SCH-48461: Difference between revisions

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 404437753

| ImageFile=SCH-48461.svg

| ImageSize=

| PIN=(3''R'',4''S'')-1,4-Bis(4-methoxyphenyl)-3-(3-phenylpropyl)azetidin-2-one

| OtherNames=

| Section1 = {{Chembox Identifiers

| CASNo_Ref = {{cascite|correct|??}}

| CASNo=148260-92-8

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = T0H910M40A

| PubChem=132832

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 23541

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 117230

| SMILES = COc1ccc(cc1)[C@@H]2[C@H](C(=O)N2c3ccc(cc3)OC)CCCc4ccccc4

| InChI = 1/C26H27NO3/c1-29-22-15-11-20(12-16-22)25-24(10-6-9-19-7-4-3-5-8-19)26(28)27(25)21-13-17-23(30-2)18-14-21/h3-5,7-8,11-18,24-25H,6,9-10H2,1-2H3/t24-,25-/m1/s1

| InChIKey = IMNTVVOUWFPRSB-JWQCQUIFBU

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 1S/C26H27NO3/c1-29-22-15-11-20(12-16-22)25-24(10-6-9-19-7-4-3-5-8-19)26(28)27(25)21-13-17-23(30-2)18-14-21/h3-5,7-8,11-18,24-25H,6,9-10H2,1-2H3/t24-,25-/m1/s1

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = IMNTVVOUWFPRSB-JWQCQUIFSA-N

| Section2 = {{Chembox Properties

| Formula = C₂₆H₂₇NO₃

| MolarMass = 401.49748

| Appearance=

| Density=

| MeltingPt=

| BoilingPt=

| Solubility=

| Section3 = {{Chembox Hazards

| MainHazards =

| FlashPt =

| AutoignitionPt =

'''SCH-48461''' is a [[cholesterol absorption inhibitor]].<ref name="pmid7669087">{{cite journal |vauthors=Salisbury BG, Davis HR, Burrier RE, etal |title=Hypocholesterolemic activity of a novel inhibitor of cholesterol absorption, SCH 48461 |journal=Atherosclerosis |volume=115 |issue=1 |pages=45–63 |date=May 1995 |pmid=7669087 |doi= 10.1016/0021-9150(94)05499-9}}</ref><ref name="pmid11144997">{{cite journal |vauthors=Dujovne CA, Bays H, Davidson MH, etal |title=Reduction of LDL cholesterol in patients with primary hypercholesterolemia by SCH 48461: results of a multicenter dose-ranging study |journal=J Clin Pharmacol |volume=41 |issue=1 |pages=70–8 |date=January 2001 |pmid=11144997 |doi= 10.1177/00912700122009854|s2cid=30737100 |url=http://jcp.sagepub.com/cgi/pmidlookup?view=long&pmid=11144997}}</ref>

During the early phases of an [[NPC1L1]] inhibitor discovery program at [[Schering-Plough]], conformationally restricted analogs based on the [[2-azetidinone]] backbone were targeted by Burnett and co-workers.<ref>{{cite journal | doi = 10.1021/jm00038a001 | title=2-Azetidinones as Inhibitors of Cholesterol Absorption | journal=Journal of Medicinal Chemistry | date=1994 | volume=37 | issue=12 | pages=1733–1736 | first=Duane A. | last=Burnett | pmid=8021912}}</ref> Early in the biological evaluation, it became apparent that even though the in vitro ACAT inhibitory activity of these analogs was modest (e.g., [[IC50|IC₅₀]] values of 2–50 mM), they exhibited significant activity in a cholesterol-fed hamster model (CFH). The discovery of the prototypical 2-azetidinone CAI, SCH-48461 (ACAT IC₅₀ ~26 mM, ED₅₀ of CE reduction in hamsters ~2.2 mpk) and the details of the first-generation SAR have been described in detail.<ref>{{cite journal | doi = 10.1021/jm960405n | title=2-Azetidinone Cholesterol Absorption Inhibitors: Structure−Activity Relationships on the Heterocyclic Nucleus | journal=Journal of Medicinal Chemistry | date=1996 | volume=39 | issue=19 | pages=3684–3693 | first=John W. | last=Clader | pmid=8809157}}</ref>

[[Category:Phenol ethers]]