Synthesis of some substituted pyrazinopyridoindoles and 3D QSAR studies along with related compounds: piperazines, piperidines, pyrazinoisoquinolines, and diphenhydramine, and its semi-rigid analogs as antihistamines (H1).
3D QSAR studies on the title compounds led to the development of a model with three biophoric sites and six secondary sites viz. H-acceptor (ACC), H-donor (DON), heteroatom (presence), hydrophobic (hydrophobicity), steric (refractivity), and a ring (presence) along with total hydrophobicity and total refractivity as global properties. The model predicted the test set of compounds reasonably well. Three of the five newly synthesized 2-substituted octahydropyrazinopyridoindoles have shown potent antihistaminic H(1) activity with less toxicity and sedation potential.
Saxena
Mridula
M
Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226001, India.
Gaur
Stuti
S
Prathipati
Philip
P
Saxena
Anil K
AK
D000818:Animals; D004155:Diphenhydramine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D012640:Seizures / Q000188:drug therapy
D006633:Histamine Antagonists; D007211:Indoles; D010879:Piperazines; D010880:Piperidines; D004155:Diphenhydramine