Compounds containing benzo[d][1,3]oxathiole, benzo[d][1,3]oxathiole 3-oxide or benzo[d][1,3]oxathiole 3,3-dioxide and methods/uses thereof as agonists of g protein-coupled receptor 119

{
  "publication_number": "US10906894B2",
  "country": "US",
  "kind": "B2",
  "title": "Compounds containing benzo[d][1,3]oxathiole, benzo[d][1,3]oxathiole 3-oxide or benzo[d][1,3]oxathiole 3,3-dioxide and methods/uses thereof as agonists of g protein-coupled receptor 119",
  "abstract": "There are provided compounds containing benzo[d][1,3]oxathiole, benzo[d][1,3]oxathiole 3-oxide, and benzo[d][1,3]oxathiole 3,3-dioxide, as well as uses/methods related thereto, including treatment of diseases and condition associated with GPR119 dysregulation, Type 2 diabetes mellitus, and related metabolic disorders.",
  "claims": [
    "1. A compound having formula (A-I): or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-I), or complex thereof, wherein: X 1 is selected from the group consisting of O, and SO 2; X 2 is selected from the group consisting of O, and SO 2; when X 1 is O, X 2 is not O; when X 2 is O, X 1 is not O; when X 1 is SO 2, X 2 is not SO 2; when X 2 is SO 2, X 1 is not SO 2; X 3 is selected from the group consisting of CH, CF and N; X 4 is at each occurrence is independently selected from the group consisting of CH and N; A is selected from the group consisting of R is selected from the group consisting of R 1 is selected from the group consisting of hydrogen, C(O)O-tert-butyl, and R 2a is selected from the group consisting of hydrogen and C 1-6 alkyl; R 2b is selected from the group consisting of hydrogen and C 1-6 alkyl; R 3 is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C(O)R 9, C(O)NR 10a R 10b, CH 2 C(O)OR 10a, R 4 is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C(O)R 9, C(O)OR 10, C(O)NR 10a R 10b, R 5 is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C(O)R 9, C(O)OR 10, C(O)NR 10a R 10b, R 6 is selected from the group consisting of NHR 11, and CH 2 NHR 12; R 7a is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 3-7 branched alkyl, C 1-6 haloalkyl, and C 1-6 alkoxy; R 7b is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 3-7 branched alkyl, C 1-6 haloalkyl, and C 1-6 alkoxy; R 7c is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 3-7 branched alkyl, C 1-6 haloalkyl, and C 1-6 alkoxy; R 8 is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl; R 9 is selected from the group consisting of C 1-6 alkyl, C 3-7 branched alkyl, and R 10 is selected from the group consisting of C 1-6 alkyl and C 3-7 branched alkyl; R 10a is selected from the group consisting of hydrogen, C 1-6 alkyl, and C 3-7 branched alkyl; R 10b is selected from the group consisting of hydrogen, C 1-6 alkyl, and C 3-7 branched alkyl; R 11 is selected from the group consisting of R 12 is selected from the group consisting of R 13a is at each occurrence independently selected from the group consisting of hydrogen, C 1-6 alkyl, and C 3-7 branched alkyl; R 13b is at each occurrence independently selected from the group consisting of hydrogen, C 1-6 alkyl, and C 3-7 branched alkyl; R 14a is at each occurrence independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 3-7 branched alkyl, and C(O)O-tert-butyl; R 14b is at each occurrence independently selected from the group consisting of hydrogen, C 1-6 alkyl, and C 3-7 branched alkyl; X 5 is selected from the group consisting of N and CR 7b; n 1 is 1 or 2; n 2 is 1 or 2; and m is 1, 2, 3, 4, 5, 6, or 7; wherein when A R is and R 5 is C(O)OR 10, then one or both of n 1 and n 2 is 1; and with the proviso that the compound excludes any compound having formula (A-1a) wherein: R 15 is: hydrogen; C 1 -C 5 alkyl; halogen-substituted C 1 -C 5 alkyl; acyl selected from the group C 1 -C 5 alkyl(C═O) and phenyl(C═O); substituted heteroaryl representing a monocyclic aromatic group with two nitrogen atoms which is substituted by a halogen or (C 1 -C 5) alkyl; (C 1 -C 3) alkylsulphonyl; or phenylsulphonyl; and R 16a, R 16b, R 16c and R 16d are hydrogen or one or two substitutents simultaneously selected from halogen, (C 1 -C 3) alkyl, halogen-substituted (C 1 -C 3)alkyl, (C 1 -C 3)alkylsulphonyl or cyano.",
    "2. The compound according to claim 1, having formula (A-V) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-V), or a complex thereof, or having formula (A-VI) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-VI), or a complex thereof, or having formula (A-VII) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-VII), or a complex thereof, or having formula (A-VIII) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-VIII), or a complex thereof, or having formula (A-IX) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-IX), or a complex thereof.",
    "3. The compound according to claim 2, having formula (A-XII) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-XII), or a complex thereof, or having formula (A-XIII) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-XIII), or a complex thereof, or having formula (A-XIV) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-XIV), or a complex thereof, or having formula (A-XV) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-XV), or a complex thereof, or having formula (A-XVI) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-XVI), or a complex thereof, or having formula (A-XVII) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-XVII), or a complex thereof, or having formula (A-XVIII) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-XVIII), or a complex thereof, or having formula (A-XIX) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-XIX), or a complex thereof, or having formula (A-XX) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-XX), or a complex thereof, or having formula (A-XXI) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-XXI), or a complex thereof, or having formula (A-XXII) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-XXII), or a complex thereof, or having formula (A-XXIII) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-XXIII), or a complex thereof.",
    "4. The compound according to claim 1 having formula (A-III) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-III), or a complex thereof.",
    "5. The compound according to claim 4, having formula (A-X) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-X), or a complex thereof, or having formula (A-XI) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-XI), or a complex thereof.",
    "6. The compound according to claim 1 having formula (A-IV) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (A-IV), or a complex thereof.",
    "7. The compound according to claim 1, wherein X 3 is selected from the group consisting of CF and N.",
    "8. A compound, which is: 6-((3-fluoro-4-((1-isopropylpiperidin-4-ylmethoxy)phenyl)-2H-benzo[1,3]oxathiole 3,3-dioxide; 6-((3-fluoro-4-((1-tert-butylpiperidin-4-ylmethoxy)phenyl)-2H-benzo[1,3]oxathiole 3,3-dioxide; 4-((4-3,3-dioxido-2H-benzo[d][1,3]oxathiol-6-yl)-2-fluorophenyoxy)methyl)-N,N-dimethylpiperidine-1-carboxamide; tert-butyl (2-(4-((4-(3,3-dioxido-2H-benzo[d][1,3]oxathiol-6-yl)-2-fluorophenoxy)methyl)piperidin-1-yl)-2-oxoethyl)carbamate; (2-(4-((4-(3,3-dioxido-2H-benzo[d][1,3]oxathiol-6-yl)-2-fluorophenoxy)methyl)piperidin-1-yl)ethan-1-one; tert-butyl (S)-(1-(4-((4-(3,3-dioxido-2H-benzo[d][1,3]oxathiol-6-yl)-2-fluorophenoxy)methyl)piperidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamate; ((S)-2-amino-1-(4-((4-(3,3-dioxido--2H-benzo[d][1,3]oxathiol-6-yl)-2-fluorophenoxy)methyl)piperidin-1-yl)-)-3-methylbutan-1-one; 4-((4-3,3-dioxido-2H-benzo[d][1,3]oxathiol-6-yl)-2-fluorophenyoxy)methyl)-piperidine-1-carboxamide; 1-4-((4-3,3-dioxido-2H-benzo[1,3]oxathiol-6-yl)-2-fluorophenyoxy)methyl)-piperidin-1-yl)-2-methylpropan-1-one; ethyl-2-(4-{[4-(3,3-dioxido-2H-benzo[d][1,3]oxathiol-6-yl)-2-fluorophenyoxy)methyl)-piperidin-1-yl)acetic acid; 6-(4-((1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)methoxy-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3,3-dioxide; tert-butyl 4-(((5-(3,3-dioxido-2H-benzo[d][1,3]oxathiol-6-yl)pyrimidin-2-yl)oxy)methyl)piperidine-1-carboxylate; 6-(2-(piperidin-4-ylmethoxy)pyrimidin-5-yl)-2H-benzo[d][1,3]oxathiole 3,3-dioxide; 6-(2-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)methoxy)pyrimidin-5-yl)-2H-benzo[d][1,3]oxathiole 3,3-dioxide; 5-(4-((1-5-chloropyrimidin-2-yl)piperidin-4-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3,3-dioxide; 6-(4-((1-(4-chloro-1,3,5-triazin-2-yl)piperidin-4-yl)methoxy)-3-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3,3-dioxide; 6-(4-((1-(1,3,5-triazin-2-yl)piperidin-4-yl)methoxy)-3-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3,3-dioxide; tert-butyl 3-((4-(3,3-dioxido-2H-benzo[d][1,3]oxathiol-6-yl)-2-fluorophenoxy)methyl)azetidine-1-carboxylate; 6-(4-(azetidin-3-ylmethoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3,3-dioxide; 6-(4-((1-(5-chloropyrimidin-2-yl)azetidin-3-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3,3-dioxide; 6-(3-fluoro-4-((1-(3-isopropyl-1,2,4-oxadiazol-5-yl)azetidin-3-yl)methoxy)phenyl)-2H-benzo[d][1,3]oxathiole 3,3-dioxide; tert-butyl 4-(5-((4-(3,3-dioxido-2H-benzo[d][1,3]oxathiol-6-yl)-2-fluorophenoxy)methyl)thiazol-2-yl)piperidine-1-carboxylate; 6-(3-fluoro-4-((2-(piperidin-4-yl)thiazol-5-yl)methoxy)phenyl)-2H-benzo[d][1,3]oxathiole 3,3-dioxide; 6-(4-((2-(1-(5-chloropyrimidin-2-yl)piperidin-4-yl)thiazol-5-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole-3,3-dioxide; 6-(3-fluoro-4-((1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)methoxy)phenyl)-2H-benzo[d][1,3]oxathiole 3,3-dioxide; tert-butyl 4-(4-(3,3-dioxido-2H-benzo[d][1,3]oxathiol-6-yl)-2-fluorophenyl]piperazine-1-carboxylate; 6-(3-fluoro-4-(piperazine-1-yl)phenyl)-2H-benzo[d][1,3]oxathiole 3,3-dioxide; 6-(4-(5-chloropyrimidin-2-yl)piperazin-1-yl)-3-fluorophenyl-2H-benzo[d][1,3]oxathiole 3,3-dioxide; 6-(4-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3,3-dioxide; 6-(3-fluoro-4-(1-(5-isopropylpyrimidin-2-yl)piperidin-4-yl)methoxy)phenyl-2H-benzo[d][1,3]oxathiole 3,3-dioxide; 6-(3-fluoro-4-(1-(5-methoxypyrimidin-2-yl)piperidin-4-yl)methoxy)phenyl-2H-benzo[d][1,3]oxathiole 3,3-dioxide; (R)-6-(4-((1-(5-ethylpyrimidin-2-yl)pyrrolidin-2-yl)methoxy)-3-fluorophenyl-2H-benzo[d]oxathiole 3,3-dioxide; tert-butyl 4-(((2-(3,3-dioxido-2H-benzo[d][1,3]oxathiol-6-yl)pyrimidin-5-yl)oxy)methyl)piperidine-1-carboxylate; 6-(5-(piperidin-4-ylmethoxy)pyrimidin-2-yl)-2H-benzo[d][1,3]oxathiole 3,3-dioxide hydrochloride; 6-(5-((1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)methoxy)pyrimidin-2-yl)-2H-benzo[d][1,3]oxathiole 3,3-dioxide; (S)-6-(4-((1-(5-ethylpyrimidin-2-yl)pyrrolidin-2-yl)methoxy)-3-fluorophenyl-2H-benzo[d]oxathiole 3,3-dioxide; (S)-6-(4-((1-(5-ethylpyrimidin-2-yl)pyrrolidin-3-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3,3-dioxide; (S)-6-(4-((1-(5-chloropyrimidin-2-yl)pyrrolidin-3-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3,3-dioxide; (S)-6-(4-((1-(4-ethylpyrimidin-2-yl)pyrrolidin-3-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3,3-dioxide; or a pharmaceutically acceptable form thereof.",
    "9. A composition comprising at least one compound according to claim 1 an anti-diabetic agent.",
    "10. A method of treating a disease associated with GPR119 dysregulation, said method comprising administering to a subject an effective amount of at least one compound according to claim 1.",
    "11. A compound having formula (B-I): or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-I), or complex thereof, wherein: X 1 is selected from the group consisting of O, S and SO; X 2 is selected from the group consisting of O, S and SO; when X 1 is O, X 2 is not O; when X 2 is O, X 1 is not O; when X 1 is S, X 2 is not S; when X 2 is S, X 1 is not S; when X 1 is SO, X 2 is not SO; when X 2 is SO, X 1 is not SO; X 3 is selected from the group consisting of CH, CF and N; X 4 at each occurrence is independently selected from the group consisting of CH and N; A is selected from the group consisting of R is selected from the group consisting of R 1 is selected from the group consisting of hydrogen, C(O)O-tert-butyl, and R 2a is selected from the group consisting of hydrogen and C 1-6 alkyl; R 2b is selected from the group consisting of hydrogen and C 1-6 alkyl; R 3 is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C(O)R 9, C(O)OR 10, C(O)NR 10a R 10b, CH 2 C(O)OR 10a, R 4 is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C(O)R 9, C(O) C(O)OR 10, C(O)NR 10a R 10b, R 5 is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C(O)R 9, C(O)OR 10, C(O)NR 10a R 10b, R 6 is selected from the group consisting of NHR 11, and CH 2 NHR 12; R 7a is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 3-7 branched alkyl, C 1-6 haloalkyl, and C 1-6 alkoxy; R 7b is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 3-7 branched alkyl, C 1-6 haloalkyl, and C 1-6 alkoxy; R 7c is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 3-7 branched alkyl, C 1-6 haloalkyl, and C 1-6 alkoxy; R 8 is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 3-7 branched alkyl, and C 3-7 cycloalkyl; R 9 is selected from the group consisting of C 1-6 alkyl, C 3-7 branched alkyl, and R 10 is selected from the group consisting of C 1-6 alkyl and C 3-7 branched alkyl; R 10a is selected from the group consisting of hydrogen, C 1-6 alkyl, and C 3-7 branched alkyl; R 10b is selected from the group consisting of hydrogen, C 1-6 alkyl, and C 3-7 branched alkyl; R 11 is selected from the group consisting of R 12 is selected from the group consisting of R 13a is at each occurrence independently selected from the group consisting of hydrogen, C 1-6 alkyl, and C 3-7 branched alkyl; R 13b is at each occurrence independently selected from the group consisting of hydrogen, C 1-6 alkyl, and C 3-7 branched alkyl; R 14a is at each occurrence independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 3-7 branched alkyl, and C(O)O-tert-butyl; R 14b is at each occurrence independently selected from the group consisting of hydrogen, C 1-6 alkyl, and C 3-7 branched alkyl; X 5 is selected from the group consisting of N and CR 7b; n 1 is 1 or 2; n 2 is 1 or 2; and m is 1, 2, 3, 4, 5, 6, or 7.",
    "12. The compound according to claim 11, having formula (B-V) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-V), or a complex thereof, or having formula (B-VI) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-VI), or a complex thereof, or having formula (B-VII) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-VII), or a complex thereof, or having formula (B-VIII) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-VIII), or a complex thereof, or having formula (B-IX) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-IX), or a complex thereof.",
    "13. The compound according to claim 12, having formula (B-XII) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-XII), or a complex thereof, or having formula (B-XIII) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-XIII), or a complex thereof, or having formula (B-XIV) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-XIV), or a complex thereof, or having formula (B-XV) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-XV), or a complex thereof, or having formula (B-XVI) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-XVI), or a complex thereof, or having formula (B-XVII) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-XVII), or a complex thereof, or having formula (B-XVIII) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-XVIII), or a complex thereof, or having formula (B-XIX) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-XIX), or a complex thereof, or having formula (B-XX) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-XX), or a complex thereof, or having formula (B-XXI) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-XXI), or a complex thereof, or having formula (B-XXII) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-XXII), or a complex thereof, or having formula (B-XXIII) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-XXIII), or a complex thereof.",
    "14. The compound according to claim 11 having formula (B-III) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-III), or a complex thereof.",
    "15. The compound according to claim having formula (B-X) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-X), or a complex thereof, or having formula (B-XI) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-XI), or a complex thereof.",
    "16. The compound according to claim 11 having formula (B-IV) or an enantiomer, diastereomer, hydrate, solvate, or pharmaceutically acceptable salt of formula (B-IV), or a complex thereof.",
    "17. The compound according to claim 11, wherein X 3 is selected from the group consisting of CF and N.",
    "18. A compound, which is: 5-(4-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; 6-(4-((1-(5-ethylpyrimidin-2-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole-3-oxide; 1-(4-((2-fluoro-4-(3-oxido-2H-benzo[d][1,3]oxathiol-6-yl)phenoxy)methyl)-piperidin-1-yl)-3-methylbutane-1-one; 6-(3-fluoro-4-((1-(5-methoxypyrimidin-2-yl)piperidin-4-yl)methoxy)phenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; 6-(4-((1-(4-ethylpyrimidin-2-yl)piperidin-4-yl)methoxy)-3-(fluorophenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; 2-(4-((4-benzo[d][1,3]oxathiol-6-yl)-2-fluorophenoxy)methyl)piperidin-1-yl)-4-ethylpyrimidine; 6-(4-((1-(5-ethoxypyrimidin-2-yl)piperidin-4-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; 6-(3-fluoro-4-((1-(5-isopropylpyrimidin-2-yl)piperidin-4-yl)methoxy)phenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; 6-(3-fluoro-4-((1-(5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)methoxy)phenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; 6-(3-fluoro-4-(piperidin-4-yl)methoxy)phenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; tert-butyl-4-((2-fluoro-4-(3-oxido-2H-benzo[d][1,3]oxathiol-6-yl)phenoxy)methyl) piperidine-1-carboxylate; (S)-6-(4-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; (R)-6-(4-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; 6-(4-((1-(4-ethylpyrimidin-2-yl)piperidin-4-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; 4-((4-((benzo[d][1,3]oxathiol-6-yl)-2-fluorophenoxy)methyl)piperidine; 2-((4-((4-(benzo[d][1,3]oxathiol-6-yl)-2-fluorophenoxy)methyl)piperidin-1-yl)-5-ethylpyrimidine; 2-((4-((4-(benzo[d][1,3]oxathiol-6-yl)-2-fluorophenoxy)methyl)piperidin-1-yl)-5-isopropylpyrimidine; 2-(4-((4-((benzo[d][1,3]oxathiol-6-yl)-2-fluorophenoxy)methyl)piperidin-1-yl)-5-methoxpyrimidine; 1-(4-((4-(benzo[d][1,3]oxathiol-6-yl)-2-fluorophenoxy)methyl)piperidin-1-yl)-3-methylbutan-1-one; tert-butyl-(R)-4-((2-fluoro-4-(3-oxido-2H-benzo[d][1,3]oxathiol-6-yl)phenoxy)methyl) piperidine-1-carboxylate; (R)-6-(3-fluoro-4-(piperidin-4-ylmethoxy)phenyl)-2H-benzo[d][1.3]oxathiole 3-oxide; tert-butyl-(S)-4-((2-fluoro-4-(3-oxido-2H-benzo[d][1.3]oxathiol-6-yl)phenoxy)methyl) piperidine-1-carboxylate; (S)-6-(3-fluoro-4-(piperidin-4-ylmethoxy)phenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; (S)-6-(4-((1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; (S)-6-(3-fluoro-4-((1-5-isopropylpyrimidin-2-yl)piperidin-4-yl)methoxy)phenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; (S)-6-(3-fluoro-4-((1-5-methoxypyrimidin-2-yl)piperidin-4-yl)methoxy)phenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; (R)-6-(3-fluoro-4-((1-(5-methoxypyrimidin-2-yl)piperidin-4-yl)methoxy)phenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; (R)-6-(4-((1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)methoxy)phenyl)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; (R)-6-(3-fluoro-4-((1-(5-isopropylpyrimidin-2-yl)piperidin-4-yl)methoxy)phenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; tert-butyl (R)-4-(((5-(3-oxido-2H-benzo[d][1,3]oxathiol-6-yl]pyrimidin-2-yl)oxy)methyl)piperidine-1-carboxylate; (R)-6-(2-(piperidin-4-ylmethoxy)pyrimidin-5-yl)-2H-benzo[d][1,3]oxathiole 3-oxide; (R)-6-(2-((1-(5-chloropyridin-2-yl)piperidin-4-yl)methoxy)pyrimidin-5-yl)-2H-benzo[d][1,3]oxathiole 3-oxide; (S)-6-(4-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; tert-butyl (S)-4-(((5-(3-oxido-2H-benzo[d][1,3]oxathiol-6-yl)pyrimidin-2-yl)oxy)methyl)piperidine-1-carboxylate; (S)-6-(2-(piperidin-4-ylmethoxy)pyrimidin-5-yl)-2H-benzo[d][1,3]oxathiole 3-oxide; (S)-6-(2-((1-(5-chloropyrimidin-2-yl)piperidin-4-yl)methoxy)pyrimidin-5-yl)-2H-benzo[d][1,3]oxathiole 3-oxide; tert-butyl (3R)-3-((2-fluoro-4-(3-oxido-2H-benzo[d][1,3]oxathiol-6-yl)phenoxy)methyl) pyrrolidine-1-carboxylate; 6-(3-fluoro-4(((R)-pyrrolidin-3-yl)methoxy)phenyl)-2H-benzo[d][1,3]oxathiole 3-oxide 6-(4-(((R)-1-(5-Ethylpyrimidin-2-yl)pyrrolidin-3-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; (R)-3-((4-benzo[d][1,3]oxathiol-6-yl)-2-fluorophenoxy)methyl)pyrrolidine; (R)-2-(3-((4-benzo[d][1,3]oxathiol-6-yl)-2-fluorophenoxy)methyl)pyrrolidin-1-yl)-5-ethylpyrimidine; (S)-6-(4-(((S)-1-(5-ethylpyrimidin-2-yl)pyrrolidin-3-yl)methoxy)-3-flurophenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; (R)-6-(4-(((S)-1-(5-ethylpyrimidin-2-yl)pyrrolidin-3-yl)methoxy-3-flurophenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; (S)-6-(4-(((R)-1-(5-ethylpyrimidin-2-yl)pyrrolidin-3-yl)methoxy-3-flurophenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; (R)-6-(4-(((R)-1-(5-ethylpyrimidin-2-yl)pyrrolidin-3-yl)methoxy-3-flurophenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; (S)-6-(4-(((S)-1-(5-chloropyrimidin-2-yl)pyrrolidin-3-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; (S)-6-(4-(((S)-1-(4-ethylpyrimidin-2-yl)pyrrolidine-3-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; (R)-6-(4-(((S)-1-(4-ethylpyrimidin-2-yl)pyrrolidine-3-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; (R)-6-(4-(((S)-1-(5-chloropyrimidin-2-yl)pyrrolidine-3-yl)methoxy)-3-fluorophenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; (S)-6-(4-(((S)-1-(5-ethylpyrimidin-2-yl)pyrrolidine-3-yl)methoxy)phenyl)-2H-benzo[d][1,3]oxathiole 3-oxide; or a pharmaceutically acceptable form thereof.",
    "19. A composition comprising at least one compound according to claim 11 and an anti-diabetic agent.",
    "20. A method of treating a disease associated with GPR119 dysregulation, said method comprising administering to a subject an effective amount of at least one compound according to claim 11.",
    "21. A compound of structure or a pharmaceutically acceptable salt thereof.",
    "22. A compound of structure or a pharmaceutically acceptable salt thereof.",
    "23. A compound of structure or a pharmaceutically acceptable salt thereof."
  ],
  "description_excerpt": "The present invention(s) relates to benzo[d][1,3]oxathioles, benzo[d][1,3]oxathiole 3-oxides, benzo[d][1,3]oxathiole 3,3-dioxides, and related compounds and pharmaceutical compositions comprising the compounds, as well as uses and methods related thereto.\n\nInsulin is a hormone that regulates blood sugar produced by the pancreas. Diabetes is a chronic disease that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. Hyperglycemia, or raised blood sugar, is a common effect of uncontrolled diabetes and over time leads to serious damage to many of the body's systems, especially the nerves and blood vessels. The global prevalence of diabetes is estimated to be over 9% of adults aged 18+ years, corresponding to about 2-fold increase in the last ten years. There are three types of diabetes: Type 1 also known as insulin-dependent or juvenile requires daily administration of insulin. Type 2 diabetes (T2DM) also known as non-insulin dependent diabetes mellitus results from the body's ineffective use or ability to regulate insulin. Gestational diabetes is a condition where the blood glucose values are above normal but below those characteristic of diabetes occurring during pregnancy. Diabetes increases the risk of heart failure, stroke, neuropathy in the feet, retinopathy which is an important cause of blindness and kidney failure.",
  "cpc": [
    "C07D 411/12",
    "A61K 31/454",
    "A61K 31/506",
    "A61K 31/513",
    "A61K 31/53",
    "A61P 3/10",
    "A61P 43/00",
    "C07D 411/14",
    "C07D 413/12",
    "C07D 413/14",
    "C07D 417/12",
    "C07D 417/14"
  ],
  "ipc": [
    "C07D 411/12",
    "C07D 411/14",
    "C07D 417/14",
    "C07D 413/12",
    "C07D 413/14",
    "C07D 417/12"
  ],
  "assignees": [
    "Pramana Pharmaceuticals Inc"
  ],
  "inventors": [
    "Tarek Suhayl Mansour",
    "Mikhail Chafeev",
    "Mikhail Yudin",
    "Yury Gezentsvey",
    "Aleksandr Nikitin"
  ],
  "filing_date": "2017-06-08",
  "publication_date": "2021-02-02",
  "grant_date": "2021-02-02",
  "priority_date": "2016-06-09",
  "application_number": "US-201716307914-A",
  "family_id": "60578338",
  "cited_by_count": 3,
  "citations": [
    "CA1117944A",
    "EP0157603A2",
    "WO2005121121A2",
    "US20080103141A1",
    "WO2009050522A1",
    "US20140274701A1",
    "RU2576037C1"
  ]
}