Nonpeptide Angiotensin II Receptor Antagonists: Synthesis, Biological Activities, and Structure−Activity Relationships of Imidazole-5-carboxylic Acids Bearing Alkyl, Alkenyl, and Hydroxyalkyl Substituents at the 4-Position and Their Related Compounds
A series of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related compounds were prepared and evaluated for their antagonistic activities to the angiotensin II (AII) receptor. Among them, the 4-(1-hydroxyalkyl)imidazole derivatives had...
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| Veröffentlicht in: | Journal of medicinal chemistry 1996-01, Vol.39 (1), p.323-338 |
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| container_title | Journal of medicinal chemistry |
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| creator | Yanagisawa, Hiroaki Amemiya, Yoshiya Kanazaki, Takuro Shimoji, Yasuo Fujimoto, Koichi Kitahara, Yoshiko Sada, Toshio Mizuno, Makoto Ikeda, Masahiro Miyamoto, Shuichi Furukawa, Youji Koike, Hiroyuki |
| description | A series of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related compounds were prepared and evaluated for their antagonistic activities to the angiotensin II (AII) receptor. Among them, the 4-(1-hydroxyalkyl)imidazole derivatives had strong binding affinity to the AII receptor and potently inhibited the AII-induced pressor response by intravenous administration. Various esters of these acids showed potent and long-lasting antagonistic activity by oral administration. The most promising compounds were (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (CS-866) and (pivaloyloxy)methyl esters of 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[(2‘-1H-tetrazol-5-ylbiphenyl-4-yl)methyl]imidazole-5-carboxylic acid (26c). A study involving stereochemical comparison of 26c with the acetylated C-terminal pentapeptide of AII was also undertaken. |
| doi_str_mv | 10.1021/jm950450f |
| format | Article |
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Among them, the 4-(1-hydroxyalkyl)imidazole derivatives had strong binding affinity to the AII receptor and potently inhibited the AII-induced pressor response by intravenous administration. Various esters of these acids showed potent and long-lasting antagonistic activity by oral administration. The most promising compounds were (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (CS-866) and (pivaloyloxy)methyl esters of 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[(2‘-1H-tetrazol-5-ylbiphenyl-4-yl)methyl]imidazole-5-carboxylic acid (26c). A study involving stereochemical comparison of 26c with the acetylated C-terminal pentapeptide of AII was also undertaken.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm950450f</identifier><identifier>PMID: 8568823</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Acetylation ; Adrenal Cortex - drug effects ; Amino Acid Sequence ; Angiotensin II - antagonists & inhibitors ; Angiotensin II - pharmacology ; Angiotensin Receptor Antagonists ; Animals ; Antihypertensive agents ; Antihypertensive Agents - chemical synthesis ; Antihypertensive Agents - chemistry ; Antihypertensive Agents - metabolism ; Antihypertensive Agents - pharmacology ; Biological and medical sciences ; Biological Availability ; Cardiovascular system ; Cattle ; Imidazoles - chemical synthesis ; Imidazoles - chemistry ; Imidazoles - metabolism ; Imidazoles - pharmacology ; In Vitro Techniques ; Kinetics ; Male ; Medical sciences ; Models, Molecular ; Molecular Conformation ; Molecular Sequence Data ; Molecular Structure ; Pharmacology. Drug treatments ; Rats ; Rats, Wistar ; Receptors, Angiotensin - metabolism ; Structure-Activity Relationship</subject><ispartof>Journal of medicinal chemistry, 1996-01, Vol.39 (1), p.323-338</ispartof><rights>Copyright © 1996 American Chemical Society</rights><rights>1996 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a377t-3468252afcd4ba5384249abedfae2fe10cce357b849d1d87ff3bc787027fb7973</citedby><cites>FETCH-LOGICAL-a377t-3468252afcd4ba5384249abedfae2fe10cce357b849d1d87ff3bc787027fb7973</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm950450f$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm950450f$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2965155$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8568823$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yanagisawa, Hiroaki</creatorcontrib><creatorcontrib>Amemiya, Yoshiya</creatorcontrib><creatorcontrib>Kanazaki, Takuro</creatorcontrib><creatorcontrib>Shimoji, Yasuo</creatorcontrib><creatorcontrib>Fujimoto, Koichi</creatorcontrib><creatorcontrib>Kitahara, Yoshiko</creatorcontrib><creatorcontrib>Sada, Toshio</creatorcontrib><creatorcontrib>Mizuno, Makoto</creatorcontrib><creatorcontrib>Ikeda, Masahiro</creatorcontrib><creatorcontrib>Miyamoto, Shuichi</creatorcontrib><creatorcontrib>Furukawa, Youji</creatorcontrib><creatorcontrib>Koike, Hiroyuki</creatorcontrib><title>Nonpeptide Angiotensin II Receptor Antagonists: Synthesis, Biological Activities, and Structure−Activity Relationships of Imidazole-5-carboxylic Acids Bearing Alkyl, Alkenyl, and Hydroxyalkyl Substituents at the 4-Position and Their Related Compounds</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>A series of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related compounds were prepared and evaluated for their antagonistic activities to the angiotensin II (AII) receptor. Among them, the 4-(1-hydroxyalkyl)imidazole derivatives had strong binding affinity to the AII receptor and potently inhibited the AII-induced pressor response by intravenous administration. Various esters of these acids showed potent and long-lasting antagonistic activity by oral administration. The most promising compounds were (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (CS-866) and (pivaloyloxy)methyl esters of 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[(2‘-1H-tetrazol-5-ylbiphenyl-4-yl)methyl]imidazole-5-carboxylic acid (26c). A study involving stereochemical comparison of 26c with the acetylated C-terminal pentapeptide of AII was also undertaken.</description><subject>Acetylation</subject><subject>Adrenal Cortex - drug effects</subject><subject>Amino Acid Sequence</subject><subject>Angiotensin II - antagonists & inhibitors</subject><subject>Angiotensin II - pharmacology</subject><subject>Angiotensin Receptor Antagonists</subject><subject>Animals</subject><subject>Antihypertensive agents</subject><subject>Antihypertensive Agents - chemical synthesis</subject><subject>Antihypertensive Agents - chemistry</subject><subject>Antihypertensive Agents - metabolism</subject><subject>Antihypertensive Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Biological Availability</subject><subject>Cardiovascular system</subject><subject>Cattle</subject><subject>Imidazoles - chemical synthesis</subject><subject>Imidazoles - chemistry</subject><subject>Imidazoles - metabolism</subject><subject>Imidazoles - pharmacology</subject><subject>In Vitro Techniques</subject><subject>Kinetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Models, Molecular</subject><subject>Molecular Conformation</subject><subject>Molecular Sequence Data</subject><subject>Molecular Structure</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, Angiotensin - metabolism</subject><subject>Structure-Activity Relationship</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkc9u1DAQxiMEKqVw4AGQfAAkpAYcO84fbtsVtCsKVN3lHDn2ZNfbxA62gxpOHOHKI_ZFwGFXe-I0o_l--mY0XxQ9TfDrBJPkzbYrGU4Zbu5FxwkjOE4LnN6PjjEmJCYZoQ-jR85tMcY0IfQoOipYVhSEHkd_PhndQ--VBDTTa2U8aKc0WizQNYggGBvmnq-NVs67t3c_fqHlqP0GnHKn6EyZ1qyV4C2aCa--Ka8gjLmWaOntIPxg4e7n7702Bs-We2W026jeIdOgRack_25aiFksuK3N7dgqEcyUdOgMuFV6jWbtzdieTgX01Ez2F6O0AeaThJZD7bzyA2jvEPconIfS-Mo4NS37x682oOxuP0g0N11vBi3d4-hBw1sHT_b1JPry_t1qfhFffj5fzGeXMad57mOaZgVhhDdCpjVntEhJWvIaZMOBNJBgIYCyvC7SUiayyJuG1iIvckzyps7LnJ5EL3e-vTVfB3C-6pQT0LZcgxlclQeIpSUN4KsdKKxxzkJT9VZ13I5Vgqsp7OoQdmCf7U2HugN5IPfpBv35XucuRNRYroVyB4yUGUsYC1i8w0LCcHuQub2pspzmrFpdLavyw-o6O08_VkngX-x4Lly1NYPV4XP_Oe8vo23VEA</recordid><startdate>19960105</startdate><enddate>19960105</enddate><creator>Yanagisawa, Hiroaki</creator><creator>Amemiya, Yoshiya</creator><creator>Kanazaki, Takuro</creator><creator>Shimoji, Yasuo</creator><creator>Fujimoto, Koichi</creator><creator>Kitahara, Yoshiko</creator><creator>Sada, Toshio</creator><creator>Mizuno, Makoto</creator><creator>Ikeda, Masahiro</creator><creator>Miyamoto, Shuichi</creator><creator>Furukawa, Youji</creator><creator>Koike, Hiroyuki</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19960105</creationdate><title>Nonpeptide Angiotensin II Receptor Antagonists: Synthesis, Biological Activities, and Structure−Activity Relationships of Imidazole-5-carboxylic Acids Bearing Alkyl, Alkenyl, and Hydroxyalkyl Substituents at the 4-Position and Their Related Compounds</title><author>Yanagisawa, Hiroaki ; Amemiya, Yoshiya ; Kanazaki, Takuro ; Shimoji, Yasuo ; Fujimoto, Koichi ; Kitahara, Yoshiko ; Sada, Toshio ; Mizuno, Makoto ; Ikeda, Masahiro ; Miyamoto, Shuichi ; Furukawa, Youji ; Koike, Hiroyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a377t-3468252afcd4ba5384249abedfae2fe10cce357b849d1d87ff3bc787027fb7973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Acetylation</topic><topic>Adrenal Cortex - drug effects</topic><topic>Amino Acid Sequence</topic><topic>Angiotensin II - antagonists & inhibitors</topic><topic>Angiotensin II - pharmacology</topic><topic>Angiotensin Receptor Antagonists</topic><topic>Animals</topic><topic>Antihypertensive agents</topic><topic>Antihypertensive Agents - chemical synthesis</topic><topic>Antihypertensive Agents - chemistry</topic><topic>Antihypertensive Agents - metabolism</topic><topic>Antihypertensive Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Biological Availability</topic><topic>Cardiovascular system</topic><topic>Cattle</topic><topic>Imidazoles - chemical synthesis</topic><topic>Imidazoles - chemistry</topic><topic>Imidazoles - metabolism</topic><topic>Imidazoles - pharmacology</topic><topic>In Vitro Techniques</topic><topic>Kinetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Models, Molecular</topic><topic>Molecular Conformation</topic><topic>Molecular Sequence Data</topic><topic>Molecular Structure</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptors, Angiotensin - metabolism</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yanagisawa, Hiroaki</creatorcontrib><creatorcontrib>Amemiya, Yoshiya</creatorcontrib><creatorcontrib>Kanazaki, Takuro</creatorcontrib><creatorcontrib>Shimoji, Yasuo</creatorcontrib><creatorcontrib>Fujimoto, Koichi</creatorcontrib><creatorcontrib>Kitahara, Yoshiko</creatorcontrib><creatorcontrib>Sada, Toshio</creatorcontrib><creatorcontrib>Mizuno, Makoto</creatorcontrib><creatorcontrib>Ikeda, Masahiro</creatorcontrib><creatorcontrib>Miyamoto, Shuichi</creatorcontrib><creatorcontrib>Furukawa, Youji</creatorcontrib><creatorcontrib>Koike, Hiroyuki</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yanagisawa, Hiroaki</au><au>Amemiya, Yoshiya</au><au>Kanazaki, Takuro</au><au>Shimoji, Yasuo</au><au>Fujimoto, Koichi</au><au>Kitahara, Yoshiko</au><au>Sada, Toshio</au><au>Mizuno, Makoto</au><au>Ikeda, Masahiro</au><au>Miyamoto, Shuichi</au><au>Furukawa, Youji</au><au>Koike, Hiroyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nonpeptide Angiotensin II Receptor Antagonists: Synthesis, Biological Activities, and Structure−Activity Relationships of Imidazole-5-carboxylic Acids Bearing Alkyl, Alkenyl, and Hydroxyalkyl Substituents at the 4-Position and Their Related Compounds</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1996-01-05</date><risdate>1996</risdate><volume>39</volume><issue>1</issue><spage>323</spage><epage>338</epage><pages>323-338</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>A series of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related compounds were prepared and evaluated for their antagonistic activities to the angiotensin II (AII) receptor. Among them, the 4-(1-hydroxyalkyl)imidazole derivatives had strong binding affinity to the AII receptor and potently inhibited the AII-induced pressor response by intravenous administration. Various esters of these acids showed potent and long-lasting antagonistic activity by oral administration. The most promising compounds were (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (CS-866) and (pivaloyloxy)methyl esters of 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[(2‘-1H-tetrazol-5-ylbiphenyl-4-yl)methyl]imidazole-5-carboxylic acid (26c). A study involving stereochemical comparison of 26c with the acetylated C-terminal pentapeptide of AII was also undertaken.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>8568823</pmid><doi>10.1021/jm950450f</doi><tpages>16</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Journal of medicinal chemistry, 1996-01, Vol.39 (1), p.323-338 |
| issn | 0022-2623 1520-4804 |
| language | eng |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Acetylation Adrenal Cortex - drug effects Amino Acid Sequence Angiotensin II - antagonists & inhibitors Angiotensin II - pharmacology Angiotensin Receptor Antagonists Animals Antihypertensive agents Antihypertensive Agents - chemical synthesis Antihypertensive Agents - chemistry Antihypertensive Agents - metabolism Antihypertensive Agents - pharmacology Biological and medical sciences Biological Availability Cardiovascular system Cattle Imidazoles - chemical synthesis Imidazoles - chemistry Imidazoles - metabolism Imidazoles - pharmacology In Vitro Techniques Kinetics Male Medical sciences Models, Molecular Molecular Conformation Molecular Sequence Data Molecular Structure Pharmacology. Drug treatments Rats Rats, Wistar Receptors, Angiotensin - metabolism Structure-Activity Relationship |
| title | Nonpeptide Angiotensin II Receptor Antagonists: Synthesis, Biological Activities, and Structure−Activity Relationships of Imidazole-5-carboxylic Acids Bearing Alkyl, Alkenyl, and Hydroxyalkyl Substituents at the 4-Position and Their Related Compounds |
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