JPS63250396A - 3'-azido-3'-deoxythymidine derivative - Google Patents
3'-azido-3'-deoxythymidine derivativeInfo
- Publication number
- JPS63250396A JPS63250396A JP8349687A JP8349687A JPS63250396A JP S63250396 A JPS63250396 A JP S63250396A JP 8349687 A JP8349687 A JP 8349687A JP 8349687 A JP8349687 A JP 8349687A JP S63250396 A JPS63250396 A JP S63250396A
- Authority
- JP
- Japan
- Prior art keywords
- azido
- deoxythymidine
- formula
- halogen
- benzyl
- 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.)
- Pending
Links
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical class O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 title abstract description 10
- 125000002252 acyl group Chemical group 0.000 claims abstract description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 abstract description 17
- 239000002904 solvent Substances 0.000 abstract description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 abstract description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract description 11
- 125000000217 alkyl group Chemical group 0.000 abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 abstract description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 abstract description 6
- 229910000104 sodium hydride Inorganic materials 0.000 abstract description 6
- 239000012312 sodium hydride Substances 0.000 abstract description 6
- 229910052794 bromium Inorganic materials 0.000 abstract description 4
- 229910052801 chlorine Inorganic materials 0.000 abstract description 4
- 229910052731 fluorine Inorganic materials 0.000 abstract description 4
- 229910052740 iodine Inorganic materials 0.000 abstract description 3
- 150000002366 halogen compounds Chemical class 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract description 2
- 239000002246 antineoplastic agent Substances 0.000 abstract 1
- 239000003443 antiviral agent Substances 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000004519 manufacturing process Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- -1 2-methylprobionyl Chemical group 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000012230 colorless oil Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 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 4
- OAIVIYSBZFEOIU-UHFFFAOYSA-N chloroform;propan-2-one Chemical compound CC(C)=O.ClC(Cl)Cl OAIVIYSBZFEOIU-UHFFFAOYSA-N 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 230000000840 anti-viral effect Effects 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- LDOLZPLGBOMIJY-GSLILNRNSA-N 1-[(2r,4s,5s)-4-azido-5-(1-hydroxyethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound C1[C@H](N=[N+]=[N-])[C@@H](C(O)C)O[C@H]1N1C(=O)NC(=O)C(C)=C1 LDOLZPLGBOMIJY-GSLILNRNSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 229960003962 trifluridine Drugs 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- JQZAEUFPPSRDOP-UHFFFAOYSA-N 1-chloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1 JQZAEUFPPSRDOP-UHFFFAOYSA-N 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- IHCCLXNEEPMSIO-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 IHCCLXNEEPMSIO-UHFFFAOYSA-N 0.000 description 1
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
- DFGKGUXTPFWHIX-UHFFFAOYSA-N 6-[2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]acetyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)C1=CC2=C(NC(O2)=O)C=C1 DFGKGUXTPFWHIX-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- VSQQQLOSPVPRAZ-RRKCRQDMSA-N trifluridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C(F)(F)F)=C1 VSQQQLOSPVPRAZ-RRKCRQDMSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
産業上の利用分野
本発明は、新規な3′−アジド−3′−デオキシチミジ
ン誘導体に関する。DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to novel 3'-azido-3'-deoxythymidine derivatives.
従来の技術及びその問題点
3′−アジド−3′−デオキシチミジン(IIa)はH
orvltz等(J 、 Org、 Chell、。Prior art and its problems 3'-azido-3'-deoxythymidine (IIa) is H
orvltz et al. (J, Org, Chell,.
1964.29,2074)により、α、α、α−トリ
フルオロー3′−アジド−3′−デオキシチミジン(I
[b)はLin等(J 、 Med、 Chem、。1964.29, 2074), α,α,α-trifluoro-3′-azido-3′-deoxythymidine (I
[b) Lin et al. (J, Med, Chem.
1983.26,1691)により合成された化合物で
あり、抗ウィルス作用あるいは抗腫瘍作用が知られてい
る。特に3′−アジド−3′−デオキシチミジンは後天
的免疫不全症候群(AIDS)の病原ウィルスであるH
I V (hua+an1mmunodef1c1e
nt virus )に対し、強い増殖抑制効果が開示
されており、治療上極めて有用な化合物と考えられてい
る( M 1 tusuga等、Proc。1983.26, 1691), and is known to have antiviral or antitumor effects. In particular, 3'-azido-3'-deoxythymidine is a virus that causes acquired immunodeficiency syndrome (AIDS).
I V (hua+an1mmunodef1c1e
nt virus), and is considered to be a very therapeutically useful compound (M 1 tusuga et al., Proc.
Natl、Acad、Sci、USA、1985.82
゜7096) 。Natl, Acad, Sci, USA, 1985.82
゜7096).
(II a) (II b)問題
点を解決するための手段
本発明者らは、これ等化合物(IIa)、(IIb)の
作用増強、副作用の軽減等を目的とした誘導体化を種々
検討し、当初の目的を達成し得る誘導体を合成するのに
成功し、本発明を完成した。(IIa) (IIb) Means for Solving the Problems The present inventors have investigated various derivatizations of these compounds (IIa) and (IIb) for the purpose of enhancing their effects and reducing their side effects. succeeded in synthesizing a derivative capable of achieving the original purpose and completed the present invention.
即ち、本発明は一般式 (式中、Xは、水素原子又はフッ素原子を示す。That is, the present invention is based on the general formula (In the formula, X represents a hydrogen atom or a fluorine atom.
Rは、低級アルキル基、ベンジル基、)\ロゲン置換ベ
ンジル基、低級アシル基又はベンゾイル基を示す。)で
表わされる3′−アジド−3′−デオキシチミジン誘導
体に係る。R represents a lower alkyl group, a benzyl group, )\logen-substituted benzyl group, a lower acyl group, or a benzoyl group. 3'-azido-3'-deoxythymidine derivative represented by
上記本発明化合物は、抗腫瘍作用、抗ウィルス作用を有
し、医薬として有用である。The above-mentioned compounds of the present invention have antitumor and antiviral effects and are useful as medicines.
上記一般式(I)中Rで示される低級アルキル基として
は炭素数1〜6のアルキル基、例えばメチル、エチル、
プロピル、イソプロピル、ブチル、5ec−ブチル、t
ert−ブチル、ヘキシル基等の直鎖状、分枝状のアル
キル基を挙げることができる。低級アシル基としては炭
素数2〜6のアシル基、具体的にはアセチル、プロピオ
ニル、2−メチルプロビオニル、ピバロイル、2−メチ
ルブチリル、ヘキサノイル基等を例示できる。ハロゲン
置換ベンジル基としては、フッ素、塩素、臭素、ヨウ素
のハロゲン原子がフェニル環上に置換したものが、具体
的には4−フルオロベンジル、2−クロルベンジル、4
−クロルベンジル、2゜4−ジクロルベンジル、4−ブ
ロムベンジル基等が挙げられる。The lower alkyl group represented by R in the above general formula (I) is an alkyl group having 1 to 6 carbon atoms, such as methyl, ethyl,
Propyl, isopropyl, butyl, 5ec-butyl, t
Examples include linear and branched alkyl groups such as ert-butyl and hexyl groups. Examples of lower acyl groups include acyl groups having 2 to 6 carbon atoms, specifically acetyl, propionyl, 2-methylprobionyl, pivaloyl, 2-methylbutyryl, hexanoyl, and the like. Examples of halogen-substituted benzyl groups include those in which a halogen atom of fluorine, chlorine, bromine, or iodine is substituted on the phenyl ring, specifically 4-fluorobenzyl, 2-chlorobenzyl, 4-fluorobenzyl,
-chlorobenzyl, 2°4-dichlorobenzyl, 4-brombenzyl and the like.
以下、本発明誘導体の製造方法につき詳述する。The method for producing the derivative of the present invention will be described in detail below.
本発明化合物は、例えば次に示す二つの製造法により製
造される。The compound of the present invention can be produced, for example, by the following two production methods.
く製法A〉
一般式(I)中Rが低級アルキル基、ベンジル基、ハロ
ゲン置換ベンジル基の化合物は、例えば公知の3′−ア
ジド−3′−デオキシチミジン(IIa)、あるいはα
、α、α−トリフルオロー3′−アジド−3′−デオキ
シチミジン(nb)を溶媒中、塩基の存在下に一般式
%式%()
(式中、R′は、低級アルキル基、ベンジル基又はハロ
ゲン置換ベンジル基を示す。Yは塩素、臭素、沃素のハ
ロゲン原子を示す)で表わされるハロゲン化合物と反応
させる事により得られる。Production method A> The compound in which R in the general formula (I) is a lower alkyl group, a benzyl group, or a halogen-substituted benzyl group is, for example, the known 3'-azido-3'-deoxythymidine (IIa) or α
, α,α-trifluoro-3'-azido-3'-deoxythymidine (nb) in a solvent in the presence of a base with the general formula % formula % () (wherein R' is a lower alkyl group, a benzyl group or a halogen-substituted benzyl group (Y represents a halogen atom of chlorine, bromine, or iodine).
ここで用いられる溶媒としては、該反応に悪影響を与え
るものでない限り特に限定されず、従来公知のものを広
く使用でき、具体的には、ベンゼン、トルエン、キシレ
ン等の芳香族炭化水素、エーテル、テトラヒドロフラン
、ジオキサン等のエーテル類、アセトニトリル、ピリジ
ン、ジメチルホルムアミド、ジメチルスルホキサイド等
の慣用の非プロトン性溶媒を単独であるいは複数混合し
て用いる事ができる。塩基としてはこの種反応に通常用
いられる各種のものをいずれも使用でき、特に例えば水
素化ナトリウム、水素化カリウム等のアルカリ金属ハイ
ドライド、水酸化リチウム、水酸化ナトリウム、水酸化
カリウム等のアルカリ金属水酸化物、ナトリウムメトキ
シド等のアルカリ金属アルコキサイド、カリウムter
t−ブトキシド、ブチルリチウム、カリウムジシラジド
等の有機アルカリ金属、酸化銀、硝酸銀等が好適に用い
られる。該塩基の使用量としては式(na)あるいは(
nb)で表わされる化合物に対し、通常1〜10倍モル
程度、好ましくは2〜5倍モル程度が用いられる。ハロ
ゲン化合物(I[)の使用割合は式(II a)あるい
は(II b’)で表わされる化合物に対し、通常1〜
10倍モル比、好ましくは1〜5倍モル比とするのが適
当である。反応温度は特に限定されるものではないが、
通常0〜100℃前後、好ましくは室温〜60℃程度と
するのが望ましい。反応時間は使用する溶媒、塩基の種
類により異るが一般に0.5〜10時間程度で反応は完
結する。The solvent used here is not particularly limited as long as it does not adversely affect the reaction, and a wide variety of conventionally known solvents can be used. Specifically, aromatic hydrocarbons such as benzene, toluene, xylene, ether, Ethers such as tetrahydrofuran and dioxane, and conventional aprotic solvents such as acetonitrile, pyridine, dimethylformamide and dimethyl sulfoxide can be used alone or in combination. As the base, any of the various bases commonly used in this type of reaction can be used, especially alkali metal hydrides such as sodium hydride and potassium hydride, alkali metal waters such as lithium hydroxide, sodium hydroxide, potassium hydroxide, etc. oxide, alkali metal alkoxide such as sodium methoxide, potassium ter
Organic alkali metals such as t-butoxide, butyllithium, potassium disilazide, silver oxide, silver nitrate, etc. are preferably used. The amount of the base to be used is the formula (na) or (
It is usually used in an amount of about 1 to 10 times, preferably about 2 to 5 times, the amount of the compound represented by nb). The proportion of the halogen compound (I[) to be used is usually 1 to 1 to the compound represented by formula (II a) or (II b').
A suitable molar ratio is 10 times, preferably 1 to 5 times. Although the reaction temperature is not particularly limited,
The temperature is usually about 0 to 100°C, preferably about room temperature to 60°C. Although the reaction time varies depending on the type of solvent and base used, the reaction is generally completed in about 0.5 to 10 hours.
く製法B〉
又、一般式(I)中Rが低級アシル基、ベンゾイル基で
ある化合物は、例えば式(IIb)で表わされる化合物
を出発原料とし、溶媒中、一般式%式%()
(式中、R′は、低級アシル基又はベンゾイル基を示す
。Y′は、フッ素、塩素、臭素、沃素のハロゲン原子、
低級アシルオキシ基、ベンゾイルオキシ基、置換ベンゾ
イルオキシ基又はイミダゾール基を示す)で表わされる
化合物と反応させることにより得られる。ここで用いら
れる溶媒としては、該反応に悪影響を与えるものでない
限り特に限定されず、従来公知のものを広く使用でき、
具体的には前記製法Aで使用する溶媒の他メチルエチル
ケトン、アセトン等のケトン類、塩化メチレン、クロロ
ホルム等のハロゲン化炭化水素類等の溶媒を単独である
いは複数混合して用いることができる。上記反応系内に
は塩基を存在させるのが好ましく、斯かる塩基としては
この種反応に通常用いられる各種のものをいずれも使用
でき、特に例えば水素化ナトリウム、カリウムtert
−ブトキシド、トリエチルアミン、ピリジン、イミダゾ
ール等が好ましく使用される。本反応に於ける塩基及び
一般式(IV)の化合物の使用割合、反応時間、反応温
度の各条件は前記製法Aと同様である。Production method B> In addition, a compound in which R in the general formula (I) is a lower acyl group or a benzoyl group can be prepared by using, for example, a compound represented by the formula (IIb) as a starting material and converting the general formula % formula % () in a solvent. In the formula, R' represents a lower acyl group or a benzoyl group. Y' is a halogen atom of fluorine, chlorine, bromine, or iodine,
It can be obtained by reacting with a compound represented by a lower acyloxy group, a benzoyloxy group, a substituted benzoyloxy group, or an imidazole group. The solvent used here is not particularly limited as long as it does not adversely affect the reaction, and a wide variety of conventionally known solvents can be used.
Specifically, in addition to the solvent used in the above-mentioned production method A, solvents such as ketones such as methyl ethyl ketone and acetone, and halogenated hydrocarbons such as methylene chloride and chloroform can be used alone or in combination. It is preferable to have a base present in the reaction system, and any of the various bases commonly used in this type of reaction can be used, particularly sodium hydride, potassium tert, etc.
-butoxide, triethylamine, pyridine, imidazole, etc. are preferably used. The conditions in this reaction, such as the ratio of the base and the compound of general formula (IV) used, the reaction time, and the reaction temperature, are the same as those in Production Method A above.
上記の方法で得られる化合物(I)は、通常公知の分離
精製手段、例えばシリカゲルカラムクロマトグラフィー
により、単離、精製され得る。Compound (I) obtained by the above method can be isolated and purified by commonly known separation and purification means, such as silica gel column chromatography.
かくして得られた本発明化合物は一般式(IIa)及び
(IIb)に比し、優れた抗腫瘍作用、抗ウィルス作用
を示し、これ等の疾患の治療に対し有用である。The thus-obtained compounds of the present invention exhibit superior antitumor and antiviral effects compared to general formulas (IIa) and (IIb), and are useful for the treatment of these diseases.
実施例
以下に実施例を挙げて、本発明化合物についてより具体
的に説明する。尚、各実施例で得られた化合物の核磁気
共鳴スペクトルの分析結果を示すが、これ等は全てDM
SOds中、TMSを内部標準として測定したδ値であ
る。EXAMPLES The compounds of the present invention will be explained in more detail with reference to Examples below. The analysis results of nuclear magnetic resonance spectra of the compounds obtained in each example are shown, but all of these are DM.
This is the δ value measured in SOds using TMS as an internal standard.
実施例 1
3′−アジド−5′−メチル−3′−デオキシチミジン
の製造
3′−アジド−3′−デオキシチミジン2、67g (
10gmol)をテトラヒドロフラン(以下THFと略
す)30或に溶解し、水冷下カリウムtert−ブトキ
シ2.8g (25in+ol)及びヨウ化メチル1.
56g (11mmol)を加え室温に戻し5時間攪
拌した。飽和塩化アンモニウム水溶液を加えて攪拌後、
トルエンで抽出した。Example 1 Production of 3'-azido-5'-methyl-3'-deoxythymidine 2.67 g of 3'-azido-3'-deoxythymidine (
10 gmol) was dissolved in 30 g of tetrahydrofuran (hereinafter abbreviated as THF), and under water cooling, 2.8 g (25 in+ol) of potassium tert-butoxy and 1.0 g of methyl iodide were added.
56 g (11 mmol) was added, the temperature was returned to room temperature, and the mixture was stirred for 5 hours. After adding saturated ammonium chloride aqueous solution and stirring,
Extracted with toluene.
抽出液を水洗し無水硫酸ナトリウムで乾燥した。The extract was washed with water and dried over anhydrous sodium sulfate.
溶媒を留去した後、得られる残留物をシリカゲルカラム
クロマトグラフィーに付し、クロロホルム−アセトン(
80: 20. V/ V) 溶出部ヨリ3′−アジド
ー5′−メチル−3′−デオキシチミジン2.62g(
収率93%)を無色油状物として得た。After distilling off the solvent, the resulting residue was subjected to silica gel column chromatography and chloroform-acetone (
80: 20. V/V) 2.62 g of 3'-azido-5'-methyl-3'-deoxythymidine (
Yield: 93%) was obtained as a colorless oil.
NMRスペクトル
1.79 (3H,s、5−CH5)
2.2C1〜2.58 (2H,m、H2′)3.35
(3H,s、OCH3)
3、 56 (2H,d、 H5’ )3、 89 (
LH,q、 H3’ )4.41 (IH,q、H4”
)
6.11 (IH,t、Hl ’ )
7.55 (IH,s、H6)
11.30 (IH,brs、N、H)実施例 2
3′−アジド−5′−ベンジル−3′−デオキシチミジ
ンの製造
3′−アジド−3′−デオキシチミジン2.67 g
(10mmol)をTHF30−に溶解し、水冷下水素
化ナトリウムO−6g (25mmol)を加え室温に
戻し30分間攪拌した。臭化ベンジル1、88g (1
1mmol)を加え50℃にて4時間加熱攪拌した。放
冷後飽和塩化アンモニウム水溶液を加えて攪拌しトルエ
ンで抽出した。抽出液を水洗し、無水硫酸ナトリウムで
乾燥した。溶媒を留去した後、得られる残留物をシリカ
ゲルカラムクロマトグラフィーに付し、クロロホルム−
アセトン(85: 15. V/V) 溶出部ヨIQ
3’ −7ジドー5′−ベンジル−3′−デオキシチミ
ジン3、 22g (収率90%)を無色油状物として
得た。NMR spectrum 1.79 (3H, s, 5-CH5) 2.2C1-2.58 (2H, m, H2') 3.35
(3H, s, OCH3) 3, 56 (2H, d, H5') 3, 89 (
LH, q, H3') 4.41 (IH, q, H4"
) 6.11 (IH, t, Hl') 7.55 (IH, s, H6) 11.30 (IH, brs, N, H) Example 2 3'-azido-5'-benzyl-3'- Production of deoxythymidine 2.67 g of 3'-azido-3'-deoxythymidine
(10 mmol) was dissolved in THF30-, and under water cooling, 6 g (25 mmol) of sodium hydride was added thereto, the temperature was returned to room temperature, and the mixture was stirred for 30 minutes. Benzyl bromide 1, 88g (1
1 mmol) was added thereto, and the mixture was heated and stirred at 50° C. for 4 hours. After cooling, a saturated aqueous ammonium chloride solution was added, stirred, and extracted with toluene. The extract was washed with water and dried over anhydrous sodium sulfate. After distilling off the solvent, the resulting residue was subjected to silica gel column chromatography, and chloroform-
Acetone (85: 15. V/V) Elution area IQ
3.22 g (yield 90%) of 3'-7 dido 5'-benzyl-3'-deoxythymidine was obtained as a colorless oil.
NMRスペクトル
1、 59 (3H,s、 5 CH3)2.20
〜2.60 (2H,m、H2’ )3.60〜3
.80 (2H,m、H5′ )3.88〜4.10
(IH,s、H3′ )4.38〜4.64 (3
H,m、H”及び6、 13 (LH,t、H”
)7.35 (5H,brs、芳香族H)7.52
(IH,s、H6)
11、 30 (LH,brs、NH)実施例 3
3′ −アジド−5′−p−クロロベンジル−3′ −
デオキシチミジンの製造
3′−アジド−3′−デオキシチミジン2、 67g
(10mmol)をTHF30mQに溶解し、水冷下水
素化ナトリウム0. 6g (25mn+of)を加え
、室温に戻し30分間攪拌した。塩化p−クロロベンジ
ル1.77 g (11mn+ol)及びヨウ化ナトリ
ム0. 15g (1mmol)を加え50℃にて5時
間加熱攪拌した。放冷後飽和塩化アンモニウム水溶液を
加えて攪拌し、トルエンで抽出した。NMR spectrum 1, 59 (3H,s, 5 CH3) 2.20
~2.60 (2H, m, H2')3.60~3
.. 80 (2H, m, H5') 3.88-4.10
(IH, s, H3') 4.38~4.64 (3
H, m, H” and 6, 13 (LH, t, H”
) 7.35 (5H, brs, aromatic H) 7.52
(IH, s, H6) 11, 30 (LH, brs, NH) Example 3 3'-azido-5'-p-chlorobenzyl-3'-
Production of deoxythymidine 3'-azido-3'-deoxythymidine 2, 67g
(10 mmol) was dissolved in 30 mQ of THF, and the solution was cooled with water with 0.0% sodium hydride. 6 g (25 mn+of) was added, the temperature was returned to room temperature, and the mixture was stirred for 30 minutes. p-chlorobenzyl chloride 1.77 g (11 mn+ol) and sodium iodide 0. 15 g (1 mmol) was added, and the mixture was heated and stirred at 50° C. for 5 hours. After cooling, a saturated aqueous ammonium chloride solution was added, stirred, and extracted with toluene.
抽出液を水洗し、無水硫酸ナトリウムで乾燥した。The extract was washed with water and dried over anhydrous sodium sulfate.
溶媒を留去した後、得られる残留物をシリカゲルカラム
クロマトグラフィーに付し、クロロホルム−アセトン(
85: 15. V/V)溶出部より3′−アジド−5
′−p−クロロベンジル−3′−デオキシチミジン3.
37g (収率86%)を無色油状物として得た。After distilling off the solvent, the resulting residue was subjected to silica gel column chromatography and chloroform-acetone (
85: 15. V/V) 3'-Azide-5 from the elution part
'-p-chlorobenzyl-3'-deoxythymidine3.
37 g (86% yield) was obtained as a colorless oil.
NMRスペクトル
1.62 (3H,s、5−CH3)
2.20〜2.60 (2H,m、H2’ )3、 6
0〜3. 82 (2H,m、 Hラ ′ )3.
92〜4.12 (IH,m、H” ’ )4、40〜
4.64 (3H,m、 H”及び6.15 (IH,
t、Hl ’ )
7.40 (IH,brs、芳香族H)7.51 (I
H,s、H6)
11.33 (IH,brs、NH)
実施例 4
3′−アジド−5′−メチル−3′−デオキシ−α、α
、α−トリフルオロチミジンの製造3′ −アジド−3
′−デオキシ−α、α、α−トリフルオロチミジン3.
21 g (10mmol)をTHF 30111Q
に溶解し、水冷下水素化ナトリウム0、 6g (25
mmol)を加え、室温に戻し30分間攪拌した。ヨウ
化メチル1. 56g (llIIImol)を加え室
温にて8時間攪拌した。飽和塩化アンモニウム水溶液を
加えて攪拌後、トルエンで抽出した。抽出液を水洗し、
無水硫酸ナトリウムで乾燥した。溶媒を留去した後、得
られる残留物をシリカゲルカラムクロマトグラフィーに
付し、クロロホルム−アセトン(90: 10.V/V
)溶出部より3′−アジド−5′−メチル−3′−デオ
キシ−α、α、α−トリフルオロチミジン1.21g(
収率36%)を淡黄色油状物として得た。NMR spectrum 1.62 (3H, s, 5-CH3) 2.20-2.60 (2H, m, H2') 3, 6
0-3. 82 (2H, m, Hla')3.
92~4.12 (IH, m, H"') 4,40~
4.64 (3H, m, H” and 6.15 (IH,
t, Hl') 7.40 (IH, brs, aromatic H) 7.51 (I
H, s, H6) 11.33 (IH, brs, NH) Example 4 3'-azido-5'-methyl-3'-deoxy-α, α
, production of α-trifluorothymidine 3′-azide-3
'-deoxy-α,α,α-trifluorothymidine3.
21 g (10 mmol) of THF 30111Q
Dissolved in 0.6 g (25 g) of sodium hydride under water cooling.
mmol) was added thereto, the temperature was returned to room temperature, and the mixture was stirred for 30 minutes. Methyl iodide1. 56 g (III mol) was added and stirred at room temperature for 8 hours. After adding a saturated aqueous ammonium chloride solution and stirring, the mixture was extracted with toluene. Wash the extract with water,
It was dried with anhydrous sodium sulfate. After distilling off the solvent, the resulting residue was subjected to silica gel column chromatography, and chloroform-acetone (90:10.V/V
) 1.21 g of 3'-azido-5'-methyl-3'-deoxy-α,α,α-trifluorothymidine (
Yield: 36%) was obtained as a pale yellow oil.
NMRスペクトル
2.30〜2.62 (2H,m、H2’ )3.33
(3H,s、OCH3)
3.40〜3.80 (2H,m、H5′ )3.9
6〜4. 12 (IH,m、H3′ )4.39
(IH,q、H” )
6.00 (IH,t、H” )
8.44 (LH,d、H6)
11、 90 (IH,brs、NH)実施例 5
3′−アジド−5′−アセチル−3′−デオキシ−α、
α、α−トリフルオロチミジンの製造3′−アジド−3
′−デオキシ−α、α、α−トリフルオロチミジン3.
21 g (10IIImol)をジクロロメタン1
0或に溶解し、トリエチルアミン2. 53g (25
mmol)及び無水酢酸1.53g (15mmol)
を加え室温にて5時間攪拌した。NMR spectrum 2.30-2.62 (2H, m, H2') 3.33
(3H, s, OCH3) 3.40-3.80 (2H, m, H5') 3.9
6-4. 12 (IH, m, H3')4.39
(IH, q, H") 6.00 (IH, t, H") 8.44 (LH, d, H6) 11, 90 (IH, brs, NH) Example 5 3'-azido-5'- Acetyl-3'-deoxy-α,
Production of α, α-trifluorothymidine 3′-azide-3
'-deoxy-α,α,α-trifluorothymidine3.
21 g (10III mol) in dichloromethane 1
0 and triethylamine 2. 53g (25
mmol) and acetic anhydride 1.53 g (15 mmol)
was added and stirred at room temperature for 5 hours.
5%塩酸水溶液10mQを加え攪拌後、ジクロロメタン
で抽出した。抽出液を飽和食塩水で洗浄し、無水硫酸ナ
トリウムで乾燥した。溶媒を留去した後、得られる残留
物をシリカゲルカラムクロマトグラフィーに付し、タロ
ロホルムーアセトン(90: 10. V/V)溶出部
より3′−アジド−5′−アセチル−3′−デオキシ−
α、α、α−トリフルオロチミジン3.34g (収率
92%)を無色油状物として得た。After adding 10 mQ of 5% aqueous hydrochloric acid and stirring, the mixture was extracted with dichloromethane. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. After distilling off the solvent, the resulting residue was subjected to silica gel column chromatography, and 3'-azido-5'-acetyl-3'-deoxy was extracted from the taloloformacetone (90: 10. V/V) eluate. −
3.34 g (yield 92%) of α,α,α-trifluorothymidine was obtained as a colorless oil.
NMRスペクトル
2.05 (3H,s、−CCH3)
2.20〜2.80 (2H,m、H2’ )3.
96〜4.56 (4H,m、H3’ 。NMR spectrum 2.05 (3H, s, -CCH3) 2.20-2.80 (2H, m, H2')3.
96-4.56 (4H, m, H3'.
H4を及びH5′)
6.01 (IH,t、H” )
8.10 (IH,d、H6)
11.94 (IH,brs、NH)
実施例 6
3′ −アジド−5′ −ベンゾイル−3′ −デオキ
シ−α、α、α−トリフルオロチミジンの製3′−アジ
ドー3′−デオキシ−α、α、α−トリフルオロチミジ
ン3. 21 g (10mmol)をピリジン10或
に溶解し、塩化ベンゾイル11.48g (10,5m
n+ol)及び4−ジメチルアミノピリジン0. 12
2g (1mmol)を加え室温にて3時間攪拌した。H4 and H5') 6.01 (IH, t, H'') 8.10 (IH, d, H6) 11.94 (IH, brs, NH) Example 6 3'-azido-5'-benzoyl- Preparation of 3'-deoxy-α,α,α-trifluorothymidine 3.21 g (10 mmol) of 3'-azido 3'-deoxy-α,α,α-trifluorothymidine was dissolved in 10 pyridine and chlorinated. Benzoyl 11.48g (10.5m
n+ol) and 4-dimethylaminopyridine 0. 12
2 g (1 mmol) was added and stirred at room temperature for 3 hours.
溶媒を濃縮後ジクロロメタン及び水を加え、ジクロロメ
タンで抽出した。After concentrating the solvent, dichloromethane and water were added, followed by extraction with dichloromethane.
抽出液を飽和食塩水で洗浄後、無水硫酸す) IJウム
で乾燥した。溶媒を留去した後、得られる残留物をシリ
カゲルカラムクロマトグラフィーに付し、クロロホルム
−アセトン(90: 10. V/V)溶出部より3′
−アジド−5′−ベンゾイル−3′−デオキシ−α、α
、α−トリフルオロチミジン3.74g (収率88%
)を無色油状物として得た。The extract was washed with saturated saline and dried over anhydrous sulfuric acid. After distilling off the solvent, the resulting residue was subjected to silica gel column chromatography, and 3'
-azido-5'-benzoyl-3'-deoxy-α,α
, α-trifluorothymidine 3.74g (yield 88%
) was obtained as a colorless oil.
NMRスペクトル
2.30〜2.90 (2H,m、H2’ )4.18
〜4.42 (IH,m、H3’ )4.40〜4
.80 (3H,m、H”及びH5′ )
6.08 (LH,t、H” )
7、30〜8. 10 (5H,m、芳香族H)8.1
1 (IH,d、H6)
11.80 (IH,brs、NH)(以 上)NMR spectrum 2.30-2.90 (2H, m, H2') 4.18
~4.42 (IH, m, H3')4.40~4
.. 80 (3H, m, H" and H5') 6.08 (LH, t, H") 7, 30-8. 10 (5H, m, aromatic H)8.1
1 (IH, d, H6) 11.80 (IH, brs, NH) (or more)
Claims (1)
ジル基、低級アシル基又はベンゾイル基を示す。)で表
わされる3′−アジド−3′−デオキシチミジン誘導体
。[Claims] [1] General formula ▲ Numerical formulas, chemical formulas, tables, etc. , lower acyl group or benzoyl group).
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP8349687A JPS63250396A (en) | 1987-04-03 | 1987-04-03 | 3'-azido-3'-deoxythymidine derivative |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP8349687A JPS63250396A (en) | 1987-04-03 | 1987-04-03 | 3'-azido-3'-deoxythymidine derivative |
Publications (1)
Publication Number | Publication Date |
---|---|
JPS63250396A true JPS63250396A (en) | 1988-10-18 |
Family
ID=13804087
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP8349687A Pending JPS63250396A (en) | 1987-04-03 | 1987-04-03 | 3'-azido-3'-deoxythymidine derivative |
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Country | Link |
---|---|
JP (1) | JPS63250396A (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10294220B2 (en) * | 2015-02-26 | 2019-05-21 | University Of Kentucky Research Foundation | Compositions and methods for treating retinal degradation |
US10864212B2 (en) | 2013-08-01 | 2020-12-15 | University Of Kentucky Research Foundation | Compositions and methods for treating retinal degradation |
US11219623B2 (en) | 2015-02-26 | 2022-01-11 | University Of Kentucky Research Foundation | Inflammasome inhibition for the treatment of Parkinson's disease, Alzheimer's disease and multiple sclerosis |
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JPS59216899A (en) * | 1983-05-23 | 1984-12-06 | Taiho Yakuhin Kogyo Kk | 2'-deoxy-5-trifluoromethyluridine derivative, its preparation, and antitumor agent containing it |
JPS6061593A (en) * | 1983-09-14 | 1985-04-09 | Taiho Yakuhin Kogyo Kk | 2'-deoxy-5-trifluoromethyluridine derivative and antitumor agent containing the same |
JPS61257925A (en) * | 1985-03-16 | 1986-11-15 | ザ ウエルカム フアウンデ−シヨン リミテツド | Antiviral nucleoside |
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Publication number | Priority date | Publication date | Assignee | Title |
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JPS59216899A (en) * | 1983-05-23 | 1984-12-06 | Taiho Yakuhin Kogyo Kk | 2'-deoxy-5-trifluoromethyluridine derivative, its preparation, and antitumor agent containing it |
JPS6061593A (en) * | 1983-09-14 | 1985-04-09 | Taiho Yakuhin Kogyo Kk | 2'-deoxy-5-trifluoromethyluridine derivative and antitumor agent containing the same |
JPS61257925A (en) * | 1985-03-16 | 1986-11-15 | ザ ウエルカム フアウンデ−シヨン リミテツド | Antiviral nucleoside |
Cited By (9)
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US10864212B2 (en) | 2013-08-01 | 2020-12-15 | University Of Kentucky Research Foundation | Compositions and methods for treating retinal degradation |
US11602535B2 (en) | 2013-08-01 | 2023-03-14 | University Of Kentucky Research Foundation | Compositions and methods for treating retinal degradation |
US10294220B2 (en) * | 2015-02-26 | 2019-05-21 | University Of Kentucky Research Foundation | Compositions and methods for treating retinal degradation |
AU2016225037B2 (en) * | 2015-02-26 | 2021-06-17 | University Of Kentucky Research Foundation | Compositions and methods for treating retinal degradation |
US11219623B2 (en) | 2015-02-26 | 2022-01-11 | University Of Kentucky Research Foundation | Inflammasome inhibition for the treatment of Parkinson's disease, Alzheimer's disease and multiple sclerosis |
US11717520B2 (en) | 2015-02-26 | 2023-08-08 | University Of Kentucky Research Foundation | Compositions and methods for treating retinal degradation |
AU2021232790B2 (en) * | 2015-02-26 | 2023-10-05 | University Of Kentucky Research Foundation | Compositions and Methods for Treating Retinal Degradation |
US11998547B2 (en) | 2015-02-26 | 2024-06-04 | University Of Kentucky Research Foundation | Compositions and methods for treating multiple sclerosis |
US12097201B2 (en) | 2015-02-26 | 2024-09-24 | University Of Kentucky Research Foundation | Compositions and methods for treating retinal degradation |
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