SG11201809652PA - Treatment of skin lesions - Google Patents

Abstract

INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property 111111101111 0 DOI 010111110101111 0 111 Oil Mil 11111001101111111110 lil Oil lil Organization International Bureau (10) International Publication Number (43) International Publication Date ......0\"\"1 WO 2017/198347 Al 23 November 2017 (23.11.2017) WIPO I PCT (51) International Patent Classification: trasse 49b, 8102 Oberengstringen (CH). STUETZ, Anton; A61K 31/00 (2006.01) A61K 31/5386 (2006.01) Teichweg 4, 4813 Altmiinster (CH). SEYKORA, John, T.; A61K 31/5377 (2006.01) A61P 17/02 (2006.01) 202 Laurel Lane, Broomall, PA 19008 (US). BEAUFILS, (21) International Application Number: Florent; 28 rue des ecureuils, 68870 Bartenheim (FR). PCT/EP2017/025137 (74) Agent: SPERRLE, Martin; Austrasse 24, 4051 Basel (22) International Filing Date: (CH). 17 May 2017 (17.05.2017) (81) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, (26) Publication Language: English CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, (30) Priority Data: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, 62/338,111 18 May 2016 (18.05.2016) US HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, KP, KR, 17151843.4 17 January 2017 (17.01.2017) EP KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (71) Applicants: PIQUR THERAPEUTICS AG [CH/CH]; PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, Hochbergerstrasse 60c, 4057 Basel (CH). THE TRUS- SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TEES OF THE UNIVERSITY OF PENNESYLVANIA TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. _ [US/US]; 3160 Chestnut Street, Suite 200, Philadelphia, PA (84) Designated States (unless otherwise indicated, for every 19104 (US). kind of regional protection available): ARIPO (BW, GH, (72) Inventors: FABBRO, Doriano; Im Lee 54, 4144 Ar- GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, leshiem (CH). HEBEISEN, Paul; St. Albanring 184, 4052 UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, Basel (CH). HILLMANN-WUELLNER, Petra; Dorfs- TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, = = Title: TREATMENT OF SKIN LESIONS (54) = R 2 1. 1 , 2F . ,. , R ,,), ,4 W F 0 R3_ R4 x';'\"\" , ...,.... . , N > _ = ,..i, (II) ' :::: N N H 2 = — (I) = = A A = = = : The present invention is relates to a compound of formula (I), wherein X 1 , X 2 and X 3 are, independently of each other, N (57) CH; with the proviso that at least two of X 1 X 2 and X are N; Y is N or CH; W is H or F; with the proviso that when W is F, then X 3 1 , X 2 X 3 are N; R 1 and R 2 are independently of each other (i) a morpholinyl of formula (II) wherein the arrow denotes the bond in formula or — and - (I); and wherein R 3 and R are independently of each other H, C 4 1 -C 3 alkyl optionally substituted with one or two OH, C 1 -C 2 fluoroalkyl, Ci -C2alkoxy, ClalkoxyCj-C3alkyl, CN, or C(0)0-Ci-C2alkyl; or R 3 and R 4 form together a bivalent residue -R 5 R 6 - selected from C1- Ir -- - iv C3alkylene optionally substituted with 1 to 4 F, -CH2-0-CH2-, -CH2-NH-CH2-, or any of the structures wherein the arrows denote the M bonds in formula (II); or (ii) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally GC c:N substituted by 1 to 3 R 7 ; wherein R 7 is independently at each occurrence C1-C3alkyl optionally substituted with one or two OH, C1- C2fluoroalkyl, --.... Ci-C2alkoxyCj-C3alkyl, C3-C6cycloalkyl; or two R 7 substituents form together a bivalent residue-R R - selected from 8 9 IN p is Il Ci-C3alkylene optionally substituted with 1 to 4 F, -CH2-0-CH2- or -O-CH2CH2-O-; with the proviso that at least one of R 1 and © a morpholinyl of formula II; and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in el the prevention or treatment of a skin lesion in a subject. [Continued on next page] WO 2017/198347 Al MIDEDIMOMOIDEIROIDEMOMMUNDOMOHMEMIDIMIE EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: — as to applicant's entitlement to apply patent (Rule 4.17(H)) for and be granted a Published: — with international search report (Art. 21(3))