(Aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-n- methyl-2-[4-(2-pyridinyl)-phenyl]-acetamide, pharmaceutical formulations, methods of manufacture and uses thereof
The present invention relates to the field of anti-viral active agents, particularly to salts, more particularly to a maleate salt of the free base of N-[5-(aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)-phenyl]-acetamide, to pharmaceutical formulations thereof as well as to methods for the production of these salts. The present invention also relates to the use of theses salts and of respective pharmaceutical formulations thereof in methods of treatment and/or prevention of human herpes simplex virus infections, particulary infections caused by HSV-1 and HSV-2.
1 . A sulfonate salt of the free base of N-[5-(amino-sulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acetamide, wherein said sulfonate salt is benzenesulfonate salt having characteristic XRPD peaks at 7.7, 10.4, 10.7, 12.4, 15.5, 15.9, 17.8, 19.4, 19.8, 20.9, 23.1, 24.9, 25.3, 26.3 and 26.7 2theta as determined by using a compendial method as per “Ph. Eur” and/or “USP” methods.
2 . The sulfonate salt according to claim 1 , wherein said benzenesulfonate has a solubility in water of about 0.229 mg/mL as determined by using a compendial method as per “Ph. Eur” and/or “USP” methods.
3 . A pharmaceutical composition comprising the sulfonate salt as defined in claim 1 , wherein said pharmaceutical composition further comprises at least one pharmaceutically acceptable excipient.
4 . The pharmaceutical composition according to claim 3 , further comprising another pharmaceutically active ingredient selected from the group consisting of anti-inflammatory agents, anti-viral agents, centrally and peripherally acting analgesics, and local anesthetics.
5 . The pharmaceutical composition according to claim 3 , further comprising an ultraviolet radiation blocking agent selected from a group consisting of octisalate, titanium dioxide, zinc oxide, PABA, homosalate, trolamine salicylate, dioxybenzone, sulisobenzone, oxybenzone, avobenzone, ecasmule, meradimate, cinoxate and octocrylene.
6 . A method for treating herpes virus infections comprising:
administering the pharmaceutical composition of claim 3 to a subject in need thereof.
7 . A topical pharmaceutical formulation comprising the sulfonate salt as defined in claim 1 , and wherein said formulation is formulated for administration as a patch, cream, ointment, salve, gel, skin lotion, wax formulation, lipstick, tonic, mousse, foam, film, emulsion, paste, solution, oil, or lipogel.
8 . The topical pharmaceutical formulation according to claim 7 , wherein the said sulfonate salt is present in an amount of 5.0% w/w, and
wherein the topical pharmaceutical formulation is either an ointment, a gel, or a cream.
9 . A method for treating herpes virus infections comprising:
administering the topical pharmaceutical formulation of claim 7 to a subject in need thereof.
10 . The method of claim 9 , wherein the topical pharmaceutical formulation is administered to the skin and/or mucosal surfaces of the subject.
11 . The method of claim 10 , wherein said administration is to the face, mouth, genitals and/or eyes of the subject.
12 . The method of claim 9 , wherein the topical pharmaceutical formulation is administered 5 times a day over a period of 4 days.
13 . A method for treating herpes virus infections comprising:
administering the sulfonate salt of claim 1 to a subject in need thereof.
14 . A sulfonate salt of the free base of N-[5-(amino-sulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acetamide, wherein said sulfonate salt is mono ethane sulfonate having characteristic XRPD peaks at 6.6, 13.2, 19.8, 20.8, 21.2, 21.8, 22.7, 25.4, 25.8, 26.5, 29.4 and 33.3 2theta as determined by using a compendial method as per “Ph. Eur” and/or “USP” methods.
15 . The sulfonate salt according to claim 14 , wherein said mono ethane sulfonate has a solubility in water of about 0.606 mg/mL as determined by using a compendial method as per “Ph. Eur” and/or “USP” methods.
16 . A pharmaceutical composition comprising the sulfonate salt as defined in claim 14 , wherein said pharmaceutical composition further comprises at least one pharmaceutically acceptable excipient.
17 . A method for treating herpes virus infections comprising:
administering the pharmaceutical composition of claim 16 to a subject in need thereof.
18 . The pharmaceutical composition according to claim 16 , further comprising another pharmaceutically active ingredient selected from the group consisting of anti-inflammatory agents, anti-viral agents, centrally and peripherally acting analgesics, and local anesthetics.
19 . A method for treating herpes virus infections comprising:
administering the sulfonate salt of claim 14 to a subject in need thereof.
20 . A sulfonate salt of the free base of N-[5-(amino-sulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acetamide, wherein said sulfonate salt is hemiethane-1,2-disulfonate having characteristic XRPD peaks at 10.6, 11.8, 12.4, 13.2, 16.3, 18.0, 19.1, 19.5, 20.1, 21.3, 21.8, 22.7, 23.7, 24.8 and 25.8 2theta as determined by using a compendial method as per “Ph. Eur” and/or “USP” methods.
21 . The sulfonate salt according to claim 20 , wherein said hemiethane-1,2-disulfonate has a solubility in water of about 0.434 mg/mL as determined by using a compendial method as per “Ph. Eur” and/or “USP” methods.
22 . A pharmaceutical composition comprising the sulfonate salt as defined in claim 20 , wherein said pharmaceutical composition further comprises at least one pharmaceutically acceptable excipient.
23 . A method for treating herpes virus infections comprising:
administering the pharmaceutical composition of claim 22 to a subject in need thereof.
24 . The pharmaceutical composition according to claim 22 , further comprising another pharmaceutically active ingredient selected from the group consisting of anti-inflammatory agents, anti-viral agents, centrally and peripherally acting analgesics, and local anesthetics.
25 . A method for treating herpes virus infections comprising:
administering the sulfonate salt of claim 20 to a subject in need thereof.