4-[3,4-Dioxo-2-(1,2,2-trimethyl-propylamino)-cyclobut-1-enylamino]-3-ethyl-benzonitrile

ID: ALA2062142

PubChem CID: 9883778

Max Phase: Preclinical

Molecular Formula: C19H23N3O2

Molecular Weight: 325.41

Molecule Type: Small molecule

Names and Identifiers

Synonyms: WAY-133537 | WAY-133537|CHEMBL2062142|(+)-(R)-4-[3,4-dioxo-2-(1,2,2-trimethyl-propylamino)-cyclobut-1-enylamino]-3-ethylbenzonitrile|SCHEMBL4258934|KDOHDKFUZYPGPN-LLVKDONJSA-N|BDBM50475963|4-[[2-[[(2R)-3,3-dimethylbutan-2-yl]amino]-3,4-dioxocyclobuten-1-yl]amino]-3-ethylbenzonitrile

Canonical SMILES:  CCc1cc(C#N)ccc1Nc1c(N[C@H](C)C(C)(C)C)c(=O)c1=O

Standard InChI:  InChI=1S/C19H23N3O2/c1-6-13-9-12(10-20)7-8-14(13)22-16-15(17(23)18(16)24)21-11(2)19(3,4)5/h7-9,11,21-22H,6H2,1-5H3/t11-/m1/s1

Standard InChI Key:  KDOHDKFUZYPGPN-LLVKDONJSA-N

Molfile:  

     RDKit          2D

 24 25  0  0  1  0  0  0  0  0999 V2000
    3.8625   -5.8167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6875   -5.8167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6875   -4.9875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8625   -4.9875    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1500   -6.2292    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.2667   -6.3917    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.4292   -5.8042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4333   -4.1500    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.0667   -6.1792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.2875   -4.5625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7167   -6.2167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2625   -4.4042    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.2875   -4.4042    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.6500   -6.7667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0000   -5.8042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.4292   -4.9750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0000   -4.9750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7167   -4.5625    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7167   -7.0417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.0667   -7.3417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.2292   -6.1917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.2250   -7.3500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.2792   -5.4000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0000   -7.4542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  2  0
  3  4  1  0
  4  1  1  0
  5  1  1  0
  6  2  1  0
  7  5  1  0
  8 10  3  0
  9  6  1  0
 10 17  1  0
 11  7  2  0
 12  3  2  0
 13  4  2  0
 14  9  1  0
 15 11  1  0
 16  7  1  0
 17 18  1  0
 18 16  2  0
 19 11  1  0
 20 14  1  0
 21 14  1  0
 22 14  1  0
  9 23  1  6
 24 19  1  0
  2  3  1  0
 15 17  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA2062142

   (+)-(R)-4-[3,4-dioxo-2-(1,2,2-trimethyl-propylamino)-cyclobut-1-enylamino]-3-ethylbenzonitrile

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: 325.41

Molecular Weight (Monoisotopic): 325.1790

AlogP: 3.31

#Rotatable Bonds: 5

Polar Surface Area: 81.99

Molecular Species: NEUTRAL

HBA: 5

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 5

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 11.92

CX Basic pKa: ┄

CX LogP: 3.85

CX LogD: 3.85

Aromatic Rings: 2

Heavy Atoms: 24

QED Weighted: 0.82

Np Likeness Score: -0.92

References

1. Butera JA, Antane MM, Antane SA, Argentieri TM, Freeden C, Graceffa RF, Hirth BH, Jenkins D, Lennox JR, Matelan E, Norton NW, Quagliato D, Sheldon JH, Spinelli W, Warga D, Wojdan A, Woods M..  (2000)  Design and SAR of novel potassium channel openers targeted for urge urinary incontinence. 1. N-Cyanoguanidine bioisosteres possessing in vivo bladder selectivity.,  43  (6): [PMID:10737752] [10.1021/jm9905099]

2. Gilbert AM, Antane MM, Argentieri TM, Butera JA, Francisco GD, Freeden C, Gundersen EG, Graceffa RF, Herbst D, Hirth BH, Lennox JR, McFarlane G, Norton NW, Quagliato D, Sheldon JH, Warga D, Wojdan A, Woods M..  (2000)  Design and SAR of novel potassium channel openers targeted for urge urinary incontinence. 2. Selective and potent benzylamino cyclobutenediones.,  43  (6): [PMID:10737753] [10.1021/jm9905108]

3. Coghlan MJ, Carroll WA, Gopalakrishnan M..  (2001)  Recent developments in the biology and medicinal chemistry of potassium channel modulators: update from a decade of progress.,  44  (11): [PMID:11356099] [10.1021/jm000484+]

4. Turner SC, Carroll WA, White TK, Brune ME, Buckner SA, Gopalakrishnan M, Fabiyi A, Coghlan MJ, Scott VE, Castle NA, Daza AV, Milicic I, Sullivan JP..  (2003)  Structure-activity relationship of a novel class of naphthyl amide KATP channel openers.,  13  (10): [PMID:12729655] [10.1016/s0960-894x(03)00205-1]

5. Carroll WA, Altenbach RJ, Bai H, Brioni JD, Brune ME, Buckner SA, Cassidy C, Chen Y, Coghlan MJ, Daza AV, Drizin I, Fey TA, Fitzgerald M, Gopalakrishnan M, Gregg RJ, Henry RF, Holladay MW, King LL, Kort ME, Kym PR, Milicic I, Tang R, Turner SC, Whiteaker KL, Yi L, Zhang H, Sullivan JP..  (2004)  Synthesis and structure-activity relationships of a novel series of 2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide K(ATP) channel openers: discovery of (-)-(9S)-9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9- hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A-278637), a potent K(ATP) opener that selectively inhibits spontaneous bladder contractions.,  47  (12): [PMID:15163196] [10.1021/jm030356w]

6. Altenbach RJ, Brune ME, Buckner SA, Coghlan MJ, Daza AV, Fabiyi A, Gopalakrishnan M, Henry RF, Khilevich A, Kort ME, Milicic I, Scott VE, Smith JC, Whiteaker KL, Carroll WA..  (2006)  Effects of substitution on 9-(3-bromo-4-fluorophenyl)-5,9-dihydro-3H,4H-2,6-dioxa-4- azacyclopenta[b]naphthalene-1,8-dione, a dihydropyridine ATP-sensitive potassium channel opener.,  49  (23): [PMID:17154517] [10.1021/jm060549u]

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

8. Chasák J, Šlachtová V, Urban M, Brulíková L..  (2021)  Squaric acid analogues in medicinal chemistry.,  209  [PMID:33035923] [10.1016/j.ejmech.2020.112872]

Source

Source(1):

• Scientific Literature