ID: ALA2403888

Max Phase: Preclinical

Molecular Formula: C35H47N5O9S

Molecular Weight: 713.85

Molecule Type: Small molecule

Representations

Canonical SMILES:  C=C[C@@H]1C[C@]1(NC(=O)[C@@H]1C[C@@H](Oc2nccc3cc(OC)ccc23)CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)C(=O)NS(=O)(=O)C1CC1

Standard InChI:  InChI=1S/C35H47N5O9S/c1-9-21-18-35(21,31(43)39-50(45,46)24-11-12-24)38-28(41)26-17-23(48-29-25-13-10-22(47-8)16-20(25)14-15-36-29)19-40(26)30(42)27(33(2,3)4)37-32(44)49-34(5,6)7/h9-10,13-16,21,23-24,26-27H,1,11-12,17-19H2,2-8H3,(H,37,44)(H,38,41)(H,39,43)/t21-,23-,26+,27-,35-/m1/s1

Standard InChI Key:  IYWRCNFZPNEADN-CXODAYGWSA-N

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

Properties

Molecular Weight: 713.85

Molecular Weight (Monoisotopic): 713.3094

AlogP: 3.20

#Rotatable Bonds: 11

Polar Surface Area: 182.33

Molecular Species: ACID

HBA: 10

HBD: 3

#RO5 Violations: 1

HBA (Lipinski): 14

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.75

CX Basic pKa: 5.09

CX LogP: 2.17

CX LogD: 1.91

Aromatic Rings: 2

Heavy Atoms: 50

QED Weighted: 0.29

Np Likeness Score: -0.18

References

1. Bailey MD, Bordeleau J, Garneau M, Leblanc M, Lemke CT, O'Meara J, White PW, Llinàs-Brunet M..  (2013)  Peptide backbone replacement of hepatitis C virus NS3 serine protease C-terminal cleavage product analogs: discovery of potent succinamide inhibitors.,  23  (15): [PMID:23773863] [10.1016/j.bmcl.2013.05.045]

2. Scola PM, Wang AX, Good AC, Sun LQ, Combrink KD, Campbell JA, Chen J, Tu Y, Sin N, Venables BL, Sit SY, Chen Y, Cocuzza A, Bilder DM, D'Andrea S, Zheng B, Hewawasam P, Ding M, Thuring J, Li J, Hernandez D, Yu F, Falk P, Zhai G, Sheaffer AK, Chen C, Lee MS, Barry D, Knipe JO, Li W, Han YH, Jenkins S, Gesenberg C, Gao Q, Sinz MW, Santone KS, Zvyaga T, Rajamani R, Klei HE, Colonno RJ, Grasela DM, Hughes E, Chien C, Adams S, Levesque PC, Li D, Zhu J, Meanwell NA, McPhee F..  (2014)  Discovery and early clinical evaluation of BMS-605339, a potent and orally efficacious tripeptidic acylsulfonamide NS3 protease inhibitor for the treatment of hepatitis C virus infection.,  57  (5): [PMID:24555570] [10.1021/jm401840s]

3. Sun LQ, Mull E, Zheng B, D'Andrea S, Zhao Q, Wang AX, Sin N, Venables BL, Sit SY, Chen Y, Chen J, Cocuzza A, Bilder DM, Mathur A, Rampulla R, Chen BC, Palani T, Ganesan S, Arunachalam PN, Falk P, Levine S, Chen C, Friborg J, Yu F, Hernandez D, Sheaffer AK, Knipe JO, Han YH, Schartman R, Donoso M, Mosure K, Sinz MW, Zvyaga T, Rajamani R, Kish K, Tredup J, Klei HE, Gao Q, Ng A, Mueller L, Grasela DM, Adams S, Loy J, Levesque PC, Sun H, Shi H, Sun L, Warner W, Li D, Zhu J, Wang YK, Fang H, Cockett MI, Meanwell NA, McPhee F, Scola PM..  (2016)  Discovery of a Potent Acyclic, Tripeptidic, Acyl Sulfonamide Inhibitor of Hepatitis C Virus NS3 Protease as a Back-up to Asunaprevir with the Potential for Once-Daily Dosing.,  59  (17): [PMID:27564532] [10.1021/acs.jmedchem.6b00821]

4. Wang AX, Chen J, Zhao Q, Sun LQ, Friborg J, Yu F, Hernandez D, Good AC, Klei HE, Rajamani R, Mosure K, Knipe JO, Li D, Zhu J, Levesque PC, McPhee F, Meanwell NA, Scola PM..  (2017)  Structure-activity relationships of 4-hydroxy-4-biaryl-proline acylsulfonamide tripeptides: A series of potent NS3 protease inhibitors for the treatment of hepatitis C virus.,  27  (3): [PMID:28011221] [10.1016/j.bmcl.2016.12.013]

5. Venables BL, Sin N, Wang AX, Sun LQ, Tu Y, Hernandez D, Sheaffer A, Lee M, Dunaj C, Zhai G, Barry D, Friborg J, Yu F, Knipe J, Sandquist J, Falk P, Parker D, Good AC, Rajamani R, McPhee F, Meanwell NA, Scola PM..  (2018)  P3-P4 ureas and reverse carbamates as potent HCV NS3 protease inhibitors: Effective transposition of the P4 hydrogen bond donor.,  28  (10): [PMID:29650290] [10.1016/j.bmcl.2018.04.009]

Source

Source(1):

• Scientific Literature