AZAMULIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H38N4O4S
Molecular Weight	478.648
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12C(=O)CC[C@]13CC[C@@H](C)[C@@]2(C)[C@@H](C[C@@](C)(CC)[C@@H](O)[C@@H]3C)OC(=O)CSC4=NN=C(N)N4

InChI

InChIKey=FMHQJXGMLMSMLC-WBUYAQKGSA-N

InChI=1S/C24H38N4O4S/c1-6-22(4)11-16(32-17(30)12-33-21-26-20(25)27-28-21)23(5)13(2)7-9-24(14(3)19(22)31)10-8-15(29)18(23)24/h13-14,16,18-19,31H,6-12H2,1-5H3,(H3,25,26,27,28)/t13-,14+,16-,18+,19+,22-,23+,24+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14709627 | https://www.bioaustralis.com/pdfs/catalogue.pdf | https://www.ncbi.nlm.nih.gov/pubmed/18330977

Azamulin [14-O-(5-(2-amino-1,3,4-triazolyl)thioacetyl)-dihydromutilin] is an azole derivative of the pleuromutilin class of antiinfectives. Azamulin is a selective, irreversible inhibitor of cytochrome P450 (CYP) 3A isoforms (IC50 values range from 26 to 240 nM for CYP3A4 and CYP3A4/5 from different sources). It is at least 50-fold less potent against CYP2J2 and 100-fold less effective against all other CYP isoforms. Azamulin potently blocks the hydroxylation of testosterone and midazolam by CYP3A4. Azamulin exhibited remarkable antibacterial activity against all Gram-positive pathogens including MRSA, PRSP, and VRE, except for E. faecalis.

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cytochrome P450 2J2 4 Target ID: CHEMBL3491 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14709627	Inhibitor 8297	6.6 µM [IC50]
Cytochrome P450 3A 22 Target ID: CHEMBL2364675 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14709627	Inhibitor 8297	0.026 µM [IC50]
Cytochrome P450 3A5 2 Target ID: CHEMBL3019 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14709627	Inhibitor 8297	0.38 µM [IC50]
Cytochrome P450 3A7 1 Target ID: CHEMBL3341582 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14709627	Inhibitor 8297	0.34 µM [IC50]
Streptococcus pneumoniae 25 Target ID: CHEMBL347 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14709627	Inhibitor 8297
Staphylococcus aureus 67 Target ID: CHEMBL352 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14709627	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gram-positive bacterial infections 8 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18330977	Primary		Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Automated screening with confirmation of mechanism-based inactivation of CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2 in pooled human liver microsomes.	2005 Aug	15860655

Patents

Sample Use Guides

In Vivo Use Guide

Lethal S. aureus (MSSA) systemic infection model in mice: ED50 of 13.3 mg/kg, po

Route of Administration: Oral

In Vitro Use Guide

Preincubation of 4.8 uM and 9.6 uM azamulin (concentrations 20 and 40 times the IC50, respectively) for 5 min with a CYP3A-enriched Human Liver Microsomes (HLM) pool in the presence of NADPH prior to a 1:20 dilution into a testosterone reaction mix eliminated more than 90% of the testosterone 6beta-hydroxylase activity compared with preincubation in the absence of NADPH.

Name

Type

Language

AZAMULIN

Official Name

English

azamulin [INN]

Common Name

English

((5-AMINO-S-TRIAZOL-3-YL)THIO)ACETIC ACID, 8-ESTER WITH (3AS,4R,5S,6R,8R,9R,9AR,10R)-6-ETHYLOCTAHYDRO-5,8-DIHYDROXY-4,6,9,10-TETRAMETHYL-3A,9-PROPANO-3AH-CYCLOPENTACYCLOOCTEN-1(4H)-ONE

Common Name

English

14-((5-AMINO-4H-1,2,4-TRIAZOL-3-YL)-THIOACETOXY)-14-DEOXY-19,20-DIHYDROMUTILIN

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C52588