Claims for Patent: 10,533,032

Summary for Patent: 10,533,032

Title:	Crystalline form of benzylbenzene SGLT2 inhibitor
Abstract:	Provided are crystalline forms of a compound having an inhibitory effect on sodium-dependent glucose cotransporter SGLT2. The invention also provides pharmaceutical compositions, methods of preparing the crystalline compound, and methods of using the crystalline compound, independently or in combination with other therapeutic agents, for treating diseases and conditions which are affected by SGLT or SGLT2 inhibition.
Inventor(s):	Cai Mengzhuang, Liu Qian, Xu Ge, Lv Binhua, Seed Brian, Roberge Jacques
Assignee:	THERACOS SUB, LLC
Application Number:	US15804074
Patent Claims:	2. The method of claim 1 , wherein said crystalline form of (2S claim 1 ,3R claim 1 ,4R claim 1 ,5S claim 1 ,6R)-2-(4-chloro-3-(4-(2-cyclopropoxyethoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3 claim 1 ,4 claim 1 ,5-triol is characterized by an XRPD that further comprises peaks at 5.4 claim 1 , 11.3 claim 1 , 11.9 claim 1 , 16.3 claim 1 , 20.6 claim 1 , 21.2 claim 1 , 22.8 claim 1 , 23.0 claim 1 , 23.4 claim 1 , 23.6 claim 1 , 23.9 claim 1 , 24.7 claim 1 , 25.4 claim 1 , 25.8 claim 1 , 27.8 and 28.2 degrees 2θ claim 1 , ±0.1 degrees 2θ claim 1 , wherein said XRPD is made using CuKradiation.3. The method of claim 1 , wherein said crystalline form of (2S claim 1 ,3R claim 1 ,4R claim 1 ,5S claim 1 ,6R)-2-(4-chloro-3-(4-(2-cyclopropoxyethoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3 claim 1 ,4 claim 1 ,5-triol is characterized by a Raman spectra that further comprises peaks at about 1178 claim 1 , 1205 claim 1 , 1212 claim 1 , 1608 claim 1 , 2945 claim 1 , 3010 and 3063 cm.4. The method of claim 1 , wherein said crystalline form of (2S claim 1 ,3R claim 1 ,4R claim 1 ,5S claim 1 ,6R)-2-(4-chloro-3-(4-(2-cyclopropoxyethoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3 claim 1 ,4 claim 1 ,5-triol is characterized by a Raman spectra that comprises peaks at about 144 claim 1 , 189 claim 1 , 216 claim 1 , 226 claim 1 , 284 claim 1 , 315 claim 1 , 353 claim 1 , 387 claim 1 , 419 claim 1 , 432 claim 1 , 449 claim 1 , 503 claim 1 , 530 claim 1 , 565 claim 1 , 594 claim 1 , 638 claim 1 , 688 claim 1 , 716 claim 1 , 728 claim 1 , 755 claim 1 , 790 claim 1 , 825 claim 1 , 850 claim 1 , 884 claim 1 , 901 claim 1 , 919 claim 1 , 934 claim 1 , 974 claim 1 , 984 claim 1 , 1014 claim 1 , 1030 claim 1 , 1052 claim 1 , 1070 claim 1 , 1120 claim 1 , 1134 claim 1 , 1178 claim 1 , 1205 claim 1 , 1212 claim 1 , 1229 claim 1 , 1302 claim 1 , 1323 claim 1 , 1343 claim 1 , 1380 claim 1 , 1422 claim 1 , 1438 claim 1 , 1457 claim 1 , 1572 claim 1 , 1585 claim 1 , 1608 claim 1 , 2844 claim 1 , 2919 claim 1 , 2945 claim 1 , 2963 claim 1 , 2997 claim 1 , 3010 claim 1 , 3028 claim 1 , 3051 claim 1 , 3063 claim 1 , 3085 claim 1 , and 3095 cm.5. The method of claim 1 , wherein said crystalline form of (2S claim 1 ,3R claim 1 ,4R claim 1 ,5S claim 1 ,6R)-2-(4-chloro-3-(4-(2-cyclopropoxyethoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3 claim 1 ,4 claim 1 ,5-triol is characterized by a differential scanning calorimetry (DSC) endotherm at about 136° C.7. The method of claim 1 , wherein said disease or condition is selected from the group consisting of type 1 diabetes mellitus claim 1 , type 2 diabetes mellitus claim 1 , hyperglycemia claim 1 , diabetic complications claim 1 , insulin resistance claim 1 , metabolic syndrome claim 1 , hyperinsulinemia claim 1 , hypertension claim 1 , hyperuricemia claim 1 , obesity claim 1 , edema claim 1 , dyslipidemia claim 1 , chronic heart failure claim 1 , atherosclerosis claim 1 , and cancer.8. The method of claim 1 , wherein said disease or condition is type 1 diabetes mellitus.9. The method of claim 1 , wherein said disease or condition is type 2 diabetes mellitus.10. The method of claim 1 , wherein said disease or condition is diabetic complications and said diabetic complications are selected from the group consisting of retinopathy claim 1 , nephropathy claim 1 , renal disease claim 1 , neuropathy claim 1 , ulcers claim 1 , micro- and macroangiopathies claim 1 , and diabetic foot disease.11. The method of claim 1 , wherein said subject is a human.12. The method of claim 9 , wherein said subject is a human.13. The method of claim 1 , further comprising administering an additional therapeutic agent.14. The method of claim 13 , wherein said additional therapeutic agent is selected form the group consisting of an antidiabetic agent claim 13 , a lipid-lowering agent claim 13 , an agent for treating diabetic complications claim 13 , an anti-obesity agent claim 13 , and anti-hypertensive agent claim 13 , an antihyperuicemic agent claim 13 , and an agent for treating chronic heart failure.15. The method of claim 13 , wherein said additional therapeutic agent is an antidiabetic agent.16. The method of claim 15 , wherein and said antidiabetic agent is selected from the group consisting of insulin and insulin mimetics claim 15 , acetohexamide claim 15 , carbutamide claim 15 , chlorpropamide claim 15 , glibenclamide claim 15 , glibornuride claim 15 , gliclazide claim 15 , glimepiride claim 15 , glipizide claim 15 , gliquidone claim 15 , glisoxepide claim 15 , glyburide claim 15 , glyclopyramide claim 15 , tolazamide claim 15 , tolcyclamide claim 15 , tolbutamide claim 15 , JTT-608 claim 15 , glybuzole claim 15 , metformin claim 15 , buformin claim 15 , phenformin claim 15 , repaglinide claim 15 , nateglinide claim 15 , mitiglinide claim 15 , rosiglitazone claim 15 , pioglitazone claim 15 , isaglitazone claim 15 , netoglitazone claim 15 , rivoglitazone claim 15 , balaglitazone claim 15 , darglitazone claim 15 , CLX-0921 claim 15 , farglitazar claim 15 , metaglidasen claim 15 , MBX-2044 claim 15 , GI 262570 claim 15 , GW1929 claim 15 , GW7845 claim 15 , muraglitazar claim 15 , naveglitazar claim 15 , tesaglitazar claim 15 , peliglitazar claim 15 , JTT-501 claim 15 , GW-409544 claim 15 , GW-501516 claim 15 , PLX204 claim 15 , GlaxoSmithKline 625019 claim 15 , GlaxoSmithKline 677954 claim 15 , ALRT-268 claim 15 , AGN-4204 claim 15 , MX-6054 claim 15 , AGN-194204 claim 15 , LG-100754 claim 15 , bexarotene claim 15 , acarbose claim 15 , miglitol claim 15 , L-783281 claim 15 , UCL-1397 claim 15 , sitagliptin claim 15 , vildagliptin claim 15 , denagliptin claim 15 , saxagliptin claim 15 , alogliptin claim 15 , dutogliptin claim 15 , NVP-DPP728 claim 15 , P93/01 claim 15 , P32/98 claim 15 , FE 99901 claim 15 , TS-021 claim 15 , TSL-225 claim 15 , GRC8200 claim 15 , KR61639 claim 15 , PNU-177496 claim 15 , CP-368296 claim 15 , CS-917 claim 15 , MB05032 claim 15 , AZD-7545 claim 15 , FR-225659 claim 15 , carbenoxolone claim 15 , INCB13739 claim 15 , BAY-27-9955 claim 15 , NN-2501 claim 15 , NNC-92-1687 claim 15 , exenatide claim 15 , liraglutide claim 15 , LY-315902 claim 15 , and GlaxoSmithKline 716155.17. The method of claim 13 , wherein said additional therapeutic agent is an agent for treating diabetic complications.18. The method of claim 17 , wherein said an agent for treating diabetic complications is selected from the group consisting of epalrestat claim 17 , imirestat claim 17 , tolrestat claim 17 , minalrestat claim 17 , ponalrestat claim 17 , zopolrestat claim 17 , fidarestat claim 17 , ascorbyl gamolenate claim 17 , ADN-138 claim 17 , BAL-ARI8 claim 17 , ZD-5522 claim 17 , GP-1447 claim 17 , IDD598 claim 17 , risarestat claim 17 , zenarestat claim 17 , methosorbinil claim 17 , AL-1567 claim 17 , M-16209 claim 17 , AD-5467 claim 17 , AS-3201 claim 17 , NZ314 claim 17 , SG-210 claim 17 , JTT-811 claim 17 , lindolrestat claim 17 , sorbinil claim 17 , pyridoxamine claim 17 , OPB-9195 claim 17 , ALT-946 claim 17 , ALT-711 claim 17 , pimagedine claim 17 , ALT-711 claim 17 , sulodexide claim 17 , 5-hydroxy-1-methylhydantoin claim 17 , insulin-like growth factor-I claim 17 , platelet-derived growth factor claim 17 , epidermal growth factor claim 17 , nerve growth factor claim 17 , uridine claim 17 , uboxistaurin claim 17 , midostaurin claim 17 , mexiletine claim 17 , oxcarbazepine claim 17 , dexlipotam claim 17 , GPI-5232 claim 17 , GPI-5693 claim 17 , carnitine claim 17 , levacecamine claim 17 , and levocarnitine.19. The method of claim 13 , wherein said additional therapeutic agent is an antihypertensive agent.20. The method of claim 19 , wherein said an agent for treating diabetic complications is selected from the group consisting of bimoclomol claim 19 , captopril claim 19 , enalapril claim 19 , fosinopril claim 19 , lisinopril claim 19 , perindopril claim 19 , quinapril claim 19 , ramipril claim 19 , thiorphan claim 19 , omapatrilat claim 19 , MDL-100240 claim 19 , fasidotril claim 19 , sampatrilat claim 19 , GW-660511 claim 19 , mixanpril claim 19 , SA-7060 claim 19 , SLV-306 claim 19 , ecadotril claim 19 , candesartan cilexetil claim 19 , eprosartan claim 19 , irbesartan claim 19 , losartan claim 19 , olmesartan medoxomil claim 19 , telmisartan claim 19 , valsartan claim 19 , tasosartan claim 19 , enoltasosartan claim 19 , CGS 35066 claim 19 , CGS 26303 claim 19 , CGS31447 claim 19 , SM-19712 claim 19 , racleer claim 19 , sitaxsentan claim 19 , ambrisentan claim 19 , TBC-3214 claim 19 , BMS-182874 claim 19 , BQ-610 claim 19 , TA-0201 claim 19 , PD180988 claim 19 , BMS-193884 claim 19 , darusentan claim 19 , TBC-3711 claim 19 , bosentan claim 19 , tezosentan claim 19 , J-104132 claim 19 , YM-598 claim 19 , 50139 claim 19 , SB-234551 claim 19 , ATZ-1993 claim 19 , RO-61-1790 claim 19 , ABT-546 claim 19 , enlasentan claim 19 , BMS207940 claim 19 , hydrochlorothiazide claim 19 , bendroflumethiazide claim 19 , trichlormethiazide claim 19 , indapamide claim 19 , metolazone claim 19 , furosemide claim 19 , bumetanide claim 19 , torsemide claim 19 , chlorthalidone claim 19 , metolazone claim 19 , cyclopenthiazide claim 19 , hydroflumethiazide claim 19 , tripamide claim 19 , mefruside claim 19 , benzylhydrochlorothiazide claim 19 , penflutizide claim 19 , methyclothiazide claim 19 , azosemide claim 19 , etacrynic acid claim 19 , torasemide claim 19 , piretanide claim 19 , meticrane claim 19 , potassium canrenoate claim 19 , spironolactone claim 19 , triamterene claim 19 , aminophylline claim 19 , cicletanine claim 19 , LLU-alpha claim 19 , isosorbide claim 19 , D-mannitol claim 19 , D-sorbitol claim 19 , fructose claim 19 , glycerin claim 19 , acetazolamide claim 19 , methazolamide claim 19 , OPC-31260 claim 19 , lixivaptan claim 19 , conivaptan claim 19 , amlodipine claim 19 , bepridil claim 19 , diltiazem claim 19 , felodipine claim 19 , isradipine claim 19 , nicardipen claim 19 , nimodipine claim 19 , verapamil claim 19 , S-verapamil claim 19 , aranidipine claim 19 , efonidipine claim 19 , barnidipine claim 19 , benidipine claim 19 , manidipine claim 19 , cilnidipine claim 19 , nisoldipine claim 19 , nitrendipine claim 19 , nifedipine claim 19 , nilvadipine claim 19 , felodipine claim 19 , pranidipine claim 19 , lercanidipine claim 19 , isradipine claim 19 , elgodipine claim 19 , azelnidipine claim 19 , lacidipine claim 19 , vatanidipine claim 19 , lemildipine claim 19 , diltiazem claim 19 , clentiazem claim 19 , fasudil claim 19 , bepridil claim 19 , gallopamil claim 19 , indapamide claim 19 , todralazine claim 19 , hydralazine claim 19 , cadralazine claim 19 , budralazine claim 19 , acebutolol claim 19 , bisoprolol claim 19 , esmolol claim 19 , propanolol claim 19 , atenolol claim 19 , labetalol claim 19 , carvedilol claim 19 , metoprolol claim 19 , amosulalol claim 19 , terazosin claim 19 , bunazosin claim 19 , prazosin claim 19 , doxazosin claim 19 , propranolol claim 19 , atenolol claim 19 , metoprolol claim 19 , carvedilol claim 19 , nipradilol claim 19 , celiprolol claim 19 , nebivolol claim 19 , betaxolol claim 19 , pindolol claim 19 , tertatolol claim 19 , bevantolol claim 19 , timolol claim 19 , carteolol claim 19 , bisoprolol claim 19 , bopindolol claim 19 , nipradilol claim 19 , penbutolol claim 19 , acebutolol claim 19 , tilisolol claim 19 , nadolol claim 19 , urapidil claim 19 , indoramin claim 19 , clonidine claim 19 , methyldopa claim 19 , CHF-1035 claim 19 , guanabenz acetate claim 19 , guanfacine claim 19 , moxonidine claim 19 , lofexidine claim 19 , talipexole claim 19 , reserpine claim 19 , warfarin claim 19 , dicumarol claim 19 , phenprocoumon claim 19 , acenocoumarol claim 19 , anisindione claim 19 , phenindione claim 19 , ximelagatran claim 19 , aspirin claim 19 , clopidogrel claim 19 , ticlopidine claim 19 , dipyridamole claim 19 , cilostazol claim 19 , ethyl icosapentate claim 19 , sarpogrelate claim 19 , dilazep claim 19 , trapidil claim 19 , and beraprost.