4-Cyano-1H-imidazole-2-carboxylic Acid{2-Cyclohex-1-enyl-4-[1-(2-dimethylamino-acetyl)-piperidin-4-yl]-phenyl}-amide

ID: ALA1908842

Chembl Id: CHEMBL1908842

Max Phase: Preclinical

Molecular Formula: C26H32N6O2

Molecular Weight: 460.58

Molecule Type: Small molecule

Names and Identifiers

Synonyms: JNJ-28312141

Synonyms from Alternative Forms(1): JNJ-28312141

Canonical SMILES:  CN(C)CC(=O)N1CCC(c2ccc(NC(=O)c3nc(C#N)c[nH]3)c(C3=CCCCC3)c2)CC1

Standard InChI:  InChI=1S/C26H32N6O2/c1-31(2)17-24(33)32-12-10-18(11-13-32)20-8-9-23(22(14-20)19-6-4-3-5-7-19)30-26(34)25-28-16-21(15-27)29-25/h6,8-9,14,16,18H,3-5,7,10-13,17H2,1-2H3,(H,28,29)(H,30,34)

Standard InChI Key:  GUBJNPWVIUFSTR-UHFFFAOYSA-N

Alternative Forms

1. Alternative Forms:

   

   ALA1908842

   5-Cyano-N-(5-(1-(2-(dimethylamino)acetyl)piperidin-4-yl)-2',3',4',5'-tetrahydro-[1,1'-biphenyl]-2-yl)-1H-imidazole-2-carboxamide hydrochloride

2. Parent:

   

   ALA1908842

   ---

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: 460.58

Molecular Weight (Monoisotopic): 460.2587

AlogP: 3.76

#Rotatable Bonds: 6

Polar Surface Area: 105.12

Molecular Species: NEUTRAL

HBA: 5

HBD: 2

#RO5 Violations: 0

HBA (Lipinski): 8

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 7.17

CX Basic pKa: 7.77

CX LogP: 2.27

CX LogD: 2.40

Aromatic Rings: 2

Heavy Atoms: 34

QED Weighted: 0.68

Np Likeness Score: -1.01

References

1. Illig CR, Manthey CL, Wall MJ, Meegalla SK, Chen J, Wilson KJ, Ballentine SK, Desjarlais RL, Schubert C, Crysler CS, Chen Y, Molloy CJ, Chaikin MA, Donatelli RR, Yurkow E, Zhou Z, Player MR, Tomczuk BE..  (2011)  Optimization of a potent class of arylamide colony-stimulating factor-1 receptor inhibitors leading to anti-inflammatory clinical candidate 4-cyano-N-[2-(1-cyclohexen-1-yl)-4-[1-[(dimethylamino)acetyl]-4-piperidinyl]phenyl]-1H-imidazole-2-carboxamide (JNJ-28312141).,  54  (22): [PMID:22039836] [10.1021/jm200900q]

2. Illig CR, Manthey CL, Meegalla SK, Wall MJ, Chen J, Wilson KJ, DesJarlais RL, Ballentine SK, Schubert C, Crysler CS, Chen Y, Molloy CJ, Chaikin MA, Donatelli RR, Yurkow E, Zhou Z, Player MR, Tomczuk BE..  (2013)  Enhancement of kinase selectivity in a potent class of arylamide FMS inhibitors.,  23  (23): [PMID:24138939] [10.1016/j.bmcl.2013.09.061]

3.  (2020)  Compositions and methods for treating beta-globinopathies, 

4. Caldwell TM, Ahn YM, Bulfer SL, Leary CB, Hood MM, Lu WP, Vogeti L, Vogeti S, Kaufman MD, Wise SC, Le Bourdonnec B, Smith BD, Flynn DL..  (2022)  Discovery of vimseltinib (DCC-3014), a highly selective CSF1R switch-control kinase inhibitor, in clinical development for the treatment of Tenosynovial Giant Cell Tumor (TGCT).,  74  [PMID:35961460] [10.1016/j.bmcl.2022.128928]

5. Caldwell TM, Kaufman MD, Wise SC, Mi Ahn Y, Hood MM, Lu WP, Patt WC, Samarakoon T, Vogeti L, Vogeti S, Yates KM, Bulfer SL, Le Bourdonnec B, Smith BD, Flynn DL..  (2022)  Discovery of acyl ureas as highly selective small molecule CSF1R kinase inhibitors.,  74  [PMID:35961461] [10.1016/j.bmcl.2022.128929]

6. Shi K, Zhang J, Zhou E, Wang J, Wang Y..  (2022)  Small-Molecule Receptor-Interacting Protein 1 (RIP1) Inhibitors as Therapeutic Agents for Multifaceted Diseases: Current Medicinal Chemistry Insights and Emerging Opportunities.,  65  (22.0): [PMID:36346971] [10.1021/acs.jmedchem.2c01518]

7. Amrhein JA, Wang G, Berger BT, Berger LM, Kalampaliki AD, Krämer A, Knapp S, Hanke T..  (2023)  Design and Synthesis of Pyrazole-Based Macrocyclic Kinase Inhibitors Targeting BMPR2.,  14  (6): [PMID:37312836] [10.1021/acsmedchemlett.3c00127]

Source

Source(2):

• Scientific Literature
• Patent Bioactivity Data