Polycyclo Ring System Having The Diazine Ring As One Of The Cyclos Patents (Class 544/244)
-
Patent number: 6147211Abstract: The invention relates to a compound of formula (I) ##STR1## Wherein: B is adenine, guanine or hypoxanthineZ is hydrogen or a negative chargeR is --[CH.sub.2 CH(R.sup.1)--O].sub.n -R.sup.2, --CH.sub.2 CH.sub.2 X, in whichR.sup.1 is hydrogen or (C.sub.1 -.sub.6) alkylR.sup.2 is hydrogen or (C.sub.1 -.sub.6) alkyln is a number from 1 to 6X is OH, F, NR.sup.3 R.sup.4R.sup.3 and R.sup.4 are independently from each other hydrogen or (C.sub.1 -.sub.6) alkyland to methods of enzymatically treating these compounds with biocatalysts having cyclic phosphodiesterase activity.Type: GrantFiled: October 6, 1998Date of Patent: November 14, 2000Assignee: Novartis AGInventors: Oreste Ghisalba, Guy Joel Christian Marais, Pierre Martin
-
Patent number: 6127539Abstract: A cyclopentenecarboxamide derivative represented by the formula (I): ##STR1## and a method for preparing the cyclopentencarboxamide derivative. A bicycloamide derivative represented by the formula (II): ##STR2## and a method for preparing the bicycloamide derivative.Type: GrantFiled: June 30, 1998Date of Patent: October 3, 2000Assignee: Kuraray Co., Ltd.Inventors: Nobuya Katagiri, Chikara Kaneko, Junko Sato, Masahiro Torihara, Koichi Kanehira, Yoshin Tamai
-
Patent number: 6127540Abstract: Nucleotide analogues having the general formula (I) and pharmaceutically acceptable derivatives: ##STR1## wherein n is 0 or an integer; X is O or S, CH.sub.2, CH--halogen, CH--N.sub.3, or C.dbd.CH.sub.2 ;Q and U are independently selected from: O, S, and CH(R.sub.a) wherein R.sub.a is hydrogen, OH, halogen, N.sub.3, NH.sub.2, SH, carboxyl, C.sub.1-6 alkyl or R.sub.a is CH.sub.2 (R.sub.b) wherein R.sub.b is hydrogen, OH, SH, NH.sub.2, C.sub.1-6 alkyl or carboxyl; or both Q and U are CH when Q and U are linked by a double bond;Z is selected from: O, a C.sub.1-6 alkoxy, a C.sub.1-6 thioalkyl, a C.sub.1-6 aminoalkyl, (CH.sub.2).sub.m wherein m is 0 or an integer, and N(R.sub.c).sub.2 wherein both R.sub.c are independently hydrogen or a C.sub.1-6 alkyl; andR2 is a purine or pyrimidine base or an analogue or derivative thereof. Members of this series of analogues possess anti-viral activity.Type: GrantFiled: October 4, 1999Date of Patent: October 3, 2000Assignee: BioChem Pharma, Inc.Inventors: Nghe Nguyen-Ba, Miguel Quimpere, Laval Chan Chun Kong, William L. Brown, Gervais Dionne
-
Patent number: 6121296Abstract: This invention is directed to transition-state analog compounds and to the use of said compounds as inhibitors of nucleoside hydrolase and transferase enzyme activity of parasites. This invention is further directed to the use of said compounds to treat infections and diseases caused by certain bacterial and plant toxins.Type: GrantFiled: February 2, 1998Date of Patent: September 19, 2000Assignee: Albert Einstein College of Medicine of Yeshiva UniversityInventors: Vern L. Schramm, Benjamin Horenstein
-
Patent number: 6107302Abstract: The invention relates to an anhydrous crystalline form of (2-[2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy]ethyl L-valinate hydrochloride (otherwise known as valaciclovir hydrochloride) and a process for preparing it.Type: GrantFiled: September 22, 1997Date of Patent: August 22, 2000Assignee: Glaxo Wellcome Inc.Inventors: Barry Howard Carter, Jane Muse Partin, Peter Gregory Varlashkin, Richard Augustus Winnike, William Bayne Grubb, III, Gregory Alan Conway, Philip George Lake, David Michael Skinner, David James Whatrup
-
Patent number: 6103707Abstract: The present invention relates to 9-(2-deoxy-2-fluoro-4-thio-beta-D-arabinofuranosyl)purine derivatives having antiviral activity, represented by formula [I]: ##STR1## wherein B represents a base selected from the group consisting of purine, azapurine and deazapurine, which may be substituted with halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, amino, alkylamino, hydroxyl, hydroxyamino, aminoxy, alkoxy, mercapto, alkylmercapto, aryl, aryloxy or cyano; and R represents a hydrogen atom or a phosphoric acid residue, and to a process for the production and use thereof.Type: GrantFiled: June 29, 1998Date of Patent: August 15, 2000Assignee: Yamasa CorporationInventors: Kohei Yamada, Yuichi Yoshimura, Haruhiko Machida, Mikari Watanabe
-
Patent number: 6087497Abstract: 9-Substituted purine derivatives of formula (4) ##STR1## are prepared by debenzylating a compound of formula (3): ##STR2##Type: GrantFiled: July 23, 1998Date of Patent: July 11, 2000Assignee: Ajinomoto Co., Inc.Inventors: Kunisuke Izawa, Hiroshi Shiragami, Keizo Yamashita
-
Patent number: 6080734Abstract: The present invention is directed to new phospholipid derivatives of acyclovir and ganciclovir that link a lipid moiety, which represents a substituted C3 backbone, to acyclovir or ganciclovir via phosphate or thiophosphate. The compounds are particularly suitable for the therapy of viral infections.Type: GrantFiled: December 11, 1998Date of Patent: June 27, 2000Assignee: Roche Diagnostic GmbHInventors: Harald Zilch, Dieter Herrmann
-
Patent number: 6069249Abstract: Novel compounds are provided that comprise esters of antiviral phosphonomethoxy nucleotide analogs with carbonates and/or carbamates having the structure --OC(R.sup.2).sub.2 OC(O)X(R).sub.a, wherein R.sup.2 independently is H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro or OR.sup.3 in which R.sup.3 is C.sub.1 -C.sub.12 alkyl; X is N or O; R is independently H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro, --O--, --N.dbd., --NR.sup.4 --, --N(R.sup.4).sub.2 -- or OR.sup.3, R.sup.4 independently is --H or C.sub.1 -C.sub.Type: GrantFiled: May 19, 1999Date of Patent: May 30, 2000Assignee: Gilead Sciences, Inc.Inventors: Murty N. Arimilli, Kenneth C. Cundy, Joseph P. Dougherty, Choung U. Kim, Reza Oliyai, Valentino J. Stella
-
Patent number: 6063774Abstract: Neuroprotective agents have forumula I ##STR1## wherein a is a ring of 6 to 8 members; n and n' are 1 or 2,R.sub.2 is hydrogen or oxygen of carbonyl,R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 independently include hydrogen, alkyl, aralkyl, and carboxyalkyl.Type: GrantFiled: April 29, 1998Date of Patent: May 16, 2000Assignee: Warner-Lambert CompanyInventor: Sham Nikam
-
Patent number: 6057305Abstract: Resolved enantiomers of the formula ##STR1## wherein B is a purine or pyrimidine base or aza and/or deaza analogs thereof are useful in antiviral pharmaceutical compositions to treat retroviral infections.Type: GrantFiled: August 5, 1992Date of Patent: May 2, 2000Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting, v.z.w.Inventors: Antonin Holy, Hana Dvorakova, Erik Desire Alice DeClercq, Jan Marie Rene Balzarini
-
Patent number: 6043230Abstract: Novel compounds are provided that comprise esters of antiviral phosphonomethoxy nucleotide analogs with carbonates and/or carbamates having the structure -OC(R.sup.2).sub.2 OC(O) X(R).sub.a, wherein R.sup.2 independently is H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro or OR.sup.3 in which R.sup.3 is C.sub.1 -C12 alkyl; X is N or O; R is independently H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, axido, nitro, --O--, --N.dbd., --NR.sup.4 --, --N(R.sup.4).sub.2 -- or OR.sup.3, R.sup.4 independently is --H or C.sub.1 -C.sub.Type: GrantFiled: May 19, 1999Date of Patent: March 28, 2000Assignee: Gilead Sciences, Inc.Inventors: Murty N. Arimilli, Kenneth C. Cundy, Joseph P. Dougherty, Choung U. Kim, Reza Oliyai, Valentino J. Stella
-
Patent number: 6037335Abstract: Phosphonate-nucleotide ester compounds of the formula (I) have excellent antiviral activity and antineoplastic activity. Further, they can be orally administered. ##STR1## wherein ring A represents ##STR2## wherein R.sup.1 and R.sup.2 independently represent hydrogen, halogen, hydroxyl, mercapto, C.sub.6 -C.sub.10 arylthio or amino; R.sup.3 represents C.sub.1 -C.sub.4 alkyl or ethyl having one or more substituents selected from the group consisting of fluorine, C.sub.1 -C.sub.4 alkoxy, phenoxy, C.sub.7 -C.sub.10 phenylalkoxy and C.sub.2 -C.sub.5 acyloxy; R.sup.4 represents ethyl having one or more substituents selected from the group consisting of fluorine, C.sub.1 -C.sub.4 alkoxy, phenoxy, C.sub.7 -C.sub.10 phenylalkoxy and C.sub.2 -C.sub.5 acyloxy; X, Y and Z independently represent methyne or nitrogen atom; or a pharmaceutically acceptable salt thereof.Type: GrantFiled: October 2, 1997Date of Patent: March 14, 2000Assignee: Mitsubishi Chemical CorporationInventors: Hideaki Takashima, Naoko Inoue, Masaru Ubasawa, Kouichi Sekiya, Shingo Yabuuchi
-
Patent number: 6034087Abstract: Nucleoside derivatives represented by formula (I); ##STR1## wherein, R.sub.1 represents hydrogen, phosphate or phosphonate group, R.sub.2 represents substituted or unsubstituted pyrimidine or purine base, and Z represents S, SO, SO.sub.2, O or C; or pharmaceutically acceptable salts thereof. Compound (I) can be obtained by reacting a compound of the formula (II); ##STR2## wherein, R.sub.7 represents hydrogen or hydroxy-protecting group, L represents aromatic or nonaromatic acyl, halide or alkoxy, and Z represents S, SO, SO.sub.2, O or C, with a base.Type: GrantFiled: June 11, 1997Date of Patent: March 7, 2000Assignee: Chong Kun Dang Corp.Inventors: Jung Woo Kim, Chong Ryul Lee, Koo Hun Chung, Soon Kil Ahn, Kyung Hoi Cha, Hoe Joo Son, Sung Jo Choi, Byeong Seon Jeong, Kyeong Bok Min
-
Patent number: 6031096Abstract: Disclosed are novel prodrugs represented by the following structural formula: ##STR1## Z is oxygen or sulfur; Y is, together with a hydroxy group, acyclovir or an analog of acyclovir; A is a substituted benzyl group with one or more protected hydroxy or protected amine groups in the ortho or para positions, relative to the phosphate ester, which can be converted in vivo to a hydroxy or amino group. Also disclosed is a method of treating a viral infection in an individual or animal. The method comprises administering to the individual or animal a therapeutically effective amount of a prodrug represented by structural formula shown above.Type: GrantFiled: May 15, 1998Date of Patent: February 29, 2000Assignee: Drug Innovation & Design, Inc.Inventors: Arnold Glazier, Milka Yanachkova, Ivan Yanachkov
-
Patent number: 6005107Abstract: Nucleotide analogues having the general formula (I) and pharmaceutically acceptable derivatives: ##STR1## wherein n is 0 or an integer; X is O or S, CH.sub.2, CH-halogen, CH--N.sub.3, or C.dbd.CH.sub.2 ;Q and U are independently selected from: O, S, and CH(R.sub.a) wherein R.sub.a is hydrogen, OH, halogen, N.sub.3, NH.sub.2, SH, carboxyl, C.sub.1-6 alkyl or R.sub.a is CH.sub.2 (R.sub.b) wherein R.sub.b is hydrogen, OH, SH, NH.sub.2, C.sub.1-6 alkyl or carboxyl; or both Q and U are CH when Q and U are linked by a double bond;Z is selected from: O, a C.sub.1-6 alkoxy, a C.sub.1-6 thioalkyl, a C.sub.1-6 aminoalkyl, (CH.sub.2).sub.m wherein m is 0 or an integer, and N(R.sub.c).sub.2 wherein both R.sub.c are independently hydrogen or a C.sub.1-6 alkyl; andR2 is a purine or pyrimidine base or an analogue or derivative thereof. Members of this series of analogues possess anti-viral activity.Type: GrantFiled: June 4, 1997Date of Patent: December 21, 1999Assignee: BioChem Pharma, Inc.Inventors: Nghe Nguyen-Ba, Miguel Quimpere, Laval Chan Chun Kong, William L. Brown, Gervais Dionne
-
Patent number: 5994321Abstract: A series of guanine analogs and physiological salts thereof, which are useful as virus inhibitors and as antiviral agents in the treatment of viral disease, having the basic structures of: ##STR1## wherein B is H, CH.sub.3 or NH.sub.2 ; C is NH.sub.2 or SCH.sub.3 ; D is N or CH; E is O, S or Se; and G is selected from a group consisting of alkanes, alkenes, ethers, esters, hydrocarbons, amines and heterocyclic compounds, is herein disclosed. In I and III, A is O, S or Se while in II, A is NH.sub.2, OH, NHOH, OCH.sub.3 or SCH.sub.3. In I and II, F is 0, S or Se, while in III, F is F is 0, S, Se or NH. These compounds may be formulated with a physiological carrier, and used either alone or in combination with, for example, acyclovir or ganciclovir or another therapeutic agent, for the treatment of conditions resulting from viral infections.Type: GrantFiled: June 10, 1997Date of Patent: November 30, 1999Assignee: Aronex Pharmaceuticals, Inc.Inventors: Arthur F. Lewis, Ganapathi R. Revankar
-
Patent number: 5977089Abstract: Compounds are provided that comprise esters of antiviral phosphonomethoxy nucleotide analogs with carbonates and/or carbamates having the structure --OC(R.sup.2).sub.2 OC(O)X(R).sub.a, wherein R.sup.2 independently is H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro or OR.sup.3 in which R.sup.3 is C.sub.1 -C.sub.12 alkyl; X is N or O; R is independently H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro, --O--, --N.dbd., --NR.sup.4 --, --N(R.sup.4).sub.2 -- or OR.sup.3, R.sup.4 independently is --H or C.sub.1 -C.sub.Type: GrantFiled: November 6, 1998Date of Patent: November 2, 1999Assignee: Gilead Sciences, Inc.Inventors: Murty N. Arimilli, Kenneth C. Cundy, Joseph P. Dougherty, Choung U. Kim, Reza Oliyai, Valentino J. Stella
-
Patent number: 5977061Abstract: Novel PMP, PME and HPMP and related compounds containing N-6 substituted 2,6-diaminopurine and adenine bases are provided. These compounds are useful in a variety of utilities, including as intermediates in the preparation of flame retardants, diagnostic reagents and therapeutics, including antivirals. Of particular note are compounds otherwise not known to possess anti-DNA viral activity that become potent inhibitors of DNA viruses upon substitution of the N-6 site, thereby providing a novel and unexpected and surprising use for such compounds.Type: GrantFiled: April 21, 1995Date of Patent: November 2, 1999Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting, v.z.w.Inventors: Antonin Holy, Erik Desire Alice De Clercq
-
Patent number: 5955610Abstract: Nucleotide analogues having the general formula (I) and pharmaceutically acceptable derivatives: ##STR1## wherein n is 0 or an integer; X is O or S, CH.sub.2, CH-halogen, CH--N.sub.3, or C.dbd.CH.sub.2 ;Q and U are independently selected from: O, S, and CH(R.sub.a) wherein R.sub.a is hydrogen, OH, halogen, N.sub.3, NH.sub.2, SH, carboxyl, C.sub.1-6 alkyl or R.sub.a is CH.sub.2 (R.sub.b) wherein R.sub.b is hydrogen, OH, SH, NH.sub.2, C.sub.1-6 alkyl or carboxyl; or both Q and U are CH when Q and U are linked by a double bond;Z is selected from: O, a C.sub.1-6 alkoxy, a C.sub.1-6 thioalkyl, a C.sub.1-6 aminoalkyl, (CH.sub.2).sub.m wherein m is 0 or an integer, and N(R.sub.c).sub.2 wherein both R.sub.c are independently hydrogen or a C.sub.1-6 alkyl; andR2 is a purine or pyrimidine base or an analogue or derivative thereof. Members of this series of analogues possess anti-viral activity.Type: GrantFiled: June 4, 1997Date of Patent: September 21, 1999Assignee: Biochem Pharma, Inc.Inventors: Nghe Nguyen-Ba, Miguel Quimpere, Laval Chan Chun Kong, William L. Brown, Gervais Dionne
-
Patent number: 5935946Abstract: The invention provides a composition comprising bis(POC)PMPA and fumaric acid (1:1). The composition is useful as an intermediate for the preparation of antiviral compounds, or is useful for administration to patients for antiviral therapy or prophylaxis. The composition is particularly useful when administered orally. The invention also provides methods to make PMPA and intermediates in PMPA synthesis. Embodiments include lithium t-butoxide, 9-(2-hydroxypropyl) adenine and diethyl p-toluenesulfonylmethoxyphosphonate in an organic solvent such as DMF. The reaction results in diethyl PMPA preparations containing an improved by-product profile compared to diethyl PMPA made by prior methods.Type: GrantFiled: July 25, 1997Date of Patent: August 10, 1999Assignee: Gilead Sciences, Inc.Inventors: John D. Munger, Jr., John C. Rohloff, Lisa M. Schultze
-
Patent number: 5935956Abstract: The invention relates to fused pyridazine compounds, in particular pyrido ?h!cinnoline, pyrido?h!cinnolinone, pyridocyclopenta?1,2-c!pyridazine, pyridocyclopenta?1,2-c!pyridazinone, pyridocyclohepta?1,2-c!pyridazine and pyridocyclohepta?1,2-c!pyridazinone derivatives, their use as medicaments and pharmaceutical compositions comprising them.Type: GrantFiled: September 5, 1997Date of Patent: August 10, 1999Assignee: Astra Pharmaceuticals Ltd.Inventors: John Bantick, Simon Hirst, Matthew Perry
-
Patent number: 5932559Abstract: The invention concerns the treatment of hyperandrogenic conditions in humans by the formation of a novel mechanism-based irreversible inhibitor of human 5.alpha.-reductase enzymes from 3-oxo-4-oxa and 4-thiasteroids having a 1,2-double bond and the pyridine-nucleotide cofactor of the 5.alpha.-reductase enzyme, NADPH. The invention further relates to the isolated inhibitor-cofactor complex.Type: GrantFiled: April 23, 1998Date of Patent: August 3, 1999Assignee: Merck & Co., Inc.Inventors: Herb G. Bull, Georgianna Harris, Robert W. Myers
-
Patent number: 5922695Abstract: Novel compounds are provided that comprise esters of antiviral phosphonomethoxy nucleotide analogs with carbonates and/or carbamates having the structure --OC(R.sup.2).sub.2 OC(O)X(R).sub.a, wherein R.sup.2 independently is H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro or OR.sup.3 in which R.sup.3 is C.sub.1 -C12 alkyl; X is N or O; R is independently H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro, --O--, --N.dbd., --NR.sup.4 --, --N(R.sup.4).sub.2 -- or OR.sup.3, R.sup.4 independently is --H or C.sub.1 -C.sub.Type: GrantFiled: July 25, 1997Date of Patent: July 13, 1999Assignee: Gilead Sciences, Inc.Inventors: Murty N. Arimilli, Kenneth C. Cundy, Joseph P. Dougherty, Choung U. Kim, Reza Oliyai, Valentino J. Stella
-
Patent number: 5922866Abstract: The present invention provides a novel process for preparing a series of quinazolin-4-one derivatives in high yields with reduced amounts of byproducts, the process comprising reacting, in the presence of a base, a trialkylsilyl halide with a compound represented by the formula ##STR1## wherein; R.sup.5 is a phenyl group which may have 1 to 3 substituents each selected from a lower alkyl group, a lower alkoxy group or a halogen atom, a lower alkyl group, a phenyl-lower alkyl group which may have a halogen atom as a substituent on the phenyl ring, a lower alkenyl group, a lower alkoxy-lower alkyl group or a lower alkynyl group; R.sup.6 is a lower alkyl group, a halogen-substituted lower alkyl group, a lower alkoxycarbonyl group or a phenyl group which may have, as a substituent, a lower alkyl group or a group of the formula ##STR2## wherein A is an oxygen atom or a single bond, Z is a lower alkylene group, R.sup.7 is a lower alkyl group and R.sup.Type: GrantFiled: February 25, 1998Date of Patent: July 13, 1999Assignee: Otsuka Pharmaceutical Factory, Inc.Inventors: Kazuyoshi Miyata, Yasuhisa Kurogi, Yasuhiro Sakai, Yoshihiko Tsuda
-
Patent number: 5922696Abstract: Disclosed are novel unsaturated phosphonate derivatives of certain purines or pyrimidines useful as antiviral agents, methods useful for their preparation and use of these compounds as antiviral agents effective against DNA viruses, retroviruses and viruses involved in tumor formation.Type: GrantFiled: August 10, 1998Date of Patent: July 13, 1999Assignee: Merrell Pharmaceuticals Inc.Inventors: Patrick Casara, Jean-Fran.cedilla.ois Nave, Serge Halazy
-
Patent number: 5910600Abstract: A bisphosphite compound of the following formula (A): ##STR1## wherein --Ar--Ar-- is a bisarylene group represented by any one of the formulae (A-I) to (A-III) defined in the specification, and each of Z.sub.1 to Z.sub.4 is a C.sub.4-20 aromatic or heteroaromatic group which may have a substituent, wherein each of substituents on carbon atoms of an aromatic ring adjacent to the carbon atom bonded to the oxygen atom in each of Z.sub.1 to Z.sub.4, is a C.sub.0-2 group, and each pair of Z.sub.1 and Z.sub.2, and Z.sub.3 and Z.sub.4, are not bonded to each other.Type: GrantFiled: April 28, 1997Date of Patent: June 8, 1999Assignee: Mitsubishi Chemical CorporationInventors: Hisao Urata, Hiroaki Itagaki, Eitaro Takahashi, Yasuhiro Wada, Yoshiyuki Tanaka, Yasukazu Ogino
-
Patent number: 5877166Abstract: Cyclic and acyclic 2-aminopurine phosphonate nucleotide analogs useful to treat herpes viral infections are provided in enantiomerically pure form. Pharmaceutical compositions and methods for treating herpes viral infections are provided as well, as is a chiral synthesis for preparing the novel compounds in enantiomerically pure form.Type: GrantFiled: April 28, 1997Date of Patent: March 2, 1999Assignee: SRI InternationalInventors: Elmer J. Reist, Wallace W. Bradford, Nurulain T. Zaveri
-
Patent number: 5874577Abstract: Unprotected adenine, 6-chloropurine, 2,6-diaminopurine, and 2-amino-6-chloropurine have been directly coupled with 2-(diethoxyphosphonomethoxy)ethanol under a disclosed method to provide acyclic phosphonate nucleotide analogues which are intermediates for antiviral agents such as 9-?2-(phosphonomethoxy)ethyl!adenine (PMEA) and its analogues having a structure of formula I: ##STR1## wherein Z represents N or CH; R.sub.1 represents hydrogen, alkyl, aryl, or arylalkyl; R.sub.2 and R.sub.3 are independently selected from H, OH, halo, NH.sub.2, C.sub.6 H.sub.5 CH.sub.2 O, or R.sub.4 R.sub.5 N wherein R.sub.4 and R.sub.5 are independently selected from alkyl, aryl, or arylalkyl.Type: GrantFiled: April 2, 1997Date of Patent: February 23, 1999Assignee: MediChem Research, Inc.Inventors: Wei Chen, Michael T. Flavin, Ze-Qi Xu
-
Patent number: 5869467Abstract: This invention relates to new nucleotide analogues and solves the technical problem of their use as biologically active compounds. The subject of this invention are N-(2-phosphonylmethoxyethyl) and N-(3-hydroxy-2-phosphonylmethoxypropyl) derivatives of pyrimidine and purine bases, easily accessible from heterocyolic bases and their N-(2-hydroxyethyl) or N-(2,3-dihydroxypropyl) derivatives. Some of the compounds, according to this invention, exhibit a marked antiviral activity or can be converted into such active compounds by chemical transformations.Type: GrantFiled: March 28, 1995Date of Patent: February 9, 1999Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.Inventors: Antonin Holy, Ivan Rosenberg, Erik D. A. De Clercq
-
Patent number: 5854237Abstract: Tricyclic diazepines of the formula: ##STR1## wherein A, B, D, E, F, Y and Z are defined in the specification which compounds have vasopressin and oxytocin antagonist activity.Type: GrantFiled: June 17, 1997Date of Patent: December 29, 1998Assignee: American Cyanamid CompanyInventors: Jay Donald Albright, Marvin Fred Reich, Fuk-Wah Sum, Efren Guillermo Delos Santos
-
Patent number: 5854228Abstract: A series of compounds of Formula I which have anti-tumor activity, and are useful in treating viral infections, their compositions and use. ##STR1## In Formula I B is a purine or pyrimidine base; alk.sub.1 alk.sub.2 and alk.sub.3 are chemical bonds or alkylene groups; Q is hydrogen or hydroxyl; and R.sub.1 -R.sub.4 are hydrogen or alkyl.Type: GrantFiled: June 7, 1995Date of Patent: December 29, 1998Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.Inventors: Robert W. Webb, II, Joanne J. Bronson, John C. Martin
-
Patent number: 5843943Abstract: Novel, heterocyclic compounds having at least one ring nitrogen, disclosed side chains and, in some embodiments, an oxygen ortho to the ring nitrogen inhibit inflammatory responses associated with TNF-.alpha. and fibroblast proliferation in vivo and in vitro. The compounds of the invention neither appreciably inhibit the activity of cAMP phosphodiesterase nor the hydrolysis of phosphatidic acid, and are neither cytotoxic nor cytostatic. Preferred compounds of the invention are esters. Methods for the use of the novel compounds to inhibit ceramide-mediated intracellular responses to stimuli in vivo (particularly TNF-.alpha.) are also described. The methods are expected to be of use in reducing inflammatory responses (for example, after angioplasty), in limiting fibrosis (for example, of the liver in cirrhosis), in inhibiting cell senescence, cell apoptosis and UV induced cutaneous immune suppression.Type: GrantFiled: June 7, 1995Date of Patent: December 1, 1998Assignee: The Regents of the University of CaliforniaInventors: Dennis A. Carson, Howard B. Cottam, D. Bruce Wasson
-
Patent number: 5840716Abstract: A phosphonate nucleotide compound having antiviral activity and is useful for an orally available and highly safe antiviral agent, which is represented by the following formula (I): ##STR1## wherein R.sup.1 represents hydrogen, a C.sub.1 -C.sub.6 alkoxy, a halogen-substituted C.sub.1 -C.sub.4 alkoxy, halogen, amino, or nitro; R.sup.2 and R.sup.3 independently represent hydrogen, a C.sub.1 -C.sub.22 alkyl, an acyloxymethy, an acylthioethyl, or a halogen-substituted ethyl; R.sup.4 represents hydrogen, a C.sub.1 -C.sub.4 alkyl, a C.sub.1 -C.sub.4 hydroxyalkyl, or a halogen-substituted C.sub.1 -C.sub.4 alkyl; and X represents carbon or nitrogen.Type: GrantFiled: January 17, 1997Date of Patent: November 24, 1998Assignee: Mitsubishi Chemical CorporationInventors: Masaru Ubasawa, Kouichi Sekiya, Hideaki Takashima, Naoko Ueda, Satoshi Yuasa, Naohiro Kamiya
-
Patent number: 5837871Abstract: Provided are compounds of the following formulae:A phosphonomethoxymethyoxymethyl purine/pyrimidine derivative of the formula ##STR1## wherein X and X' are the same or different and are hydrogen or alkyl. R and R' are the same or different and are hydrogen, alkyl, hydroyalkyl or alkanoyl andB is a purine or pyrimidine base.Type: GrantFiled: June 7, 1995Date of Patent: November 17, 1998Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting, v.z.w.Inventors: Choung Un Kim, John C. Martin, Bing Uh Luh, Peter F. Misco
-
Patent number: 5831092Abstract: Purine derivatives in which a desired substituent is introduced into the 9-position only are synthesized by first introducing an easily-removable substituent in the 7-position of a purine base of natural purine nucleosides obtained through fermentation or derivatives thereof, then hydrolyzing the ribose moiety to form purine derivatives having the substituent in the 7-position, subsequently introducing the desired substituent in the 9-position, and then removing the substituent in the 7-position.Type: GrantFiled: February 20, 1996Date of Patent: November 3, 1998Assignee: Ajinomoto Co., Inc.Inventors: Kunisuke Izawa, Hiroshi Shiragami, Keizo Yamashita
-
Patent number: 5817811Abstract: Processes are described for preparing substituted N-ethylglycine derivatives of the formula ##STR1## in which PG is an amino protecting group which is labile towards weak acids and is of the urethane type or the trityl type, X is NH or O, and B' represents bases which are customary in nucleotide chemistry and whose exocyclic amino and/or hydroxyl groups are protected by suitable known protecting groups, and the salts thereof.Type: GrantFiled: September 3, 1996Date of Patent: October 6, 1998Assignee: Hoechst AktiengesellschaftInventors: Gerhard Breipohl, Eugen Uhlmann, David William Will
-
Patent number: 5817812Abstract: A cyclopentenecarboxamide derivative represented by the formula (I): ##STR1## and a method for preparing the cyclopentencarboxamide derivative. A bicycloamide derivative represented by the formula (II): ##STR2## and a method for preparing the bicycloamide derivative.Type: GrantFiled: November 14, 1996Date of Patent: October 6, 1998Assignee: Kuraray Co., Ltd.Inventors: Nobuya Katagiri, Chikara Kaneko, Junko Sato, Masahiro Torihara, Koichi Kanehira, Yoshin Tamai
-
Patent number: 5817647Abstract: Disclosed are novel unsaturated acetylene phosphonate derivatives of certain purines or pyrimidines useful as antiviral agents, methods useful for their preparation and use of these compounds as antiviral agents effective against DNA viruses, retroviruses and viruses involved in tumor formation.Type: GrantFiled: November 17, 1995Date of Patent: October 6, 1998Assignee: Merrell Pharmaceuticals Inc.Inventors: Patrick Casara, Jean-Fran.cedilla.ois Nave, Serge Halazy
-
Patent number: 5804583Abstract: Derivatives of bicyclic heterocycles comprising a pyrimidone ring fused to another 5, 6, or 7 membered nitrogen heterocycle which is C-substituted, through a methylene bridge, by a biphenyl group.Type: GrantFiled: December 18, 1996Date of Patent: September 8, 1998Assignee: Istituto Luso Farmaco D'ItaliaInventors: Aldo Salimbeni, Davide Poma, Anna Renzetti, Carlo Scolastico
-
Patent number: 5798344Abstract: The invention provides a phosphonic diester derivative of the formula: ##STR1## wherein R.sup.1 -R.sup.7 are substituent groups, as defined in the specification.The derivatives according to the invention are useful as therapeutic or preventive compositions for hyperlipidemia, hypertension, and diabetes.Type: GrantFiled: September 5, 1996Date of Patent: August 25, 1998Assignee: Otsuka Pharmaceutical Factory, Inc.Inventors: Yasuhisa Kuroki, Kazuyoshi Miyata, Yoshihiko Tsuda, Yasuhide Inoue, Jun Kanaya, Keigo Sato
-
Patent number: 5798340Abstract: Nucleotide analogs characterized by the presence of an amidate lirked amino acid or an ester linked group which is bonded to the phosphorus atom of phosphonate nucleotide analogs are disclosed. The analogs comprise a phosphoamidate or ester bond that is hydrolysed in vivo to yield a corresponding phosphonate nucleotide analog. Methods and intermediates for the synthesis and use are described.Type: GrantFiled: May 6, 1996Date of Patent: August 25, 1998Assignee: Gilead Sciences, Inc.Inventors: Norbert W. Bischofberger, Robert J. Jones, Murty N. Arimilli, Michael S. Louie, Ernest J. Prisbe, William A. Lee
-
Patent number: 5792868Abstract: Herein is disclosed a novel and industrially advantageous process for synthesizing acyclic nucleosides such as acyclovir and ganciclovir from ribonucleosides, which process comprises adding an acid catalyst and an acid anhydride to a solution of a ribonucleoside such as guanosine and an ester derivative of an acyclic sugar, and heating the mixture, whereby a transglycosilation reaction takes place between the ribose moiety of the ribonucleoside and the ester derivative of the acyclic sugar.Herein is also disclosed an industrially favorable method for the separation of 9-substituted purine nucleosides which are important intermediates for the synthesis of acyclic nucleosides such as acyclovir, ganciclovir, and the like from ribonucleosides, which method comprises crystallizing only the 9-isomer from a solution or suspension containing both a 9-substituted purine nucleoside and a 7-substituted purine nucleoside by cooling the solution or/and by adding a crystallizing solvent thereto.Type: GrantFiled: March 18, 1994Date of Patent: August 11, 1998Assignee: Ajinomoto Co., Inc.Inventors: Kunisuke Izawa, Yoshihito Koguchi, Hiroshi Shiragami
-
Patent number: 5789394Abstract: Nucleotide analogues having the general formula (I) and pharmaceutically acceptable derivatives: ##STR1## wherein n is 0 or an integer; X is O or S, CH.sub.2, CH-halogen, CH--N.sub.3, or C.dbd.CH.sub.2 ;Q and U are independently selected from: O, S, and CH(R.sub.a) wherein R.sub.a is hydrogen, OH, halogen, N.sub.3, NH.sub.2, SH, carboxyl, C.sub.1-6 alkyl or R.sub.a is CH.sub.2 (R.sub.b) wherein R.sub.b is hydrogen, OH, SH, NH.sub.2, C.sub.1-6 alkyl or carboxyl; or both Q and U are CH when Q and U are linked by a double bond;Z is selected from: O, a C.sub.1-6 alkoxy, a C.sub.1-6 thioalkyl, a C.sub.1-6 aminoalkyl, (CH.sub.2).sub.m wherein m is 0 or an integer, and N(R.sub.c).sub.2 wherein both R.sub.c are independently hydrogen or a C.sub.1-6, alkyl; andR2 is a purine or pyrimidine base or an analogue or derivative thereof are disclosed. Members of this series of analogues possess anti-viral activity.Type: GrantFiled: April 29, 1996Date of Patent: August 4, 1998Inventors: Nghe Nguyen-Ba, Miguel Quimpere, Laval Chan Chung Kong, William L. Brown, Gervais Dionne
-
Patent number: 5789589Abstract: Disclosed are novel prodrugs represented by the following structural formulas: ##STR1## Z is oxygen or sulfur; n is 1 or 2; Y is, together with a hydroxy group, acyclovir or an analog of acyclovir; A is a group which can be metabolized in vivo to a give a modified A such that the phosphoester bond (modified A)--O undergoes cleavage in vivo. Also disclosed is a method of treating a viral infection in an individual or animal. The method comprises administering to the individual or animal a therapeutically effective amount of a prodrug represented by structural formula shown above.Type: GrantFiled: April 22, 1996Date of Patent: August 4, 1998Assignee: Drug Innovation & Design, Inc.Inventor: Arnold Glazier
-
Patent number: 5763440Abstract: Compounds with fungicidal properties having formula I ##STR1## wherein W is CH.sub.3 --O--A.dbd.C(-)--CO(V)CH.sub.3 ;A is N or CH;V is O or NH;R.sub.4 and R.sub.5 are independently selected from hydrogen and substituted or unsubstituted alkyl and aryl groups and Q is substituted or unsubstituted aryl groups.Type: GrantFiled: June 7, 1996Date of Patent: June 9, 1998Assignee: Rohm and Haas CompanyInventors: Ronald Ross, Steven Howard Shaber
-
Patent number: 5756486Abstract: The internally cyclized congeners of hydroxy-substituted nucleotide analogues have been found to exhibit substantially lower toxicity in vivo than their uncyclized analogues, while retaining essentially the same antiviral activity. This was unexpected because the prior art suggested that the cyclic analogues offered no significant advantages in respect to toxicity. This finding permits the administration of much greater doses of the cyclic congeners than otherwise would have been possible and allows the clinician to omit toxicity ameliorating interventions. Novel compounds are provided for use in the method of this invention. Novel methods for the preparation of these compounds also are provided.Type: GrantFiled: September 5, 1996Date of Patent: May 26, 1998Assignee: Gilead Sciences, Inc.Inventors: Petr Alexander, Murty Arimilli, Norbert Bischofberger, Michael J. M. Hitchcock
-
Patent number: 5753635Abstract: This invention is directed to purine derivatives of the following formulae: ##STR1## wherein Z.sup.1 is --O--, --N(R.sup.10)-- or --CH.sub.2 O--;Z.sup.2 is --O--, --N(R.sup.10)-- or --OCH.sub.2 --;R.sup.1 and R.sup.4 are each independently hydrogen, halo, alkyl, --OR.sup.10, --C(O)OR.sup.10, --C(O)N(R.sup.10)R.sup.11, --N(R.sup.10)R.sup.11, --N(R.sup.10)C(O)R.sup.10, or --N(H)S(O).sub.2 R.sup.13 ;R.sup.2 is --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.10, --C(NH)N(H)C(O)OR.sup.13, --C(NH)N(H)C(O)R.sup.10, --C(NH)N(H)S(O).sub.2 R.sup.13, or --C(NH)N(H)C(O)N(H)R.sup.10 ;R.sup.3 is halo, alkyl, haloalkyl, haloalkoxy, ureido, cyano, guanidino, --OR.sup.10, --C(NH)NH.sub.2, --C(NH)N(H)OR.sup.10, --C(O)N(R.sup.10)R.sup.11, --R.sup.12 --C(O)N(R.sup.10)R.sup.11, --CH(OH)C(O)N(R.sup.10)R.sup.11, --N(R.sup.10)R.sup.11, --R.sup.12 --N(R.sup.10)R.sup.11, --C(O)OR.sup.10, --R.sup.12 --C(O)OR.sup.10, --N(R.sup.10)C(O)R.sup.Type: GrantFiled: August 16, 1996Date of Patent: May 19, 1998Assignee: Berlex Laboratories, Inc.Inventors: Brad O. Buckman, Raju Mohan, Michael M. Morrissey
-
Patent number: 5744600Abstract: A compound of the Formula I or Formula II ##STR1## wherein R.sup.1 and R.sup.2 are independently hydrogen, hydroxy, chlorine, fluorine, bromine, or an organic substituent having 1 to 5 carbon atoms and selected from acyloxy having a hydrocarbon stem of 1 to 4 carbon atoms, alkoxy, alkylthio, amino, alkylamino and dialkylamino;R.sup.3 and R.sup.4 are independently hydrogen, or organic phosphonic ester substituents having 1 to 12 carbon atoms and selected from alkyl, alkenyl, aryl, and aralkyl; andB is a heterocyclic group selected from the group consisting of pyrimidine, purine, triazine, deazapurine, and triazole, attached through a ring nitrogen atom thereof optionally substituted with 1 to 3 substituents selected from the group consisting of hydroxy, mercapto, amino, hydrazino, fluoro, chloro, bromo, iodo, C.sub.1 to C.sub.3 alkyl, C2-C3 alkenyl, C2-C3 haloalkenyl, C1-C3 alkoxy, and C1-C3 alkylthio;and the pharmaceutically acceptable acid addition, metal, and amine salts thereof.Type: GrantFiled: December 16, 1994Date of Patent: April 28, 1998Assignees: Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.Inventors: Muzammil M. Mansuri, John C. Martin, Thomas W. Hudyma, Joanne J. Bronson, Louis M. Ferrara
-
Patent number: RE36187Abstract: This invention relates to the use of acyclic substituted pyrrolo?2,3-d!pyrimidine nucleoside analogs in the treatment of viral infections. Such substituted compounds retain antiviral properties present in their parent compounds, yet exhibit significantly decreased levels of cytotoxicity, thereby having therapeutic potential as antiviral agents.Type: GrantFiled: August 5, 1994Date of Patent: April 6, 1999Assignee: The Regents of the University of MichiganInventors: Leroy B. Townsend, John G. Drach, Charles Shipman, Jr., Jeffrey S. Pudlo