Back to results
US 12,152,048 B2Granted
Nitroxoline prodrug and use thereof
AssigneeJiangsu Yahong Meditech Co., Ltd.
InventorsYijun Deng, Liang Wu, Ke Pan
Life of this patent
Estimating the term…
Abstract
Provided are a nitroxoline prodrug and a use thereof. Specifically, provided are a compound represented by formula (I) or a pharmaceutically acceptable salt thereof, a preparation method therefor, a composition containing the compound, and a use thereof in the preparation of anti-infective and antitumor drugs, and definitions of groups in formula (I) are as stated in the specification. The compound represented by formula (I) has better pharmacokinetic parameters such as solubility, blood medicine concentration, or half-life period than nitroxoline. The compound represented by formula (I) can reduce the frequency of drug administration, and has potential for application in other fields other than the field of urinary tracts.
Claims12
A compound of formula (II),
- or a mesomer, racemate, enantiomer, or diastereomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof,
- wherein,
- R1 is selected from the group consisting of hydrogen and C1-6 alkyl;
- R4, R5 and R6 are each independently selected from the group consisting of hydrogen, halogen, alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR12, —SR12, —C(O)R1, —C(O)OR12, —C(O)—(CH)m—C(O)R11, —OC(O)R11, —NRaRb, —N(Rc)C(O)Rd, —C(O)N(Ra)(Rb), —N(Rc)S(O)pRd, —S(O)pN(Ra)(Rb), —O(CH2)mO(CH2)qR12 and —N(Rc)C(O)—(CH)m—N(Rc)C(O)Rd, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally further substituted by one or more substituents selected from the group consisting of halogen, amino, nitro, cyano, hydroxy, thiol, alkyl, alkoxy, alkenyl, alkynyl, OR12, SR12, NRaRb, —COR11, —C(O)OR12, —OC(O)R11, —N(Rc)C(O)Rd, —O(CH2)mO(CH2)qR12, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl, wherein the aryl, arylalkyl, heteroaryl and heteroarylalkyl are optionally further substituted by one or more substituents selected from the group consisting of halogen, amino, nitro, cyano, hydroxy, thiol, carboxy, alkoxycarbonyl, oxo, alkyl and alkoxy;
- or
- any one of R4, R5 and R6 is hydrogen, and the remaining two together with the carbon atom to which they are attached form a cycloalkyl or heterocyclyl, wherein the cycloalkyl or heterocyclyl is optionally further substituted by one or more substituents selected from the group consisting of halogen, amino, nitro, cyano, hydroxy, thiol, alkyl, alkoxy, alkenyl, alkynyl, —C(O)R11, —C(O)OR12, —OC(O)R11, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- R11 and R12 are each independently selected from the group consisting of hydrogen, halogen, hydroxy, cyano, amino, carboxy, alkoxycarbonyl, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally further substituted by one or more substituents selected from the group consisting of halogen, amino, nitro, cyano, hydroxy, thiol, carboxy, alkoxycarbonyl, oxo, alkyl, alkoxy, —NRaRb, —ORd, —N(Rc)C(O)Rd, —C(O)N(Ra)(Rb), —N(Rc)S(O)pRd, —S(O)pN(Ra)(Rb), alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- Ra and Rb are each independently selected from the group consisting of hydrogen, halogen, hydroxy, cyano, amino, carboxy, alkoxycarbonyl, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the amino, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally further substituted by one or more substituents selected from the group consisting of halogen, amino, nitro, cyano, hydroxy, thiol, carboxy, alkoxycarbonyl, oxo, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- or, Ra and Rb together with the atoms to which they are attached form a heterocyclyl, wherein the heterocyclyl is optionally further substituted by one or more substituents selected from the group consisting of halogen, amino, nitro, cyano, oxo, hydroxy, thiol, carboxy, alkoxycarbonyl, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- Rc and Rd are each independently selected from the group consisting of hydrogen, halogen, hydroxy, cyano, amino, carboxy, alkoxycarbonyl, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the amino, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally further substituted by one or more substituents selected from the group consisting of halogen, amino, nitro, cyano, hydroxy, thiol, carboxy, alkoxycarbonyl, oxo, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- m is selected from an integer from 0 to 6;
- p is selected from the group consisting of 0, 1 and 2;
- and
- q is selected from an integer from 0 to 6.
11 more elements
A compound of formula (III),
- or a mesomer, racemate, enantiomer, or diastereomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof,
- wherein,
- R1 is selected from the group consisting of hydrogen and C1-6 alkyl;
- R4 and R5 are each independently selected from the group consisting of hydrogen, halogen, alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR12, —SR12, —C(O)R11, —C(O)OR12, —OC(O)R11, —NRaRb, —N(Rc)C(O)Rd, —C(O)N(Ra)(Rb), —N(Rc)S(O)pRd, —S(O)pN(Ra)(Rb), —O(CH2)mO(CH2)qR12 and —N(Rc)C(O)—(CH)m—N(Rc)C(O)Rd, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally further substituted by one or more substituents selected from the group consisting of halogen, amino, nitro, cyano, hydroxy, thiol, alkyl, alkoxy, alkenyl, alkynyl, OR12, SR12, NRaRb, —C(O)R11, —C(O)OR12, —O(O)CR11, —(CH)m—OC(O)R11, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl;
- or
- R4, R5 and N atom together form a heterocyclyl, wherein the heterocyclyl is optionally further substituted by one or more substituents selected from the group consisting of halogen, amino, nitro, cyano, hydroxy, thiol, alkyl, alkoxy, alkenyl, alkynyl, —C(O)R11, —C(O)OR12, —O(O)CR11, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- R11 and R12 are each independently selected from the group consisting of hydrogen, halogen, hydroxy, cyano, amino, carboxy, alkoxycarbonyl, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally further substituted by one or more substituents selected from the group consisting of halogen, amino, nitro, cyano, hydroxy, thiol, carboxy, alkoxycarbonyl, oxo, alkyl, alkoxy, —NRaRb, —ORd, —N(Rc)C(O)Rd, —C(O)N(Ra)(Rb), —N(Rc)S(O)pRd, —S(O)pN(Ra)(Rb), alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- Ra and Rb are each independently selected from the group consisting of hydrogen, halogen, hydroxy, cyano, amino, carboxy, alkoxycarbonyl, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the amino, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally further substituted by one or more substituents selected from the group consisting of halogen, amino, nitro, cyano, hydroxy, thiol, carboxy, alkoxycarbonyl, oxo, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- or, Ra and Rb together with the atoms to which they are attached form a heterocyclyl, wherein the heterocyclyl is optionally further substituted by one or more substituents selected from the group consisting of halogen, amino, nitro, cyano, oxo, hydroxy, thiol, carboxy, alkoxycarbonyl, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- Rc and Rd are each independently selected from the group consisting of hydrogen, halogen, hydroxy, cyano, amino, carboxy, alkoxycarbonyl, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the amino, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are optionally further substituted by one or more substituents selected from the group consisting of halogen, amino, nitro, cyano, hydroxy, thiol, carboxy, alkoxycarbonyl, oxo, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- m is selected from an integer from 0 to 6;
- p is selected from the group consisting of 0, 1 and 2;
- and
- q is selected from an integer from 0 to 6.
11 more elements
A compound selecting from the group consisting of:
- or a mesomer, racemate, enantiomer, or diastereomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.