Prophylactic or therapeutic agent for porphyria

Inventors: Tsuyoshi Suzuki (Osaka, JP); Masahiro Kondo (Osaka, JP); Fumihiro Takahashi (Osaka, JP); Akihito Ogasawara (Osaka, JP); Kazumi Hyoudou (Osaka, JP)

Assignee: TANABE PHARMA CORPORATION

A61K31/454 A61P7/00

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Quick Facts

Patent No.: US 12667563
App. No.: 18/009,107
Granted: Jun 30, 2026
Kind: B2

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Abstract

A medicament for treatment or prevention of porphyria, comprising 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid or a pharmaceutically acceptable salt or cocrystal thereof as an active ingredient, wherein the dose of the 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid or the pharmaceutically acceptable salt or cocrystal thereof is 50 to 500 mg/day.

Claims (22)

1 . A method for treating porphyria, comprising:

administering to a subject in need thereof at least one of 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid, a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable or cocrystal thereof,

wherein a dose of the 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid or the pharmaceutically acceptable salt or cocrystal thereof is in a range of 50 to 500 mg/day.

2 . The method according to claim 1 , wherein the dose of the 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid or the pharmaceutically acceptable salt or cocrystal thereof is in a range of 100 to 300 mg/day.

3 . The method according to claim 1 , wherein the dose of the 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid or the pharmaceutically acceptable salt or cocrystal thereof is 100 mg/day, 200 mg/day, or 300 mg/day.

4 . The method according to claim 1 , wherein the porphyria is erythropoietic protoporphyria, X-linked porphyria, congenital erythropoietic porphyria, variegate porphyria, acute intermittent porphyria, porphyria cutanea tarda, or hereditary coproporphyria.

5 . The method according to claim 4 , wherein the porphyria is erythropoietic protoporphyria or X-linked porphyria.

6 . The method according to claim 1 , wherein at least one of the 1-{2-[(3 S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid, the pharmaceutically acceptable salt thereof, and the pharmaceutically acceptable cocrystal thereof is a cocrystal of 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid and phosphoric acid.

7 . The method according to claim 1 , wherein the porphyria is at least one of erythropoietic protoporphyria, X-linked porphyria, congenital erythropoietic porphyria, variegate porphyria, acute intermittent porphyria, porphyria cutanea tarda, and hereditary coproporphyria.

8 . The method according to claim 1 , wherein the porphyria is at least one of erythropoietic protoporphyria and X-linked porphyria.

9 . The method according to claim 1 , wherein the dose of the 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid or the pharmaceutically acceptable salt or cocrystal thereof is in a range of 50 to 300 mg/day.

10 . The method according to claim 1 , wherein the dose of the 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid or the pharmaceutically acceptable salt or cocrystal thereof is 50 mg/day, 100 mg/day, 200 mg/day, or 300 mg/day.

11 . The method according to claim 1 , wherein the dose of the 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid or the pharmaceutically acceptable salt or cocrystal thereof is administered intravenously, orally, percutaneously, or topically.

12 . The method according to claim 1 , wherein the dose of the 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid or the pharmaceutically acceptable salt or cocrystal thereof is administered orally.

13 . The method according to claim 1 , wherein the subject in need thereof is a patient with a history of phototoxic reactions from at least one of erythropoietic protoporphyria and X-linked porphyria.

14 . The method according to claim 1 , wherein the dose of the 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid or the pharmaceutically acceptable salt or cocrystal thereof is administered to the subject in need thereof in the range of 50 to 500 mg/day such that a time to prodromal symptoms including burning, tingling, itching and stinging is increased and that a number of sunlight-induced pain events is decreased.

15 . The method according to claim 9 , wherein the dose of the 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid or the pharmaceutically acceptable salt or cocrystal thereof is administered to the subject in need thereof in the range of 50 to 300 mg/day such that a time to prodromal symptoms including burning, tingling, itching and stinging is increased and that a number of sunlight-induced pain events is decreased.

16 . The method according to claim 1 , wherein the pharmaceutically acceptable cocrystal of the 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid is administered to the subject in need thereof in the range of 50 to 500 mg/day.

17 . The method according to claim 1 , wherein the pharmaceutically acceptable salt of the 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid is administered to the subject in need thereof in the range of 50 to 500 mg/day.

18 . The method according to claim 1 , wherein the dose of the 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid or the pharmaceutically acceptable salt or cocrystal thereof administered to the subject in need thereof is 50 mg/day, 100 mg/day, 200 mg/day, or 300 mg/day such that a time to prodromal symptoms including burning, tingling, itching and stinging is increased and that a number of sunlight-induced pain events is decreased.

19 . The method according to claim 13 , wherein the pharmaceutically acceptable cocrystal of the 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid is administered orally to the subject in need thereof in the range of 50 to 300 mg/day such that a time to prodromal symptoms including burning, tingling, itching and stinging is increased and that a number of sunlight-induced pain events is decreased.

20 . The method according to claim 13 , wherein the pharmaceutically acceptable salt of the 1-{2-[(3S,4R)-1-{[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl)pyrrolidin-3-yl]carbonyl}-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid is administered orally to the subject in need thereof in the range of 50 to 300 mg/day such that a time to prodromal symptoms including burning, tingling, itching and stinging is increased and that a number of sunlight-induced pain events is decreased.