RU2017143184A - NEW DERIVATIVES 3,5-DIVINYL-PYRAZOLE FOR MEDICAL APPLICATION - Google Patents

Claims (46)

1. The claims The compound of formula (I)

or its pharmaceutically acceptable salt, hydrate or solvate, where: R ₁ , R ₂ , R ₃ , R ₄ - are chosen independently and represent H, halogen, OH, C _1-6 alkoxy, NO ₂ , -C (= S) NHR ^A , -C (= O) OR ^A , -S (= O) ₂ OR ^A , -C (= S) OR ^A , -S ( = O) ₂ NHR ^A , -C (= O) NHR ^A , -S (= O) ₂ NR ^A R ^B or- ^C (= O) NR ^A R ^B ; R _X is selected from the group —C (= S) NHR ^A , —C (= O) OR ^A , —S (= O) ₂ OR ^B , —C (= S) OR ^B , -S (= O) ₂ NHR ^A , -C (= O) NHR ^A , -S (= O) ₂ NR ^A R ^B , -C (= O) NR ^A R ^B , 5-6-membered partially or completely unsaturated heterocycle containing 1 to 2 N atoms; R ^A is independently selected and represents C _1-6 alkyl, C _1-8 alkoxy, partially or fully halogenated C _1-8 alkyl or C _5-6 cycloalkyl; R ^B - is chosen independently and represents H, C _1-8 alkyl, C _1-8 alkoxy, or partially or fully halogenated C _1-8 alkyl; alternatively, in cases where any of R ₁ , R ₂ , R ₃ , R ₄ , R _X is -S (= O) ₂ NR ^A R ^B or- ^C (= O) NR ^A R ^B , R ^A and R ^B together with the nitrogen atom to which they are attached, can form a saturated cycle containing from 5 to 6 atoms; R _p - is independently selected and represents a C ₁ - ₆ -alkyl, partially or completely halogenated C _1-6 alkyl; R _m - is independently selected and represents H, C ₁ - ₆ -alkyl, partially or completely halogenated C _1-8 alkyl; alternatively, the adjacent R _p and R _m groups together with the two oxygen atoms to which they are attached, and the two carbon atoms of the benzene ring, can form a non-aromatic cycle containing from 5 to 6 atoms. 2. The compound according to claim 1, in which R ₁ , R ₂ , R ₃ , R ₄ - are chosen independently and represent H, halogen, NO ₂ ; R _X - represents -C (= S) NHR ^A , -C (= O) OR ^A , -C (= S) OR ^B , -C (= O) NHR ^A , -S (= O) ₂ NR ^A R ^B , -C (= O) NR ^A R ^B or a 5-6-membered partially or fully unsaturated heterocycle containing 1 to 2 N atoms; R ^A is independently selected and represents C _1-6 alkyl, C _1-8 alkoxy, partially or fully halogenated C _1-8 alkyl; R ^B - is chosen independently and represents H, C _1-8 alkyl, C _1-8 alkoxy, partially or fully halogenated C _1-8 alkyl; alternatively, in cases where R _X is —C (═O) NR ^A R ^B , R ^A and R ^B together with the nitrogen atom to which they are attached, may form an unsaturated cycle containing from 5 to 6 atoms; R _p is independently selected and represents CH ₃ , partially or fully halogenated C _1-6 alkyl; R _m is selected independently and represents H, CH ₃ , partially or fully halogenated C _1-8 -alkyl. 3. The compound according to claim 1, in which: R ₁ , R ₂ , R ₃ , R ₄ - are chosen independently and represent H, halogen, NO ₂ ; R _X - represents -C (= S) NHR ^A , -C (= O) OR ^A , -C (= S) OR ^B , -C (= O) NHR ^A , -S (= O) ₂ NR ^A R ^B , -C (= O) NR ^A R ^B or a 5-6-membered partially or fully unsaturated heterocycle containing 1 to 2 N atoms; R ^A is independently selected and represents C _1-6 alkyl, C _1-8 alkoxy, partially or fully halogenated C _1-8 alkyl; R ^B - is chosen independently and represents H, C _1-8 alkyl, C _1-8 alkoxy, partially or fully halogenated C _1-8 alkyl; alternatively, in cases where R _X is —C (═O) NR ^A R ^B , R ^A and R ^B together with the nitrogen atom to which they are attached, may form an unsaturated cycle containing from 5 to 6 atoms; R _p - is independently selected and represents a CH _3, partially or completely halogenated C ₁ - ₆ -alkyl; R _m - is chosen independently and represents H, CH ₃ , partially or fully halogenated C ₁ - ₈ -alkyl; however, the neighboring groups R _p and R _m together with the two oxygen atoms to which they are attached, and the two carbon atoms of the benzene ring, form a non-aromatic cycle containing from 5 to 6 atoms. 4. The compound according to claim 1, selected from the group and representing:

5. The use of a compound according to claim 1 as an inhibitor of P-glycoprotein. 6. The use of a compound according to claim 1 for the preparation of a pharmaceutical composition for the treatment of diseases associated with the activity of P-glycoprotein. 7. The use according to claim 6, in which the disease is characterized by multidrug resistance caused by the activity of P-glycoprotein. 8. Pharmaceutical composition for the treatment of diseases associated with the activity of P-glycoprotein, characterized in that it contains an effective amount of the compound according to claim 1 and a pharmaceutically acceptable carrier, solvent and / or excipient. 9. The pharmaceutical composition according to claim 8, which further comprises a chemotherapeutic or pharmacotherapeutic agent. 10. The pharmaceutical composition according to claim 9, wherein the chemotherapeutic agent is etoposide, doxorubicin, vinblastine, ticarcillin, carbpenicillin, mezlocillin, azlocillin, ceftbiprol, ceftaroline, ceftholosan or methotrexate. 11. The pharmaceutical composition according to claim 9, in which the pharmacotherapeutic agent is digoxin or dexamethasone.