ID: ALA24461

Max Phase: Preclinical

Molecular Formula: C20H17N3O4S

Molecular Weight: 395.44

Molecule Type: Small molecule

Representations

Synonyms (1): BMS-193884
Synonyms from Alternative Forms(1):

Canonical SMILES:  Cc1noc(NS(=O)(=O)c2ccccc2-c2ccc(-c3ncco3)cc2)c1C

Standard InChI:  InChI=1S/C20H17N3O4S/c1-13-14(2)22-27-19(13)23-28(24,25)18-6-4-3-5-17(18)15-7-9-16(10-8-15)20-21-11-12-26-20/h3-12,23H,1-2H3

Standard InChI Key:  LJGUZUROJOJEMI-UHFFFAOYSA-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: 395.44

Molecular Weight (Monoisotopic): 395.0940

AlogP: 4.41

#Rotatable Bonds: 5

Polar Surface Area: 98.23

Molecular Species: ACID

HBA: 6

HBD: 1

#RO5 Violations: 0

HBA (Lipinski): 7

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 5.52

CX Basic pKa: 1.69

CX LogP: 3.17

CX LogD: 2.27

Aromatic Rings: 4

Heavy Atoms: 28

QED Weighted: 0.54

Np Likeness Score: -1.38

References

1. Wermuth CG..  (2004)  Selective optimization of side activities: another way for drug discovery.,  47  (6): [PMID:14998318] [10.1021/jm030480f]

2. Murugesan N, Gu Z, Spergel S, Young M, Chen P, Mathur A, Leith L, Hermsmeier M, Liu EC, Zhang R, Bird E, Waldron T, Marino A, Koplowitz B, Humphreys WG, Chong S, Morrison RA, Webb ML, Moreland S, Trippodo N, Barrish JC..  (2003)  Biphenylsulfonamide endothelin receptor antagonists. 4. Discovery of N-[[2'-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1'-biphenyl]- 2-yl]methyl]-N,3,3-trimethylbutanamide (BMS-207940), a highly potent and orally active ET(A) selective antagonist.,  46  (1): [PMID:12502366] [10.1021/jm020289q]

3. Wu C, Decker ER, Blok N, Bui H, You TJ, Wang J, Bourgoyne AR, Knowles V, Berens KL, Holland GW, Brock TA, Dixon RA..  (2004)  Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist.,  47  (8): [PMID:15055997] [10.1021/jm030528p]

4. Murugesan N, Gu Z, Stein PD, Spergel S, Mathur A, Leith L, Liu EC, Zhang R, Bird E, Waldron T, Marino A, Morrison RA, Webb ML, Moreland S, Barrish JC..  (2000)  Biphenylsulfonamide endothelin receptor antagonists. 2. Discovery of 4'-oxazolyl biphenylsulfonamides as a new class of potent, highly selective ET(A) antagonists.,  43  (16): [PMID:10956219] [10.1021/jm000105c]

5. Murugesan N, Tellew JE, Gu Z, Kunst BL, Fadnis L, Cornelius LA, Baska RA, Yang Y, Beyer SM, Monshizadegan H, Dickinson KE, Panchal B, Valentine MT, Chong S, Morrison RA, Carlson KE, Powell JR, Moreland S, Barrish JC, Kowala MC, Macor JE..  (2002)  Discovery of N-isoxazolyl biphenylsulfonamides as potent dual angiotensin II and endothelin A receptor antagonists.,  45  (18): [PMID:12190306] [10.1021/jm020138n]

6. Murugesan N, Gu Z, Stein PD, Spergel S, Bisaha S, Liu EC, Zhang R, Webb ML, Moreland S, Barrish JC..  (2002)  Biphenylsulfonamide endothelin receptor antagonists. Part 3: structure-activity relationship of 4'-heterocyclic biphenylsulfonamides.,  12  (4): [PMID:11844662] [10.1016/s0960-894x(01)00791-0]

7. Murugesan N, Gu Z, Fadnis L, Tellew JE, Baska RA, Yang Y, Beyer SM, Monshizadegan H, Dickinson KE, Valentine MT, Humphreys WG, Lan SJ, Ewing WR, Carlson KE, Kowala MC, Zahler R, Macor JE..  (2005)  Dual angiotensin II and endothelin A receptor antagonists: synthesis of 2'-substituted N-3-isoxazolyl biphenylsulfonamides with improved potency and pharmacokinetics.,  48  (1): [PMID:15634011] [10.1021/jm049548x]

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

9. Boss C, Bolli MH, Gatfield J..  (2016)  From bosentan (Tracleer®) to macitentan (Opsumit®): The medicinal chemistry perspective.,  26  (15): [PMID:27321813] [10.1016/j.bmcl.2016.06.014]

Source

Source(1):

• Scientific Literature