WO2010018555A4 - Quinoline compounds containing a dibemethin group - Google Patents

Quinoline compounds containing a dibemethin group Download PDF

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Publication number
WO2010018555A4
WO2010018555A4 PCT/IB2009/053578 IB2009053578W WO2010018555A4 WO 2010018555 A4 WO2010018555 A4 WO 2010018555A4 IB 2009053578 W IB2009053578 W IB 2009053578W WO 2010018555 A4 WO2010018555 A4 WO 2010018555A4
Authority
WO
WIPO (PCT)
Prior art keywords
compound according
compound
chloro
methyl
methylaminomethyl
Prior art date
Application number
PCT/IB2009/053578
Other languages
French (fr)
Other versions
WO2010018555A3 (en
WO2010018555A2 (en
Inventor
Roger Hunter
Timothy John Egan
Vincent Kudakwashe Zishiri
Original Assignee
University Of Cape Town
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by University Of Cape Town filed Critical University Of Cape Town
Priority to AP2011005602A priority Critical patent/AP2848A/en
Publication of WO2010018555A2 publication Critical patent/WO2010018555A2/en
Publication of WO2010018555A3 publication Critical patent/WO2010018555A3/en
Publication of WO2010018555A4 publication Critical patent/WO2010018555A4/en
Priority to ZA2011/01772A priority patent/ZA201101772B/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D215/38—Nitrogen atoms
    • C07D215/42—Nitrogen atoms attached in position 4
    • C07D215/46—Nitrogen atoms attached in position 4 with hydrocarbon radicals, substituted by nitrogen atoms, attached to said nitrogen atoms
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

4-Amino-7-chloroquinolines are described containing dibenzylmethylamine (dibemethin) side chains attached via a methylene bridge to the amino group of the quinoline showing strong antimalarial and resistance reversing activity. The compounds are of the general formula (I), wherein X1, X2, X3 and X4 are independently selected from the group consisting of H, alkoxy, amido, optionally substituted amino, cyano, halo, haloalkyl, hydroxyl, nitro, sulphonamide and trifluoromethyl; Y is CH or N; m, n, p, q, r and s are independently from 0 to 5; R1, R2, R3 and R4 are independently selected from the group consisting of H, optionally substituted alkyl, alkenyl, alkynyl cycloalkyl, aryl, heteroaryl and heterocyclyl, wherein R3 and R4 together with the carbon atoms to which they are joined optionally form a six membered ring; or pharmaceutically acceptable salts thereof. Pharmaceutical compositions containing at least one of these compounds are also described for treating or preventing malaria.

Claims

57AMENDED CLAIMS [Received by the International Bureau on 18 July 2010 (18.07.10]
1. A compound having formula (I):
Figure imgf000002_0001
(I) wherein
X1, X2, X3.3nd.X4 are independently selected-from the group consisting of H, alkoxy, amido, optionally substituted amino, cyano, halo, haloalkyl, hydroxy], nitro, sulphonamide and trifluoromethyl; Y is CH or N; m, q and s are independently from 0 to 5; n, p and r are independently from 1 to 5;
R1, R2, R3 and R4 are independently selected from the group consisting of H, optionally substituted alky!, alkenyl, alkynyl cycloalkyl, aryl, heteroaryl and heterocyclyl, wherein
R3 and R4 together with the carbon atoms to which they are joined optionally form a six membered ring; or a pharmaceutically acceptable salt thereof.
2. A compound according to claim 1 , wherein the six membered ring formed by R3 and R4 has one or more substituents independently selected from the group consisting of H, alkoxy, amido, optionally substituted amino, cyano, halo, haloalkyl, hydroxyl, nitro, sulphonamide and trifluoromethyl. 58
3. A compound according to claim 1, which is /V-[{2-(/V-Benzyl-Λ/- methylaminomethyl)pheny!}methyl]-7-chloro-4^uinolinamine.
4. A compound according to claim 1, which is Λ/-[{3-(Λ/-Benzyl-A/- methylaminomethyl)pheπy|}methyl]-7-chloro-4-quinoliπamine.
5. A compound according to claim 1, which is /V-[{4~(A/-Beπzyl-Λ/- methylaminomethyl)phenyl}methyl]-7-chloro-4-quiπolinamine.
6. A compound according to claim 1 , which is Λ/-[{2-(/V-p-Chlorobenzyl-Λ/- methylamiπomethyl)phenyl}methyl]-7-chloro-4-quinolinamine.
7. A compound according to claim 1, which is Λ/-[{3-(Λ/-p-Chlorobenzyl-/V- methylaminomethyl)phenyl}methyl]-7-chloro-4-quinolinamiπe.
8. A compound according to claim 1 , which is /V-[{4-(Λ/-p-Chlorobenzyl-Λ/- methylaminomethyl)phenyl}methyl]-7-chIoro-4-quinolinamine.
9. A compound according to claim 1, which is 7-Chloro-Λ/-[{2-(Λ/-p- methoxybenzyl-Λ/-methylaminomethyl)phenyl}methyl]-4-quinolinamine.
10. A compound according to claim 1 , which is 7-Chloro-/V-[{3-(/V-p- methoxybenzyl-Λ/-methylaminomethyl)phenyl}methyl]-4-quinolinamine.
11. A compound according to claim 1, which is 7-Chloro-/V-[{4-{Λ/-p- Methoxybeπzyl-Λ/-methylaminomethyl)phenyl}methyl]-4-quinolinamiπe.
12. A compound according to claim 1, which is 7-Chloro-Λ/-[{2-(Λ/-p- dimethylaminobenzyl-Λ/-methyIaminomethyl)pheπyl}methyl]- 4-quiπolinamine.
13. A compound according to claim 1 , which is 7-Chloro-/V-[{3-(/V-p- Dimethylaminobenzy!-Λ/-methylaminomethyl)phenyl}methyl]- 4-quinolinamiπe.
14. A compound according to claim 1, which is 7-Chloro-Λ/-[{4-(Λ/-p- dimethyIaminobenzy|-Λ/-methylaminomethy|)phenyl}methyI]-4-quinolinamine. 59
15. A compound according to any one of claims 1 to 14, for use in a method of preventing and/or treating malaria.
16. A compound according to claim 15, wherein the malaria is caused by strains of Plasmodium falciparum.
17. A compound according to claim 16, wherein the P. falciparum strains are chloroquiπe sensitive or chloroquine resistant.
18. A pharmaceutical composition including a compound as claimed in any one of claims 1 to 17 and a pharmaceutically acceptable carrier.
19. A pharmaceutical composition according to claim 18, which includes a second antimalarial compound.
20. A pharmaceutical composition according to claim 19 wherein the second antimalarial compound is chloroquine.
21. Use of a compound as claimed in any one of claims 1 to 17 in a method of making a medicament for use in a method of preventing and/or treating malaria.
22. A method of preventing and/or treating malaria, the method comprising administering an effective amount of a compound as claimed in any one of claims 1 to 17 to an animal in need thereof.
23. A method according to claim 22, wherein the animal is a human.
24. A method according to either of claims 22 or 23, wherein the compound is administered with a second antimalarial compound.
25. A method according to claim 24, wherein the second antimalarial compound is chloroquine.
PCT/IB2009/053578 2008-08-14 2009-08-13 Quinoline compounds containing a dibemethin group WO2010018555A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AP2011005602A AP2848A (en) 2008-08-14 2009-08-13 Quinoline compounds containing a dibemethin group
ZA2011/01772A ZA201101772B (en) 2008-08-14 2011-03-08 Quinoline antimalarials containing a chloroquine resistance reversing dibemethin group

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
ZA2008/07021 2008-08-14
ZA200807021 2008-08-14
ZA200807022 2008-08-14
ZA2008/07022 2008-08-14

Publications (3)

Publication Number Publication Date
WO2010018555A2 WO2010018555A2 (en) 2010-02-18
WO2010018555A3 WO2010018555A3 (en) 2010-07-15
WO2010018555A4 true WO2010018555A4 (en) 2010-09-10

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2009/053578 WO2010018555A2 (en) 2008-08-14 2009-08-13 Quinoline compounds containing a dibemethin group

Country Status (2)

Country Link
AP (1) AP2848A (en)
WO (1) WO2010018555A2 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX2018004109A (en) 2015-10-05 2018-09-27 Univ Columbia Activators of autophagic flux and phospholipase d and clearance of protein aggregates including tau and treatment of proteinopathies.

Also Published As

Publication number Publication date
WO2010018555A3 (en) 2010-07-15
AP2011005602A0 (en) 2011-04-30
WO2010018555A2 (en) 2010-02-18
AP2848A (en) 2014-02-28

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