LBP-1 (drug)

LBP-1

Identifiers
IUPAC name 2-{4-[(3-[7-chloro-1-(oxan-4-ylmethyl)indol-3-yl]-1,2,4-oxadiazol-5-yl)methyl]piperazin-1-yl}acetamide
CAS Number	1050478-18-6
PubChem (CID)	25006676
ChemSpider	28530409
Chemical and physical data
Formula	C23H29ClN6O3
Molar mass	472.97 g/mol
3D model (Jmol)	Interactive image
SMILES ClC1=C(N(CC2CCOCC2)C=C3C4=NOC(CN5CCN(CC(N)=O)CC5)=N4)C3=CC=C1
InChI InChI=1S/C23H29ClN6O3/c24-19-3-1-2-17-18(13-30(22(17)19)12-16-4-10-32-11-5-16)23-26-21(33-27-23)15-29-8-6-28(7-9-29)14-20(25)31/h1-3,13,16H,4-12,14-15H2,(H2,25,31) Key:AKWUNZFZIXEOPV-UHFFFAOYSA-N

LBP-1 is a drug originally developed by Organon for the treatment of neuropathic pain,^[1][2] and subsequently further developed by Merck after they acquired Organon's patents following their merger with Schering-Plough.^[3][4][5] It acts as a potent and selective cannabinoid receptor agonist, with high potency at both the CB₁ and CB₂ receptors, but low penetration of the blood–brain barrier. This makes LBP-1 peripherally selective, and while it was effective in animal models of neuropathic pain and allodynia, it did not produce cannabinoid-appropriate responding suggestive of central effects, at any dose tested.^[6]

See also

• Org 28312
• Org 28611
• PTI-1
• PTI-2

References

1. Julia Adam. Indole Derivatives. Patent WO 2008/101995
2. Paul David Ratcliffe, Julia Adam-Worrall, Angus John Morrison, Stuart John Francis, Takao Kiyoi. Indole Derivatives. Patent US 7763732
3. Morrison AJ, Adam JM, Baker JA, Campbell RA, Clark JK, Cottney JE, Deehan M, Easson AM, Fields R, Francis S, Jeremiah F, Keddie N, Kiyoi T, McArthur DR, Meyer K, Ratcliffe PD, Schulz J, Wishart G, Yoshiizumi K. Design, synthesis, and structure-activity relationships of indole-3-heterocycles as agonists of the CB1 receptor. Bioorganic and Medicinal Chemistry Letters. 2011 Jan 1;21(1):506-9. PMID 21075630
4. Kiyoi T, Adam JM, Clark JK, Davies K, Easson AM, Edwards D, Feilden H, Fields R, Francis S, Jeremiah F, McArthur D, Morrison AJ, Prosser A, Ratcliffe PD, Schulz J, Wishart G, Baker J, Campbell R, Cottney JE, Deehan M, Epemolu O, Evans L. Discovery of potent and orally bioavailable heterocycle-based cannabinoid CB1 receptor agonists. Bioorganic and Medicinal Chemistry Letters. 2011 Mar 15;21(6):1748-53. PMID 21316962
5. Ratcliffe P, Adam JM, Baker J, Bursi R, Campbell R, Clark JK, Cottney JE, Deehan M, Easson AM, Ecker D, Edwards D, Epemolu O, Evans L, Fields R, Francis S, Harradine P, Jeremiah F, Kiyoi T, McArthur D, Morrison A, Passier P, Pick J, Schnabel PG, Schulz J, Steinbrede H, Walker G, Westwood P, Wishart G, de Haes JU. Design, synthesis and structure-activity relationships of (indo-3-yl) heterocyclic derivatives as agonists of the CB1 receptor. Discovery of a clinical candidate. Bioorganic and Medicinal Chemistry Letters. 2011 Apr 15;21(8):2541-6. PMID 21411321
6. Adam JM, Clark JK, Davies K, Everett K, Fields R, Francis S, Jeremiah F, Kiyoi T, Maidment M, Morrison A, Ratcliffe P, Prosser A, Schulz J, Wishart G, Baker J, Boyce S, Campbell R, Cottney JE, Deehan M, Martin I. Low brain penetrant CB1 receptor agonists for the treatment of neuropathic pain. Bioorganic and Medicinal Chemistry Letters. 2012 Apr 15;22(8):2932-7. PMID 22421020