(R)-Warfarin
Cat. No. B565621
M. Wt: 308.3 g/mol
InChI Key: PJVWKTKQMONHTI-OAHLLOKOSA-N
Attention: For research use only. Not for human or veterinary use.
Patent
US04734282
Procedure details
Control, blank, and experimental reaction mixtures were made for each experiment. Control and blank reaction mixtures were made up with vitamin K and without vitamin K, respectively. Experimental reaction mixtures contained both vitamin K and a vitamin K antagonist. The control reaction mixture contained 3.00 ml of microsomal suspension, 0.81 ml of buffer II, 1.20 ml of an ATP-generating system (final concentrations: 1 mM ATP, 10 mM phosphocreatine, 2.5 mM Mg[acetate]2 ·4H2O, 20 μg/ml creatine phosphokinase [52 U/ml]), 0.60 ml of NADH (final concentration 2 mM), 0.30 ml of dithiothreitol (final concentration 7 mM) dissolved in buffer II, 0.060 ml of NaH14CO3 (1.0 μCi/μl; added 0.5 min prior to reaction initiation), and at the time of reaction initiation 0.030 ml of vitamin K1 (final concentration 20 μg/ml) diluted in 0.85% sodium chloride solution. This vitamin K concentration is associated with maximal in vitro incorporation of added H14CO3 into vitamin K-dependent substrate proteins (J. Biol. Chem. 251, 2770-2776). The blank reaction mixture consisted of the same components except that vitamin K was replaced by an equal volume of isotonic saline. The experimental reaction mixtures were made up in the same way as the control reaction mixtures with the exceptions that: (1) a volume of buffer II was replaced by a volume of buffer II containing an inhibitor of vitamin K-dependent carboxylation, and (2) all individual volumes were two-thirds of those in the control reaction mixtures. The sodium salts of TCP, phenindione, and warfarin were formed in aqueous sodium hydroxide solution (J. Am. Chem. Soc. 83, 2676-2679) and were freely soluble in buffer II at all concentrations used in these studies. Chloro-K1 was formulated as an oil-in-water emulsion with Tween 80 (5% v/v final concentration), while chloro-K3 was formulated as a suspension in Tween 80 (5% v/v final concentration) (Molecular Pharmacology 10, 373-380).
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Three
[Compound]
Name
( 1 )
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Four
[Compound]
Name
II
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Five
[Compound]
Name
II
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Six
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Seven
[Compound]
Name
( 2 )
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Seven
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Nine
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Ten
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Eleven
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Twelve
[Compound]
Name
microsomal suspension
Quantity
3 mL
Type
reactant
Reaction Step Thirteen
[Compound]
Name
II
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Fourteen
Name
Name
Name
Identifiers
|
REACTION_CXSMILES
|
P([O:13][CH2:14][C@H:15]1[O:19][C@@H:18](N2C3N=CN=C(N)C=3N=C2)[C@H:17](O)[C@@H:16]1[OH:31])(OP(OP(O)(O)=O)(O)=O)(=O)O.[CH3:32][C:33]1[C:43](=O)[C:42]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[C:35](=[O:36])[C:34]=1[CH2:45]/[CH:46]=[C:47](/CCC[C@@H](CCC[C@@H](CCCC(C)C)C)C)\[CH3:48].[OH-:65].[Na+]>[Cl-].[Na+]>[CH:32]1[CH:40]=[CH:41][C:42]([CH:37]2[C:35](=[O:36])[C:34]3[CH:45]=[CH:46][CH:47]=[CH:48][C:39]=3[C:38]2=[O:65])=[CH:43][CH:33]=1.[CH3:46][C:45]([CH2:34][CH:35]([C:15]1[C:14](=[O:13])[O:19][C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:17]=2[C:16]=1[OH:31])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:65] |f:2.3,4.5|
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
[OH-].[Na+]
|
Step Two
|
Name
|
|
|
Quantity
|
0.03 mL
|
|
Type
|
reactant
|
|
Smiles
|
CC1=C(C(=O)C=2C=CC=CC2C1=O)C/C=C(\C)/CCC[C@H](C)CCC[C@H](C)CCCC(C)C
|
Step Three
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Four
[Compound]
|
Name
|
( 1 )
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Five
[Compound]
|
Name
|
II
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Six
[Compound]
|
Name
|
II
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Seven
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
[Compound]
|
Name
|
( 2 )
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Eight
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
[Cl-].[Na+]
|
Step Nine
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Ten
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Eleven
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Twelve
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Thirteen
[Compound]
|
Name
|
microsomal suspension
|
|
Quantity
|
3 mL
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Fourteen
[Compound]
|
Name
|
II
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Fifteen
|
Name
|
|
|
Quantity
|
1.2 mL
|
|
Type
|
reactant
|
|
Smiles
|
P(O)(=O)(OP(=O)(O)OP(=O)(O)O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N1C=NC=2C(N)=NC=NC12)O)O
|
Conditions
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Control, blank, and experimental reaction mixtures
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Control and blank reaction mixtures
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Experimental reaction
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The control reaction mixture
|
CONCENTRATION
|
Type
|
CONCENTRATION
|
|
Details
|
concentrations
|
DISSOLUTION
|
Type
|
DISSOLUTION
|
|
Details
|
1 mM ATP, 10 mM phosphocreatine, 2.5 mM Mg[acetate]2 ·4H2O, 20 μg/ml creatine phosphokinase [52 U/ml]), 0.60 ml of NADH (final concentration 2 mM), 0.30 ml of dithiothreitol (final concentration 7 mM) dissolved in buffer II, 0.060 ml of NaH14CO3 (1.0 μCi/μl
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
added 0.5 min
|
|
Duration
|
0.5 min
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
to reaction initiation), and
|
CONCENTRATION
|
Type
|
CONCENTRATION
|
|
Details
|
This vitamin K concentration
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
of added H14CO3 into vitamin K-dependent substrate proteins (J. Biol. Chem. 251, 2770-2776)
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The blank reaction mixture
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The experimental reaction mixtures
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
were made up in the same way as the control reaction mixtures with the exceptions that
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
in the control reaction mixtures
|
Outcomes
Product
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
|
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
C=1C=CC(=CC1)C2C(=O)C=3C=CC=CC3C2=O
|
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CC(=O)CC(C=1C=CC=CC1)C2=C(C=3C=CC=CC3OC2=O)O
|
Source
|
Source
|
Open Reaction Database (ORD) |
|
Description
|
The Open Reaction Database (ORD) is an open-access schema and infrastructure for structuring and sharing organic reaction data, including a centralized data repository. The ORD schema supports conventional and emerging technologies, from benchtop reactions to automated high-throughput experiments and flow chemistry. Our vision is that a consistent data representation and infrastructure to support data sharing will enable downstream applications that will greatly improve the state of the art with respect to computer-aided synthesis planning, reaction prediction, and other predictive chemistry tasks. |
Patent
US04734282
Procedure details
Control, blank, and experimental reaction mixtures were made for each experiment. Control and blank reaction mixtures were made up with vitamin K and without vitamin K, respectively. Experimental reaction mixtures contained both vitamin K and a vitamin K antagonist. The control reaction mixture contained 3.00 ml of microsomal suspension, 0.81 ml of buffer II, 1.20 ml of an ATP-generating system (final concentrations: 1 mM ATP, 10 mM phosphocreatine, 2.5 mM Mg[acetate]2 ·4H2O, 20 μg/ml creatine phosphokinase [52 U/ml]), 0.60 ml of NADH (final concentration 2 mM), 0.30 ml of dithiothreitol (final concentration 7 mM) dissolved in buffer II, 0.060 ml of NaH14CO3 (1.0 μCi/μl; added 0.5 min prior to reaction initiation), and at the time of reaction initiation 0.030 ml of vitamin K1 (final concentration 20 μg/ml) diluted in 0.85% sodium chloride solution. This vitamin K concentration is associated with maximal in vitro incorporation of added H14CO3 into vitamin K-dependent substrate proteins (J. Biol. Chem. 251, 2770-2776). The blank reaction mixture consisted of the same components except that vitamin K was replaced by an equal volume of isotonic saline. The experimental reaction mixtures were made up in the same way as the control reaction mixtures with the exceptions that: (1) a volume of buffer II was replaced by a volume of buffer II containing an inhibitor of vitamin K-dependent carboxylation, and (2) all individual volumes were two-thirds of those in the control reaction mixtures. The sodium salts of TCP, phenindione, and warfarin were formed in aqueous sodium hydroxide solution (J. Am. Chem. Soc. 83, 2676-2679) and were freely soluble in buffer II at all concentrations used in these studies. Chloro-K1 was formulated as an oil-in-water emulsion with Tween 80 (5% v/v final concentration), while chloro-K3 was formulated as a suspension in Tween 80 (5% v/v final concentration) (Molecular Pharmacology 10, 373-380).
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Three
[Compound]
Name
( 1 )
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Four
[Compound]
Name
II
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Five
[Compound]
Name
II
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Six
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Seven
[Compound]
Name
( 2 )
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Seven
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Nine
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Ten
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Eleven
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Twelve
[Compound]
Name
microsomal suspension
Quantity
3 mL
Type
reactant
Reaction Step Thirteen
[Compound]
Name
II
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Fourteen
Name
Name
Name
Identifiers
|
REACTION_CXSMILES
|
P([O:13][CH2:14][C@H:15]1[O:19][C@@H:18](N2C3N=CN=C(N)C=3N=C2)[C@H:17](O)[C@@H:16]1[OH:31])(OP(OP(O)(O)=O)(O)=O)(=O)O.[CH3:32][C:33]1[C:43](=O)[C:42]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[C:35](=[O:36])[C:34]=1[CH2:45]/[CH:46]=[C:47](/CCC[C@@H](CCC[C@@H](CCCC(C)C)C)C)\[CH3:48].[OH-:65].[Na+]>[Cl-].[Na+]>[CH:32]1[CH:40]=[CH:41][C:42]([CH:37]2[C:35](=[O:36])[C:34]3[CH:45]=[CH:46][CH:47]=[CH:48][C:39]=3[C:38]2=[O:65])=[CH:43][CH:33]=1.[CH3:46][C:45]([CH2:34][CH:35]([C:15]1[C:14](=[O:13])[O:19][C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:17]=2[C:16]=1[OH:31])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:65] |f:2.3,4.5|
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
[OH-].[Na+]
|
Step Two
|
Name
|
|
|
Quantity
|
0.03 mL
|
|
Type
|
reactant
|
|
Smiles
|
CC1=C(C(=O)C=2C=CC=CC2C1=O)C/C=C(\C)/CCC[C@H](C)CCC[C@H](C)CCCC(C)C
|
Step Three
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Four
[Compound]
|
Name
|
( 1 )
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Five
[Compound]
|
Name
|
II
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Six
[Compound]
|
Name
|
II
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Seven
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
[Compound]
|
Name
|
( 2 )
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Eight
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
[Cl-].[Na+]
|
Step Nine
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Ten
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Eleven
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Twelve
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Thirteen
[Compound]
|
Name
|
microsomal suspension
|
|
Quantity
|
3 mL
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Fourteen
[Compound]
|
Name
|
II
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Fifteen
|
Name
|
|
|
Quantity
|
1.2 mL
|
|
Type
|
reactant
|
|
Smiles
|
P(O)(=O)(OP(=O)(O)OP(=O)(O)O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N1C=NC=2C(N)=NC=NC12)O)O
|
Conditions
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Control, blank, and experimental reaction mixtures
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Control and blank reaction mixtures
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Experimental reaction
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The control reaction mixture
|
CONCENTRATION
|
Type
|
CONCENTRATION
|
|
Details
|
concentrations
|
DISSOLUTION
|
Type
|
DISSOLUTION
|
|
Details
|
1 mM ATP, 10 mM phosphocreatine, 2.5 mM Mg[acetate]2 ·4H2O, 20 μg/ml creatine phosphokinase [52 U/ml]), 0.60 ml of NADH (final concentration 2 mM), 0.30 ml of dithiothreitol (final concentration 7 mM) dissolved in buffer II, 0.060 ml of NaH14CO3 (1.0 μCi/μl
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
added 0.5 min
|
|
Duration
|
0.5 min
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
to reaction initiation), and
|
CONCENTRATION
|
Type
|
CONCENTRATION
|
|
Details
|
This vitamin K concentration
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
of added H14CO3 into vitamin K-dependent substrate proteins (J. Biol. Chem. 251, 2770-2776)
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The blank reaction mixture
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The experimental reaction mixtures
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
were made up in the same way as the control reaction mixtures with the exceptions that
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
in the control reaction mixtures
|
Outcomes
Product
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
|
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
C=1C=CC(=CC1)C2C(=O)C=3C=CC=CC3C2=O
|
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CC(=O)CC(C=1C=CC=CC1)C2=C(C=3C=CC=CC3OC2=O)O
|
Source
|
Source
|
Open Reaction Database (ORD) |
|
Description
|
The Open Reaction Database (ORD) is an open-access schema and infrastructure for structuring and sharing organic reaction data, including a centralized data repository. The ORD schema supports conventional and emerging technologies, from benchtop reactions to automated high-throughput experiments and flow chemistry. Our vision is that a consistent data representation and infrastructure to support data sharing will enable downstream applications that will greatly improve the state of the art with respect to computer-aided synthesis planning, reaction prediction, and other predictive chemistry tasks. |
Patent
US04734282
Procedure details
Control, blank, and experimental reaction mixtures were made for each experiment. Control and blank reaction mixtures were made up with vitamin K and without vitamin K, respectively. Experimental reaction mixtures contained both vitamin K and a vitamin K antagonist. The control reaction mixture contained 3.00 ml of microsomal suspension, 0.81 ml of buffer II, 1.20 ml of an ATP-generating system (final concentrations: 1 mM ATP, 10 mM phosphocreatine, 2.5 mM Mg[acetate]2 ·4H2O, 20 μg/ml creatine phosphokinase [52 U/ml]), 0.60 ml of NADH (final concentration 2 mM), 0.30 ml of dithiothreitol (final concentration 7 mM) dissolved in buffer II, 0.060 ml of NaH14CO3 (1.0 μCi/μl; added 0.5 min prior to reaction initiation), and at the time of reaction initiation 0.030 ml of vitamin K1 (final concentration 20 μg/ml) diluted in 0.85% sodium chloride solution. This vitamin K concentration is associated with maximal in vitro incorporation of added H14CO3 into vitamin K-dependent substrate proteins (J. Biol. Chem. 251, 2770-2776). The blank reaction mixture consisted of the same components except that vitamin K was replaced by an equal volume of isotonic saline. The experimental reaction mixtures were made up in the same way as the control reaction mixtures with the exceptions that: (1) a volume of buffer II was replaced by a volume of buffer II containing an inhibitor of vitamin K-dependent carboxylation, and (2) all individual volumes were two-thirds of those in the control reaction mixtures. The sodium salts of TCP, phenindione, and warfarin were formed in aqueous sodium hydroxide solution (J. Am. Chem. Soc. 83, 2676-2679) and were freely soluble in buffer II at all concentrations used in these studies. Chloro-K1 was formulated as an oil-in-water emulsion with Tween 80 (5% v/v final concentration), while chloro-K3 was formulated as a suspension in Tween 80 (5% v/v final concentration) (Molecular Pharmacology 10, 373-380).
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Three
[Compound]
Name
( 1 )
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Four
[Compound]
Name
II
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Five
[Compound]
Name
II
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Six
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Seven
[Compound]
Name
( 2 )
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Seven
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Nine
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Ten
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Eleven
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Twelve
[Compound]
Name
microsomal suspension
Quantity
3 mL
Type
reactant
Reaction Step Thirteen
[Compound]
Name
II
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Fourteen
Name
Name
Name
Identifiers
|
REACTION_CXSMILES
|
P([O:13][CH2:14][C@H:15]1[O:19][C@@H:18](N2C3N=CN=C(N)C=3N=C2)[C@H:17](O)[C@@H:16]1[OH:31])(OP(OP(O)(O)=O)(O)=O)(=O)O.[CH3:32][C:33]1[C:43](=O)[C:42]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[C:35](=[O:36])[C:34]=1[CH2:45]/[CH:46]=[C:47](/CCC[C@@H](CCC[C@@H](CCCC(C)C)C)C)\[CH3:48].[OH-:65].[Na+]>[Cl-].[Na+]>[CH:32]1[CH:40]=[CH:41][C:42]([CH:37]2[C:35](=[O:36])[C:34]3[CH:45]=[CH:46][CH:47]=[CH:48][C:39]=3[C:38]2=[O:65])=[CH:43][CH:33]=1.[CH3:46][C:45]([CH2:34][CH:35]([C:15]1[C:14](=[O:13])[O:19][C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:17]=2[C:16]=1[OH:31])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:65] |f:2.3,4.5|
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
[OH-].[Na+]
|
Step Two
|
Name
|
|
|
Quantity
|
0.03 mL
|
|
Type
|
reactant
|
|
Smiles
|
CC1=C(C(=O)C=2C=CC=CC2C1=O)C/C=C(\C)/CCC[C@H](C)CCC[C@H](C)CCCC(C)C
|
Step Three
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Four
[Compound]
|
Name
|
( 1 )
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Five
[Compound]
|
Name
|
II
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Six
[Compound]
|
Name
|
II
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Seven
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
[Compound]
|
Name
|
( 2 )
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Eight
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
[Cl-].[Na+]
|
Step Nine
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Ten
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Eleven
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Twelve
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Thirteen
[Compound]
|
Name
|
microsomal suspension
|
|
Quantity
|
3 mL
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Fourteen
[Compound]
|
Name
|
II
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Fifteen
|
Name
|
|
|
Quantity
|
1.2 mL
|
|
Type
|
reactant
|
|
Smiles
|
P(O)(=O)(OP(=O)(O)OP(=O)(O)O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N1C=NC=2C(N)=NC=NC12)O)O
|
Conditions
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Control, blank, and experimental reaction mixtures
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Control and blank reaction mixtures
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Experimental reaction
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The control reaction mixture
|
CONCENTRATION
|
Type
|
CONCENTRATION
|
|
Details
|
concentrations
|
DISSOLUTION
|
Type
|
DISSOLUTION
|
|
Details
|
1 mM ATP, 10 mM phosphocreatine, 2.5 mM Mg[acetate]2 ·4H2O, 20 μg/ml creatine phosphokinase [52 U/ml]), 0.60 ml of NADH (final concentration 2 mM), 0.30 ml of dithiothreitol (final concentration 7 mM) dissolved in buffer II, 0.060 ml of NaH14CO3 (1.0 μCi/μl
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
added 0.5 min
|
|
Duration
|
0.5 min
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
to reaction initiation), and
|
CONCENTRATION
|
Type
|
CONCENTRATION
|
|
Details
|
This vitamin K concentration
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
of added H14CO3 into vitamin K-dependent substrate proteins (J. Biol. Chem. 251, 2770-2776)
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The blank reaction mixture
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The experimental reaction mixtures
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
were made up in the same way as the control reaction mixtures with the exceptions that
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
in the control reaction mixtures
|
Outcomes
Product
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
|
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
C=1C=CC(=CC1)C2C(=O)C=3C=CC=CC3C2=O
|
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CC(=O)CC(C=1C=CC=CC1)C2=C(C=3C=CC=CC3OC2=O)O
|
Source
|
Source
|
Open Reaction Database (ORD) |
|
Description
|
The Open Reaction Database (ORD) is an open-access schema and infrastructure for structuring and sharing organic reaction data, including a centralized data repository. The ORD schema supports conventional and emerging technologies, from benchtop reactions to automated high-throughput experiments and flow chemistry. Our vision is that a consistent data representation and infrastructure to support data sharing will enable downstream applications that will greatly improve the state of the art with respect to computer-aided synthesis planning, reaction prediction, and other predictive chemistry tasks. |
Patent
US04734282
Procedure details
Control, blank, and experimental reaction mixtures were made for each experiment. Control and blank reaction mixtures were made up with vitamin K and without vitamin K, respectively. Experimental reaction mixtures contained both vitamin K and a vitamin K antagonist. The control reaction mixture contained 3.00 ml of microsomal suspension, 0.81 ml of buffer II, 1.20 ml of an ATP-generating system (final concentrations: 1 mM ATP, 10 mM phosphocreatine, 2.5 mM Mg[acetate]2 ·4H2O, 20 μg/ml creatine phosphokinase [52 U/ml]), 0.60 ml of NADH (final concentration 2 mM), 0.30 ml of dithiothreitol (final concentration 7 mM) dissolved in buffer II, 0.060 ml of NaH14CO3 (1.0 μCi/μl; added 0.5 min prior to reaction initiation), and at the time of reaction initiation 0.030 ml of vitamin K1 (final concentration 20 μg/ml) diluted in 0.85% sodium chloride solution. This vitamin K concentration is associated with maximal in vitro incorporation of added H14CO3 into vitamin K-dependent substrate proteins (J. Biol. Chem. 251, 2770-2776). The blank reaction mixture consisted of the same components except that vitamin K was replaced by an equal volume of isotonic saline. The experimental reaction mixtures were made up in the same way as the control reaction mixtures with the exceptions that: (1) a volume of buffer II was replaced by a volume of buffer II containing an inhibitor of vitamin K-dependent carboxylation, and (2) all individual volumes were two-thirds of those in the control reaction mixtures. The sodium salts of TCP, phenindione, and warfarin were formed in aqueous sodium hydroxide solution (J. Am. Chem. Soc. 83, 2676-2679) and were freely soluble in buffer II at all concentrations used in these studies. Chloro-K1 was formulated as an oil-in-water emulsion with Tween 80 (5% v/v final concentration), while chloro-K3 was formulated as a suspension in Tween 80 (5% v/v final concentration) (Molecular Pharmacology 10, 373-380).
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Three
[Compound]
Name
( 1 )
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Four
[Compound]
Name
II
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Five
[Compound]
Name
II
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Six
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Seven
[Compound]
Name
( 2 )
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Seven
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Nine
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Ten
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Eleven
[Compound]
Name
vitamin K
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Twelve
[Compound]
Name
microsomal suspension
Quantity
3 mL
Type
reactant
Reaction Step Thirteen
[Compound]
Name
II
Quantity
0 (± 1) mol
Type
reactant
Reaction Step Fourteen
Name
Name
Name
Identifiers
|
REACTION_CXSMILES
|
P([O:13][CH2:14][C@H:15]1[O:19][C@@H:18](N2C3N=CN=C(N)C=3N=C2)[C@H:17](O)[C@@H:16]1[OH:31])(OP(OP(O)(O)=O)(O)=O)(=O)O.[CH3:32][C:33]1[C:43](=O)[C:42]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[C:35](=[O:36])[C:34]=1[CH2:45]/[CH:46]=[C:47](/CCC[C@@H](CCC[C@@H](CCCC(C)C)C)C)\[CH3:48].[OH-:65].[Na+]>[Cl-].[Na+]>[CH:32]1[CH:40]=[CH:41][C:42]([CH:37]2[C:35](=[O:36])[C:34]3[CH:45]=[CH:46][CH:47]=[CH:48][C:39]=3[C:38]2=[O:65])=[CH:43][CH:33]=1.[CH3:46][C:45]([CH2:34][CH:35]([C:15]1[C:14](=[O:13])[O:19][C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:17]=2[C:16]=1[OH:31])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:65] |f:2.3,4.5|
|
Inputs
Step One
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
[OH-].[Na+]
|
Step Two
|
Name
|
|
|
Quantity
|
0.03 mL
|
|
Type
|
reactant
|
|
Smiles
|
CC1=C(C(=O)C=2C=CC=CC2C1=O)C/C=C(\C)/CCC[C@H](C)CCC[C@H](C)CCCC(C)C
|
Step Three
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Four
[Compound]
|
Name
|
( 1 )
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Five
[Compound]
|
Name
|
II
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Six
[Compound]
|
Name
|
II
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Seven
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
[Compound]
|
Name
|
( 2 )
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Eight
|
Name
|
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
solvent
|
|
Smiles
|
[Cl-].[Na+]
|
Step Nine
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Ten
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Eleven
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Twelve
[Compound]
|
Name
|
vitamin K
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Thirteen
[Compound]
|
Name
|
microsomal suspension
|
|
Quantity
|
3 mL
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Fourteen
[Compound]
|
Name
|
II
|
|
Quantity
|
0 (± 1) mol
|
|
Type
|
reactant
|
|
Smiles
|
|
Step Fifteen
|
Name
|
|
|
Quantity
|
1.2 mL
|
|
Type
|
reactant
|
|
Smiles
|
P(O)(=O)(OP(=O)(O)OP(=O)(O)O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N1C=NC=2C(N)=NC=NC12)O)O
|
Conditions
Other
|
Conditions are dynamic
|
1
|
|
Details
|
See reaction.notes.procedure_details.
|
Workups
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Control, blank, and experimental reaction mixtures
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Control and blank reaction mixtures
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
Experimental reaction
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The control reaction mixture
|
CONCENTRATION
|
Type
|
CONCENTRATION
|
|
Details
|
concentrations
|
DISSOLUTION
|
Type
|
DISSOLUTION
|
|
Details
|
1 mM ATP, 10 mM phosphocreatine, 2.5 mM Mg[acetate]2 ·4H2O, 20 μg/ml creatine phosphokinase [52 U/ml]), 0.60 ml of NADH (final concentration 2 mM), 0.30 ml of dithiothreitol (final concentration 7 mM) dissolved in buffer II, 0.060 ml of NaH14CO3 (1.0 μCi/μl
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
added 0.5 min
|
|
Duration
|
0.5 min
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
to reaction initiation), and
|
CONCENTRATION
|
Type
|
CONCENTRATION
|
|
Details
|
This vitamin K concentration
|
ADDITION
|
Type
|
ADDITION
|
|
Details
|
of added H14CO3 into vitamin K-dependent substrate proteins (J. Biol. Chem. 251, 2770-2776)
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The blank reaction mixture
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
The experimental reaction mixtures
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
were made up in the same way as the control reaction mixtures with the exceptions that
|
CUSTOM
|
Type
|
CUSTOM
|
|
Details
|
in the control reaction mixtures
|
Outcomes
Product
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
|
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
C=1C=CC(=CC1)C2C(=O)C=3C=CC=CC3C2=O
|
|
Name
|
|
|
Type
|
product
|
|
Smiles
|
CC(=O)CC(C=1C=CC=CC1)C2=C(C=3C=CC=CC3OC2=O)O
|
Source
|
Source
|
Open Reaction Database (ORD) |
|
Description
|
The Open Reaction Database (ORD) is an open-access schema and infrastructure for structuring and sharing organic reaction data, including a centralized data repository. The ORD schema supports conventional and emerging technologies, from benchtop reactions to automated high-throughput experiments and flow chemistry. Our vision is that a consistent data representation and infrastructure to support data sharing will enable downstream applications that will greatly improve the state of the art with respect to computer-aided synthesis planning, reaction prediction, and other predictive chemistry tasks. |
