CA2015671C - Derives de phosphonomethoxytetrahydrofuranyl-purine/pyrimidine - Google Patents

Derives de phosphonomethoxytetrahydrofuranyl-purine/pyrimidine Download PDF

Info

Publication number: CA2015671C
Authority: CA; Canada
Prior art keywords: beta; purine; methoxy; thymine; erythrofuranosyl
Prior art date: 1989-05-15
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

CA002015671A

Other languages

English (en)

Other versions

CA2015671A1 (fr

Inventor

Choung U. Kim

John C. Martin

Bing Y. Luh

Peter F. Misco

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.)

Stichting Rega VZW

Institute of Organic Chemistry and Biochemistry CAS

Original Assignee

Stichting Rega VZW

Institute of Organic Chemistry and Biochemistry CAS

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.)

1989-05-15

Filing date

1990-04-27

Publication date

2000-04-25

1990-04-27 Application filed by Stichting Rega VZW, Institute of Organic Chemistry and Biochemistry CAS filed Critical Stichting Rega VZW

1990-04-27 Priority to CA002297294A priority Critical patent/CA2297294C/fr

1990-11-15 Publication of CA2015671A1 publication Critical patent/CA2015671A1/fr

2000-04-25 Application granted granted Critical

2000-04-25 Publication of CA2015671C publication Critical patent/CA2015671C/fr

2010-04-27 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

BTRAURKQNWJCBW-UHFFFAOYSA-N [2-(oxolan-2-yl)-7H-purin-8-yl]oxymethylphosphonic acid Chemical class P(=O)(O)(O)COC1=NC2=NC(=NC=C2N1)C1OCCC1 BTRAURKQNWJCBW-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 112
KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims abstract description 83
230000000840 anti-viral effect Effects 0.000 claims abstract description 25
125000000217 alkyl group Chemical group 0.000 claims abstract description 24
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims abstract description 17
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 17
239000001257 hydrogen Substances 0.000 claims abstract description 16
125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 claims abstract description 13
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 8
-1 tetrahydro-2-furyl-1-substituted pyrimidine Chemical class 0.000 claims description 126
RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 108
UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 88
OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 80
229940113082 thymine Drugs 0.000 claims description 59
229960000643 adenine Drugs 0.000 claims description 56
229930024421 Adenine Natural products 0.000 claims description 52
229940104302 cytosine Drugs 0.000 claims description 45
GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 43
LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims description 40
ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 28
125000004432 carbon atom Chemical group C* 0.000 claims description 24
FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 claims description 24
239000007787 solid Substances 0.000 claims description 22
239000003814 drug Substances 0.000 claims description 20
150000003839 salts Chemical class 0.000 claims description 20
229940075420 xanthine Drugs 0.000 claims description 20
241000700605 Viruses Species 0.000 claims description 19
UHUHBFMZVCOEOV-UHFFFAOYSA-N 1h-imidazo[4,5-c]pyridin-4-amine Chemical compound NC1=NC=CC2=C1N=CN2 UHUHBFMZVCOEOV-UHFFFAOYSA-N 0.000 claims description 16
CRYCZDRIXVHNQB-UHFFFAOYSA-N 2-amino-8-bromo-3,7-dihydropurin-6-one Chemical compound N1C(N)=NC(=O)C2=C1N=C(Br)N2 CRYCZDRIXVHNQB-UHFFFAOYSA-N 0.000 claims description 15
DJGMEMUXTWZGIC-UHFFFAOYSA-N 2-amino-8-methyl-3,7-dihydropurin-6-one Chemical compound N1C(N)=NC(=O)C2=C1N=C(C)N2 DJGMEMUXTWZGIC-UHFFFAOYSA-N 0.000 claims description 15
LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 claims description 15
RHIULBJJKFDJPR-UHFFFAOYSA-N 5-ethyl-1h-pyrimidine-2,4-dione Chemical compound CCC1=CNC(=O)NC1=O RHIULBJJKFDJPR-UHFFFAOYSA-N 0.000 claims description 15
KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical compound IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 claims description 15
JHEKLAXXCHLMNM-UHFFFAOYSA-N 5-propyl-1h-pyrimidine-2,4-dione Chemical compound CCCC1=CNC(=O)NC1=O JHEKLAXXCHLMNM-UHFFFAOYSA-N 0.000 claims description 15
KXBCLNRMQPRVTP-UHFFFAOYSA-N 6-amino-1,5-dihydroimidazo[4,5-c]pyridin-4-one Chemical compound O=C1NC(N)=CC2=C1N=CN2 KXBCLNRMQPRVTP-UHFFFAOYSA-N 0.000 claims description 15
CZJGCEGNCSGRBI-UHFFFAOYSA-N 6-amino-5-ethyl-1h-pyrimidin-2-one Chemical compound CCC1=CNC(=O)N=C1N CZJGCEGNCSGRBI-UHFFFAOYSA-N 0.000 claims description 15
229960003087 tioguanine Drugs 0.000 claims description 15
WYDKPTZGVLTYPG-UHFFFAOYSA-N 2,8-diamino-3,7-dihydropurin-6-one Chemical compound N1C(N)=NC(=O)C2=C1N=C(N)N2 WYDKPTZGVLTYPG-UHFFFAOYSA-N 0.000 claims description 14
YCFWZXAEOXKNHL-UHFFFAOYSA-N 2-amino-8-chloro-3,7-dihydropurin-6-one Chemical compound N1C(N)=NC(=O)C2=C1N=C(Cl)N2 YCFWZXAEOXKNHL-UHFFFAOYSA-N 0.000 claims description 14
TXGWTBFCLADKKR-UHFFFAOYSA-N 2-amino-8-hydrazinyl-3,7-dihydropurin-6-one Chemical compound N1=C(N)NC(=O)C2=C1N=C(NN)N2 TXGWTBFCLADKKR-UHFFFAOYSA-N 0.000 claims description 14
ZFTBZKVVGZNMJR-UHFFFAOYSA-N 5-chlorouracil Chemical compound ClC1=CNC(=O)NC1=O ZFTBZKVVGZNMJR-UHFFFAOYSA-N 0.000 claims description 14
ZRYZBEQILKESAW-UHFFFAOYSA-N 5-ethenyl-1h-pyrimidine-2,4-dione Chemical compound C=CC1=CNC(=O)NC1=O ZRYZBEQILKESAW-UHFFFAOYSA-N 0.000 claims description 14
LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims description 14
CLGFIVUFZRGQRP-UHFFFAOYSA-N 7,8-dihydro-8-oxoguanine Chemical compound O=C1NC(N)=NC2=C1NC(=O)N2 CLGFIVUFZRGQRP-UHFFFAOYSA-N 0.000 claims description 14
229940035893 uracil Drugs 0.000 claims description 14
MWBWWFOAEOYUST-UHFFFAOYSA-N 2-aminopurine Chemical compound NC1=NC=C2N=CNC2=N1 MWBWWFOAEOYUST-UHFFFAOYSA-N 0.000 claims description 13
MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 claims description 13
ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 13
229910052736 halogen Inorganic materials 0.000 claims description 13
150000002367 halogens Chemical class 0.000 claims description 13
UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 claims description 12
RYYIULNRIVUMTQ-UHFFFAOYSA-N 6-chloroguanine Chemical compound NC1=NC(Cl)=C2N=CNC2=N1 RYYIULNRIVUMTQ-UHFFFAOYSA-N 0.000 claims description 10
241001430294 unidentified retrovirus Species 0.000 claims description 10
239000003085 diluting agent Substances 0.000 claims description 9
241001465754 Metazoa Species 0.000 claims description 8
206010028980 Neoplasm Diseases 0.000 claims description 8
125000004122 cyclic group Chemical group 0.000 claims description 8
150000003212 purines Chemical class 0.000 claims description 8
230000000798 anti-retroviral effect Effects 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
150000003230 pyrimidines Chemical class 0.000 claims description 6
150000001768 cations Chemical class 0.000 claims description 5
239000007788 liquid Substances 0.000 claims description 5
SUJXOJITWGTEDJ-UHFFFAOYSA-N [5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxymethylphosphonic acid;sodium Chemical compound [Na].[Na].O=C1NC(=O)C(C)=CN1C1OCC(OCP(O)(O)=O)C1 SUJXOJITWGTEDJ-UHFFFAOYSA-N 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 4
150000004965 peroxy acids Chemical class 0.000 claims description 3
108091034117 Oligonucleotide Proteins 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
125000000547 substituted alkyl group Chemical group 0.000 claims description 2
230000000118 anti-neoplastic effect Effects 0.000 claims 4
229940034982 antineoplastic agent Drugs 0.000 claims 3
238000004519 manufacturing process Methods 0.000 claims 2
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims 1
238000009795 derivation Methods 0.000 claims 1
125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 43
230000000259 anti-tumor effect Effects 0.000 abstract description 9
150000002431 hydrogen Chemical class 0.000 abstract description 4
208000036142 Viral infection Diseases 0.000 abstract description 3
230000009385 viral infection Effects 0.000 abstract description 3
125000002768 hydroxyalkyl group Chemical group 0.000 abstract description 2
125000003342 alkenyl group Chemical group 0.000 abstract 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 abstract 1
150000002118 epoxides Chemical class 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 113
239000000243 solution Substances 0.000 description 83
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 68
238000005160 1H NMR spectroscopy Methods 0.000 description 57
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 51
239000003921 oil Substances 0.000 description 47
239000003480 eluent Substances 0.000 description 44
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 39
101150041968 CDC13 gene Proteins 0.000 description 38
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 35
229910052757 nitrogen Inorganic materials 0.000 description 34
238000004458 analytical method Methods 0.000 description 29
238000003756 stirring Methods 0.000 description 29
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 28
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
239000003039 volatile agent Substances 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 23
239000012071 phase Substances 0.000 description 23
239000000843 powder Substances 0.000 description 23
239000000741 silica gel Substances 0.000 description 21
229910002027 silica gel Inorganic materials 0.000 description 21
239000002904 solvent Substances 0.000 description 21
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 20
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
238000000034 method Methods 0.000 description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
239000012267 brine Substances 0.000 description 15
239000000047 product Substances 0.000 description 13
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 12
239000012230 colorless oil Substances 0.000 description 12
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 12
239000000725 suspension Substances 0.000 description 12
210000004027 cell Anatomy 0.000 description 11
239000000376 reactant Substances 0.000 description 11
229940079593 drug Drugs 0.000 description 10
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241000725303 Human immunodeficiency virus Species 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
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WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
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JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 8
RMLUKZWYIKEASN-UHFFFAOYSA-M sodium;2-amino-9-(2-hydroxyethoxymethyl)purin-6-olate Chemical compound [Na+].O=C1[N-]C(N)=NC2=C1N=CN2COCCO RMLUKZWYIKEASN-UHFFFAOYSA-M 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
241000282414 Homo sapiens Species 0.000 description 7
241000714177 Murine leukemia virus Species 0.000 description 7
241000700584 Simplexvirus Species 0.000 description 7
238000004440 column chromatography Methods 0.000 description 7
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 7
230000008569 process Effects 0.000 description 7
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FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 6
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 6
238000010790 dilution Methods 0.000 description 6
239000012895 dilution Substances 0.000 description 6
238000007912 intraperitoneal administration Methods 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
238000011321 prophylaxis Methods 0.000 description 6
238000010898 silica gel chromatography Methods 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
PAYVFOKLWBTLHT-UHFFFAOYSA-N 9-(diethoxyphosphorylmethoxymethoxymethyl)purin-6-amine Chemical compound N1=CN=C2N(COCOCP(=O)(OCC)OCC)C=NC2=C1N PAYVFOKLWBTLHT-UHFFFAOYSA-N 0.000 description 5
229910017974 NH40H Inorganic materials 0.000 description 5
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
239000002253 acid Substances 0.000 description 5
238000003556 assay Methods 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
201000010099 disease Diseases 0.000 description 5
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238000004108 freeze drying Methods 0.000 description 5
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150000007523 nucleic acids Chemical class 0.000 description 5
102000039446 nucleic acids Human genes 0.000 description 5
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229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 5
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BOGWEPJBZZQGBF-UHFFFAOYSA-N 1-(5-methoxyoxolan-2-yl)-5-methylpyrimidine-2,4-dione Chemical compound O1C(OC)CCC1N1C(=O)NC(=O)C(C)=C1 BOGWEPJBZZQGBF-UHFFFAOYSA-N 0.000 description 4
UNSHCXBDOOUKBV-UHFFFAOYSA-N 1-(diethoxyphosphorylmethoxymethoxymethyl)-5-methylpyrimidine-2,4-dione Chemical compound CCOP(=O)(OCC)COCOCN1C=C(C)C(=O)NC1=O UNSHCXBDOOUKBV-UHFFFAOYSA-N 0.000 description 4
MUXHHUSSEMREJK-UHFFFAOYSA-N 1-[4-(dimethoxyphosphorylmethoxy)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound C1C(OCP(=O)(OC)OC)COC1N1C(=O)NC(=O)C(C)=C1 MUXHHUSSEMREJK-UHFFFAOYSA-N 0.000 description 4
ZADRKLKWSMAWBO-UHFFFAOYSA-N 2-(chloromethoxy)ethylselanylbenzene Chemical compound ClCOCC[Se]C1=CC=CC=C1 ZADRKLKWSMAWBO-UHFFFAOYSA-N 0.000 description 4
QWECSWDTBPYBDX-UHFFFAOYSA-N 4-amino-1-(diethoxyphosphorylmethoxymethoxymethyl)pyrimidin-2-one Chemical compound CCOP(=O)(OCC)COCOCN1C=CC(N)=NC1=O QWECSWDTBPYBDX-UHFFFAOYSA-N 0.000 description 4
HWOLBGMKDMXPCR-UHFFFAOYSA-N 6-chloro-9-(diethoxyphosphorylmethoxymethoxymethyl)purin-2-amine Chemical compound N1=C(N)N=C2N(COCOCP(=O)(OCC)OCC)C=NC2=C1Cl HWOLBGMKDMXPCR-UHFFFAOYSA-N 0.000 description 4
206010001513 AIDS related complex Diseases 0.000 description 4
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238000005481 NMR spectroscopy Methods 0.000 description 4
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OIERWUPLBOKSRB-UHFFFAOYSA-N dimethoxyphosphorylmethanol Chemical compound COP(=O)(CO)OC OIERWUPLBOKSRB-UHFFFAOYSA-N 0.000 description 4
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DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 3
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RBDGIKWWVAASAK-UHFFFAOYSA-N [Na].C1C(P(O)(=O)OC)COC1N1C(=O)NC(=O)C(C)=C1 Chemical compound [Na].C1C(P(O)(=O)OC)COC1N1C(=O)NC(=O)C(C)=C1 RBDGIKWWVAASAK-UHFFFAOYSA-N 0.000 description 1
BMONFMGTQSQJET-UHFFFAOYSA-N [Na].N1C(N)=NC=2N=CNC2C1=O Chemical compound [Na].N1C(N)=NC=2N=CNC2C1=O BMONFMGTQSQJET-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
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229910001413 alkali metal ion Inorganic materials 0.000 description 1
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239000011230 binding agent Substances 0.000 description 1
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239000001506 calcium phosphate Substances 0.000 description 1
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235000011010 calcium phosphates Nutrition 0.000 description 1
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GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 1
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239000012043 crude product Substances 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
HKYGSMOFSFOEIP-UHFFFAOYSA-N dichloro(dichloromethoxy)methane Chemical compound ClC(Cl)OC(Cl)Cl HKYGSMOFSFOEIP-UHFFFAOYSA-N 0.000 description 1
150000005690 diesters Chemical class 0.000 description 1
229960004132 diethyl ether Drugs 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
DLLJVQNYBYOKGS-UHFFFAOYSA-N ethoxyethane;pentane Chemical compound CCCCC.CCOCC DLLJVQNYBYOKGS-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
229960002949 fluorouracil Drugs 0.000 description 1
238000009472 formulation Methods 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
230000005484 gravity Effects 0.000 description 1
244000144993 groups of animals Species 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000000099 in vitro assay Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000011081 inoculation Methods 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
210000003292 kidney cell Anatomy 0.000 description 1
239000008101 lactose Substances 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
150000002736 metal compounds Chemical class 0.000 description 1
229910000000 metal hydroxide Inorganic materials 0.000 description 1
150000004692 metal hydroxides Chemical class 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
HSVRULHNEDWIGE-UHFFFAOYSA-N n-(6-chloro-9-ethenoxypurin-2-yl)acetamide Chemical compound CC(=O)NC1=NC(Cl)=C2N=CN(OC=C)C2=N1 HSVRULHNEDWIGE-UHFFFAOYSA-N 0.000 description 1
239000002773 nucleotide Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
229920002866 paraformaldehyde Polymers 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000000825 pharmaceutical preparation 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
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 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
150000003009 phosphonic acids Chemical class 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
238000002962 plaque-reduction assay 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
238000012809 post-inoculation Methods 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
230000001177 retroviral effect Effects 0.000 description 1
201000005404 rubella Diseases 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
239000002356 single layer Substances 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000008259 solid foam Substances 0.000 description 1
239000012453 solvate Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000000758 substrate Substances 0.000 description 1
238000000967 suction filtration Methods 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
230000004797 therapeutic response Effects 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
238000004448 titration Methods 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
SIOVKLKJSOKLIF-HJWRWDBZSA-N trimethylsilyl (1z)-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(/C)=N\[Si](C)(C)C SIOVKLKJSOKLIF-HJWRWDBZSA-N 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
239000001226 triphosphate Substances 0.000 description 1
235000011178 triphosphate Nutrition 0.000 description 1
UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
229910052721 tungsten Inorganic materials 0.000 description 1
238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
241001529453 unidentified herpesvirus Species 0.000 description 1
241000712461 unidentified influenza virus Species 0.000 description 1
208000007089 vaccinia Diseases 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
210000003501 vero cell Anatomy 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
238000002424 x-ray crystallography Methods 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA002015671A 1989-05-15 1990-04-27 Derives de phosphonomethoxytetrahydrofuranyl-purine/pyrimidine Expired - Lifetime CA2015671C (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA002297294A CA2297294C (fr)	1989-05-15	1990-04-27	Derives de phosphonomethoxymethylpurine/pyrimidine

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date
US35230389A	1989-05-15	1989-05-15
US352,303		1989-05-15
US48165990A	1990-02-22	1990-02-22
US481,659		1990-02-22

Related Child Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002297294A Division CA2297294C (fr)	1989-05-15	1990-04-27	Derives de phosphonomethoxymethylpurine/pyrimidine

Publications (2)

Publication Number	Publication Date
CA2015671A1 CA2015671A1 (fr)	1990-11-15
CA2015671C true CA2015671C (fr)	2000-04-25

Family

ID=26997478

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002015671A Expired - Lifetime CA2015671C (fr)	1989-05-15	1990-04-27	Derives de phosphonomethoxytetrahydrofuranyl-purine/pyrimidine

Country Status (1)

Country	Link
CA (1)	CA2015671C (fr)

1990
- 1990-04-27 CA CA002015671A patent/CA2015671C/fr not_active Expired - Lifetime

Also Published As

Publication number	Publication date
CA2015671A1 (fr)	1990-11-15

Legal Events

Date	Code	Title	Description
1990-07-19	EEER	Examination request
2010-04-27	MKEX	Expiry

Publication	Publication Date	Title
CA2479846C (fr)	2007-07-24	Derives de phosphonomethoxymethylpurine/pyrimidine
US5688778A (en)	1997-11-18	Nucleoside analogs
US5663159A (en)	1997-09-02	Prodrugs of phosphonates
US6653296B1 (en)	2003-11-25	Antiretroviral enantiomeric nucleotide analogs
KR950009195B1 (ko)	1995-08-16	항 비루스성 포스포노메톡시알킬렌 푸린 및 피리미딘 유도체
US5854228A (en)	1998-12-29	Antiviral phosphonomethoxyalkylene purine and pyrimidine derivatives
US5208221A (en)	1993-05-04	Antiviral (phosphonomethoxy) methoxy purine/pyrimidine derivatives
US6818633B2 (en)	2004-11-16	Antiviral compounds and methods for synthesis and therapy
KR0184530B1 (ko)	1999-05-15	항비루스 비고리 포스포노메톡시알킬치환, 알켄일 및 알킨일 퓨린 및 피리미딘 유도체
AU2002315625A1 (en)	2003-05-29	6-2'-(phosphonomethoxy)alkoxy pyrimidine derivatives having antiviral activity
CA2015671C (fr)	2000-04-25	Derives de phosphonomethoxytetrahydrofuranyl-purine/pyrimidine
AU646594B2 (en)	1994-02-24	Nucleoside analogs
HK1063430B (en)	2017-10-13	6-[2-(phosphonomethoxy)alkoxy]pyrimidine derivatives having antiviral activity
HK1010053B (en)	1999-06-11	Prodrugs of phosphonates