Motilide [EM574] [Idremcinal]

Cat.# BLS0050

StructureOrigin: semi-synthetic
CH3HOH3COCH3H3CCH3NO HOCH3CH3OCH3O

MotilideOOOCA Index Name: 8,9-Didehydro-N-demethyl-9-deoxoCH
CH3 3O

HOH3C

CAS Registry Number: 110480-13-2
6-deoxy-6,9-epoxy-N-(1methylethyl)-Erythromycin

CH3

Appearance: white powder

CH3
OH

Molecular Formula/ Weight: C39H69NO12=743.98

CH3

Melting Point: 110-112℃ Purity: >97% by HPLC
Solubility:
pKa:

Sol.

Inso.

log P:

Background Information:
Motilides are a series of erythromycin derivatives (especially EM 522, EM 523, EM536 and EM 574) (Table 1)
which showed gastrointestinal motor stimulating (GMS) activity without antibacterial activity (1-4). The GMS
activity is very similar to the effect caused by the hormone motilin (Fig. 1).
Motilides induce phase Ill-like contractions, which are similar to those induced by motilin, in the humangastrointestinal tract during the interdigestive state in dogs and humans. EM574 is a motilin receptor agonist
in the human gastric antrum in vitro, using contraction studies of muscle strips and isolated myocytes,
receptor binding assay and tissue section autoradiography. EM574 stimulated contractions of muscle strips ina concentration-dependent manner (10-7-10-5 M), and this contractile effect was unaffected by pretreatment
with atropine or tetrodotoxin. Isolated myocytes contracted in response to EM574 with a peak shortening at
10-7 M, which was comparable to the response to motilin (5-10).
EM574 displaced specifically 125I-motilin bound to smooth muscle homogenates with a Kd value of 7.8 x 10-9
M, compared with 4.5 x 10-9 M for motilin. Film autoradiograms showed that 125I-motilin-binding sites were loc
We applied a rational computational procedure consisting of conformational analysis and a novel superposing
Furthermore, EM574 has an orexigenic activity with affinity for growth-hormone secretagogue receptor (GSH-R
Handling and Storage:
Store at -20℃.

References:

1. S. Ōmura et al., J. Antibiot., 38, 1631-1632 (1985)
2. S. Ōmura et al., J. Med. Chem., 30, 1941-1943 (1987)
3. K. Tsuzuki et al., Chem. Pharm. Bull., 37, 2687-2700 (1989)

Synthesized by Organic Chemistry Group, The Kitasato Institute.
(ID#: 110480132S)

Antibacterial Activity and Gastrointestinal Motor
Stimulating (GMS) Activity of Motilides
Antibacterial activity

CompoundGMS activity2)(MIC, µg/ml)1)

EM A0.21

EM 2015010EM 523>10018

EM 574>100248

EM 536>10028901) Staphylococcus aureus ATCC 6538P, agar dilution method.
2) GMS activity was estimated by 2 X 2 points pallel line assay.
MeMeNO
9MeHOMeMeHO 6Me HOO

MeOO

MeOOO

HO6Me HOO

MeOH
MeErythromycin A (EM A)

O9MeO

MeO

EM 201
EM 523
EM 574

OO

HO6

Me HO
O

MeOH
Me

R = MeR = EtR = i-Pr

IMe+NMeO

MeMeHOOMeO

MeMeMeHOOMeO

MeMeMeHON

9MeMeR

MeO

MeO

O

OMeO

EM 536MeOH
MeEM
574(30µg/Kg)
EM A(30µg/Kg)

Gastrointestinal
constraction induced
EMEM
A (30µg/Kg)
Gastrointestinal
Constraction
Inducedbyby
574 (30µg/Kg)

Displacement
Iodinated
Motilin
Bindingof Motilides
Displacement ofofiodinatedmotilinbindingof motilides

Hydrophobic (HP)
H-acceptor (HA)
H-donor (HD)
HP1EM 536 (Motilide)
HP4HOOHA8DA11 HO

HA9O

HP5ODA10N
HA7 HOOO
HP2HP3OO HA6Motilin
HP1HA7HD10H O HP3 H+N
N
H3N
NOO
HA6OOH

H-donor/acceptor (DA)HP2HA8HP4O
NH

HO

HP5H
N

OO
HODA9O—ON
H O
HD11H
NO
N
HO
H
NO

NH2O
NH

H
NOO
NH+

H2N

NH2Three-dimensional Structure-activity Relationship Analysis between Motilin andMotilide Using Conformational Analysis and a Novel Molecular Superposing Method
H. Gouda et al., Chem.Pharm.Bull, 48,1835 (2000)