JPS61500224A - 腫瘍性組織を放射線に対して増感する医薬組成物 - Google Patents
腫瘍性組織を放射線に対して増感する医薬組成物Info
- Publication number
- JPS61500224A JPS61500224A JP59504070A JP50407084A JPS61500224A JP S61500224 A JPS61500224 A JP S61500224A JP 59504070 A JP59504070 A JP 59504070A JP 50407084 A JP50407084 A JP 50407084A JP S61500224 A JPS61500224 A JP S61500224A
- Authority
- JP
- Japan
- Prior art keywords
- deoxycytidine
- chloro
- fluoro
- tetrahydrouridine
- deamination
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 230000005855 radiation Effects 0.000 title claims description 21
- 230000001235 sensitizing effect Effects 0.000 title claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 7
- 230000001613 neoplastic effect Effects 0.000 title claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 48
- 238000000034 method Methods 0.000 claims description 34
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 claims description 26
- 238000011282 treatment Methods 0.000 claims description 20
- IDYKCXHJJGMAEV-RRKCRQDMSA-N 4-amino-5-fluoro-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound C1=C(F)C(N)=NC(=O)N1[C@@H]1O[C@H](CO)[C@@H](O)C1 IDYKCXHJJGMAEV-RRKCRQDMSA-N 0.000 claims description 19
- UCKYOOZPSJFJIZ-FMDGEEDCSA-N (4r)-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N[C@H](O)CC1 UCKYOOZPSJFJIZ-FMDGEEDCSA-N 0.000 claims description 17
- 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 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 230000000637 radiosensitizating effect Effects 0.000 claims description 16
- 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 claims description 15
- CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 13
- 238000006481 deamination reaction Methods 0.000 claims description 11
- 239000003112 inhibitor Substances 0.000 claims description 11
- NGGRGTWYSXYVDK-RRKCRQDMSA-N 4-amino-5-chloro-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound C1=C(Cl)C(N)=NC(=O)N1[C@@H]1O[C@H](CO)[C@@H](O)C1 NGGRGTWYSXYVDK-RRKCRQDMSA-N 0.000 claims description 10
- 230000009615 deamination Effects 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
- 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 claims description 7
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 claims description 7
- -1 bromo, iodo Chemical group 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 229940104230 thymidine Drugs 0.000 claims description 7
- 206010070834 Sensitisation Diseases 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 230000037396 body weight Effects 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 230000008313 sensitization Effects 0.000 claims description 6
- NGGRGTWYSXYVDK-UHFFFAOYSA-N NSC 371331 Natural products C1=C(Cl)C(N)=NC(=O)N1C1OC(CO)C(O)C1 NGGRGTWYSXYVDK-UHFFFAOYSA-N 0.000 claims description 5
- 125000001246 bromo group Chemical group Br* 0.000 claims description 5
- 125000001475 halogen functional group Chemical group 0.000 claims description 5
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 229940009098 aspartate Drugs 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 125000002346 iodo group Chemical group I* 0.000 claims 3
- UDLONBHFIDEJHY-UAKXSSHOSA-N 4-amino-5-chloro-1-[(2r,3r,4r,5r)-3-chloro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound C1=C(Cl)C(N)=NC(=O)N1[C@H]1[C@H](Cl)[C@H](O)[C@@H](CO)O1 UDLONBHFIDEJHY-UAKXSSHOSA-N 0.000 claims 2
- 238000005576 amination reaction Methods 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 230000000694 effects Effects 0.000 description 23
- ZZKNRXZVGOYGJT-VKHMYHEASA-N (2s)-2-[(2-phosphonoacetyl)amino]butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)CP(O)(O)=O ZZKNRXZVGOYGJT-VKHMYHEASA-N 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 17
- 238000002474 experimental method Methods 0.000 description 16
- 231100000419 toxicity Toxicity 0.000 description 14
- 230000001988 toxicity Effects 0.000 description 14
- 108020004414 DNA Proteins 0.000 description 11
- 238000001959 radiotherapy Methods 0.000 description 10
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 102100029588 Deoxycytidine kinase Human genes 0.000 description 7
- 108010033174 Deoxycytidine kinase Proteins 0.000 description 7
- 230000006378 damage Effects 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 102100031565 Cytidine and dCMP deaminase domain-containing protein 1 Human genes 0.000 description 6
- 108010031325 Cytidine deaminase Proteins 0.000 description 6
- 238000013459 approach Methods 0.000 description 6
- 230000035899 viability Effects 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 239000002777 nucleoside Substances 0.000 description 5
- MXHRCPNRJAMMIM-SHYZEUOFSA-N 2'-deoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-SHYZEUOFSA-N 0.000 description 4
- KISUPFXQEHWGAR-RRKCRQDMSA-N 4-amino-5-bromo-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound C1=C(Br)C(N)=NC(=O)N1[C@@H]1O[C@H](CO)[C@@H](O)C1 KISUPFXQEHWGAR-RRKCRQDMSA-N 0.000 description 4
- 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 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 229960002949 fluorouracil Drugs 0.000 description 4
- WEVJJMPVVFNAHZ-RRKCRQDMSA-N ibacitabine Chemical compound C1=C(I)C(N)=NC(=O)N1[C@@H]1O[C@H](CO)[C@@H](O)C1 WEVJJMPVVFNAHZ-RRKCRQDMSA-N 0.000 description 4
- 239000002207 metabolite Substances 0.000 description 4
- 239000012730 sustained-release form Substances 0.000 description 4
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 3
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 3
- 206010021143 Hypoxia Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- RZCIEJXAILMSQK-JXOAFFINSA-N TTP Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 RZCIEJXAILMSQK-JXOAFFINSA-N 0.000 description 3
- 108010022394 Threonine synthase Proteins 0.000 description 3
- 102000005497 Thymidylate Synthase Human genes 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000006240 deamidation Effects 0.000 description 3
- MXHRCPNRJAMMIM-UHFFFAOYSA-N desoxyuridine Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-UHFFFAOYSA-N 0.000 description 3
- 229960000961 floxuridine Drugs 0.000 description 3
- 230000001146 hypoxic effect Effects 0.000 description 3
- 125000003835 nucleoside group Chemical group 0.000 description 3
- 150000003230 pyrimidines Chemical class 0.000 description 3
- 239000002534 radiation-sensitizing agent Substances 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000005909 tumor killing Effects 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- NCMVOABPESMRCP-SHYZEUOFSA-N 2'-deoxycytosine 5'-monophosphate Chemical class O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 NCMVOABPESMRCP-SHYZEUOFSA-N 0.000 description 2
- CKTSBUTUHBMZGZ-ULQXZJNLSA-N 4-amino-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-tritiopyrimidin-2-one Chemical compound O=C1N=C(N)C([3H])=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-ULQXZJNLSA-N 0.000 description 2
- NJCXGFKPQSFZIB-RRKCRQDMSA-N 5-chloro-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Cl)=C1 NJCXGFKPQSFZIB-RRKCRQDMSA-N 0.000 description 2
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 2
- HFEKDTCAMMOLQP-RRKCRQDMSA-N 5-fluorodeoxyuridine monophosphate Chemical compound O1[C@H](COP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C(F)=C1 HFEKDTCAMMOLQP-RRKCRQDMSA-N 0.000 description 2
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
- 102000016234 Deoxycytidylate deaminases Human genes 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 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 2
- 230000001925 catabolic effect Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 108010015012 dCMP deaminase Proteins 0.000 description 2
- 108010000742 dTMP kinase Proteins 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 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
- 230000010534 mechanism of action Effects 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- 238000011170 pharmaceutical development Methods 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 231100000444 skin lesion Toxicity 0.000 description 2
- 206010040882 skin lesion Diseases 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 2
- 229940045145 uridine Drugs 0.000 description 2
- UIYWFOZZIZEEKJ-XVFCMESISA-N 1-[(2r,3r,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound F[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 UIYWFOZZIZEEKJ-XVFCMESISA-N 0.000 description 1
- GBBJCSTXCAQSSJ-JVZYCSMKSA-N 1-[(2r,3s,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@@H](F)[C@H](O)[C@@H](CO)O1 GBBJCSTXCAQSSJ-JVZYCSMKSA-N 0.000 description 1
- BICGOULMPJLRQV-MYINAIGISA-N 1-[(2s,4s,5r)-2-bromo-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound C1[C@H](O)[C@@H](CO)O[C@@]1(Br)N1C(=O)NC(=O)C=C1 BICGOULMPJLRQV-MYINAIGISA-N 0.000 description 1
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
- CBOKZNLSFMZJJA-PEBGCTIMSA-N 3-Deazauridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)C=C(O)C=C1 CBOKZNLSFMZJJA-PEBGCTIMSA-N 0.000 description 1
- YWSSYJCGTNLVFS-MYINAIGISA-N 4-amino-1-[(2s,4s,5r)-2-chloro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@]1(Cl)O[C@H](CO)[C@@H](O)C1 YWSSYJCGTNLVFS-MYINAIGISA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 108010018956 CTP synthetase Proteins 0.000 description 1
- 235000014036 Castanea Nutrition 0.000 description 1
- 241001070941 Castanea Species 0.000 description 1
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 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
- 241000699670 Mus sp. Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 241000282376 Panthera tigris Species 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 102100037357 Thymidylate kinase Human genes 0.000 description 1
- 241001504592 Trachurus trachurus Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000011256 aggressive treatment Methods 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002501 antifilarial agent Substances 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 229940124274 edetate disodium Drugs 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 1
- 229960004413 flucytosine Drugs 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000002977 hyperthermial effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 201000005264 laryngeal carcinoma Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 210000005170 neoplastic cell Anatomy 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000006824 pyrimidine synthesis Effects 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
Classifications
-
- 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
- C07H19/06—Pyrimidine radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0038—Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
- A61N2005/1092—Details
- A61N2005/1098—Enhancing the effect of the particle by an injected agent or implanted device
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (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 |
|---|---|---|---|
| US54569383A | 1983-10-26 | 1983-10-26 | |
| US545693 | 1983-10-26 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61500224A true JPS61500224A (ja) | 1986-02-06 |
| JPH0586376B2 JPH0586376B2 (https=) | 1993-12-10 |
Family
ID=24177186
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59504070A Granted JPS61500224A (ja) | 1983-10-26 | 1984-10-26 | 腫瘍性組織を放射線に対して増感する医薬組成物 |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0160079B1 (https=) |
| JP (1) | JPS61500224A (https=) |
| AU (1) | AU583801B2 (https=) |
| DE (1) | DE3481172D1 (https=) |
| WO (1) | WO1985001871A1 (https=) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4815448A (en) * | 1985-03-19 | 1989-03-28 | Mills Randell L | Mossbauer cancer therapy |
| ATE132350T1 (de) | 1985-03-19 | 1996-01-15 | Randell L Mills | Verfahren und system zur erzielung einer lokalen mössbauer-absorption in einem organischen medium |
| US4815447A (en) * | 1985-03-19 | 1989-03-28 | Mills Randell L | Mossbauer cancer therapy |
| NZ330360A (en) * | 1997-06-02 | 1999-03-29 | Hoffmann La Roche | 5'-deoxy-cytidine derivatives, their manufacture and use as antitumoral agents |
| EP0882734B1 (en) * | 1997-06-02 | 2009-08-26 | F. Hoffmann-La Roche Ag | 5'-Deoxy-cytidine derivatives |
| US6417168B1 (en) * | 1998-03-04 | 2002-07-09 | The Trustees Of The University Of Pennsylvania | Compositions and methods of treating tumors |
| ATE339960T1 (de) * | 1999-03-01 | 2006-10-15 | Halogenetics Inc | Verwendung von zusammensetzungen enthaltend cldc als strahlungssensibilisatoren in der behandlung von neoplastischen erkrankungen |
| US6933287B1 (en) | 1999-03-01 | 2005-08-23 | Sheldon B. Greer | Dramatic simplification of a method to treat neoplastic disease by radiation |
| JO2778B1 (en) | 2007-10-16 | 2014-03-15 | ايساي انك | Certain Compounds, Compositions and Methods |
| AU2010234562B2 (en) | 2009-04-06 | 2016-05-12 | Taiho Pharmaceutical Co., Ltd. | Combination of cytidine-based antineoplastic drugs with cytidine deaminase inhibitor and use thereof in the treatment of cancer |
| US8609631B2 (en) | 2009-04-06 | 2013-12-17 | Eisai Inc. | Compositions and methods for treating cancer |
| UY32546A (es) | 2009-04-06 | 2010-10-29 | Eisai Inc | Composiciones y metodos para tratar cancer |
| JP5687687B2 (ja) | 2009-04-06 | 2015-03-18 | 大塚製薬株式会社 | 癌を治療するための(2’−デオキシ−リボフラノシル)−1,3,4,7−テトラヒドロ−(1,3)ジアゼピン−2−オン誘導体 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3870700A (en) * | 1973-05-29 | 1975-03-11 | Miles Lab | 2-halogeno-2-deoxy-5-(substituted)uridines |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4017606A (en) * | 1973-10-04 | 1977-04-12 | The Upjohn Company | Organic compounds and process |
| CS184526B1 (en) * | 1976-02-19 | 1978-08-31 | Dieter Cech | 2'-halogen-2'-deoxy-5-fluoruridine,3',5-di-o-benzoyl-derivatives and process for preparing thereof |
| US4210638A (en) * | 1978-03-17 | 1980-07-01 | Pcr, Inc. | Antiviral composition and method of treating virus diseases |
-
1984
- 1984-10-26 EP EP84904049A patent/EP0160079B1/en not_active Expired - Lifetime
- 1984-10-26 WO PCT/US1984/001735 patent/WO1985001871A1/en not_active Ceased
- 1984-10-26 DE DE8484904049T patent/DE3481172D1/de not_active Expired - Lifetime
- 1984-10-26 JP JP59504070A patent/JPS61500224A/ja active Granted
- 1984-10-26 AU AU36107/84A patent/AU583801B2/en not_active Ceased
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3870700A (en) * | 1973-05-29 | 1975-03-11 | Miles Lab | 2-halogeno-2-deoxy-5-(substituted)uridines |
Also Published As
| Publication number | Publication date |
|---|---|
| DE3481172D1 (de) | 1990-03-08 |
| WO1985001871A1 (en) | 1985-05-09 |
| EP0160079B1 (en) | 1990-01-31 |
| EP0160079A4 (en) | 1986-05-14 |
| EP0160079A1 (en) | 1985-11-06 |
| JPH0586376B2 (https=) | 1993-12-10 |
| AU583801B2 (en) | 1989-05-11 |
| AU3610784A (en) | 1985-05-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4894364A (en) | Method and materials for sensitizing neoplastic tissue to radiation | |
| JP4117901B2 (ja) | デオキシヌクレオチド合成の阻害剤を使用することによって逆転写酵素依存ウイルスの複製を阻害する新規な方法 | |
| Gandhi et al. | A proof-of-principle pharmacokinetic, pharmacodynamic, and clinical study with purine nucleoside phosphorylase inhibitor immucillin-H (BCX-1777, forodesine) | |
| US6579857B1 (en) | Combination cancer therapy comprising adenosine and deaminase enzyme inhibitors | |
| Hertel et al. | Evaluation of the antitumor activity of gemcitabine (2′, 2′-difluoro-2′-deoxycytidine) | |
| JPS61500224A (ja) | 腫瘍性組織を放射線に対して増感する医薬組成物 | |
| US8796241B2 (en) | Therapy of tumors and infectious agents deficient in methylthioadenosine phosphorylase | |
| Calabresi | Current status of clinical investigations with 6-azauridine, 5-iodo-2′-deoxyuridine, and related derivatives | |
| Grifantini | Tiazofurine ICN pharmaceuticals | |
| Huang et al. | Effects of cytotoxicity of 2-chloro-2′-deoxyadenosine and 2-bromo-2′-deoxyadenosine on cell growth, clonogenicity, DNA synthesis, and cell cycle kinetics | |
| JP2013540112A (ja) | Hcv感染を治療するための併用療法 | |
| JPS634809B2 (https=) | ||
| Lynch et al. | Treatment of mouse neoplasms with high doses of tubercidin | |
| Rich | Irradiation plus 5-fluorouracil: cellular mechanisms of action and treatment schedules | |
| Lawrence et al. | The effects of leucovorin and dipyridamole on fluoropyrimidine-induced radiosensitization | |
| CN1447692A (zh) | 药物释放至肝细胞和治疗黄病毒感染的方法 | |
| EP3563856A1 (en) | Pharmaceutical composition for treating cancer and use thereof | |
| Deen et al. | Response of 9L tumor cells in vitro to spirohydantoin mustard | |
| CA1269658A (en) | Method and materials for sensitizing neoplastic tissue to radiation | |
| Coucke et al. | The ribonucleoside diphosphate reductase inhibitor (E)-2′-deoxy-(fluoromethylene) cytidine as a cytotoxic radiosensitizer in vitro | |
| RU2314807C2 (ru) | Комбинированная противоопухолевая терапия, включающая использование замещенных акрилоилпроизводных дистамицина и лучевой терапии | |
| Fujimoto et al. | Hypothetical mechanism of therapeutic synergism induced by the combination of 6-thioguanine and 3-[(4-amino-2-methyl-5-pyrimidinyl) methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride | |
| Yen et al. | Phase I pharmacodynamic study of time and sequence dependency of hydroxyurea in combination with gemcitabine: a California Cancer Consortium Trial | |
| US5496810A (en) | Pyrimidine deoxyribonucleoside potentiation of combination therapy based on 5-fluorouracil and interferon | |
| US20190046470A1 (en) | New use of tumor gene methylation regulator and anti-tumor drugs |