ID: ALA37251

Max Phase: Preclinical

Molecular Formula: C24H22N6O3S

Molecular Weight: 474.55

Molecule Type: Small molecule

Representations

Canonical SMILES:  Cc1cc(C(=O)Nc2ccc(-c3ccccc3S(N)(=O)=O)cc2)n(-c2cccc(C(=N)N)c2)n1

Standard InChI:  InChI=1S/C24H22N6O3S/c1-15-13-21(30(29-15)19-6-4-5-17(14-19)23(25)26)24(31)28-18-11-9-16(10-12-18)20-7-2-3-8-22(20)34(27,32)33/h2-14H,1H3,(H3,25,26)(H,28,31)(H2,27,32,33)

Standard InChI Key:  APFKCRTWNKCURW-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: 474.55

Molecular Weight (Monoisotopic): 474.1474

AlogP: 3.03

#Rotatable Bonds: 6

Polar Surface Area: 156.95

Molecular Species: BASE

HBA: 6

HBD: 4

#RO5 Violations: 0

HBA (Lipinski): 9

HBD (Lipinski): 6

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 10.06

CX Basic pKa: 11.38

CX LogP: 1.99

CX LogD: 0.08

Aromatic Rings: 4

Heavy Atoms: 34

QED Weighted: 0.25

Np Likeness Score: -1.71

References

1. Song Y, Clizbe L, Bhakta C, Teng W, Li W, Wu Y, Jia ZJ, Zhang P, Wang L, Doughan B, Su T, Kanter J, Woolfrey J, Wong P, Huang B, Tran K, Sinha U, Park G, Reed A, Malinowski J, Hollenbach S, Scarborough RM, Zhu BY..  (2002)  Design, synthesis, and SAR of substituted acrylamides as factor Xa inhibitors.,  12  (11): [PMID:12031331] [10.1016/s0960-894x(02)00199-3]

2. Jia ZJ, Wu Y, Huang W, Goldman E, Zhang P, Woolfrey J, Wong P, Huang B, Sinha U, Park G, Reed A, Scarborough RM, Zhu BY..  (2002)  Design, synthesis and biological activity of novel non-amidine factor Xa inhibitors. Part 1: P(1) structure-activity relationships of the substituted 1-(2-Naphthyl)-1H-pyrazole-5-carboxylamides.,  12  (12): [PMID:12039583] [10.1016/s0960-894x(02)00239-1]

3. Lam PY, Clark CG, Li R, Pinto DJ, Orwat MJ, Galemmo RA, Fevig JM, Teleha CA, Alexander RS, Smallwood AM, Rossi KA, Wright MR, Bai SA, He K, Luettgen JM, Wong PC, Knabb RM, Wexler RR..  (2003)  Structure-based design of novel guanidine/benzamidine mimics: potent and orally bioavailable factor Xa inhibitors as novel anticoagulants.,  46  (21): [PMID:14521405] [10.1021/jm020578e]

4. Pruitt JR, Pinto DJ, Galemmo RA, Alexander RS, Rossi KA, Wells BL, Drummond S, Bostrom LL, Burdick D, Bruckner R, Chen H, Smallwood A, Wong PC, Wright MR, Bai S, Luettgen JM, Knabb RM, Lam PY, Wexler RR..  (2003)  Discovery of 1-(2-aminomethylphenyl)-3-trifluoromethyl-N- [3-fluoro-2'-(aminosulfonyl)[1,1'-biphenyl)]-4-yl]-1H-pyrazole-5-carboxyamide (DPC602), a potent, selective, and orally bioavailable factor Xa inhibitor(1).,  46  (25): [PMID:14640539] [10.1021/jm030212h]

5. Smallheer JM, Alexander RS, Wang J, Wang S, Nakajima S, Rossi KA, Smallwood A, Barbera F, Burdick D, Luettgen JM, Knabb RM, Wexler RR, Jadhav PK..  (2004)  SAR and factor IXa crystal structure of a dual inhibitor of factors IXa and Xa.,  14  (21): [PMID:15454208] [10.1016/j.bmcl.2004.08.034]

6. Pinto DJ, Smallheer JM, Cheney DL, Knabb RM, Wexler RR..  (2010)  Factor Xa inhibitors: next-generation antithrombotic agents.,  53  (17): [PMID:20503967] [10.1021/jm100146h]

7. Xie Z, Tian Y, Lv X, Xiao X, Zhan M, Cheng K, Li S, Liao C..  (2018)  The selectivity and bioavailability improvement of novel oral anticoagulants: An overview.,  146  [PMID:29407959] [10.1016/j.ejmech.2018.01.067]

Source

Source(1):

• Scientific Literature