LAZABEMIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C8H10ClN3O
Molecular Weight	199.638
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NCCNC(=O)C1=NC=C(Cl)C=C1

InChI

InChIKey=JZXRLKWWVNUZRB-UHFFFAOYSA-N

InChI=1S/C8H10ClN3O/c9-6-1-2-7(12-5-6)8(13)11-4-3-10/h1-2,5H,3-4,10H2,(H,11,13)

HIDE SMILES / InChI

Molecular Formula	C8H10ClN3O
Molecular Weight	199.638
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7931245
Curator's Comment: https://www.ncbi.nlm.nih.gov/pubmed/12359039 | https://www.thepharmaletter.com/article/blow-for-roche-as-phase-iii-tempium-trials-are-discontinued

Lazabemide is a reversible and selective inhibitor of monoamine oxidase B (MAO-B) that was under clinical development against Parkinson's disease, Alzheimer's disease and as an aid to smoking cessation. The development of the drug was discontinued due to liver toxicity.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Monoamine oxidase B 72 Target ID: CHEMBL2039 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24012182	Inhibitor 8297		0.091 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Alzheimer’s disease 272 Sources: http://www.europeanneuropsychopharmacology.com/article/S0924-977X(99)80017-0/abstract	Primary	Phase III 656	Unknown Approved Use Unknown
Parkinson's disease 226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8489205	Primary	Phase III 656	Unknown Approved Use Unknown
Smoking 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12359039	Primary	Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Ro 19-6327, a reversible and highly selective monoamine, oxidase B inhibitor: a novel tool to explore the MAO-B function in humans.	1990	2122653
Monoamine oxidase B (MAO B) inhibitor therapy in Parkinson's disease: the degree and reversibility of human brain MAO B inhibition by Ro 19 6327.	1993 Oct	8413955
Lazabemide (Ro 19-6327), a reversible and highly sensitive MAO-B inhibitor: preclinical and clinical findings.	1994	7931245
Increased monoamine oxidase B activity in plaque-associated astrocytes of Alzheimer brains revealed by quantitative enzyme radioautography.	1994 Sep	7816197
Molecular neuroanatomy of human monoamine oxidases A and B revealed by quantitative enzyme radioautography and in situ hybridization histochemistry.	1996 Feb	9045087
Effect of lazabemide on the progression of disability in early Parkinson's disease. The Parkinson Study Group.	1996 Jul	8687199
Increased density of catalytic sites and expression of brain monoamine oxidase A in humans with hepatic encephalopathy.	1997 Mar	9048767
Safety study of lazabemide (Ro19-6327), a new MAO-B inhibitor, on cardiac arrhythmias and blood pressure of patients with Parkinson's disease.	1999 Nov-Dec	10626094
Antioxidant activity of the monoamine oxidase B inhibitor lazabemide.	2000 Sep 1	10927030
Differential substrate specificity of monoamine oxidase in the rat heart and renal cortex.	2003 Jul 11	12818349
Locomotor effects of imidazoline I2-site-specific ligands and monoamine oxidase inhibitors in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway.	2004 Dec	15545290
SL25.1131 [3(S),3a(S)-3-methoxymethyl-7-[4,4,4-trifluorobutoxy]-3,3a,4,5-tetrahydro-1,3-oxazolo[3,4-a]quinolin-1-one], a new, reversible, and mixed inhibitor of monoamine oxidase-A and monoamine oxidase-B: biochemical and behavioral profile.	2004 Sep	15178694
Docking studies on monoamine oxidase-B inhibitors: estimation of inhibition constants (K(i)) of a series of experimentally tested compounds.	2005 Oct 15	16137882
Novel reversible monoamine oxidase A inhibitors: highly potent and selective 3-(1H-pyrrol-3-yl)-2-oxazolidinones.	2011 Dec 8	22017497
Up-regulation of the isoenzymes MAO-A and MAO-B in the human basal ganglia and pons in Huntington's disease revealed by quantitative enzyme radioautography.	2011 Jan 25	21075085

Patents

Sample Use Guides

In Vivo Use Guide

In clinical trial against Parkinson's disease, lazabemide was administered orally at doses 25-200 mg/day

Route of Administration: Oral

In Vitro Use Guide

Lazabemide inhibited recombinant human MAO-B with IC50 of 0.091 uM.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:50:48 GMT 2023` Edited by `admin` on `Sat Dec 16 16:50:48 GMT 2023`
Record UNII	420HD787N9
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LAZABEMIDE

Official Name

English

2-PYRIDINECARBOXAMIDE, N-(2-AMINOETHYL)-5-CHLORO-

Systematic Name

English

LAZABEMIDE [MART.]

Common Name

English

lazabemide [INN]

Common Name

English

LAZABEMIDE [MI]

Common Name

English

RO 19-6327/000

Code

English

N-(2-Aminoethyl)-5-chloropicolinamide

Systematic Name

English

RO-19-6327/000

Code

English

Lazabemide [WHO-DD]

Common Name

English

RO-196327

Code

English

LAZABEMIDE [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C667