ABSTRACT
Immobilized Cu(OAc)(2)-bis(oxazolines) via hydrogen bonding by SBA-15 was applied to asymmetric Henry reaction, and good enantioselectivities were obtained (up to 83% ee) between 2-methoxybenzaldehyde and CH(3)NO(2) in isopropyl alcohol (iPrOH). The catalyst could be reused seven times without any obvious loss in enantioselectivity. For the first time, this facile and clean immobilization method is applied to the use of bis(oxazolines) complexes.
Subject(s)
Copper/chemistry , Organometallic Compounds/chemistry , Benzaldehydes/chemistry , Catalysis , Hydrogen Bonding , Methane/analogs & derivatives , Methane/chemistry , Nitroparaffins/chemistry , Silicon Dioxide/chemistry , StereoisomerismABSTRACT
A series of 6-substituted carbamoyl benzimidazoles were designed and synthesised as new nonpeptidic angiotensin II AT(1) receptor antagonists. The preliminary pharmacological evaluation revealed a nanomolar AT(1) receptor binding affinity for all compounds in the series, and a potent antagonistic activity in an isolated rabbit aortic strip functional assay for compounds 6f, 6g, 6h and 6k was also demonstrated. Furthermore, evaluation in spontaneous hypertensive rats and a preliminary toxicity evaluation showed that compound 6g is an orally active AT(1) receptor antagonist with low toxicity.
Subject(s)
Angiotensin II Type 1 Receptor Blockers/chemical synthesis , Benzimidazoles/chemistry , Drug Design , Receptor, Angiotensin, Type 1/chemistry , Angiotensin II Type 1 Receptor Blockers/chemistry , Angiotensin II Type 1 Receptor Blockers/pharmacology , Animals , Benzimidazoles/chemical synthesis , Benzimidazoles/pharmacology , Biphenyl Compounds/chemical synthesis , Biphenyl Compounds/chemistry , Biphenyl Compounds/pharmacology , Blood Pressure/drug effects , Models, Molecular , Protein Binding , Rabbits , Rats , Rats, Inbred SHR , Receptor, Angiotensin, Type 1/metabolism , Structure-Activity RelationshipABSTRACT
A series of 6-substituted aminocarbonyl benzimidazole derivatives were designed and synthesized as nonpeptidic angiotensin II AT(1) receptor antagonists. The preliminary pharmacological evaluation revealed nanomolar AT(1) receptor binding affinity and good AT(1) receptor selectivity over AT(2) receptor for all compounds of the series, a potent antagonistic activity in isolated rabbit aortic strip functional assay for compounds 6b, 6d and 6i was also demonstrated. Furthermore, evaluation in spontaneous hypertensive rats and a preliminary toxicity evaluation showed that compound 6i is an orally active AT(1) receptor antagonist with low toxicity.
Subject(s)
Angiotensin II Type 1 Receptor Blockers/chemistry , Angiotensin II Type 1 Receptor Blockers/pharmacology , Benzimidazoles/chemistry , Benzimidazoles/pharmacology , Receptor, Angiotensin, Type 1/metabolism , Angiotensin II Type 1 Receptor Blockers/chemical synthesis , Angiotensin II Type 1 Receptor Blockers/toxicity , Animals , Benzimidazoles/chemical synthesis , Benzimidazoles/toxicity , Blood Pressure/drug effects , Drug Design , Models, Molecular , Rats , Rats, Inbred SHRABSTRACT
Functional imidazolium ionic liquids have been developed as a new class of versatile catalysts. C(2)-symmetric imidazolium-tagged bis(oxazoline) ligands were prepared, and the anions of the ligands were altered. The catalysts based on the new ligands and Cu(OAc)(2)·H(2)O were applied in asymmetric Henry reactions between various aldehydes 3 and CH(3)NO(2)4. The catalysts achieved a high level of enantioselectivity; product (R)-5n was attained at 94% ee in MeOH. Moreover, the catalyst could be recycled 6 times without an obvious loss of activity or enantioselectivity. In addition, a theoretical mechanistic study was conducted to explain the origin of the enantioselectivity.