Biomaterial Database

Malonamic acid derivatives as M1 selective muscarinic receptor antagonists. 1991

M Turconi, and A Banfi, and G B Schiavi, and A Donetti

Boehringer Ingelheim Italy (Istituto de Angeli S.P.A.), Milano.

A series of malonamic acid esters with suitable amino alcohols, typical of antimuscarinic compounds, was synthesized and the affinities for the three pharmacologically defined muscarinic receptor subtypes, namely M1, M2 and M3, were evaluated by radioligand displacement experiments. It was found that the esters with 3-quinuclidinol 7b, 7f-g, 8 and 9 are ligands with intermediate to high affinity for the M1 receptors, for which they show a preferential binding. Unexpectedly, the ester 7a with tropine bound with negligible affinity to all the receptors investigated. The introduction of a phenyl group on the carboxamido moiety of 7b gave compound 9, which showed an affinity for the M1 receptor comparable with that of the reference drug Pirenzepine 1.

UI	MeSH Term	Description	Entries
D008314	Malonates	Derivatives of malonic acid (the structural formula CH2(COOH)2), including its salts and esters.
D009206	Myocardium	The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.	Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010890	Pirenzepine	An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as CIMETIDINE and RANITIDINE. It is generally well tolerated by patients.	Gastrotsepin,Gastrozepin,L-S 519,LS-519,Piren-Basan,Pirenzepin,Pirenzepin Von Ct,Pirenzepin-Ratiopharm,Pirenzepine Dihydrochloride,Pyrenzepine,Ulcoprotect,Ulgescum,Dihydrochloride, Pirenzepine,LS 519,LS519,Piren Basan,Pirenzepin Ratiopharm,Von Ct, Pirenzepin
D002540	Cerebral Cortex	The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.	Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013363	Submandibular Gland	One of two salivary glands in the neck, located in the space bound by the two bellies of the digastric muscle and the angle of the mandible. It discharges through the submandibular duct. The secretory units are predominantly serous although a few mucous alveoli, some with serous demilunes, occur. (Stedman, 25th ed)	Submaxillary Gland,Gland, Submandibular,Gland, Submaxillary,Glands, Submandibular,Glands, Submaxillary,Submandibular Glands,Submaxillary Glands
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018727	Muscarinic Antagonists	Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system.	Antimuscarinic,Antimuscarinic Agent,Antimuscarinic Agents,Cholinergic Muscarinic Antagonist,Muscarinic Antagonist,Antimuscarinics,Cholinergic Muscarinic Antagonists,Agent, Antimuscarinic,Agents, Antimuscarinic,Antagonist, Cholinergic Muscarinic,Antagonist, Muscarinic,Antagonists, Cholinergic Muscarinic,Antagonists, Muscarinic,Muscarinic Antagonist, Cholinergic,Muscarinic Antagonists, Cholinergic
D066298	In Vitro Techniques	Methods to study reactions or processes taking place in an artificial environment outside the living organism.	In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In