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Record Information

Version

5.0

Status

Expected but not Quantified

Creation Date

2012-09-06 15:16:52 UTC

Update Date

2022-03-07 02:52:03 UTC

HMDB ID

HMDB0015614

Secondary Accession Numbers

HMDB15614

Metabolite Identification

Common Name

Ibudilast

Description

Ibudilast, also known as ketas or AV-411, belongs to the class of organic compounds known as pyrazolopyridines. Pyrazolopyridines are compounds containing a pyrazolopyridine skeleton, which consists of a pyrazole fused to a pyridine. Pyrazole is 5-membered ring consisting of three carbon atoms and two adjacent nitrogen centers. Pyridine is a 6-membered ring with four carbon and one nitrogen atoms. Ibudilast is a drug which is used for the treatment of multiple sclerosis, asthma, and cerebrovascular disease. Ibudilast is a moderately basic compound (based on its pKa). Ibudilast is principally a PDE4 inhibitor but has also been shown to act as an antagonist at the toll-like receptor 4 (TLR4). Ibudilast crosses the blood–brain barrier and suppresses glial cell activation. Ibudilast ophthalmic solution is indicated for the treatment of allergic conjunctivitis and hay fever. In Japan, ibudilast oral capsules are approved for the treatment of asthma, and for improvement of dizziness secondary to chronic cerebral circulation impairment associated with sequelae of cerebral infarction. It may have some use reducing methamphetamine, opioid, and alcohol addiction. It is unknown if the PDE4-inhibiting properties potentiate the effects of TLR4 inactivation and/or vice versa, despite that some of their effects are shared, such as inflammation reducing properties. Ibudilast(IBD) (development codes: AV-411 or MN-166) is an anti-inflammatory drug used mainly in Japan, which acts as a phosphodiesterase inhibitor, inhibiting the PDE4 subtype to the greatest extent, but also showing significant inhibition of other PDE subtypes. TLR4 antagonists theoretically reverse the increase in pain and inflammation caused by most TLR4 agonists, which include many opiate and opioid drugs. This activity has been shown to make ibudilast useful in the treatment of neuropathic pain and it not only enhances analgesia produced by opioid drugs, but also reduces the development of tolerance. This likely plays a large part in its effect, specifically its synergy with opioid drugs, its anti-inflammatory effect, and its own painkilling effect. It inhibits platelet aggregation, and may also be useful in the treatment of multiple sclerosis.

Structure

MOL 3D MOL SDF 3D SDF PDB 3D PDB SMILES InChI

HMDB0015614
     RDKit          3D
Ibudilast
 35 36  0  0  0  0  0  0  0  0999 V2000
    2.8475    0.6942    0.7625 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3582   -0.5418    0.0263 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4888   -0.9487   -0.9069 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.1552   -0.2988   -0.7841 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2100   -0.4984   -2.0195 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1092    0.1613   -0.2489 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1076   -0.6824    0.1952 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0872   -2.1448    0.1551 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2061   -2.6486    1.0762 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5421   -2.6040   -1.2493 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1010    0.0858    0.6298 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8101    1.3545    0.4919 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5322    2.4636    0.7990 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9558    3.6848    0.5339 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6916    3.8013   -0.0237 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0144    2.6638   -0.3237 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5683    1.4428   -0.0557 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6276    0.3136    1.4888 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.0075    1.0718    1.3908 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.2476    1.4725    0.0886 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.2010   -1.3002    0.8206 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.4992   -0.7423   -0.4453 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.4052   -2.0073   -1.1985 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.4577   -0.3356   -1.8370 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1304   -2.6281    0.3489 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7785   -2.9191    2.0650 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7522   -3.5112    0.6308 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9450   -1.8486    1.2488 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6678   -2.5810   -1.2687 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1442   -3.6220   -1.4222 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1406   -1.8760   -1.9695 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5131    2.4539    1.2318 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4704    4.5999    0.7523 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2753    4.7839   -0.2179 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.0089    2.6915   -0.7651 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  2  4  1  0
  4  5  2  0
  4  6  1  0
  6  7  1  0
  7  8  1  0
  8  9  1  0
  8 10  1  0
  7 11  2  0
 11 12  1  0
 12 13  1  0
 13 14  2  0
 14 15  1  0
 15 16  2  0
 16 17  1  0
 17  6  2  0
 17 12  1  0
  1 18  1  0
  1 19  1  0
  1 20  1  0
  2 21  1  0
  3 22  1  0
  3 23  1  0
  3 24  1  0
  8 25  1  0
  9 26  1  0
  9 27  1  0
  9 28  1  0
 10 29  1  0
 10 30  1  0
 10 31  1  0
 13 32  1  0
 14 33  1  0
 15 34  1  0
 16 35  1  0
M  END


  Mrv0541 02231218072D          

 17 18  0  0  0  0            999 V2000
    4.9232   -0.6075    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.0791    1.4232    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.8597    1.6746    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.8597    0.3468    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1662    1.0106    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.3412    1.0106    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0791    0.5981    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.5650   -1.0515    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.1159   -0.4374    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.5787    1.7252    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.5787    0.2962    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3645    0.1856    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8213   -1.8357    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7577   -0.8814    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3645    1.8357    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6500    0.5981    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6500    1.4232    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  9  2  0  0  0  0
  2  3  1  0  0  0  0
  2  7  1  0  0  0  0
  2 15  1  0  0  0  0
  3  6  2  0  0  0  0
  4  6  1  0  0  0  0
  4  7  2  0  0  0  0
  4  9  1  0  0  0  0
  5  6  1  0  0  0  0
  5 10  1  0  0  0  0
  5 11  1  0  0  0  0
  7 12  1  0  0  0  0
  8  9  1  0  0  0  0
  8 13  1  0  0  0  0
  8 14  1  0  0  0  0
 12 16  2  0  0  0  0
 15 17  2  0  0  0  0
 16 17  1  0  0  0  0
M  END
> <DATABASE_ID>
HMDB0015614

> <DATABASE_NAME>
hmdb

> <SMILES>
CC(C)C(=O)C1=C2C=CC=CN2N=C1C(C)C

> <INCHI_IDENTIFIER>
InChI=1S/C14H18N2O/c1-9(2)13-12(14(17)10(3)4)11-7-5-6-8-16(11)15-13/h5-10H,1-4H3

> <INCHI_KEY>
ZJVFLBOZORBYFE-UHFFFAOYSA-N

> <FORMULA>
C14H18N2O

> <MOLECULAR_WEIGHT>
230.3055

> <EXACT_MASS>
230.141913208

> <JCHEM_ACCEPTOR_COUNT>
2

> <JCHEM_AVERAGE_POLARIZABILITY>
26.31048727736632

> <JCHEM_BIOAVAILABILITY>
1

> <JCHEM_DONOR_COUNT>
0

> <JCHEM_FORMAL_CHARGE>
0

> <JCHEM_GHOSE_FILTER>
1

> <JCHEM_IUPAC>
2-methyl-1-[2-(propan-2-yl)pyrazolo[1,5-a]pyridin-3-yl]propan-1-one

> <ALOGPS_LOGP>
3.36

> <JCHEM_LOGP>
3.679244931333334

> <ALOGPS_LOGS>
-3.11

> <JCHEM_MDDR_LIKE_RULE>
0

> <JCHEM_NUMBER_OF_RINGS>
2

> <JCHEM_PHYSIOLOGICAL_CHARGE>
0

> <JCHEM_PKA_STRONGEST_ACIDIC>
16.124110910397867

> <JCHEM_PKA_STRONGEST_BASIC>
1.855180020373627

> <JCHEM_POLAR_SURFACE_AREA>
34.370000000000005

> <JCHEM_REFRACTIVITY>
79.375

> <JCHEM_ROTATABLE_BOND_COUNT>
3

> <JCHEM_RULE_OF_FIVE>
1

> <ALOGPS_SOLUBILITY>
1.79e-01 g/l

> <JCHEM_TRADITIONAL_IUPAC>
ibudilast

> <JCHEM_VEBER_RULE>
1

$$$$

HMDB0015614
     RDKit          3D
Ibudilast
 35 36  0  0  0  0  0  0  0  0999 V2000
    2.8475    0.6942    0.7625 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3582   -0.5418    0.0263 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4888   -0.9487   -0.9069 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.1552   -0.2988   -0.7841 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2100   -0.4984   -2.0195 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1092    0.1613   -0.2489 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1076   -0.6824    0.1952 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0872   -2.1448    0.1551 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2061   -2.6486    1.0762 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5421   -2.6040   -1.2493 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1010    0.0858    0.6298 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8101    1.3545    0.4919 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5322    2.4636    0.7990 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9558    3.6848    0.5339 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6916    3.8013   -0.0237 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0144    2.6638   -0.3237 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5683    1.4428   -0.0557 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6276    0.3136    1.4888 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.0075    1.0718    1.3908 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.2476    1.4725    0.0886 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.2010   -1.3002    0.8206 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.4992   -0.7423   -0.4453 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.4052   -2.0073   -1.1985 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.4577   -0.3356   -1.8370 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1304   -2.6281    0.3489 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7785   -2.9191    2.0650 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7522   -3.5112    0.6308 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9450   -1.8486    1.2488 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6678   -2.5810   -1.2687 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1442   -3.6220   -1.4222 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1406   -1.8760   -1.9695 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5131    2.4539    1.2318 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4704    4.5999    0.7523 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2753    4.7839   -0.2179 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.0089    2.6915   -0.7651 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  2  4  1  0
  4  5  2  0
  4  6  1  0
  6  7  1  0
  7  8  1  0
  8  9  1  0
  8 10  1  0
  7 11  2  0
 11 12  1  0
 12 13  1  0
 13 14  2  0
 14 15  1  0
 15 16  2  0
 16 17  1  0
 17  6  2  0
 17 12  1  0
  1 18  1  0
  1 19  1  0
  1 20  1  0
  2 21  1  0
  3 22  1  0
  3 23  1  0
  3 24  1  0
  8 25  1  0
  9 26  1  0
  9 27  1  0
  9 28  1  0
 10 29  1  0
 10 30  1  0
 10 31  1  0
 13 32  1  0
 14 33  1  0
 15 34  1  0
 16 35  1  0
M  END

HEADER    PROTEIN                                 23-FEB-12   NONE
TITLE     NULL                                                        
COMPND    NULL                                                        
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   23-FEB-12         0                                  
HETATM    1  O   UNK     0       9.190  -1.134   0.000  0.00  0.00           O+0
HETATM    2  N   UNK     0       5.748   2.657   0.000  0.00  0.00           N+0
HETATM    3  N   UNK     0       7.205   3.126   0.000  0.00  0.00           N+0
HETATM    4  C   UNK     0       7.205   0.647   0.000  0.00  0.00           C+0
HETATM    5  C   UNK     0       9.644   1.886   0.000  0.00  0.00           C+0
HETATM    6  C   UNK     0       8.104   1.886   0.000  0.00  0.00           C+0
HETATM    7  C   UNK     0       5.748   1.116   0.000  0.00  0.00           C+0
HETATM    8  C   UNK     0       6.655  -1.963   0.000  0.00  0.00           C+0
HETATM    9  C   UNK     0       7.683  -0.816   0.000  0.00  0.00           C+0
HETATM   10  C   UNK     0      10.414   3.220   0.000  0.00  0.00           C+0
HETATM   11  C   UNK     0      10.414   0.553   0.000  0.00  0.00           C+0
HETATM   12  C   UNK     0       4.414   0.346   0.000  0.00  0.00           C+0
HETATM   13  C   UNK     0       7.133  -3.427   0.000  0.00  0.00           C+0
HETATM   14  C   UNK     0       5.148  -1.645   0.000  0.00  0.00           C+0
HETATM   15  C   UNK     0       4.414   3.427   0.000  0.00  0.00           C+0
HETATM   16  C   UNK     0       3.080   1.116   0.000  0.00  0.00           C+0
HETATM   17  C   UNK     0       3.080   2.657   0.000  0.00  0.00           C+0
CONECT    1    9                                                            
CONECT    2    3    7   15                                                  
CONECT    3    2    6                                                       
CONECT    4    6    7    9                                                  
CONECT    5    6   10   11                                                  
CONECT    6    3    4    5                                                  
CONECT    7    2    4   12                                                  
CONECT    8    9   13   14                                                  
CONECT    9    1    4    8                                                  
CONECT   10    5                                                            
CONECT   11    5                                                            
CONECT   12    7   16                                                       
CONECT   13    8                                                            
CONECT   14    8                                                            
CONECT   15    2   17                                                       
CONECT   16   12   17                                                       
CONECT   17   15   16                                                       
MASTER        0    0    0    0    0    0    0    0   17    0   36    0
END

COMPND    HMDB0015614
HETATM    1  C1  UNL     1       2.848   0.694   0.762  1.00  0.00           C  
HETATM    2  C2  UNL     1       2.358  -0.542   0.026  1.00  0.00           C  
HETATM    3  C3  UNL     1       3.489  -0.949  -0.907  1.00  0.00           C  
HETATM    4  C4  UNL     1       1.155  -0.299  -0.784  1.00  0.00           C  
HETATM    5  O1  UNL     1       1.210  -0.498  -2.020  1.00  0.00           O  
HETATM    6  C5  UNL     1      -0.109   0.161  -0.249  1.00  0.00           C  
HETATM    7  C6  UNL     1      -1.108  -0.682   0.195  1.00  0.00           C  
HETATM    8  C7  UNL     1      -1.087  -2.145   0.155  1.00  0.00           C  
HETATM    9  C8  UNL     1      -2.206  -2.649   1.076  1.00  0.00           C  
HETATM   10  C9  UNL     1      -1.542  -2.604  -1.249  1.00  0.00           C  
HETATM   11  N1  UNL     1      -2.101   0.086   0.630  1.00  0.00           N  
HETATM   12  N2  UNL     1      -1.810   1.355   0.492  1.00  0.00           N  
HETATM   13  C10 UNL     1      -2.532   2.464   0.799  1.00  0.00           C  
HETATM   14  C11 UNL     1      -1.956   3.685   0.534  1.00  0.00           C  
HETATM   15  C12 UNL     1      -0.692   3.801  -0.024  1.00  0.00           C  
HETATM   16  C13 UNL     1       0.014   2.664  -0.324  1.00  0.00           C  
HETATM   17  C14 UNL     1      -0.568   1.443  -0.056  1.00  0.00           C  
HETATM   18  H1  UNL     1       3.628   0.314   1.489  1.00  0.00           H  
HETATM   19  H2  UNL     1       2.007   1.072   1.391  1.00  0.00           H  
HETATM   20  H3  UNL     1       3.248   1.472   0.089  1.00  0.00           H  
HETATM   21  H4  UNL     1       2.201  -1.300   0.821  1.00  0.00           H  
HETATM   22  H5  UNL     1       4.499  -0.742  -0.445  1.00  0.00           H  
HETATM   23  H6  UNL     1       3.405  -2.007  -1.198  1.00  0.00           H  
HETATM   24  H7  UNL     1       3.458  -0.336  -1.837  1.00  0.00           H  
HETATM   25  H8  UNL     1      -0.130  -2.628   0.349  1.00  0.00           H  
HETATM   26  H9  UNL     1      -1.779  -2.919   2.065  1.00  0.00           H  
HETATM   27  H10 UNL     1      -2.752  -3.511   0.631  1.00  0.00           H  
HETATM   28  H11 UNL     1      -2.945  -1.849   1.249  1.00  0.00           H  
HETATM   29  H12 UNL     1      -2.668  -2.581  -1.269  1.00  0.00           H  
HETATM   30  H13 UNL     1      -1.144  -3.622  -1.422  1.00  0.00           H  
HETATM   31  H14 UNL     1      -1.141  -1.876  -1.970  1.00  0.00           H  
HETATM   32  H15 UNL     1      -3.513   2.454   1.232  1.00  0.00           H  
HETATM   33  H16 UNL     1      -2.470   4.600   0.752  1.00  0.00           H  
HETATM   34  H17 UNL     1      -0.275   4.784  -0.218  1.00  0.00           H  
HETATM   35  H18 UNL     1       1.009   2.691  -0.765  1.00  0.00           H  
CONECT    1    2   18   19   20
CONECT    2    3    4   21
CONECT    3   22   23   24
CONECT    4    5    5    6
CONECT    6    7   17   17
CONECT    7    8   11   11
CONECT    8    9   10   25
CONECT    9   26   27   28
CONECT   10   29   30   31
CONECT   11   12
CONECT   12   13   17
CONECT   13   14   14   32
CONECT   14   15   33
CONECT   15   16   16   34
CONECT   16   17   35
END

HMDB0015614
     RDKit          3D
Ibudilast
 35 36  0  0  0  0  0  0  0  0999 V2000
    2.8475    0.6942    0.7625 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3582   -0.5418    0.0263 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4888   -0.9487   -0.9069 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.1552   -0.2988   -0.7841 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2100   -0.4984   -2.0195 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1092    0.1613   -0.2489 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1076   -0.6824    0.1952 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0872   -2.1448    0.1551 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2061   -2.6486    1.0762 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5421   -2.6040   -1.2493 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1010    0.0858    0.6298 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8101    1.3545    0.4919 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5322    2.4636    0.7990 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9558    3.6848    0.5339 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6916    3.8013   -0.0237 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0144    2.6638   -0.3237 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5683    1.4428   -0.0557 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6276    0.3136    1.4888 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.0075    1.0718    1.3908 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.2476    1.4725    0.0886 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.2010   -1.3002    0.8206 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.4992   -0.7423   -0.4453 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.4052   -2.0073   -1.1985 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.4577   -0.3356   -1.8370 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1304   -2.6281    0.3489 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7785   -2.9191    2.0650 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7522   -3.5112    0.6308 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9450   -1.8486    1.2488 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6678   -2.5810   -1.2687 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1442   -3.6220   -1.4222 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1406   -1.8760   -1.9695 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5131    2.4539    1.2318 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4704    4.5999    0.7523 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2753    4.7839   -0.2179 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.0089    2.6915   -0.7651 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  2  4  1  0
  4  5  2  0
  4  6  1  0
  6  7  1  0
  7  8  1  0
  8  9  1  0
  8 10  1  0
  7 11  2  0
 11 12  1  0
 12 13  1  0
 13 14  2  0
 14 15  1  0
 15 16  2  0
 16 17  1  0
 17  6  2  0
 17 12  1  0
  1 18  1  0
  1 19  1  0
  1 20  1  0
  2 21  1  0
  3 22  1  0
  3 23  1  0
  3 24  1  0
  8 25  1  0
  9 26  1  0
  9 27  1  0
  9 28  1  0
 10 29  1  0
 10 30  1  0
 10 31  1  0
 13 32  1  0
 14 33  1  0
 15 34  1  0
 16 35  1  0
M  END

View in JSmol View Stereo Labels

Synonyms

Value	Source
Ketas	Kegg
2-Isopropyl-3-isobutyrylpyrazolo(1,5-a)pyridine	HMDB
3-Isobutyryl-2-isopropyl-pyrazolo(1,5-a)pyridine	HMDB
3-Isobutyryl-2-isopropylpyrazolo(1,5-a)pyridine	HMDB
3-Isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine	HMDB
AV-411	HMDB
Eyevinal	HMDB
I0157_sigma	HMDB
Ibudilastum	HMDB
Ke tas	HMDB
Lopac-I-0157	HMDB
MN-166	HMDB
Tocris-1694	HMDB
UNII-m0TTH61XC5	HMDB

Chemical Formula

C₁₄H₁₈N₂O

Average Molecular Weight

230.3055

Monoisotopic Molecular Weight

230.141913208

IUPAC Name

2-methyl-1-[2-(propan-2-yl)pyrazolo[1,5-a]pyridin-3-yl]propan-1-one

Traditional Name

ibudilast

CAS Registry Number

50847-11-5

SMILES

CC(C)C(=O)C1=C2C=CC=CN2N=C1C(C)C

InChI Identifier

InChI=1S/C14H18N2O/c1-9(2)13-12(14(17)10(3)4)11-7-5-6-8-16(11)15-13/h5-10H,1-4H3

InChI Key

ZJVFLBOZORBYFE-UHFFFAOYSA-N

Chemical Taxonomy

Description

Belongs to the class of organic compounds known as pyrazolopyridines. Pyrazolopyridines are compounds containing a pyrazolopyridine skeleton, which consists of a pyrazole fused to a pyridine. Pyrazole is 5-membered ring consisting of three carbon atoms and two adjacent nitrogen centers. Pyridine is a 6-membered ring with four carbon and one nitrogen atoms.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Pyrazolopyridines

Sub Class

Not Available

Direct Parent

Pyrazolopyridines

Alternative Parents

Substituents

Pyrazolopyridine
Aryl alkyl ketone
Aryl ketone
Pyridine
Azole
Pyrazole
Heteroaromatic compound
Vinylogous amide
Ketone
Azacycle
Organic nitrogen compound
Hydrocarbon derivative
Organic oxide
Organopnictogen compound
Organooxygen compound
Organonitrogen compound
Organic oxygen compound
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Ontology

Physiological effect

Not Available

Disposition

Biological location

Non-excretory biofluid

Biofluid or Excreta

Blood (PMID: 21059682)

Excreta

Biofluid or Excreta

Urine (PMID: 21059682)

Cellular substructure

Cytoplasm (HMDB: HMDB0015614)
Membrane (HMDB: HMDB0015614)

Source

Exogenous

Exogenous (HMDB: HMDB0015614)

Process

Not Available

Role

Not Available

Physical Properties

State

Solid

Experimental Molecular Properties

Property	Value	Reference
Melting Point	Not Available	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	0.18 g/L	Not Available
LogP	Not Available	Not Available

Experimental Chromatographic Properties

Not Available

Predicted Molecular Properties

Property	Value	Source
Water Solubility	0.18 g/L	ALOGPS
logP	3.36	ALOGPS
logP	3.68	ChemAxon
logS	-3.1	ALOGPS
pKa (Strongest Acidic)	16.12	ChemAxon
pKa (Strongest Basic)	1.86	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	34.37 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	79.38 m³·mol⁻¹	ChemAxon
Polarizability	26.31 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted Chromatographic Properties

Predicted Collision Cross Sections

Predictor	Adduct Type	CCS Value (Å²)	Reference
DarkChem	[M+H]+	152.934	31661259
DarkChem	[M-H]-	153.729	31661259
DeepCCS	[M+H]+	160.07	30932474
DeepCCS	[M-H]-	157.712	30932474
DeepCCS	[M-2H]-	190.598	30932474
DeepCCS	[M+Na]+	166.163	30932474
AllCCS	[M+H]+	150.8	32859911
AllCCS	[M+H-H2O]+	146.8	32859911
AllCCS	[M+NH4]+	154.4	32859911
AllCCS	[M+Na]+	155.5	32859911
AllCCS	[M-H]-	159.1	32859911
AllCCS	[M+Na-2H]-	159.1	32859911
AllCCS	[M+HCOO]-	159.3	32859911

Predicted Retention Times

Underivatized

Chromatographic Method	Retention Time	Reference
Measured using a Waters Acquity ultraperformance liquid chromatography (UPLC) ethylene-bridged hybrid (BEH) C18 column (100 mm × 2.1 mm; 1.7 μmparticle diameter). Predicted by Afia on May 17, 2022. Predicted by Afia on May 17, 2022.	5.82 minutes	32390414
Predicted by Siyang on May 30, 2022	17.1862 minutes	33406817
Predicted by Siyang using ReTip algorithm on June 8, 2022	1.17 minutes	32390414
AjsUoB = Accucore 150 Amide HILIC with 10mM Ammonium Formate, 0.1% Formic Acid	25.0 seconds	40023050
Fem_Long = Waters ACQUITY UPLC HSS T3 C18 with Water:MeOH and 0.1% Formic Acid	2343.3 seconds	40023050
Fem_Lipids = Ascentis Express C18 with (60:40 water:ACN):(90:10 IPA:ACN) and 10mM NH4COOH + 0.1% Formic Acid	581.5 seconds	40023050
Life_Old = Waters ACQUITY UPLC BEH C18 with Water:(20:80 acetone:ACN) and 0.1% Formic Acid	202.7 seconds	40023050
Life_New = RP Waters ACQUITY UPLC HSS T3 C18 with Water:(30:70 MeOH:ACN) and 0.1% Formic Acid	307.4 seconds	40023050
RIKEN = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid	155.3 seconds	40023050
Eawag_XBridgeC18 = XBridge C18 3.5u 2.1x50 mm with Water:MeOH and 0.1% Formic Acid	691.9 seconds	40023050
BfG_NTS_RP1 =Agilent Zorbax Eclipse Plus C18 (2.1 mm x 150 mm, 3.5 um) with Water:ACN and 0.1% Formic Acid	718.4 seconds	40023050
HILIC_BDD_2 = Merck SeQuant ZIC-HILIC with ACN(0.1% formic acid):water(16 mM ammonium formate)	108.7 seconds	40023050
UniToyama_Atlantis = RP Waters Atlantis T3 (2.1 x 150 mm, 5 um) with ACN:Water and 0.1% Formic Acid	1361.4 seconds	40023050
BDD_C18 = Hypersil Gold 1.9µm C18 with Water:ACN and 0.1% Formic Acid	477.9 seconds	40023050
UFZ_Phenomenex = Kinetex Core-Shell C18 2.6 um, 3.0 x 100 mm, Phenomenex with Water:MeOH and 0.1% Formic Acid	1577.1 seconds	40023050
SNU_RIKEN_POS = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid	483.5 seconds	40023050
RPMMFDA = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid	406.1 seconds	40023050
MTBLS87 = Merck SeQuant ZIC-pHILIC column with ACN:Water and :ammonium carbonate	387.1 seconds	40023050
KI_GIAR_zic_HILIC_pH2_7 = Merck SeQuant ZIC-HILIC with ACN:Water and 0.1% FA	520.6 seconds	40023050
Meister zic-pHILIC pH9.3 = Merck SeQuant ZIC-pHILIC column with ACN:Water 5mM NH4Ac pH9.3 and 5mM ammonium acetate in water	8.3 seconds	40023050

Predicted Kovats Retention Indices

Underivatized

Metabolite	SMILES	Kovats RI Value	Column Type	Reference
Ibudilast	CC(C)C(=O)C1=C2C=CC=CN2N=C1C(C)C	2420.5	Standard polar	33892256
Ibudilast	CC(C)C(=O)C1=C2C=CC=CN2N=C1C(C)C	1903.1	Standard non polar	33892256
Ibudilast	CC(C)C(=O)C1=C2C=CC=CN2N=C1C(C)C	1785.4	Semi standard non polar	33892256

Spectra

GC-MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Predicted GC-MS	Predicted GC-MS Spectrum - Ibudilast GC-MS (Non-derivatized) - 70eV, Positive	splash10-00ko-9620000000-41b0ba218eb72a30b29c	2017-09-01	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - Ibudilast GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	Wishart Lab	View Spectrum

MS/MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Experimental LC-MS/MS	LC-MS/MS Spectrum - Ibudilast LC-ESI-qTof , Positive-QTOF	splash10-000i-1900000000-857f6720dd17fb2547d1	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Ibudilast , positive-QTOF	splash10-000w-3910000000-7c4d5c86420e4e74cdb1	2017-09-14	HMDB team, MONA	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Ibudilast 10V, Positive-QTOF	splash10-001i-1490000000-e05398fd5b7ddcf160e1	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Ibudilast 20V, Positive-QTOF	splash10-00di-9330000000-8fca320ae4500967062f	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Ibudilast 40V, Positive-QTOF	splash10-05fr-9200000000-f809e94dd2a3af4982fd	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Ibudilast 10V, Negative-QTOF	splash10-004i-0190000000-29d8c7d8254601f09a23	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Ibudilast 20V, Negative-QTOF	splash10-0a6r-0940000000-91b751bd446800ac3fe4	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Ibudilast 40V, Negative-QTOF	splash10-0btl-2920000000-e768231925a9299b5328	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Ibudilast 10V, Positive-QTOF	splash10-001i-0090000000-5a3d2f6ed0a80e005143	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Ibudilast 20V, Positive-QTOF	splash10-001i-1190000000-8b174dc132cb6ac2651b	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Ibudilast 40V, Positive-QTOF	splash10-006w-2900000000-a9dd3e6970b4fcaffd46	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Ibudilast 10V, Negative-QTOF	splash10-004i-0090000000-aa5e22fd3aed8a7657c7	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Ibudilast 20V, Negative-QTOF	splash10-004r-0890000000-6c7384878a8fa5c86666	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Ibudilast 40V, Negative-QTOF	splash10-00ke-0900000000-37e60538e4767bd87892	2021-10-11	Wishart Lab	View Spectrum

Biological Properties

Cellular Locations

Cytoplasm
Membrane

Biospecimen Locations

Blood
Urine

Tissue Locations

Not Available

Pathways

Not Available

Name	SMPDB/PathBank	KEGG

Normal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Expected but not Quantified	Not Quantified	Not Available	Not Available	Taking drug identified by DrugBank entry DB05266	21059682	details
Urine	Expected but not Quantified	Not Quantified	Not Available	Not Available	Taking drug identified by DrugBank entry DB05266	21059682	details

Abnormal Concentrations

Not Available

Associated Disorders and Diseases

Disease References

None

Associated OMIM IDs

None

External Links

DrugBank ID

DB05266

Phenol Explorer Compound ID

Not Available

FooDB ID

Not Available

KNApSAcK ID

Not Available

Chemspider ID

3543

KEGG Compound ID

Not Available

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

Ibudilast

METLIN ID

Not Available

PubChem Compound

3671

PDB ID

Not Available

ChEBI ID

123745

Food Biomarker Ontology

Not Available

VMH ID

Not Available

MarkerDB ID

Not Available

Good Scents ID

Not Available

References

Synthesis Reference

Not Available

Material Safety Data Sheet (MSDS)

Not Available

General References

Cho Y, Crichlow GV, Vermeire JJ, Leng L, Du X, Hodsdon ME, Bucala R, Cappello M, Gross M, Gaeta F, Johnson K, Lolis EJ: Allosteric inhibition of macrophage migration inhibitory factor revealed by ibudilast. Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11313-8. doi: 10.1073/pnas.1002716107. Epub 2010 Jun 8. [PubMed:20534506 ]
Rodgers KM, Bercum FM, McCallum DL, Rudy JW, Frey LC, Johnson KW, Watkins LR, Barth DS: Acute neuroimmune modulation attenuates the development of anxiety-like freezing behavior in an animal model of traumatic brain injury. J Neurotrauma. 2012 Jul 1;29(10):1886-97. doi: 10.1089/neu.2011.2273. Epub 2012 Apr 26. [PubMed:22435644 ]
Snider SE, Hendrick ES, Beardsley PM: Glial cell modulators attenuate methamphetamine self-administration in the rat. Eur J Pharmacol. 2013 Feb 15;701(1-3):124-30. doi: 10.1016/j.ejphar.2013.01.016. Epub 2013 Jan 31. [PubMed:23375937 ]

Enzymes

Enzyme Details

1. cGMP-inhibited 3',5'-cyclic phosphodiesterase A

General function:: Involved in catalytic activity
Specific function:: Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (By similarity).
Gene Name:: PDE3A
Uniprot ID:: Q14432
Molecular weight:: 124978.06

References

Yamazaki T, Anraku T, Matsuzawa S: Ibudilast, a mixed PDE3/4 inhibitor, causes a selective and nitric oxide/cGMP-independent relaxation of the intracranial vertebrobasilar artery. Eur J Pharmacol. 2011 Jan 15;650(2-3):605-11. doi: 10.1016/j.ejphar.2010.10.033. Epub 2010 Oct 29. [PubMed:21036126 ]

Enzyme Details

2. cAMP-specific 3',5'-cyclic phosphodiesterase 4B

General function:: Involved in catalytic activity
Specific function:: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents.
Gene Name:: PDE4B
Uniprot ID:: Q07343
Molecular weight:: 64351.765

References

Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K: Preferential inhibition of human phosphodiesterase 4 by ibudilast. Life Sci. 2006 May 1;78(23):2663-8. Epub 2005 Nov 28. [PubMed:16313925 ]

Enzyme Details

3. cAMP-specific 3',5'-cyclic phosphodiesterase 4C

General function:: Involved in catalytic activity
Specific function:: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:: PDE4C
Uniprot ID:: Q08493
Molecular weight:: 79900.795

References

Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K: Preferential inhibition of human phosphodiesterase 4 by ibudilast. Life Sci. 2006 May 1;78(23):2663-8. Epub 2005 Nov 28. [PubMed:16313925 ]

Enzyme Details

4. cAMP-specific 3',5'-cyclic phosphodiesterase 4D

General function:: Involved in catalytic activity
Specific function:: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:: PDE4D
Uniprot ID:: Q08499
Molecular weight:: 91114.1

References

Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K: Preferential inhibition of human phosphodiesterase 4 by ibudilast. Life Sci. 2006 May 1;78(23):2663-8. Epub 2005 Nov 28. [PubMed:16313925 ]

Enzyme Details

5. cAMP-specific 3',5'-cyclic phosphodiesterase 4A

General function:: Involved in 3',5'-cyclic-nucleotide phosphodiesterase activity
Specific function:: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
Gene Name:: PDE4A
Uniprot ID:: P27815
Molecular weight:: 98142.155

References

Yagi K, Tada Y, Kitazato KT, Tamura T, Satomi J, Nagahiro S: Ibudilast inhibits cerebral aneurysms by down-regulating inflammation-related molecules in the vascular wall of rats. Neurosurgery. 2010 Mar;66(3):551-9; discussion 559. doi: 10.1227/01.NEU.0000365771.89576.77. [PubMed:20124930 ]
Yamazaki T, Anraku T, Matsuzawa S: Ibudilast, a mixed PDE3/4 inhibitor, causes a selective and nitric oxide/cGMP-independent relaxation of the intracranial vertebrobasilar artery. Eur J Pharmacol. 2011 Jan 15;650(2-3):605-11. doi: 10.1016/j.ejphar.2010.10.033. Epub 2010 Oct 29. [PubMed:21036126 ]
Huang Z, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K: Preferential inhibition of human phosphodiesterase 4 by ibudilast. Life Sci. 2006 May 1;78(23):2663-8. Epub 2005 Nov 28. [PubMed:16313925 ]

Showing metabocard for Ibudilast (HMDB0015614)

MOL for HMDB0015614 (Ibudilast)

3D MOL for HMDB0015614 (Ibudilast)

3D SDF for HMDB0015614 (Ibudilast)

3D-SDF for HMDB0015614 (Ibudilast)

PDB for HMDB0015614 (Ibudilast)

3D PDB for HMDB0015614 (Ibudilast)

SMILES for HMDB0015614 (Ibudilast)

INCHI for HMDB0015614 (Ibudilast)

Structure for HMDB0015614 (Ibudilast)

3D Structure for HMDB0015614 (Ibudilast)

Predicted Collision Cross Sections

Predicted Retention Times

Underivatized

Predicted Kovats Retention Indices

Underivatized

GC-MS Spectra

MS/MS Spectra

Enzymes

References

References

References

References

References