Method of resolution and antiviral activity of 1, 3-oxathiolane nucleoside enantiomers

19 Pages·2013·1.96 MB·English

US005892025A
United States Patent [19] [11] Patent Number: 5,892,025
Liotta et al. [45] Date of Patent: Apr. 6, 1999
[54] METHOD OF RESOLUTION AND 5,486,520 1/1996 Belleau et al. .
ANTIVIRAL ACTIVITY OF 1,3 5,521,161 5/1996 Malley et al. .
OXATHIOLANE NUCLEOSIDE 5,532,246 7/1996 Belleau et al. .
ENANTIOMERS 5,538,975 7/1996 Dionne .
5,539,116 7/1996 Liotta et al. .
[75] Inventors: Dennis C. Liotta, McDonough; 5,587,480 12/1996 Belleau et al..
5,618,820 4/1997 Dionne.
Raymond F. Schinazi, Decatur, both of
7,686,617 7/1996 Cheng.
Ga.; Woo-Baeg Choi, North Brunswick,
7,718,806 6/1991 Cheng.
NJ. 7,785,545 10/1991 Cheng.
[73] Assignee: Emory University, Atlanta, Ga. FOREIGN PATENT DOCUMENTS
665187 2/1992 Australia .
[21] Appl. No.: 115,780
630913 9/1992 Australia .
0 206 497 12/1986 European Pat. Off. .
[22] Filed: Jul. 14, 1998
0 217 580 4/1987 European Pat. Off. .
0 285 884 4/1987 European Pat. Off. .
Related US. Application Data
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1995, which is a continuation of Ser. No. 092,248, Jul. 15,
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[51] Int. Cl.6 ....................... .. A61K 31/70; A61K 31/505
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[52] US. Cl. .......................... .. 536/46; 544/317; 544/310; 0 515 144 11/1992 European Pat. Off. .
544/212; 544/276; 544/277; 544/313; 544/229; 0 515 156 11/1992 European Pat. Off. .
549/310 0 515 157 11/1992 European Pat. Off. .
0 526 253 2/1993 European Pat. Off. .
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U.S. Patent 5,892,025
Apr. 6, 1999 Sheet 1 0f 5
NH2
/ F
4L I
o N
F/G. 7
U.S. Patent Apr. 6, 1999 Sheet 2 of5 5,892,025
s
R= alkyi, silyl, acyll 1' ZgggglNG
2. CARBOXYLIC
ANHYDRIDE
H 0 NH2
0 N OJ\N N \
RO-k y *R 0 a JL R0 QR
0 k0 Z0 N’ }O ,
S or S 3),‘,
x = OSiR1R2R3, NHSiR1R2R3
Enzymatic Y = CH3 9 H 1 eTC- R‘ = Acy|
HYdI'OWSiS Z =S|R1R2R3
iR= Acyi)
0 NH
H~NJ3Y N, 2y t - Product obtained
| )j depends on X.
H012o j Oj
NH2 NH2
° W" “*J"
R" /“\o OJ\N Lipase HO OJ‘N
‘<8 kj
o -—-> 0
R" = alkyl, substituted alkyl; X=H, F, alkyl, halogen, etc.
Lipase =pig liver esterase, porcine pancreatic lipase.
Amano IDS-800, subtilisin, etc.
F/G 2
5,892,025
U.S. Patent Apr. 6, 1999 Sheet 3 of5
U P s 8 O O
TIME ELAPSED (h)
F/G. 3
100
80
+ FTC (+)
1
U.S. Patent Apr. 6, 1999 Sheet 4 of5 5,892,025
100 c
80
5 so
‘I
9 _ . . _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __
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