HRP20230095T1 - Spoj 1,3-di-supstituiranog ketena i njegova primjena - Google Patents

Spoj 1,3-di-supstituiranog ketena i njegova primjena Download PDF

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HRP20230095T1
HRP20230095T1 HRP20230095TT HRP20230095T HRP20230095T1 HR P20230095 T1 HRP20230095 T1 HR P20230095T1 HR P20230095T T HRP20230095T T HR P20230095TT HR P20230095 T HRP20230095 T HR P20230095T HR P20230095 T1 HRP20230095 T1 HR P20230095T1
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alkyl
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halogen
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Xiong Cai
Changgeng Qian
Chunqiang YE
Qijie HE
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Bebetter Med Inc.
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Claims (12)

1. Spoj 1,3-disupstituiranog ketena ili njegova farmaceutski prihvatljiva sol ili njegov stereoizomer naznačen time, da spoj ima strukturu prikazanu formulom (II): [image] pri čemu: R1, R2 su svaki neovisno izabrani iz grupe koju čine: H, halogen, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C8 cikloalkil, C3-C8 cikloalkilmetil, C1-C6 alkoksi, i hidroksil; R3, R4 su svaki neovisno izabrani iz grupe koju čine: H, halogen, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C8 cikloalkil, C3-C8 cikloalkilmetil, C1-C6 alkoksi, i hidroksil, i R3, R4 nisu istovremeno H ; ili R3, R4 su vezani tako da formiraju 3-8-člani karbociklični prsten ili 3-8-člani heterociklični prsten; R5 je OR6; R6 je izabran iz grupe koju čine: H, C1-C6 alkil, C3-C8 cikloalkil, i C3-C8 cikloalkilmetil; Y je O; i prsten A je izabran iz grupe koju čine: [image] [image] [image] [image] [image] [image] pri čemu: X1, X2, X3, X4, X5, X6, X7 su svaki neovisno izabrani iz grupe koju čine: CR9, CR12 i N, i najmanje jedan od X1, X2, X3, i X4 je CR12; R9 je izabran iz grupe koju čine: H, halogen, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C8 cikloalkil, C3-C8 cikloalkilmetil, halogen-supstituirani C1-C6 alkil, hidroksi-supstituirani C1-C6 alkil, alkoksi-supstituirani C1-C6 alkil, amino-supstituirani C1-C6 alkil, C1-C4 alkilamino-supstituirani C1-C6 alkil, aril, heteroaril, nitro, cijano, -OR, -N(R)2, -SR, -C(O)OR, - C(O)N(R)2, -C(O)R, -S(O)R, -S(O)2R, -S(O)2N(R)2, i -N(R)C(O)R; R10 je izabran iz grupe koju čine: H, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C8 cikloalkil, C3-C8 cikloalkilmetil, halogen-supstituirani C1-C6 alkil, hidroksi-supstituirani C1-C6 alkil, alkoksi-supstituirani C1-C6 alkil, amino-supstituirani C1-C6 alkil, i C1-C4 alkilamino-supstituirani C1-C6 alkil; R11 je izabran iz grupe koju čine: H, -SR, -OR, -N(R)2, C1-C6 alkil, C3-C8 cikloalkil, i C3-C8 cikloalkilmetil; R12 je izabran iz grupe koju čine: : H, -SR, -OR, -N(R)2, C1-C6 alkil, C3-C8 cikloalkil, i C3-C8 cikloalkilmetil; n je izabran iz grupe koju čine: 0, 1, i 2; svaki od R je izabran iz grupe koju čine: H, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C8 cikloalkil, C3-C8 cikloalkilmetil, halogen-supstituirani C1-C6 alkil, hidroksi-supstituirani C1-C6 alkil, alkoksi-supstituirani C1-C6 alkil, amino-supstituirani C1-C6 alkil, i C1-C4 alkilamino-supstituirani C1-C6 alkil.
2. Spoj1,3-disupstituiranog ketena prema zahtjevu 1 ili njegova farmaceutski prihvatljiva sol ili njegov stereoizomer, naznačen time , da je prsten A izabran iz grupe koju čine: [image] [image]
3. Spoj 1,3-disupstituiranog ketena prema zahtjevu 2 ili njegova farmaceutski prihvatljiva sol ili njegov stereoizomer, naznačen time, da je prsten A izabran iz grupe koju čine: [image] [image]
4. Spoj 1,3-disupstituiranog ketena prema zahtjevu 1 ili njegova farmaceutski prihvatljiva sol ili njegov stereoizomer, naznačen time, da je R9 izabran iz grupe koju čine: H, metil, etil, izopropil, i trifluorometil.
5. Spoj 1,3-disupstituiranog ketena prema zahtjevu 1 ili njegova farmaceutski prihvatljiva sol ili njegov stereoizomer, naznačen time, da je R12 izabran iz grupe koju čine: H, -SR, - OR, -N(R)2, i C1-C6 alkil; u kojoj je R izabran iz grupe koju čine: H, i C1-C6 alkil.
6. Spoj 1,3-disupstituiranog ketena prema zahtjevu 1 ili njegova farmaceutski prihvatljiva sol ili njegov stereoizomer, naznačen time , da su R1, R2 oba metil, ili R1, R2 su oba klor.
7. Spoj 1,3-disupstituiranog ketena prema zahtjevu 1 ili njegova farmaceutski prihvatljiva sol ili njegov stereoizomer, naznačen time, R1, R2 su svaki neovisno izabrani iz grupe koju čine: H, C1-C6 alkil, C1-C6 alkoksi, i halogen; R3, R4 su svaki neovisno izabrani iz grupe koju čine: H, C1-C6 alkil, C1-C6 alkoksi, i halogen; ili R3, R4 su vezani tako da formiraju 3-8-člani karbociklični prsten; R6 je izabran iz grupe koju čine H i C1-C6 alkil; prsten A je izabran iz grupe koju čine: [image] [image] R9 je izabran iz grupe koju čine: H, halogen, C1-C6 alkil, C3-C8 cikloalkil, C3-C8 cikloalkilmetil, halogen-supstituirani C1-C6 alkil, hidroksi-supstituirani C1-C6 alkil, alkoksi-supstituirani C1-C6 alkil, amino-supstituirani C1-C6 alkil, C1-C4 alkilamino-supstituirani C1-C6 alkil, nitro, cijano, -OR, -N(R)2, -SR, -C(O)OR, -C(O)N(R)2, -C(O)R, -S(O)R, -S(O)2R, -S(O)2N(R)2, i - N(R)C(O)R; R11 je izabran iz grupe koju čine: H, -SR, -OR, -N(R)2, i C1-C6 alkil; R12 je izabran iz grupe koju čine: H, -SR, -OR, -N(R)2, i C1-C6 alkil; n je izabran iz grupe koju čine: 0, 1, i 2; svaki od R je izabran iz grupe koju čine: H, C1-C6 alkil, C3-C8 cikloalkil, C3-C8 cikloalkilmetil, i halogen-supstituirani C1-C6 alkil.
8. Spoj 1,3-disupstituiranog ketena prema zahtjevu 1 ili njegova farmaceutski prihvatljiva sol ili njegov stereoizomer, naznačen time, R1, R2 su svaki neovisno izabrani iz grupe koju čine: C1-C3 alkil, halogen i C1-C3 alkoksi; R3, R4 su svaki neovisno izabrani iz grupe koju čine: C1-C6 alkil; R6je izabran iz: H; prsten A je izabran iz grupe koju čine: [image] [image] R9 je izabran iz grupe koju čine: H, halogen, C1-C6 alkil, halogen-supstituiran C1-C6 alkil, hidroksi-supstituiran C1-C6 alkil, alkoksi-supstituiran C1-C6 alkil, -OR, -N(R)2, -SR, -C(O)OR, -C(O)N(R)2, -C(O)R, -S(O)R, -S(O)2R, -S(O)2N(R)2, i -N(R)C(O)R; R12 je izabran iz grupe koju čine: H, -SR, -OR, i C1-C6 alkil; n je izabran iz grupe koju čine: 0, i 1; svaki od R je neovisno izabran iz grupe koju čine: H, C1-C6 alkil, C3-C8 cikloalkil, C3-C8 cikloalkilmetil, i halogen-supstituirani C1-C6 alkil.
9. Spoj 1,3-disupstituiranog ketena prema zahtjevu 1 ili njegova farmaceutski prihvatljiva sol ili njegov stereoizomer, naznačen time, da je spoj 1,3-disupstituiranog ketena izabran iz grupe koju čine: [image] [image] [image] [image] [image] [image] [image]
10. Spoj 1,3-disupstituiranog ketena ili njegova farmaceutski prihvatljiva sol ili njegov stereoizomer prema bilo kojem od zahtjeva 1-9 za upotrebu u liječenju bolesti povezane s abnormalnom regulacijom PPAR, a bolest povezana s abnormalnom regulacijom PPAR uključuje bolest povezanu s abnormalnim metabolizmom lipida i glukoze, bolest povezanu s upalom i abnormalnom fibrozom, kardiovaskularnu bolest, bolest bubrega i degenerativnu bolest mozga.
11. Spoj 1,3-disupstituiranog ketena ili njegova farmaceutski prihvatljiva sol ili njegov stereoizomer za upotrebu prema zahtjevu 10, naznačen time, što bolest povezana s abnormalnom regulacijom PPAR obuhvaća: nealkoholnu bolest masne jetre, nealkoholni hepatitis, kolestazu jetre, dijabetes, pretilost, srčanu slabost, aterosklerozu, kroničnu bolest bubrega, otkazivanje bubrega i Alzheimerovu bolest.
12. Farmaceutski sastav za prevenciju ili liječenje bolesti povezanih s abnormalnom regulacijom PPAR, naznačen time, da aktivna supstanca sadrži spoj 1,3-disupstituiranog ketena ili njegovu farmaceutski prihvatljivu sol ili njegov stereoizomer prema bilo kojem od zahtjeva 1-9.
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