1-(2-Aminoethyl)-2-(piperidin-4-yl)-1H-benzo[d]imidazole-5-carboxamide

ID: ALA3622826

PubChem CID: 122192069

Max Phase: Preclinical

Molecular Formula: C15H21N5O

Molecular Weight: 287.37

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  NCCn1c(C2CCNCC2)nc2cc(C(N)=O)ccc21

Standard InChI:  InChI=1S/C15H21N5O/c16-5-8-20-13-2-1-11(14(17)21)9-12(13)19-15(20)10-3-6-18-7-4-10/h1-2,9-10,18H,3-8,16H2,(H2,17,21)

Standard InChI Key:  XMMZUEFCWDQOPI-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 21 23  0  0  0  0  0  0  0  0999 V2000
   -2.3155    0.7475    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0028    1.5132    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0028   -1.5132    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3155   -0.7475    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.6217   -1.4865    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.6319   -2.6865    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.6560   -0.8780    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.2917   -0.7475    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.2917    0.7475    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7138    1.2033    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.5889    0.0182    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7138   -1.2033    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.1812    2.6271    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6500    2.9355    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0896    0.0290    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0244    4.0756    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.9397   -1.2009    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.4347   -1.0783    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.0761    0.2776    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.2225    1.5110    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.7275    1.3885    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  9  1  0
  8  3  1  0
  3  4  2  0
  4  1  1  0
  4  5  1  0
  5  6  1  0
  5  7  2  0
  8  9  2  0
  9 10  1  0
 10 11  1  0
 11 12  2  0
 12  8  1  0
 10 13  1  0
 13 14  1  0
 11 15  1  0
 14 16  1  0
 15 17  1  0
 15 21  1  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 20 21  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA3622826

   ---

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: 287.37

Molecular Weight (Monoisotopic): 287.1746

AlogP: 0.56

#Rotatable Bonds: 4

Polar Surface Area: 98.96

Molecular Species: BASE

HBA: 5

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 5

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 10.18

CX LogP: -0.24

CX LogD: -4.96

Aromatic Rings: 2

Heavy Atoms: 21

QED Weighted: 0.76

Np Likeness Score: -1.22

References

1. Kim MK, Shin H, Park KS, Kim H, Park J, Kim K, Nam J, Choo H, Chong Y..  (2015)  Benzimidazole Derivatives as Potent JAK1-Selective Inhibitors.,  58  (18): [PMID:26351728] [10.1021/acs.jmedchem.5b01263]

2. Kim H, Kim MK, Choo H, Chong Y..  (2016)  Novel JAK1-selective benzimidazole inhibitors with enhanced membrane permeability.,  26  (14): [PMID:27261178] [10.1016/j.bmcl.2016.05.078]

3. McDermott, Ultan U and 24 more authors.  2007-12-11  Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling.  [PMID:18077425]

4. Changelian, Paul S PS and 13 more authors.  2008-02-15  The specificity of JAK3 kinase inhibitors.  [PMID:18094329]

5. Jiang, Jian-kang and 12 more authors.  2008-12-25  Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550).  [PMID:19053756]

6. Pardanani, A A and 5 more authors.  2009-08  CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients.  [PMID:19295546]

7. Zarrinkar, Patrick P PP and 15 more authors.  2009-10-01  AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).  [PMID:19654408]

8. Fridman, Jordan S JS and 21 more authors.  2010-05-01  Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050.  [PMID:20363976]

9. Flanagan, Mark E ME and 22 more authors.  2010-12-23  Discovery of CP-690,550: a potent and selective Janus kinase (JAK) inhibitor for the treatment of autoimmune diseases and organ transplant rejection.  [PMID:21105711]

10. Malerich, Jeremiah P JP and 6 more authors.  2010-12-15  Diamino-1,2,4-triazole derivatives are selective inhibitors of TYK2 and JAK1 over JAK2 and JAK3.  [PMID:21106455]

11. Ioannidis, Stephanos S and 20 more authors.  2011-01-13  Discovery of 5-chloro-N2-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (AZD1480) as a novel inhibitor of the Jak/Stat pathway.  [PMID:21138246]

12. William, Anthony D AD and 18 more authors.  2011-07-14  Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma.  [PMID:21604762]

13. Goh, K C KC and 15 more authors.  2012-02  TG02, a novel oral multi-kinase inhibitor of CDKs, JAK2 and FLT3 with potent anti-leukemic properties.  [PMID:21860433]

14. Purandare, A V AV and 28 more authors.  2012-02  Characterization of BMS-911543, a functionally selective small-molecule inhibitor of JAK2.  [PMID:22015772]

15. Kulagowski, Janusz J JJ and 29 more authors.  2012-06-28  Identification of imidazo-pyrrolopyridines as novel and potent JAK1 inhibitors.  [PMID:22591402]

16. Dugan, Benjamin J BJ and 18 more authors.  2012-06-14  A selective, orally bioavailable 1,2,4-triazolo[1,5-a]pyridine-based inhibitor of Janus kinase 2 for use in anticancer therapy: discovery of CEP-33779.  [PMID:22594690]

17. Nakaya, Y Y and 11 more authors.  2011-07  Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms.  [PMID:22829185]

18. Hanan, Emily J EJ and 22 more authors.  2012-11-26  Discovery of potent and selective pyrazolopyrimidine janus kinase 2 inhibitors.  [PMID:23061660]

19. Soth, Michael M and 38 more authors.  2013-01-10  3-Amido pyrrolopyrazine JAK kinase inhibitors: development of a JAK3 vs JAK1 selective inhibitor and evaluation in cellular and in vivo models.  [PMID:23214979]

20. Van Rompaey, Luc L and 16 more authors.  2013-10-01  Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases.  [PMID:24006460]

21. Kim, Mi Kyoung MK, Shin, Heerim H, Cho, Seo Young SY and Chong, Youhoon Y.  2014-02-01  Linear propargylic alcohol functionality attached to the indazole-7-carboxamide as a JAK1-specific linear probe group.  [PMID:24398382]

22. McDonnell, Mark E ME and 6 more authors.  2014-02-15  Anilino-monoindolylmaleimides as potent and selective JAK3 inhibitors.  [PMID:24461299]

23. Works, Melissa G MG and 11 more authors.  2014-10-01  Inhibition of TYK2 and JAK1 ameliorates imiquimod-induced psoriasis-like dermatitis by inhibiting IL-22 and the IL-23/IL-17 axis.  [PMID:25156366]

24. Coffey, Greg G and 8 more authors.  2014-12  The novel kinase inhibitor PRT062070 (Cerdulatinib) demonstrates efficacy in models of autoimmunity and B-cell cancer.  [PMID:25253883]

25. Menet, Christel J CJ and 18 more authors.  2014-11-26  Triazolopyridines as selective JAK1 inhibitors: from hit identification to GLPG0634.  [PMID:25369270]

26. Tanimoto, Atsuo A and 10 more authors.  2015-01  Pharmacological properties of JTE-052: a novel potent JAK inhibitor that suppresses various inflammatory responses in vitro and in vivo.  [PMID:25387665]

27. Yamagishi, Hiroaki H and 10 more authors.  2015-08-01  Discovery of 3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-2(1H)-one derivatives as novel JAK inhibitors.  [PMID:26059596]

28. Tan, Li L and 18 more authors.  2015-08-27  Development of Selective Covalent Janus Kinase 3 Inhibitors.  [PMID:26258521]

29. Wan, Honghe H and 34 more authors.  2015-08-13  Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms.  [PMID:26288683]

30. Simov, Vladimir V and 15 more authors.  2016-04-01  Structure-based design and development of (benz)imidazole pyridones as JAK1-selective kinase inhibitors.  [PMID:26927423]

31. Liang, Xuewu X and 6 more authors.  2016-06-15  Design, synthesis and preliminary biological evaluation of 4-aminopyrazole derivatives as novel and potent JAKs inhibitors.  [PMID:27137359]

32. Lee, Sun-Mi SM and 11 more authors.  2016-11-01  The discovery of 2,5-isomers of triazole-pyrrolopyrimidine as selective Janus kinase 2 (JAK2) inhibitors versus JAK1 and JAK3.  [PMID:27555284]

33. Ito, Misato M and 11 more authors.  2017-01  A novel JAK inhibitor, peficitinib, demonstrates potent efficacy in a rat adjuvant-induced arthritis model.  [PMID:28117214]

34. Jarusiewicz, Jamie A JA and 6 more authors.  2017-05-31  Discovery of a Diaminopyrimidine FLT3 Inhibitor Active against Acute Myeloid Leukemia.  [PMID:28580438]

35. Puleo, David E DE and 7 more authors.  2017-06-08  Identification and Characterization of JAK2 Pseudokinase Domain Small Molecule Binders.  [PMID:28626521]

36. Liang, Jun J and 32 more authors.  2017-09-15  Identification of an imidazopyridine scaffold to generate potent and selective TYK2 inhibitors that demonstrate activity in an in vivo psoriasis model.  [PMID:28830649]

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

38. Vazquez, Michael L ML and 34 more authors.  2018-02-08  Identification of N-{cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propane-1-sulfonamide (PF-04965842): A Selective JAK1 Clinical Candidate for the Treatment of Autoimmune Diseases.  [PMID:29298069]

39. Chough, Chieyeon C and 5 more authors.  2018-05-01  Development of selective inhibitors for the treatment of rheumatoid arthritis: (R)-3-(3-(Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile as a JAK1-selective inhibitor.  [PMID:29452839]

40. Fensome, Andrew A and 32 more authors.  2018-10-11  Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841).  [PMID:30113844]

41. Hamaguchi, Hisao H and 9 more authors.  2018-10-01  Discovery and structural characterization of peficitinib (ASP015K) as a novel and potent JAK inhibitor.  [PMID:30145050]

42. 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]

43. Elsayed, Mohamed S A MSA and 9 more authors.  2018-12-13  Application of Sequential Palladium Catalysis for the Discovery of Janus Kinase Inhibitors in the Benzo[ c]pyrrolo[2,3- h][1,6]naphthyridin-5-one (BPN) Series.  [PMID:30460842]

44. Yin, Yuan Y and 5 more authors.  2019-04-15  Discovery of novel selective Janus kinase 2 (JAK2) inhibitors bearing a 1H-pyrazolo[3,4-d]pyrimidin-4-amino scaffold.  [PMID:30846405]

45. Yu, Ru-Nan RN and 6 more authors.  2019-04-15  Structure-based design and synthesis of pyrimidine-4,6-diamine derivatives as Janus kinase 3 inhibitors.  [PMID:30853331]

46. Spergel, Steven H SH and 24 more authors.  2019-03-14  Discovery of a JAK1/3 Inhibitor and Use of a Prodrug To Demonstrate Efficacy in a Model of Rheumatoid Arthritis.  [PMID:30891131]

47. Liang, Xuewu X and 11 more authors.  2019-04-25  Discovery of Novel Janus Kinase (JAK) and Histone Deacetylase (HDAC) Dual Inhibitors for the Treatment of Hematological Malignancies.  [PMID:30901208]

48. Zak, Mark M and 28 more authors.  2019-06-15  Discovery of a class of highly potent Janus Kinase 1/2 (JAK1/2) inhibitors demonstrating effective cell-based blockade of IL-13 signaling.  [PMID:30981576]

49. Wang, Wanqi W and 16 more authors.  2019-06-15  Design, synthesis and structure-activity relationship study of aminopyridine derivatives as novel inhibitors of Janus kinase 2.  [PMID:30981578]

50. Moslin, Ryan R and 28 more authors.  2019-07-17  Identification of N-Methyl Nicotinamide and N-Methyl Pyridazine-3-Carboxamide Pseudokinase Domain Ligands as Highly Selective Allosteric Inhibitors of Tyrosine Kinase 2 (TYK2).  [PMID:31314518]

51. Wrobleski, Stephen T ST and 31 more authors.  2019-07-18  Highly Selective Inhibition of Tyrosine Kinase 2 (TYK2) for the Treatment of Autoimmune Diseases: Discovery of the Allosteric Inhibitor BMS-986165.  [PMID:31318208]

52. Yang, Tao and 13 more authors.  2019-11-27  Discovery of Potent and Orally Effective Dual Janus Kinase 2/FLT3 Inhibitors for the Treatment of Acute Myelogenous Leukemia and Myeloproliferative Neoplasms.  [PMID:31670517]

53. Ren, Jing and 11 more authors.  2020-01-15  Design and synthesis of boron-containing diphenylpyrimidines as potent BTK and JAK3 dual inhibitors.  [PMID:31843459]

54. Shu, Lei and 9 more authors.  2020-04-01  Design, synthesis, and pharmacological evaluation of 4- or 6-phenyl-pyrimidine derivatives as novel and selective Janus kinase 3 inhibitors.  [PMID:32097841]

55. Ma, Xiangyu and 6 more authors.  2020-04-15  Discovery and optimization of 2-aminopyridine derivatives as novel and selective JAK2 inhibitors.  [PMID:32122740]

56. Fensome, Andrew and 23 more authors.  2020-05-15  Design and optimization of a series of 4-(3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-2-amines: Dual inhibitors of TYK2 and JAK1.  [PMID:32253095]

57. Su, Qibin and 26 more authors.  2020-05-14  Discovery of (2R)-N-[3-[2-[(3-Methoxy-1-methyl-pyrazol-4-yl)amino]pyrimidin-4-yl]-1H-indol-7-yl]-2-(4-methylpiperazin-1-yl)propenamide (AZD4205) as a Potent and Selective Janus Kinase 1 Inhibitor.  [PMID:32297743]

58. Gerstenberger, Brian S and 23 more authors.  2020-11-25  Discovery of Tyrosine Kinase 2 (TYK2) Inhibitor (PF-06826647) for the Treatment of Autoimmune Diseases.  [PMID:32787094]

59. Yang, Tao and 13 more authors.  2020-12-10  N-(Pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine Derivatives as Selective Janus Kinase 2 Inhibitors for the Treatment of Myeloproliferative Neoplasms.  [PMID:33256400]

60. Liu, Chunjian and 24 more authors.  2021-01-14  Discovery of BMS-986202: A Clinical Tyk2 Inhibitor that Binds to Tyk2 JH2.  [PMID:33370104]

61. Zhang, Chufeng and 9 more authors.  2021-02-25  Discovery of 3-(4-(2-((1H-Indol-5-yl)amino)-5-fluoropyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile Derivatives as Selective TYK2 Inhibitors for the Treatment of Inflammatory Bowel Disease.  [PMID:33593051]

Source

Source(1):

• Scientific Literature