Inhibitors and methods of inhibiting bacterial and viral pathogens
View Patent ↗Compounds, pharmaceutical compositions and methods for treating viral and bacterial infections, by administering certain thiourea compounds, specifically acylthiourea, carboximidoylthiourea and S-alkyl isothiourea derivatives and analogs, in therapeutically effective amounts are disclosed.
1. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the following general Formula II or a pharmaceutically acceptable salt thereof:
wherein
X is selected from the group consisting of oxygen and NH;
Y is selected from the group consisting of: —CH 2 —, —C(═O)—, —C(═S)— and —C(═NH)—;
A is selected from the group consisting of: N and CR 5 ;
B is selected from the group consisting of: N and CR 6 ;
R 1 is selected from the group consisting of: hydrogen and ethyl;
R 2 is selected from the group consisting of: hydrogen and chloro;
R 3 is selected from the group consisting of: hydrogen, methoxy, amino and hydroxyl;
R 4 is selected from the group consisting of: hydrogen, chloro and amino;
R 5 is selected from the group consisting of hydrogen and aminomethyl; and
R 6 is selected from the group consisting of hydrogen, amino and aminomethyl and wherein R 3 and R 4 cannot both be hydrogen.
2. The composition of claim 1 , wherein X is oxygen.
3. The composition of claim 1 , wherein Y is —CH 2 —.
4. The composition of claim 1 , wherein Y is —C(═O)—.
5. The composition of claim 1 , wherein A is C—H.
6. The composition of claim 1 , wherein B is C—H.
7. The composition of claim 1 , wherein R 1 is hydrogen.
8. The composition of claim 1 , wherein R 2 is hydrogen.
9. The composition of claim 1 , wherein R 3 is methoxy.
10. The composition of claim 1 , wherein R 4 is chloro.
11. The composition of claim 1 , wherein each of R 5 and R 6 is hydrogen.
12. The composition of claim 1 , wherein the compound of Formula II is selected from the group consisting of: N-[4-[(4-tert-butylbenzoyl)-carbamothioylamino]-2-hydroxy-phenyl]-2-chloro-benzamide; 4-tert-butyl-N-[[4-[(2-chlorophenyl)-methylamino]-3-methoxy-phenyl]-carbamothioyl]-benzamide; N-[2-amino-4-[(4-tert-butylbenzoyl)-carbamothioylamino]-phenyl]-2-chloro-benzamide hydrochloride; 4-tert-butyl-N-[[4-[(2-chlorobenzene-carbothioyl)amino]-3-methoxy-phenyl]-carbamothioyl]benzamide; 4-(aminomethyl)-N-[4-[(4-tert-butylbenzoyl)-carbamothioylamino]-2-methoxy-phenyl]benzamide hydrochloride; N-[4-[(4-tert-butylbenzene-carboximidoyl)-carbamothioylamino]-2-methoxy-phenyl]-2-chloro-benzamide; 4-tert-butyl-N-[[4-[(2-chlorobenzene-carboximidoyl)amino]-3-methoxy-phenyl]-carbamothioyl]benzamide; 3-(aminomethyl)-N-[4-[(4-tert-butylbenzoyl)-carbamothioylamino]-2-methoxy-phenyl]benzamide hydrochloride; 2-amino-N-[4-[(4-tert-butylbenzoyl)-carbamothioylamino]-2-methoxy-phenyl]benzamide; N-[4-[(4-tert-butylbenzoyl)-carbamothioylamino]-2-methoxy-phenyl]pyridine-3-carboxamide; N-[4-[(4-tert-butylbenzoyl)-carbamothioylamino]-2-methoxy-phenyl]pyridine-4-carboxamide; N-[[4-[(4-aminobenzoyl)amino]-3-methoxy-phenyl]-carbamothioyl]-4-tert-butyl-benzamide hydrochloride; N-[4-[(4-tert-butylbenzoyl)-carbamothioyl-ethyl-amino]-2-methoxy-phenyl]-2-chloro-benzamide; and N-[4-[(4-tert-butylbenzoyl)-carbamothioylamino]-2-methoxy-phenyl]-2-chloro-benzamide.
13. The composition of claim 12 , wherein the compound of Formula II is N-[2-amino-4-[(4-tert-butylbenzoyl)-carbamothioylamino]-phenyl]-2-chloro-benzamide hydrochloride.
14. The composition of claim 12 , wherein the compound of Formula II is N-[4-[(4-tert-butylbenzoyl)-carbamothioylamino]-2-methoxy-phenyl]-2-chloro-benzamide.
15. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the following general Formula II or a pharmaceutically acceptable salt thereof:
wherein
X is selected from the group consisting of oxygen and NH;
Y is selected from the group consisting of: —CH 2 —, —C(═O)—, —C(═S)— and —C(═NH)—;
A is selected from the group consisting of: N and CR 5 ;
B is selected from the group consisting of: N and CR 6 ;
R 1 is selected from the group consisting of: hydrogen and ethyl;
R 2 is selected from the group consisting of: hydrogen and chloro;
R 3 is methoxy;
R 4 is selected from the group consisting of: hydrogen, chloro and amino;
R 5 is selected from the group consisting of hydrogen and aminomethyl; and
R 6 is selected from the group consisting of hydrogen, amino and aminomethyl.
16. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the following general Formula II or a pharmaceutically acceptable salt thereof:
wherein
X is selected from the group consisting of oxygen and NH;
Y is selected from the group consisting of: —CH 2 —, —C(═O)—, —C(═S)— and —C(═NH)—;
A is selected from the group consisting of: N and CR 5 ;
B is selected from the group consisting of: N and CR 6 ;
R 1 is selected from the group consisting of: hydrogen and ethyl;
R 2 is selected from the group consisting of: hydrogen and chloro;
R 3 is selected from the group consisting of: hydrogen, methoxy, amino and hydroxyl;
R 4 is chloro;
R 5 is selected from the group consisting of hydrogen and aminomethyl; and
R 6 is selected from the group consisting of hydrogen, amino and aminomethyl.
17. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and N-[4-[(4-tert-butylbenzoyl)-carbamothioylamino]-2-methoxy-phenyl]-2-chloro-benzamide.
18. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and N-[(4-benzamido-2-chloro-phenyl)carbamothioyl]-4-tert-butyl-benzamide.