{"id":"https://openalex.org/W2012735547","doi":"https://doi.org/10.1021/jm00087a010","title":"A new class of bradykinin antagonists: synthesis and in vitro activity of bissuccinimidoalkane peptide dimers","display_name":"A new class of bradykinin antagonists: synthesis and in vitro activity of bissuccinimidoalkane peptide dimers","publication_year":1992,"publication_date":"1992-05-01","ids":{"openalex":"https://openalex.org/W2012735547","doi":"https://doi.org/10.1021/jm00087a010","mag":"2012735547","pmid":"https://pubmed.ncbi.nlm.nih.gov/1578482"},"language":"en","primary_location":{"id":"doi:10.1021/jm00087a010","doi":"https://doi.org/10.1021/jm00087a010","is_oa":false,"landing_page_url":"https://doi.org/10.1021/jm00087a010","pdf_url":null,"source":{"id":"https://openalex.org/S162030435","display_name":"Journal of Medicinal Chemistry","issn_l":"0022-2623","issn":["0022-2623","1520-4804"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","jufo-3","ki-jl-2","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Medicinal Chemistry","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5075795213","display_name":"John C. Cheronis","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"John C. Cheronis","raw_affiliation_strings":["Cortech, Inc., Denver, Colorado 80221"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cortech, Inc., Denver, Colorado 80221","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5108200487","display_name":"Eric T. Whalley","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Eric T. Whalley","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"Khe T. Nguyen","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Khe T. Nguyen","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5085451688","display_name":"Shad R. Eubanks","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Shad R. Eubanks","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5010048631","display_name":"Lisa G. Allen","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Lisa G. Allen","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110097084","display_name":"Matthew J. Duggan","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Matthew J. Duggan","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5025531594","display_name":"Sharon D. Loy","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Sharon D. Loy","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5114893543","display_name":"Kathryn A. Bonham","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Kathryn A. Bonham","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5023993494","display_name":"James K. Blodgett","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"James K. Blodgett","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":6.0084,"has_fulltext":false,"cited_by_count":128,"citation_normalized_percentile":{"value":0.96794974,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":88,"max":98},"biblio":{"volume":"35","issue":"9","first_page":"1563","last_page":"1572"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11917","display_name":"Coagulation, Bradykinin, Polyphosphates, and Angioedema","score":0.8417999744415283,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T11917","display_name":"Coagulation, Bradykinin, Polyphosphates, and Angioedema","score":0.8417999744415283,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10911","display_name":"Chemical Synthesis and Analysis","score":0.14669999480247498,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10274","display_name":"Heterocyclic Compound Synthesis and Bioactivity","score":0.00139999995008111,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/bradykinin-receptor-antagonists","display_name":"bradykinin receptor antagonists","score":0.9890000224113464},{"id":"https://openalex.org/keywords/peptide-dimers","display_name":"peptide dimers","score":0.7860000133514404},{"id":"https://openalex.org/keywords/peptide-dimerization","display_name":"peptide dimerization","score":0.7369999885559082},{"id":"https://openalex.org/keywords/linker-length","display_name":"linker length","score":0.4970000088214874},{"id":"https://openalex.org/keywords/duration-of-action","display_name":"duration of action","score":0.703000009059906},{"id":"https://openalex.org/keywords/smooth-muscle-contraction","display_name":"smooth muscle contraction","score":0.8100000023841858},{"id":"https://openalex.org/keywords/guinea-pig-ileum","display_name":"guinea pig ileum","score":0.9319999814033508},{"id":"https://openalex.org/keywords/rat-uterus","display_name":"rat uterus","score":0.9539999961853027},{"id":"https://openalex.org/keywords/partial-agonism","display_name":"partial agonism","score":0.8669999837875366},{"id":"https://openalex.org/keywords/bradykinin","display_name":"bradykinin","score":0.7059999704360962}],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.8911638259887695},{"id":"https://openalex.org/C2779591629","wikidata":"https://www.wikidata.org/wiki/Q24745328","display_name":"Bradykinin","level":3,"score":0.8739103674888611},{"id":"https://openalex.org/C2777454769","wikidata":"https://www.wikidata.org/wiki/Q11172462","display_name":"Methylene","level":2,"score":0.7042330503463745},{"id":"https://openalex.org/C57992300","wikidata":"https://www.wikidata.org/wiki/Q2066956","display_name":"Potency","level":3,"score":0.6583147644996643},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.6344736218452454},{"id":"https://openalex.org/C2776885963","wikidata":"https://www.wikidata.org/wiki/Q245204","display_name":"Antagonist","level":3,"score":0.5697577595710754},{"id":"https://openalex.org/C2777226302","wikidata":"https://www.wikidata.org/wiki/Q233345","display_name":"Ileum","level":2,"score":0.5199845433235168},{"id":"https://openalex.org/C2779281246","wikidata":"https://www.wikidata.org/wiki/Q172847","display_name":"Peptide","level":2,"score":0.4864818751811981},{"id":"https://openalex.org/C2780557392","wikidata":"https://www.wikidata.org/wiki/Q523796","display_name":"Linker","level":2,"score":0.46466219425201416},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.39810293912887573},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.277188777923584},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.1997445523738861},{"id":"https://openalex.org/C155647269","wikidata":"https://www.wikidata.org/wiki/Q243455","display_name":"Medicinal chemistry","level":1,"score":0.13681334257125854},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.0},{"id":"https://openalex.org/C111919701","wikidata":"https://www.wikidata.org/wiki/Q9135","display_name":"Operating system","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000595","descriptor_name":"Amino Acid Sequence","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001920","descriptor_name":"Bradykinin","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":true},{"descriptor_ui":"D001920","descriptor_name":"Bradykinin","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D001920","descriptor_name":"Bradykinin","qualifier_ui":"Q000138","qualifier_name":"chemical synthesis","is_major_topic":false},{"descriptor_ui":"D001920","descriptor_name":"Bradykinin","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006168","descriptor_name":"Guinea Pigs","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007082","descriptor_name":"Ileum","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D008969","descriptor_name":"Molecular Sequence Data","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009119","descriptor_name":"Muscle Contraction","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D009130","descriptor_name":"Muscle, Smooth","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D009130","descriptor_name":"Muscle, Smooth","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":false},{"descriptor_ui":"D009215","descriptor_name":"Myometrium","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D066298","descriptor_name":"In Vitro Techniques","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/jm00087a010","doi":"https://doi.org/10.1021/jm00087a010","is_oa":false,"landing_page_url":"https://doi.org/10.1021/jm00087a010","pdf_url":null,"source":{"id":"https://openalex.org/S162030435","display_name":"Journal of Medicinal Chemistry","issn_l":"0022-2623","issn":["0022-2623","1520-4804"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","jufo-3","ki-jl-2","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Medicinal Chemistry","raw_type":"journal-article"},{"id":"pmid:1578482","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/1578482","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of medicinal chemistry","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.6240000128746033,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2399250882","https://openalex.org/W2033417489","https://openalex.org/W2050852845","https://openalex.org/W2949343250","https://openalex.org/W1997490817","https://openalex.org/W2011650011","https://openalex.org/W2481022045","https://openalex.org/W1512854076","https://openalex.org/W2043188275","https://openalex.org/W2418628324"],"abstract_inverted_index":{"A":[0],"systematic":[1],"study":[2,21,46],"on":[3,89],"the":[4,7,54,70,110,206,212,222,237,242,290,305,324,340,344],"dimerization":[5,25,73,124,148,267,319],"of":[6,19,44,50,72,83,109,120,141,147,205,214,226,244,307,310,328,334,339],"bradykinin":[8],"(BK)":[9],"antagonist":[10,142,292],"D-Arg0-Arg1-Pro2-Hyp3-Gly4-Phe5-Ser6-D-Phe":[11,293],"7-Leu8-Arg9":[12],"has":[13],"been":[14],"performed.":[15],"The":[16,41,80,259],"first":[17],"part":[18,43],"this":[20,45],"involved":[22],"compounds":[23],"wherein":[24,53],"was":[26,58,74,264,296],"carried":[27],"out":[28],"by":[29,211],"sequentially":[30],"replacing":[31],"each":[32],"amino":[33],"acid":[34],"with":[35,39,135,266,337],"cysteine":[36],"and":[37,104,117,248,271,330],"cross-linking":[38],"bismaleimidohexane.":[40],"second":[42],"utilized":[47],"a":[48,145,318],"series":[49],"bissuccinimidoalkane":[51],"dimers":[52,85],"intervening":[55],"methylene":[56,215,230],"chain":[57],"varied":[59],"systematically":[60],"from":[61],"n":[62,66,255,272],"=":[63,67,273],"2":[64,164,190],"to":[65,228],"12":[68],"while":[69],"point":[71],"held":[75],"constant":[76],"at":[77,125,268],"position":[78,126,149,269],"6.":[79],"biological":[81],"activities":[82,116],"these":[84],"were":[86,286],"then":[87],"evaluated":[88],"BK-induced":[90],"smooth":[91],"muscle":[92],"contraction":[93],"in":[94,246,250,262,284,331,343],"two":[95,223],"different":[96],"isolated":[97],"tissue":[98],"preparations:":[99],"guinea":[100,178],"pig":[101,179],"ileum":[102],"(GPI)":[103],"rat":[105,153],"uterus":[106],"(RU).":[107],"Several":[108],"dimeric":[111,133],"BK":[112,308,341],"antagonists":[113,309,342],"displayed":[114],"remarkable":[115],"long":[118],"durations":[119],"action.":[121],"In":[122],"addition,":[123],"4,":[127,174,200],"7,":[128,175,201],"8,":[129,176,202],"or":[130],"9":[131],"produced":[132],"analogues":[134],"markedly":[136],"reduced":[137],"potency.":[138],"Rank":[139],"order":[140],"potency":[143,285,329],"as":[144,151,209,277],"function":[146],"is":[150],"follows:":[152],"uterus,":[154],"6":[155,181,270,274],"greater":[156,159,162,165,168,172,182,185,188,191,194,198,256],"than":[157,160,163,166,169,173,183,186,189,192,195,199,257],"5":[158,184],"0":[161,196],"1":[167,193],"3":[170,187],"much":[171,197],"9;":[177],"ileum,":[180],"9.":[203],"Evaluation":[204],"linker":[207],"length":[208,239],"represented":[210],"number":[213],"units":[216],"indicated":[217],"an":[218],"optimal":[219],"distance":[220],"between":[221],"monomeric":[224,291],"peptides":[225],"six":[227],"eight":[229],"moieties.":[231],"These":[232,301],"studies":[233],"also":[234,287],"revealed":[235],"that":[236,304,321],"carbon-chain":[238],"significantly":[240],"affected":[241],"duration":[243,333],"action":[245,335],"vitro":[247,263],"resulted":[249],"partial":[251],"agonism":[252],"effects":[253,283],"when":[254,289],"8.":[258],"optimum":[260],"activity":[261],"achieved":[265],"(designated":[275],"herein":[276],"compound":[278],"25;":[279],"alternatively,":[280],"CP-0127).":[281],"Similar":[282],"seen":[288],"7-Phe8-Arg9":[294],"(NPC-567)":[295],"dimerized":[297],"using":[298,317],"similar":[299],"chemistry.":[300],"results":[302],"suggest":[303],"development":[306],"significant":[311],"therapeutic":[312],"potential":[313],"may":[314],"be":[315],"possible":[316],"strategy":[320],"can":[322],"overcome":[323],"heretofore":[325],"limiting":[326],"problems":[327],"vivo":[332],"found":[336],"many":[338],"literature.":[345]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":1},{"year":2023,"cited_by_count":1},{"year":2022,"cited_by_count":2},{"year":2021,"cited_by_count":2},{"year":2020,"cited_by_count":1},{"year":2017,"cited_by_count":2},{"year":2015,"cited_by_count":1},{"year":2014,"cited_by_count":1},{"year":2013,"cited_by_count":1},{"year":2012,"cited_by_count":5}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}