Icn Pharmaceuticals, Inc.

Brigham Young University

Nucleic Acid Research Institute

Other

Warner-lambert Company

Viratek Inc.

Roland K Robins

Ganapathi R Revankar

Joseph T Witkowski

Prem C Srivastava

Dennis A Shuman

Howard B Cottam

Dennis Joseph McNamara

Phillip D Cook

Ganesh D Kini

Kay H Boswell

Robert J Rousseau

Stanley Charles Bell

Robert H Chen

Michael C Goodman

William O Weigle

William J Hennen

Darrell E O'Brien

Thomas Novinson

Yu-An Chang

Leon F Christensen

Rich B Meyer, Jr

Yogesh S Sanghvi

Abdul M Mian

Naeem B Hanna

Brahma S Sharma

Frank A Lehmkuhl

Compounds of the structure: ##STR1## wherein R.sub.4, R.sub.5, R.sub.6 and R.sub.7 individually are H, OH or C.sub.1 -C.sub.18 O-acyl and R.sub.3 is H, C.sub.1 -C.sub.18 acyl or ##STR2## or R.sub.5 and R.sub.7 are H or OH, R.sub.6 is H and together R.sub.3 and R.sub.4 are ##STR3## and X is .dbd.O or .dbd.S; Y is --OH, --SH, --Nh.sub.2 or halogen; and Z is H , --Nh.sub.2, --OH or halogen; wherein halogen is Cl or Br; or pharmaceutically acceptable salt thereof are useful as antivirals, antitumors, antimetastatics and as immune system enhancers.

Immune system enhancing

.alpha. and .beta.-ribonucleosides of substituted pyrimido[5,4-d]pyrimidines are used in treating malignant tumors in vivo. A novel synthesis for preparing these compounds and other related compounds is further disclosed.

Substituted pyrimido[5,4-d]pyrimidine nucleosides

6-Sulfenamide, 6-sulfinamide and 6-sulfonamide purines, purine nucleosides, purine nucleotides and 3 and 7 deaza and 8 aza derivatives thereof of structure: ##STR1## wherein Z is H or --NH.sub.2 ;

6-sulfenamide, 6-sulfinamide and 6-sulfonamide purines, purine

7,8-Disubstituted guanosine nucleoside derivatives are found to be potent immune response enhancing agents in human and animal cells. 7-Substituents are hydrocarbyl radicals having a length greater than ethyl and less than about decyl. 8-Substituents are .dbd.O, .dbd.S, .dbd.Se and .dbd.NCN. Compositions and methods of use are also disclosed.

Immunostimulating guanine derivatives, compositions and methods

The triazole nucleosides 1-(5'-O-sulfamoyl-.beta.-D-ribofuranosyl)[1,2,4]triazole-3-carboxamide, 1-(5'-O-sulfamoyl-.beta.-D-ribofuranosyl)[1,2,4]triazole-3-thiocarboxamide and 1-(5'-O-sulfamoyl-.beta.-D-ribofuranosyl)[1,2,4]triazole-3-carbonitrile ar e prepared and used as antiparasitic agents.

Antiparasitic 5'-sulfamoyl nucleosides

##STR1## 6-Amino-1-(2-deoxy-.alpha.D-erythro-pentofuranosyl)imidazo [4,5-C]pyridin-4-one (also know as .alpha.-2'-deoxy-3-deazaguanosine) is non mitogenic to human peripheral blood lymphocytes; however, it displays a potent immunoenhancing activity on human T cells. This compound causes a marked increase in both phytohemagglutinin and Concanavalin A induced proliferation of T cells. When added during allogeneic mixed lymphocyte response, it also potentiates the proliferation of alloreative T cells. The compound shows no potentiating effect on B lymphocytes activated either with Staphylococcus aureus cowan or Pokeweed mitogen, suggesting that it is mainly a T cell function immunopotentiator. The compound overcomes induced immunosuppression and is able to restore depressed proliferative responses of T cells. Further it potentiates the generation of antigen-specific primary cytotoxic T lymphocytes.

T cell immunopotentiator

A novel class of alkyl-1-(.beta.-D-ribofuranosyl)[1,2,4]triazole-3-carboximidates of the formula: ##STR1## wherein R.sub.1 is methyl or ethyl and R.sub.2 is .beta.-D-ribofuranosyl, are useful as anti-leukemic agents.

Synthesis and anti-leukemic activity of

Compounds of the structure: ##STR1## wherein R.sub.1 and R.sub.2 individually are H or C.sub.1 -C.sub.18 acyl and R.sub.3 is H, C.sub.1 -C.sub.18 acyl or ##STR2## or R.sub.1 is H and together R.sub.2 and R.sub.3 are ##STR3## and X is .dbd.O or .dbd.S, Y is --OH, --SH, --NH.sub.2 or halogen, and Z is H, --NH.sub.2, --OH or halogen, wherein halogen is Cl or Br, or a pharmaceutically acceptable salt thereof are useful as antivirals, antitumors and as immune system enhancers.

Antiviral methods utilizing ribofuranosylthiazolo[4,5-d]pyrimdine

The compound 8-Chloroadenosine 3',5'-cyclic phosphate is used to treat malignant tumors in warm blooded animals. Two novel single step syntheses of 8-chloroadenosine 3',5'-cyclic phosphate and other related adenine and adenosine compounds from corresponding adenosine 3', 5'-cyclic phosphate and other respective related adenosine compounds are disclosed.

8-Chloroadenosine 3', 5'-cyclic monophosphate preparations

Nucleotide compounds are provided, namely 2-chloro-2'-deoxyadenosine 5'-phosphate compounds (I) especially as the monosodium and disodium salt, as well as a method for their production, pharmaceutical compositions comprising the compounds, and methods of treatment using the compounds in dosage form. The compounds of the invention have pharmacological properties and are useful antimicrobial agents, antiviral agents, and antileukemic agents. ##STR1##

Methods of using 2-chloro-2'-deoxyadenosine-5'-phosphate and its salts

A method that is direct and stereospecific is provided for the production of 2'-deoxyadenosine derivatives and related analogs. The method comprises glycosylation of the sodium salt of 2,6-dichloropurine or 6-chloropurine and ammonolysis of the glycosylate to obtain the corresponding 2-chloro-2'-deoxyadenosine or 2'-deoxyadenosine.

Method for the production of 2'-deoxyadenosine compounds

Nucleotide and nucleoside compounds are provided, namely 2-halo-2'-deoxyadenosine 5'-phosphate compounds (I) especially as the monosodium and disodium salt, and 2-iodo-2'-deoxyadenosine (II); as well as a method for their production, pharmaceutical compositions comprising the compounds, and methods of treatment using the compounds in dosage form. The compounds of the invention have pharmacological properties and are useful antimicrobial agents, antiviral agents, and antileukemic agents. ##STR1##

Compound 2-iodo-2'-deoxyadenosine

The compound 2-.beta.-D-ribofuranosylthiazole-4-carboxamide is used to treat malignant tumors in warm blooded animals. Esters of this compound such as 2-(2,3,5-tri-O-acetyl-.beta.-D-ribofuranosyl)thiazole-4-carboxamide and 2-(5-O-phosphoryl-.beta.-D-ribofuranosyl)thiazole-4-carboxamide are also useful for treating tumors in warm blooded animals.

Treatment of malignant tumors with

A class of novel 2-.beta.-D-ribofuranosylselenazole-4-carboxamide nucleoside and nucleotide compounds and methods for their production are provided. Compounds of the class typically have pharmacological properties, especially antitumor and antiviral properties, and are well tolerated, being useful, for example, in treating tumors and viral infections in warm blooded animals.

Growing community of inventors

Santa Ana, CA, United States of America

Roland K Robins