2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

ID: ALA2059435

Chembl Id: CHEMBL2059435

Cas Number: 1352064-70-0

PubChem CID: 56965957

Max Phase: Preclinical

Molecular Formula: C25H29Cl2NO4

Molecular Weight: 478.42

Molecule Type: Small molecule

Names and Identifiers

Synonyms: AM-8553 | AM-8553|CHEMBL2059435|1352064-70-0|{(3r,5r,6s)-5-(3-Chlorophenyl)-6-(4-Chlorophenyl)-1-[(2s,3s)-2-Hydroxypentan-3-Yl]-3-Methyl-2-Oxopiperidin-3-Yl}acetic Acid|AM 8553|SCHEMBL9991837|YUALYRLIFVPOHL-VPLUBSIMSA-N|BDBM50388626|AKOS040745550|2-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-1-((2S,3S)-2-hydroxypentan-3-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid|HY-18052|PD145462|CS-0007199|Q27451341|0R3

Canonical SMILES:  CC[C@@H]([C@H](C)O)N1C(=O)[C@@](C)(CC(=O)O)C[C@H](c2cccc(Cl)c2)[C@H]1c1ccc(Cl)cc1

Standard InChI:  InChI=1S/C25H29Cl2NO4/c1-4-21(15(2)29)28-23(16-8-10-18(26)11-9-16)20(17-6-5-7-19(27)12-17)13-25(3,24(28)32)14-22(30)31/h5-12,15,20-21,23,29H,4,13-14H2,1-3H3,(H,30,31)/t15-,20+,21-,23+,25+/m0/s1

Standard InChI Key:  YUALYRLIFVPOHL-VPLUBSIMSA-N

Alternative Forms

1. Parent:

   

   ALA2059435

   {(3r,5r,6s)-5-(3-Chlorophenyl)-6-(4-Chlorophenyl)-1-[(2s,3s)-2-Hydroxypentan-3-Yl]-3-Methyl-2-Oxopiperidin-3-Yl}acetic Acid

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: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 478.42

Molecular Weight (Monoisotopic): 477.1474

AlogP: 5.69

#Rotatable Bonds: 7

Polar Surface Area: 77.84

Molecular Species: ACID

HBA: 3

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 5

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 4.47

CX Basic pKa: ┄

CX LogP: 5.47

CX LogD: 2.63

Aromatic Rings: 2

Heavy Atoms: 32

QED Weighted: 0.54

Np Likeness Score: -0.08

References

1. Bernard D, Zhao Y, Wang S..  (2012)  AM-8553: a novel MDM2 inhibitor with a promising outlook for potential clinical development.,  55  (11): [PMID:22624960] [10.1021/jm3007068]

2. Rew Y, Sun D, Gonzalez-Lopez De Turiso F, Bartberger MD, Beck HP, Canon J, Chen A, Chow D, Deignan J, Fox BM, Gustin D, Huang X, Jiang M, Jiao X, Jin L, Kayser F, Kopecky DJ, Li Y, Lo MC, Long AM, Michelsen K, Oliner JD, Osgood T, Ragains M, Saiki AY, Schneider S, Toteva M, Yakowec P, Yan X, Ye Q, Yu D, Zhao X, Zhou J, Medina JC, Olson SH..  (2012)  Structure-based design of novel inhibitors of the MDM2-p53 interaction.,  55  (11): [PMID:22524527] [10.1021/jm300354j]

3. Sun D, Li Z, Rew Y, Gribble M, Bartberger MD, Beck HP, Canon J, Chen A, Chen X, Chow D, Deignan J, Duquette J, Eksterowicz J, Fisher B, Fox BM, Fu J, Gonzalez AZ, Gonzalez-Lopez De Turiso F, Houze JB, Huang X, Jiang M, Jin L, Kayser F, Liu JJ, Lo MC, Long AM, Lucas B, McGee LR, McIntosh J, Mihalic J, Oliner JD, Osgood T, Peterson ML, Roveto P, Saiki AY, Shaffer P, Toteva M, Wang Y, Wang YC, Wortman S, Yakowec P, Yan X, Ye Q, Yu D, Yu M, Zhao X, Zhou J, Zhu J, Olson SH, Medina JC..  (2014)  Discovery of AMG 232, a potent, selective, and orally bioavailable MDM2-p53 inhibitor in clinical development.,  57  (4): [PMID:24456472] [10.1021/jm401753e]

4. Yu M, Wang Y, Zhu J, Bartberger MD, Canon J, Chen A, Chow D, Eksterowicz J, Fox B, Fu J, Gribble M, Huang X, Li Z, Liu JJ, Lo MC, McMinn D, Oliner JD, Osgood T, Rew Y, Saiki AY, Shaffer P, Yan X, Ye Q, Yu D, Zhao X, Zhou J, Olson SH, Medina JC, Sun D..  (2014)  Discovery of Potent and Simplified Piperidinone-Based Inhibitors of the MDM2-p53 Interaction.,  5  (8): [PMID:25147610] [10.1021/ml500142b]

5.  (2016)  Piperidinone derivatives as MDM2 inhibitors for the treatment of cancer, 

Source

Source(2):

• Scientific Literature
• BindingDB Database