2-(2-Bromo-2,2-difluoro-acetylamino)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylic acid o-tolylamide

ID: ALA4074929

PubChem CID: 129897070

Max Phase: Preclinical

Molecular Formula: C19H19BrF2N2O2S

Molecular Weight: 457.34

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cc1ccccc1NC(=O)c1c(NC(=O)C(F)(F)Br)sc2c1CCCCC2

Standard InChI:  InChI=1S/C19H19BrF2N2O2S/c1-11-7-5-6-9-13(11)23-16(25)15-12-8-3-2-4-10-14(12)27-17(15)24-18(26)19(20,21)22/h5-7,9H,2-4,8,10H2,1H3,(H,23,25)(H,24,26)

Standard InChI Key:  VLFFBQAZZDJCHK-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 27 29  0  0  0  0  0  0  0  0999 V2000
   33.8102  -13.9707    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   34.0646  -13.1940    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.4016  -12.7119    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.4012  -11.8947    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.1087  -11.4857    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   32.6933  -11.4864    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   34.1083  -10.6685    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.8153  -10.2641    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.8152   -9.4476    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.1068   -9.0386    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.3969   -9.4519    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   33.4005  -10.2670    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   34.8421  -12.9425    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   35.4487  -13.4902    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   36.2262  -13.2387    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   35.2777  -14.2893    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   35.8842  -14.8369    0.0000 Br  0  0  0  0  0  0  0  0  0  0  0  0
   34.5001  -14.5407    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   35.0608  -15.0768    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   35.5222  -10.6740    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.7430  -13.1977    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.9925  -13.9698    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   32.5436  -14.6525    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.9779  -12.9112    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.7334  -14.7299    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.2777  -13.3314    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   31.1719  -14.1406    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 22  1  1  0
  1  2  1  0
  2  3  2  0
  3 21  1  0
  3  4  1  0
  4  5  1  0
  4  6  2  0
  5  7  1  0
  7  8  2  0
  8  9  1  0
  9 10  2  0
 10 11  1  0
 11 12  2  0
 12  7  1  0
  2 13  1  0
 13 14  1  0
 14 15  2  0
 14 16  1  0
 16 17  1  0
 16 18  1  0
 16 19  1  0
  8 20  1  0
 21 22  2  0
 22 23  1  0
 21 24  1  0
 23 25  1  0
 24 26  1  0
 25 27  1  0
 26 27  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4074929

   ---

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: 457.34

Molecular Weight (Monoisotopic): 456.0319

AlogP: 5.50

#Rotatable Bonds: 4

Polar Surface Area: 58.20

Molecular Species: NEUTRAL

HBA: 3

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 4

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 9.16

CX Basic pKa: ┄

CX LogP: 6.28

CX LogD: 6.27

Aromatic Rings: 2

Heavy Atoms: 27

QED Weighted: 0.47

Np Likeness Score: -1.94

References

1. Truong EC, Phuan PW, Reggi AL, Ferrera L, Galietta LJV, Levy SE, Moises AC, Cil O, Diez-Cecilia E, Lee S, Verkman AS, Anderson MO..  (2017)  Substituted 2-Acylaminocycloalkylthiophene-3-carboxylic Acid Arylamides as Inhibitors of the Calcium-Activated Chloride Channel Transmembrane Protein 16A (TMEM16A).,  60  (11): [PMID:28493701] [10.1021/acs.jmedchem.7b00020]

2. Choi SH,Ryu S,Sim K,Song C,Shin I,Kim SS,Lee YS,Park JY,Sim T.  (2020)  Anti-glioma effects of 2-aminothiophene-3-carboxamide derivatives, ANO1 channel blockers.,  208  [PMID:32906067] [10.1016/j.ejmech.2020.112688]

3. Wang Y, Hu X, Huang H, Jin Z, Gao J, Guo Y, Zhong Y, Li Z, Zong X, Wang K, Zhang L, Liu Z..  (2022)  Optimization of 4-arylthiophene-3-carboxylic acid derivatives as inhibitors of ANO1: Lead optimization studies toward their analgesic efficacy for inflammatory pain.,  237  [PMID:35512566] [10.1016/j.ejmech.2022.114413]

4. Tradtrantip, Lukmanee L, Namkung, Wan W and Verkman, A S AS.  2010-01  Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels.  [PMID:19808995]

5. Kumar, Satish; Namkung, Wan; Verkman, A S and Sharma, Pawan K.  2012-07-15  Novel 5-substituted benzyloxy-2-arylbenzofuran-3-carboxylic acids as calcium activated chloride channel inhibitors.  [PMID:22739085]

6. Truong, Eric C EC and 11 more authors.  2017-06-08  Substituted 2-Acylaminocycloalkylthiophene-3-carboxylic Acid Arylamides as Inhibitors of the Calcium-Activated Chloride Channel Transmembrane Protein 16A (TMEM16A).  [PMID:28493701]

7. Seo, Yohan Y and 5 more authors.  2018-12-05  Synthesis and biological evaluation of novel Ani9 derivatives as potent and selective ANO1 inhibitors.  [PMID:30347323]

8. Choi, Seung-Hye and 8 more authors.  2020-12-15  Anti-glioma effects of 2-aminothiophene-3-carboxamide derivatives, ANO1 channel blockers.  [PMID:32906067]

Source

Source(1):

• Scientific Literature