(1R,9S,12S,13S,14S,17R,18Z,21S,23S,24R,25S,27R)-12-[(1E)-1-[(1R,3R,4S)-4-chloro-3-methoxycyclohexyl]prop-1-en-2-yl]-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0^{4,9}]octacos-18-ene-2,3,10,16-tetrone

• ChemBase ID: 221
• Molecular Formular: C43H68ClNO11
• Molecular Mass: 810.45312
• Monoisotopic Mass: 809.44808968
• SMILES: Cl[C@@H]1[C@H](OC)C[C@@H](CC1)/C=C(/[C@H]1OC(=O)[C@H]2N(C(=O)C(=O)[C@@]3(O[C@@H]([C@@H](OC)C[C@H]3C)[C@@H](OC)C[C@@H](C/C(=C\[C@@H](C(=O)C[C@@H](O)[C@@H]1C)CC)/C)C)O)CCCC2)\C
• Canonical SMILES: CC[C@H]1/C=C(/C)\C[C@@H](C)C[C@H](OC)[C@H]2O[C@](O)([C@@H](C[C@@H]2OC)C)C(=O)C(=O)N2[C@H](C(=O)O[C@@H]([C@H]([C@@H](CC1=O)O)C)/C(=C/[C@@H]1CC[C@@H]([C@@H](C1)OC)Cl)/C)CCCC2
• InChI: InChI=1S/C43H68ClNO11/c1-10-30-18-24(2)17-25(3)19-36(53-8)39-37(54-9)21-27(5)43(51,56-39)40(48)41(49)45-16-12-11-13-32(45)42(50)55-38(28(6)33(46)23-34(30)47)26(4)20-29-14-15-31(44)35(22-29)52-7/h18,20,25,27-33,35-39,46,51H,10-17,19,21-23H2,1-9H3/b24-18-,26-20+/t25-,27+,28-,29-,30+,31-,32-,33-,35+,36-,37-,38+,39+,43+/m0/s1
• InChIKey: KASDHRXLYQOAKZ-KDCWXYOMSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (1R,9S,12S,13S,14S,17R,18Z,21S,23S,24R,25S,27R)-12-[(1E)-1-[(1R,3R,4S)-4-chloro-3-methoxycyclohexyl]prop-1-en-2-yl]-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0^{4,9}]octacos-18-ene-2,3,10,16-tetrone
• IUPAC Traditional name: elidel
• Brand Name: Elidel
• Synonyms: ASM 981; SDZ ASM 981; pimecrolimus; Pimecrolimus

Database IDs

• CAS Number: 137071-32-0
• PubChem SID: 160963684; 46505748
• PubChem CID: 17753757

CALCULATED PROPERTIES

JChem

• Acid pKa: 9.955626
• H Acceptors: 10
• H Donor: 2
• LogD (pH = 5.5): 6.808116
• LogD (pH = 7.4): 6.806926
• Log P: 6.808131
• Molar Refractivity: 214.0262 cm^3
• Polarizability: 84.57097 Å^3
• Polar Surface Area: 158.13 Å^2
• Rotatable Bonds: 6
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 4.36
• LOG S: -5.73
• Solubility (Water): 1.52e-03 g/l

PROPERTIES

Physical Property

• Hydrophobicity(logP): 4.4

DETAILS

DrugBank - DB00337

• Drug Groups: approved; investigational
• Description: Pimecrolimus is an immunomodulating agent used in the treatment of atopic dermatitis (eczema). It is currently available as a topical cream, once marketed by Novartis, (however Galderma will be promoting the molecule in Canada in early 2007) under the trade name Elidel. [Wikipedia]
• Indication: For treatment of mild to moderate atopic dermatitis.
• Pharmacology: Pimecrolimus is a chemical that is used to treat atopic dermatitis (eczema). Atopic dermatitis is a skin condition characterized by redness, itching, scaling and inflammation of the skin. The cause of atopic dermatitis is not known; however, scientists believe that it may be due to activation of the immune system by various environmental or emotional triggers. Scientists do not know exactly how pimecrolimus reduces the manifestations of atopic dermatitis, but pimecrolimus reduces the action of T-cells and mast cells which are part of the immune system and contribute to responses of the immune system. Pimecrolimus prevents the activation of T-cells by blocking the effects of chemicals (cytokines) released by the body that stimulate T-cells. Pimecrolimus also reduces the ability of mast cells to release chemicals that promote inflammation.
• Toxicity: Side effects include burning sensation, irritation, pruritus, erythema, and skin infections, at the application site.
• Affected Organisms: Humans and other mammals
• Biotransformation: No drug metabolism was observed in human skin in vitro. Oral administration yielded metabolites produced from O-demethylation and oxygenation reactions.
• Absorption: Because of the low systemic absorption of pimecrolimus following topical application the calculation of standard pharmacokinetic measures such as AUC, C_max, half-life, etc. cannot be reliably done.
• Protein Binding: 74%-87% (in vitro, bound to plasma proteins)
• Elimination: 80% of the drug is excreted in the feces.
• References: Grassberger M, Baumruker T, Enz A, Hiestand P, Hultsch T, Kalthoff F, Schuler W, Schulz M, Werner FJ, Winiski A, Wolff B, Zenke G: A novel anti-inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology. Br J Dermatol. 1999 Aug;141(2):264-73. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

REFERENCES

• Grassberger M, Baumruker T, Enz A, Hiestand P, Hultsch T, Kalthoff F, Schuler W, Schulz M, Werner FJ, Winiski A, Wolff B, Zenke G: A novel anti-inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology. Br J Dermatol. 1999 Aug;141(2):264-73. Pubmed