Molecular hybridization yields triazole bronchodilators for the treatment of COPD
[Display omitted] A 1,2,4-triazole motif was employed as a bioisostere for the ester commonly used in muscarinic antagonists, and subsequent integrative conjugation to a β2 agonist quinolinone furnished a new class of bifunctional MABAs for the treatment of COPD. Medicinal chemistry optimization usi...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry letters Jg. 25; H. 22; S. 5121 - 5126 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
England
Elsevier Ltd
15.11.2015
|
| Schlagworte: | |
| ISSN: | 0960-894X, 1464-3405, 1464-3405 |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| Abstract | [Display omitted]
A 1,2,4-triazole motif was employed as a bioisostere for the ester commonly used in muscarinic antagonists, and subsequent integrative conjugation to a β2 agonist quinolinone furnished a new class of bifunctional MABAs for the treatment of COPD. Medicinal chemistry optimization using the principles of ‘inhalation by design’ furnished a clinical candidate with desirable pharmacological, pharmacokinetic and biopharmaceutical properties. |
|---|---|
| AbstractList | A 1,2,4-triazole motif was employed as a bioisostere for the ester commonly used in muscarinic antagonists, and subsequent integrative conjugation to a β2 agonist quinolinone furnished a new class of bifunctional MABAs for the treatment of COPD. Medicinal chemistry optimization using the principles of 'inhalation by design' furnished a clinical candidate with desirable pharmacological, pharmacokinetic and biopharmaceutical properties. A 1,2,4-triazole motif was employed as a bioisostere for the ester commonly used in muscarinic antagonists, and subsequent integrative conjugation to a β2 agonist quinolinone furnished a new class of bifunctional MABAs for the treatment of COPD. Medicinal chemistry optimization using the principles of 'inhalation by design' furnished a clinical candidate with desirable pharmacological, pharmacokinetic and biopharmaceutical properties.A 1,2,4-triazole motif was employed as a bioisostere for the ester commonly used in muscarinic antagonists, and subsequent integrative conjugation to a β2 agonist quinolinone furnished a new class of bifunctional MABAs for the treatment of COPD. Medicinal chemistry optimization using the principles of 'inhalation by design' furnished a clinical candidate with desirable pharmacological, pharmacokinetic and biopharmaceutical properties. [Display omitted] A 1,2,4-triazole motif was employed as a bioisostere for the ester commonly used in muscarinic antagonists, and subsequent integrative conjugation to a β2 agonist quinolinone furnished a new class of bifunctional MABAs for the treatment of COPD. Medicinal chemistry optimization using the principles of ‘inhalation by design’ furnished a clinical candidate with desirable pharmacological, pharmacokinetic and biopharmaceutical properties. |
| Author | James, Kim Stuart, Emilio F. Feeder, Neil Patel, Sheena Watson, Jessica Roberts, Dannielle F. Selby, Matthew D. Glossop, Paul Kenyon, Amy S. Jones, Rhys M. Strang, Ross S. Jones, Lyn H. Wright, Karen N. Clarke, Nick Trevethick, Michael A. Burrows, Jane |
| Author_xml | – sequence: 1 givenname: Lyn H. surname: Jones fullname: Jones, Lyn H. email: lyn.jones@pfizer.com organization: WorldWide Medicinal Chemistry, 610 Main Street, Cambridge, MA 02139, USA – sequence: 2 givenname: Jane surname: Burrows fullname: Burrows, Jane organization: Pharmaceutical Sciences, Pfizer, Ramsgate Road, Sandwich CT13 9NJ, UK – sequence: 3 givenname: Neil surname: Feeder fullname: Feeder, Neil organization: Pharmaceutical Sciences, Pfizer, Ramsgate Road, Sandwich CT13 9NJ, UK – sequence: 4 givenname: Paul surname: Glossop fullname: Glossop, Paul organization: WorldWide Medicinal Chemistry, Pfizer, Ramsgate Road, Sandwich CT13 9NJ, UK – sequence: 5 givenname: Kim surname: James fullname: James, Kim organization: WorldWide Medicinal Chemistry, Pfizer, Ramsgate Road, Sandwich CT13 9NJ, UK – sequence: 6 givenname: Rhys M. surname: Jones fullname: Jones, Rhys M. organization: Pharmacokinetics, Dynamics and Metabolism, 610 Main Street, Cambridge, MA 02139, USA – sequence: 7 givenname: Amy S. surname: Kenyon fullname: Kenyon, Amy S. organization: WorldWide Medicinal Chemistry, Pfizer, Ramsgate Road, Sandwich CT13 9NJ, UK – sequence: 8 givenname: Sheena surname: Patel fullname: Patel, Sheena organization: Allergy and Respiratory Biology, Pfizer, Ramsgate Road, Sandwich CT13 9NJ, UK – sequence: 9 givenname: Dannielle F. surname: Roberts fullname: Roberts, Dannielle F. organization: WorldWide Medicinal Chemistry, Pfizer, Ramsgate Road, Sandwich CT13 9NJ, UK – sequence: 10 givenname: Matthew D. surname: Selby fullname: Selby, Matthew D. organization: WorldWide Medicinal Chemistry, Pfizer, Ramsgate Road, Sandwich CT13 9NJ, UK – sequence: 11 givenname: Ross S. surname: Strang fullname: Strang, Ross S. organization: WorldWide Medicinal Chemistry, Pfizer, Ramsgate Road, Sandwich CT13 9NJ, UK – sequence: 12 givenname: Emilio F. surname: Stuart fullname: Stuart, Emilio F. organization: Allergy and Respiratory Biology, Pfizer, Ramsgate Road, Sandwich CT13 9NJ, UK – sequence: 13 givenname: Michael A. surname: Trevethick fullname: Trevethick, Michael A. organization: Allergy and Respiratory Biology, Pfizer, Ramsgate Road, Sandwich CT13 9NJ, UK – sequence: 14 givenname: Jessica surname: Watson fullname: Watson, Jessica organization: Allergy and Respiratory Biology, Pfizer, Ramsgate Road, Sandwich CT13 9NJ, UK – sequence: 15 givenname: Karen N. surname: Wright fullname: Wright, Karen N. organization: Allergy and Respiratory Biology, Pfizer, Ramsgate Road, Sandwich CT13 9NJ, UK – sequence: 16 givenname: Nick surname: Clarke fullname: Clarke, Nick organization: Allergy and Respiratory Biology, Pfizer, Ramsgate Road, Sandwich CT13 9NJ, UK |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26471092$$D View this record in MEDLINE/PubMed |
| BookMark | eNp9kMFqGzEQQEVJaOy0P9BD2WMv6452tasV9FKctAkkOIEGehNaaRbLaFepJAecr48cO5cechpmeG8Ob05OJj8hIV8oLCjQ9vtm0Y_aLSqgTT4sALoPZEZZy8qaQXNCZiBaKDvB_p6ReYwbAMqAsY_krGoZpyCqGbm_9Q711qlQrHd9sMY-q2T9VOwsOhOLFKx6zkjRBz_ptTfWqeRDLAYfirTGDKBKI06p8EOxXN1dfCKng3IRPx_nOXn4dflneVXerH5fL3_elJoBpFKrViikRmgFBgAH3vWMC9M0repMxzj0mDegmorBiNrUnA8cTGPYIED39Tn5dvj7GPy_LcYkRxs1Oqcm9NsoKa-6tuVdLTL69Yhu-xGNfAx2VGEn3zJkoDsAOvgYAw5S2_TaIQVlnaQg98XlRu6Ly33x_S0Xz2r1n_r2_V3px0HCHOjJYpBRW5w0GhtQJ2m8fU9_AVi6mr0 |
| CitedBy_id | crossref_primary_10_1002_slct_202204339 crossref_primary_10_1186_s12951_020_00703_5 crossref_primary_10_1016_j_arabjc_2017_11_005 crossref_primary_10_1002_jhet_3234 crossref_primary_10_3390_molecules25225450 crossref_primary_10_1016_j_drudis_2016_07_009 crossref_primary_10_1002_ddr_70132 crossref_primary_10_1039_D5MD00028A |
| Cites_doi | 10.1183/09031936.00067013 10.1211/jpp.60.8.0012 10.1021/jm5013227 10.1039/c1md00140j 10.1164/rccm.200904-0492OC 10.1016/j.pupt.2012.06.007 10.1021/jm501915g 10.1021/jm00114a016 10.1021/jm2007535 10.1124/mol.110.069120 10.2174/0929867311320120003 10.2174/0929867311320120002 10.1016/j.bmcl.2010.10.132 10.1136/thx.2007.087213 10.1164/rccm.201204-0596PP 10.4155/fmc.11.106 10.1016/B978-0-12-396493-9.00003-0 10.1016/S0928-0987(98)00057-8 |
| ContentType | Journal Article |
| Copyright | 2015 Elsevier Ltd Copyright © 2015 Elsevier Ltd. All rights reserved. |
| Copyright_xml | – notice: 2015 Elsevier Ltd – notice: Copyright © 2015 Elsevier Ltd. All rights reserved. |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1016/j.bmcl.2015.10.008 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic |
| 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: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine Anatomy & Physiology Chemistry |
| EISSN | 1464-3405 |
| EndPage | 5126 |
| ExternalDocumentID | 26471092 10_1016_j_bmcl_2015_10_008 S0960894X15301177 |
| Genre | Journal Article |
| GroupedDBID | --- --K --M .~1 0R~ 1B1 1RT 1~. 1~5 23N 4.4 457 4G. 5GY 5VS 7-5 71M 8P~ 9JM 9JN AABNK AACTN AAEDT AAEDW AAIAV AAIKJ AAKOC AALRI AAOAW AAQFI AARLI AATCM AAXUO ABBQC ABFNM ABGSF ABJNI ABLVK ABMAC ABMZM ABUDA ABYKQ ABZDS ACDAQ ACGFS ACIUM ACRLP ADBBV ADECG ADEZE ADUVX AEBSH AEHWI AEKER AENEX AFKWA AFTJW AFXIZ AFZHZ AGHFR AGUBO AGYEJ AHHHB AIEXJ AIKHN AITUG AJBFU AJOXV AJRQY AJSZI ALCLG ALMA_UNASSIGNED_HOLDINGS AMFUW AMRAJ ANZVX AXJTR BKOJK BLXMC BNPGV CS3 D0L DOVZS EBS EFJIC EFLBG EJD EO8 EO9 EP2 EP3 F5P FDB FIRID FLBIZ FNPLU FYGXN G-Q GBLVA IHE J1W KOM LCYCR LZ2 M29 M2Z M34 M41 MO0 N9A O-L O9- OAUVE OGGZJ OZT P-8 P-9 P2P PC. Q38 RIG ROL RPZ SCC SDF SDG SDP SES SPC SPCBC SSH SSK SSP SSU SSZ T5K YK3 ZMT ~02 ~G- .HR 53G 6TJ 9DU AAQXK AATTM AAXKI AAYWO AAYXX ABWVN ABXDB ACIEU ACLOT ACNNM ACRPL ACVFH ADCNI ADMUD ADNMO ADXHL AEIPS AEUPX AFFNX AFJKZ AFPUW AGQPQ AGRDE AIGII AIIUN AKBMS AKRWK AKYEP ANKPU APXCP ASPBG AVWKF AZFZN CITATION EFKBS FEDTE FGOYB G-2 HEA HMK HMO HMS HMT HVGLF HZ~ R2- SAE SCB SEW SOC SPT WUQ XPP Y6R ZY4 ~HD AGCQF AGRNS CGR CUY CVF ECM EIF NPM 7X8 |
| ID | FETCH-LOGICAL-c400t-ca69ae1d9ca0d00ef78b479d556a8d8470be9d501c19fd93d377f70d5d4f90cb3 |
| ISICitedReferencesCount | 10 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000364535000021&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 0960-894X 1464-3405 |
| IngestDate | Sat Sep 27 21:26:48 EDT 2025 Mon Jul 21 05:55:05 EDT 2025 Sat Nov 29 07:07:43 EST 2025 Tue Nov 18 21:28:57 EST 2025 Fri Feb 23 02:17:08 EST 2024 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 22 |
| Keywords | MABA Bifunctional Inhalation by design Bronchodilator COPD |
| Language | English |
| License | Copyright © 2015 Elsevier Ltd. All rights reserved. |
| LinkModel | OpenURL |
| MergedId | FETCHMERGED-LOGICAL-c400t-ca69ae1d9ca0d00ef78b479d556a8d8470be9d501c19fd93d377f70d5d4f90cb3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| OpenAccessLink | https://doi.org/10.7270/q2jq12v7 |
| PMID | 26471092 |
| PQID | 1728667839 |
| PQPubID | 23479 |
| PageCount | 6 |
| ParticipantIDs | proquest_miscellaneous_1728667839 pubmed_primary_26471092 crossref_citationtrail_10_1016_j_bmcl_2015_10_008 crossref_primary_10_1016_j_bmcl_2015_10_008 elsevier_sciencedirect_doi_10_1016_j_bmcl_2015_10_008 |
| PublicationCentury | 2000 |
| PublicationDate | 2015-11-15 |
| PublicationDateYYYYMMDD | 2015-11-15 |
| PublicationDate_xml | – month: 11 year: 2015 text: 2015-11-15 day: 15 |
| PublicationDecade | 2010 |
| PublicationPlace | England |
| PublicationPlace_xml | – name: England |
| PublicationTitle | Bioorganic & medicinal chemistry letters |
| PublicationTitleAlternate | Bioorg Med Chem Lett |
| PublicationYear | 2015 |
| Publisher | Elsevier Ltd |
| Publisher_xml | – name: Elsevier Ltd |
| References | Vestbo, Hurd, Agusti, Jones, Vogelmeier, Anzueto, Barnes, Fabbri, Martinez, Nishimura, Stockley, Sin, Rodriguez-Roisin (b0005) 2013; 187 Singh, Brooks, Hagan, Cahn, O’Connor (b0025) 2008; 63 Sladen, Clarke, Perros-Huguet, Yeadon (b0110) 2011; 183 Carter, Noronha-Blob, Audia, Dupont, McPherson, Natalie, Rzeszotarski, Spagnuolo, Waid, Kaiser (b0085) 1991; 34 Cazzola, Lopez-Campos, Puente-Maestu (b0015) 2013; 42 Hilton, Osborne, Kenyon, Baldock, Bunnage, Burrows, Clarke, Coghlan, Entwistle, Fairman, Feeder, James, Jones, Laouar, Lunn, Marshall, Newman, Patel, Selby, Spence, Stuart, Summerhill, Trevethick, Wright, Yeadon, Price, Jones (b0075) 2011; 2 Watson, Strawbridge, Brown, Campany, Coghlan, Trevethick (b0100) 2008; 22 Fuso, Mores, Valente, Malerba, Montuschi (b0030) 2013; 20 Hughes, McNamara, Steinfeld (b0045) 2012; 51 Osborne, Clarke, Glossop, Kenyon, Liu, Patel, Summerhill, Jones (b0080) 2011; 54 Hughes, Jones (b0040) 2011; 3 Jones, Baldock, Bunnage, Burrows, Clarke, Coghlan, Entwistle, Fairman, Feeder, Fulton, Hilton, James, Jones, Kenyon, Marshall, Newman, Osborne, Patel, Selby, Stuart, Trevethick, Wright, Price (b0095) 2011; 21 Montuschi, Ciabattoni (b0010) 2015; 58 Welte, Miravitlles, Hernandez, Eriksson, Peterson, Polanowski, Kessler (b0020) 2009; 180 Xu, Sim, Go (b0060) 1999; 8 Steinfeld, Hughes, Klein, Smith, Mammen (b0090) 2011; 79 Trubetskoy, Finel, Trubetskoy (b0105) 2008; 60 Yang, Hu, Huang (b0065) 2008; 30 McNamara, Steinfeld, Pulido-Rios, Stangeland, Hegde, Mammen, Martin (b0050) 2012; 25 Montuschi, Macagno, Valente, Fuso (b0035) 2013; 20 Hughes, Chen, Hegde, Jasper, Jaw-Tsai, Lee, McNamara, Pulido-Rios, Steinfeld, Mammen (b0055) 2015; 58 Jones, L. H.; Roberts, D. F.; Strang, R. S. 2010; Vol. WO2010004517. Cazzola (10.1016/j.bmcl.2015.10.008_b0015) 2013; 42 Osborne (10.1016/j.bmcl.2015.10.008_b0080) 2011; 54 Trubetskoy (10.1016/j.bmcl.2015.10.008_b0105) 2008; 60 Watson (10.1016/j.bmcl.2015.10.008_b0100) 2008; 22 10.1016/j.bmcl.2015.10.008_b0070 Singh (10.1016/j.bmcl.2015.10.008_b0025) 2008; 63 Carter (10.1016/j.bmcl.2015.10.008_b0085) 1991; 34 Vestbo (10.1016/j.bmcl.2015.10.008_b0005) 2013; 187 Montuschi (10.1016/j.bmcl.2015.10.008_b0035) 2013; 20 Hughes (10.1016/j.bmcl.2015.10.008_b0045) 2012; 51 Jones (10.1016/j.bmcl.2015.10.008_b0095) 2011; 21 Welte (10.1016/j.bmcl.2015.10.008_b0020) 2009; 180 Hughes (10.1016/j.bmcl.2015.10.008_b0040) 2011; 3 Montuschi (10.1016/j.bmcl.2015.10.008_b0010) 2015; 58 McNamara (10.1016/j.bmcl.2015.10.008_b0050) 2012; 25 Hughes (10.1016/j.bmcl.2015.10.008_b0055) 2015; 58 Sladen (10.1016/j.bmcl.2015.10.008_b0110) 2011; 183 Steinfeld (10.1016/j.bmcl.2015.10.008_b0090) 2011; 79 Hilton (10.1016/j.bmcl.2015.10.008_b0075) 2011; 2 Xu (10.1016/j.bmcl.2015.10.008_b0060) 1999; 8 Yang (10.1016/j.bmcl.2015.10.008_b0065) 2008; 30 Fuso (10.1016/j.bmcl.2015.10.008_b0030) 2013; 20 |
| References_xml | – volume: 58 start-page: 4131 year: 2015 ident: b0010 publication-title: J. Med. Chem. – reference: Jones, L. H.; Roberts, D. F.; Strang, R. S. 2010; Vol. WO2010004517. – volume: 3 start-page: 1585 year: 2011 ident: b0040 publication-title: Future Med. Chem. – volume: 63 start-page: 592 year: 2008 ident: b0025 publication-title: Thorax – volume: 8 start-page: 39 year: 1999 ident: b0060 publication-title: Eur. J. Pharm. Sci. – volume: 30 start-page: 8 year: 2008 ident: b0065 publication-title: Huaxue Shiji – volume: 20 start-page: 1477 year: 2013 ident: b0030 publication-title: Curr. Med. Chem. – volume: 42 start-page: 885 year: 2013 ident: b0015 publication-title: Eur. Respir. J. – volume: 60 start-page: 1061 year: 2008 ident: b0105 publication-title: J. Pharm. Pharmacol. – volume: 20 start-page: 1464 year: 2013 ident: b0035 publication-title: Curr. Med. Chem. – volume: 187 start-page: 347 year: 2013 ident: b0005 publication-title: Am. J. Respir. Crit. Care Med. – volume: 58 start-page: 2609 year: 2015 ident: b0055 publication-title: J. Med. Chem. – volume: 2 start-page: 870 year: 2011 ident: b0075 publication-title: Med. Chem. Commun. – volume: 25 start-page: 357 year: 2012 ident: b0050 publication-title: Pulm. Pharmacol. Ther. – volume: 21 start-page: 2759 year: 2011 ident: b0095 publication-title: Bioorg. Med. Chem. Lett. – volume: 34 start-page: 3065 year: 1991 ident: b0085 publication-title: J. Med. Chem. – volume: 22 start-page: 69 year: 2008 ident: b0100 publication-title: Fund. Clin. Pharm. – volume: 180 start-page: 741 year: 2009 ident: b0020 publication-title: Am. J. Respir. Crit. Care Med. – volume: 51 start-page: 71 year: 2012 ident: b0045 publication-title: Prog. Med. Chem. – volume: 54 start-page: 6998 year: 2011 ident: b0080 publication-title: J. Med. Chem. – volume: 183 start-page: A3099 year: 2011 ident: b0110 publication-title: Am. J. Respir. Crit. Care Med. – volume: 79 start-page: 389 year: 2011 ident: b0090 publication-title: Mol. Pharmacol. – volume: 42 start-page: 885 year: 2013 ident: 10.1016/j.bmcl.2015.10.008_b0015 publication-title: Eur. Respir. J. doi: 10.1183/09031936.00067013 – volume: 60 start-page: 1061 year: 2008 ident: 10.1016/j.bmcl.2015.10.008_b0105 publication-title: J. Pharm. Pharmacol. doi: 10.1211/jpp.60.8.0012 – volume: 58 start-page: 4131 year: 2015 ident: 10.1016/j.bmcl.2015.10.008_b0010 publication-title: J. Med. Chem. doi: 10.1021/jm5013227 – volume: 2 start-page: 870 year: 2011 ident: 10.1016/j.bmcl.2015.10.008_b0075 publication-title: Med. Chem. Commun. doi: 10.1039/c1md00140j – volume: 22 start-page: 69 year: 2008 ident: 10.1016/j.bmcl.2015.10.008_b0100 publication-title: Fund. Clin. Pharm. – volume: 183 start-page: A3099 year: 2011 ident: 10.1016/j.bmcl.2015.10.008_b0110 publication-title: Am. J. Respir. Crit. Care Med. – volume: 180 start-page: 741 year: 2009 ident: 10.1016/j.bmcl.2015.10.008_b0020 publication-title: Am. J. Respir. Crit. Care Med. doi: 10.1164/rccm.200904-0492OC – volume: 25 start-page: 357 year: 2012 ident: 10.1016/j.bmcl.2015.10.008_b0050 publication-title: Pulm. Pharmacol. Ther. doi: 10.1016/j.pupt.2012.06.007 – volume: 58 start-page: 2609 year: 2015 ident: 10.1016/j.bmcl.2015.10.008_b0055 publication-title: J. Med. Chem. doi: 10.1021/jm501915g – volume: 30 start-page: 8 year: 2008 ident: 10.1016/j.bmcl.2015.10.008_b0065 publication-title: Huaxue Shiji – volume: 34 start-page: 3065 year: 1991 ident: 10.1016/j.bmcl.2015.10.008_b0085 publication-title: J. Med. Chem. doi: 10.1021/jm00114a016 – volume: 54 start-page: 6998 year: 2011 ident: 10.1016/j.bmcl.2015.10.008_b0080 publication-title: J. Med. Chem. doi: 10.1021/jm2007535 – volume: 79 start-page: 389 year: 2011 ident: 10.1016/j.bmcl.2015.10.008_b0090 publication-title: Mol. Pharmacol. doi: 10.1124/mol.110.069120 – volume: 20 start-page: 1477 year: 2013 ident: 10.1016/j.bmcl.2015.10.008_b0030 publication-title: Curr. Med. Chem. doi: 10.2174/0929867311320120003 – volume: 20 start-page: 1464 year: 2013 ident: 10.1016/j.bmcl.2015.10.008_b0035 publication-title: Curr. Med. Chem. doi: 10.2174/0929867311320120002 – volume: 21 start-page: 2759 year: 2011 ident: 10.1016/j.bmcl.2015.10.008_b0095 publication-title: Bioorg. Med. Chem. Lett. doi: 10.1016/j.bmcl.2010.10.132 – volume: 63 start-page: 592 year: 2008 ident: 10.1016/j.bmcl.2015.10.008_b0025 publication-title: Thorax doi: 10.1136/thx.2007.087213 – ident: 10.1016/j.bmcl.2015.10.008_b0070 – volume: 187 start-page: 347 year: 2013 ident: 10.1016/j.bmcl.2015.10.008_b0005 publication-title: Am. J. Respir. Crit. Care Med. doi: 10.1164/rccm.201204-0596PP – volume: 3 start-page: 1585 year: 2011 ident: 10.1016/j.bmcl.2015.10.008_b0040 publication-title: Future Med. Chem. doi: 10.4155/fmc.11.106 – volume: 51 start-page: 71 year: 2012 ident: 10.1016/j.bmcl.2015.10.008_b0045 publication-title: Prog. Med. Chem. doi: 10.1016/B978-0-12-396493-9.00003-0 – volume: 8 start-page: 39 year: 1999 ident: 10.1016/j.bmcl.2015.10.008_b0060 publication-title: Eur. J. Pharm. Sci. doi: 10.1016/S0928-0987(98)00057-8 |
| SSID | ssj0014044 |
| Score | 2.2030127 |
| Snippet | [Display omitted]
A 1,2,4-triazole motif was employed as a bioisostere for the ester commonly used in muscarinic antagonists, and subsequent integrative... A 1,2,4-triazole motif was employed as a bioisostere for the ester commonly used in muscarinic antagonists, and subsequent integrative conjugation to a β2... |
| SourceID | proquest pubmed crossref elsevier |
| SourceType | Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 5121 |
| SubjectTerms | Adrenergic beta-2 Receptor Agonists - chemical synthesis Adrenergic beta-2 Receptor Agonists - pharmacokinetics Adrenergic beta-2 Receptor Agonists - pharmacology Animals Bifunctional Biological Availability Bronchoconstriction - drug effects Bronchodilator Bronchodilator Agents - chemical synthesis Bronchodilator Agents - pharmacokinetics Bronchodilator Agents - pharmacology CHO Cells COPD Cricetulus Dogs Humans Inhalation by design Ipratropium - pharmacology MABA Muscarinic Antagonists - chemical synthesis Muscarinic Antagonists - pharmacokinetics Muscarinic Antagonists - pharmacology Pulmonary Disease, Chronic Obstructive - drug therapy Rats Receptor, Muscarinic M3 - antagonists & inhibitors Salmeterol Xinafoate - pharmacology Tiotropium Bromide - pharmacology Triazoles - chemical synthesis Triazoles - pharmacokinetics Triazoles - pharmacology |
| Title | Molecular hybridization yields triazole bronchodilators for the treatment of COPD |
| URI | https://dx.doi.org/10.1016/j.bmcl.2015.10.008 https://www.ncbi.nlm.nih.gov/pubmed/26471092 https://www.proquest.com/docview/1728667839 |
| Volume | 25 |
| WOSCitedRecordID | wos000364535000021&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVESC databaseName: Elsevier SD Freedom Collection Journals 2021 customDbUrl: eissn: 1464-3405 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0014044 issn: 0960-894X databaseCode: AIEXJ dateStart: 19950101 isFulltext: true titleUrlDefault: https://www.sciencedirect.com providerName: Elsevier |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1db9MwFLW6DQEvCDoG5WMyEuOlyhQ3H44fy2gFqOtA6qS-RY7tiE5dWvoxrfwGfjTXsZ2waZvGAy9Ra9Vt1HN8c5N7rg9C7zuCQ4xTzCNKcC_shLmXcBbDusok5VQSqbLSbIIOh8l4zL41Gr9dL8zFlBZFcnnJ5v8VahgDsHXr7D_AXX0pDMBrAB2OADsc7wX8sTO8bf_Y6HYs22jZ3mit2rKtbTp-aUlhtpgVEPvkZMpLxx2nN6yl51qpcWL9013ddzIzPlCi5IytzOs9RpxxXHtaNgjVykRnBjDYFHUnxMe13vvRcIjXlf2-UtJwSD-crrRBU7iSz-ZXhIz2QQWJdMeeadW0sTWMQy8IfTOkbhizAbkT_UU807VswytkJ-TGuG8eQZwdZudC15NIdFhK9pL6Kucq-8OTtH86GKSj3nh0EPTnPz3tQKYr9QfBJ8OGLbTToRGDGLnT_dIbf62qUqFfmgNXJ22bsIxe8PpP35bo3HYjUyY0o6foib0TwV3DoGeooYom2u0WwIbzDf6AS21wWXRpokdHDt4menhs5Ri76HvFNXyFa9hwDTuu4Wtcw8A1DFzDFdfwLMeaa8_Rab83OvrsWY8OT0D0X3mCx4wrIpngvvR9ldMkCymTURTzRELq42cK3vlEEJZLFsiA0pz6MpJhznyRBXtouwAivkQ44X6cE5olsfZ4yBmPWBIpP6AqJ3mgeAsR94emwm5gr31UpqlTKp6lGoRUg6DHAIQWaldz5mb7ljs_HTmcUpuAmsQyBZ7dOe-dAzUFMHTJDZbObL1MtftbDPlgwFrohUG7Og-4FdFC6M6re8x-jR7XS-oN2l4t1uoteiAuVpPlYh9t0XGyb9n6B56RvEU |
| 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=Molecular+hybridization+yields+triazole+bronchodilators+for+the+treatment+of+COPD&rft.jtitle=Bioorganic+%26+medicinal+chemistry+letters&rft.au=Jones%2C+Lyn+H&rft.au=Burrows%2C+Jane&rft.au=Feeder%2C+Neil&rft.au=Glossop%2C+Paul&rft.date=2015-11-15&rft.issn=1464-3405&rft.eissn=1464-3405&rft.volume=25&rft.issue=22&rft.spage=5121&rft_id=info:doi/10.1016%2Fj.bmcl.2015.10.008&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0960-894X&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0960-894X&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0960-894X&client=summon |