(R)-3-((2-chloro-5-(2,2-difluoroethyl)-8-fluoro-5H-dibenzo[b,e][1,4]diazepin-11-yl)amino)-N-isopropylpyrrolidine-1-carboxamide

ID: ALA5274607

Max Phase: Preclinical

Molecular Formula: C23H25ClF3N5O

Molecular Weight: 479.93

Names and Identifiers

Canonical SMILES:  CC(C)NC(=O)N1CC[C@@H](NC2=Nc3cc(F)ccc3N(CC(F)F)c3ccc(Cl)cc32)C1

Standard InChI:  InChI=1S/C23H25ClF3N5O/c1-13(2)28-23(33)31-8-7-16(11-31)29-22-17-9-14(24)3-5-19(17)32(12-21(26)27)20-6-4-15(25)10-18(20)30-22/h3-6,9-10,13,16,21H,7-8,11-12H2,1-2H3,(H,28,33)(H,29,30)/t16-/m1/s1

Standard InChI Key:  OINGHOPGNMYCAB-MRXNPFEDSA-N

Molfile:  

 
     RDKit          2D

 33 36  0  0  0  0  0  0  0  0999 V2000
    3.5846    3.2151    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6667    2.3942    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4055    2.0659    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0099    1.9017    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.2438    2.2575    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1617    3.0784    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.5871    1.7649    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.5871    0.9440    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7935    0.6977    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3284    1.3545    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4925    1.3545    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9029    0.6430    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7238    0.6430    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2437    0.0136    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0373    0.2325    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.6393   -0.3146    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.4055   -0.0684    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
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   -2.0522   -0.8072    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3134   -1.1629    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3134   -1.9838    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6019   -2.3942    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.1094   -1.9838    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6019   -3.2151    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5746   -0.8072    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0273   -1.3545    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7935   -1.1081    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9850   -0.3146    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7786   -0.0684    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    0.3831    0.2325    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4104    0.0136    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7935    2.0112    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
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 29 30  1  0
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 31 32  2  0
 12 32  1  0
 26 32  1  0
 10 33  1  0
  7 33  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA5274607

   ---

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type:

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 479.93

Molecular Weight (Monoisotopic): 479.1700

AlogP: 5.06

#Rotatable Bonds: 4

Polar Surface Area: 59.97

Molecular Species: NEUTRAL

HBA: 4

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 6

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: ┄

CX Basic pKa: 4.27

CX LogP: 3.98

CX LogD: 3.98

Aromatic Rings: 2

Heavy Atoms: 33

QED Weighted: 0.64

Np Likeness Score: -1.69

References

1. Chow HY, Karchugina S, Groendyke BJ, Toenjes S, Hatcher J, Donovan KA, Fischer ES, Abalakov G, Faezov B, Dunbrack R, Gray NS, Chernoff J..  (2022)  Development and Utility of a PAK1-Selective Degrader.,  65  (23.0): [PMID:36416208] [10.1021/acs.jmedchem.2c00756]

2. Hall, Matthew D and 8 more authors.  2009-05-28  Synthesis, activity, and pharmacophore development for isatin-beta-thiosemicarbazones with selective activity toward multidrug-resistant cells.  [PMID:19397322]

3. Dolan, Bridget M BM and 9 more authors.  2013-04-02  Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486.  [PMID:23509247]

4. Licciulli, Silvia S and 11 more authors.  2013-10-04  FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas.  [PMID:23960073]

5. Ogura, Masato M and 6 more authors.  2016-04-01  Prenylated quinolinecarboxylic acid derivative suppresses immune response through inhibition of PAK2.  [PMID:26827943]

6. Rudolph, Joachim J and 28 more authors.  2016-06-09  Chemically Diverse Group I p21-Activated Kinase (PAK) Inhibitors Impart Acute Cardiovascular Toxicity with a Narrow Therapeutic Window.  [PMID:27167326]

7. Farag, Ahmed Karam AK and 5 more authors.  2017-12-01  Novel LCK/FMS inhibitors based on phenoxypyrimidine scaffold as potential treatment for inflammatory disorders.  [PMID:29107425]

8. Klaeger, Susan S and 47 more authors.  2017-12-01  The target landscape of clinical kinase drugs.  [PMID:29191878]

9. Narayan, Satya S and 7 more authors.  2019-01-01  ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells.  [PMID:30384048]

Source

Source(1):

• Scientific Literature