Claims
- 1. A compound of the formula I
- 2. The compound of claim 1 of the formula Ia
- 3. The compound of claim 2 of the formula IIb
- 4. The compound of claim 1 of the formula Ib
- 5. The compound of claim 4 of the formula IIa
- 6. The compound of claim 5 wherein
n and n1 are 1; R1 is H, methyl, phenyl or benzyl; R2 is H; R3 is H, —CH3, —CH(CH3)2, —CH2—CH(CH3)2, —CHCH3—CH2—CH3, —CH2—C6H5, —CH2CH2—S—CH3, —CH2OH, —CH(OH)—CH3, —CH2—SH, —CH2—C6H4OH, —CH2-CO—NH2, —CH2—CH2—CO—NH2, —CH2—COOH, —CH2—CH2—COOH, —(CH2)4—NH2, —(CH2)3—NH—C(NH2)—NH2, 1-guanidinoprop-3-yl, benzyl, 4-hydroxybenzyl, imidazol-4-yl, indol-3-yl, methoxyphenyl or ethoxyphenyl; and R4 is methyl, ethyl, propyl, isopropyl, butyl, t-butyl, phenyl, benzyl, 1-pyridyl, 3-pyridyl, 1-pyrimidinyl, pivaloyloxymethyl, N-ethylmorpholino, N-2-propylmorpholino, methoxyethyl, 4-N-methylpiperidyl, 3-N-methylpiperidyl, 2-, 3-, and 4-N,N-dimethylaminophenyl and 2-, 3-, and 4-N,N-diethylaminophenyl or 1-ethylpiperazinyl.
- 7. The compound of claim 6 wherein B is cytosin-1-yl, 6-azacytosin-1-yl, adenin-9-yl, guanin-9-yl or 2,6-diaminopurin-9-yl, and X1 is O.
- 8. The compound of claim 1 of the formula Id
- 9. The compound of claim 8 wherein L1 is of the formula III
- 10. The compound of claim 9 wherein
n and n1 are 1; R is N-ethylmorpholino, pivaloyloxymethyl, phenyl, benzyl, isopropyl, t-butyl, ethyl, isopropyl, butyl, adamantoyloxymethyl, 3-methoxyphenyl, 2-carboethoxyphenyl, 4-fluorophenyl, 2,4-difluorophenyl, 3,5-dimethoxyphenyl, 2,4-dichlorophenyl, 2-ethoxyphenyl, 3-dimethylaminophenyl, 4-trifluoromethylbenzyl, 2-ethylsalicyl, —O—CH2—O—C(O)—C10H16, —C6H4—CH2—N(CH3)2, —CH2—CH2F, —CH2—CH2Cl, —CH2—CF3, —CH2—CCl3, R5, NHR6 or N(R6)2 wherein,
R5 is CH2C(O)N(R6)2, CH2C(O)OR6, CH2OC(O)R6, CH(R6)OC(O)R6, CH2C(R6)2CH2OH, or CH2OR6, and R6 is C1-C20 alkyl which is unsubstituted or substituted by substituents independently selected from the group consisting of OH, O, N and halogen (1 to 5 halogen atoms), C6-C20 aryl which is unsubstituted or substituted by substituents independently selected from the group consisting of OH, O, N and halogen (1 to 5 halogen atoms) or C7-C20 aryl-alkyl which is unsubstituted or substituted by substituents independently selected from the group consisting of OH, O, N and halogen (1 to 5 halogen atoms); R1 is H, methyl, ethyl, isopropyl, phenyl or benzyl; R2 is H; R3 is H, —CH3, —CH(CH3)2, —CH2—CH(CH3)2, —CHCH3—CH2—CH3, —CH2—C6H5, —CH2CH2—S—CH3, —CH2OH, —CH(OH)—CH3, —CH2—SH, —CH2—C6H4OH, —CH2-CO—NH2, —CH2—CH2—CO—NH2, —CH2—COOH, —CH2—CH2—COOH, —(CH2)4—NH2, —(CH2)3—NH—C(NH2)—NH2, 1-guanidinoprop-3-yl, benzyl, 4-hydroxybenzyl, imidazol-4-yl, indol-3-yl, methoxyphenyl or ethoxyphenyl; and R4 is methyl, ethyl, propyl, isopropyl, butyl, t-butyl, phenyl, benzyl, 1-pyridyl, 3-pyridyl, 1-pyrimidinyl, pivaloyloxymethyl, N-ethylmorpholino, N-2-propylmorpholino, methoxyethyl, 4-N-methylpiperidyl, 3-N-methylpiperidyl, 2-, 3-, and 4-N,N-dimethylaminophenyl and 2-, 3-, and 4-N,N-diethylaminophenyl or 1-ethylpiperazinyl.
- 11. The compound of claim 10 wherein Z is —CHR7—R11—(CH2)m1—C(R8)((CH2)m2(R9))—(CH2)m3—R10—(CH2)m4—,
- 12. The compound of claim 11 wherein
Z is —CH2—O—CH2—CH2—, —CH2—O—CH2—CH(CH2OH)—, —CH2—O—CH2—CH(CH2F)—, —CH2—O—CH2—CH(CH3)—, —CH2—O—CH2—CH(CH═CH2)— or —CH2—O—CH2—CH(CH2N3)—, or is of formula IV or V 60wherein R25 and R29 are O; R26 is CH; R27 and R28 are H; and B is adenin-9-yl, 1-deazaadenin-9-yl, 3-deazaadenin-9-yl, 7-deaza-8-azaadenin-9-yl, 8-azaadenin-9-yl, guanin-9-yl, 2, 6-diaminopurin-9-yl, 2-aminopurin-9-yl, thymin-1-yl, cytosin-1-yl, 5-fluorocytosin-1-yl, 6-azacytosin-1-yl, 5-methylcytosin-1-yl, 5-bromovinyluracil-1-yl, 5-fluorouracil-1-yl or 5-trifluoromethyluracil-1-yl.
- 13. The compound of claim 1 of the formula Ic
- 14. The compound of claim 13 of the formula IIc
- 15. A compound of the formula (OR31)(OR31)P(O)-Z1-B or (OR)(OR31)P(O)-Z1-B, wherein;
B is a base; Z1 is selected from the group consisting of —CH2—O—CH2—CH2—, —CH2—O—C#H(CH2OH)—CH2—, —CH2—O—C#H(CH3)—CH2—, —CH2—O—C#H(CH2F)—CH2—, —CH2—O—C#H(CH═CH2)—CH2— and —CH2—O—C#H(CH2N3)—CH2—; R is H,
C3-C24 1-acyloxy-1-alkyl, C6-C24 1-acyloxy-1-aryl-1-alkyl, C3-C24 1-acyloxy-2-alkoxy-1-alkyl, C3-C24 1-acyloxy-2-halo-1-alkyl, C1-C20 alkyl which is unsubstituted or substituted by substituents independently selected from the group consisting of OH, O, N and halogen (F, Cl, Br, I), C3-C20 aryl which is unsubstituted or substituted by substituents independently selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, cyano, nitro, OH, O, N and halogen, or C4-C20 aryl-alkyl which is unsubstituted or substituted in the aryl moiety by substituents independently selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, cyano, nitro, OH, O, N and halogen; R31 is C3-C6 aryl substituted by 3 to 5 halogen atoms or 1 to 2 atoms or groups independently selected from the group consisting of halogen, C1-C12 alkoxy, cyano, nitro, hydroxy, C1-C12 haloalkyl, C1-C12 alkyl, C2-C12 alkenyl or C2-C12 alkynyl, or C1-C4 alkylene-C3-C6 aryl substituted in the aryl moiety by 3 to 5 halogen atoms or 1 to 2 atoms or groups independently selected from the group consisting of halogen, C1-C12 alkoxy, cyano, nitro, hydroxy, C1-C12 haloalkyl, C1-C12 alkyl, C2-C12 alkenyl or C2-C12 alkynyl, provided that when Z1 is —CH2—O—CH2—CH2— and B is adenin-9-yl, both R31 are not 4-nitrobenzyl or 4-trifluoromethyl-benzyl.
- 16. The compound of claim 15 wherein R31 is 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-ethoxy-5-hydroxyphenyl, 2-ethoxy-4-hydroxyphenyl 3,5-dimethoxyphenyl, 2,4-difluorophenyl, 2-(haloalkyl)-phenyl, 3-(haloalkyl)phenyl, 4-(haloalkyl)-phenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2-ethoxyphenyl, 2-carboethoxyphenyl, 3-carboethoxyphenyl, 4-carboethoxyphenyl, or 2-haloalkylbenzyl, 3-haloalkylbenzyl or 4-haloalkylbenzyl.
- 17. The compound of claim 15 wherein B is cytosin-1-yl, 6-azacytosin-1-yl, 5-fluorocytosin-1-yl, adenin-9-yl, guanin-9-yl or 2, 6-diaminopurin-9-yl.
- 18. A compound of the formula
- 19. The compound of claim 18 wherein R31 is 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-ethoxy-5-hydroxyphenyl, 2-ethoxy-4-hydroxyphenyl 3,5-dimethoxyphenyl, 2,4-difluorophenyl, 2-(haloalkyl)-phenyl, 3-(haloalkyl)phenyl, 4-(haloalkyl)-phenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2-ethoxyphenyl, 2-carboethoxyphenyl, 3-carboethoxyphenyl, 4-carboethoxyphenyl, or 2-haloalkylbenzyl, 3-haloalkylbenzyl or 4-haloalkylbenzyl.
- 20. The compound of claim 18 wherein B is cytosin-1-yl, 6-azacytosin-1-yl, 5-fluorocytosin-1-yl, adenin-9-yl, guanin-9-yl or 2,6-diaminopurin-9-yl.
- 21. A compound of the formula (OR35)(OR35)P(O)-Z-B, wherein;
B is a base; R35 is independently H,
C3-C24 1-acyloxy-1-alkyl, C6-C24 1-acyloxy-1-aryl-1-alkyl, C3-C24 1-acyloxy-2-alkoxy-1-alkyl, C3-C24 1-acyloxy-2-halo-1-alkyl, C1-C20 alkyl which is unsubstituted or substituted by substituents independently selected from the group consisting of OH, O, N and halogen (F, Cl, Br, I), C3-C20 aryl which is unsubstituted or substituted by substituents independently selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl (1 to 3 halogen atoms), cyano, nitro, OH, O, N and halogen, C4-C20 aryl-alkyl which is unsubstituted or substituted in the aryl moiety by substituents independently selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl (1 to 3 halogen atoms), cyano, nitro, OH, O, N and halogen, C3-C6 aryl substituted by 3 to 5 halogen atoms or 1 to 2 atoms or groups independently selected from the group consisting of halogen, C1-C12 alkoxy, cyano, nitro, hydroxy, C1-C12 haloalkyl, C1-C12 alkyl, C2-C12 alkenyl or C2-C12 alkynyl, or C1-C4 alkylene-C3-C6 aryl substituted in the aryl moiety by 3 to 5 halogen atoms or 1 to 2 atoms or groups independently selected from the group consisting of halogen, C1-C12 alkoxy, cyano, nitro, hydroxy, C1-C12 haloalkyl, C1-C12 alkyl, C2-C12 alkenyl or C2-C12 alkynyl; Z-B is selected from the group consisting of 65wherein
the carbon atom designated # is in the R, S or RS configuration, R25 is CH2, CHF or O; R26 is CH or S, provided that when R25 is CH, R26 is not S; R27 is H, OH, halogen, N3, C1-C4 alkyl, C1-C4 alkoxy or when, R26 is S, R27 is absent; R28 is H, OH, halogen, N3, C1-C4 alkyl or C1-C4 alkoxy; R29 is O, S, CH2, CHF or CF2; R33 is H, OH, TBSO, halogen, cyano, CH2N3, C1-C4 alkyl, C1-C4 alkoxy, CH2OH or azido; and R34 is H, CH2CN or CF3, with the proviso that, for structure XXX, when R25 is O or CH2 and R29 CH2 or O, R35 is not H or C1-C6 alkyl.
- 22. The compound of claim 21 wherein R35 is independently phenyl, benzyl, adamantoyl oxymethyl, pivaloyloxymethyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-ethoxy-5-hydroxyphenyl, 2-ethoxy-4-hydroxyphenyl 3,5-dimethoxyphenyl, 2,4-difluorophenyl, 2-(haloalkyl)-phenyl, 3-(haloalkyl)phenyl, 4-(haloalkyl)-phenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2-ethoxyphenyl, 2-carboethoxyphenyl, 3-carboethoxyphenyl, 4-carboethoxyphenyl, or 2-haloalkylbenzyl, 3-haloalkylbenzyl or 4-haloalkylbenzyl.
- 23. The compound of claim 21 wherein B is cytosin-1-yl, 6-azacytosin-1-yl, 5-fluorocytosin-1-yl, thymin-1-yl, adenin-9-yl, guanin-9-yl or 2,6-diaminopurin-9-yl.
- 24. The compound of claim 1 where L1 or L2 is an immunogenic peptide or protein.
- 25. An antibody capable of binding specifically to a compound of claim 24.
- 26. A compound of formula I, wherein the compound is labeled with a detectable moiety selected from the group of an enzyme, radioisotope, stable free radical, fluorophor, and a chemiluminescent group.
CROSS REFERENCED TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. Ser. No. 10/778,856, filed Feb. 13, 2004, pending, which is a continuation of U.S. Ser. No. 09/801,164, filed Mar. 7, 2001, now abandoned, which is a continuation of U.S. Ser. No. 09/247,497, filed Feb. 10, 1999, now U.S. Pat. No. 6,225,460, which is a continuation of U.S. Ser. No. 09/071,420, filed May 1, 1998, now abandoned, which is a divisional application of Ser. No. 08/617,849, filed May 6, 1996, now U.S. Pat. No. 5,798,340, which is a continuation of PCT/US94/10539, filed Sep. 16, 1994, which is a continuation-in-part application of U.S. Ser. No. 08/193,341, filed Feb. 8, 1994, now abandoned, which is a continuation-in-part of U.S. Ser. No. 08/123,483, filed Sep. 17, 1993, now U.S. Pat. No. 5,656,745.
Divisions (1)
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09071420 |
May 1998 |
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Continuations (5)
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Continuation in Parts (2)
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Patent Application
20040242465
