NOVEL COMPOUNDS AND METHODS FOR THERAPY
First Claim
Patent Images
1. A compound having structure (1) whereinY independently is —
- OR3;
an amino acid, amino acid amide or amino acid ester or amino acid thioester linked through an amino group of the amino acid;
R1 is CH3 or H;
R2′
and R2 independently are H, halo, NH2, NH(R10), N(R10)2 or X, but at least one R2 or R2′
is X;
R3 independently is H;
unsubstituted aryl, heterocycle, C1-C12 alkyl, C2-C12 alkenyl or C2-C12 alkynyl;
or aryl, heterocycle, C1-C12 alkyl, C2-C12 alkenyl or C2-C12 alkynyl substituted by C1-C12 alkoxy, halo, carboxyl, carboxylester, hydroxyl, amino, CN, NO2, OH, thiol, thiolester, azido, arylamino, C1-C12 haloalkyl (1-6 halogen atoms), C2-C12 alkenyl or C2-C12 alkynyl;
X is —
OR10,R10 is unsubstituted C1-C15 alkyl, C2-C15 alkenyl, C6-C15 arylalkenyl, C6-C15 arylalkynyl, C2-C15 alkynyl, C1-C6-alkylamino-C1-C6 alkyl, C5-C15 aralkyl, C6-C15 heteroaralkyl, C5-C6 aryl, C2-C6 heterocycloalkyl;
or C2-C15 alkyl, C3-C15 alkenyl, C6-C15 arylalkenyl, C3-C15 alkynyl, C7-C15 arylalkynyl, C1-C6-alkylamino-C1-C6 alkyl, C5-C15 aralkyl, C6-C15 heteroalkyl or C3-C6 heterocycloalkyl wherein 1 to 2 methylene groups in the alkyl moiety not adjacent to the oxygen of —
OR10 have been replaced by —
O—
, —
S—
or N(R3);
or one of the foregoing R10 groups which is substituted with 1 to 3 of halo, R3, CN or N3;
Z is N or CH, provided that the heterocyclic nucleus varies from purine by no more than one Z;
and the therapeutically acceptable salts and/or enriched optical isomers thereof.
1 Assignment
0 Petitions
Accused Products
Abstract
Novel compounds having structure (1)
wherein Z, Y, R1, R2′ and R2 are defined in the specification, are provided for use in the treatment of tumors and the prophylaxis or treatment of viral infections.
-
Citations
23 Claims
-
1. A compound having structure (1)
wherein Y independently is — - OR3;
an amino acid, amino acid amide or amino acid ester or amino acid thioester linked through an amino group of the amino acid;R1 is CH3 or H; R2′
and R2 independently are H, halo, NH2, NH(R10), N(R10)2 or X, but at least one R2 or R2′
is X;R3 independently is H;
unsubstituted aryl, heterocycle, C1-C12 alkyl, C2-C12 alkenyl or C2-C12 alkynyl;
or aryl, heterocycle, C1-C12 alkyl, C2-C12 alkenyl or C2-C12 alkynyl substituted by C1-C12 alkoxy, halo, carboxyl, carboxylester, hydroxyl, amino, CN, NO2, OH, thiol, thiolester, azido, arylamino, C1-C12 haloalkyl (1-6 halogen atoms), C2-C12 alkenyl or C2-C12 alkynyl;X is —
OR10,R10 is unsubstituted C1-C15 alkyl, C2-C15 alkenyl, C6-C15 arylalkenyl, C6-C15 arylalkynyl, C2-C15 alkynyl, C1-C6-alkylamino-C1-C6 alkyl, C5-C15 aralkyl, C6-C15 heteroaralkyl, C5-C6 aryl, C2-C6 heterocycloalkyl; or C2-C15 alkyl, C3-C15 alkenyl, C6-C15 arylalkenyl, C3-C15 alkynyl, C7-C15 arylalkynyl, C1-C6-alkylamino-C1-C6 alkyl, C5-C15 aralkyl, C6-C15 heteroalkyl or C3-C6 heterocycloalkyl wherein 1 to 2 methylene groups in the alkyl moiety not adjacent to the oxygen of —
OR10 have been replaced by —
O—
, —
S—
or N(R3);or one of the foregoing R10 groups which is substituted with 1 to 3 of halo, R3, CN or N3; Z is N or CH, provided that the heterocyclic nucleus varies from purine by no more than one Z; and the therapeutically acceptable salts and/or enriched optical isomers thereof. - View Dependent Claims (14, 15, 16, 17, 19, 21, 22, 23)
- OR3;
-
2. A compound having structure (3):
-
wherein Y independently is —
OR3;
an amino acid, amino acid amide or amino acid ester or amino acie thioester linked through an amino group of the amino acid;R1 is CH3 or H; R2 is —
OR10;R3 independently is H;
unsubstituted aryl, heterocycle, C1-C12 alkyl, C2-C12 alkenyl or C2-C12 alkynyl;
or aryl, heterocycle, C1-C12 alkyl, C2-C12 alkenyl or C2-C12 alkynyl substituted by C1-C12 alkoxy, halo, carboxyl, carboxylester, hydroxyl, amino, CN, NO2, OH, thiol, thiolester, azido, arylamino, C1-C12 haloalkyl (1-6 halogen atoms), C2-C12 alkenyl or C2-C12 alkynyl;
wherein when R3 is unsubstituted C1-C12 alkyl, 1 to 4 methylene groups on R3 not adjacent to the oxygen of —
OR3 is optionally replaced by —
O—
or —
S—
or —
C(O)—
;R10 is unsubstituted C1-C15 alkyl, C2-C15 alkenyl, C6-C15 arylalkenyl, C6-C15 arylalkynyl, C2-C15 alkynyl, C1-C6-alkylamino-C1-C6 alkyl-, C5-C15 aralkyl, C6-C15 heteroaralkyl, C5-C6 aryl, C2-C6 heterocycloalkyl; or R10 is C1-C15 alkyl, C3-C15 alkenyl, C6-C15 arylalkenyl, C3-C15 alkynyl, C6-C15 arylalkynyl, C1-C6-alkylamino-C1-C6 alkyl-, C5-C15 aralkyl, C6-C15 heteroalkyl or C3-C6 heterocycloalkyl wherein 1 to 2 methylene groups in the alkyl moiety not adjacent to the oxygen of —
OR10 have been replaced by —
O—
, —
S—
or N(R3);or one of the foregoing R10 groups is substituted with 1 to 3 of halo, R3, CN or N3; and therapeutically acceptable salts and/or enriched optical isomers thereof.
-
-
3. A compound having structure (3), wherein Y independently is —
- OR3;
an amino acid, amino acid amide or amino acid ester or amino acid thioester linked through an amino group of the amino acid, or a group of the structure (2)provided that at least one Y is a group of structure (2); R1 is CH3 or H; R2′
is —
OR10;R3 independently is H;
unsubstituted aryl, heterocycle, C1-C12 alkyl, C2-C12 alkenyl or C2-C12 alkynyl;
or aryl, heterocycle, C1-C12 alkyl, C2-C12 alkenyl or C2-C12 alkynyl substituted by C1-C12 alkoxy, halo, carboxyl, carboxylester, hydroxyl, amino, CN, NO2, OH, thiol, thiolester, azido, arylamino, C1-C12 haloalkyl (1-6 halogen atoms), C2-C12 alkenyl or C2-C12 alkynyl;
wherein when R3 is unsubstituted C1-C12 alkyl, 1 to 4 methylene groups on R3 not adjacent to the oxygen of —
OR3 is optionally replaced by —
O—
or —
S—
or —
C(O)—
;R10 is unsubstituted C1-C15 alkyl, C2-C15 alkenyl, C6-C15 arylalkenyl, C6-C15 arylalkynyl, C2-C15 alkynyl, C1-C6-alkylamino-C1-C6 alkyl-, C5-C15 aralkyl, C6-C15 heteroaralkyl, C5-C6 aryl, C2-C6 heterocycloalkyl; or R10 is C2-C15 alkyl, C3-C15 alkenyl, C6-C15 arylalkenyl, C3-C15 alkynyl, C6-C15 arylalkynyl, C1-C6-alkylamino-C1-C6 alkyl-, C5-C15 aralkyl, C6-C15 heteroalkyl or C3-C6 heterocycloalkyl wherein 1 to 2 methylene groups in the alkyl moiety not adjacent to the oxygen of —
OR10 have been replaced by —
O—
, —
S—
or N(R3);or one of the foregoing R10 groups is substituted with 1 to 3 of halo, R3, CN or N3; and therapeutically acceptable salts and/or enriched optical isomers thereof.
- OR3;
-
4. A compound having structure (4):
-
wherein each Ra independently is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C6-C10 aryl-C1-C4 alkyl-, wherein Ra and the nitrogen on the —
NH—
optionally form a (5-7) membered ring;each Rb independently is C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C6-C10 aryl-C1-C4 alkyl-; R10 is C1-C8 alkyl, or C2-C8 alkenyl, or C2-C8 alkynyl, wherein C1-C8 alkyl is optionally substituted by one C1-C4 alkoxy group; and
therapeutically acceptable salts and/or enriched optical isomers thereof.- View Dependent Claims (5)
-
-
6. A compound of structure (5):
-
wherein each Rb independently is C1-C8 alkyl, or C2-C8 alkenyl, or C2-C8 alkynyl, or C6-C10 aryl-C1-C4 alkyl-;
R10 is C1-C8 alkyl, or C2-C8 alkenyl, or C2-C8 alkynyl, wherein C1-C8 alkyl is optionally substituted by one C1-C4 alkoxy group; and
therapeutically acceptable salts and/or enriched optical isomers thereof.- View Dependent Claims (7, 18, 20)
-
-
8. A compound having structure (6):
-
wherein Ra is C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C6-C10 aryl-C1-C4 alkyl-, wherein Ra and the nitrogen on the —
NH—
optionally form a (5-7) membered ring;Rb is C1-C8 alkyl, or C2-C8 alkenyl, or C2-C8 alkynyl, or C6-C10 aryl-C1-C4 alkyl-; Rc is C6-C10 aryl that is optionally substituted by one or two substituents selected from halogen, cyano, or C1-C4 alkyl; R10 is C1-C4 alkyl; and
therapeutically acceptable salts and/or enriched optical isomers thereof.- View Dependent Claims (9)
-
-
10. A compound having structure (7):
-
wherein each Rc independently is C1-C4 alkyl that is substituted by one C1-C4 alkyl-O—
C(O)—
O—
group;
R10 is C1-C4 alkyl; and
therapeutically acceptable salts and/or enriched optical isomers thereof.
-
-
11. A compound having structure (8):
-
wherein R2′
is C4-C7 cycloalkyl-NH—
;
each Ra independently is C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, wherein Ra and the nitrogen on the —
NH—
optionally form a (5-7) membered ring;
each Rb independently is C1-C8 alkyl, or C2-C8 alkenyl, or C2-C8 alkynyl, or C6-C10 arylC1-C4 alkyl-; and
therapeutically acceptable salts and/or enriched optical isomers thereof.
-
-
12. A compound having structure (9):
-
wherein R2′
is C4-C7 cycloalkyl-NH—
;
each Ra independently is C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, wherein Ra and the nitrogen on the —
NH—
optionally form a (5-7) membered ring;
Rb is C1-C8 alkyl, or C2-C8 alkenyl, or C2-C8 alkynyl, or C6-C10 aryl-C1-C4 alkyl-;
Rc is Rc is C6-C10 aryl that is optionally substituted by one or two substituents selected from halogen, cyano, or C1-C4 alkyl; and
therapeutically acceptable salts and/or enriched optical isomers thereof.
-
-
13. A compound having structure (10):
-
wherein Rb independently is C1-C8 alkyl, or C2-C8 alkenyl, or C2-C8 alkynyl, or C6-C10 aryl-C1-C4 alkyl-; and
therapeutically acceptable salts and/or enriched optical isomers thereof. Preferably, Rb is C1-C4 alkyl.
-
Specification
-
- Resources
Litigation Campaign Assessment
Thank you for your request. You will receive a custom alert email when the Litigation Campaign Assessment is available.
×
-
Current AssigneeGilead Sciences Inc.
-
Original AssigneeGilead Sciences Inc.
-
InventorsRay, Andrian S., Birkus, Gabriel, Watkins, William J., Tumas, Daniel B.
-
Granted Patent
-
Time in Patent OfficeDays
-
Field of Search
-
US Class Current424/85.200
-
CPC Class CodesA61P 31/20 for DNA virusesA61P 35/00 Antineoplastic agentsA61P 35/02 specific for leukemiaA61P 43/00 Drugs for specific purposes...C07F 9/65616 containing the ring system ...
