A series of halogenated (F, Cl, Br, I), pyrimido and diazepino homologs of mazindol were prepared and evaluated for their ability to displace [3H]WIN 35,428 binding and to inhibit uptake of [3H]dopamine (DA) in rat striatal tissue. All of the compounds except for the 2'-chloro (6) and 2'-bromo (16) analogs of mazindol displaced [3H]WIN 35,428 binding and inhibited [3H]DA uptake more effectively than (R)-cocaine. Structure-activity studies indicated that best inhibition of [3H]WIN 35,428 binding occurred in the imidazo series with compounds containing one or two Cl or Br atoms in the 3'- or 4'-position of the free phenyl group. Replacement of the imidazo ring by a pyrimido or diazepino ring enhanced binding inhibition. The most potent inhibitors of [3H]WIN 35,428 binding and [3H]DA uptake were 6-(3'-chlorophenyl)-2,3,4,6-tetrahydropyrimido[2,1-alpha]isoind ol-6-ol (23; IC50 1.0 nM; 8 x mazindol) and 7-(3',4'-dichlorophenyl)-2,3,4,5-tetrahydro-7H-diazepino[2,1-alpha ]isoindol-7-ol (28; IC50 0.26 nM; 32 x mazindol), respectively. No significant differences was found between binding and uptake inhibition. Mazindol and the pyrimido and diazepino homologs 24 and 27 showed a selectivity for the DA uptake over the serotonin (5-HT) uptake site of 5-, 250-, and 465-fold, respectively, and displayed weak or no affinity for a variety of neurotransmitter receptor sites.

A series of 5-aryl-2,3-dihydroimidazo[2,1-a]isoquinolines previously reported to be platelet activating factor (PAF) receptor antagonists were evaluated for potential antitumor activity. Several compounds, such as the 5-(4'-tert-butylphenyl) (65), 5-[4'-(trimethylsilyl)phenyl] (69), and 5-(4'-cyclohexylphenyl) (71) analogs showed very good cytotoxicity against several tumor cell lines. 5-[4'-(Piperidinomethyl)phenyl]-2,3-dihydroimidazo[2,1- a]isoquinoline (SDZ 62-434, 53) was more effective on a milligram per kilogram basis than the clinical cytostatic agent edelfosine (1) in increasing survivors and decreasing tumor volume in the oral mouse Meth A fibrosarcoma assay. It was selected for further development and is currently in phase I clinical trials in cancer patients.

In an effort to determine the effect of modification of the imidazo[2,1-a]isoquinoline portion of the PAF-receptor antagonist SDZ 64-412 (1), several new analogs were prepared and evaluated in vitro and in vivo. One of these, 5-[4-[2-(3,4,5-trimethoxyphenyl)ethyl]phenyl]-2,3-dihydroimidazo [1,2-a]thieno[2,3-c]pyridine (6) was 4-5 times more potent than 1 in inhibiting PAF-induced bronchoconstriction and hemoconcentration when administered po to the guinea pig.

Ether phospholipids have demonstrated both in vitro and in vivo activity against a wide variety of tumor cell lines. The known cyclic ether phospholipid, SRI 62-834, was used as the model to prepare eight novel phospholipids containing a cyclic ether. All of the compounds were as effective as ET-18-OCH3 in their ability to activate macrophage-induced cytotoxicity against the Abelson-8.1 tumor cell line but varied in their direct cytotoxic effects. One of the new compounds, SDZ 62-406, was selected for in vivo studies and showed oral and i.v. activity in the mouse MethA fibrosarcoma model in the same range as ET-18-OCH3. No correlation was found between the direct or macrophage-activated cytotoxicity and the ability of the compounds to inhibit or promote platelet-activating factor (PAF)-induced aggregation of human platelets.

PAF-acether (platelet-activating factor) (1-O-alkyl-2-acetyl-sn-glycerol-3-phosphorylcholine) induces platelet-dependent bronchoconstriction in the guinea-pig which correlates with its in vivo thrombocytopenic effect. We investigated the influence of modifications of the polar head group in position 3 of the glycerol skeleton of PAF-acether on guinea-pig platelet activation and bronchoconstriction. PAF-acether itself induced concentration-dependent platelet activation (EC50 for aggregatin = 0.41 and EC20 for secretion of ATP = 0.56 nM). The 3-phosphoryl-N-methyl-morpholino ethanol analogue was slightly more active than PAF-acether and the 3-phosphoryl- N-methyl-piperidinium ethanol, 3-phopshoryl-(N-methyl-piperidino-3') methanol and 3-phosphoryl-(N- methyl-hydroxy-4') piperidine analogues were equieffective to PAF-acether in activating platelets. The 3-phosphoryl- piperidino ethanol analogue was 8 times less active than PAF-acether; the 3-phosphoryl-morpholino ethanol analogue and the 1-O-octadecyl-2-O-acetyl-3-O-((trimethyl-ammonio)-propyl) glycerol were inactive up to 1 μM. Our data show that the choline head group is not a compulsory requirement for activity. When injected i.v. to the propranolol-treated guinea-pigs, the platelet-activating analogues also induced bronchoconstriction. Two PAF-acether antagonists, compounds 48740 RP and BN 52021, inhibited PAF-acether-induced platelet activation when added to PRP at the final concentration of 0.1 mM (aggregation inhibited by 91 ± 4 and by 94 ± 3% respect.; secretion inhibited by 80 ±12 and 79 ± 10% respectively, mean ± S.E.M., n = 4). Both antagonists also suppressed platelet activation and in vivo bronchoconstriction, thrombocytopenia, leukopenia and hypotension induced by PAF-acether and the various analogues. Our results indicate that PAF-acether and the analogues studied trigger platelet activation and the consequent bronchoconstriction through mechanisms which share sensitivity to same antagonists.

AbstractDie Metallierung der beiden Phenyl‐imidazoline (Ia) und (Ib) liefert die Dilithium‐Verbindungen (II).

A series of 5-aryl-2,3,5,6-tetrahydroimidazo[2,1-a]isoquinolin-5-ols was prepared and evaluated for potential antidepressant activity in the reserpine-induced hypothermia model and selected central nervous system and autonomic activity tests. Several members of the series, notably the 4-chloro- and 4-fluorophenyl analogues, demonstrated pharmacological activity in the range of imipramine. Both compounds provided a marked potentiation of the 5-hydroxytryptophan-facilitated monosynaptic spike in the spinal cat preparation.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDirected lithiation of 2-phenyl- and 2-(o-methylphenyl)imidazolineWilliam J. Houlihan and Vincent A. ParrinoCite this: J. Org. Chem. 1982, 47, 26, 5177–5180Publication Date (Print):December 1, 1982Publication History Published online1 May 2002Published inissue 1 December 1982https://pubs.acs.org/doi/10.1021/jo00147a027https://doi.org/10.1021/jo00147a027research-articleACS PublicationsRequest reuse permissionsArticle Views224Altmetric-Citations37LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

AbstractDie Kondensation der bekannten Dilithio‐Verbindung (I) mit den Benzoesäureestern (II) liefert die cyclischen Alkohole (III), die mit den Benzoylverbindungen (IV) im Gleichgewicht stehen und bei der Dehydratisierung in die Imidazole (V) übergehen, aus denen die Azepinone (VI) erhalten werden.

Chemischer InformationsdienstVolume 13, Issue 18 Heterocyclic Compounds ChemInform Abstract: NOVEL CYCLOADDITION PRODUCTS FORMED BY THE MODIFIED MADELUNG INDOLE SYNTHESIS W. J. HOULIHAN, W. J. HOULIHANSearch for more papers by this authorY. UIKE, Y. UIKESearch for more papers by this authorV. A. PARRINO, V. A. PARRINOSearch for more papers by this author W. J. HOULIHAN, W. J. HOULIHANSearch for more papers by this authorY. UIKE, Y. UIKESearch for more papers by this authorV. A. PARRINO, V. A. PARRINOSearch for more papers by this author First published: May 4, 1982 https://doi.org/10.1002/chin.198218208AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume13, Issue18May 4, 1982 RelatedInformation

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNovel cycloaddition products formed by the modified Madelung indole synthesisWilliam J. Houlihan, Yasuyuki Uike, and Vincent A. ParrinoCite this: J. Org. Chem. 1981, 46, 22, 4515–4517Publication Date (Print):October 1, 1981Publication History Published online1 May 2002Published inissue 1 October 1981https://pubs.acs.org/doi/10.1021/jo00335a039https://doi.org/10.1021/jo00335a039research-articleACS PublicationsRequest reuse permissionsArticle Views544Altmetric-Citations35LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

A convenient three step synthesis of 9 H ‐dibenz[ c,f ]imidazo[1,2‐ a ]azepin‐9‐ones from readily available 2‐phenylimidazoline and a methyl benzoate is described.

AbstractBeim Erhitzen mit Basen erhält man aus den Amiden (I) bzw. (VII) über diskutierte Zwischenstufen die Indole (II) bzw. (VIII).

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIndanols. IV.1 IndanoxypropanolaminesSeymour L. Shapiro, Vincent A. Parrino, Elaine S. Isaacs, and Louis. FreedmanCite this: J. Med. Chem. 1962, 5, 1, 69–76Publication Date (Print):January 1, 1962Publication History Published online1 May 2002Published inissue 1 January 1962https://doi.org/10.1021/jm01236a009RIGHTS & PERMISSIONSArticle Views53Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (409 KB) Get e-Alerts

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTGuanamines. V. ChloromethylguanaminesSEYMOUR L. SHAPIRO, ELAINE S. ISAACS, VINCENT A. PARRINO, and LOUIS FREEDMANCite this: J. Org. Chem. 1961, 26, 1, 68–74Publication Date (Print):January 1, 1961Publication History Published online1 May 2002Published inissue 1 January 1961https://pubs.acs.org/doi/10.1021/jo01060a015https://doi.org/10.1021/jo01060a015research-articleACS PublicationsRequest reuse permissionsArticle Views188Altmetric-Citations19LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

A series of mercurated N-allylguanamines has been prepared and evaluated as mercurial diuretics. The experimental data reflect that compounds of varying diuretic activity are obtainable by appropriate group variation within I. Diuretic activity is also found in a series of tris-mercurials synthesized by mercuration of tri-allylcyanurate.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTGuanamine DiureticsSeymour L. Shapiro, Vincent A. Parrino, Karl Geiger, Sidney Kobrin, and Louis FreedmanCite this: J. Am. Chem. Soc. 1957, 79, 18, 5064–5071Publication Date (Print):September 1, 1957Publication History Published online1 May 2002Published inissue 1 September 1957https://pubs.acs.org/doi/10.1021/ja01575a064https://doi.org/10.1021/ja01575a064research-articleACS PublicationsRequest reuse permissionsArticle Views169Altmetric-Citations23LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts