page: 3605 year: 2004 end-page: 3611 ident: b0080 article-title: Stromelysin-2 (matrix metalloproteinase 10) is inducible in lymphoma cells and accelerates the growth of lymphoid tumors in vivo publication-title: J. Immunol. contributor: fullname: St-Pierre – volume: 17 start-page: 463 year: 2001 end-page: 516 ident: b0015 article-title: How matrix metalloproteinases regulate cell behavior publication-title: Annu. Rev. Cell Dev. Biol. contributor: fullname: Werb – volume: 186 year: 2020, ident: b0200 article-title: Battle tactics against MMP-9; discovery of novel non-hydroxamate MMP-9 inhibitors endowed with PI3K/AKT signaling attenuation and caspase 3/7 activation publication-title: Eur. J. Med. Chem. contributor: fullname: Teleb – volume: 74 start-page: 423 year: 2004 end-page: 427 ident: b0235 article-title: Synthesis of 2-(Pyrazol-1-yl)pyrimidine Derivatives by Cyclocondensation of Ethyl Acetoacetate (6-Methyl-4-oxo-3,4-dihydropyrimidin-2-yl)hydrazone with Aromatic Aldehydes publication-title: Russ. J. Gen. Chem. contributor: fullname: Chubraev – volume: 7 start-page: 12 year: 2016 end-page: 24 ident: b0250 article-title: Cyclocondensation reactions of hydrazonoyl chlorides with some azines: synthesis of new fused heterocycles of expected microbiological activity publication-title: IJOC contributor: fullname: Saad – volume: 51 start-page: 2432 year: 2008 end-page: 2438 ident: b0275 article-title: Ligand binding efficiency: trends, physical basis and implications publication-title: J. Med. Chem. contributor: fullname: Bembenek – volume: 55 start-page: 2247 year: 2006 end-page: 2255 ident: b0195 article-title: Studies on mechanisms of the rearrangement of thieno[3,2-e][1,2,4]triazolo[4,3-c]pyrimidines into thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidines publication-title: Russ. Chem. Bull. Int. Ed. contributor: fullname: Steglenko – volume: 43 start-page: 2497 year: 1987 end-page: 2504 ident: b0245 article-title: On triazoles XI. Structure elucidation of isomeric 1,2,4-triazolopyrimidinones publication-title: Tetrahedron contributor: fullname: Dyortsok – volume: 27 start-page: 5287 year: 2009 end-page: 5297 ident: b0050 article-title: Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer publication-title: J. Clin. Oncol. contributor: fullname: Moses – volume: 8 start-page: 1445 year: 2013 end-page: 1461 ident: b0130 article-title: Strategic targeting of multiple water-mediated interactions: a concise and rational structure-based design approach to potent and selective MMP-13 inhibitors publication-title: ChemMedChem contributor: fullname: Riedl – volume: 30 start-page: 2515 year: 1977 end-page: 2525 ident: b0190 article-title: Isomerizations in to the Dimroth rearrangement. III. The conversion of simple s-Triazolo[4,3-a]pyrimidines into their [1,5-a] Isomers publication-title: Aust. J. Chem. contributor: fullname: Nagamatsu – volume: 16 start-page: 494 year: 2016 ident: b0210 article-title: Serum MMP7, MMP10 and MMP12 level as negative prognostic markers in colon cancer patients publication-title: BMC Cancer contributor: fullname: Ulrich – volume: 17 start-page: 990 year: 2009 end-page: 1005 ident: b0165 article-title: High throughput screening of potentially selective MMP-13 exosite inhibitors utilizing a triple-helical FRET substrate publication-title: Bioorg. Med. Chem. contributor: fullname: Fields – volume: 1803 start-page: 72 year: 2010 end-page: 94 ident: b0370 article-title: To bind zinc or not to bind zinc: an examination of innovative approaches to improved metalloproteinase inhibition publication-title: BBA-Mol. Cell Res. contributor: fullname: Cohen – volume: 73 start-page: 463 year: 2003 end-page: 466 ident: b0380 article-title: Unified synthetic approach to 2-substituted 6-methylisocytosines and their 5-bromo derivatives publication-title: Russ. J. Gen. Chem. contributor: fullname: Pavlovich – volume: 13 start-page: 904 year: 2014 end-page: 927 ident: b0055 article-title: Is there new hope for therapeutic matrix metalloproteinase inhibition? publication-title: Nat. Rev. Drug Discov. contributor: fullname: Libert – volume: 17 start-page: 314 year: 2016 ident: b0135 article-title: Molecular recognition of the catalytic zinc (II) Ion in MMP-13: structure-based evolution of an allosteric inhibitor to dual binding mode inhibitors with improved lipophilic ligand efficiencies publication-title: Int. J. Mol. Sci. contributor: fullname: Riedl – volume: 49 start-page: 5125 year: 2008 end-page: 5128 ident: b0265 article-title: Pyrazolo[3,4- publication-title: Tetrahedron Lett. contributor: fullname: Almerico – volume: 15 start-page: 1490 year: 1998 ident: b0345 article-title: Correlating partitioning and Caco-2 cell permeability of structurally diverse small molecular weight compounds publication-title: Pharm. Res. contributor: fullname: Hawi – volume: 6 start-page: 41 year: 2013 ident: 10.1016/j.bioorg.2020.103616_b0160 article-title: Polypharmacology: drug discovery for the future publication-title: Expert Rev. Clin. Phar. doi: 10.1586/ecp.12.74 contributor: fullname: Reddy – volume: 13 start-page: 9585 year: 2017 ident: 10.1016/j.bioorg.2020.103616_b0110 article-title: Targeted polypharmacology: discovery of a highly potent non-hydroxamate dual matrix metalloproteinase (MMP)-10/-13 inhibitor publication-title: J. Med. Chem. doi: 10.1021/acs.jmedchem.7b01001 contributor: fullname: Senn – start-page: 147 year: 2003 ident: 10.1016/j.bioorg.2020.103616_b0325 article-title: High-speed chemistry libraries: assessment of druglikeness publication-title: Pract. Med. Chem. doi: 10.1016/B978-012744481-9/50014-3 contributor: fullname: Polinsky – volume: 99 start-page: 2735 year: 1999 ident: 10.1016/j.bioorg.2020.103616_b0025 article-title: Design and therapeutic application of matrix metalloproteinase inhibitors publication-title: Chem. Rev. doi: 10.1021/cr9804543 contributor: fullname: Whittaker – volume: 60 start-page: 5816 year: 2017 ident: 10.1016/j.bioorg.2020.103616_b0140 article-title: Structure-based design and synthesis of potent and selective matrix metalloproteinase 13 inhibitors publication-title: J. Med. Chem. doi: 10.1021/acs.jmedchem.7b00514 contributor: fullname: Choi – volume: 6 start-page: 777 year: 2004 ident: 10.1016/j.bioorg.2020.103616_b0060 article-title: MMP-10 is overexpressed, proteolytically active, and a potential target for therapeutic intervention in human lung carcinomas publication-title: Neoplasia doi: 10.1593/neo.04283 contributor: fullname: Gill – volume: 18 start-page: 977 year: 2011 ident: 10.1016/j.bioorg.2020.103616_b0095 article-title: New hope for the treatment of osteoarthritis through selective inhibition of MMP-13 publication-title: Curr. Med. Chem. doi: 10.2174/092986711794940905 contributor: fullname: Li – volume: 6 start-page: 334 year: 2008 ident: 10.1016/j.bioorg.2020.103616_b0185 article-title: The Dimroth rearrangement: synthesis and interconversion of isomeric triazolothienopyrimidines publication-title: J. Chem. Res. doi: 10.3184/030823408X327875 contributor: fullname: Hamed – volume: 30 start-page: 2515 year: 1977 ident: 10.1016/j.bioorg.2020.103616_b0190 article-title: Isomerizations in to the Dimroth rearrangement. III. The conversion of simple s-Triazolo[4,3-a]pyrimidines into their [1,5-a] Isomers publication-title: Aust. J. Chem. doi: 10.1071/CH9772515 contributor: fullname: Brown – volume: 14 start-page: 197 year: 2004 ident: 10.1016/j.bioorg.2020.103616_b0085 article-title: Ten years in the life of an enzyme: the story of the human MMP-13 (Collagenase-3) publication-title: Mod. Rheumatol. doi: 10.3109/s10165-004-0292-7 contributor: fullname: Tardif – volume: 54 start-page: 3244 year: 2006 ident: 10.1016/j.bioorg.2020.103616_b0090 article-title: MatrixMetalloproteinase 10 promotion of collagenolysis via procollagenase activation: implications for cartilage degradation in arthritis publication-title: Arthritis Rheum. doi: 10.1002/art.22167 contributor: fullname: Barksby – volume: 49 start-page: 5125 year: 2008 ident: 10.1016/j.bioorg.2020.103616_b0265 article-title: Pyrazolo[3,4-d][1,2,3]triazolo[1,5-a]pyrimidine: a new ring system through Dimroth rearrangement publication-title: Tetrahedron Lett.. doi: 10.1016/j.tetlet.2008.06.104 contributor: fullname: Lauria – volume: 92 start-page: 827 year: 2003 ident: 10.1016/j.bioorg.2020.103616_b0020 article-title: Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry publication-title: Circ. Res. doi: 10.1161/01.RES.0000070112.80711.3D contributor: fullname: Visse – volume: 19 start-page: 1446 year: 2002 ident: 10.1016/j.bioorg.2020.103616_b0315 article-title: Rate-limited steps of human oral absorption and QSAR studies publication-title: Pharm. Res. doi: 10.1023/A:1020444330011 contributor: fullname: Zhao – volume: 1 start-page: 420 year: 2010 ident: 10.1016/j.bioorg.2020.103616_b0295 article-title: Defining desirable cental nervous system drug space through the alignment of molecular properties, invitro ADME, safety attributes publication-title: ACS Chem. Neurosci. doi: 10.1021/cn100007x contributor: fullname: Wager – volume: 14 start-page: 763 issue: 6 year: 1997 ident: 10.1016/j.bioorg.2020.103616_b0350 article-title: In vitro permeability across Caco-2 cells (colonic) can predict in vivo (small intestinal) absorption in man-fact or myth publication-title: Pharm. Res. doi: 10.1023/A:1012102522787 contributor: fullname: Yee – volume: 8 start-page: 221 year: 2007 ident: 10.1016/j.bioorg.2020.103616_b0005 article-title: Matrix metalloproteinases and the regulation of tissue remodelling publication-title: Nat. Rev. Mol. Cell Biol. doi: 10.1038/nrm2125 contributor: fullname: Page-McCaw – volume: 8 start-page: 1445 year: 2013 ident: 10.1016/j.bioorg.2020.103616_b0130 article-title: Strategic targeting of multiple water-mediated interactions: a concise and rational structure-based design approach to potent and selective MMP-13 inhibitors publication-title: ChemMedChem contributor: fullname: Fischer – volume: 26 start-page: 222 year: 2002 ident: 10.1016/j.bioorg.2020.103616_b0075 article-title: Stromelysin-2 overexpression in human esophageal squamous cell carcinoma: potential clinical implications publication-title: Cancer Detect. Prev. doi: 10.1016/S0361-090X(02)00035-1 contributor: fullname: Mathew – volume: 1, 6(1) start-page: 1 year: 2019 ident: 10.1016/j.bioorg.2020.103616_b0105 article-title: Matrix metalloproteinase 13, a new target for therapy in Alzheimer's disease publication-title: Genes Diseases. doi: 10.1016/j.gendis.2019.02.004 contributor: fullname: Paumier – volume: 17 start-page: 463 year: 2001 ident: 10.1016/j.bioorg.2020.103616_b0015 article-title: How matrix metalloproteinases regulate cell behavior publication-title: Annu. Rev. Cell Dev. Biol. doi: 10.1146/annurev.cellbio.17.1.463 contributor: fullname: Sternlicht – volume: 1 start-page: 31 year: 2013 ident: 10.1016/j.bioorg.2020.103616_b0285 article-title: Lipophilicity indices for drug development publication-title: J. Appl. Biopharm. Pharmacokinet. contributor: fullname: Arnott – volume: 3 start-page: 812 issue: 5 year: 2008 ident: 10.1016/j.bioorg.2020.103616_b0375 article-title: Zinc-binding groups modulate selective inhibition of MMPs publication-title: ChemMedChem: Chem. Enabling Drug Discov. doi: 10.1002/cmdc.200700290 contributor: fullname: Agrawal – volume: 27 start-page: 5287 year: 2009 ident: 10.1016/j.bioorg.2020.103616_b0050 article-title: Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer publication-title: J. Clin. Oncol. doi: 10.1200/JCO.2009.23.5556 contributor: fullname: Roy – ident: 10.1016/j.bioorg.2020.103616_b0365 – volume: 55 start-page: 2247 year: 2006 ident: 10.1016/j.bioorg.2020.103616_b0195 article-title: Studies on mechanisms of the rearrangement of thieno[3,2-e][1,2,4]triazolo[4,3-c]pyrimidines into thieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidines publication-title: Russ. Chem. Bull. Int. Ed. doi: 10.1007/s11172-006-0579-2 contributor: fullname: Vorobev – ident: 10.1016/j.bioorg.2020.103616_b0155 – ident: 10.1016/j.bioorg.2020.103616_b0270 doi: 10.1016/B978-0-12-417205-0.00015-8 – volume: 26 start-page: 500 issue: 4 year: 2005 ident: 10.1016/j.bioorg.2020.103616_b0355 article-title: Predictive model of blood-brain barrier penetration of organic compounds publication-title: Acta Pharmacol. Sin. doi: 10.1111/j.1745-7254.2005.00068.x contributor: fullname: Ma – volume: 336 start-page: 707 issue: 3 year: 2004 ident: 10.1016/j.bioorg.2020.103616_b0040 article-title: Crystal structure of the catalytic domain of human matrix metalloproteinase 10 publication-title: J. Mol. Biol. doi: 10.1016/j.jmb.2003.12.033 contributor: fullname: Bertini – volume: 7 start-page: 12 issue: 1 year: 2016 ident: 10.1016/j.bioorg.2020.103616_b0250 article-title: Cyclocondensation reactions of hydrazonoyl chlorides with some azines: synthesis of new fused heterocycles of expected microbiological activity publication-title: IJOC doi: 10.4236/ijoc.2017.71002 contributor: fullname: Mohamed – volume: 12 start-page: 181 issue: 2 year: 2005 ident: 10.1016/j.bioorg.2020.103616_b0150 article-title: Structural basis for the highly selective inhibition of MMP-13 publication-title: Chem. Biol. doi: 10.1016/j.chembiol.2004.11.014 contributor: fullname: Engel – volume: 43 start-page: 2497 year: 1987 ident: 10.1016/j.bioorg.2020.103616_b0245 article-title: On triazoles XI. Structure elucidation of isomeric 1,2,4-triazolopyrimidinones publication-title: Tetrahedron doi: 10.1016/S0040-4020(01)81656-2 contributor: fullname: Reiter – volume: 55 start-page: 3261 year: 2012 ident: 10.1016/j.bioorg.2020.103616_b0290 article-title: Structure-activity relationships, ligand efficiency, and lipophilic efficiency profiles of benzophenone-type inhibitors of the multidrug transporter P-glycoprotein publication-title: J. Med. Chem. doi: 10.1021/jm201705f contributor: fullname: Jabeen – volume: 88 start-page: 28 issue: 1 year: 1999 ident: 10.1016/j.bioorg.2020.103616_b0340 article-title: MDCK (Madin–Darby canine kidney) cells: a tool for membrane permeability screening publication-title: J. Pharm. Sci. doi: 10.1021/js9803205 contributor: fullname: Irvine – volume: 6 start-page: 192 year: 2017 ident: 10.1016/j.bioorg.2020.103616_b0125 article-title: Targeted fluoro positioning for the discovery of a potent and highly selective matrix metalloproteinase inhibitor publication-title: ChemistryOpen doi: 10.1002/open.201600158 contributor: fullname: Fischer – year: 2018 ident: 10.1016/j.bioorg.2020.103616_b0205 contributor: fullname: Ferlay – volume: 17 start-page: 314 year: 2016 ident: 10.1016/j.bioorg.2020.103616_b0135 article-title: Molecular recognition of the catalytic zinc (II) Ion in MMP-13: structure-based evolution of an allosteric inhibitor to dual binding mode inhibitors with improved lipophilic ligand efficiencies publication-title: Int. J. Mol. Sci. doi: 10.3390/ijms17030314 contributor: fullname: Fischer – volume: vol. 75 start-page: 79 year: 1999 ident: 10.1016/j.bioorg.2020.103616_b0180 article-title: Dimroth Rearrangement. Translocation of heteroatoms in heterocyclic rings and its role in ring transformations of heterocycles contributor: fullname: ElAshry – volume: 31 start-page: 2464 year: 2011 ident: 10.1016/j.bioorg.2020.103616_b0100 article-title: Selective inhibition of matrix metalloproteinase-13 increases collagen content of established mouse atherosclerosis publication-title: Arterioscler. Thromb. Vasc. Biol. doi: 10.1161/ATVBAHA.111.231563 contributor: fullname: Quillard – volume: 73 start-page: 463 year: 2003 ident: 10.1016/j.bioorg.2020.103616_b0380 article-title: Unified synthetic approach to 2-substituted 6-methylisocytosines and their 5-bromo derivatives publication-title: Russ. J. Gen. Chem. doi: 10.1023/A:1024926507658 contributor: fullname: Erkin – volume: 173 start-page: 3605 year: 2004 ident: 10.1016/j.bioorg.2020.103616_b0080 article-title: Stromelysin-2 (matrix metalloproteinase 10) is inducible in lymphoma cells and accelerates the growth of lymphoid tumors in vivo publication-title: J. Immunol. doi: 10.4049/jimmunol.173.6.3605 contributor: fullname: Van Themsche – volume: 17 start-page: 990 issue: 3 year: 2009 ident: 10.1016/j.bioorg.2020.103616_b0165 article-title: High throughput screening of potentially selective MMP-13 exosite inhibitors utilizing a triple-helical FRET substrate publication-title: Bioorg. Med. Chem. doi: 10.1016/j.bmc.2008.03.004 contributor: fullname: Lauer-Fields – ident: 10.1016/j.bioorg.2020.103616_b0240 – volume: 83 start-page: 354 year: 2019 ident: 10.1016/j.bioorg.2020.103616_b0320 article-title: Design, synthesis and pharmacological evaluation of some substituted dihydropyrimidines with L-/T-type calcium channel blocking activities publication-title: Bioorg. Chem. doi: 10.1016/j.bioorg.2018.10.054 contributor: fullname: Teleb – volume: 45 start-page: 2615 year: 2002 ident: 10.1016/j.bioorg.2020.103616_b0310 article-title: Molecular properties that influence the oral bioavailability of drug candidates publication-title: J. Med. Chem. doi: 10.1021/jm020017n contributor: fullname: Veber – volume: 168 start-page: 340 year: 2019 ident: 10.1016/j.bioorg.2020.103616_b0385 article-title: Design, synthesis and biological evaluation of novel α-acyloxy carboxamides via Passerini reaction as caspase 3/7 activators publication-title: Eur. J. Med. Chem. doi: 10.1016/j.ejmech.2019.02.051 contributor: fullname: Salah Ayoup – volume: 51 start-page: 2432 year: 2008 ident: 10.1016/j.bioorg.2020.103616_b0275 article-title: Ligand binding efficiency: trends, physical basis and implications publication-title: J. Med. Chem. doi: 10.1021/jm701255b contributor: fullname: Reynolds – volume: vol. 101 start-page: 162 year: 2010 ident: 10.1016/j.bioorg.2020.103616_b0175 article-title: Recent advances in Dimroth rearrangement. A valuable tool for synthesis of heterocycles contributor: fullname: El Ashry – volume: 9 start-page: 188 issue: 1 year: 2009 ident: 10.1016/j.bioorg.2020.103616_b0215 article-title: Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: New findings and review of the literature publication-title: BMC Cancer doi: 10.1186/1471-2407-9-188 contributor: fullname: Köhrmann – volume: 12 start-page: 1157 year: 2017 ident: 10.1016/j.bioorg.2020.103616_b0145 article-title: Recent research advances in selective matrix metalloproteinase-13 inhibitors as anti-osteoarthritis agents publication-title: ChemMedChem doi: 10.1002/cmdc.201700349 contributor: fullname: Xie – volume: 66 start-page: 3301 issue: 18 year: 2010 ident: 10.1016/j.bioorg.2020.103616_b0255 article-title: Reaction of 1-substituted 3, 5-diamino-1, 2, 4-triazoles with β-keto esters: synthesis and new rearrangement of mesoionic 3-amino-2H-[1,2,4] triazolo-[4,3-a] pyrimidin-5-ones publication-title: Tetrahedron doi: 10.1016/j.tet.2010.03.009 contributor: fullname: Chernyshev – volume: 274 start-page: 21491 year: 1999 ident: 10.1016/j.bioorg.2020.103616_b0035 article-title: Matrix metalloproteinases publication-title: J. Biol. Chem. doi: 10.1074/jbc.274.31.21491 contributor: fullname: Nagase – volume: 1155 start-page: 720 year: 2018 ident: 10.1016/j.bioorg.2020.103616_b0260 article-title: Synthesis, spectroscopic characterization and computational chemical study of 5-cyano-2-thiouracil derivatives as potential antimicrobial agents publication-title: J. Mol. Struct. doi: 10.1016/j.molstruc.2017.11.066 contributor: fullname: Rizk – volume: 10 start-page: 195 issue: 3 year: 2000 ident: 10.1016/j.bioorg.2020.103616_b0335 article-title: Optimized conditions for prediction of intestinal drug permeability using Caco-2 cells publication-title: Eur. J. Pharm. Sci. doi: 10.1016/S0928-0987(00)00076-2 contributor: fullname: Yamashita – volume: 69 start-page: 562 year: 2006 ident: 10.1016/j.bioorg.2020.103616_b0010 article-title: Structure and function of matrix metalloproteinases and TIMPs publication-title: Cardiovasc. Res. doi: 10.1016/j.cardiores.2005.12.002 contributor: fullname: Nagase – volume: 64 start-page: 4 year: 2012 ident: 10.1016/j.bioorg.2020.103616_b0300 article-title: Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings publication-title: Adv. Drug Deliv. Rev. doi: 10.1016/j.addr.2012.09.019 contributor: fullname: Lipinski – volume: 6 start-page: 217 year: 1999 ident: 10.1016/j.bioorg.2020.103616_b0225 article-title: Crystal structures of MMP-1 and -13 reveal the structural basis for selectivity of collagenase inhibitors publication-title: Nat. Struct. Biol. doi: 10.1038/6657 contributor: fullname: Lovejoy – volume: 72 start-page: 145 year: 1992 ident: 10.1016/j.bioorg.2020.103616_b0230 article-title: Reactions with 6-methyl-2-thiouracil synthesis of dipyrimidino[ 2,1-b: 1',2'-c]thiazine. A new ring system publication-title: Phosphorus, Sulfur Silicon Relat. Elem. doi: 10.1080/10426509208031548 contributor: fullname: Abdel-Fattah – volume: 6 year: 2011 ident: 10.1016/j.bioorg.2020.103616_b0065 article-title: MMP-10/stromelysin-2 promotes invasion of head and neck cancer publication-title: PLoS ONE doi: 10.1371/journal.pone.0025438 contributor: fullname: Deraz – ident: 10.1016/j.bioorg.2020.103616_b0220 – volume: 13 start-page: 904 year: 2014 ident: 10.1016/j.bioorg.2020.103616_b0055 article-title: Is there new hope for therapeutic matrix metalloproteinase inhibition? publication-title: Nat. Rev. Drug Discov. doi: 10.1038/nrd4390 contributor: fullname: Vandenbroucke – volume: 8 start-page: 203 year: 2009 ident: 10.1016/j.bioorg.2020.103616_b0280 article-title: The influence of lead discovery strategies on the properties of drug candidates publication-title: Nat. Rev. Drug Discov. doi: 10.1038/nrd2796 contributor: fullname: Keserü – volume: 1803 start-page: 72 issue: 1 year: 2010 ident: 10.1016/j.bioorg.2020.103616_b0370 article-title: To bind zinc or not to bind zinc: an examination of innovative approaches to improved metalloproteinase inhibition publication-title: BBA-Mol. Cell Res. contributor: fullname: Jacobsen – ident: 10.1016/j.bioorg.2020.103616_b0305 – volume: 13 start-page: 2087 year: 2007 ident: 10.1016/j.bioorg.2020.103616_b0030 article-title: Matrix metalloproteinase inhibitors: new challenges in the era of post broad-spectrum inhibitors publication-title: Curr. Pharm. Des. doi: 10.2174/138161207781039706 contributor: fullname: Nuti – volume: 87 start-page: 249 issue: 3–4 year: 2005 ident: 10.1016/j.bioorg.2020.103616_b0045 article-title: Crystal structures of MMPs in complex with physiological and pharmacological inhibitors publication-title: Biochimie doi: 10.1016/j.biochi.2004.11.019 contributor: fullname: Maskos – volume: 16 start-page: 494 issue: 1 year: 2016 ident: 10.1016/j.bioorg.2020.103616_b0210 article-title: Serum MMP7, MMP10 and MMP12 level as negative prognostic markers in colon cancer patients publication-title: BMC Cancer doi: 10.1186/s12885-016-2515-7 contributor: fullname: Klupp – volume: 22 start-page: 5487 year: 2014 ident: 10.1016/j.bioorg.2020.103616_b0120 article-title: Thieno[2,3-d]Pyrimidine-2-Carboxamides Bearing a Carboxyben- zene Group at 5-Position: Highly Potent, Selective, and Orally Available MMP-13 Inhibitors Interacting with the S1″ Binding Site publication-title: Bioorg. Med. Chem. doi: 10.1016/j.bmc.2014.07.025 contributor: fullname: Nara – volume: 186 year: 2020 ident: 10.1016/j.bioorg.2020.103616_b0200 article-title: Battle tactics against MMP-9; discovery of novel non-hydroxamate MMP-9 inhibitors endowed with PI3K/AKT signaling attenuation and caspase 3/7 activation via Ugi bis-amide synthesis publication-title: Eur. J. Med. Chem. doi: 10.1016/j.ejmech.2019.111875 contributor: fullname: Ayoup – volume: 43 start-page: 3714 year: 2000 ident: 10.1016/j.bioorg.2020.103616_b0330 article-title: Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties publication-title: J. Med. Chem. doi: 10.1021/jm000942e contributor: fullname: Ertl – volume: 37 start-page: 149 year: 2002 ident: 10.1016/j.bioorg.2020.103616_b0070 article-title: The structure, regulation, and function of human matrix metalloproteinase-13 publication-title: Crit. Rev. Biochem. Mol. Biol. doi: 10.1080/10409230290771483 contributor: fullname: Leeman – ident: 10.1016/j.bioorg.2020.103616_b0360 – volume: 57 start-page: 8886 year: 2014 ident: 10.1016/j.bioorg.2020.103616_b0115 article-title: Discovery of novel, highly potent, and selective quinazoline-2-carboxamide-based matrix metalloproteinase (MMP)-13 inhibitors without a zinc binding group using a structure-based design approach publication-title: J. Med. Chem. doi: 10.1021/jm500981k contributor: fullname: Nara – volume: 74 start-page: 423 year: 2004 ident: 10.1016/j.bioorg.2020.103616_b0235 article-title: Synthesis of 2-(Pyrazol-1-yl)pyrimidine Derivatives by Cyclocondensation of Ethyl Acetoacetate (6-Methyl-4-oxo-3,4-dihydropyrimidin-2-yl)hydrazone with Aromatic Aldehydes publication-title: Russ. J. Gen. Chem. doi: 10.1023/B:RUGC.0000030401.30369.4d contributor: fullname: Erkin – volume: 60 start-page: 608 issue: 2 year: 2017 ident: 10.1016/j.bioorg.2020.103616_b0170 article-title: Discovery of novel, highly potent, and selective matrix metalloproteinase (MMP)-13 inhibitors with a 1, 2, 4-triazol-3-yl moiety as a zinc binding group using a structure-based design approach publication-title: J. Med. Chem. doi: 10.1021/acs.jmedchem.6b01007 contributor: fullname: Nara – volume: 15 start-page: 1490 issue: 9 year: 1998 ident: 10.1016/j.bioorg.2020.103616_b0345 article-title: Correlating partitioning and Caco-2 cell permeability of structurally diverse small molecular weight compounds publication-title: Pharm. Res. doi: 10.1023/A:1011930411574 contributor: fullname: Yazdanian |
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•Novel hydrazones 6–10 were cyclized to isomeric triazolo[4,3-a]pyrimidines 12–19.•5-Oxo-1,2,4-triazolo[4,3-a]pyrimidines exhibited higher... Recently, interest in matrix metalloproteinases (MMPs) -10 and -13 has been revitalized with the growing knowledge on their relevance within the MMPs network... |
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SubjectTerms | Anticancer Cell Line, Tumor Dimroth rearrangement Drug Design Drug Screening Assays, Antitumor Humans Matrix Metalloproteinase 10 - metabolism Matrix Metalloproteinase 13 - metabolism Matrix Metalloproteinase Inhibitors - chemistry Matrix Metalloproteinase Inhibitors - pharmacology MMP-10/13 Molecular Docking Simulation Neoplasms - drug therapy Neoplasms - metabolism Polypharmacology Pyridines - chemistry Pyridines - pharmacology Pyrimidine Structure-Activity Relationship Triazoles - chemistry Triazoles - pharmacology Triazolopyrimidine |
Title | Structure-based design and optimization of pyrimidine- and 1,2,4-triazolo[4,3-a]pyrimidine-based matrix metalloproteinase-10/13 inhibitors via Dimroth rearrangement towards targeted polypharmacology |
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