tert-butyl N-[(2S)-1-[(2S,4R)-2-{[(1R,2S)-1-[(cyclopropanesulfonyl)carbamoyl]-2-ethenylcyclopropyl]carbamoyl}-4-[(7-methoxy-2-phenylquinolin-4-yl)oxy]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate

ID: ALA414993

Chembl Id: CHEMBL414993

PubChem CID: 16729699

Max Phase: Preclinical

Molecular Formula: C41H51N5O9S

Molecular Weight: 789.95

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  C=C[C@@H]1C[C@]1(NC(=O)[C@@H]1C[C@@H](Oc2cc(-c3ccccc3)nc3cc(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/C41H51N5O9S/c1-9-25-22-41(25,37(49)45-56(51,52)28-16-17-28)44-35(47)32-20-27(23-46(32)36(48)34(39(2,3)4)43-38(50)55-40(5,6)7)54-33-21-30(24-13-11-10-12-14-24)42-31-19-26(53-8)15-18-29(31)33/h9-15,18-19,21,25,27-28,32,34H,1,16-17,20,22-23H2,2-8H3,(H,43,50)(H,44,47)(H,45,49)/t25-,27-,32+,34-,41-/m1/s1

Standard InChI Key:  YMHQYWPVQDRYSQ-LMPQEXDPSA-N

Alternative Forms

1. Parent:

   

   ALA414993

   tert-butyl N-[(1S)-1-[(2S,4R)-2-[[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinyl-cyclopropyl]carbamoyl]-4-[(7-methoxy-2-phenyl-4-quinolyl)oxy]pyrrolidine-1-carbonyl]-2,2-dimethyl-propyl]carbamate

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: 789.95

Molecular Weight (Monoisotopic): 789.3407

AlogP: 4.87

#Rotatable Bonds: 12

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: 3.76

CX Basic pKa: 5.60

CX LogP: 3.22

CX LogD: 3.73

Aromatic Rings: 3

Heavy Atoms: 56

QED Weighted: 0.21

Np Likeness Score: -0.20

References

1. Rönn R, Gossas T, Sabnis YA, Daoud H, Kerblom E, Danielson UH, Sandström A..  (2007)  Evaluation of a diverse set of potential P1 carboxylic acid bioisosteres in hepatitis C virus NS3 protease inhibitors.,  15  (12): [PMID:17449253] [10.1016/j.bmc.2007.03.089]

2. Meanwell NA..  (2011)  Synopsis of some recent tactical application of bioisosteres in drug design.,  54  (8): [PMID:21413808] [10.1021/jm1013693]

3. 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]

4. 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]

5. Meanwell NA..  (2016)  2015 Philip S. Portoghese Medicinal Chemistry Lectureship. Curing Hepatitis C Virus Infection with Direct-Acting Antiviral Agents: The Arc of a Medicinal Chemistry Triumph.,  59  (16): [PMID:27501244] [10.1021/acs.jmedchem.6b00915]

Source

Source(1):

• Scientific Literature