US20170313665A1 - Hydroxyalkyl-substituted phenyltriazole derivatives and uses thereof - Google Patents
Hydroxyalkyl-substituted phenyltriazole derivatives and uses thereof Download PDFInfo
- Publication number
- US20170313665A1 US20170313665A1 US15/523,061 US201515523061A US2017313665A1 US 20170313665 A1 US20170313665 A1 US 20170313665A1 US 201515523061 A US201515523061 A US 201515523061A US 2017313665 A1 US2017313665 A1 US 2017313665A1
- Authority
- US
- United States
- Prior art keywords
- triazol
- chlorophenyl
- methyl
- trifluoro
- dihydro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 0 *[2*]C.B[2*]C.[1*]C(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(C)(F)F)C2=O)=NN1C1=CC=CC=C1 Chemical compound *[2*]C.B[2*]C.[1*]C(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(C)(F)F)C2=O)=NN1C1=CC=CC=C1 0.000 description 12
- LKKRWPKFXDAWPJ-JTQLQIEISA-N COC(=O)CN1N=C(C2=CC=C(Cl)C=C2)N(C[C@H](O)C(F)(F)F)C1=O Chemical compound COC(=O)CN1N=C(C2=CC=C(Cl)C=C2)N(C[C@H](O)C(F)(F)F)C1=O LKKRWPKFXDAWPJ-JTQLQIEISA-N 0.000 description 3
- MBNXMROVVRRAJA-TYJDENFWSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(C(F)(F)F)=C1 Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(C(F)(F)F)=C1 MBNXMROVVRRAJA-TYJDENFWSA-N 0.000 description 2
- ZECGDKYVWRLBNY-LBPRGKRZSA-N CCC(=O)CN1N=C(C2=CC=C(Cl)C=C2)N(C[C@H](O)C(F)(F)F)C1=O Chemical compound CCC(=O)CN1N=C(C2=CC=C(Cl)C=C2)N(C[C@H](O)C(F)(F)F)C1=O ZECGDKYVWRLBNY-LBPRGKRZSA-N 0.000 description 2
- SKHPVKDLMYKDMV-ZEQHVICYSA-N B.COC(=O)CCC(=O)CNC(=O)C1=CC=C(Cl)C=C1.COC(=O)CCl.COC(=O)CN1N=C(C2=CC=C(Cl)C=C2)N(CC(O)C(F)(F)F)C1=O.COC(=O)CN1N=C(C2=CC=C(Cl)C=C2)N(C[C@@H](O)C(F)(F)F)C1=O.COC(=O)CN1N=C(C2=CC=C(Cl)C=C2)N(C[C@H](O)C(F)(F)F)C1=O.COC(=O)CN=C=O.NNC(=O)C1=CC=C(Cl)C=C1.O=C(O)CN1C(=O)NN=C1C1=CC=C(Cl)C=C1.O=C1NN=C(C2=CC=C(Cl)C=C2)N1CC(=O)C(F)(F)F.O=C1NN=C(C2=CC=C(Cl)C=C2)N1CC(O)C(F)(F)F.[2HH].[NaH] Chemical compound B.COC(=O)CCC(=O)CNC(=O)C1=CC=C(Cl)C=C1.COC(=O)CCl.COC(=O)CN1N=C(C2=CC=C(Cl)C=C2)N(CC(O)C(F)(F)F)C1=O.COC(=O)CN1N=C(C2=CC=C(Cl)C=C2)N(C[C@@H](O)C(F)(F)F)C1=O.COC(=O)CN1N=C(C2=CC=C(Cl)C=C2)N(C[C@H](O)C(F)(F)F)C1=O.COC(=O)CN=C=O.NNC(=O)C1=CC=C(Cl)C=C1.O=C(O)CN1C(=O)NN=C1C1=CC=C(Cl)C=C1.O=C1NN=C(C2=CC=C(Cl)C=C2)N1CC(=O)C(F)(F)F.O=C1NN=C(C2=CC=C(Cl)C=C2)N1CC(O)C(F)(F)F.[2HH].[NaH] SKHPVKDLMYKDMV-ZEQHVICYSA-N 0.000 description 1
- WRWVYKBRGUSSIO-PEYOIHGTSA-N CC(C)(C)O[K].COC(=O)CBr.COC(=O)CN1N=C(C2=CC=C(Cl)C=C2)N(C[C@H](O)C(F)(F)F)C1=O.O=C1NN=C(C2=CC=C(Cl)C=C2)N1CC(=O)C(F)(F)F.O=C1NN=C(C2=CC=C(Cl)C=C2)N1C[C@H](O)C(F)(F)F Chemical compound CC(C)(C)O[K].COC(=O)CBr.COC(=O)CN1N=C(C2=CC=C(Cl)C=C2)N(C[C@H](O)C(F)(F)F)C1=O.O=C1NN=C(C2=CC=C(Cl)C=C2)N1CC(=O)C(F)(F)F.O=C1NN=C(C2=CC=C(Cl)C=C2)N1C[C@H](O)C(F)(F)F WRWVYKBRGUSSIO-PEYOIHGTSA-N 0.000 description 1
- HDHGODNJCZVSGL-LBPRGKRZSA-N CC(F)(F)[C@@H](O)CN1C(=O)N(CC(=O)CN)N=C1C1=CC=C(Cl)C=C1 Chemical compound CC(F)(F)[C@@H](O)CN1C(=O)N(CC(=O)CN)N=C1C1=CC=C(Cl)C=C1 HDHGODNJCZVSGL-LBPRGKRZSA-N 0.000 description 1
- OECQSTSLOORQDJ-LYNSQETBSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1 Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1 OECQSTSLOORQDJ-LYNSQETBSA-N 0.000 description 1
- PPCNIJXGSUNFNP-KLLZUTDZSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC(Cl)=CC(Cl)=C1 Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC(Cl)=CC(Cl)=C1 PPCNIJXGSUNFNP-KLLZUTDZSA-N 0.000 description 1
- ADPVGKJNUUDAKE-KLLZUTDZSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC(Cl)=CC=C1Cl Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC(Cl)=CC=C1Cl ADPVGKJNUUDAKE-KLLZUTDZSA-N 0.000 description 1
- AELVCSCLEHUOCA-KLLZUTDZSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC(F)=CC(Cl)=C1 Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC(F)=CC(Cl)=C1 AELVCSCLEHUOCA-KLLZUTDZSA-N 0.000 description 1
- VCVRIIDLAKHHKF-KLLZUTDZSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC(F)=CC(F)=C1 Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC(F)=CC(F)=C1 VCVRIIDLAKHHKF-KLLZUTDZSA-N 0.000 description 1
- TXHPTHDEZVDGOD-KLLZUTDZSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC(F)=CC=C1Cl Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC(F)=CC=C1Cl TXHPTHDEZVDGOD-KLLZUTDZSA-N 0.000 description 1
- GDWJOHZEUIDISD-KLLZUTDZSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=C(F)C(Cl)=C1 Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=C(F)C(Cl)=C1 GDWJOHZEUIDISD-KLLZUTDZSA-N 0.000 description 1
- JZXZEMWQRZYDBW-KLLZUTDZSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=C(F)C=C1Cl Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=C(F)C=C1Cl JZXZEMWQRZYDBW-KLLZUTDZSA-N 0.000 description 1
- AFBAXCGPBVGFKF-TYJDENFWSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(C(F)F)=C1 Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(C(F)F)=C1 AFBAXCGPBVGFKF-TYJDENFWSA-N 0.000 description 1
- AZXOTZCWQDJCLY-TYJDENFWSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(Cl)=C1 Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(Cl)=C1 AZXOTZCWQDJCLY-TYJDENFWSA-N 0.000 description 1
- KDSOXPWHPQGZOA-NBFOKTCDSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(Cl)=C1Cl Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(Cl)=C1Cl KDSOXPWHPQGZOA-NBFOKTCDSA-N 0.000 description 1
- XLHPSYMPHMEBEM-NBFOKTCDSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(Cl)=C1F Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(Cl)=C1F XLHPSYMPHMEBEM-NBFOKTCDSA-N 0.000 description 1
- LMCFYRMGTWJDNW-TYJDENFWSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(F)=C1 Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(F)=C1 LMCFYRMGTWJDNW-TYJDENFWSA-N 0.000 description 1
- CFQGBADCANUOKR-NBFOKTCDSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(F)=C1Cl Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(F)=C1Cl CFQGBADCANUOKR-NBFOKTCDSA-N 0.000 description 1
- HPTSEKSTHUKZRX-NBFOKTCDSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(F)=C1F Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(F)=C1F HPTSEKSTHUKZRX-NBFOKTCDSA-N 0.000 description 1
- IAJBSIGOAQAIRI-TYJDENFWSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(OC(F)F)=C1 Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(OC(F)F)=C1 IAJBSIGOAQAIRI-TYJDENFWSA-N 0.000 description 1
- AISVFEMEWAYAQO-RUINGEJQSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC=C1 Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC=C1 AISVFEMEWAYAQO-RUINGEJQSA-N 0.000 description 1
- ADRJCNVKGYNWJK-TYJDENFWSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC=C1C(F)(F)F Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC=C1C(F)(F)F ADRJCNVKGYNWJK-TYJDENFWSA-N 0.000 description 1
- UEPVLORYRWERPC-TYJDENFWSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC=C1Cl Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC=C1Cl UEPVLORYRWERPC-TYJDENFWSA-N 0.000 description 1
- ZLLCUINSVGJSHR-TYJDENFWSA-N CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC=C1F Chemical compound CC(O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC=C1F ZLLCUINSVGJSHR-TYJDENFWSA-N 0.000 description 1
- KGRZMUFPGFQNNU-IBYPIGCZSA-N CC1=CC(N2N=C(CN3N=C(C4=CC=C(Cl)C=C4)N(C[C@H](O)C(F)(F)F)C3=O)N=C2C(C)O)=CC=C1 Chemical compound CC1=CC(N2N=C(CN3N=C(C4=CC=C(Cl)C=C4)N(C[C@H](O)C(F)(F)F)C3=O)N=C2C(C)O)=CC=C1 KGRZMUFPGFQNNU-IBYPIGCZSA-N 0.000 description 1
- KCVPFBTYHJAOFU-IBYPIGCZSA-N CC1=CC=CC=C1N1N=C(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)N=C1C(C)O Chemical compound CC1=CC=CC=C1N1N=C(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)N=C1C(C)O KCVPFBTYHJAOFU-IBYPIGCZSA-N 0.000 description 1
- GWZQLMNDQHJWSB-KRWDZBQOSA-N CC1=CC=CC=C1N1N=C(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)N=C1CO Chemical compound CC1=CC=CC=C1N1N=C(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)N=C1CO GWZQLMNDQHJWSB-KRWDZBQOSA-N 0.000 description 1
- ULFJOTBYRGVTCC-PKDNWHCCSA-N CCC1=CC=CC=C1N1N=C(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)N=C1C(C)O Chemical compound CCC1=CC=CC=C1N1N=C(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)N=C1C(C)O ULFJOTBYRGVTCC-PKDNWHCCSA-N 0.000 description 1
- URESPRTVIFVPRA-ZJFPTPTDSA-N COC1=CC=C(F)C=C1N1N=C(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)N=C1C(C)O Chemical compound COC1=CC=C(F)C=C1N1N=C(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)N=C1C(C)O URESPRTVIFVPRA-ZJFPTPTDSA-N 0.000 description 1
- UCBICGCDJUXKFA-UWBLVGDVSA-N COC1=CC=CC=C1N1N=C(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)N=C1C(C)O Chemical compound COC1=CC=CC=C1N1N=C(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)N=C1C(C)O UCBICGCDJUXKFA-UWBLVGDVSA-N 0.000 description 1
- WKYCWEGMICVNLX-KRWDZBQOSA-N COC1=CC=CC=C1N1N=C(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)N=C1CO Chemical compound COC1=CC=CC=C1N1N=C(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)N=C1CO WKYCWEGMICVNLX-KRWDZBQOSA-N 0.000 description 1
- QPERQXVOWLCCJD-QNDGGIRCSA-N C[C@@H](O)C(=N)N.C[C@H](O)C(=N)N Chemical compound C[C@@H](O)C(=N)N.C[C@H](O)C(=N)N QPERQXVOWLCCJD-QNDGGIRCSA-N 0.000 description 1
- OECQSTSLOORQDJ-KCJUWKMLSA-N C[C@@H](O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1 Chemical compound C[C@@H](O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1 OECQSTSLOORQDJ-KCJUWKMLSA-N 0.000 description 1
- AZXOTZCWQDJCLY-PXAZEXFGSA-N C[C@@H](O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(Cl)=C1 Chemical compound C[C@@H](O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(Cl)=C1 AZXOTZCWQDJCLY-PXAZEXFGSA-N 0.000 description 1
- LMCFYRMGTWJDNW-PXAZEXFGSA-N C[C@@H](O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(F)=C1 Chemical compound C[C@@H](O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(F)=C1 LMCFYRMGTWJDNW-PXAZEXFGSA-N 0.000 description 1
- UEPVLORYRWERPC-PXAZEXFGSA-N C[C@@H](O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC=C1Cl Chemical compound C[C@@H](O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC=C1Cl UEPVLORYRWERPC-PXAZEXFGSA-N 0.000 description 1
- OECQSTSLOORQDJ-KWQFWETISA-N C[C@H](O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1 Chemical compound C[C@H](O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1 OECQSTSLOORQDJ-KWQFWETISA-N 0.000 description 1
- AZXOTZCWQDJCLY-SJCJKPOMSA-N C[C@H](O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(Cl)=C1 Chemical compound C[C@H](O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(Cl)=C1 AZXOTZCWQDJCLY-SJCJKPOMSA-N 0.000 description 1
- LMCFYRMGTWJDNW-SJCJKPOMSA-N C[C@H](O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(F)=C1 Chemical compound C[C@H](O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC(F)=C1 LMCFYRMGTWJDNW-SJCJKPOMSA-N 0.000 description 1
- UEPVLORYRWERPC-SJCJKPOMSA-N C[C@H](O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC=C1Cl Chemical compound C[C@H](O)C1=NC(CN2N=C(C3=CC=C(Cl)C=C3)N(C[C@H](O)C(F)(F)F)C2=O)=NN1C1=CC=CC=C1Cl UEPVLORYRWERPC-SJCJKPOMSA-N 0.000 description 1
- DYLKTKZFTXKKFU-INIZCTEOSA-N O=C1N(CC2=NN(C3=CC(F)=CC(Cl)=C3)C(CO)=N2)N=C(C2=CC=C(Cl)C=C2)N1C[C@H](O)C(F)(F)F Chemical compound O=C1N(CC2=NN(C3=CC(F)=CC(Cl)=C3)C(CO)=N2)N=C(C2=CC=C(Cl)C=C2)N1C[C@H](O)C(F)(F)F DYLKTKZFTXKKFU-INIZCTEOSA-N 0.000 description 1
- CHSILNGVDWHEAJ-INIZCTEOSA-N O=C1N(CC2=NN(C3=CC(F)=CC(F)=C3)C(CO)=N2)N=C(C2=CC=C(Cl)C=C2)N1C[C@H](O)C(F)(F)F Chemical compound O=C1N(CC2=NN(C3=CC(F)=CC(F)=C3)C(CO)=N2)N=C(C2=CC=C(Cl)C=C2)N1C[C@H](O)C(F)(F)F CHSILNGVDWHEAJ-INIZCTEOSA-N 0.000 description 1
- CQCGLWUPSPPBBY-INIZCTEOSA-N O=C1N(CC2=NN(C3=CC(F)=CC=C3Cl)C(CO)=N2)N=C(C2=CC=C(Cl)C=C2)N1C[C@H](O)C(F)(F)F Chemical compound O=C1N(CC2=NN(C3=CC(F)=CC=C3Cl)C(CO)=N2)N=C(C2=CC=C(Cl)C=C2)N1C[C@H](O)C(F)(F)F CQCGLWUPSPPBBY-INIZCTEOSA-N 0.000 description 1
- GBPJUHNUSIGJBG-INIZCTEOSA-N O=C1N(CC2=NN(C3=CC=CC(Cl)=C3)C(CO)=N2)N=C(C2=CC=C(Cl)C=C2)N1C[C@H](O)C(F)(F)F Chemical compound O=C1N(CC2=NN(C3=CC=CC(Cl)=C3)C(CO)=N2)N=C(C2=CC=C(Cl)C=C2)N1C[C@H](O)C(F)(F)F GBPJUHNUSIGJBG-INIZCTEOSA-N 0.000 description 1
- FVJJYTZFOAEEFG-INIZCTEOSA-N O=C1N(CC2=NN(C3=CC=CC(F)=C3)C(CO)=N2)N=C(C2=CC=C(Cl)C=C2)N1C[C@H](O)C(F)(F)F Chemical compound O=C1N(CC2=NN(C3=CC=CC(F)=C3)C(CO)=N2)N=C(C2=CC=C(Cl)C=C2)N1C[C@H](O)C(F)(F)F FVJJYTZFOAEEFG-INIZCTEOSA-N 0.000 description 1
- QXSMHJYKQTZSPY-INIZCTEOSA-N O=C1N(CC2=NN(C3=CC=CC=C3C(F)(F)F)C(CO)=N2)N=C(C2=CC=C(Cl)C=C2)N1C[C@H](O)C(F)(F)F Chemical compound O=C1N(CC2=NN(C3=CC=CC=C3C(F)(F)F)C(CO)=N2)N=C(C2=CC=C(Cl)C=C2)N1C[C@H](O)C(F)(F)F QXSMHJYKQTZSPY-INIZCTEOSA-N 0.000 description 1
- PLGISEQGTKQAGY-INIZCTEOSA-N O=C1N(CC2=NN(C3=CC=CC=C3Cl)C(CO)=N2)N=C(C2=CC=C(Cl)C=C2)N1C[C@H](O)C(F)(F)F Chemical compound O=C1N(CC2=NN(C3=CC=CC=C3Cl)C(CO)=N2)N=C(C2=CC=C(Cl)C=C2)N1C[C@H](O)C(F)(F)F PLGISEQGTKQAGY-INIZCTEOSA-N 0.000 description 1
- QIFYQCSEJVGOAB-JTQLQIEISA-N O=C1N(CC2=NNC(CO)=N2)N=C(C2=CC=C(Cl)C=C2)N1C[C@H](O)C(F)(F)F Chemical compound O=C1N(CC2=NNC(CO)=N2)N=C(C2=CC=C(Cl)C=C2)N1C[C@H](O)C(F)(F)F QIFYQCSEJVGOAB-JTQLQIEISA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D249/12—Oxygen or sulfur atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Definitions
- the liquid content of the human body is subject to various physiological control mechanisms, the purpose of which is to keep it constant (volume homeostasis).
- both the volume filling of the vascular system and also the osmolarity of the plasma are continuously recorded by appropriate sensors (baroreceptors and osmoreceptors).
- the information which these sensors supply to the relevant centers in the brain regulates drinking behaviour and controls fluid excretion via the kidneys by means of humoral and neural signals.
- the peptide hormone vasopressin is of central importance in this [Schrier R. W., Abraham W. T., New Engl. J. Med. 341, 577-585 (1999)].
- Vasopressin exerts its action mainly via binding to three receptors, which are classified as V1a, V1b and V2 receptors and which belong to the family of G protein-coupled receptors.
- V1a receptors are mainly located on the cells of the vascular smooth musculature. Their activation gives rise to vasoconstriction, as a result of which the peripheral resistance and blood pressure rise. Apart from this, V1a receptors are also detectable in the liver.
- V1b receptors also named V3 receptors
- vasopressin regulates the basal and stress-induced secretion of adrenocorticotropic hormone (ACTH) via the V1b receptor.
- CSH corticotropin-releasing hormone
- V2 receptors are located in the distal tubular epithelium and the epithelium of the collecting tubules in the kidney. Their activation renders these epithelia permeable to water. This phenomenon is due to the incorporation of aquaporins (special water channels) in the luminal membrane of the epithelial cells.
- V2 receptor antagonists cause increased water excretion, without substantially increasing the excretion of electrolytes. This means that with V2 antagonist drugs, volume homeostasis can be restored without affecting electrolyte homeostasis.
- drugs with V2 antagonistic activity appear particularly suitable for the treatment of all disease conditions which are associated with an overloading of the body with water, without the electrolytes being adequately increased in parallel.
- hyponatremia sodium concentration ⁇ 135 mmol/L
- hyponatremia sodium concentration ⁇ 135 mmol/L
- comatose states and death are imminent.
- hypovolemic euvolemic
- hypervolemic hyponatremia The forms of hypervolemia with edema formation are clinically significant. Typical examples of these are the syndrome of inappropriate ADH/vasopressin secretion (SIADH) (e.g.
- V1a and V2 vasopressin receptors
- V1a and V2 vasopressin receptors
- V1a and V2 vasopressin receptors
- the provision of such combined vasopressin antagonists also appears to make sense inasmuch as a volume diminution mediated solely via V2 receptor blockade can entail the stimulation of osmoreceptors and, as a result, may lead to a further compensatory increase in vasopressin release.
- vasopressin such as for example vasoconstriction and heart muscle hypertrophy
- WO 2011/104322-A1 a particular group of bis-aryl-bonded 1,2,4-triazol-3-ones, including 5-phenyl-1,2,4-triazol-3-yl and 1-phenyl-1,2,3-triazol-4-yl derivatives thereof, has been disclosed as antagonists of vasopressin V1a and/or V2 receptors being useful for the treatment and/or prevention of cardiovascular diseases.
- candidate compounds were frequently compromised by an unsatisfactory aquaretic potency when evaluated in vivo following peroral administration to conscious rats.
- a robust aquaretic efficacy is a desirable prerequisite for the treatment of disease conditions that are associated with an overloading of the body with water, such as, for example, in congestive heart failure.
- a significant increase in aquaretic potency would also help towards reducing the amount of substance which is going to be required to achieve and maintain the desired therapeutic effect, thus limiting the potential for unacceptable side effects and/or unwanted drug-drug interactions during the treatment of patients which might already be at high risk, such as, for example, in acute or chronic heart failure or renal failure.
- the technical problem to be solved according to the present invention may therefore be seen in identifying and providing new compounds that act as potent antagonists of both vasopressin V1a and V2 receptors and, in addition, exhibit a substantial increase in aquaretic potency in vivo.
- Compounds according to the invention are the compounds of the formula (I) and their salts, solvates and solvates of the salts, the compounds included in the formula (I) of the formulae mentioned in the following and their salts, solvates and solvates of the salts, and the compounds included in the formula (I) and mentioned in the following as process products and/or embodiment examples and their salts, solvates and solvates of the salts, where the compounds included in the formula (I) and mentioned in the following are not already salts, solvates and solvates of the salts.
- Solvates in the context of the invention are designated as those forms of the compounds according to the invention which form a complex in the solid or liquid state by stoichiometric coordination with solvent molecules. Hydrates are a specific form of solvates, in which the coordination takes place with water. Hydrates are preferred solvates in the context of the present invention.
- the compounds of this invention may, either by nature of asymmetric centers or by restricted rotation, be present in the form of isomers (enantiomers, diastereomers). Any isomer may be present in which the asymmetric center is in the (R)-, (S)-, or (R,S)-configuration.
- isotopes for example of deuterium
- isotopes can lead to particular therapeutic benefits as a consequence of greater metabolic stability of the compound, for example an extension of the half-life in the body or a reduction in the active dose required.
- modifications of the compounds according to the invention may therefore in some cases also constitute a preferred embodiment of the present invention.
- Isotopic variants of the compounds according to the invention can be prepared by processes known to those skilled in the art, for example by the methods described below and the methods described in the working examples, by using corresponding isotopic modifications of the particular reagents and/or starting compounds therein.
- the present invention relates to compounds of formula (I), wherein
- the present invention relates to compounds according to formula (I) selected from the group consisting of the following compounds
- R 1 , R 2A and R 2B have the meanings described above, optionally followed, where appropriate, by (i) separating the compounds of formula (I) thus obtained into their respective diastereomers, preferably using chromatographic methods, and/or (ii) converting the compounds of formula (I) into their respective hydrates, solvates, salts and/or hydrates or solvates of the salts by treatment with the corresponding solvents and/or acids or bases.
- the 1,2,4-triazole derivative of formula (V) produced by this reaction may also be present in other tautomeric forms, such as (V-A) or (V-B)
- the compounds of the invention are suitable for treating urological diseases and diseases of the male and female urogenital system such as, for example, benign prostatic syndrome (BPS), benign prostatic hyperplasia (BPH), benign prostatic enlargement (BPE), bladder outlet obstruction (BOO), lower urinary tract syndromes (LUTS), neurogenic overactive bladder (OAB), interstitial cystitis (IC), urinary incontinence (UI), for example mixed, urge, stress and overflow incontinence (MUI, UUI, SUI, OUI), pelvic pains, erectile dysfunction and female sexual dysfunction.
- BPS benign prostatic syndrome
- BPH benign prostatic hyperplasia
- BPE benign prostatic enlargement
- BOO bladder outlet obstruction
- LUTS lower urinary tract syndromes
- OAB neurogenic overactive bladder
- IC interstitial cystitis
- UI urinary incontinence
- MUI urinary incontinence
- MUI UUI, SUI, OUI
- reaction mixture was stirred at room temperature for 5 days, after which extra boronic acid (54.4 mg, 0.36 mmol, 0.5 eq.) was added due to incomplete conversion.
- extra boronic acid 54.4 mg, 0.36 mmol, 0.5 eq.
- the reaction mixture was diluted with MTBE and then quenched with aqueous hydrochloric acid (0.5 M). After phase separation, the aqueous phase was extracted twice with MTBE. The combined organic phases were dried over sodium sulfate, filtered, and concentrated in vacuo.
- the crude product was purified by preparative HPLC [method 4], and the desired compound (73 mg, 0.14 mmol) was obtained (yield 22.4%, 98% purity).
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Gastroenterology & Hepatology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14191491.1 | 2014-11-03 | ||
| EP14191491 | 2014-11-03 | ||
| PCT/EP2015/075200 WO2016071212A1 (en) | 2014-11-03 | 2015-10-30 | Hydroxyalkyl-substituted phenyltriazole derivatives and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US20170313665A1 true US20170313665A1 (en) | 2017-11-02 |
Family
ID=51897095
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US15/523,061 Abandoned US20170313665A1 (en) | 2014-11-03 | 2015-10-30 | Hydroxyalkyl-substituted phenyltriazole derivatives and uses thereof |
| US14/930,157 Active 2035-11-27 US9771352B2 (en) | 2014-11-03 | 2015-11-02 | Hydroxyalkyl-substituted phenyltriazole derivatives and uses thereof |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US14/930,157 Active 2035-11-27 US9771352B2 (en) | 2014-11-03 | 2015-11-02 | Hydroxyalkyl-substituted phenyltriazole derivatives and uses thereof |
Country Status (40)
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10927098B2 (en) | 2016-10-20 | 2021-02-23 | Bayer Pharma Aktiengesellschaft | Hydroxyalkyl-substituted triazole derivatives and uses thereof |
| US11091463B2 (en) | 2016-05-03 | 2021-08-17 | Bayer Pharma Aktiengesellschaft | Amide-substituted pyridinyltriazole derivatives and uses thereof |
| US11149023B2 (en) | 2017-10-24 | 2021-10-19 | Bayer Pharma Aktiengesellschaft | Substituted triazole derivatives and uses thereof |
| US11173151B2 (en) | 2017-10-24 | 2021-11-16 | Bayer Aktiengesellschaft | Substituted triazole derivatives and uses thereof |
| US11230540B2 (en) | 2017-10-24 | 2022-01-25 | Bayer Pharma Aktiengesellschaft | Substituted triazole derivatives and uses thereof |
| US11298367B2 (en) | 2017-10-24 | 2022-04-12 | Bayer Aktiengesellschaft | Prodrugs of substituted triazole derivatives and uses thereof |
| US11331314B2 (en) | 2017-10-24 | 2022-05-17 | Bayer Pharma Aktiengesellschaft | Amine substituted triazole derivatives and uses thereof |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2539326B1 (de) | 2010-02-27 | 2017-05-03 | Bayer Intellectual Property GmbH | Bis-arylverknüpfte aryltriazolone und ihre verwendung |
| US10138236B2 (en) | 2014-09-24 | 2018-11-27 | Bayer Pharma Aktiengesellschaft | Factor xia-inhibiting pyridobenzazepine and pyridobenzazocine derivatives |
| CN107949562B (zh) | 2015-06-09 | 2021-07-23 | 拜耳制药股份公司 | 毒蕈碱性m2受体的正性变构调节剂 |
| US10525041B2 (en) | 2016-05-03 | 2020-01-07 | Bayer Pharma Aktiengesellschaft | Fluoroalkyl-substituted aryltriazole derivatives and uses thereof |
| EP3452457B1 (en) * | 2016-05-03 | 2020-03-18 | Bayer Pharma Aktiengesellschaft | Oxoalkyl-substituted phenyltriazole derivatives and uses thereof |
| CN113105403A (zh) | 2016-05-03 | 2021-07-13 | 拜耳制药股份公司 | 制备5-羟基烷基-取代的1-苯基-1,2,4-三唑衍生物的方法 |
| US10526314B2 (en) | 2016-05-03 | 2020-01-07 | Bayer Aktiengesellschaft | Hydroxyalkyl-substituted heteroaryltriazole derivatives and uses thereof |
| AR108265A1 (es) | 2016-05-03 | 2018-08-01 | Bayer Pharma AG | Derivados de feniltriazol sustituidos con amida y usos de estos |
| WO2017191117A1 (en) | 2016-05-03 | 2017-11-09 | Bayer Pharma Aktiengesellschaft | V1a receptor antagonists for use in the treatment of renal diseases |
| US20190119251A1 (en) | 2016-05-03 | 2019-04-25 | Bayer Pharma Aktiengesellschaft | Amide-substituted aryltriazole derivatives and uses thereof |
| WO2018011017A1 (de) | 2016-07-11 | 2018-01-18 | Bayer Pharma Aktiengesellschaft | 7-substituierte 1-pyridyl-naphthyridin-3-carbonsäureamide und ihre verwendung |
| EP3296298A1 (de) | 2016-09-14 | 2018-03-21 | Bayer Pharma Aktiengesellschaft | 7-substituierte 1-aryl-naphthyridin-3-carbonsäureamide und ihre verwendung |
| JOP20190045A1 (ar) | 2016-09-14 | 2019-03-14 | Bayer Ag | مركبات أميد حمض 1- أريل-نفثيريدين-3-كربوكسيليك مستبدلة في الموضع 7 واستخدامها. |
| JOP20190080A1 (ar) | 2016-10-14 | 2019-04-11 | Bayer Pharma AG | مركبات مشتقة من 6-(1h-بيرازول-1-يل) بيريميدين-4- أمين مستبدل واستخداماتها |
| WO2018149929A1 (en) * | 2017-02-16 | 2018-08-23 | Bayer Pharma Aktiengesellschaft | Combination of reporter gene assays and transcriptional analysis |
| EP3700897A1 (en) | 2017-10-24 | 2020-09-02 | Bayer Pharma Aktiengesellschaft | Substituted triazole derivatives and uses thereof |
| WO2019081291A1 (en) | 2017-10-24 | 2019-05-02 | Bayer Aktiengesellschaft | PRODRUGS OF SUBSTITUTED TRIAZOLE DERIVATIVES AND USES THEREOF |
| CN111225917A (zh) | 2017-10-24 | 2020-06-02 | 拜耳股份公司 | 取代咪唑并吡啶酰胺及其用途 |
| EP3740236A1 (de) | 2018-01-16 | 2020-11-25 | Bayer Aktiengesellschaft | Unterstützung bei der behandlung von herzinsuffizienz |
| EP3553081A1 (en) | 2018-04-12 | 2019-10-16 | Bayer Aktiengesellschaft | Atrial natriuretic peptide engrafted antibodies |
| EP3553082A1 (en) | 2018-04-12 | 2019-10-16 | Bayer Aktiengesellschaft | Brain natriuretic peptide engrafted antibodies |
| EP3553079A1 (en) | 2018-04-12 | 2019-10-16 | Bayer Aktiengesellschaft | C-type natriuretic peptide engrafted antibodies |
| CA3100096A1 (en) | 2018-05-15 | 2019-11-21 | Bayer Aktiengesellschaft | 1,3-thiazol-2-yl substituted benzamides for the treatment of diseases associated with nerve fiber sensitization |
| CA3100221A1 (en) | 2018-05-17 | 2019-11-21 | Bayer Aktiengesellschaft | Substituted dihydropyrazolo pyrazine carboxamide derivatives |
| WO2020216669A1 (de) | 2019-04-23 | 2020-10-29 | Bayer Aktiengesellschaft | Phenylsubstituierte imidazopyridinamide und ihre verwendung |
| CN110082451B (zh) * | 2019-05-23 | 2021-12-24 | 南京趣酶生物科技有限公司 | 一种2-氯-1-(6-氟-色满-2-)乙醇手性醇中间体制备过程的sfc检测方法 |
| WO2021094210A1 (en) | 2019-11-12 | 2021-05-20 | Bayer Aktiengesellschaft | Substituted pyrazine carboxamide derivatives as prostaglandin ep3 receptor antagonists |
| WO2021094208A1 (en) | 2019-11-12 | 2021-05-20 | Bayer Aktiengesellschaft | Substituted imidazo pyrimidine ep3 antagonists |
| WO2021094209A1 (en) | 2019-11-12 | 2021-05-20 | Bayer Aktiengesellschaft | Substituted pyrrolo triazine carboxamide derivatives as prostaglandin ep3 receptor antagonists |
| EP3822268A1 (en) | 2019-11-15 | 2021-05-19 | Bayer Aktiengesellschaft | Substituted hydantoinamides as adamts7 antagonists |
| EP3822265A1 (en) | 2019-11-15 | 2021-05-19 | Bayer AG | Substituted hydantoinamides as adamts7 antagonists |
| CN115916197A (zh) | 2020-04-22 | 2023-04-04 | 拜耳公司 | 用于治疗和/或预防心血管和/或肾脏疾病的非奈利酮和sglt2抑制剂的组合 |
| EP3900722A1 (en) | 2020-04-22 | 2021-10-27 | Bayer AG | Combination of finerenone and pecavaptan for the treatment and/or prevention of cardiovascular and/or renal diseases |
| WO2021259852A1 (en) | 2020-06-25 | 2021-12-30 | Bayer Aktiengesellschaft | Process for preparing 5-(alkoxycarbonyl)-and 5-(carboxamide)-1-aryl-1,2,4-triazole derivatives |
| WO2022112213A1 (en) | 2020-11-30 | 2022-06-02 | Bayer Aktiengesellschaft | Crystalline forms of 3-[[3-(4-chlorophenyl)-5-oxo-4-((2s)-3,3,3-trifluoro- 2-hydroxypropyl)-4,5-dihydro-1h-1,2,4-triazol-1-yl]methyl]-1-[3- (trifluoromethyl)pyridin-2-yl]-1h-1,2,4-triazole-5-carboxamide |
| MX2023006903A (es) | 2020-12-10 | 2023-06-26 | Bayer Ag | Acidos pirazol piperidin carboxilicos sustituidos. |
| EP4011874A1 (en) | 2020-12-10 | 2022-06-15 | Bayer Aktiengesellschaft | Substituted pyrazolo piperidine carboxylic acids |
| EP4011873A1 (en) | 2020-12-10 | 2022-06-15 | Bayer Aktiengesellschaft | Substituted pyrazolo piperidine carboxylic acids |
| EP4259140A1 (en) | 2020-12-10 | 2023-10-18 | Bayer Aktiengesellschaft | The use of sgc activators for the treatment of ophthalmologic diseases |
| CN116829545A (zh) | 2020-12-10 | 2023-09-29 | 拜耳公司 | 取代的吡唑基哌啶羧酸 |
| WO2022214206A1 (en) | 2021-04-08 | 2022-10-13 | Bayer Aktiengesellschaft | Combination of finerenone and pecavaptan for the treatment and/or prevention of cardiovascular and/or renal diseases |
| WO2023237577A1 (en) | 2022-06-09 | 2023-12-14 | Bayer Aktiengesellschaft | Soluble guanylate cyclase activators for use in the treatment of heart failure with preserved ejection fraction in women |
Family Cites Families (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3042466A1 (de) | 1980-11-11 | 1982-06-16 | A. Nattermann & Cie GmbH, 5000 Köln | N-substituierte (omega) -(2-oxo-4-imidazolin-l-yl)-alkansaeure-derivate, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate |
| US5468448A (en) | 1989-12-28 | 1995-11-21 | Ciba-Geigy Corporation | Peroxide disinfection method and devices therefor |
| DE4107857A1 (de) | 1991-03-12 | 1992-09-17 | Thomae Gmbh Dr K | Cyclische harnstoffderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| EP0586513A1 (en) | 1991-05-10 | 1994-03-16 | Merck & Co. Inc. | Acidic aralkyl triazole derivatives active as angiotensin ii antagonists |
| US5326776A (en) | 1992-03-02 | 1994-07-05 | Abbott Laboratories | Angiotensin II receptor antagonists |
| SK94393A3 (en) | 1992-09-11 | 1994-08-10 | Thomae Gmbh Dr K | Cyclic derivatives of urea, process for their production and their pharmaceutical agents with the content of those |
| GB9301192D0 (en) | 1993-06-09 | 1993-06-09 | Trott Francis W | Flower shaped mechanised table |
| US6844005B2 (en) | 2002-02-25 | 2005-01-18 | Trutek Corp | Electrostatically charged nasal application product with increased strength |
| FR2708608B1 (fr) | 1993-07-30 | 1995-10-27 | Sanofi Sa | Dérivés de N-sulfonylbenzimidazolone, leur préparation, les compositions pharmaceutiques en contenant. |
| US5897858A (en) | 1994-02-03 | 1999-04-27 | Schering-Plough Healthcare Products, Inc. | Nasal spray compositions exhibiting increased retention in the nasal cavity |
| US20010020100A1 (en) | 1994-06-14 | 2001-09-06 | G.D. Searle & Co. | N-substituted-1, 2, 4-triazolone compounds for treatment of cardiovascular disorders |
| WO1999031099A1 (en) | 1997-12-17 | 1999-06-24 | Merck & Co., Inc. | Integrin receptor antagonists |
| DE19816882A1 (de) | 1998-04-17 | 1999-10-21 | Boehringer Ingelheim Pharma | Triazolone mit neuroprotektiver Wirkung |
| DK1100789T3 (da) | 1998-07-24 | 2005-05-23 | Bayer Cropscience Ag | Substituerede benzoylcyclohexandioner |
| DE19834047A1 (de) | 1998-07-29 | 2000-02-03 | Bayer Ag | Substituierte Pyrazolderivate |
| DE19834044A1 (de) | 1998-07-29 | 2000-02-03 | Bayer Ag | Neue substituierte Pyrazolderivate |
| DE19914140A1 (de) | 1999-03-27 | 2000-09-28 | Bayer Ag | Substituierte Benzoylpyrazole |
| KR20020005653A (ko) | 1999-04-01 | 2002-01-17 | 실버스타인 아써 에이. | 소르비톨 디하이드로게나제 저해제로서의 아미노피리미딘 |
| DE19920791A1 (de) | 1999-05-06 | 2000-11-09 | Bayer Ag | Substituierte Benzoylisoxazole |
| DE19921424A1 (de) | 1999-05-08 | 2000-11-09 | Bayer Ag | Substituierte Benzoylketone |
| DE19929348A1 (de) | 1999-06-26 | 2000-12-28 | Bayer Ag | Verfahren zur Herstellung von 2-Heterocyclylmethyl-benzoesäurederivaten |
| US6531142B1 (en) | 1999-08-18 | 2003-03-11 | The Procter & Gamble Company | Stable, electrostatically sprayable topical compositions |
| DE19943636A1 (de) | 1999-09-13 | 2001-03-15 | Bayer Ag | Neuartige Dicarbonsäurederivate mit pharmazeutischen Eigenschaften |
| DE19943639A1 (de) | 1999-09-13 | 2001-03-15 | Bayer Ag | Dicarbonsäurederivate mit neuartigen pharmazeutischen Eigenschaften |
| DE19943635A1 (de) | 1999-09-13 | 2001-03-15 | Bayer Ag | Neuartige Aminodicarbonsäurederivate mit pharmazeutischen Eigenschaften |
| DE19943634A1 (de) | 1999-09-13 | 2001-04-12 | Bayer Ag | Neuartige Dicarbonsäurederivate mit pharmazeutischen Eigenschaften |
| AR027575A1 (es) | 2000-03-06 | 2003-04-02 | Bayer Ag | Benzoilciclohexenonas substituidas |
| US7080644B2 (en) | 2000-06-28 | 2006-07-25 | Microdose Technologies, Inc. | Packaging and delivery of pharmaceuticals and drugs |
| AR031176A1 (es) | 2000-11-22 | 2003-09-10 | Bayer Ag | Nuevos derivados de pirazolpiridina sustituidos con piridina |
| WO2002066447A1 (en) | 2001-02-21 | 2002-08-29 | Ono Pharmaceutical Co., Ltd. | 4h-1,2,4-triazole-3(2h)-thione deratives as sphingomyelinase inhibitors |
| DE10110749A1 (de) | 2001-03-07 | 2002-09-12 | Bayer Ag | Substituierte Aminodicarbonsäurederivate |
| DE10110750A1 (de) | 2001-03-07 | 2002-09-12 | Bayer Ag | Neuartige Aminodicarbonsäurederivate mit pharmazeutischen Eigenschaften |
| US20040071757A1 (en) | 2001-11-20 | 2004-04-15 | David Rolf | Inhalation antiviral patch |
| DE10220570A1 (de) | 2002-05-08 | 2003-11-20 | Bayer Ag | Carbamat-substituierte Pyrazolopyridine |
| AU2004221891B2 (en) | 2003-03-14 | 2009-11-19 | Merck Sharp & Dohme Corp. | Monocyclic anilide spirohydantoin CGRP receptor antagonists |
| KR20060066141A (ko) | 2003-06-27 | 2006-06-15 | 버글린 코퍼레이션 오브 워싱턴 | 사과 및 연한 코아를 가지거나 피트를 가진 다른 과일들을작은 응력을 가지고 정확하게 코아제거하고슬라이스절단하기 위한 기계 |
| JP4698604B2 (ja) * | 2003-12-22 | 2011-06-08 | ファイザー・インク | バソプレシン・アンタゴニストとしてのトリアゾール誘導体 |
| EP1722788A4 (en) | 2004-03-08 | 2008-02-13 | Wyeth Corp | MODULATORS OF IONIC CHANNELS |
| US20070281937A1 (en) | 2004-03-08 | 2007-12-06 | Robert Zelle | Ion Channel Modulators |
| US20070225333A1 (en) | 2004-04-28 | 2007-09-27 | Bryans Justin S | 3-Heterocyclyl-4-Phenyl-Triazole Derivatives as Inhibitors of the Vasopressin Via Receptor |
| US7642275B2 (en) | 2004-12-16 | 2010-01-05 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| WO2006117657A1 (en) | 2005-05-03 | 2006-11-09 | Ranbaxy Laboratories Limited | Triazolone derivatives as anti-inflammatory agents |
| DE102006024024A1 (de) | 2006-05-23 | 2007-11-29 | Bayer Healthcare Aktiengesellschaft | Substituierte Arylimidazolone und -triazolone sowie ihre Verwendung |
| BRPI0810996A2 (pt) * | 2007-04-26 | 2015-01-27 | Lundbeck & Co As H | Composto, método para o tratamento de uma doença, uso de um composto, composição farmcêutica, e, kit. |
| DE102008060967A1 (de) | 2008-12-06 | 2010-06-10 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Phenylsulfonyltriazolone und ihre Verwendung |
| DE102010001064A1 (de) | 2009-03-18 | 2010-09-23 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 2-Acetamido-5-Aryl-1,2,4-triazolone und deren Verwendung |
| DE102009013642A1 (de) | 2009-03-18 | 2010-09-23 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Phenylalaninderivate und deren Verwendung |
| DE102009028929A1 (de) | 2009-08-27 | 2011-07-07 | Bayer Schering Pharma Aktiengesellschaft, 13353 | Heterocyclisch-substituierte 2-Acetamido-5-Aryl-1,2,4-triazolone und deren Verwendung |
| EP2539326B1 (de) * | 2010-02-27 | 2017-05-03 | Bayer Intellectual Property GmbH | Bis-arylverknüpfte aryltriazolone und ihre verwendung |
| DE102010021637A1 (de) | 2010-05-26 | 2011-12-01 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 5-Fluor-1H-Pyrazolopyridine und ihre Verwendung |
| EP2708539A1 (de) | 2010-07-09 | 2014-03-19 | Bayer Intellectual Property GmbH | Annellierte pyrimidine und triazine und ihre verwendung zur behandlung bzw. prophylaxe von herz-kreislauf-erkrankungen |
| DE102010040187A1 (de) | 2010-09-02 | 2012-03-08 | Bayer Schering Pharma Aktiengesellschaft | Substituierte N-Phenethyl-triazolonacetamide und ihre Verwendung |
| DE102010040233A1 (de) | 2010-09-03 | 2012-03-08 | Bayer Schering Pharma Aktiengesellschaft | Bicyclische Aza-Heterocyclen und ihre Verwendung |
| DE102010043379A1 (de) | 2010-11-04 | 2012-05-10 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 6-Fluor-1H-Pyrazolo[4,3-b]pyridine und ihre Verwendung |
| US9604976B2 (en) | 2012-03-22 | 2017-03-28 | Spero Gyrase, Inc. | Antibacterial compounds |
| WO2015052065A1 (de) * | 2013-10-07 | 2015-04-16 | Bayer Pharma Aktiengesellschaft | Cyclische thienouracil-carboxamide und ihre verwendung |
-
2015
- 2015-10-30 AU AU2015342017A patent/AU2015342017B2/en not_active Ceased
- 2015-10-30 MX MX2017005479A patent/MX2017005479A/es active IP Right Grant
- 2015-10-30 AR ARP150103529A patent/AR102487A1/es unknown
- 2015-10-30 EP EP15788389.3A patent/EP3215498B1/en active Active
- 2015-10-30 UY UY0001036383A patent/UY36383A/es not_active Application Discontinuation
- 2015-10-30 SI SI201530445T patent/SI3215498T1/sl unknown
- 2015-10-30 RS RS20181378A patent/RS58049B1/sr unknown
- 2015-10-30 JP JP2017523872A patent/JP6623220B2/ja not_active Expired - Fee Related
- 2015-10-30 PL PL15788389T patent/PL3215498T3/pl unknown
- 2015-10-30 WO PCT/EP2015/075200 patent/WO2016071212A1/en active Application Filing
- 2015-10-30 HU HUE15788389A patent/HUE040696T2/hu unknown
- 2015-10-30 DK DK15788389.3T patent/DK3215498T3/en active
- 2015-10-30 MY MYPI2017701506A patent/MY186908A/en unknown
- 2015-10-30 KR KR1020177011653A patent/KR20170081178A/ko not_active Application Discontinuation
- 2015-10-30 MA MA40893A patent/MA40893B1/fr unknown
- 2015-10-30 ES ES15788389T patent/ES2697902T3/es active Active
- 2015-10-30 PT PT15788389T patent/PT3215498T/pt unknown
- 2015-10-30 CU CU2017000057A patent/CU24462B1/es unknown
- 2015-10-30 SG SG11201703199UA patent/SG11201703199UA/en unknown
- 2015-10-30 PE PE2017000788A patent/PE20170945A1/es unknown
- 2015-10-30 BR BR112017009204-2A patent/BR112017009204A2/pt not_active Application Discontinuation
- 2015-10-30 CN CN201580059512.8A patent/CN107074783B/zh not_active Expired - Fee Related
- 2015-10-30 EA EA201790951A patent/EA032137B1/ru not_active IP Right Cessation
- 2015-10-30 TW TW104135707A patent/TWI694072B/zh not_active IP Right Cessation
- 2015-10-30 CA CA2966256A patent/CA2966256A1/en not_active Abandoned
- 2015-10-30 LT LTEP15788389.3T patent/LT3215498T/lt unknown
- 2015-10-30 US US15/523,061 patent/US20170313665A1/en not_active Abandoned
- 2015-11-02 JO JOP/2015/0271A patent/JO3503B1/ar active
- 2015-11-02 US US14/930,157 patent/US9771352B2/en active Active
-
2017
- 2017-03-23 IL IL251354A patent/IL251354B/en active IP Right Grant
- 2017-04-26 SV SV2017005426A patent/SV2017005426A/es unknown
- 2017-04-27 SA SA517381429A patent/SA517381429B1/ar unknown
- 2017-04-27 PH PH12017500802A patent/PH12017500802A1/en unknown
- 2017-04-28 DO DO2017000109A patent/DOP2017000109A/es unknown
- 2017-04-28 EC ECIEPI201726733A patent/ECSP17026733A/es unknown
- 2017-05-02 CL CL2017001087A patent/CL2017001087A1/es unknown
- 2017-05-03 GT GT201700094A patent/GT201700094A/es unknown
- 2017-05-03 CO CONC2017/0004471A patent/CO2017004471A2/es unknown
- 2017-06-02 ZA ZA2017/03802A patent/ZA201703802B/en unknown
-
2018
- 2018-10-23 HR HRP20181742TT patent/HRP20181742T1/hr unknown
- 2018-11-19 CY CY181101217T patent/CY1120941T1/el unknown
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11091463B2 (en) | 2016-05-03 | 2021-08-17 | Bayer Pharma Aktiengesellschaft | Amide-substituted pyridinyltriazole derivatives and uses thereof |
| US10927098B2 (en) | 2016-10-20 | 2021-02-23 | Bayer Pharma Aktiengesellschaft | Hydroxyalkyl-substituted triazole derivatives and uses thereof |
| US11149023B2 (en) | 2017-10-24 | 2021-10-19 | Bayer Pharma Aktiengesellschaft | Substituted triazole derivatives and uses thereof |
| US11173151B2 (en) | 2017-10-24 | 2021-11-16 | Bayer Aktiengesellschaft | Substituted triazole derivatives and uses thereof |
| US11230540B2 (en) | 2017-10-24 | 2022-01-25 | Bayer Pharma Aktiengesellschaft | Substituted triazole derivatives and uses thereof |
| US11298367B2 (en) | 2017-10-24 | 2022-04-12 | Bayer Aktiengesellschaft | Prodrugs of substituted triazole derivatives and uses thereof |
| US11331314B2 (en) | 2017-10-24 | 2022-05-17 | Bayer Pharma Aktiengesellschaft | Amine substituted triazole derivatives and uses thereof |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9771352B2 (en) | Hydroxyalkyl-substituted phenyltriazole derivatives and uses thereof | |
| US10800746B2 (en) | Oxoalkyl-substituted phenyltriazole derivatives and uses thereof | |
| AU2017259870B2 (en) | Amide-substituted pyridinyltriazole derivatives and uses thereof | |
| US10525041B2 (en) | Fluoroalkyl-substituted aryltriazole derivatives and uses thereof | |
| US10526314B2 (en) | Hydroxyalkyl-substituted heteroaryltriazole derivatives and uses thereof | |
| US10927098B2 (en) | Hydroxyalkyl-substituted triazole derivatives and uses thereof | |
| US20190119251A1 (en) | Amide-substituted aryltriazole derivatives and uses thereof | |
| EP3700897A1 (en) | Substituted triazole derivatives and uses thereof | |
| US11230540B2 (en) | Substituted triazole derivatives and uses thereof | |
| EP3452468A1 (en) | Amide-substituted aryltriazole derivatives and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AS | Assignment |
Owner name: BAYER PHARMA AKTIENGESELLSCHAFT, GERMANY Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:SCHMECK, CARSTEN, DR.;GERISCH, MICHAEL, DR.;GRIEBENOW, NILS, DR.;AND OTHERS;SIGNING DATES FROM 20170330 TO 20170413;REEL/FRAME:042180/0017 |
|
| STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |