ID: ALA1255794

Max Phase: Phase

Molecular Formula: C33H43N3O6

Molecular Weight: 577.72

Molecule Type: Small molecule

Representations

Synonyms (5): Aplaviroc | AK-602 | GSK-873140 | GW-873140 | GW873140
Synonyms from Alternative Forms(5):

Canonical SMILES:  CCCCN1C(=O)[C@@H]([C@H](O)C2CCCCC2)NC(=O)C12CCN(Cc1ccc(Oc3ccc(C(=O)O)cc3)cc1)CC2

Standard InChI:  InChI=1S/C33H43N3O6/c1-2-3-19-36-30(38)28(29(37)24-7-5-4-6-8-24)34-32(41)33(36)17-20-35(21-18-33)22-23-9-13-26(14-10-23)42-27-15-11-25(12-16-27)31(39)40/h9-16,24,28-29,37H,2-8,17-22H2,1H3,(H,34,41)(H,39,40)/t28-,29-/m1/s1

Standard InChI Key:  GWNOTCOIYUNTQP-FQLXRVMXSA-N

Molecule Features

Natural Product: Yes

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

Properties

Molecular Weight: 577.72

Molecular Weight (Monoisotopic): 577.3152

AlogP: 4.58

#Rotatable Bonds: 10

Polar Surface Area: 119.41

Molecular Species: ACID

HBA: 6

HBD: 3

#RO5 Violations: 1

HBA (Lipinski): 9

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 4.30

CX Basic pKa: 7.94

CX LogP: 1.48

CX LogD: 1.40

Aromatic Rings: 2

Heavy Atoms: 42

QED Weighted: 0.38

Np Likeness Score: -0.18

References

1. Nichols WG, Steel HM, Bonny T, Adkison K, Curtis L, Millard J, Kabeya K, Clumeck N..  (2008)  Hepatotoxicity observed in clinical trials of aplaviroc (GW873140).,  52  (3): [PMID:18070967] [10.1128/aac.00821-07]

2. Stupple PA, Batchelor DV, Corless M, Dorr PK, Ellis D, Fenwick DR, Galan SR, Jones RM, Mason HJ, Middleton DS, Perros M, Perruccio F, Platts MY, Pryde DC, Rodrigues D, Smith NN, Stephenson PT, Webster R, Westby M, Wood A..  (2011)  An imidazopiperidine series of CCR5 antagonists for the treatment of HIV: the discovery of N-{(1S)-1-(3-fluorophenyl)-3-[(3-endo)-3-(5-isobutyryl-2-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]propyl}acetamide (PF-232798).,  54  (1): [PMID:21128663] [10.1021/jm100978n]

3. Chen M, Vijay V, Shi Q, Liu Z, Fang H, Tong W..  (2011)  FDA-approved drug labeling for the study of drug-induced liver injury.,  16  (15-16): [PMID:21624500] [10.1016/j.drudis.2011.05.007]

4. Liu Z, Shi Q, Ding D, Kelly R, Fang H, Tong W..  (2011)  Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).,  7  (12): [PMID:22194678] [10.1371/journal.pcbi.1002310]

5. Pease J, Horuk R..  (2012)  Chemokine receptor antagonists.,  55  (22): [PMID:22931505] [10.1021/jm300682j]

6. Chen M, Suzuki A, Thakkar S, Yu K, Hu C, Tong W..  (2016)  DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.,  21  (4): [PMID:26948801] [10.1016/j.drudis.2016.02.015]

7. Shah HR, Savjani JK..  (2018)  Recent updates for designing CCR5 antagonists as anti-retroviral agents.,  147  [PMID:29425816] [10.1016/j.ejmech.2018.01.085]

8. Arimont M, Sun SL, Leurs R, Smit M, de Esch IJP, de Graaf C..  (2017)  Structural Analysis of Chemokine Receptor-Ligand Interactions.,  60  (12): [PMID:28165741] [10.1021/acs.jmedchem.6b01309]

Source

Source(1):

• Scientific Literature