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Record Information

Version

5.0

Status

Expected but not Quantified

Creation Date

2012-09-06 15:16:51 UTC

Update Date

2022-03-07 02:51:51 UTC

HMDB ID

HMDB0015058

Secondary Accession Numbers

HMDB15058

Metabolite Identification

Common Name

Levosimendan

Description

Levosimendan, also known as simdax, belongs to the class of organic compounds known as phenylhydrazines. Phenylhydrazines are compounds containing a phenylhydrazide moiety, which consists of a hydrazide substituent attached to a phenyl group. Levosimendan is marketed as a 2.5 mg/mL concentrated solution for IV infusion. Levosimendan is a drug which is used for short term treatment of acutely decompensated severe chronic heart failure (chf). also being investigated for use/treatment in heart disease. Levosimendan is a strong basic compound (based on its pKa). It also has a vasodilatory effect, by opening adenosine triphosphate (ATP)-sensitive potassium channels in vascular smooth muscle to cause smooth muscle relaxation. However, the drug was proven to be superior to dobutamine for treating patients with a history of CHF or those on beta-blocker therapy when they are hospitalized with acute decompensations.The Orion Corporation originally developed levosimendan and applied for a new drug application in 1998 in the U.S. In total, the clinical data base includes more than 3500 patients in Phase IIb and III double-blind randomized studies. Levosimendan (INN) is a calcium sensitiser used in the management of acutely decompensated congestive heart failure. Initially, Orion obtained the approval to market the drug in Sweden in 2000. It is marketed under the trade name Simdax (Orion Corporation). Common adverse drug reactions (≥1% of patients) associated with levosimendan therapy include: headache, hypotension, arrhythmias (atrial fibrillation, extrasystoles, Atrial tachycardia, ventricular tachycardia), myocardial ischaemia, hypokalaemia and/or nausea (Rossi, 2006).

Structure

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

HMDB0015058
     RDKit          3D
Levosimendan
 33 34  0  0  0  0  0  0  0  0999 V2000
   -3.1017    1.5517   -0.2302 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7460    0.1763   -0.6986 C   0  0  2  0  0  0  0  0  0  0  0  0
   -4.0031   -0.6862   -0.7530 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.3126   -1.2819    0.5704 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.4827   -1.3865    1.0148 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2296   -1.7502    1.3586 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9605   -1.2491    1.0991 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7078   -0.3858    0.1863 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3237    0.0520    0.0284 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0115    0.9851   -0.9232 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3378    1.3598   -1.0293 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2986    0.8237   -0.2153 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6531    1.2409   -0.3617 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.6611    0.7191    0.4475 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.2891   -0.3588    0.1236 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.9347   -1.0251   -1.0956 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6471   -1.5568   -2.0843 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.3212   -0.8897    0.9557 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.1762   -1.3278    1.6195 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.9741   -0.1058    0.7350 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.6730   -0.4859    0.8528 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0277    1.5270    0.3678 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2789    1.9690    0.3805 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2938    2.2127   -1.1018 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3660    0.2238   -1.7590 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8064   -1.4931   -1.4903 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.8705   -0.1156   -1.1071 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.3808   -2.4665    2.1296 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7477    1.4023   -1.5564 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.5959    2.0990   -1.7850 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.9203    1.9417   -1.0729 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.7637   -0.5061    1.3596 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.3821   -1.2134    1.5880 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  1  0
  4  5  2  0
  4  6  1  0
  6  7  1  0
  7  8  2  0
  8  9  1  0
  9 10  2  0
 10 11  1  0
 11 12  2  0
 12 13  1  0
 13 14  1  0
 14 15  2  3
 15 16  1  0
 16 17  3  0
 15 18  1  0
 18 19  3  0
 12 20  1  0
 20 21  2  0
  8  2  1  0
 21  9  1  0
  1 22  1  0
  1 23  1  0
  1 24  1  0
  2 25  1  6
  3 26  1  0
  3 27  1  0
  6 28  1  0
 10 29  1  0
 11 30  1  0
 13 31  1  0
 20 32  1  0
 21 33  1  0
M  END

922
  Mrv0541 02231215062D          

 21 22  0  0  1  0            999 V2000
    9.5092   -2.0130    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.3658   -1.6005    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.0802   -2.0130    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.5079    0.8745    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.7934    0.4620    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.0790    2.5245    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.6500    0.0495    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.0802   -0.3630    0.0000 C   0  0  2  0  0  0  0  0  0  0  0  0
    8.7947   -0.7755    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.3658   -0.7755    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.0802    0.4620    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.6513   -0.3630    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.7947   -1.6005    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9369   -0.7755    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.6513    0.4620    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2223   -0.3630    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9369    0.8745    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2223    0.4620    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0790    0.8745    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0790    1.6995    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3644    0.4620    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1 13  2  0  0  0  0
  2  3  1  0  0  0  0
  2 10  2  0  0  0  0
  3 13  1  0  0  0  0
  4  5  1  0  0  0  0
  4 18  1  0  0  0  0
  5 19  2  0  0  0  0
  6 20  3  0  0  0  0
  7 21  3  0  0  0  0
  8  9  1  0  0  0  0
  8 10  1  0  0  0  0
  8 11  1  6  0  0  0
  9 13  1  0  0  0  0
 10 12  1  0  0  0  0
 12 14  2  0  0  0  0
 12 15  1  0  0  0  0
 14 16  1  0  0  0  0
 15 17  2  0  0  0  0
 16 18  2  0  0  0  0
 17 18  1  0  0  0  0
 19 20  1  0  0  0  0
 19 21  1  0  0  0  0
M  END
> <DATABASE_ID>
HMDB0015058

> <DATABASE_NAME>
hmdb

> <SMILES>
C[C@@H]1CC(=O)NN=C1C1=CC=C(NN=C(C#N)C#N)C=C1

> <INCHI_IDENTIFIER>
InChI=1S/C14H12N6O/c1-9-6-13(21)19-20-14(9)10-2-4-11(5-3-10)17-18-12(7-15)8-16/h2-5,9,17H,6H2,1H3,(H,19,21)/t9-/m1/s1

> <INCHI_KEY>
WHXMKTBCFHIYNQ-SECBINFHSA-N

> <FORMULA>
C14H12N6O

> <MOLECULAR_WEIGHT>
280.2847

> <EXACT_MASS>
280.107259036

> <JCHEM_ACCEPTOR_COUNT>
6

> <JCHEM_AVERAGE_POLARIZABILITY>
28.667628399288695

> <JCHEM_BIOAVAILABILITY>
1

> <JCHEM_DONOR_COUNT>
2

> <JCHEM_FORMAL_CHARGE>
0

> <JCHEM_GHOSE_FILTER>
1

> <JCHEM_IUPAC>
1-cyano-N-{4-[(4R)-4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl]phenyl}methanecarbohydrazonoyl cyanide

> <ALOGPS_LOGP>
2.69

> <JCHEM_LOGP>
2.161618159333333

> <ALOGPS_LOGS>
-3.50

> <JCHEM_MDDR_LIKE_RULE>
0

> <JCHEM_NUMBER_OF_RINGS>
2

> <JCHEM_PHYSIOLOGICAL_CHARGE>
0

> <JCHEM_PKA>
11.812153749237616

> <JCHEM_PKA_STRONGEST_ACIDIC>
10.534338350334115

> <JCHEM_PKA_STRONGEST_BASIC>
4.907396004091678

> <JCHEM_POLAR_SURFACE_AREA>
113.42999999999998

> <JCHEM_REFRACTIVITY>
77.6308

> <JCHEM_ROTATABLE_BOND_COUNT>
3

> <JCHEM_RULE_OF_FIVE>
1

> <ALOGPS_SOLUBILITY>
8.81e-02 g/l

> <JCHEM_TRADITIONAL_IUPAC>
levosimendan

> <JCHEM_VEBER_RULE>
0

$$$$

HMDB0015058
     RDKit          3D
Levosimendan
 33 34  0  0  0  0  0  0  0  0999 V2000
   -3.1017    1.5517   -0.2302 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7460    0.1763   -0.6986 C   0  0  2  0  0  0  0  0  0  0  0  0
   -4.0031   -0.6862   -0.7530 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.3126   -1.2819    0.5704 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.4827   -1.3865    1.0148 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2296   -1.7502    1.3586 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9605   -1.2491    1.0991 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7078   -0.3858    0.1863 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3237    0.0520    0.0284 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0115    0.9851   -0.9232 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3378    1.3598   -1.0293 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2986    0.8237   -0.2153 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6531    1.2409   -0.3617 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.6611    0.7191    0.4475 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.2891   -0.3588    0.1236 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.9347   -1.0251   -1.0956 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6471   -1.5568   -2.0843 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.3212   -0.8897    0.9557 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.1762   -1.3278    1.6195 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.9741   -0.1058    0.7350 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.6730   -0.4859    0.8528 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0277    1.5270    0.3678 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2789    1.9690    0.3805 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2938    2.2127   -1.1018 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3660    0.2238   -1.7590 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8064   -1.4931   -1.4903 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.8705   -0.1156   -1.1071 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.3808   -2.4665    2.1296 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7477    1.4023   -1.5564 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.5959    2.0990   -1.7850 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.9203    1.9417   -1.0729 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.7637   -0.5061    1.3596 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.3821   -1.2134    1.5880 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  1  0
  4  5  2  0
  4  6  1  0
  6  7  1  0
  7  8  2  0
  8  9  1  0
  9 10  2  0
 10 11  1  0
 11 12  2  0
 12 13  1  0
 13 14  1  0
 14 15  2  3
 15 16  1  0
 16 17  3  0
 15 18  1  0
 18 19  3  0
 12 20  1  0
 20 21  2  0
  8  2  1  0
 21  9  1  0
  1 22  1  0
  1 23  1  0
  1 24  1  0
  2 25  1  6
  3 26  1  0
  3 27  1  0
  6 28  1  0
 10 29  1  0
 11 30  1  0
 13 31  1  0
 20 32  1  0
 21 33  1  0
M  END

HEADER    PROTEIN                                 23-FEB-12   NONE
TITLE     NULL                                                        
COMPND    MOLECULE: 922                                               
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   23-FEB-12         0                                  
HETATM    1  O   UNK     0      17.751  -3.758   0.000  0.00  0.00           O+0
HETATM    2  N   UNK     0      13.749  -2.988   0.000  0.00  0.00           N+0
HETATM    3  N   UNK     0      15.083  -3.758   0.000  0.00  0.00           N+0
HETATM    4  N   UNK     0       8.415   1.632   0.000  0.00  0.00           N+0
HETATM    5  N   UNK     0       7.081   0.862   0.000  0.00  0.00           N+0
HETATM    6  N   UNK     0       5.747   4.712   0.000  0.00  0.00           N+0
HETATM    7  N   UNK     0       3.080   0.092   0.000  0.00  0.00           N+0
HETATM    8  C   UNK     0      15.083  -0.678   0.000  0.00  0.00           C+0
HETATM    9  C   UNK     0      16.417  -1.448   0.000  0.00  0.00           C+0
HETATM   10  C   UNK     0      13.749  -1.448   0.000  0.00  0.00           C+0
HETATM   11  C   UNK     0      15.083   0.862   0.000  0.00  0.00           C+0
HETATM   12  C   UNK     0      12.416  -0.678   0.000  0.00  0.00           C+0
HETATM   13  C   UNK     0      16.417  -2.988   0.000  0.00  0.00           C+0
HETATM   14  C   UNK     0      11.082  -1.448   0.000  0.00  0.00           C+0
HETATM   15  C   UNK     0      12.416   0.862   0.000  0.00  0.00           C+0
HETATM   16  C   UNK     0       9.748  -0.678   0.000  0.00  0.00           C+0
HETATM   17  C   UNK     0      11.082   1.632   0.000  0.00  0.00           C+0
HETATM   18  C   UNK     0       9.748   0.862   0.000  0.00  0.00           C+0
HETATM   19  C   UNK     0       5.747   1.632   0.000  0.00  0.00           C+0
HETATM   20  C   UNK     0       5.747   3.172   0.000  0.00  0.00           C+0
HETATM   21  C   UNK     0       4.414   0.862   0.000  0.00  0.00           C+0
CONECT    1   13                                                            
CONECT    2    3   10                                                       
CONECT    3    2   13                                                       
CONECT    4    5   18                                                       
CONECT    5    4   19                                                       
CONECT    6   20                                                            
CONECT    7   21                                                            
CONECT    8    9   10   11                                                  
CONECT    9    8   13                                                       
CONECT   10    2    8   12                                                  
CONECT   11    8                                                            
CONECT   12   10   14   15                                                  
CONECT   13    1    3    9                                                  
CONECT   14   12   16                                                       
CONECT   15   12   17                                                       
CONECT   16   14   18                                                       
CONECT   17   15   18                                                       
CONECT   18    4   16   17                                                  
CONECT   19    5   20   21                                                  
CONECT   20    6   19                                                       
CONECT   21    7   19                                                       
MASTER        0    0    0    0    0    0    0    0   21    0   44    0
END

COMPND    HMDB0015058
HETATM    1  C1  UNL     1      -3.102   1.552  -0.230  1.00  0.00           C  
HETATM    2  C2  UNL     1      -2.746   0.176  -0.699  1.00  0.00           C  
HETATM    3  C3  UNL     1      -4.003  -0.686  -0.753  1.00  0.00           C  
HETATM    4  C4  UNL     1      -4.313  -1.282   0.570  1.00  0.00           C  
HETATM    5  O1  UNL     1      -5.483  -1.386   1.015  1.00  0.00           O  
HETATM    6  N1  UNL     1      -3.230  -1.750   1.359  1.00  0.00           N  
HETATM    7  N2  UNL     1      -1.961  -1.249   1.099  1.00  0.00           N  
HETATM    8  C5  UNL     1      -1.708  -0.386   0.186  1.00  0.00           C  
HETATM    9  C6  UNL     1      -0.324   0.052   0.028  1.00  0.00           C  
HETATM   10  C7  UNL     1       0.012   0.985  -0.923  1.00  0.00           C  
HETATM   11  C8  UNL     1       1.338   1.360  -1.029  1.00  0.00           C  
HETATM   12  C9  UNL     1       2.299   0.824  -0.215  1.00  0.00           C  
HETATM   13  N3  UNL     1       3.653   1.241  -0.362  1.00  0.00           N  
HETATM   14  N4  UNL     1       4.661   0.719   0.447  1.00  0.00           N  
HETATM   15  C10 UNL     1       5.289  -0.359   0.124  1.00  0.00           C  
HETATM   16  C11 UNL     1       4.935  -1.025  -1.096  1.00  0.00           C  
HETATM   17  N5  UNL     1       4.647  -1.557  -2.084  1.00  0.00           N  
HETATM   18  C12 UNL     1       6.321  -0.890   0.956  1.00  0.00           C  
HETATM   19  N6  UNL     1       7.176  -1.328   1.619  1.00  0.00           N  
HETATM   20  C13 UNL     1       1.974  -0.106   0.735  1.00  0.00           C  
HETATM   21  C14 UNL     1       0.673  -0.486   0.853  1.00  0.00           C  
HETATM   22  H1  UNL     1      -4.028   1.527   0.368  1.00  0.00           H  
HETATM   23  H2  UNL     1      -2.279   1.969   0.380  1.00  0.00           H  
HETATM   24  H3  UNL     1      -3.294   2.213  -1.102  1.00  0.00           H  
HETATM   25  H4  UNL     1      -2.366   0.224  -1.759  1.00  0.00           H  
HETATM   26  H5  UNL     1      -3.806  -1.493  -1.490  1.00  0.00           H  
HETATM   27  H6  UNL     1      -4.871  -0.116  -1.107  1.00  0.00           H  
HETATM   28  H7  UNL     1      -3.381  -2.467   2.130  1.00  0.00           H  
HETATM   29  H8  UNL     1      -0.748   1.402  -1.556  1.00  0.00           H  
HETATM   30  H9  UNL     1       1.596   2.099  -1.785  1.00  0.00           H  
HETATM   31  H10 UNL     1       3.920   1.942  -1.073  1.00  0.00           H  
HETATM   32  H11 UNL     1       2.764  -0.506   1.360  1.00  0.00           H  
HETATM   33  H12 UNL     1       0.382  -1.213   1.588  1.00  0.00           H  
CONECT    1    2   22   23   24
CONECT    2    3    8   25
CONECT    3    4   26   27
CONECT    4    5    5    6
CONECT    6    7   28
CONECT    7    8    8
CONECT    8    9
CONECT    9   10   10   21
CONECT   10   11   29
CONECT   11   12   12   30
CONECT   12   13   20
CONECT   13   14   31
CONECT   14   15   15
CONECT   15   16   18
CONECT   16   17   17   17
CONECT   18   19   19   19
CONECT   20   21   21   32
CONECT   21   33
END

HMDB0015058
     RDKit          3D
Levosimendan
 33 34  0  0  0  0  0  0  0  0999 V2000
   -3.1017    1.5517   -0.2302 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7460    0.1763   -0.6986 C   0  0  2  0  0  0  0  0  0  0  0  0
   -4.0031   -0.6862   -0.7530 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.3126   -1.2819    0.5704 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.4827   -1.3865    1.0148 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2296   -1.7502    1.3586 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9605   -1.2491    1.0991 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7078   -0.3858    0.1863 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3237    0.0520    0.0284 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0115    0.9851   -0.9232 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3378    1.3598   -1.0293 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.2986    0.8237   -0.2153 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.6531    1.2409   -0.3617 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.6611    0.7191    0.4475 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.2891   -0.3588    0.1236 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.9347   -1.0251   -1.0956 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6471   -1.5568   -2.0843 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.3212   -0.8897    0.9557 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.1762   -1.3278    1.6195 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.9741   -0.1058    0.7350 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.6730   -0.4859    0.8528 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0277    1.5270    0.3678 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2789    1.9690    0.3805 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2938    2.2127   -1.1018 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3660    0.2238   -1.7590 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8064   -1.4931   -1.4903 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.8705   -0.1156   -1.1071 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.3808   -2.4665    2.1296 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7477    1.4023   -1.5564 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.5959    2.0990   -1.7850 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.9203    1.9417   -1.0729 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.7637   -0.5061    1.3596 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.3821   -1.2134    1.5880 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  1  0
  4  5  2  0
  4  6  1  0
  6  7  1  0
  7  8  2  0
  8  9  1  0
  9 10  2  0
 10 11  1  0
 11 12  2  0
 12 13  1  0
 13 14  1  0
 14 15  2  3
 15 16  1  0
 16 17  3  0
 15 18  1  0
 18 19  3  0
 12 20  1  0
 20 21  2  0
  8  2  1  0
 21  9  1  0
  1 22  1  0
  1 23  1  0
  1 24  1  0
  2 25  1  6
  3 26  1  0
  3 27  1  0
  6 28  1  0
 10 29  1  0
 11 30  1  0
 13 31  1  0
 20 32  1  0
 21 33  1  0
M  END

View in JSmol View Stereo Labels

Synonyms

Value	Source
Levosimendanum	ChEBI
Simdax	ChEBI
Levosimedan	HMDB
Simadax	HMDB
Dextrosimendan	HMDB
((4-(1,4,5,6-Tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazono)propanedinitrile	HMDB
Simendan	HMDB

Chemical Formula

C₁₄H₁₂N₆O

Average Molecular Weight

280.2847

Monoisotopic Molecular Weight

280.107259036

IUPAC Name

1-cyano-N-{4-[(4R)-4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl]phenyl}methanecarbohydrazonoyl cyanide

Traditional Name

levosimendan

CAS Registry Number

141505-33-1

SMILES

C[C@@H]1CC(=O)NN=C1C1=CC=C(NN=C(C#N)C#N)C=C1

InChI Identifier

InChI=1S/C14H12N6O/c1-9-6-13(21)19-20-14(9)10-2-4-11(5-3-10)17-18-12(7-15)8-16/h2-5,9,17H,6H2,1H3,(H,19,21)/t9-/m1/s1

InChI Key

WHXMKTBCFHIYNQ-SECBINFHSA-N

Chemical Taxonomy

Description

Belongs to the class of organic compounds known as phenylhydrazines. Phenylhydrazines are compounds containing a phenylhydrazide moiety, which consists of a hydrazide substituent attached to a phenyl group.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Phenylhydrazines

Direct Parent

Phenylhydrazines

Alternative Parents

Substituents

Phenylhydrazine
Pyridazinone
Pyridazine
Carboxylic acid derivative
Hydrazone
Carbonitrile
Nitrile
Organoheterocyclic compound
Azacycle
Organic nitrogen compound
Organooxygen compound
Organonitrogen compound
Organic oxygen compound
Organopnictogen compound
Carbonyl group
Hydrocarbon derivative
Organic oxide
Aromatic heteromonocyclic compound

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

nitrile (CHEBI:50567 )
pyridazinone (CHEBI:50567 )
hydrazone (CHEBI:50567 )

Ontology

Not Available

Urine (PMID: 21059682)

Non-excretory biofluid

Biofluid or Excreta

Blood (PMID: 21059682)

Cellular substructure

Membrane (HMDB: HMDB0015058)

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	0.088 g/L	Not Available
LogP	Not Available	Not Available

Experimental Chromatographic Properties

Not Available

Predicted Molecular Properties

Property	Value	Source
Water Solubility	0.088 g/L	ALOGPS
logP	2.69	ALOGPS
logP	2.16	ChemAxon
logS	-3.5	ALOGPS
pKa (Strongest Acidic)	10.53	ChemAxon
pKa (Strongest Basic)	4.91	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	6	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	113.43 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	77.63 m³·mol⁻¹	ChemAxon
Polarizability	28.67 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted Chromatographic Properties

Predicted Collision Cross Sections

Predictor	Adduct Type	CCS Value (Å²)	Reference
DarkChem	[M+H]+	166.911	31661259
DarkChem	[M-H]-	167.678	31661259
DeepCCS	[M+H]+	161.191	30932474
DeepCCS	[M-H]-	158.833	30932474
DeepCCS	[M-2H]-	192.779	30932474
DeepCCS	[M+Na]+	168.005	30932474
AllCCS	[M+H]+	164.2	32859911
AllCCS	[M+H-H2O]+	160.7	32859911
AllCCS	[M+NH4]+	167.5	32859911
AllCCS	[M+Na]+	168.4	32859911
AllCCS	[M-H]-	167.6	32859911
AllCCS	[M+Na-2H]-	167.4	32859911
AllCCS	[M+HCOO]-	167.2	32859911

Predicted Kovats Retention Indices

Underivatized

Metabolite	SMILES	Kovats RI Value	Column Type	Reference
Levosimendan	C[C@@H]1CC(=O)NN=C1C1=CC=C(NN=C(C#N)C#N)C=C1	3579.8	Standard polar	33892256
Levosimendan	C[C@@H]1CC(=O)NN=C1C1=CC=C(NN=C(C#N)C#N)C=C1	2681.2	Standard non polar	33892256
Levosimendan	C[C@@H]1CC(=O)NN=C1C1=CC=C(NN=C(C#N)C#N)C=C1	3024.9	Semi standard non polar	33892256

Derivatized

Derivative Name / Structure	SMILES	Kovats RI Value	Column Type	Reference
Levosimendan,1TMS,isomer #1	C[C@@H]1CC(=O)N([Si](C)(C)C)N=C1C1=CC=C(NN=C(C#N)C#N)C=C1	2914.1	Semi standard non polar	33892256
Levosimendan,1TMS,isomer #1	C[C@@H]1CC(=O)N([Si](C)(C)C)N=C1C1=CC=C(NN=C(C#N)C#N)C=C1	2777.3	Standard non polar	33892256
Levosimendan,1TMS,isomer #1	C[C@@H]1CC(=O)N([Si](C)(C)C)N=C1C1=CC=C(NN=C(C#N)C#N)C=C1	5568.6	Standard polar	33892256
Levosimendan,1TMS,isomer #2	C[C@@H]1CC(=O)NN=C1C1=CC=C(N(N=C(C#N)C#N)[Si](C)(C)C)C=C1	2989.1	Semi standard non polar	33892256
Levosimendan,1TMS,isomer #2	C[C@@H]1CC(=O)NN=C1C1=CC=C(N(N=C(C#N)C#N)[Si](C)(C)C)C=C1	2850.5	Standard non polar	33892256
Levosimendan,1TMS,isomer #2	C[C@@H]1CC(=O)NN=C1C1=CC=C(N(N=C(C#N)C#N)[Si](C)(C)C)C=C1	5682.7	Standard polar	33892256
Levosimendan,2TMS,isomer #1	C[C@@H]1CC(=O)N([Si](C)(C)C)N=C1C1=CC=C(N(N=C(C#N)C#N)[Si](C)(C)C)C=C1	2779.7	Semi standard non polar	33892256
Levosimendan,2TMS,isomer #1	C[C@@H]1CC(=O)N([Si](C)(C)C)N=C1C1=CC=C(N(N=C(C#N)C#N)[Si](C)(C)C)C=C1	2784.3	Standard non polar	33892256
Levosimendan,2TMS,isomer #1	C[C@@H]1CC(=O)N([Si](C)(C)C)N=C1C1=CC=C(N(N=C(C#N)C#N)[Si](C)(C)C)C=C1	5395.4	Standard polar	33892256
Levosimendan,1TBDMS,isomer #1	C[C@@H]1CC(=O)N([Si](C)(C)C(C)(C)C)N=C1C1=CC=C(NN=C(C#N)C#N)C=C1	3199.4	Semi standard non polar	33892256
Levosimendan,1TBDMS,isomer #1	C[C@@H]1CC(=O)N([Si](C)(C)C(C)(C)C)N=C1C1=CC=C(NN=C(C#N)C#N)C=C1	3003.7	Standard non polar	33892256
Levosimendan,1TBDMS,isomer #1	C[C@@H]1CC(=O)N([Si](C)(C)C(C)(C)C)N=C1C1=CC=C(NN=C(C#N)C#N)C=C1	5624.5	Standard polar	33892256
Levosimendan,1TBDMS,isomer #2	C[C@@H]1CC(=O)NN=C1C1=CC=C(N(N=C(C#N)C#N)[Si](C)(C)C(C)(C)C)C=C1	3187.6	Semi standard non polar	33892256
Levosimendan,1TBDMS,isomer #2	C[C@@H]1CC(=O)NN=C1C1=CC=C(N(N=C(C#N)C#N)[Si](C)(C)C(C)(C)C)C=C1	3066.3	Standard non polar	33892256
Levosimendan,1TBDMS,isomer #2	C[C@@H]1CC(=O)NN=C1C1=CC=C(N(N=C(C#N)C#N)[Si](C)(C)C(C)(C)C)C=C1	5666.2	Standard polar	33892256
Levosimendan,2TBDMS,isomer #1	C[C@@H]1CC(=O)N([Si](C)(C)C(C)(C)C)N=C1C1=CC=C(N(N=C(C#N)C#N)[Si](C)(C)C(C)(C)C)C=C1	3205.2	Semi standard non polar	33892256
Levosimendan,2TBDMS,isomer #1	C[C@@H]1CC(=O)N([Si](C)(C)C(C)(C)C)N=C1C1=CC=C(N(N=C(C#N)C#N)[Si](C)(C)C(C)(C)C)C=C1	3187.0	Standard non polar	33892256
Levosimendan,2TBDMS,isomer #1	C[C@@H]1CC(=O)N([Si](C)(C)C(C)(C)C)N=C1C1=CC=C(N(N=C(C#N)C#N)[Si](C)(C)C(C)(C)C)C=C1	5354.6	Standard polar	33892256

Spectra

GC-MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Predicted GC-MS	Predicted GC-MS Spectrum - Levosimendan GC-MS (Non-derivatized) - 70eV, Positive	splash10-0l6r-2190000000-95c9a8cdabf61909acac	2017-09-01	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - Levosimendan 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 - Levosimendan LC-ESI-qTof , Positive-QTOF	splash10-001i-0390000000-88e46fb95115eb7b2d26	2017-09-14	HMDB team, MONA	View Spectrum
Experimental LC-MS/MS	LC-MS/MS Spectrum - Levosimendan , positive-QTOF	splash10-001i-0390000000-88e46fb95115eb7b2d26	2017-09-14	HMDB team, MONA	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Levosimendan 10V, Positive-QTOF	splash10-01q9-1290000000-6d9a7b470636a54e587e	2016-08-01	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Levosimendan 20V, Positive-QTOF	splash10-0gx0-1390000000-90a2f0832ca10328f83c	2016-08-01	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Levosimendan 40V, Positive-QTOF	splash10-000f-9620000000-c8bae586e1e611afe4c6	2016-08-01	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Levosimendan 10V, Negative-QTOF	splash10-004i-4090000000-267416d8b7d793ecaf28	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Levosimendan 20V, Negative-QTOF	splash10-0006-9150000000-f151e544be5e67b5ad21	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Levosimendan 40V, Negative-QTOF	splash10-004l-9010000000-532ba1389514437da33a	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Levosimendan 10V, Positive-QTOF	splash10-001i-0090000000-5a694436ae56bc0fded4	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Levosimendan 20V, Positive-QTOF	splash10-001i-0190000000-47192e7bd78a3e6e189b	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Levosimendan 40V, Positive-QTOF	splash10-000i-1930000000-5a28d318150afb2c5a9c	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Levosimendan 10V, Negative-QTOF	splash10-004i-0090000000-d2087bfe0706f27ab273	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Levosimendan 20V, Negative-QTOF	splash10-004i-2090000000-6f5783406fb63b34609e	2021-10-11	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Levosimendan 40V, Negative-QTOF	splash10-0aor-5490000000-cd828b665b63c98858cb	2021-10-11	Wishart Lab	View Spectrum

Biological Properties

Cellular Locations

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 DB00922	21059682	details
Urine	Expected but not Quantified	Not Quantified	Not Available	Not Available	Taking drug identified by DrugBank entry DB00922	21059682	details

Abnormal Concentrations

Not Available

Associated Disorders and Diseases

Disease References

None

Associated OMIM IDs

None

External Links

DrugBank ID

DB00922

Phenol Explorer Compound ID

Not Available

FooDB ID

Not Available

KNApSAcK ID

Not Available

Chemspider ID

2298414

KEGG Compound ID

Not Available

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

Levosimendan

METLIN ID

Not Available

PubChem Compound

3033825

PDB ID

Not Available

ChEBI ID

50567

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

Kasikcioglu HA, Cam N: A review of levosimendan in the treatment of heart failure. Vasc Health Risk Manag. 2006;2(4):389-400. [PubMed:17323593 ]
Mebazaa A, Nieminen MS, Packer M, Cohen-Solal A, Kleber FX, Pocock SJ, Thakkar R, Padley RJ, Poder P, Kivikko M: Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. JAMA. 2007 May 2;297(17):1883-91. [PubMed:17473298 ]
MedicinesComplete [Link]

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

Szilagyi S, Pollesello P, Levijoki J, Haikala H, Bak I, Tosaki A, Borbely A, Edes I, Papp Z: Two inotropes with different mechanisms of action: contractile, PDE-inhibitory and direct myofibrillar effects of levosimendan and enoximone. J Cardiovasc Pharmacol. 2005 Sep;46(3):369-76. [PubMed:16116344 ]

Enzyme Details

2. ATP-sensitive inward rectifier potassium channel 11

General function:: Involved in inward rectifier potassium channel activity
Specific function:: This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium
Gene Name:: KCNJ11
Uniprot ID:: Q14654
Molecular weight:: 43540.4

References

Yildiz O: Vasodilating mechanisms of levosimendan: involvement of K+ channels. J Pharmacol Sci. 2007 May;104(1):1-5. Epub 2007 Apr 24. [PubMed:17452812 ]

Enzyme Details

3. Troponin C, slow skeletal and cardiac muscles

General function:: Involved in calcium ion binding
Specific function:: Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components:Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments
Gene Name:: TNNC1
Uniprot ID:: P63316
Molecular weight:: 18402.4

References

Kleerekoper Q, Putkey JA: Drug binding to cardiac troponin C. J Biol Chem. 1999 Aug 20;274(34):23932-9. [PubMed:10446160 ]
Levijoki J, Pollesello P, Kaivola J, Tilgmann C, Sorsa T, Annila A, Kilpelainen I, Haikala H: Further evidence for the cardiac troponin C mediated calcium sensitization by levosimendan: structure-response and binding analysis with analogs of levosimendan. J Mol Cell Cardiol. 2000 Mar;32(3):479-91. [PubMed:10731446 ]
Sorsa T, Heikkinen S, Abbott MB, Abusamhadneh E, Laakso T, Tilgmann C, Serimaa R, Annila A, Rosevear PR, Drakenberg T, Pollesello P, Kilpelainen I: Binding of levosimendan, a calcium sensitizer, to cardiac troponin C. J Biol Chem. 2001 Mar 23;276(12):9337-43. Epub 2000 Dec 11. [PubMed:11113122 ]
Sorsa T, Pollesello P, Permi P, Drakenberg T, Kilpelainen I: Interaction of levosimendan with cardiac troponin C in the presence of cardiac troponin I peptides. J Mol Cell Cardiol. 2003 Sep;35(9):1055-61. [PubMed:12967628 ]
Lehmann A, Boldt J, Lang J, Isgro F, Blome M: [Is levosimendan an inoprotective drug in patients with acute coronary syndrome undergoing surgical revascularization?]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2003 Sep;38(9):577-82. [PubMed:12975736 ]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Enzyme Details

4. ATP-sensitive inward rectifier potassium channel 8

General function:: Involved in inward rectifier potassium channel activity
Specific function:: This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by external barium
Gene Name:: KCNJ8
Uniprot ID:: Q15842
Molecular weight:: 47967.5

References

Yildiz O: Vasodilating mechanisms of levosimendan: involvement of K+ channels. J Pharmacol Sci. 2007 May;104(1):1-5. Epub 2007 Apr 24. [PubMed:17452812 ]

Showing metabocard for Levosimendan (HMDB0015058)

MOL for HMDB0015058 (Levosimendan)

3D MOL for HMDB0015058 (Levosimendan)

3D SDF for HMDB0015058 (Levosimendan)

3D-SDF for HMDB0015058 (Levosimendan)

PDB for HMDB0015058 (Levosimendan)

3D PDB for HMDB0015058 (Levosimendan)

SMILES for HMDB0015058 (Levosimendan)

INCHI for HMDB0015058 (Levosimendan)

Structure for HMDB0015058 (Levosimendan)

3D Structure for HMDB0015058 (Levosimendan)

Predicted Collision Cross Sections

Predicted Kovats Retention Indices

Underivatized

Derivatized

GC-MS Spectra

MS/MS Spectra

Enzymes

References

References

References

References