Design, synthesis and structural exploration of novel fluorinated dabigatran derivatives as direct thrombin inhibitors
Twenty-one fluorinated dabigatran derivatives were designed based on the bioisosteric principle. All derivatives were synthesised and evaluated for their thrombin inhibitory activity in vitro. Among these compounds, 14h, 14m, 14s and 14t were potent and the activity was in the range of reference dru...
Saved in:
| Published in: | European journal of medicinal chemistry Vol. 96; pp. 122 - 138 |
|---|---|
| Main Authors: | , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
ISSY-LES-MOULINEAUX
Elsevier Masson SAS
26.05.2015
Elsevier |
| Subjects: | |
| ISSN: | 0223-5234, 1768-3254 |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Abstract | Twenty-one fluorinated dabigatran derivatives were designed based on the bioisosteric principle. All derivatives were synthesised and evaluated for their thrombin inhibitory activity in vitro. Among these compounds, 14h, 14m, 14s and 14t were potent and the activity was in the range of reference drug, dabigatran. Three structural changes were introduced in these 21 compounds to elucidate the structure–activity relationship of the drugs. In addition, prodrugs of compounds 14h and 14s were developed to investigate their anticoagulant activities in vivo. In these experiments, compound 16 showed a fairly strong inhibitory effect on thrombin-induced platelet aggregation, and demonstrated potent activity for inhibiting arteriovenous thrombosis with an inhibition rate of (73 ± 6) %, which was comparable to that of dabigatran etexilate (76 ± 2) %. Moreover, molecular docking studies were performed to understand the binding interactions of active compounds 14h, 14s and 14t with thrombin protein (PDB ID:1KTS). Contour maps obtained from the 3D-QSAR model are meaningful in designing more active molecules to act as direct inhibitors of thrombin.
[Display omitted]
•Twenty-one novel fluorinated dabigatran derivatives were designed and synthesized.•All compounds efficiently inhibited thrombin at nanomolar levels in vitro.•Compound 14s showed the best inhibitory activity against thrombin (IC50 = 3.23 nM).•Compound 16 exhibited a potent inhibition against arteriovenous thrombosis in vivo.•Computational studies were performed to explain the inhibitory mechanism and SAR. |
|---|---|
| AbstractList | Twenty-one fluorinated dabigatran derivatives were designed based on the bioisosteric principle. All derivatives were synthesised and evaluated for their thrombin inhibitory activity in vitro. Among these compounds, 14h, 14m, 14s and 14t were potent and the activity was in the range of reference drug, dabigatran. Three structural changes were introduced in these 21 compounds to elucidate the structure activity relationship of the drugs. In addition, prodrugs of compounds 14h and 14s were developed to investigate their anticoagulant activities in vivo. In these experiments, compound 16 showed a fairly strong inhibitory effect on thrombin-induced platelet aggregation, and demonstrated potent activity for inhibiting arteriovenous thrombosis with an inhibition rate of (73 +/- 6) %, which was comparable to that of dabigatran etexilate (76 +/- 2) %. Moreover, molecular docking studies were performed to understand the binding interactions of active compounds 14h, 14s and 14t with thrombin protein (PDB ID:1 KTS). Contour maps obtained from the 3D-QSAR model are meaningful in designing more active molecules to act as direct inhibitors of thrombin. (C) 2015 Elsevier Masson SAS. All rights reserved. Twenty-one fluorinated dabigatran derivatives were designed based on the bioisosteric principle. All derivatives were synthesised and evaluated for their thrombin inhibitory activity in vitro. Among these compounds, 14h, 14m, 14s and 14t were potent and the activity was in the range of reference drug, dabigatran. Three structural changes were introduced in these 21 compounds to elucidate the structure–activity relationship of the drugs. In addition, prodrugs of compounds 14h and 14s were developed to investigate their anticoagulant activities in vivo. In these experiments, compound 16 showed a fairly strong inhibitory effect on thrombin-induced platelet aggregation, and demonstrated potent activity for inhibiting arteriovenous thrombosis with an inhibition rate of (73 ± 6) %, which was comparable to that of dabigatran etexilate (76 ± 2) %. Moreover, molecular docking studies were performed to understand the binding interactions of active compounds 14h, 14s and 14t with thrombin protein (PDB ID:1KTS). Contour maps obtained from the 3D-QSAR model are meaningful in designing more active molecules to act as direct inhibitors of thrombin. [Display omitted] •Twenty-one novel fluorinated dabigatran derivatives were designed and synthesized.•All compounds efficiently inhibited thrombin at nanomolar levels in vitro.•Compound 14s showed the best inhibitory activity against thrombin (IC50 = 3.23 nM).•Compound 16 exhibited a potent inhibition against arteriovenous thrombosis in vivo.•Computational studies were performed to explain the inhibitory mechanism and SAR. Twenty-one fluorinated dabigatran derivatives were designed based on the bioisosteric principle. All derivatives were synthesised and evaluated for their thrombin inhibitory activity in vitro. Among these compounds, 14h, 14m, 14s and 14t were potent and the activity was in the range of reference drug, dabigatran. Three structural changes were introduced in these 21 compounds to elucidate the structure-activity relationship of the drugs. In addition, prodrugs of compounds 14h and 14s were developed to investigate their anticoagulant activities in vivo. In these experiments, compound 16 showed a fairly strong inhibitory effect on thrombin-induced platelet aggregation, and demonstrated potent activity for inhibiting arteriovenous thrombosis with an inhibition rate of (73 ± 6) %, which was comparable to that of dabigatran etexilate (76 ± 2) %. Moreover, molecular docking studies were performed to understand the binding interactions of active compounds 14h, 14s and 14t with thrombin protein (PDB ID:1KTS). Contour maps obtained from the 3D-QSAR model are meaningful in designing more active molecules to act as direct inhibitors of thrombin. |
| Author | Ren, Wei-Xin Dong, Ming-Hui Li, Mei-Lin Ren, Yu-Jie |
| Author_xml | – sequence: 1 givenname: Mei-Lin surname: Li fullname: Li, Mei-Lin – sequence: 2 givenname: Yu-Jie surname: Ren fullname: Ren, Yu-Jie email: clab@sit.edu.cn – sequence: 3 givenname: Ming-Hui surname: Dong fullname: Dong, Ming-Hui – sequence: 4 givenname: Wei-Xin surname: Ren fullname: Ren, Wei-Xin |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25874337$$D View this record in MEDLINE/PubMed |
| BookMark | eNqNkU1vEzEQhi1URNPCP0DIRyRIGHvtzS6HSih8SpW49G75Y7ZxtLGD7Q303-OyoQcOwMlzeJ53rHkvyFmIAQl5zmDFgLVvdivc7dFuVxyYXIFYAeOPyIKt227ZcCnOyAI4b5aSN-KcXOS8AwDZAjwh51x2a9E06wU5vsfsb8Nrmu9C2dY5Ux0czSVNtkxJjxR_HMaYdPEx0DjQEI840mGcYvJBF3TUaeNvdUk6UIfJHyt6xBqTqfMJbaFlm-Le-EB92HrjS0z5KXk86DHjs9N7SW4-frjZfF5ef_30ZfPuemkFdGXZYGtAS9sCG4xzQyvBaa57w7iF3gxS951rBBixlrxthYUOBgk4aKm10c0leTnHHlL8NmEuau-zxXHUAeOUFWs71jMQfV_RFyd0Mnt06pD8Xqc79ftUFXg1A9_RxCFbj8HiA1Zv20i5ZlzWifFKd_9Pb3z5dd9NnEKpqphVm2LOCYcHjYG6r17t1Fy9uq9egVDzxrd_aPYUW6vx47_kq1nGWsbRY1KnL88VKhf93wN-Ak_VzPY |
| CitedBy_id | crossref_primary_10_1016_j_ejmech_2021_114035 crossref_primary_10_1007_s11172_023_4099_0 crossref_primary_10_1038_s41587_022_01337_8 crossref_primary_10_1134_S1070363223140359 crossref_primary_10_1007_s10967_025_10091_5 crossref_primary_10_1016_j_bmc_2015_11_025 crossref_primary_10_1007_s00894_018_3582_2 crossref_primary_10_1371_journal_pone_0142774 crossref_primary_10_1016_j_ejmech_2016_12_010 crossref_primary_10_3390_molecules200611046 crossref_primary_10_1002_hlca_201500527 crossref_primary_10_3390_ijms22062817 crossref_primary_10_1016_j_ejmech_2016_12_015 crossref_primary_10_1080_07391102_2020_1815580 crossref_primary_10_1097_FJC_0000000000001493 crossref_primary_10_3389_fphar_2022_1074576 crossref_primary_10_3390_molecules28093851 crossref_primary_10_1002_ardp_202300206 crossref_primary_10_1016_j_ejmech_2016_05_020 crossref_primary_10_1016_j_ijbiomac_2018_01_084 |
| Cites_doi | 10.1097/HCO.0b013e3283540857 10.1021/jm3013757 10.1111/j.1538-7836.2007.02500.x 10.1021/op700134j 10.1016/j.ejmech.2013.06.034 10.1016/j.thromres.2011.11.001 10.1016/j.ejmech.2011.03.019 10.1161/hc0802.104331 10.1039/B610213C 10.1126/science.1131943 10.1161/ATVBAHA.108.179788 10.1007/s00204-011-0720-3 10.1016/j.jfluchem.2006.01.011 10.3810/pgm.2013.07.2683 10.1016/j.ejmech.2014.09.036 10.1111/j.1538-7836.2004.01100.x 10.1016/j.jfluchem.2006.06.007 10.1111/j.1365-2125.2007.02899.x 10.1136/heartjnl-2012-302101 10.1007/s00101-003-0602-z 10.1160/TH09-11-0758 10.1016/j.jacc.2012.03.019 10.1021/jm040129+ 10.1177/0091270004268446 10.1016/j.ejmech.2014.01.025 10.1021/jm800219f 10.1111/j.1538-7836.2005.01365.x 10.1016/j.cjca.2013.03.002 10.1016/S0960-894X(01)00842-3 10.1007/s11239-007-0108-7 10.1021/jm0109513 10.1039/b610213c 10.1186/1756-8722-4-53 |
| ContentType | Journal Article |
| Copyright | 2015 Elsevier Masson SAS Copyright © 2015 Elsevier Masson SAS. All rights reserved. |
| Copyright_xml | – notice: 2015 Elsevier Masson SAS – notice: Copyright © 2015 Elsevier Masson SAS. All rights reserved. |
| DBID | AAYXX CITATION 17B 1KM BLEPL DTL EGQ GVOUP CGR CUY CVF ECM EIF NPM 7U8 7X8 C1K JXQ |
| DOI | 10.1016/j.ejmech.2015.04.012 |
| DatabaseName | CrossRef Web of Knowledge Index Chemicus Web of Science Core Collection Science Citation Index Expanded Web of Science Primary (SCIE, SSCI & AHCI) Web of Science - Science Citation Index Expanded - 2015 Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed TOXLINE MEDLINE - Academic Environmental Sciences and Pollution Management Toxline |
| DatabaseTitle | CrossRef Web of Science MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) TOXLINE MEDLINE - Academic Environmental Sciences and Pollution Management |
| DatabaseTitleList | Web of Science MEDLINE TOXLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 1KM name: Index Chemicus url: https://www.webofscience.com/wos/woscc/search-with-editions?editions=WOS.IC sourceTypes: Enrichment Source Index Database – sequence: 3 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Chemistry Pharmacy, Therapeutics, & Pharmacology |
| EISSN | 1768-3254 |
| EndPage | 138 |
| ExternalDocumentID | 25874337 000355712500012 10_1016_j_ejmech_2015_04_012 S0223523415002615 |
| Genre | Research Support, Non-U.S. Gov't Journal Article |
| GrantInformation_xml | – fundername: Science and Technology Commission of Shanghai Municipality; Science & Technology Commission of Shanghai Municipality (STCSM) grantid: 13142201001; 13DZ1930402; 13DZ1930403 |
| GroupedDBID | --- --K --M .~1 0R~ 1RT 1~. 1~5 4.4 457 4G. 53G 5GY 5VS 7-5 71M 8P~ 9JM 9JN AACTN AAEDT AAEDW AAIAV AAIKJ AAKOC AALRI AAOAW AAQFI AARLI AATCM AAXUO ABFRF ABGSF ABJNI ABMAC ABOCM ABUDA ABYKQ ABZDS ACDAQ ACGFO ACIUM ACRLP ADBBV ADECG ADEZE ADUVX AEBSH AEFWE AEHWI AEKER AENEX AFKWA AFTJW AFXIZ AFZHZ AGHFR AGUBO AGYEJ AHHHB AIEXJ AIKHN AITUG AJBFU AJOXV AJSZI ALCLG ALMA_UNASSIGNED_HOLDINGS AMFUW AMRAJ AXJTR BKOJK BLXMC CS3 DOVZS DU5 EBS EFJIC EFLBG EJD EO8 EO9 EP2 EP3 F5P FDB FIRID FLBIZ FNPLU FYGXN G-Q GBLVA J1W KOM M2Y M34 M41 MO0 N9A O-L O9- OAUVE OGGZJ OZT P-8 P-9 P2P PC. Q38 RIG ROL RPZ SCC SDF SDG SES SPC SPCBC SSK SSP SSU SSZ T5K ~G- 1B1 29G 9DU AAQXK AATTM AAXKI AAYWO AAYXX ABFNM ABWVN ABXDB ACLOT ACNNM ACRPL ACVFH ADCNI ADMUD ADNMO AEIPS AEUPX AFJKZ AFPUW AGQPQ AGRDE AIGII AIIUN AKBMS AKRWK AKYEP ANKPU APXCP ASPBG AVWKF AZFZN CITATION EFKBS FEDTE FGOYB G-2 HMS HMT HVGLF HZ~ IHE R2- SCB SEW SOC SPT WUQ ~HD 17B 1KM BLEPL DTL GROUPED_WOS_SCIENCE_CITATION_INDEX_EXPANDED GROUPED_WOS_WEB_OF_SCIENCE AAYOK CGR CUY CVF ECM EIF NPM PKN 7U8 7X8 C1K JXQ |
| ID | FETCH-LOGICAL-c408t-3e6b0a5c601fbddf650da2a9b12c09bf5a98d340b4752664c080f50efa5aaba3 |
| ISICitedReferencesCount | 24 |
| ISICitedReferencesURI | https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestApp=WOS&DestLinkType=CitingArticles&UT=000355712500012 |
| ISSN | 0223-5234 |
| IngestDate | Thu Oct 02 06:37:11 EDT 2025 Wed Feb 19 02:09:34 EST 2025 Wed Oct 22 10:01:32 EDT 2025 Fri Dec 05 23:04:58 EST 2025 Tue Nov 18 22:39:05 EST 2025 Sat Nov 29 05:48:49 EST 2025 Fri Feb 23 02:20:08 EST 2024 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Keywords | PCHLJHIZYCJIRV-UHFFFAOYSA-N VOUZBDCMLRKPJO-UHFFFAOYSA-N Fluorinated dabigatran derivatives Anticoagulant activity VXHVCHCIBLEMEP-UHFFFAOYSA-N Synthesis GEKYNTRKYSTSLA-UHFFFAOYSA-N VAVOSXMRECUDQH-UHFFFAOYSA-N KRSAIDAGFIQHKH-UHFFFAOYSA-N BOTCGBVIRXRCMV-UHFFFAOYSA-N OOAZYCAGKGLCBH-UHFFFAOYSA-N MGYJAWXXBHSYJR-UHFFFAOYSA-N YWELKWQVPBDJPT-UHFFFAOYSA-N CROWVEKUOCYWCS-UHFFFAOYSA-N XTYGSCUQCSCHAX-UHFFFAOYSA-N OTENLGUOGPNQJN-UHFFFAOYSA-N YAJKHBQWDQUNJH-UHFFFAOYSA-N FKEYMTIYCZZRMZ-UHFFFAOYSA-N IXZRETUOHYOMNR-UHFFFAOYSA-N DIDZBBLRDSTKCE-UHFFFAOYSA-N LWEUEDJYLBHXAZ-UHFFFAOYSA-N Computer-aided simulation BPSNCXSWJKHOLW-UHFFFAOYSA-N MADJUFXLRYLAOT-UHFFFAOYSA-N FYWSZWQUPJQUBF-UHFFFAOYSA-N ZLPRAKFLAXBDOM-UHFFFAOYSA-N LYJLSFCGAWKCDC-UHFFFAOYSA-N MEDICINAL CHEMISTRY XIMELAGATRAN IN-VITRO POTENT STROKE PREVENTION ORAL ANTICOAGULANTS ETEXILATE |
| Language | English |
| License | Copyright © 2015 Elsevier Masson SAS. All rights reserved. |
| LinkModel | OpenURL |
| LogoURL | https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg |
| MergedId | FETCHMERGED-LOGICAL-c408t-3e6b0a5c601fbddf650da2a9b12c09bf5a98d340b4752664c080f50efa5aaba3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | https://doi.org/10.7270/q2q81frh |
| PMID | 25874337 |
| PQID | 1681910499 |
| PQPubID | 23479 |
| PageCount | 17 |
| ParticipantIDs | proquest_miscellaneous_1681910499 webofscience_primary_000355712500012 webofscience_primary_000355712500012CitationCount elsevier_sciencedirect_doi_10_1016_j_ejmech_2015_04_012 pubmed_primary_25874337 crossref_citationtrail_10_1016_j_ejmech_2015_04_012 crossref_primary_10_1016_j_ejmech_2015_04_012 |
| PublicationCentury | 2000 |
| PublicationDate | 2015-05-26 |
| PublicationDateYYYYMMDD | 2015-05-26 |
| PublicationDate_xml | – month: 05 year: 2015 text: 2015-05-26 day: 26 |
| PublicationDecade | 2010 |
| PublicationPlace | ISSY-LES-MOULINEAUX |
| PublicationPlace_xml | – name: ISSY-LES-MOULINEAUX – name: France |
| PublicationTitle | European journal of medicinal chemistry |
| PublicationTitleAbbrev | EUR J MED CHEM |
| PublicationTitleAlternate | Eur J Med Chem |
| PublicationYear | 2015 |
| Publisher | Elsevier Masson SAS Elsevier |
| Publisher_xml | – name: Elsevier Masson SAS – name: Elsevier |
| References | Xing, Wang, Zhou, Su, Du (bib38) 2010; 41 Liew, Eikelboom, O'Donnell (bib12) 2012; 27 Zhu, Fan, Zhong (bib37) 2012; 22 Sheng, Che, Wang, Wang, Cao, Miao (bib24) 2011; 46 Zhang (bib42) 2013; 13 Poller, Jespersen, lbrahim (bib17) 2009; 361 Fujii, Miyajima, Masuno, Kagechika (bib25) 2013; 56 Kirk (bib29) 2006; 127 Mosesson (bib34) 2005; 3 Lauria, Tutone, Barone, Almerico (bib35) 2014; 75 Bailey, Scantlebury, Smyth (bib2) 2009; 29 liu, Chen (bib36) 2013; 30 De Candia (bib43) 2012; 129 van Ryn, Stangier, Haertter, Liesenfeld, Wienen, Feuring, Clemens (bib9) 2010; 103 Zheng, Xia, Yang (bib18) 2013; 7 Isanbor, Hagan (bib30) 2006; 127 Varizhuk, Tsvetkov, Tatarinova, Kaluzhny, Florentiev, Timofeev, Shchyolkina, Borisova, Smirnov, Grokhovsky, Aseychev, Pozmogova, Wanat (bib3) 2013; 67 Stangier, Rathgen, Stahle (bib15) 2007; 64 Patkar, Mondkar, Arote, Patil, Jadhav, Hagavane, Bopalkar (bib40) 2014-10-16 Tang (bib1) 2013; 33 Hagmann (bib27) 2008; 51 Jirman, Richter, Lustig (bib39) 2009-03-10 Deyell, Cox, Bennett, Wong, Teal, Krahn (bib11) 2013; 29 Redondo, Martínez, Ramajo, Navarro-Dorado, Barez, Tejerina (bib14) 2011; 4 Kahraman, Sinishtaj, Dolan, Kensler, Peleg, Saha (bib22) 2004; 47 Narjes, Koehler, Koch, Gerlach, Colarusso, Steinkühler, Brunetti, Altamura, Francesco, Matassa (bib21) 2002; 12 Pindur, Ziegeler, Kleinschmidt (bib7) 2003; 52 Eriksson, Dahl, Bulle, Hettiarachchi, Rosencher, Bravo, Ahnfelt, Piovella, Stangier, Kalebo, Reilly (bib8) 2005; 3 Purser, Moore, Swallow, Gouverneur (bib28) 2008; 37 Han, Yang (bib19) 2010; 5 Nogueira, Rocha (bib23) 2011; 85 Teng, Sarich, Eriksson (bib4) 2004; 44 Crawley, Zanardelli, Chion, Lane (bib41) 2007; 5 Pappalardo, Scandroglio, Potapov, Stepanenko, Maj, Krabatsch, Zangrillo, Koster, Hetzer (bib6) 2012; 78 Haas (bib16) 2008; 25 Ramírez-Espinosa, Rios, Paoli, Flores-Morales, Camici, Rosa-Lugo, Hidalgo-Figueroa, Navarrete-Vázquez, Estrada-Soto (bib45) 2014; 87 Hauel, Nar, Priepke, Ries, Stassen, Wienen (bib33) 2002; 45 Zhang, Liu (bib26) 2014; 24 Kirk (bib32) 2008; 12 Müller, Faeh, Diederich (bib31) 2007; 317 Ahmad, Lip (bib44) 2012; 98 Yuan, Huang, Guo, Wu, Ma, Shu (bib13) 2014; 13 Alexander (bib10) 2008; 29 Weitz, Buller (bib5) 2002; 105 Lip, Larsen, Skjøth, Rasmussen (bib20) 2012; 60 Jirman (10.1016/j.ejmech.2015.04.012_bib39) 2009 Hagmann (10.1016/j.ejmech.2015.04.012_bib27) 2008; 51 Hauel (10.1016/j.ejmech.2015.04.012_bib33) 2002; 45 Zhang (10.1016/j.ejmech.2015.04.012_bib26) 2014; 24 Han (10.1016/j.ejmech.2015.04.012_bib19) 2010; 5 Yuan (10.1016/j.ejmech.2015.04.012_bib13) 2014; 13 Weitz (10.1016/j.ejmech.2015.04.012_bib5) 2002; 105 Bailey (10.1016/j.ejmech.2015.04.012_bib2) 2009; 29 Kahraman (10.1016/j.ejmech.2015.04.012_bib22) 2004; 47 liu (10.1016/j.ejmech.2015.04.012_bib36) 2013; 30 Ahmad (10.1016/j.ejmech.2015.04.012_bib44) 2012; 98 Sheng (10.1016/j.ejmech.2015.04.012_bib24) 2011; 46 Zhang (10.1016/j.ejmech.2015.04.012_bib42) 2013; 13 Alexander (10.1016/j.ejmech.2015.04.012_bib10) 2008; 29 van Ryn (10.1016/j.ejmech.2015.04.012_bib9) 2010; 103 Xing (10.1016/j.ejmech.2015.04.012_bib38) 2010; 41 Mosesson (10.1016/j.ejmech.2015.04.012_bib34) 2005; 3 Müller (10.1016/j.ejmech.2015.04.012_bib31) 2007; 317 Purser (10.1016/j.ejmech.2015.04.012_bib28) 2008; 37 Redondo (10.1016/j.ejmech.2015.04.012_bib14) 2011; 4 Zheng (10.1016/j.ejmech.2015.04.012_bib18) 2013; 7 Pindur (10.1016/j.ejmech.2015.04.012_bib7) 2003; 52 Zhu (10.1016/j.ejmech.2015.04.012_bib37) 2012; 22 Wanat (10.1016/j.ejmech.2015.04.012_bib3b) 2013; 125 Haas (10.1016/j.ejmech.2015.04.012_bib16) 2008; 25 Kirk (10.1016/j.ejmech.2015.04.012_bib29) 2006; 127 Isanbor (10.1016/j.ejmech.2015.04.012_bib30) 2006; 127 Kirk (10.1016/j.ejmech.2015.04.012_bib32) 2008; 12 Lauria (10.1016/j.ejmech.2015.04.012_bib35) 2014; 75 Ramírez-Espinosa (10.1016/j.ejmech.2015.04.012_bib45) 2014; 87 Fujii (10.1016/j.ejmech.2015.04.012_bib25) 2013; 56 Crawley (10.1016/j.ejmech.2015.04.012_bib41) 2007; 5 Liew (10.1016/j.ejmech.2015.04.012_bib12) 2012; 27 Nogueira (10.1016/j.ejmech.2015.04.012_bib23) 2011; 85 Tang (10.1016/j.ejmech.2015.04.012_bib1) 2013; 33 Pappalardo (10.1016/j.ejmech.2015.04.012_bib6) 2012; 78 Lip (10.1016/j.ejmech.2015.04.012_bib20) 2012; 60 Eriksson (10.1016/j.ejmech.2015.04.012_bib8) 2005; 3 Poller (10.1016/j.ejmech.2015.04.012_bib17) 2009; 361 Narjes (10.1016/j.ejmech.2015.04.012_bib21) 2002; 12 De Candia (10.1016/j.ejmech.2015.04.012_bib43) 2012; 129 Varizhuk (10.1016/j.ejmech.2015.04.012_bib3a) 2013; 67 Deyell (10.1016/j.ejmech.2015.04.012_bib11) 2013; 29 Patkar (10.1016/j.ejmech.2015.04.012_bib40) 2014 Teng (10.1016/j.ejmech.2015.04.012_bib4) 2004; 44 Stangier (10.1016/j.ejmech.2015.04.012_bib15) 2007; 64 Wanat, MA (WOS:000346795000011) 2013; 125 Haas, S (WOS:000252168600013) 2008; 25 Hagmann, WK (WOS:000258289800001) 2008; 51 Alexander, G.T. (000355712500012.4) 2008; 29 Kirk, KL (WOS:000254408400026) 2008; 12 (000355712500012.2) 2014 Narjes, F (WOS:000174280700045) 2002; 12 Muller, K (WOS:000249764300028) 2007; 317 Varizhuk, AM (WOS:000325121800011) 2013; 67 Eriksson, BI (WOS:000226380500018) 2005; 3 Hauel, NH (WOS:000175168700004) 2002; 45 Poller, L (WOS:000273181300023) 2009; 361 Xing Songsong (CSCD:3995390) 2010; 41 Nogueira, CW (WOS:000297359400002) 2011; 85 Kirk, KL (WOS:000239874500002) 2006; 127 Zhang, S.G. (000355712500012.43) 2013; 13 Teng, RL (WOS:000223414800012) 2004; 44 Ahmad, Y (WOS:000308750000004) 2012; 98 liu, X.J. (000355712500012.22) 2013; 30 Pindur, G (WOS:000188047000010) 2003; 52 (CSCD:4743673) 2013; 33 Fujii, S (WOS:000313221600014) 2013; 56 Liew, A (WOS:000305338400002) 2012; 27 Lauria, A (WOS:000333775600011) 2014; 75 Mosesson, MW (WOS:000230776000040) 2005; 3 Weitz, JI (WOS:000174141400029) 2002; 105 De Candia, E (WOS:000301583200008) 2012; 129 Purser, S (WOS:000252411800007) 2008; 37 Yuan, Z.S. (000355712500012.42) 2014; 13 Han, F. (000355712500012.13) 2010; 5 Zhu Jinjin (CSCD:4563193) 2012; 22 Deyell, MW (WOS:000324858700022) 2013; 29 Pappalardo, F (WOS:000302511800010) 2012; 78 Redondo, S (WOS:000300326700001) 2011; 4 (000355712500012.1) 2009 van Ryn, J (WOS:000279000000002) 2010; 103 Sheng, CQ (WOS:000298120500004) 2011; 46 Kahraman, M (WOS:000225952400024) 2004; 47 Lip, GYH (WOS:000307463800006) 2012; 60 Zhang Lei (CSCD:5177077) 2014; 24 Crawley, JTB (WOS:000247890900016) 2007; 5 Zheng, J. (000355712500012.45) 2013; 7 Ramirez-Espinosa, JJ (WOS:000363431300030) 2014; 87 Stangier, J (WOS:000248924500007) 2007; 64 Isanbor, C (WOS:000236926300001) 2006; 127 Bailey, AL (WOS:000263513700003) 2009; 29 |
| References_xml | – volume: 37 start-page: 320 year: 2008 end-page: 330 ident: bib28 article-title: Fluorine in medicinal chemistry publication-title: Chem. Soc. Rev. – volume: 13 start-page: 586 year: 2013 end-page: 590 ident: bib42 article-title: Research progress and evaluation on clinical application of direct thrombin inhibitor publication-title: Eval. Anal. Drug Use Hosp. Chin. – volume: 127 start-page: 1013 year: 2006 end-page: 1029 ident: bib29 article-title: Fluorine in medicinal chemistry: recent therapeutic applications of fluorinated small molecules publication-title: J. Fluor. Chem. – volume: 33 start-page: 222 year: 2013 end-page: 224 ident: bib1 article-title: Thrombosis and anti-tissue factor drug research progress publication-title: Chin. J. Gerontol. – volume: 46 start-page: 5276 year: 2011 end-page: 5282 ident: bib24 article-title: Design and synthesis of novel triazole antifungal derivatives by structure-based bioisosterism publication-title: Eur. J. Med. Chem. – volume: 317 start-page: 1881 year: 2007 end-page: 1886 ident: bib31 article-title: Fluorine in pharmaceuticals: looking beyond intuition publication-title: Science – volume: 75 start-page: 106 year: 2014 end-page: 110 ident: bib35 article-title: Multivariate analysis in the identification of biological targets for designed molecular structures: the BIOTA protocol publication-title: Eur. J. Med. Chem. – volume: 51 start-page: 4359 year: 2008 end-page: 4369 ident: bib27 article-title: The many roles for fluorine in medicinal chemistry publication-title: J. Med. Chem. – volume: 24 start-page: 214 year: 2014 end-page: 230 ident: bib26 article-title: Bioisosteric replacement and its application in drug design publication-title: Chin. J. Med. Chem. – volume: 4 start-page: 1 year: 2011 end-page: 7 ident: bib14 article-title: Pharmacological basis and clinical evidence of dabigatran therapy publication-title: J. Hematol. Oncol. – volume: 27 start-page: 331 year: 2012 end-page: 339 ident: bib12 article-title: Randomized controlled trials of new oral anticoagulants for stroke prevention in atrial fibrillation publication-title: Curr. Opin. Cardiol. – volume: 22 start-page: 204 year: 2012 end-page: 208 ident: bib37 article-title: Improved synthesis of dabigatran etexilate publication-title: Chin. J. Med. Chem. – volume: 127 start-page: 303 year: 2006 end-page: 319 ident: bib30 article-title: Fluorine in medicinal chemistry: a review of anti-cancer agents publication-title: J. Fluor. Chem. – volume: 44 start-page: 1063 year: 2004 end-page: 1071 ident: bib4 article-title: A pharmacokinetic study of the combined administration of amiodarone and ximelagatran, an oral direct thrombin inhibitor publication-title: J. Clin. Pharmacol. – volume: 3 start-page: 103 year: 2005 end-page: 111 ident: bib8 article-title: A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial publication-title: J. Thromb. Haemost. – volume: 30 start-page: 374 year: 2013 end-page: 377 ident: bib36 article-title: Synthesis of dabigatran etexilate publication-title: Chin. J. Appl. Chem. – volume: 29 start-page: 284 year: 2009 end-page: 288 ident: bib2 article-title: Thrombosis and antithrombotic therapy in women publication-title: Arterioscler. Thromb. Vasc. Biol. – year: 2014-10-16 ident: bib40 article-title: Synthesis of Dabigatran, WO2014167577 – volume: 29 start-page: 155 year: 2008 end-page: 165 ident: bib10 article-title: New oral anticoagulant atrial fibrillation: Department of Medicine publication-title: Eur. Heart. J. – volume: 12 start-page: 305 year: 2008 end-page: 321 ident: bib32 article-title: Fluorination in medicinal chemistry: methods, strategies, and recent developments publication-title: Org. Process Res. Dev. – volume: 98 start-page: 1404 year: 2012 end-page: 1406 ident: bib44 article-title: Dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation: NICE guidance publication-title: Heart – volume: 41 start-page: 321 year: 2010 end-page: 325 ident: bib38 article-title: Synthesis of dabigatran etexilate publication-title: Chin. J. Pharm. – volume: 5 start-page: 95 year: 2007 end-page: 101 ident: bib41 article-title: The central role of thrombin in hemostasis publication-title: J. Thromb. Haemost. – volume: 29 start-page: 1295 year: 2013 end-page: 1298 ident: bib11 article-title: Adopting the new anticoagulants: all aboard or all in good time publication-title: Can. J. Cardiol. – volume: 45 start-page: 1757 year: 2002 end-page: 1766 ident: bib33 article-title: Structure-based design of novel potent nonpeptide thrombin inhibitors publication-title: J. Med. Chem. – volume: 60 start-page: 738 year: 2012 end-page: 746 ident: bib20 article-title: Indirect comparisons of new oral anticoagulant drugs for efficacy and safety when used for stroke prevention in atrial fibrillation publication-title: J. Am. Coll. Cardiol. – volume: 67 start-page: 90 year: 2013 end-page: 97 ident: bib3 article-title: Synthesis, characterization and in vitro activity of thrombin-binding DNA aptamers with triazole internucleotide linkages publication-title: Eur. J. Med. Chem. – volume: 64 start-page: 292 year: 2007 end-page: 303 ident: bib15 article-title: The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate,a new oral direct thrombin inhibitor, in healthy male subjects publication-title: Br. J. Clin. Pharmacol. – volume: 52 start-page: 1171 year: 2003 end-page: 1175 ident: bib7 article-title: Melagatran und Ximelagatran publication-title: Der Anaesthesist – volume: 3 start-page: 1894 year: 2005 end-page: 1904 ident: bib34 article-title: Fibrinogen and fibrin structure and functions publication-title: J. Thromb. Haemost. – volume: 25 start-page: 52 year: 2008 end-page: 60 ident: bib16 article-title: New oral Xa and II a inhibitors:updates on clinical trial results publication-title: J. Thromb. Thromb. – volume: 56 start-page: 160 year: 2013 end-page: 166 ident: bib25 article-title: Increased hydrophobicity and estrogenic activity of simple phenols with silicon and germanium-containing substituents publication-title: J. Med. Chem. – volume: 12 start-page: 701 year: 2002 end-page: 704 ident: bib21 article-title: A designed P1 cysteine mimetic for covalent and non-covalent inhibitors of HCV NS3 protease publication-title: Bioorg. Med. Chem. Lett. – volume: 13 start-page: 947 year: 2014 end-page: 951 ident: bib13 article-title: Meta-analysis of effect and safety of dabigatran etexilate in patients with non valvular atrial fibrillation anticoagulation publication-title: Chin. J. Diffic. Complic. Cases – volume: 85 start-page: 1313 year: 2011 end-page: 1359 ident: bib23 article-title: Toxicology and pharmacology of selenium: emphasis on synthetic organoselenium compounds publication-title: Arch. Toxicol. – volume: 105 start-page: 1004 year: 2002 end-page: 1011 ident: bib5 article-title: Direct thrombin inhibitors in acute coronary syndromes: present and future publication-title: Circulation – volume: 78 start-page: 330 year: 2012 end-page: 335 ident: bib6 article-title: Argatroban anticoagulation for heparin induced thrombocytopenia in patients with ventricular assist devices publication-title: Minerva Anestesiol. – year: 2009-03-10 ident: bib39 article-title: A Method for the Preparation of Dabigatran, WO2009111997 – volume: 361 start-page: 2673 year: 2009 end-page: 2674 ident: bib17 article-title: Dabigatran versus warfarin in patients with atrial fibrillation publication-title: N. Engl. J. Med. – volume: 47 start-page: 6854 year: 2004 end-page: 6863 ident: bib22 article-title: Potent, selective and low-calcemic inhibitors of CYP24 hydroxylase: 24-sulfoximine analogues of the hormone 1α,25-dihydroxyvitamin D3 publication-title: J. Med. Chem. – volume: 7 start-page: 144 year: 2013 end-page: 145 ident: bib18 article-title: The situation of novel oral anticoagulant drugs' treatment strategies related to bleeding publication-title: Chin. J. Clin. – volume: 5 start-page: 583 year: 2010 end-page: 590 ident: bib19 article-title: Advance of antithrombotic therapy in atrial fibrillation publication-title: Clin. J. Stroke – volume: 129 start-page: 250 year: 2012 end-page: 256 ident: bib43 article-title: Mechanisms of platelet activation by thrombin: a short history publication-title: Thromb. Res. – volume: 103 start-page: 1116 year: 2010 end-page: 1127 ident: bib9 article-title: Dabigatran etexilate-a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity publication-title: Thromb. Haemost. – volume: 87 start-page: 316 year: 2014 end-page: 327 ident: bib45 article-title: Synthesis of oleanolic acid derivatives: In vitro, in vivo and in silico studies for PTP-1B inhibition publication-title: Eur. J. Med. Chem. – volume: 27 start-page: 331 year: 2012 ident: 10.1016/j.ejmech.2015.04.012_bib12 article-title: Randomized controlled trials of new oral anticoagulants for stroke prevention in atrial fibrillation publication-title: Curr. Opin. Cardiol. doi: 10.1097/HCO.0b013e3283540857 – volume: 56 start-page: 160 year: 2013 ident: 10.1016/j.ejmech.2015.04.012_bib25 article-title: Increased hydrophobicity and estrogenic activity of simple phenols with silicon and germanium-containing substituents publication-title: J. Med. Chem. doi: 10.1021/jm3013757 – volume: 41 start-page: 321 year: 2010 ident: 10.1016/j.ejmech.2015.04.012_bib38 article-title: Synthesis of dabigatran etexilate publication-title: Chin. J. Pharm. – volume: 5 start-page: 95 year: 2007 ident: 10.1016/j.ejmech.2015.04.012_bib41 article-title: The central role of thrombin in hemostasis publication-title: J. Thromb. Haemost. doi: 10.1111/j.1538-7836.2007.02500.x – volume: 361 start-page: 2673 year: 2009 ident: 10.1016/j.ejmech.2015.04.012_bib17 article-title: Dabigatran versus warfarin in patients with atrial fibrillation publication-title: N. Engl. J. Med. – volume: 33 start-page: 222 year: 2013 ident: 10.1016/j.ejmech.2015.04.012_bib1 article-title: Thrombosis and anti-tissue factor drug research progress publication-title: Chin. J. Gerontol. – volume: 12 start-page: 305 year: 2008 ident: 10.1016/j.ejmech.2015.04.012_bib32 article-title: Fluorination in medicinal chemistry: methods, strategies, and recent developments publication-title: Org. Process Res. Dev. doi: 10.1021/op700134j – volume: 29 start-page: 155 year: 2008 ident: 10.1016/j.ejmech.2015.04.012_bib10 article-title: New oral anticoagulant atrial fibrillation: Department of Medicine publication-title: Eur. Heart. J. – volume: 24 start-page: 214 year: 2014 ident: 10.1016/j.ejmech.2015.04.012_bib26 article-title: Bioisosteric replacement and its application in drug design publication-title: Chin. J. Med. Chem. – volume: 67 start-page: 90 year: 2013 ident: 10.1016/j.ejmech.2015.04.012_bib3a article-title: Synthesis, characterization and in vitro activity of thrombin-binding DNA aptamers with triazole internucleotide linkages publication-title: Eur. J. Med. Chem. doi: 10.1016/j.ejmech.2013.06.034 – volume: 13 start-page: 947 year: 2014 ident: 10.1016/j.ejmech.2015.04.012_bib13 article-title: Meta-analysis of effect and safety of dabigatran etexilate in patients with non valvular atrial fibrillation anticoagulation publication-title: Chin. J. Diffic. Complic. Cases – volume: 22 start-page: 204 year: 2012 ident: 10.1016/j.ejmech.2015.04.012_bib37 article-title: Improved synthesis of dabigatran etexilate publication-title: Chin. J. Med. Chem. – volume: 129 start-page: 250 year: 2012 ident: 10.1016/j.ejmech.2015.04.012_bib43 article-title: Mechanisms of platelet activation by thrombin: a short history publication-title: Thromb. Res. doi: 10.1016/j.thromres.2011.11.001 – volume: 46 start-page: 5276 year: 2011 ident: 10.1016/j.ejmech.2015.04.012_bib24 article-title: Design and synthesis of novel triazole antifungal derivatives by structure-based bioisosterism publication-title: Eur. J. Med. Chem. doi: 10.1016/j.ejmech.2011.03.019 – volume: 105 start-page: 1004 year: 2002 ident: 10.1016/j.ejmech.2015.04.012_bib5 article-title: Direct thrombin inhibitors in acute coronary syndromes: present and future publication-title: Circulation doi: 10.1161/hc0802.104331 – volume: 37 start-page: 320 year: 2008 ident: 10.1016/j.ejmech.2015.04.012_bib28 article-title: Fluorine in medicinal chemistry publication-title: Chem. Soc. Rev. doi: 10.1039/B610213C – volume: 317 start-page: 1881 year: 2007 ident: 10.1016/j.ejmech.2015.04.012_bib31 article-title: Fluorine in pharmaceuticals: looking beyond intuition publication-title: Science doi: 10.1126/science.1131943 – volume: 4 start-page: 1 year: 2011 ident: 10.1016/j.ejmech.2015.04.012_bib14 article-title: Pharmacological basis and clinical evidence of dabigatran therapy publication-title: J. Hematol. Oncol. – volume: 30 start-page: 374 year: 2013 ident: 10.1016/j.ejmech.2015.04.012_bib36 article-title: Synthesis of dabigatran etexilate publication-title: Chin. J. Appl. Chem. – volume: 29 start-page: 284 year: 2009 ident: 10.1016/j.ejmech.2015.04.012_bib2 article-title: Thrombosis and antithrombotic therapy in women publication-title: Arterioscler. Thromb. Vasc. Biol. doi: 10.1161/ATVBAHA.108.179788 – volume: 85 start-page: 1313 year: 2011 ident: 10.1016/j.ejmech.2015.04.012_bib23 article-title: Toxicology and pharmacology of selenium: emphasis on synthetic organoselenium compounds publication-title: Arch. Toxicol. doi: 10.1007/s00204-011-0720-3 – volume: 127 start-page: 303 year: 2006 ident: 10.1016/j.ejmech.2015.04.012_bib30 article-title: Fluorine in medicinal chemistry: a review of anti-cancer agents publication-title: J. Fluor. Chem. doi: 10.1016/j.jfluchem.2006.01.011 – volume: 125 start-page: 103 year: 2013 ident: 10.1016/j.ejmech.2015.04.012_bib3b article-title: Novel oral anticoagulants: a review of new agents publication-title: Postgrad. Med. doi: 10.3810/pgm.2013.07.2683 – volume: 87 start-page: 316 year: 2014 ident: 10.1016/j.ejmech.2015.04.012_bib45 article-title: Synthesis of oleanolic acid derivatives: In vitro, in vivo and in silico studies for PTP-1B inhibition publication-title: Eur. J. Med. Chem. doi: 10.1016/j.ejmech.2014.09.036 – volume: 3 start-page: 103 year: 2005 ident: 10.1016/j.ejmech.2015.04.012_bib8 article-title: A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial publication-title: J. Thromb. Haemost. doi: 10.1111/j.1538-7836.2004.01100.x – volume: 127 start-page: 1013 year: 2006 ident: 10.1016/j.ejmech.2015.04.012_bib29 article-title: Fluorine in medicinal chemistry: recent therapeutic applications of fluorinated small molecules publication-title: J. Fluor. Chem. doi: 10.1016/j.jfluchem.2006.06.007 – volume: 64 start-page: 292 year: 2007 ident: 10.1016/j.ejmech.2015.04.012_bib15 article-title: The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate,a new oral direct thrombin inhibitor, in healthy male subjects publication-title: Br. J. Clin. Pharmacol. doi: 10.1111/j.1365-2125.2007.02899.x – volume: 98 start-page: 1404 year: 2012 ident: 10.1016/j.ejmech.2015.04.012_bib44 article-title: Dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation: NICE guidance publication-title: Heart doi: 10.1136/heartjnl-2012-302101 – volume: 52 start-page: 1171 year: 2003 ident: 10.1016/j.ejmech.2015.04.012_bib7 article-title: Melagatran und Ximelagatran publication-title: Der Anaesthesist doi: 10.1007/s00101-003-0602-z – year: 2009 ident: 10.1016/j.ejmech.2015.04.012_bib39 – volume: 103 start-page: 1116 year: 2010 ident: 10.1016/j.ejmech.2015.04.012_bib9 article-title: Dabigatran etexilate-a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity publication-title: Thromb. Haemost. doi: 10.1160/TH09-11-0758 – volume: 5 start-page: 583 year: 2010 ident: 10.1016/j.ejmech.2015.04.012_bib19 article-title: Advance of antithrombotic therapy in atrial fibrillation publication-title: Clin. J. Stroke – year: 2014 ident: 10.1016/j.ejmech.2015.04.012_bib40 – volume: 60 start-page: 738 year: 2012 ident: 10.1016/j.ejmech.2015.04.012_bib20 article-title: Indirect comparisons of new oral anticoagulant drugs for efficacy and safety when used for stroke prevention in atrial fibrillation publication-title: J. Am. Coll. Cardiol. doi: 10.1016/j.jacc.2012.03.019 – volume: 47 start-page: 6854 year: 2004 ident: 10.1016/j.ejmech.2015.04.012_bib22 article-title: Potent, selective and low-calcemic inhibitors of CYP24 hydroxylase: 24-sulfoximine analogues of the hormone 1α,25-dihydroxyvitamin D3 publication-title: J. Med. Chem. doi: 10.1021/jm040129+ – volume: 44 start-page: 1063 year: 2004 ident: 10.1016/j.ejmech.2015.04.012_bib4 article-title: A pharmacokinetic study of the combined administration of amiodarone and ximelagatran, an oral direct thrombin inhibitor publication-title: J. Clin. Pharmacol. doi: 10.1177/0091270004268446 – volume: 75 start-page: 106 year: 2014 ident: 10.1016/j.ejmech.2015.04.012_bib35 article-title: Multivariate analysis in the identification of biological targets for designed molecular structures: the BIOTA protocol publication-title: Eur. J. Med. Chem. doi: 10.1016/j.ejmech.2014.01.025 – volume: 13 start-page: 586 year: 2013 ident: 10.1016/j.ejmech.2015.04.012_bib42 article-title: Research progress and evaluation on clinical application of direct thrombin inhibitor publication-title: Eval. Anal. Drug Use Hosp. Chin. – volume: 51 start-page: 4359 year: 2008 ident: 10.1016/j.ejmech.2015.04.012_bib27 article-title: The many roles for fluorine in medicinal chemistry publication-title: J. Med. Chem. doi: 10.1021/jm800219f – volume: 3 start-page: 1894 year: 2005 ident: 10.1016/j.ejmech.2015.04.012_bib34 article-title: Fibrinogen and fibrin structure and functions publication-title: J. Thromb. Haemost. doi: 10.1111/j.1538-7836.2005.01365.x – volume: 29 start-page: 1295 year: 2013 ident: 10.1016/j.ejmech.2015.04.012_bib11 article-title: Adopting the new anticoagulants: all aboard or all in good time publication-title: Can. J. Cardiol. doi: 10.1016/j.cjca.2013.03.002 – volume: 7 start-page: 144 year: 2013 ident: 10.1016/j.ejmech.2015.04.012_bib18 article-title: The situation of novel oral anticoagulant drugs' treatment strategies related to bleeding publication-title: Chin. J. Clin. – volume: 78 start-page: 330 year: 2012 ident: 10.1016/j.ejmech.2015.04.012_bib6 article-title: Argatroban anticoagulation for heparin induced thrombocytopenia in patients with ventricular assist devices publication-title: Minerva Anestesiol. – volume: 12 start-page: 701 year: 2002 ident: 10.1016/j.ejmech.2015.04.012_bib21 article-title: A designed P1 cysteine mimetic for covalent and non-covalent inhibitors of HCV NS3 protease publication-title: Bioorg. Med. Chem. Lett. doi: 10.1016/S0960-894X(01)00842-3 – volume: 25 start-page: 52 year: 2008 ident: 10.1016/j.ejmech.2015.04.012_bib16 article-title: New oral Xa and II a inhibitors:updates on clinical trial results publication-title: J. Thromb. Thromb. doi: 10.1007/s11239-007-0108-7 – volume: 45 start-page: 1757 year: 2002 ident: 10.1016/j.ejmech.2015.04.012_bib33 article-title: Structure-based design of novel potent nonpeptide thrombin inhibitors publication-title: J. Med. Chem. doi: 10.1021/jm0109513 – volume: 7 start-page: 144 year: 2013 ident: 000355712500012.45 article-title: The situation of novel oral anticoagulant drugs' treatment strategies related to bleeding publication-title: Chin. J. Clin – volume: 5 start-page: 583 year: 2010 ident: 000355712500012.13 article-title: Advance of antithrombotic therapy in atrial fibrillation publication-title: Clin. J. Stroke – volume: 317 start-page: 1881 year: 2007 ident: WOS:000249764300028 article-title: Fluorine in pharmaceuticals: Looking beyond intuition publication-title: SCIENCE doi: 10.1126/science.1131943 – volume: 29 start-page: 1295 year: 2013 ident: WOS:000324858700022 article-title: Adopting the New Anticoagulants: All Aboard or All in Good Time? publication-title: CANADIAN JOURNAL OF CARDIOLOGY doi: 10.1016/j.cjca.2013.03.002 – volume: 98 start-page: 1404 year: 2012 ident: WOS:000308750000004 article-title: Dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation: NICE guidance publication-title: HEART doi: 10.1136/heartjnl-2012-302101 – volume: 46 start-page: 5276 year: 2011 ident: WOS:000298120500004 article-title: Design and synthesis of novel triazole antifungal derivatives by structure-based bioisosterism publication-title: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY doi: 10.1016/j.ejmech.2011.03.019 – volume: 13 start-page: 586 year: 2013 ident: 000355712500012.43 article-title: Research progress and evaluation on clinical application of direct thrombin inhibitor publication-title: Eval. Anal. Drug Use Hosp. Chin – volume: 13 start-page: 947 year: 2014 ident: 000355712500012.42 article-title: Meta-analysis of effect and safety of dabigatran etexilate in patients with non valvular atrial fibrillation anticoagulation publication-title: Chin. J. Diffic. Complic. Cases – year: 2009 ident: 000355712500012.1 publication-title: A Method for the Preparation of Dabigatran – year: 2014 ident: 000355712500012.2 publication-title: Synthesis of Dabigatran – volume: 127 start-page: 303 year: 2006 ident: WOS:000236926300001 article-title: Fluorine in medicinal chemistry: A review of anti-cancer agents publication-title: JOURNAL OF FLUORINE CHEMISTRY doi: 10.1016/j.jfluchem.2006.01.011 – volume: 127 start-page: 1013 year: 2006 ident: WOS:000239874500002 article-title: Fluorine in medicinal chemistry: Recent therapeutic applications of fluorinated small molecules publication-title: JOURNAL OF FLUORINE CHEMISTRY doi: 10.1016/j.jfluchem.2006.06.007 – volume: 30 start-page: 374 year: 2013 ident: 000355712500012.22 article-title: Synthesis of dabigatran etexilate publication-title: Chin. J. Appl. Chem – volume: 22 start-page: 204 year: 2012 ident: CSCD:4563193 article-title: Improved synthesis of dabigatran etexilate publication-title: Chinese Journal of Medicinal Chemistry – volume: 12 start-page: 701 year: 2002 ident: WOS:000174280700045 article-title: A designed P-1 cysteine mimetic for covalent and non-covalent inhibitors of HCVNS3 protease publication-title: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS – volume: 64 start-page: 292 year: 2007 ident: WOS:000248924500007 article-title: The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects publication-title: BRITISH JOURNAL OF CLINICAL PHARMACOLOGY doi: 10.1111/j.1365-2125.2007.02899.x – volume: 47 start-page: 6854 year: 2004 ident: WOS:000225952400024 article-title: Potent, selective and low-calcemic inhibitors of CYP24 hydroxylase: 24-sulfoximine analogues of the hormone 1 alpha,25-dihydroxyvitamin D-3 publication-title: JOURNAL OF MEDICINAL CHEMISTRY doi: 10.1021/jm040129+ – volume: 87 start-page: 316 year: 2014 ident: WOS:000363431300030 article-title: Synthesis of oleanolic acid derivatives: In vitro, in vivo and in silico studies for PTP-1B inhibition publication-title: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY doi: 10.1016/j.ejmech.2014.09.036 – volume: 37 start-page: 320 year: 2008 ident: WOS:000252411800007 article-title: Fluorine in medicinal chemistry publication-title: CHEMICAL SOCIETY REVIEWS doi: 10.1039/b610213c – volume: 41 start-page: 321 year: 2010 ident: CSCD:3995390 article-title: Synthesis of Dabigatran Etexilate publication-title: Chinese Journal of Pharmaceuticals – volume: 56 start-page: 160 year: 2013 ident: WOS:000313221600014 article-title: Increased Hydrophobicity and Estrogenic Activity of Simple Phenols with Silicon and Germanium-Containing Substituents publication-title: JOURNAL OF MEDICINAL CHEMISTRY doi: 10.1021/jm3013757 – volume: 85 start-page: 1313 year: 2011 ident: WOS:000297359400002 article-title: Toxicology and pharmacology of selenium: emphasis on synthetic organoselenium compounds publication-title: ARCHIVES OF TOXICOLOGY doi: 10.1007/s00204-011-0720-3 – volume: 12 start-page: 305 year: 2008 ident: WOS:000254408400026 article-title: Fluorination in medicinal chemistry: Methods, strategies, and recent developments publication-title: ORGANIC PROCESS RESEARCH & DEVELOPMENT doi: 10.1021/op700134j – volume: 105 start-page: 1004 year: 2002 ident: WOS:000174141400029 article-title: Direct thrombin inhibitors in acute coronary syndromes - Present and future publication-title: CIRCULATION doi: 10.1161/hc0802.104331 – volume: 4 start-page: ARTN 53 year: 2011 ident: WOS:000300326700001 article-title: Pharmacological basis and clinical evidence of dabigatran therapy publication-title: JOURNAL OF HEMATOLOGY & ONCOLOGY doi: 10.1186/1756-8722-4-53 – volume: 78 start-page: 330 year: 2012 ident: WOS:000302511800010 article-title: Argatroban anticoagulation for heparin induced thrombocytopenia in patients with ventricular assist devices publication-title: MINERVA ANESTESIOLOGICA – volume: 52 start-page: 1171 year: 2003 ident: WOS:000188047000010 article-title: Melagatran and ximelagatran. Pharmacological characteristics and anaesthesiological aspects publication-title: ANAESTHESIST – volume: 3 start-page: 103 year: 2005 ident: WOS:000226380500018 article-title: A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial publication-title: JOURNAL OF THROMBOSIS AND HAEMOSTASIS – volume: 361 start-page: 2673 year: 2009 ident: WOS:000273181300023 article-title: Dabigatran versus Warfarin in Patients with Atrial Fibrillation publication-title: NEW ENGLAND JOURNAL OF MEDICINE – volume: 25 start-page: 52 year: 2008 ident: WOS:000252168600013 article-title: New oral Xa and IIa inhibitors: updates on clinical trial results publication-title: JOURNAL OF THROMBOSIS AND THROMBOLYSIS doi: 10.1007/s11239-007-0108-7 – volume: 27 start-page: 331 year: 2012 ident: WOS:000305338400002 article-title: Randomized controlled trials of new oral anticoagulants for stroke prevention in atrial fibrillation publication-title: CURRENT OPINION IN CARDIOLOGY doi: 10.1097/HCO.0b013e3283540857 – volume: 33 start-page: 222 year: 2013 ident: CSCD:4743673 publication-title: Chinese Journal of Gerontology – volume: 125 start-page: 103 year: 2013 ident: WOS:000346795000011 article-title: Novel Oral Anticoagulants: A Review of New Agents publication-title: POSTGRADUATE MEDICINE doi: 10.3810/pgm.2013.07.2683 – volume: 5 start-page: 95 year: 2007 ident: WOS:000247890900016 article-title: The central role of thrombin in hemostasis publication-title: JOURNAL OF THROMBOSIS AND HAEMOSTASIS – volume: 129 start-page: 250 year: 2012 ident: WOS:000301583200008 article-title: Mechanisms of platelet activation by thrombin: A short history publication-title: THROMBOSIS RESEARCH doi: 10.1016/j.thromres.2011.11.001 – volume: 24 start-page: 214 year: 2014 ident: CSCD:5177077 article-title: Bioisosteric replacement and its application in drug design publication-title: Chinese Journal of Medicinal Chemistry – volume: 44 start-page: 1063 year: 2004 ident: WOS:000223414800012 article-title: A pharmacokinetic study of the combined administration of amiodarone and ximelagatran, an oral direct thrombin inhibitor publication-title: JOURNAL OF CLINICAL PHARMACOLOGY doi: 10.1177/0091270004268446 – volume: 45 start-page: 1757 year: 2002 ident: WOS:000175168700004 article-title: Structure-based design of novel potent nonpeptide thrombin inhibitors publication-title: JOURNAL OF MEDICINAL CHEMISTRY doi: 10.1021/jm0109513 – volume: 51 start-page: 4359 year: 2008 ident: WOS:000258289800001 article-title: The many roles for fluorine in medicinal chemistry publication-title: JOURNAL OF MEDICINAL CHEMISTRY doi: 10.1021/jm800219f – volume: 67 start-page: 90 year: 2013 ident: WOS:000325121800011 article-title: Synthesis, characterization and in vitro activity of thrombin-binding DNA aptamers with triazole internucleotide linkages publication-title: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY doi: 10.1016/j.ejmech.2013.06.034 – volume: 3 start-page: 1894 year: 2005 ident: WOS:000230776000040 article-title: Fibrinogen and fibrin structure and functions publication-title: JOURNAL OF THROMBOSIS AND HAEMOSTASIS – volume: 29 start-page: 284 year: 2009 ident: WOS:000263513700003 article-title: Thrombosis and Antithrombotic Therapy in Women publication-title: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY doi: 10.1161/ATVBAHA.108.179788 – volume: 103 start-page: 1116 year: 2010 ident: WOS:000279000000002 article-title: Dabigatran etexilate - a novel, reversible, oral direct thrombin inhibitor: Interpretation of coagulation assays and reversal of anticoagulant activity publication-title: THROMBOSIS AND HAEMOSTASIS doi: 10.1160/TH09-11-0758 – volume: 60 start-page: 738 year: 2012 ident: WOS:000307463800006 article-title: Indirect Comparisons of New Oral Anticoagulant Drugs for Efficacy and Safety When Used for Stroke Prevention in Atrial Fibrillation publication-title: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY doi: 10.1016/j.jacc.2012.03.019 – volume: 75 start-page: 106 year: 2014 ident: WOS:000333775600011 article-title: Multivariate analysis in the identification of biological targets for designed molecular structures: The BIOTA protocol publication-title: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY doi: 10.1016/j.ejmech.2014.01.025 – volume: 29 start-page: 155 year: 2008 ident: 000355712500012.4 article-title: New oral anticoagulant atrial fibrillation: Department of Medicine publication-title: Eur. Heart. J |
| SSID | ssj0005600 |
| Score | 2.2599275 |
| Snippet | Twenty-one fluorinated dabigatran derivatives were designed based on the bioisosteric principle. All derivatives were synthesised and evaluated for their... |
| Source | Web of Science |
| SourceID | proquest pubmed webofscience crossref elsevier |
| SourceType | Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 122 |
| SubjectTerms | Animals Anticoagulant activity Anticoagulants - chemical synthesis Anticoagulants - chemistry Anticoagulants - pharmacology Antithrombins - chemical synthesis Antithrombins - chemistry Antithrombins - pharmacology Blood Coagulation - drug effects Chemistry, Medicinal Computer-aided simulation Dabigatran - chemistry Dabigatran - pharmacology Dose-Response Relationship, Drug Drug Design Fluorinated dabigatran derivatives Humans Hydrocarbons, Fluorinated - chemical synthesis Hydrocarbons, Fluorinated - chemistry Hydrocarbons, Fluorinated - pharmacology Life Sciences & Biomedicine Molecular Structure Pharmacology & Pharmacy Platelet Aggregation - drug effects Rats Rats, Sprague-Dawley Science & Technology Structure-Activity Relationship Synthesis Thrombin - antagonists & inhibitors Thrombin - metabolism |
| Title | Design, synthesis and structural exploration of novel fluorinated dabigatran derivatives as direct thrombin inhibitors |
| URI | https://dx.doi.org/10.1016/j.ejmech.2015.04.012 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestApp=WOS&DestLinkType=FullRecord&UT=000355712500012 https://www.ncbi.nlm.nih.gov/pubmed/25874337 https://www.proquest.com/docview/1681910499 |
| Volume | 96 |
| WOS | 000355712500012 |
| WOSCitedRecordID | wos000355712500012 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVESC databaseName: Elsevier SD Freedom Collection Journals 2021 customDbUrl: eissn: 1768-3254 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0005600 issn: 0223-5234 databaseCode: AIEXJ dateStart: 19950101 isFulltext: true titleUrlDefault: https://www.sciencedirect.com providerName: Elsevier |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV3JbtswECVcp0B7Kdp0c5eABYJcbBWiJIrSMXBSpEES-GCg7kmgJAqV4chBZQvxR_UfO1y0NG6a5NCLYMgUQXGeyJnhzBuE9tMw9LIkjC2fesLy_IxbMYlTK-XE4ZQwxnXVkjN2cRHMZuGk1_tV58JUC1YUwfV1ePVfRQ33QNgydfYB4m46hRvwG4QOVxA7XO8l-CMVkyGnrtwUoN5JxhHlHVdMsYplQ6jAu0ZZLJaVWAyzxVoG43GpgqY8ltQbsI8NUxhzpdjBS1mTRm-BqrzPJRjVw7z4kce5LNlzq4_f6LvmFF_ykdRF5ppoIBVScC5y6yxvM9P0gvh9bZ3mDfqOTATxOey41sk6v9H4G3QxM10YVwah8hRe58ubFQ90FWkZe93lOeyur0QnMZutmmhimK1dQDsk5p_F_FKoEydCFZ-tCdj-g3T7xmbYhCjW0W_zSPcSyV4i24tsWdN6x2E0DPpo5_Dr8ey0jSnydc5T_R51rqYKKNwezW260Lat81e1SKlA0-fombFd8KHG3AvUE8UuejKupbmLDiaaCH0zwtM2r68c4QM8aSnSNy9RpUE6wg1EMUAUtxDFHYjiZYYVRHEHoriFKO5AFPMSa4jiGqK4hegrNP1yPB2fWKYCiJV4drCyXOHHNqeJb5MsTtMMzImUOzyMiZPYYZxRHgap69mxxyhomp6kzc-oLTJOOY-5-xr1i2Uh3iLsCxakvpOCfu14LOFh5gvfSVzXDgTPEjJAbi2KKDHs-LJIyyL6FxAGyGqeutLsMHe0Z7WUIyNKPScRQPeOJz_VoIhAqPJUjxdiuS4j4kufi_RcDNAbjZZmLA4NwEJw2QDtd-HT_K8CCSgDI0d5pAeI3KfZ2MyPZM1YvXvgFLxHT9tP_wPqA7DER_Q4qVZ5-XMPPWKzYM98Vr8B-dgCxQ |
| linkProvider | Elsevier |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Design%2C+synthesis+and+structural+exploration+of+novel+fluorinated+dabigatran+derivatives+as+direct+thrombin+inhibitors&rft.jtitle=European+journal+of+medicinal+chemistry&rft.au=Li%2C+Mei-Lin&rft.au=Ren%2C+Yu-Jie&rft.au=Dong%2C+Ming-Hui&rft.au=Ren%2C+Wei-Xin&rft.date=2015-05-26&rft.issn=0223-5234&rft.volume=96&rft.spage=122&rft.epage=138&rft_id=info:doi/10.1016%2Fj.ejmech.2015.04.012&rft.externalDBID=n%2Fa&rft.externalDocID=10_1016_j_ejmech_2015_04_012 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0223-5234&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0223-5234&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0223-5234&client=summon |