(R)-4-(5-(pyrrolidin-3-ylmethoxy)-2-p-tolylpyridin-3-yl)benzonitrile

ID: ALA3134377

Cas Number: 2101305-84-2

PubChem CID: 72793898

Max Phase: Preclinical

Molecular Formula: C24H23N3O

Molecular Weight: 369.47

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cc1ccc(-c2ncc(OC[C@@H]3CCNC3)cc2-c2ccc(C#N)cc2)cc1

Standard InChI:  InChI=1S/C24H23N3O/c1-17-2-6-21(7-3-17)24-23(20-8-4-18(13-25)5-9-20)12-22(15-27-24)28-16-19-10-11-26-14-19/h2-9,12,15,19,26H,10-11,14,16H2,1H3/t19-/m1/s1

Standard InChI Key:  IQVDLEXWAPYWDT-LJQANCHMSA-N

Molfile:  

     RDKit          2D

 28 31  0  0  0  0  0  0  0  0999 V2000
   22.3123   -2.4501    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.3111   -3.2775    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.0260   -3.6904    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   23.7426   -3.2770    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.7396   -2.4465    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.0242   -2.0373    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.5999   -2.0338    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.6010   -1.2076    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.8872   -0.7954    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.1718   -1.2081    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.1747   -2.0374    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.8890   -2.4459    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.5982   -3.6897    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.8837   -3.2750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.1694   -3.6862    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.1683   -4.5122    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   20.8876   -4.9251    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.5990   -4.5115    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.4540   -4.9251    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.4598   -0.7942    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.7447   -0.3840    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   24.4526   -2.0312    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   25.1686   -2.4410    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.8816   -2.0259    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   26.6341   -2.3616    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.1838   -1.7463    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   26.7686   -1.0333    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   25.9623   -1.2081    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  4  2  0
  4  5  1  0
  5  6  2  0
  6  1  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
  1  7  1  0
 13 14  2  0
 14 15  1  0
 15 16  2  0
 16 17  1  0
 17 18  2  0
 18 13  1  0
  2 13  1  0
 16 19  1  0
 20 21  3  0
 10 20  1  0
  5 22  1  0
 22 23  1  0
 24 23  1  6
 24 25  1  0
 25 26  1  0
 26 27  1  0
 27 28  1  0
 28 24  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3134377

   (R)-4-(5-(Pyrrolidin-3-ylmethoxy)-2-(p-tolyl)pyridin-3-yl)benzonitrile

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: 369.47

Molecular Weight (Monoisotopic): 369.1841

AlogP: 4.58

#Rotatable Bonds: 5

Polar Surface Area: 57.94

Molecular Species: BASE

HBA: 4

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 4

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 10.99

CX LogP: 4.35

CX LogD: 1.27

Aromatic Rings: 3

Heavy Atoms: 28

QED Weighted: 0.71

Np Likeness Score: -0.85

References

1. Hitchin JR, Blagg J, Burke R, Burns S, Cockerill MJ, Fairweather EE, Hutton C, Jordan AM, McAndrew C, Mirza A, Mould D, Thomson GJ, Waddell I, Ogilvie DJ.  (2013)  Development and evaluation of selective, reversible LSD1 inhibitors derived from fragments,  4  (11): [10.1039/C3MD00226H]

2. Mould DP, Bremberg U, Jordan AM, Geitmann M, McGonagle AE, Somervaille TCP, Spencer GJ, Ogilvie DJ..  (2017)  Development and evaluation of 4-(pyrrolidin-3-yl)benzonitrile derivatives as inhibitors of lysine specific demethylase 1.,  27  (20): [PMID:28927796] [10.1016/j.bmcl.2017.08.052]

3. Nie Z, Shi L, Lai C, Severin C, Xu J, Del Rosario JR, Stansfield RK, Cho RW, Kanouni T, Veal JM, Stafford JA, Chen YK..  (2019)  Structure-based design and discovery of potent and selective lysine-specific demethylase 1 (LSD1) inhibitors.,  29  (1): [PMID:30409536] [10.1016/j.bmcl.2018.11.001]

4. Menna M, Fiorentino F, Marrocco B, Lucidi A, Tomassi S, Cilli D, Romanenghi M, Cassandri M, Pomella S, Pezzella M, Del Bufalo D, Zeya Ansari MS, Tomašević N, Mladenović M, Viviano M, Sbardella G, Rota R, Trisciuoglio D, Minucci S, Mattevi A, Rotili D, Mai A..  (2022)  Novel non-covalent LSD1 inhibitors endowed with anticancer effects in leukemia and solid tumor cellular models.,  237  [PMID:35525212] [10.1016/j.ejmech.2022.114410]

Source

Source(1):

• Scientific Literature