Hydroxyalkylammonium-pyrimidines and nucleoside derivatives, useful as inhibitors of inflammatory cytokines (US5679684) PATENT PLAQUES Now available US5679684: Hydroxyalkylammonium-pyrimidines and nucleoside derivatives, useful as inhibitors of inflammatory cytokines View Images (13 pages) | View Cart Add to cart: PDF (~1240 KB) | TIFF (~975 KB) | SmartPatent (~975 KB) | Fax | More choices... Inventor(s):Benson; Bradley J. , Chapel Hill, NC Chen; Xiannong , Athens, GA Cianciolo; George J. , Chapel Hill, NC Diaz; Jose-Luis , Durham, NC Ishaq; Khalid S. , Chapel Hill, NC Morris-Natschke; Susan L. , Apex, NC Uhing; Ronald J. , Durham, NC Wong; Henry , Morrisville, NC Applicant(s):Macronex, Inc., Morrisville, NC The University of N.C. at Chapel Hill, Morrisville, NC Issued/Filed Dates:Oct. 21, 1997 / June 7, 1995 Application Number:US1995000476704 IPC Class:A61K 031/505; Class:514/269; 514/050; 514/274; Field of Search:514/50,269,274 Abstract:Novel hydroxyalkylammonium-pyrimidine of the formula [Figure] and nucleoside derivatives have been found to be useful as inhibitors of inflammatory cytokines. They can be used, inter alia, in the therapy of septic shock, cachexia, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis and AIDS. The compounds are typically prepared by reaction of an iodo substituted nucleoside with the appropriately substituted hydroxyalkylamine. Attorney, Agent, or Firm:Klauber & Jackson; Primary/Assistant Examiners:Gupta; Yogendra N.; Related Applications:Application NumberApplDatePatentIssuedTitle US19940002640261994-06-22US5550132 1996-08-27 Hydroxyalkylammonium-pyrimidines or purines and nucleoside derivatives, useful as inhibitors of inflammatory cytokines U.S. References: (No patents reference this one) Patent Issued Inventor(s) Title US41995744 /1980 SchaefferMethods and compositions for treating viral infections and guanine acyclic nucleosides US51303027 /1992 Spielvogel et al.Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same US53067224 /1994 Kim et al.Thymidine derivatives and therapeutic method of use US53067324 /1994 Norris et al.Tumor necrosis factor antagonist First Claim:Show all 25 claims What is claimed is: 1. A method for inhibiting inflammatory cytokines which comprises administration to a mammal in need of such therapy of a cytokine inhibitory amount of a compound of the Formula I [Figure] R is a group of the formula [Figure] wherein R1 is one or two lower alkyl groups with the proviso that when two lower alkyl groups are present, then the nitrogen atom is quaternized; R2 is hydrogen or an alkanoyl group of 2-20 carbon atoms; n is 2-6; or R is a substituted furanyl group of the formula [Figure] wherein R1 and R2 are as hereinbefore defined; and the wavy lines indicate either stereochemical configuration; R' and R" are independently hydrogen, halogen or a lower alkyl, lower alkenyl, lower alkynyl, or aralkyl group; R'" is hydrogen, halogen, alkylthio, amino, acylamino carbamyl or azide; and the pharmaceutically acceptable salts thereof. : This application is a division of application Ser. No. 08/264,026 filed Jun. 22, 1994 now U.S. Pat. No. 5,550,132. Foreign References:PublicationCountryDateIPC Class JP00181075 Japan9 /1985 WO09217186 World Intellectual Property Organization (WIPO)10 /1992 WO09401413 World Intellectual Property Organization (WIPO)1 /1994 Other References:CA 109:38194, 1988. Parmely et al. (1993) "Adenosine and a related carbocyclic nucleoside analogue selectively inhibit tumor necrosis factor-alpha production and protect mice against endotoxin challenge" J. Immunol. 151:389-96. Ruddle et al., 1990, "An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis" J. Exp. Med. 172:1193-1200. Sood et al., 1992, "The synthesis and antineoplastic activity of 2'-deoxynucleoside-cyanoboranes in murine and human culture cells" Anticancer Research 12:335-44. Sood et al., 1990, "Boron-containing nucleic acids. 2. Synthesis of oligonucleoside boranophosphates" J. Am. Chem. Soc. 112:9000-1. Sood et al., 1989, "Boron-containing nucleic acids. 2. Synthesis of cyanoborane adducts of 2'deoxy-ucleosides" J. Am. Chem. Soc. 111:9234-5. Spielvogel et al., 1991, "From boron analogues of amino acids to boronated DNA:potential new pharmaceuticals and neutron capture agents" Pure & Appl. Chem. 63:415-8. Kolb et al. (1985) "Synthesis of 5'-[(3-Aminooxypropyl)amino]-5'-deoxyadenosine" Liebigs Annalen Der Chemie No.5:1036-40. Lee et al. (1994) "Low-molecular-weight TNF biosynthesis inhibitors: strategies and prospectives" Circulatory Shock 44:97-103. :