3-(2,4-Difluoro-phenyl)-1-[5-(4,5-diphenyl-1H-imidazol-2-ylsulfanyl)-pentyl]-1-heptyl-urea

ID: ALA274185

Chembl Id: CHEMBL274185

Cas Number: 130804-35-2

PubChem CID: 71355

Max Phase: Phase

Molecular Formula: C34H40F2N4OS

Molecular Weight: 590.78

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Lecimibide | DUP 128 | DUP-128 | Lecimibide|130804-35-2|DuP 128|DuP-128|dup128|CHEMBL274185|Lecimibide (USAN)|A7T248B302|LECIMIBIDE [USAN]|3-(2,4-difluorophenyl)-1-[5-[(4,5-diphenyl-1H-imidazol-2-yl)sulfanyl]pentyl]-1-heptylurea|3-(2,4-difluorophenyl)-1-(5-((4,5-diphenyl-1H-imidazol-2-yl)thio)pentyl)-1-heptylurea|3-(2,4-Difluorophenyl)-1-(5-((4,5-diphenylimidazol-2-yl)thio)pentyl)-1-heptylurea|Urea, N'-(2,4-difluorophenyl)-N-(5-((4,5-diphenyl-1H-imidazol-2-yl)thio)pentyl)-N-heptyl-|Lecimibide [UShow More⌵

Canonical SMILES:  CCCCCCCN(CCCCCSc1nc(-c2ccccc2)c(-c2ccccc2)[nH]1)C(=O)Nc1ccc(F)cc1F

Standard InChI:  InChI=1S/C34H40F2N4OS/c1-2-3-4-5-13-22-40(34(41)37-30-21-20-28(35)25-29(30)36)23-14-8-15-24-42-33-38-31(26-16-9-6-10-17-26)32(39-33)27-18-11-7-12-19-27/h6-7,9-12,16-21,25H,2-5,8,13-15,22-24H2,1H3,(H,37,41)(H,38,39)

Standard InChI Key:  TVXOXGBTADZYCZ-UHFFFAOYSA-N

Alternative Forms

1. Parent:

   

   ALA274185

   LECIMIBIDE

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: Yes

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 590.78

Molecular Weight (Monoisotopic): 590.2891

AlogP: 9.79

#Rotatable Bonds: 16

Polar Surface Area: 61.02

Molecular Species: NEUTRAL

HBA: 3

HBD: 2

#RO5 Violations: 2

HBA (Lipinski): 5

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 10.88

CX Basic pKa: 4.03

CX LogP: 9.78

CX LogD: 9.78

Aromatic Rings: 4

Heavy Atoms: 42

QED Weighted: 0.10

Np Likeness Score: -1.46

References

1. Maduskuie TP, Wilde RG, Billheimer JT, Cromley DA, Germain S, Gillies PJ, Higley CA, Johnson AL, Pennev P, Shimshick EJ..  (1995)  Design, synthesis, and structure--activity relationship studies for a new imidazole series of J774 macrophage specific acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors.,  38  (7): [PMID:7707310] [10.1021/jm00007a004]

2. Wilde RG, Billheimer JT, Germain SJ, Gillies PJ, Higley C, Kezar HS, Maduskuie TP, Shimshick ES, Wexler RR.  (1995)  Acyl CoA:cholesterol acyltransferase (ACAT) inhibitors: ureas bearing heterocyclic groups bioisosteric for an imidazole,  5  (2): [10.1016/0960-894X(95)00001-A]

3. Wilde RG, Billheimer JT.  (1995)  Acyl CoA:cholesterol acyltransferase (ACAT) inhibitors: ureas bearing two heterocyclic head groups,  5  (2): [10.1016/0960-894X(95)00002-B]

4. Wilde RG, Klaczkiewicz JD, Billheimer JT, Wexler RR, Gillies PJ.  (1995)  Acyl CoA:cholesterol acyltransferase (ACAT) inhibitors: heterocyclic bioisosteres for the urea group in DuP 128,  5  (2): [10.1016/0960-894X(95)00003-C]

5. Higley CA, Wilde RG, Maduskuie TP, Johnson AL, Pennev P, Billheimer JT, Robinson CS, Gillies PJ, Wexler RR..  (1994)  Acyl CoA:cholesterol acyltransferase (ACAT) inhibitors: synthesis and structure-activity relationship studies of a new series of trisubstituted imidazoles.,  37  (21): [PMID:7932580] [10.1021/jm00047a009]

6. Ashton M, Bridge A, Bush R, Dron D, Harris N, Jones G, Lythgoe D, Riddell D, Smith C.  (1992)  RP 70676: A potent systematically available inhibitor of acyl-CoA:cholesterol O-acyl transferase (ACAT),  2  (5): [10.1016/S0960-894X(00)80149-3]

7. Sliskovic DR, Krause BR, Picard JA, Anderson M, Bousley RF, Hamelehle KL, Homan R, Julian TN, Rashidbaigi ZA, Stanfield RL..  (1994)  Inhibitors of acyl-CoA: cholesterol O-acyl transferase (ACAT) as hypocholesterolemic agents. 6. The first water-soluble ACAT inhibitor with lipid-regulating activity.,  37  (5): [PMID:8126693] [10.1021/jm00031a002]

8. USP Dictionary of USAN and International Names (2010 edition) and USAN registrations 2007-date, 

9. Shibuya K, Kawamine K, Miura T, Ozaki C, Edano T, Mizuno K, Yoshinaka Y, Tsunenari Y..  (2018)  Design, synthesis and pharmacology of aortic-selective acyl-CoA: Cholesterol O-acyltransferase (ACAT/SOAT) inhibitors.,  26  (14): [PMID:29945757] [10.1016/j.bmc.2018.06.024]

10. Bhattacharjee P, Rutland N, Iyer MR..  (2022)  Targeting Sterol O-Acyltransferase/Acyl-CoA:Cholesterol Acyltransferase (ACAT): A Perspective on Small-Molecule Inhibitors and Their Therapeutic Potential.,  65  (24.0): [PMID:36473091] [10.1021/acs.jmedchem.2c01265]

Source

Source(2):

• Scientific Literature
• USP Dictionary of USAN and International Drug Names