Anti-cancer agents based on N-acyl-2, 3-dihydro-1H-pyrrolo[2,3-b] quinoline derivatives and a method of making
The present disclosure relates to novel compounds that can be used as anti-cancer agents in the prostate cancer therapy. In particular, the invention relates to N-acyl derivatives of 2,3-dihydro-1H-pyrrolo[2,3-b]quinolines having the structural Formula (I), stereoisomers, tautomers, racemics, prodrugs, metabolites thereof, or pharmaceutically acceptable salt and/or solvate thereof. The meaning of R1 is independently selected from H; C1-C6 Alkyl, cyclo-Alkyl or iso-Alkyl substituents; R2 is selected from C1-C6 Alkyl, cyclo-Alkyl or iso-Alkyl; substituted or non-substituted, fused or non-fused to substituted or non-substituted aromatic ring, aryl or heteroaryl groups. The invention also relates to methods for preparing said compounds, and to pharmaceutical compositions comprising said compounds.
1. A method of preparing N-acyl derivatives of 2,3-dihydro-1H-pyrrolo[2,3-b]quinolines having the structural Formula (I),
stereoisomers, tautomers, racemics, or pharmaceutically acceptable salt thereof, wherein
R1 is independently selected from H or a straight chain or branched C1-C6 Alkyl,
R2 is selected from C1-C6 Alkyl, substituted or nonsubstituted, fused or non-fused to substituted or non-substituted aromatic ring, aryl or heteroaryl groups, comprising the step of:
reacting a 2,3-dihydro-1H-pyrrolo[2,3-b]quinoline with a carbonyl chloride in the presence of 4-(dimethylamino)pyridine and pyridine at about room temperature,
wherein the 2,3-dihydro-1H-pyrrolo[2,3-b]quinoline has the formula:
wherein R1 is defined as above; and,
wherein the carbonyl chloride has the formula R2COCl and R2 is defined as above.
2. The method of claim 1 , wherein said suitable 2,3-dihydro-1H-pyrrolo[2,3-b]quinolines are selected from:
2,3-dihydro-1H-pyrrolo[2,3-b]quinoline;
6-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]quinoline; or
6-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]quinoline.
3. The method of claim 2 , wherein said suitable carbonyl chlorides have the formula R2COCl.
4. The method of claim 3 wherein the carbonyl chloride is selected from the group consisting of:
3,4,5-trimethoxy-1-benzenecarbonyl chloride;
3,4-dimethoxy-1-benzene-carbonyl chloride;
3-methoxy-1-benzene-carbonyl chloride;
2-methoxy-1-benzenecarbonyl chloride;
4-methyl-1-benzene-carbonyl chloride;
4-methyl-1-benzene-carbonyl chloride;
2-methyl-1-benzene-carbonyl chloride;
2-fluoro-1-benzene-carbonyl chloride;
2-bromo-1-benzene-carbonyl chloride;
3-fluoro-1-benzene-carbonyl chloride; or
4-bromo-1-benzene-carbonyl chloride.
5. The method of claim 1 wherein the carbonyl chloride is selected from the group consisting of:
3,4,5-trimethoxy-1-benzenecarbonyl chloride;
3,4-dimethoxy-1-benzene-carbonyl chloride;
3-methoxy-1-benzene-carbonyl chloride;
2-methoxy-1-benzenecarbonyl chloride;
4-methyl-1-benzene-carbonyl chloride;
4-methyl-1-benzene-carbonyl chloride;
2-methyl-1-benzene-carbonyl chloride;
2-fluoro-1-benzene-carbonyl chloride;
2-bromo-1-benzene-carbonyl chloride;
3-fluoro-1-benzene-carbonyl chloride; or
4-bromo-1-benzene-carbonyl chloride.