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US 7,314,959 B2Granted
Amino thiol compounds and compositions for use in conjunction with cancer therapy
AssigneeWisconsin Alumni Research Foundation
InventorsWilliam E. Fahl, Daniel D. Peebles, Richard C. Copp
Life of this patent
Estimating the term…
Abstract
The invention provides novel polyamine and amino thiol compounds and pharmaceutical compositions for administration in conjunction with cancer chemotherapy or radiation therapy. The compounds are administered locally to provide protection against the adverse side-effects of chemotherapy or radiation therapy, such as alopecia, mucositis and dermatitis. Pharmaceutical preparations comprising one or more chemoprotective polyamines or amino thiols formulated for topical or local delivery to epithelial or mucosal cells are disclosed. Methods of administering the pharmaceutical preparations are also disclosed.
Claims71
A compound of Formula II:
- wherein:
- A is a member selected from the group consisting of:
- J is a member selected from the group consisting of a single bond and —CH(Y)—;
- L is a member selected from the group consisting of —CH2X1, —SH, and —CHX2(X3);
- X1 is a member selected from the group consisting of —SH and —R1—SH;
- X2 and X3 are each independently a member selected from the group consisting of —H, —SH and —R1—SH, provided that at least one of X2 and X3 is other than —H or —SH;
- Y is a member selected from the group consisting of —H, alkyl, and —R2-D;
- D is a member selected from the group consisting of —OH, —SR3, and —NR3R4;
- R3 is a member selected from the group consisting of —H and lower alkyl;
- R4 is a member selected from the group consisting of —H, lower alkyl, and —R5-D;
- each Q is independently a member selected from the group consisting of —H, lower alkyl, and —R6—SR3, provided that when L is —SH, at least one of Q is other than —H;
- and
- each R1, R2, R5 and R6 is independently C1-6 alkylene;
- and,
- or a stereoisomer, pharmaceutically-acceptable salt, monoprotonated acid salt or polyprotonated acid salt thereof.
12 more elements
A pharmaceutical preparation for reducing or preventing hair loss, dermatitis, mucositis, or gastrointestinal distress caused by treatment with a chemotherapeutic agent or radiation therapy comprising:
- a compound of Formula II according to
- wherein:
- A is a member selected from the group consisting of:
- J is a member selected from the group consisting of a single bond and —CH(Y)—;
- L is a member selected from the group consisting of —CH2X1, —SH, and —CHX2(X3);
- X1 is a member selected from the group consisting of —SH and —R1—SH;
- X2 and X3 are each independently a member selected from the group consisting of —H, —SH and —R1—SH, provided that at least one of X2 and X3 is other than —H or —SH;
- Y is a member selected from the group consisting of —H, alkyl, and —R2-D;
- D is a member selected from the group consisting of —OH, —SR3, and —NR3R4;
- R3 is a member selected from the group consisting of —H and lower alkyl;
- R4 is a member selected from the group consisting of —H, lower alkyl, and —R5-D;
- each Q is independently a member selected from the group consisting of —H, lower alkyl, and —R6—SR3, provided that when L is —SH, at least one of Q is other than —H;
- and,
- each R1, R2, R5, and R6 is independently C1-6 alkylene;
- and,
- or a stereoisomer, pharmaceutically-acceptable salt, monoprotonated acid salt or polyprotonated acid salt thereof, and
- a topical delivery vehicle for locally delivering the compound to dermal or mucosal cells being a member selected from the group consisting of skin, scalp, mouth, nasoesophageal, gastrointestinal and urogenital system.
14 more elements
A method for reducing or preventing hair loss, dermatitis, mucositis or gastrointestinal distress in a patient undergoing treatment with a chemotherapeutic agent or radiation therapy, comprising administering to the patient a prophylactically or therapeutically effective amount of a pharmaceutical preparation comprising:
- the compound of Formula II according to
- wherein:
- A is a member selected from the group consisting of:
- J is a member selected from the group consisting of a single bond and —CH(Y)—;
- L is a member selected from the group consisting of —CH2X1, —SH, and —CHX2(X3);
- X1 is a member selected from the group consisting of —SH and —R1—SH;
- X2 and X3 are each independently a member selected from the group consisting of —H, —SH and —R1—SH, provided that at least one of X2 and X3 is other than —H or —SH;
- Y is a member selected from the group consisting of —H, alkyl, and —R2-D;
- D is a member selected from the group consisting of —OH, —SR3, and —NR3R4;
- R3 is a member selected from the group consisting of —H and lower alkyl;
- R4 is a member selected from the group consisting of —H, lower alkyl, and —R5—D;
- each Q is independently a member selected from the group consisting of —H, lower alkyl, and —R6—SR3, provided that when L is —SH, at least one of Q is other than —H;
- and,
- each R1, R2, R5, and R6 is independently C1-6 alkylene;
- and,
- or a stereoisomer, pharmaceutically-acceptable salt, monoprotonated acid salt or polyprotonated acid salt thereof, and
- a topical delivery vehicle for locally delivering the compound to dermal or mucosal cell members being selected from the group consisting of skin, scalp, mouth, nasoesophageal, gastrointestinal and urogenital system.
14 more elements
A method of increasing a patient's tolerance to a chemotherapeutic agent or radiation therapy comprising:
- administering the chemotherapeutic agent or radiation therapy to the patient;
- and
- administering a pharmaceutical preparation comprising:
- a compound of Formula II according to
- wherein:
- A is a member selected from the group consisting of:
- J is a member selected from the group consisting of a single bond and —CH(Y)—;
- L is a member selected from the group consisting of —CH2X1, —SH, and —CHX2(X3);
- X1 is a member selected from the group consisting of —SH and —R1—SH;
- X2 and X3 are each independently a member selected from the group consisting of —H, —SH and —R1—SH, provided that at least one of X2 and X3 other than —H or —SH;
- Y is a member selected from the group consisting of —H, alkyl, and —R2-D;
- D is a member selected from the group consisting of —OH, —SR3, and —NR3R4;
- R3 is a member selected from the group consisting of —H and lower alkyl;
- R4 is a member selected from the group consisting of —H, lower alkyl, and —R5-D;
- each Q is independently a member selected from the group consisting of —H, lower alkyl, and —R6—SR3, provided that when L is —SH, at least one of Q is other than —H;
- and,
- each R1, R2, R5, and R6 is independently C1-6 alkylene;
- and,
- or a stereoisomer, pharmaceutically-acceptable salt, monoprotonated acid salt or polyprotonated acid salt thereof, and
- a topical delivery vehicle for locally delivering the compound to dermal or mucosal cells being a member selected from the group consisting of skin, scalp, mouth, nasoesophageal, gastrointestinal and urogenital system,
- wherein the pharmaceutical preparation is administered one or more times, in an amount and for a time effective, to the patient for reducing or preventing one or more members selected from the group consisting of chemotherapy- or radiation therapy-induced hair loss, dermatitis, mucositis and gastrointestinal distress, thereby increasing the patient's tolerance to the chemotherapeutic agent or radiation therapy.
18 more elements
Dependencies are inferred from the claim text.