Piperazine substituted phenol derivative and use thereof
AssigneeChengdu MFS Pharma. Co., Ltd.
InventorsHancheng ZHANG, Jin LIU, Wensheng ZHANG, Guangwu CHEN, Haijun MA
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Abstract
A piperazine substituted phenol derivative and its applications in pharmaceutical chemistry are provided. The compound, depicted by formula I, exhibits excellent salt formation properties and water solubility, meeting formulation requirements. It also has a low minimum effective anesthetic dose, enabling rapid onset and recovery. This addresses the drawbacks of propofol and ciprofol prodrugs and lipid emulsions. The compound shows promise in developing drugs with sedative, hypnotic, and/or anesthetic effects, as well as in drugs for controlling status epilepticus.
Claims17
A compound of formula I, or a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, a prodrug thereof, a metabolite thereof, or a deuterated derivative thereof:
- wherein, R is selected from hydrogen, CORa, COCH(NH2)Ra, COORh1, CH2COORh1, a protecting group, PO(ORh1)(ORh2) or CH2OPO(ORh1)(ORh2);
- Ra is hydrogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, aryl or heteroaryl;
- Rh1, Rh2 are each independently selected from hydrogen, C1-4 alkyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, aryl or heteroaryl;
- R1, R2, R3, R4, R5, and R6 are each independently selected from hydrogen, halogen, C1-4 alkyl or 3-6 membered cycloalkyl, provided that R1, R2, R3, R4, R5, and R6 are not simultaneously methyl;
- R7, R8 are each independently selected from hydrogen, halogen, C1-4 alkyl;
- p is an integer from 0 to 8, and each R9 is independently selected from hydrogen, C1-4 alkyl, halogenated C1-4 alkyl;
- or p is an integer from 2 to 8, and two R9 groups are connected to form a ring, with the remaining R9 each independently selected from hydrogen, C1-4 alkyl, halogenated C1-4 alkyl;
- or p is an integer from 1 to 9, and one R9 is connected to the nitrogen atom attached to R10 to form a quaternary ammonium salt, with the remaining R9 each independently selected from hydrogen, C1-4 alkyl, halogenated C1-4 alkyl;
- R10 is selected from hydrogen, C1-4 alkyl, (CRb1Rb2)mCOORc, (CRb1Rb2)mCONRd1Rd2, (CRb1Rb2)nORf, (CRb1Rb2)nNRd1Rd2, (CRb1Rb2)nOCORe, (CRb1Rb2)nNRd1CORe, (CRb1Rb2)mCO(CRb3Rb4)tCOORc, or (CRb1Rb2)mCO(CRb3Rb4)tCONRd1Rd2;
- wherein, Rb1, Rb2, Rb3, and Rb4 are each independently selected from hydrogen, halogen, C1-4 alkyl, halogenated C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, aryl, heteroaryl, CN, ORf, SRf, or NRd1Rd2;
- or, Rb1 and Rb2, together with the carbon atom to which they are attached, form a 3-6 membered cyclic structure containing 0 or 1 heteroatom selected from N, O, or S;
- Rc is hydrogen, C1-4 alkyl, halogenated C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, aryl, or heteroaryl;
- Re is hydrogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, aryl, or heteroaryl;
- the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl in Rb1, Rb2, Rb3, Rb4, Rc and Re are unsubstituted or optionally substituted with one or more groups selected from halogen, C1-4 alkyl, C1-4 alkoxy, halogenated C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, 3-6 membered cycloalkyl, 3-6 membered heterocyclyl, CN, NO2, ORf, SRf, NRd1Rd2, CORi, COORf, OCORi, CONRd1Rd2, NRd1CORi, NRd1SO2Ri, or SO2Ri;
- Rd1, Rd2 are each independently selected from hydrogen or C1-4 alkyl;
- Rf is selected from hydrogen, C1-4 alkyl, or halogenated C1-4 alkyl;
- Ri is selected from hydrogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, 3-6 membered cycloalkyl, or 3-6 membered heterocyclyl;
- m is 0, 1, 2, 3, or 4;
- n is 2, 3, or 4;
- t is 1, 2, 3, or 4.
Dependencies are inferred from the claim text.