NO309025B1 - Anvendelse av substituerte adeninderivater for fremstilling av preparater til behandling av multippel sklerose - Google Patents
Anvendelse av substituerte adeninderivater for fremstilling av preparater til behandling av multippel sklerose Download PDFInfo
- Publication number
- NO309025B1 NO309025B1 NO942765A NO942765A NO309025B1 NO 309025 B1 NO309025 B1 NO 309025B1 NO 942765 A NO942765 A NO 942765A NO 942765 A NO942765 A NO 942765A NO 309025 B1 NO309025 B1 NO 309025B1
- Authority
- NO
- Norway
- Prior art keywords
- treatment
- approx
- multiple sclerosis
- formula
- administration
- Prior art date
Links
- 201000006417 multiple sclerosis Diseases 0.000 title claims abstract description 24
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical class N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 238000011282 treatment Methods 0.000 title claims description 49
- 238000002360 preparation method Methods 0.000 title description 24
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical group C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 9
- 238000001802 infusion Methods 0.000 claims description 9
- FCZOVUJWOBSMSS-UHFFFAOYSA-N 5-[(6-aminopurin-9-yl)methyl]-5-methyl-3-methylideneoxolan-2-one Chemical class C1=NC2=C(N)N=CN=C2N1CC1(C)CC(=C)C(=O)O1 FCZOVUJWOBSMSS-UHFFFAOYSA-N 0.000 claims description 7
- 229930024421 Adenine Natural products 0.000 claims description 7
- 229960000643 adenine Drugs 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 239000006187 pill Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 3
- 239000012055 enteric layer Substances 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 2
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 46
- 210000001616 monocyte Anatomy 0.000 abstract description 24
- 238000000034 method Methods 0.000 abstract description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 13
- 230000001404 mediated effect Effects 0.000 abstract description 2
- 208000035475 disorder Diseases 0.000 abstract 1
- 206010039073 rheumatoid arthritis Diseases 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 description 14
- 201000010099 disease Diseases 0.000 description 12
- -1 2-substituted-2'-deoxy-2'-fluoroadenosines Chemical class 0.000 description 11
- 230000008901 benefit Effects 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 230000006870 function Effects 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 230000036470 plasma concentration Effects 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 210000001744 T-lymphocyte Anatomy 0.000 description 7
- OOXNYFKPOPJIOT-UHFFFAOYSA-N 5-(3-bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C=12C(N)=NC=NC2=NC(C=2C=NC(=CC=2)N2CCOCC2)=CC=1C1=CC=CC(Br)=C1 OOXNYFKPOPJIOT-UHFFFAOYSA-N 0.000 description 6
- 108010076278 Adenosine kinase Proteins 0.000 description 6
- 102100032534 Adenosine kinase Human genes 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 210000001185 bone marrow Anatomy 0.000 description 6
- 239000002502 liposome Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 230000003442 weekly effect Effects 0.000 description 6
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 5
- 102000055025 Adenosine deaminases Human genes 0.000 description 5
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 5
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 5
- 101100342977 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) leu-1 gene Proteins 0.000 description 5
- 210000003719 b-lymphocyte Anatomy 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 5
- 230000002354 daily effect Effects 0.000 description 5
- 210000004980 monocyte derived macrophage Anatomy 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 239000002777 nucleoside Substances 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- HBUBKKRHXORPQB-UUOKFMHZSA-N 2-fluoroadenosine Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O HBUBKKRHXORPQB-UUOKFMHZSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 208000016192 Demyelinating disease Diseases 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 238000010254 subcutaneous injection Methods 0.000 description 3
- 239000007929 subcutaneous injection Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- OLXZPDWKRNYJJZ-RRKCRQDMSA-N 2'-deoxyadenosine Chemical class C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 OLXZPDWKRNYJJZ-RRKCRQDMSA-N 0.000 description 2
- OLXZPDWKRNYJJZ-UHFFFAOYSA-N 5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol Chemical class C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(CO)O1 OLXZPDWKRNYJJZ-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 2
- 206010012305 Demyelination Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010048393 Multiple sclerosis relapse Diseases 0.000 description 2
- 102000006386 Myelin Proteins Human genes 0.000 description 2
- 108010083674 Myelin Proteins Proteins 0.000 description 2
- 125000000815 N-oxide group Chemical group 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 229920001800 Shellac Polymers 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- BMQYVXCPAOLZOK-UHFFFAOYSA-N Trihydroxypropylpterisin Natural products OCC(O)C(O)C1=CN=C2NC(N)=NC(=O)C2=N1 BMQYVXCPAOLZOK-UHFFFAOYSA-N 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 239000003246 corticosteroid Substances 0.000 description 2
- 229960001334 corticosteroids Drugs 0.000 description 2
- 229960000258 corticotropin Drugs 0.000 description 2
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 230000005713 exacerbation Effects 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 229940100601 interleukin-6 Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 210000005012 myelin Anatomy 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- BMQYVXCPAOLZOK-XINAWCOVSA-N neopterin Chemical compound OC[C@@H](O)[C@@H](O)C1=CN=C2NC(N)=NC(=O)C2=N1 BMQYVXCPAOLZOK-XINAWCOVSA-N 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 230000007658 neurological function Effects 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 208000035824 paresthesia Diseases 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 210000003024 peritoneal macrophage Anatomy 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 238000002203 pretreatment Methods 0.000 description 2
- 229940113147 shellac Drugs 0.000 description 2
- 239000004208 shellac Substances 0.000 description 2
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 2
- 235000013874 shellac Nutrition 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- 239000001226 triphosphate Substances 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- PCNPHZJRGDBRBX-IOSLPCCCSA-N (2r,3r,4r,5r)-5-(6-amino-2-methylpurin-9-yl)-2-(hydroxymethyl)-4-sulfanyloxolan-3-ol Chemical class C12=NC(C)=NC(N)=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1S PCNPHZJRGDBRBX-IOSLPCCCSA-N 0.000 description 1
- KMQPIRJQPAVGJL-DJLDLDEBSA-N (2r,3s,5r)-5-(4-aminoimidazo[4,5-c]pyridin-1-yl)-2-(hydroxymethyl)oxolan-3-ol Chemical class C1=NC=2C(N)=NC=CC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 KMQPIRJQPAVGJL-DJLDLDEBSA-N 0.000 description 1
- UYDKYWTWCPKLJR-KVQBGUIXSA-N (2r,3s,5r)-5-(6-amino-2-bromopurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol Chemical class C1=NC=2C(N)=NC(Br)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 UYDKYWTWCPKLJR-KVQBGUIXSA-N 0.000 description 1
- LFRDGHVRPSURMV-YFKPBYRVSA-N (4s)-4,5-dihydroxypentanal Chemical compound OC[C@@H](O)CCC=O LFRDGHVRPSURMV-YFKPBYRVSA-N 0.000 description 1
- WVXRAFOPTSTNLL-NKWVEPMBSA-N 2',3'-dideoxyadenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1CC[C@@H](CO)O1 WVXRAFOPTSTNLL-NKWVEPMBSA-N 0.000 description 1
- CKTSBUTUHBMZGZ-SHYZEUOFSA-N 2'‐deoxycytidine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-SHYZEUOFSA-N 0.000 description 1
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 1
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 1
- HDBQZGJWHMCXIL-UHFFFAOYSA-N 3,7-dihydropurine-2-thione Chemical class SC1=NC=C2NC=NC2=N1 HDBQZGJWHMCXIL-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical class [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010010947 Coordination abnormal Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 102000004594 DNA Polymerase I Human genes 0.000 description 1
- 108010017826 DNA Polymerase I Proteins 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 description 1
- 108010033174 Deoxycytidine kinase Proteins 0.000 description 1
- 102100029588 Deoxycytidine kinase Human genes 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- ZRTQSJFIDWNVJW-WYMLVPIESA-N Lanoconazole Chemical class ClC1=CC=CC=C1C(CS\1)SC/1=C(\C#N)N1C=NC=C1 ZRTQSJFIDWNVJW-WYMLVPIESA-N 0.000 description 1
- 208000007093 Leukemia L1210 Diseases 0.000 description 1
- 206010025327 Lymphopenia Diseases 0.000 description 1
- 102000047918 Myelin Basic Human genes 0.000 description 1
- 101710107068 Myelin basic protein Proteins 0.000 description 1
- 108010011356 Nucleoside phosphotransferase Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 102000009097 Phosphorylases Human genes 0.000 description 1
- 108010073135 Phosphorylases Proteins 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 208000032023 Signs and Symptoms Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000037114 Symptom Flare Up Diseases 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 150000003835 adenosine derivatives Chemical class 0.000 description 1
- 238000011256 aggressive treatment Methods 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 230000001099 anti-trypanosomal effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 125000000328 arabinofuranosyl group Chemical group C1([C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 150000001479 arabinose derivatives Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- WZPBZJONDBGPKJ-VEHQQRBSSA-N aztreonam Chemical compound O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC([NH3+])=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000009615 deamination Effects 0.000 description 1
- 238000006481 deamination reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012054 flavored emulsion Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 210000005104 human peripheral blood lymphocyte Anatomy 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000002642 intravenous therapy Methods 0.000 description 1
- 150000002496 iodine Chemical class 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 208000028756 lack of coordination Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 231100001023 lymphopenia Toxicity 0.000 description 1
- 206010025382 macrocytosis Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000009115 maintenance therapy Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000002025 microglial effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 230000037360 nucleotide metabolism Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000009520 phase I clinical trial Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002719 pyrimidine nucleotide Substances 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 231100000046 skin rash Toxicity 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000007103 stamina Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/838,546 US5310732A (en) | 1986-02-03 | 1992-02-19 | 2-halo-2'-deoxyadenosines in the treatment of rheumatoid arthritis |
| PCT/US1993/001467 WO1993016706A1 (en) | 1992-02-19 | 1993-02-18 | Use of substituted adenine derivatives for treating multiple sclerosis |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO942765D0 NO942765D0 (no) | 1994-07-25 |
| NO942765L NO942765L (no) | 1994-09-13 |
| NO309025B1 true NO309025B1 (no) | 2000-12-04 |
Family
ID=25277387
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO942765A NO309025B1 (no) | 1992-02-19 | 1994-07-25 | Anvendelse av substituerte adeninderivater for fremstilling av preparater til behandling av multippel sklerose |
| NO20000762A NO322328B1 (no) | 1992-02-19 | 2000-02-16 | Anvendelse av substituerte adeninderivater til behandling av multippel sklerose |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20000762A NO322328B1 (no) | 1992-02-19 | 2000-02-16 | Anvendelse av substituerte adeninderivater til behandling av multippel sklerose |
Country Status (15)
| Country | Link |
|---|---|
| US (4) | US5310732A (da) |
| EP (1) | EP0626853B1 (da) |
| JP (1) | JP2688113B2 (da) |
| AT (1) | ATE192045T1 (da) |
| AU (1) | AU682818B2 (da) |
| BR (1) | BR9305907A (da) |
| CA (1) | CA2130275C (da) |
| CH (1) | CH684310A5 (da) |
| DE (1) | DE69328474T2 (da) |
| DK (1) | DK0626853T3 (da) |
| FI (1) | FI943805A (da) |
| HU (1) | HU218656B (da) |
| NO (2) | NO309025B1 (da) |
| RU (1) | RU2130308C1 (da) |
| WO (1) | WO1993016706A1 (da) |
Families Citing this family (66)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5310732A (en) * | 1986-02-03 | 1994-05-10 | The Scripps Research Institute | 2-halo-2'-deoxyadenosines in the treatment of rheumatoid arthritis |
| US5624913A (en) * | 1991-04-05 | 1997-04-29 | Wisconsin Alumni Research Foundation | Method reducing TNF-alpha in mammals with cerebral malaria |
| WO1993023058A1 (en) * | 1992-05-19 | 1993-11-25 | The Scripps Research Institute | Use of 2-halo adenine derivatives as therapeutic agents against chronic myelogenous leukemia |
| US5424296A (en) * | 1993-04-15 | 1995-06-13 | The Scripps Research Institute | 2-Halo-2'-deoxyadenosines as therapeutic agents against malignant astrocytoma |
| US5672622A (en) * | 1994-04-21 | 1997-09-30 | Berlex Laboratories, Inc. | Treatment of multiple sclerosis |
| US5773570A (en) * | 1994-05-20 | 1998-06-30 | The Regents Of The University Of California | Vaccine compositions and methods useful in inducing immune protection against arthritogenic peptides involved in the pathogenesis of rheumatoid arthritis |
| US7094597B1 (en) * | 1994-05-20 | 2006-08-22 | The Regents Of The University Of California | Vaccine compositions and methods useful in inducing immune protection against arthritogenic peptides involved in the pathogenesis of rheumatoid arthritis |
| WO1995032718A1 (en) * | 1994-05-26 | 1995-12-07 | The Scripps Research Institute | 2-halo-2'-deoxyadenosine treatement for inflammatory bowel disease |
| US6060501A (en) * | 1994-06-02 | 2000-05-09 | Schering Aktiengesellschaft | Combined treatment of multiple sclerosis |
| WO1996003134A1 (en) * | 1994-07-21 | 1996-02-08 | Thomas Jefferson University | Treatment of diarrhea with 2-substituted adenosine derivatives |
| US5510336A (en) * | 1994-09-06 | 1996-04-23 | Saven; Alan | 2-halo-2'-deoxyadenosine treatment for histiocytosis |
| US5641757A (en) * | 1994-12-21 | 1997-06-24 | Ortho Pharmaceutical Corporation | Stable 2-chloro-2'-deoxyadenosine formulations |
| CA2208484C (en) * | 1994-12-22 | 2008-09-23 | Ortho Pharmaceutical Corporation | Soluble 2-chloro-2'-deoxyadenosine formulations |
| AU762821B2 (en) * | 1994-12-22 | 2003-07-03 | Ortho-Mcneil Pharmaceutical, Inc. | 'Soluble 2-chloro-2'-deoxyadenosine formulations' |
| SK283821B6 (sk) * | 1995-02-10 | 2004-02-03 | Schering Aktiengesellschaft | Farmaceutické preparáty na inhibíciu tumornekrózafaktora |
| US5811073A (en) * | 1995-06-19 | 1998-09-22 | President And Fellows Of Harvard College | Method for radioisotopic detection and localization of inflammation in a host |
| US6096310A (en) * | 1997-04-15 | 2000-08-01 | Bier; Milan | Oral immunotherapy of bacterial overgrowth |
| US6617171B2 (en) | 1998-02-27 | 2003-09-09 | The General Hospital Corporation | Methods for diagnosing and treating autoimmune disease |
| US6174873B1 (en) | 1998-11-04 | 2001-01-16 | Supergen, Inc. | Oral administration of adenosine analogs |
| EP1200102A1 (en) * | 1999-07-22 | 2002-05-02 | Supergen, Inc. | Methods for treating autoimmune diseases |
| US6989377B2 (en) | 1999-12-21 | 2006-01-24 | Wisconsin Alumni Research Foundation | Treating vitamin D responsive diseases |
| US6358939B1 (en) | 1999-12-21 | 2002-03-19 | Northern Lights Pharmaceuticals, Llc | Use of biologically active vitamin D compounds for the prevention and treatment of inflammatory bowel disease |
| MXPA02008075A (es) * | 2000-02-18 | 2005-06-06 | Southern Res Inst | Metodos para sintetizar 2-cloro -9-(2 -deoxi-2 -fluoro -beta- arabinofura-nosil)- 9h- purin- 6-amina. |
| US6989146B2 (en) * | 2000-08-09 | 2006-01-24 | The Regents Of The University Of California | Stress proteins and peptides and methods of use thereof |
| US7608683B2 (en) * | 2000-08-09 | 2009-10-27 | The Regents Of The University Of California | Stress proteins and peptides and methods of use thereof |
| IL155610A0 (en) | 2000-11-01 | 2003-11-23 | Univ California | Immunomodulatory peptides derived from heat shock proteins and uses thereof |
| WO2002078446A1 (en) * | 2001-03-29 | 2002-10-10 | Bioenergy Inc. | Composition to reduce exercise-induced swelling of joints |
| US7528247B2 (en) * | 2001-08-02 | 2009-05-05 | Genzyme Corporation | Process for preparing purine nucleosides |
| US7368423B1 (en) * | 2001-12-05 | 2008-05-06 | The Scripps Research Institute | Composition and method for treating chronic allograft rejection |
| US20060135463A1 (en) * | 2002-09-27 | 2006-06-22 | Wood Christopher B | Methods and compositions for the treatment of lupus using clofarabine |
| US20060100167A1 (en) * | 2002-09-27 | 2006-05-11 | Wood Christopher B | Methods and compositions for the treatment of autoimmune disorders using clofarabine |
| US7790762B2 (en) * | 2002-10-31 | 2010-09-07 | National Jewish Health | Compounds and methods for thiol-containing compound efflux and cancer treatment |
| US20080221029A1 (en) * | 2002-10-31 | 2008-09-11 | Regents Of The University Of Colorado | Methods for treatment of thiol-containing compound deficient conditions |
| US20040087527A1 (en) * | 2002-10-31 | 2004-05-06 | Day Brian J. | Methods for treatment of thiol-containing compound deficient conditions |
| GB0228723D0 (en) * | 2002-12-09 | 2003-01-15 | Cambridge Biotechnology Ltd | Treatment of pain |
| GB0305153D0 (en) * | 2003-03-07 | 2003-04-09 | Cambridge Biotechnology Ltd | Identification of therapeutic compounds |
| MXPA05010330A (es) * | 2003-03-28 | 2006-05-31 | Ivax Corp | Formulaciones de cladribina para el mejor suministro oral y a traves de la mucosa. |
| PT1608344E (pt) * | 2003-03-28 | 2010-09-02 | Ares Trading Sa | Formulações orais de cladribina |
| UA81305C2 (en) | 2003-07-02 | 2007-12-25 | Ares Trading Sa | Formulation of cladribine (variants), cladribine-cyclodextrin complex, use of cladribine-cyclodextrin complex, mixture |
| CN100471842C (zh) * | 2003-07-24 | 2009-03-25 | 安斯泰来制药有限公司 | 喹诺酮衍生物或其盐 |
| US20070167353A1 (en) * | 2003-10-24 | 2007-07-19 | John Hilfinger | Prodrug composition |
| US7465715B2 (en) * | 2003-12-29 | 2008-12-16 | Can-Fite Biopharma, Ltd. | Method for treatment of multiple sclerosis |
| WO2005070963A1 (en) | 2004-01-12 | 2005-08-04 | Applied Molecular Evolution, Inc | Fc region variants |
| US20050277615A1 (en) * | 2004-05-17 | 2005-12-15 | Can-Fite Biopharma Ltd. | Pharmaceutical compositions having anti-inflammatory activity |
| DK1835922T3 (da) * | 2004-12-22 | 2009-08-03 | Merck Serono Sa | Kombinationsbehandling mod multipel sklerose |
| EP1827461B1 (en) * | 2004-12-22 | 2012-02-29 | Merck Serono SA | Cladribine regimen for treating multiple sclerosis |
| US8658622B2 (en) * | 2005-01-14 | 2014-02-25 | Regents Of The University Of California | Methods and compositions for preventing and treating a disease related to glycan dysregulation |
| AU2007253254B2 (en) | 2006-05-24 | 2013-01-17 | Merck Serono Sa | Cladribine regimen for treating multiple sclerosis |
| US8126690B2 (en) * | 2007-05-18 | 2012-02-28 | The Regents Of The University Of Michigan | Algorithms to predict clinical response, adherence, and shunting with thiopurines |
| US9526707B2 (en) * | 2007-08-13 | 2016-12-27 | Howard L. Elford | Methods for treating or preventing neuroinflammation or autoimmune diseases |
| US8845627B2 (en) * | 2008-08-22 | 2014-09-30 | Boston Scientific Scimed, Inc. | Regulating pressure to lower temperature in a cryotherapy balloon catheter |
| WO2010042933A2 (en) | 2008-10-10 | 2010-04-15 | Northwestern University | Inhibition and treatment of prostate cancer metastasis |
| EP2343074A1 (en) | 2009-12-23 | 2011-07-13 | Merck Serono S.A. | Use of purine analogues for treating airway diseases |
| WO2012022740A1 (en) | 2010-08-18 | 2012-02-23 | Merck Serono S.A. | Combination treatment of multiple sclerosis |
| CN105247042B (zh) | 2013-03-15 | 2021-06-11 | 普林斯顿大学理事会 | 用于高通量纯化的方法和设备 |
| EP2971287B1 (en) | 2013-03-15 | 2019-08-14 | GPB Scientific, LLC | On-chip microfluidic processing of particles |
| US20150064153A1 (en) | 2013-03-15 | 2015-03-05 | The Trustees Of Princeton University | High efficiency microfluidic purification of stem cells to improve transplants |
| GB201401465D0 (en) * | 2014-01-29 | 2014-03-12 | Roach Arthur H | Use of cladribine for treating autoimmune inflammatory disease |
| WO2016073897A1 (en) | 2014-11-06 | 2016-05-12 | Northwestern University | Inhibition of cancer cell motility |
| US10976232B2 (en) | 2015-08-24 | 2021-04-13 | Gpb Scientific, Inc. | Methods and devices for multi-step cell purification and concentration |
| EP3341893A4 (en) * | 2015-08-24 | 2019-03-06 | GPB Scientific, LLC | METHODS AND DEVICES FOR PURIFICATION AND CONCENTRATION OF MULTI-STEP CELLS |
| GB2564717A (en) | 2017-07-21 | 2019-01-23 | Chord Therapeutics S A R L | Use of cladribine for treating autoimmune neuromuscular disease |
| US10849919B2 (en) | 2017-11-24 | 2020-12-01 | Merck Patent Gmbh | Cladribine regimen for treating progressive forms of multiple sclerosis |
| CA3194812A1 (en) | 2020-09-10 | 2022-03-17 | Merck Patent Gmbh | Novel treatment regimen for the treatment of autoimmune disorders |
| GB2601786A (en) | 2020-12-10 | 2022-06-15 | Chord Therapeutics S A R L | Use of cladribine for treating immune brain disease |
| CA3209648A1 (en) | 2021-03-03 | 2022-09-09 | Ursula BOSCHERT SHAFAATIAN | Improved treatment methods using dmds for the treatment of autoimmune diseases, and biomarker for predicting and/or optimising said treatment methods |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1572068C3 (de) * | 1966-03-12 | 1976-01-08 | Hoechst Ag, 6000 Frankfurt | Lichtempfindliche Schicht zur Herstellung von Druckformen |
| US3472838A (en) * | 1967-12-01 | 1969-10-14 | Parke Davis & Co | 9 - (beta - d - arabinofuranosyl) - 6 - (amidino) purine compounds and methods for their production |
| US4826823A (en) * | 1985-02-05 | 1989-05-02 | Warner-Lambert Company | Methods of using 2-chloro-2'-deoxyadenosine-5'-phosphate and its salts |
| US4751221A (en) * | 1985-10-18 | 1988-06-14 | Sloan-Kettering Institute For Cancer Research | 2-fluoro-arabinofuranosyl purine nucleosides |
| US5106837A (en) * | 1988-03-16 | 1992-04-21 | The Scripps Research Institute | Adenosine derivatives with therapeutic activity |
| US5310732A (en) * | 1986-02-03 | 1994-05-10 | The Scripps Research Institute | 2-halo-2'-deoxyadenosines in the treatment of rheumatoid arthritis |
| GB8708050D0 (en) * | 1987-04-03 | 1987-05-07 | Wellcome Found | Therapeutic nucleosides |
| GB8725466D0 (en) | 1987-10-30 | 1987-12-02 | Hoffmann La Roche | Purine derivatives |
| NZ226672A (en) * | 1987-10-30 | 1991-07-26 | Hoffmann La Roche | 6-amino-9-(2,3-dideoxy-2-fluoro-b-d-threopentofuranosyl)-9h-purine derivatives and pharmaceutical compositions |
| US4968702A (en) * | 1989-01-17 | 1990-11-06 | American Cyanamid Company | Substituted quinolinecarboxylic acids |
-
1992
- 1992-02-19 US US07/838,546 patent/US5310732A/en not_active Expired - Lifetime
-
1993
- 1993-02-18 WO PCT/US1993/001467 patent/WO1993016706A1/en active IP Right Grant
- 1993-02-18 AU AU37249/93A patent/AU682818B2/en not_active Expired
- 1993-02-18 HU HU9402392A patent/HU218656B/hu unknown
- 1993-02-18 CH CH3143/93A patent/CH684310A5/de not_active IP Right Cessation
- 1993-02-18 CA CA002130275A patent/CA2130275C/en not_active Expired - Lifetime
- 1993-02-18 US US08/256,931 patent/US5506214A/en not_active Expired - Lifetime
- 1993-02-18 DE DE69328474T patent/DE69328474T2/de not_active Expired - Lifetime
- 1993-02-18 BR BR9305907A patent/BR9305907A/pt not_active Application Discontinuation
- 1993-02-18 EP EP93906071A patent/EP0626853B1/en not_active Expired - Lifetime
- 1993-02-18 JP JP5514960A patent/JP2688113B2/ja not_active Expired - Lifetime
- 1993-02-18 RU RU94038043A patent/RU2130308C1/ru active
- 1993-02-18 AT AT93906071T patent/ATE192045T1/de not_active IP Right Cessation
- 1993-02-18 DK DK93906071T patent/DK0626853T3/da active
-
1994
- 1994-04-26 US US08/233,056 patent/US5541164A/en not_active Expired - Lifetime
- 1994-05-19 US US08/246,328 patent/US5506213A/en not_active Expired - Lifetime
- 1994-07-25 NO NO942765A patent/NO309025B1/no not_active IP Right Cessation
- 1994-08-18 FI FI943805A patent/FI943805A/fi not_active Application Discontinuation
-
2000
- 2000-02-16 NO NO20000762A patent/NO322328B1/no not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CA2130275C (en) | 1999-06-29 |
| NO942765D0 (no) | 1994-07-25 |
| BR9305907A (pt) | 1997-10-21 |
| AU3724993A (en) | 1993-09-13 |
| CA2130275A1 (en) | 1993-09-02 |
| FI943805A (fi) | 1994-10-19 |
| ATE192045T1 (de) | 2000-05-15 |
| EP0626853B1 (en) | 2000-04-26 |
| NO20000762D0 (no) | 2000-02-16 |
| CH684310A5 (de) | 1994-08-31 |
| AU682818B2 (en) | 1997-10-23 |
| US5310732A (en) | 1994-05-10 |
| NO20000762L (no) | 1994-09-13 |
| DE69328474D1 (de) | 2000-05-31 |
| JPH07507540A (ja) | 1995-08-24 |
| JP2688113B2 (ja) | 1997-12-08 |
| HUT68030A (en) | 1995-05-29 |
| HU9402392D0 (en) | 1994-10-28 |
| US5541164A (en) | 1996-07-30 |
| WO1993016706A1 (en) | 1993-09-02 |
| DE69328474T2 (de) | 2000-09-28 |
| RU94038043A (ru) | 1996-11-20 |
| RU2130308C1 (ru) | 1999-05-20 |
| HU218656B (hu) | 2000-10-28 |
| FI943805A0 (fi) | 1994-08-18 |
| US5506213A (en) | 1996-04-09 |
| NO322328B1 (no) | 2006-09-18 |
| EP0626853A1 (en) | 1994-12-07 |
| DK0626853T3 (da) | 2000-08-07 |
| NO942765L (no) | 1994-09-13 |
| US5506214A (en) | 1996-04-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO309025B1 (no) | Anvendelse av substituerte adeninderivater for fremstilling av preparater til behandling av multippel sklerose | |
| Carson et al. | Oral antilymphocyte activity and induction of apoptosis by 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine. | |
| Hutton et al. | Phase I clinical investigation of 9-β-D-arabinofuranosyl-2-fluoroadenine 5′-monophosphate (NSC 312887), a new purine antimetabolite | |
| IE860677L (en) | Antiviral formulation | |
| JP7022069B2 (ja) | ラパドシン（Ｒａｐａｄｏｃｉｎｓ）、受動拡散型ヌクレオシド輸送体１阻害剤及びその使用 | |
| NO337276B1 (no) | Anvendelse av 10-propargyl-10-deazaaminopterin for fremstilling av et farmasøytisk middel for behandling av T-cellelymfom | |
| EP0253962B1 (en) | Use of adenosine derivatives as anti-dementia agents | |
| TWI233359B (en) | Pharmaceutical composition for treating neoplasm | |
| Broder | Pharmacodynamics of 2′, 3′-dideoxycytidine: an inhibitor of human immunodeficiency virus | |
| Omura | Inhibitors of the enzyme purine nucleoside phosphorylase as potential therapy for psoriasis | |
| SI9820003A (sl) | Zdravljenje bolezni povezano s citokini | |
| US11963971B2 (en) | Combination decitabine and cedazuridine solid oral dosage forms | |
| JPH0215524B2 (da) | ||
| Korycka et al. | Novel purine nucleoside analogues for hematological malignancies | |
| Polmar | Enzyme replacement and other biochemical approaches to the therapy of adenosine deaminase deficiency | |
| Kobayashi et al. | A phase I study of intermittent infusion cladribine in patients with solid tumors | |
| WO2009045975A1 (en) | Potent combinations of zidovudine and drugs that select for the k65r mutation in the hiv polymerase | |
| CA2191230C (en) | 2-halo-2'-deoxyadenosine treatment for inflammatory bowel disease | |
| AU735319B2 (en) | 2-halo-2'-deoxyadenosine treatment for inflammatory bowel disease | |
| RU2300381C2 (ru) | β-L-2'-ДЕЗОКСИНУКЛЕОЗИДЫ ДЛЯ ЛЕЧЕНИЯ ГЕПАТИТА В | |
| KR950007909B1 (ko) | 치매 치료제 | |
| Santana et al. | Studies of 2-Chlorodeoxyadenosine (Cladribine) at St. Jude Children’s Research Hospital | |
| IE880210L (en) | Antiviral nucleosides |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1K | Patent expired |