ATIZORAM

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H24N2O3
Molecular Weight	316.3948
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(O[C@H]2C[C@@H]3CC[C@H]2C3)C=C(C=C1)C4CNC(=O)NC4

InChI

InChIKey=LITNEAPWQHVPOK-FFSVYQOJSA-N

InChI=1S/C18H24N2O3/c1-22-15-5-4-12(14-9-19-18(21)20-10-14)8-17(15)23-16-7-11-2-3-13(16)6-11/h4-5,8,11,13-14,16H,2-3,6-7,9-10H2,1H3,(H2,19,20,21)/t11-,13+,16+/m1/s1

HIDE SMILES / InChI

Description
Sources: http://adisinsight.springer.com/drugs/800005810 | https://www.ncbi.nlm.nih.gov/pubmed/9360015 | https://www.ncbi.nlm.nih.gov/pubmed/8819523

Atizoram (CP-80633) is a phosphodiesterase IV inhibitor with bronchodilatory and antiinflammatory properties. It was in phase II trials with Pfizer in the US for the treatment of asthma, atopic dermatitis and psoriasis. Development of atizoram has been discontinued in the asthma indication and no recent development has been reported for the other indications. CP-80633 inhibits PDE4 isozymes (human lung IC50 = 1.27 uM) in the absence of effects on PDE1, PDE2, PDE3 and PDE5 isozymes (IC50 > 100 uM). It exhibits no significant selectivity for any single cloned PDE4A, B, C or D isoform.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Phosphodiesterase 4A 13 Target ID: CHEMBL254 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9360015 \| http://adisinsight.springer.com/drugs/800005810 \| https://www.ncbi.nlm.nih.gov/pubmed/8819523	Inhibitor 8504	0.5 µM [IC50]
Phosphodiesterase 4B 11 Target ID: CHEMBL275 Sources: http://adisinsight.springer.com/drugs/800005810 \| https://www.ncbi.nlm.nih.gov/pubmed/8819523	Inhibitor 8504	0.32 µM [IC50]
Phosphodiesterase 4D 14 Target ID: CHEMBL288 Sources: http://adisinsight.springer.com/drugs/800005810 \| https://www.ncbi.nlm.nih.gov/pubmed/8819523	Inhibitor 8504	0.4 µM [IC50]
Phosphodiesterase 4C 5 Target ID: CHEMBL291 Sources: http://adisinsight.springer.com/drugs/800005810 \| https://www.ncbi.nlm.nih.gov/pubmed/8819523	Inhibitor 8504	6.56 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Atopic dermatitis 64 Sources: http://adisinsight.springer.com/drugs/800005810	Primary	Phase II 1147	Unknown Approved Use Unknown
Psoriasis 87 Sources: http://adisinsight.springer.com/drugs/800005810	Primary	Phase II 1147	Unknown Approved Use Unknown
Asthma 244 Sources: http://adisinsight.springer.com/drugs/800005810	Primary	Phase II 1147	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Differential in vivo and in vitro bronchorelaxant activities of CP-80,633, a selective phosphodiesterase 4 inhibitor.	1997-08	9360015
The phosphodiesterase type 4 (PDE4) inhibitor CP-80,633 elevates plasma cyclic AMP levels and decreases tumor necrosis factor-alpha (TNFalpha) production in mice: effect of adrenalectomy.	1997-02	9023272
In vitro pharmacology of the novel phosphodiesterase type 4 inhibitor, CP-80633.	1996-09	8819523

Patents

Sample Use Guides

In Vivo Use Guide

Mice: Atizoram dose-dependently (3-32 mg/kg p.o.) elevated plasma cAMP levels and decreased systemic TNFalpha production in response to i.p. injection of lipopolysaccharide.

Route of Administration: Oral

In Vitro Use Guide

Atizoram (CP-80633) inhibits PDE4 isozymes (human lung IC50 = 1.27 uM). CP-80633 inhibits adenosine 3'-5'-cyclic monophosphate hydrolysis in partially purified human peripheral blood monocyte cytosol (IC50 = 3.52 uM), eosinophil membrane (IC50 = 1.10 uM) and T cell membrane (IC50 = 2.28 uM) preparations. Consistent with its action as a PDE4 inhibitor in whole cells, CP-80633 potentiates PGE1 dependent increases in adenosine 3'-5'-cyclic monophosphate levels in human U937 cells, and in human eosinophils, monocytes and T cells (EC200 approximately 1.0 uM). Consequently, CP-80633 inhibits many inflammatory cell functions including 1) human eosinophil superoxide anion production (IC50 < 0.6 uM), 2 C5a-(IC50 = 0.40 uM) and LTB4-(IC50 = 0.20 uM) mediated guinea pig peritoneal eosinophil chemotaxis and 3) lipopolysac-charide-induced tumor necrosis factor-alpha release from human monocytes (IC50 = 0.219 uM).

Name

Type

Language

atizoram [INN]

Preferred Name

English

ATIZORAM

Official Name

English

ATIZORAM [USAN]

Common Name

English

TETRAHYDRO-5-(4-METHOXY-3-((1S,2S,4R)-2-NORBORNYLOXY)PHENYL)-2(1H)-PYRIMIDINONE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C744