Porphyrin-polyamine conjugates for cancer therapy
First Claim
Patent Images
1. A composition comprising a compound according to the formula wherein at least one of J1, J2, J3, J4, J5, J6, J7 and J8 is independently M, where each M is independently selected from the group consisting of
—
- (B-A-B)x-G-(B-A-B)m—
(N(P)—
B-A-B)n—
Kwherein each A is independently selected from the group consisting of;
a nonentity, C1–
C12 alkyl, C2–
C12 alkenyl, C2–
C12 alkynyl, C3–
C12 cycloalkyl, C3–
C8 cycloaryl, C3–
C12 cycloalkenyl, C3–
C12 cycloalkynyl, C1–
C12 alkanol, C3–
C12 cycloalkanol, and C3–
C8 hydroxyaryl;
each B is independently selected from the group consisting of;
a nonentity, C1–
C12 alkyl, C2–
C12 alkenyl, C2–
C12 alkynyl, C3–
C12 cycloalkyl, C3–
C8 cycloaryl, C3–
C12 cycloalkenyl, C3–
C12 cycloalkynyl, C1–
C12 alkanol, C3–
C12 cycloalkanol, and C3–
C8 hydroxyaryl;
and with the proviso that each —
B-A-B—
unit contain at least one carbon atom;
wherein G is independently selected from the group consisting of —
N(P)—
, —
(C═
O)—
N(P)—
, —
N(P)—
(C═
O)—
, and a nonentity;
x is independently 0 or 1;
m is independently 0 or 1;
n is independently an integer from 0 to 20;
each P is independently selected from the group consisting of H and C1–
C12 alkyl;
each K is independently selected from the group consisting of H, C1–
C12 alkyl, C2–
C12 alkenyl, C2–
C12 alkynyl, C3–
C12 cycloalkyl, C3–
C8 cycloaryl, C3–
C12 cycloalkenyl, C3–
C12 cycloalkynyl, C1–
C12 alkanol, C3–
C12 cycloalkanol, and C3–
C8 hydroxyaryl, and Q;
where each Q is independently selected from the group consisting of
where each P is independently selected from the group consisting of H and C1–
C12 alkyl, each D is selected from the group consisting of H and C1–
C32 alkyl, y is an integer from 1 to 8, and z is an integer from 0 to 5, and where the Q moiety is attached to the remainder of the molecule at any C or N atom in the Q moiety (including C atoms in the D or P moieties) by removing a hydrogen atom, a P substituent, or a D substituent of the Q moiety to form an open valence for attachment to the remainder of the molecule;
and where the remaining members or member of J1, J2, J3, J4, J5, J6, J7 and J8 are each independently selected from the group consisting of H, —
B-A-B, —
COOH, —
SO3H, —
B-A-B—
COOH, or —
B-A-B—
SO3H, where each A and each B are independently selected as defined above and with the proviso that each —
B-A-B—
unit has at least one carbon atom;
with the proviso that M excludes moieties of the form
—
K1-G5-L5-(N(P5)-A5)n-K2where K1 is independently selected from the group consisting of C1–
C8 alkyl and where the valence to the left of K1 attaches to the porphyrin ring;
G5 is —
O—
, —
(C═
O)—
, —
C(═
O)—
O—
, —
O—
(C═
O)—
, —
O—
(C═
O)—
O—
, —
O—
(C═
O)—
N—
, —
N—
(C═
O)—
O—
, or a nonentity;
L5 is C1–
C8 alkyl, C3–
C8 cycloalkyl, C3–
C8 cycloaryl, C1–
C8 alkoxy, C1–
C8 alkyl-C3–
C8 cycloalkyl, C1–
C8 alkyl-C3–
C8 cycloaryl, C1–
C8 alkoxy-C3–
C8 cycloaryl, C3–
C8 cycloalkyl-C3–
C8 cycloaryl, C3–
C8 cycloalkyl-C1–
C8 alkyl, C3–
C8 cycloaryl-C1–
C8 alkyl, C3–
C8 cycloaryl-C1–
C8 alkoxy, C3–
C8 cycloaryl-C3–
C8 cycloalkyl, or a nonentity;
each A5 is independently selected from the group consisting of C1–
C8 alkyl, C2–
C8 alkenyl, C2–
C8 alkynyl, C3–
C8 cycloalkyl, C3–
C8 cycloaryl, C3–
C8 cycloalkenyl,and C3–
C8 cycloalkynyl;
P5 is selected from the group consisting of H and C1–
C8 alkyl;
n is an integer from 2 to 8;
and K2 is independently selected from the group consisting of H, C1–
C8 alkyl, C2–
C8 alkenyl, C2–
C8 alkynyl, C3–
C8 cycloalkyl, C3–
C8 cycloaryl, C3–
C8 cycloalkenyl, C3–
C8 cycloalkynyl, C1–
C8 alkanol, C3–
C8 cycloalkanol, and C3–
C8 hydroxyaryl;
wherein at least one K is Q, and where the Q moiety is attached to the remainder of the molecule at any N atom in the Q moiety by removing a P substituent of the Q moiety to form an open valence for attachment to the remainder of the molecule.
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Abstract
Porphyrin-polyamine conjugate compounds are disclosed which have anticancer and antitumor effects. The porphyrin moiety selectively localizes in tumors, while the polyamine moiety serves as a cytotoxic agent. Methods of making and using the porphyrin-polyamine conjugate compounds are also disclosed.
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Citations
16 Claims
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1. A composition comprising a compound according to the formula
wherein at least one of J1, J2, J3, J4, J5, J6, J7 and J8 is independently M, where each M is independently selected from the group consisting of
—- (B-A-B)x-G-(B-A-B)m—
(N(P)—
B-A-B)n—
Kwherein each A is independently selected from the group consisting of;
a nonentity, C1–
C12 alkyl, C2–
C12 alkenyl, C2–
C12 alkynyl, C3–
C12 cycloalkyl, C3–
C8 cycloaryl, C3–
C12 cycloalkenyl, C3–
C12 cycloalkynyl, C1–
C12 alkanol, C3–
C12 cycloalkanol, and C3–
C8 hydroxyaryl;each B is independently selected from the group consisting of;
a nonentity, C1–
C12 alkyl, C2–
C12 alkenyl, C2–
C12 alkynyl, C3–
C12 cycloalkyl, C3–
C8 cycloaryl, C3–
C12 cycloalkenyl, C3–
C12 cycloalkynyl, C1–
C12 alkanol, C3–
C12 cycloalkanol, and C3–
C8 hydroxyaryl;and with the proviso that each —
B-A-B—
unit contain at least one carbon atom;wherein G is independently selected from the group consisting of —
N(P)—
, —
(C═
O)—
N(P)—
, —
N(P)—
(C═
O)—
, and a nonentity;x is independently 0 or 1; m is independently 0 or 1; n is independently an integer from 0 to 20; each P is independently selected from the group consisting of H and C1–
C12 alkyl;each K is independently selected from the group consisting of H, C1–
C12 alkyl, C2–
C12 alkenyl, C2–
C12 alkynyl, C3–
C12 cycloalkyl, C3–
C8 cycloaryl, C3–
C12 cycloalkenyl, C3–
C12 cycloalkynyl, C1–
C12 alkanol, C3–
C12 cycloalkanol, and C3–
C8 hydroxyaryl, and Q;where each Q is independently selected from the group consisting of
where each P is independently selected from the group consisting of H and C1–
C12 alkyl, each D is selected from the group consisting of H and C1–
C32 alkyl, y is an integer from 1 to 8, and z is an integer from 0 to 5, and where the Q moiety is attached to the remainder of the molecule at any C or N atom in the Q moiety (including C atoms in the D or P moieties) by removing a hydrogen atom, a P substituent, or a D substituent of the Q moiety to form an open valence for attachment to the remainder of the molecule;and where the remaining members or member of J1, J2, J3, J4, J5, J6, J7 and J8 are each independently selected from the group consisting of H, —
B-A-B, —
COOH, —
SO3H, —
B-A-B—
COOH, or —
B-A-B—
SO3H, where each A and each B are independently selected as defined above and with the proviso that each —
B-A-B—
unit has at least one carbon atom;with the proviso that M excludes moieties of the form
—
K1-G5-L5-(N(P5)-A5)n-K2where K1 is independently selected from the group consisting of C1–
C8 alkyl and where the valence to the left of K1 attaches to the porphyrin ring;G5 is —
O—
, —
(C═
O)—
, —
C(═
O)—
O—
, —
O—
(C═
O)—
, —
O—
(C═
O)—
O—
, —
O—
(C═
O)—
N—
, —
N—
(C═
O)—
O—
, or a nonentity;L5 is C1–
C8 alkyl, C3–
C8 cycloalkyl, C3–
C8 cycloaryl, C1–
C8 alkoxy, C1–
C8 alkyl-C3–
C8 cycloalkyl, C1–
C8 alkyl-C3–
C8 cycloaryl, C1–
C8 alkoxy-C3–
C8 cycloaryl, C3–
C8 cycloalkyl-C3–
C8 cycloaryl, C3–
C8 cycloalkyl-C1–
C8 alkyl, C3–
C8 cycloaryl-C1–
C8 alkyl, C3–
C8 cycloaryl-C1–
C8 alkoxy, C3–
C8 cycloaryl-C3–
C8 cycloalkyl, or a nonentity;each A5 is independently selected from the group consisting of C1–
C8 alkyl, C2–
C8 alkenyl, C2–
C8 alkynyl, C3–
C8 cycloalkyl, C3–
C8 cycloaryl, C3–
C8 cycloalkenyl,and C3–
C8 cycloalkynyl;P5 is selected from the group consisting of H and C1–
C8 alkyl;n is an integer from 2 to 8; and K2 is independently selected from the group consisting of H, C1–
C8 alkyl, C2–
C8 alkenyl, C2–
C8 alkynyl, C3–
C8 cycloalkyl, C3–
C8 cycloaryl, C3–
C8 cycloalkenyl, C3–
C8 cycloalkynyl, C1–
C8 alkanol, C3–
C8 cycloalkanol, and C3–
C8 hydroxyaryl;wherein at least one K is Q, and where the Q moiety is attached to the remainder of the molecule at any N atom in the Q moiety by removing a P substituent of the Q moiety to form an open valence for attachment to the remainder of the molecule. - View Dependent Claims (7, 8, 10, 11, 14, 16)
and all salts thereof. -
16. The composition of claim 14, further comprising a pharmaceutically acceptable carrier.
- (B-A-B)x-G-(B-A-B)m—
-
2. A composition comprising a compound according to the formula
wherein at least one of J1, J2, J3, J4, J5, J6, J7 and J8 is independently M, where each M is independently selected from the group consisting of
—- (B-A-B)x-G-(B-A-B)m—
(N(P)—
B-A-B)n—
Kwherein each A is independently selected from the group consisting of;
a nonentity, C1–
C12 alkyl, C2–
C12 alkenyl, C2–
C12 alkynyl, C3–
C12 cycloalkyl, C3–
C8 cycloaryl, C3–
C12 cycloalkenyl, C3–
C12 cycloalkynyl, C1–
C12 alkanol, C3–
C12 cycloalkanol, and C3–
C8 hydroxyaryl;each B is independently selected from the group consisting of;
a nonentity, C1–
C12 alkyl, C2–
C12 alkenyl, C2–
C12 alkynyl, C3–
C12 cycloalkyl, C3–
C8 cycloaryl, C3–
C12 cycloalkenyl, C3–
C12 cycloalkynyl, C1–
C12 alkanol, C3–
C12 cycloalkanol, and C3–
C8 hydroxyaryl;and with the proviso that each —
B-A-B—
unit contain at least one carbon atom;wherein G is independently selected from the group consisting of —
N(P)—
, —
(C═
O)—
N(P)—
, —
N(P)—
(C═
O)—
, and a nonentity;x is independently 0 or 1; m is independently 0 or 1; n is independently an integer from 0 to 20; each P is independently selected from the group consisting of H and C1–
C12 alkyl;each K is independently selected from the group consisting of H, C1–
C12 alkyl, C2–
C12 alkenyl, C2–
C12 alkynyl, C3–
C12 cycloalkyl, C3–
C8 cycloaryl, C3–
C12 cycloalkenyl, C3–
C12 cycloalkynyl, C1–
C12 alkanol, C3–
C12 cycloalkanol, and C3–
C8 hydroxyaryl, and Q;where each Q is independently selected from the group consisting of
where each P is independently selected from the group consisting of H and C1–
C12 alkyl, each D is selected from the group consisting of H and C1–
C32 alkyl, y is an integer from 1 to 8, and z is an integer from 0 to 5, and where the Q moiety is attached to the remainder of the molecule at any C or N atom in the Q moiety (including C atoms in the D or P moieties) by removing a hydrogen atom, a P substituent, or a D substituent of the Q moiety to form an open valence for attachment to the remainder of the molecule;and where the remaining members or member of J1, J2, J3, J4, J5, J6, J7 and J8 are each independently selected from the group consisting of H, —
B-A-B, —
COOH, —
SO3H, —
B-A-B—
COOH, or —
B-A-B—
SO3H, where each A and each B are independently selected as defined above and with the proviso that each —
B-A-B—
unit has at least one carbon atom;with the proviso that M excludes moieties of the form
—
K1-G5-L5-(N(P5)-A5)n-K2where K1 is independently selected from the group consisting of C1–
C8 alkyl and where the valence to the left of K1 attaches to the porphyrin ring;G5 is —
O—
, —
(C═
O)—
, —
C(═
O)—
O—
, —
O—
(C═
O)—
, —
O—
(C═
O)—
O—
, —
O—
(C═
O)—
N—
, —
N—
(C═
O)—
O—
, or a nonentity;L5 is C1–
C8 alkyl, C3–
C8 cycloalkyl, C3–
C8 cycloaryl, C1–
C8 alkoxy, C1–
C8 alkyl-C3–
C8 cycloalkyl, C1–
C8 alkyl-C3–
C8 cycloaryl, C1–
C8 alkoxy-C3–
C8 cycloaryl, C3–
C8 cycloalkyl-C3–
C8 cycloaryl, C3–
C8 cycloalkyl-C1–
C8 alkyl, C3–
C8 cycloaryl-C1–
C8 alkyl, C3–
C8 cycloaryl-C1–
C8 alkoxy, C3–
C8 cycloaryl-C3–
C8 cycloalkyl, or a nonentity;each A5 is independently selected from the group consisting of C1–
C8 alkyl, C2–
C8 alkenyl, C2–
C8 alkynyl, C3–
C8 cycloalkyl, C3–
C8 cycloaryl, C3–
C8 cycloalkenyl,and C3–
C8 cycloalkynyl;P5 is selected from the group consisting of H and C1–
C8 alkyl;n is an integer from 2 to 8; and K2 is independently selected from the group consisting of H, C1–
C8 alkyl, C2–
C8 alkenyl, C2–
C8 alkynyl, C3–
C8 cycloalkyl, C3–
C8 cycloaryl, C3–
C8 cycloalkenyl, C3–
C8 cycloalkynyl, C1–
C8 alkanol, C3–
C8 cycloalkanol, and C3–
C8 hydroxyaryl;wherein at least one A substituent comprises a cyclopronyl group. - View Dependent Claims (12, 13, 15)
and all salts thereof. -
15. The composition of claim 13, further comprising a pharmaceutically acceptable carrier.
- (B-A-B)x-G-(B-A-B)m—
-
3. A composition comprising a of to the formula
where J1 and J2 are independently M and each M is independently selected from the group consisting of — - (B-A-B)-G-(B-A-B)-(N(P)—
B-A-B)n—
K;J3, J4, J6 and J8 are independently selected from methyl and ethyl; and J5 and J7 are independently selected from methyl, ethyl, and —
SO3H;wherein at least one B-A-B comprises a cycloalkyl moiety. - View Dependent Claims (4, 5)
- (B-A-B)-G-(B-A-B)-(N(P)—
-
6. A composition comprising a compound according to the formula
wherein at least one of J1, J2, J3, J4, J5, J6, J7 and J8 is independently selected from the group consisting of
—- (B-A-B)x-G-(B-A-B)m—
(N(P)—
B-A-B)n—
Kwherein each A is independently selected from the group consisting of;
a nonentity, C1–
C12 alkyl, C2–
C12 alkenyl, C2–
C12 alkynyl, C3–
C12 cycloalkyl, C3–
C8 cycloaryl, C3–
C12 cycloalkenyl, C3–
C12 cycloalkynyl, C1–
C12 alkanol, C3–
C12 cycloalkanol, and C3–
C8 hydroxyaryl;each B is independently selected from the group consisting of;
a nonentity, C1–
C12 alkyl, C2–
C12 alkenyl, C2–
C12 alkynyl, C3–
C12 cycloalkyl, C3–
C8 cycloaryl, C3–
C12 cycloalkenyl, C3–
C12 cycloalkynyl, C1–
C12 alkanol, C3–
C12 cycloalkanol, and C3–
C8 hydroxyaryl;and with the proviso that each —
B-A-B—
unit contain at least one carbon atom;wherein G is independently selected from the group consisting of —
N(P)—
, —
(C═
O)—
N(P)—
, —
N(P)—
(C═
O)—
, and a nonentity;x is independently 0 or 1; m is independently 0 or 1; n is independently an integer from 0 to 20; each P is independently selected from the group consisting of H and C1–
C12 alkyl;each K is independently selected from the group consisting of H, C1–
C12 alkyl, C2–
C12 alkenyl, C2–
C12 alkynyl, C3–
C12 cycloalkyl, C3–
C8 cycloaryl, C3–
C12 cycloalkenyl, C3–
C12 cycloalkynyl, C1–
C12 alkanol, C3–
C12 cycloalkanol, and C3–
C8 hydroxyaryl, and Q;where each Q is independently selected from the group consisting of
where each P is independently selected from the group consisting of H and C1–
C12 alkyl, each D is selected from the group consisting of H and C1–
C32 alkyl, y is an integer from 1 to 8, and z is an integer from 0 to 5, and where the Q moiety is attached to the remainder of the molecule at any C or N atom in the Q moiety (including C atoms in the D or P moieties) by removing a hydrogen atom, a P substituent, or a D substituent of the Q moiety to form an open valence for attachment to the remainder of the molecule;and where the remaining members or member of J1, J2, J3, J4, J5, J6, J7 and J8 are each independently selected from the group consisting of H, —
B-A-B, —
COOH, —
SO3H, —
B-A-B—
COOH, or —
B-A-B—
SO3H, where each A and each B are independently selected as defined above and with the proviso that each —
B-A-B—
unit has at least one carbon atom wherein each —
K is independently Q;where each Q is independently selected from the group consisting of
wherein only one D moiety is selected from the group consisting of C1–
C32 alkyl and all remaining D moieties are H;
wherein three P groups are selected from the group consisting of —
H and —
CH3;
wherein the fourth P group is absent and the Q moiety is attached to the remainder of the molecule at that valence; and
wherein y is 2, 3,or 4 and z is 0, 1, or 2. - View Dependent Claims (9)
- (B-A-B)x-G-(B-A-B)m—
Specification
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Current AssigneeCellgate, Inc. (Tbg Diagnostics Limited)
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Original AssigneeCellgate, Inc. (Tbg Diagnostics Limited)
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InventorsWang, Yu, Basu, Hirak S., Valasinas, Aldonia L., Blokhin, Andrei V., Sarkar, Aparajita, Reddy, Venodhar K., Frydman, Benjamin, Marton, Laurence J., Bhattacharya, Subhra
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Primary Examiner(s)Wilson, James O.
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Assistant Examiner(s)Fedowitz, Matthew L.
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Application NumberUS10/606,016Publication NumberTime in Patent Office1,022 DaysField of Search540/145, 534/15, 514/185, 514/410, 424/9.1US Class Current514/410CPC Class CodesA61P 35/00 Antineoplastic agentsC07D 487/22 in which the condensed syst...
