CA1278517C - Composition antivirale - Google Patents

Composition antivirale

Info

Publication number: CA1278517C
Authority: CA; Canada
Prior art keywords: compound; formula; give; solvent; acid
Prior art date: 1987-02-05
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.): Expired - Lifetime

Application number

CA000531191A

Other languages

English (en)

Inventor

Yoshio Taniyama

Naoki Yamamoto

Takumi Hamana

Ryuji Marumoto

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Takeda Pharmaceutical Co Ltd

Original Assignee

Takeda Chemical Industries Ltd

Priority date (The priority date 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 date listed.)

1987-02-05

Filing date

1987-03-05

Publication date

1991-01-02

1987-02-05 Priority claimed from JP62025074A external-priority patent/JPS6310787A/ja

1987-03-05 Application filed by Takeda Chemical Industries Ltd filed Critical Takeda Chemical Industries Ltd

1991-01-02 Application granted granted Critical

1991-01-02 Publication of CA1278517C publication Critical patent/CA1278517C/fr

2008-01-02 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

239000000203 mixture Substances 0.000 title claims description 31
230000000840 anti-viral effect Effects 0.000 title claims description 6
150000001875 compounds Chemical class 0.000 claims abstract description 67
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 14
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims abstract description 11
150000003839 salts Chemical class 0.000 claims abstract description 5
FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 claims description 10
UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 claims description 5
PMPFSQREEWMOPZ-RQJHMYQMSA-N 2-amino-9-[(1s,3r)-3-(hydroxymethyl)cyclopentyl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@H]1CC[C@@H](CO)C1 PMPFSQREEWMOPZ-RQJHMYQMSA-N 0.000 claims description 3
241000725303 Human immunodeficiency virus Species 0.000 claims description 2
230000002401 inhibitory effect Effects 0.000 claims 1
239000003443 antiviral agent Substances 0.000 abstract description 5
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
239000000243 solution Substances 0.000 description 27
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
229910001868 water Inorganic materials 0.000 description 25
239000002904 solvent Substances 0.000 description 23
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
210000004027 cell Anatomy 0.000 description 15
UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 13
238000000034 method Methods 0.000 description 13
239000000047 product Substances 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
238000003786 synthesis reaction Methods 0.000 description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
230000015572 biosynthetic process Effects 0.000 description 11
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
-1 alkoxy cyclic ethers Chemical class 0.000 description 10
239000000843 powder Substances 0.000 description 10
238000010898 silica gel chromatography Methods 0.000 description 10
239000000126 substance Substances 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
241000700605 Viruses Species 0.000 description 9
125000006239 protecting group Chemical group 0.000 description 9
125000004432 carbon atom Chemical group C* 0.000 description 8
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
239000000872 buffer Substances 0.000 description 7
238000000921 elemental analysis Methods 0.000 description 7
238000009472 formulation Methods 0.000 description 7
238000010992 reflux Methods 0.000 description 7
239000006188 syrup Substances 0.000 description 7
235000020357 syrup Nutrition 0.000 description 7
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
239000002253 acid Substances 0.000 description 6
238000010438 heat treatment Methods 0.000 description 6
101150041968 CDC13 gene Proteins 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
235000011054 acetic acid Nutrition 0.000 description 5
239000013078 crystal Substances 0.000 description 5
239000001257 hydrogen Substances 0.000 description 5
229910052739 hydrogen Inorganic materials 0.000 description 5
AFQIYTIJXGTIEY-UHFFFAOYSA-N hydrogen carbonate;triethylazanium Chemical compound OC(O)=O.CCN(CC)CC AFQIYTIJXGTIEY-UHFFFAOYSA-N 0.000 description 5
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
239000002777 nucleoside Substances 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
239000003826 tablet Substances 0.000 description 5
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
125000000848 adenin-9-yl group Chemical group [H]N([H])C1=C2N=C([H])N(*)C2=NC([H])=N1 0.000 description 4
125000003277 amino group Chemical group 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
239000007788 liquid Substances 0.000 description 4
238000000746 purification Methods 0.000 description 4
239000002212 purine nucleoside Substances 0.000 description 4
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 3
MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
238000010533 azeotropic distillation Methods 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 3
239000008187 granular material Substances 0.000 description 3
150000002431 hydrogen Chemical group 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
150000007523 nucleic acids Chemical class 0.000 description 3
108020004707 nucleic acids Proteins 0.000 description 3
102000039446 nucleic acids Human genes 0.000 description 3
150000003833 nucleoside derivatives Chemical class 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
238000006722 reduction reaction Methods 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 3
VWCUMTCXBIRRSG-UHFFFAOYSA-N 1-[chloro(diphenyl)methyl]-2-methoxybenzene Chemical compound COC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 VWCUMTCXBIRRSG-UHFFFAOYSA-N 0.000 description 2
125000002103 4,4'-dimethoxytriphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)(C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H])C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 2
PEHVGBZKEYRQSX-UHFFFAOYSA-N 7-deaza-adenine Chemical compound NC1=NC=NC2=C1C=CN2 PEHVGBZKEYRQSX-UHFFFAOYSA-N 0.000 description 2
LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
241000220479 Acacia Species 0.000 description 2
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GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
241000543381 Cliftonia monophylla Species 0.000 description 2
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
241000283073 Equus caballus Species 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
229930010555 Inosine Natural products 0.000 description 2
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235000010643 Leucaena leucocephala Nutrition 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
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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 2
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150000007933 aliphatic carboxylic acids Chemical class 0.000 description 2
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HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
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Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000531191A 1987-02-05 1987-03-05 Composition antivirale Expired - Lifetime CA1278517C (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
JP25074/1987		1987-02-05
JP62025074A JPS6310787A (ja)	1986-03-06	1987-02-05	ヌクレオシド類縁体、その製造法および抗ウイルス剤

Publications (1)

Publication Number	Publication Date
CA1278517C true CA1278517C (fr)	1991-01-02

Family

ID=12155777

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000531191A Expired - Lifetime CA1278517C (fr)	1987-02-05	1987-03-05	Composition antivirale

Country Status (1)

Country	Link
CA (1)	CA1278517C (fr)

1987
- 1987-03-05 CA CA000531191A patent/CA1278517C/fr not_active Expired - Lifetime

Legal Events

Date	Code	Title	Description
1993-07-03	MKLA	Lapsed

Publication	Publication Date	Title
AU596400B2 (en)	1990-05-03	Carbocyclic purine nucleosides, their production and use
AP160A (en)	1991-11-18	Therapeutic acyclic nucleosides.
Verheggen et al.	1995	Synthesis, biological evaluation, and structure analysis of a series of new 1, 5-anhydrohexitol nucleosides
US4957924A (en)	1990-09-18	Therapeutic valine esters of acyclovir and pharmaceutically acceptable salts thereof
EP0199451B1 (fr)	1996-03-06	Nucléosides thérapeutiques
EP0375329B1 (fr)	1995-05-31	Dérivés antiviraux de pyrimidine et de purine, leur procédé de préparation et compositions pharmaceutiques les contenant
US5079235A (en)	1992-01-07	Antiviral compounds
DK167377B1 (da)	1993-10-25	3'-azidopyrimidinnucleosider eller farmaceutisk acceptable salte eller estere deraf til anvendelse ved behandling af eller profylakse for en human retrovirusinfektion
JPH08501071A (ja)	1996-02-06	１，５−アンヒドロヘキシトールヌクレオシド類似体および該類似体の医薬としての使用
EP0158847B1 (fr)	1988-04-20	Dérivés de purine antiviraux
EP0316017B1 (fr)	1994-01-19	2',3'-Didéoxy-2'-fluoronucléosides
JPS6310787A (ja)	1988-01-18	ヌクレオシド類縁体、その製造法および抗ウイルス剤
AU637831B2 (en)	1993-06-10	Therapeutic necleosides
EP0285432A2 (fr)	1988-10-05	Nucléosides thérapeutiques
EP0219838A2 (fr)	1987-04-29	Nucléosides de purine carbocycliques, leur préparation et leur utilisation
EP0366385B1 (fr)	1993-06-09	Dérivés de guanine ayant une activité anti-virale et leurs sels pharmaceutiquement acceptables
JPH07502740A (ja)	1995-03-23	治療用ヌクレオシド
JP3146423B2 (ja)	2001-03-19	置換プリン
NO880606L (no)	1988-08-15	Nukleotidanaloger og fremgangsmaate for deres fremstilling.
US5703224A (en)	1997-12-30	Antiviral c-nucleoside derivatives
Doboszewski et al.	1995	Synthesis of β configured 2′, 3′-unsaturated pentopyranosyl nucleosides
US5126347A (en)	1992-06-30	Isomeric dideoxynuclesides
KR0142110B1 (ko)	1998-07-01	2', 3'-디데옥시-2', 3'-디데히드로누클레오시드의 제조방법
HU196406B (en)	1988-11-28	Process for production of derivatives of carbocyclic purin nucleorides and medical preparatives containing them
Hirota et al.	1992	Synthesis of Thymidine Derivatives 3′-Modified with a Polar Three-Atom Group as Potential Anti-HIV-1 Agents