Patent SG-11201810656W-A (SG)
Title: Crystalline form of (r)-4-(5-(cyclopropylethynyl)isoxazol-3-yl)-n-hydroxy-2-methyl-2-(methylsulfonyl)butanamide as an antibacterial agent
Inventor: FU JIPING
IPC: A61K31/42
Filed: 2017-06-12
Abstract: INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 21 December 2017 (21.12.2017) WIP0 I PCT 0111111010 0111 inn Oil ioo monliflo oimIE (10) International Publication Number WO 2017/216705 Al (51) International Patent Classification: C07D 261/08 (2006.01) A61P 31/04 (2006.01) A61K 31/42 (2006.01) (21) International Application Number: PCT/IB2017/053468 (22) International Filing Date: 12 June 2017 (12.06.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: PCT/CN2016/085694 14 June 2016 (14.06.2016) CN (71) Applicant: NOVARTIS AG [CH/CH]; Lichtstrasse 35, 4056 Basel (CH). (72) Inventors: FU, Jiping; Novartis Institutes for BioMedical Research Inc., 5300 Chiron Way, Emeryville, California 94608 (US). JIANG, Siyi; Beijing Novartis Pharma Co. Ltd., 4218 Jinke Road, Zhangjiang Hi-Tech Park, Shang- hai 201203 (CN). KORDIKOWSKI, Andreas; Novartis Pharma AG, Postfach, CH-4002 Basel (CH). SWEENEY, Zachary Kevin; 143 King Street, Redwood City, Califor- nia 94602 (US). (74) Agent: NOVARTIS AG; Lichtstrasse 35, 4056 Basel (CH). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, 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, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 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 for and be granted a patent (Rule 4.1700) Published: — with international search report (Art. 21(3)) (54) Title: CRYSTALLINE FORM OF (R)-4-(5-(CYCLOPROPYLETHYNYL)ISOXAZOL-3-YL)-N-HYDROXY-2-METHYL-2- (METHYLSULFONYL)BUTANAMIDE AS AN ANTIBACTERIAL AGENT O N 1-1 N_ N O 1-1 N C (A) (57) : The invention relates to a crystalline form of the (R)-4-(5- (cyclopropylethynypisoxazol-3-y1)-N-hydroxy-2-methy1-2- (methylsulfonyl)butanamide (i.e. the compound of formula (A)) with low hy- droscopicity. The compound and compositions thereof are useful to treat bac- terial infections and in particular Gram negative bacterial infections, includ- ing mult-drug resistant strains. The crystalline form is prepared by dissolving an amorphous form of the compound in a halogenated organic solvent (e.g. dichloromethane) and precipitating the crystalline form with a hydrocarbon solvent (e.g. heptane).(A)