1. A method for printing readable images onto an edible substrate using a drop on demand piezo-electric printer comprising:
a) positioning the substrate onto a high speed processing line at a speed of at least 50 ft.min.;
b) delivering the substrate to an ink jet printing station;
c) printing an ink onto the substrate to form a readable image, wherein the ink comprises a carrier comprising from 83 to 93.8 wt % propylene glycol and optionally glycerin, at least one edible surfactant comprising a lecithin-based surfactant, and less than about 5% wt % water;
d) transferring the substrate to a cooking device; and
e) cooking the substrate.
2. The method of claim 1 wherein the ink further comprises an edible colorant.
3. The method of claim 1 wherein the average surface tension of the ink is from about 24 mNm to about 44 mNm.
4. A method for printing readable images on snack chips, comprising:
a) delivering a snack chip substrate to an ink jet printing device on a high speed processing line at a speed of at least 50 ftmin.;
b) printing readable images on the substrate using an edible ink comprising a carrier comprising from 83 to 93.8 wt % propylene glycol, at least one surfactant comprising a lethicin-based surfactant, and less than about 10 wt % water, wherein satellite formation represents less than about 30% of the total printed area of a given snack chip;
c) transferring the substrate to a cooking device; and
d) cooking the substrate.
5. The method of claim 4 wherein said edible ink comprises less than about 5 wt % water.
6. The method of claim 4 wherein said edible ink further comprises a viscosity modifier comprising glycerin.
7. The method of claim 4 wherein the average surface tension of the edible ink is from about 24 mNm to about 44 mNm.
8. The method of claim 4 wherein satellite formation of the edible ink represents less than about 20% of the total printed area of a given snack chip.
9. The method of claim 4 wherein satellite formation of the edible ink represents less than about 10% of the total printed area of a given snack chip.
10. The method of claim 4 wherein satellite formation of the edible ink represents less than about 5% of the total printed area of a given snack chip.
11. A method for printing readable images on snack chips, comprising:
a) delivering a snack chip substrate to an ink jet printing device on a high speed processing line;
b) printing readable images on the substrate using an edible ink having a pH in the range of 5 to 8 and comprising dye purified to a sulfate level of less than 50 parts per million, a carrier comprising from 83 to 93.8 wt % propylene glycol, at least one surfactant comprising a lethicin-based surfactant, and less than about 10 wt % water;
c) delivering said printed substrate to a high temperature cooking device; and
d) cooking said substrate.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A compound of the formula (I)
in which
R1A represents hydrogen, fluorine, methyl, trifluoromethyl, ethyl, 1,1-difluoroethyl, 2,2,2-trifluoroethyl, n-propyl, cyclopropyl or cyclobutyl,
R1B represents hydrogen or methyl,
R2A represents hydrogen, methyl, trifluoromethyl, ethyl, 1,1-difluoroethyl, 2,2,2-tri-fluoroethyl or n-propyl, and
R2B represents hydrogen or methyl,
or
R1A and R2A are attached to one another and together with the carbon atoms to which they are attached form a cyclopropyl ring of the formula
in which R1B and R2B have the meanings mentioned above,
or
R2A and R2B are attached to one another and together with the carbon atom to which they are attached form a cyclic group of the formula
in which
n represents the number 1, 2 or 3, and
R1A and R1B have the meanings mentioned above,
R3 represents hydrogen, fluorine, methyl or trifluoromethyl,
R4 represents hydrogen, fluorine, chlorine, cyano, methyl, trifluoromethyl or ethyl,
R5A represents methyl, trifluoromethyl or ethyl, and
R5B represents trifluoromethyl,
or
R5A and R5B are attached to one another and together with the carbon atom to which they are attached form a difluoro-substituted cycloalkyl ring of the formula
R6 represents hydrogen, fluorine, chlorine, bromine, cyano, (C1-C4)-alkyl, (C2-C4)-alkenyl, cyclopropyl or cyclobutyl, where
(C1-C4)-alkyl and (C2-C4)-alkenyl may be substituted up to three times by fluorine
and
cyclopropyl and cyclobutyl may be substituted up to two times by fluorine,
and
R7 represents hydrogen, fluorine, chlorine, cyano, methyl, trifluoromethyl, ethyl, methoxy or trifluoromethoxy,
or a salt, solvate or solvate of a salt thereof.
2. The compound according to claim 1 in which
R1A represents hydrogen, methyl, trifluoromethyl, ethyl, n-propyl, cyclopropyl or cyclobutyl,
R1B represents hydrogen or methyl,
R2A represents hydrogen, methyl, trifluoromethyl, ethyl or n-propyl,
R2B represents hydrogen or methyl,
or
R2A and R2B are attached to one another and together with the carbon atom to which they are attached form a cyclic group of the formula
in which
n represents the number 1 or 2, and
R1A and R1B have the meanings mentioned above,
R3 represents hydrogen, fluorine or methyl,
R4 represents hydrogen, fluorine, chlorine, cyano, methyl or trifluoromethyl,
R5A represents methyl or ethyl,
R5B represents trifluoromethyl,
or
R5A and R5B are attached to one another and together with the carbon atom to which they are attached form a difluoro-substituted cycloalkyl ring of the formula
R6 represents fluorine, chlorine, (C1-C4)-alkyl, (C2-C3)-alkenyl, cyclopropyl or cyclobutyl, where
(C1-C4)-alkyl and (C2-C3)-alkenyl may be substituted up to three times by fluorine
and
cyclopropyl and cyclobutyl may be substituted up to two times by fluorine, and
R7 represents hydrogen, fluorine, chlorine, methyl or methoxy,
or a salt, solvate or solvate of a salt thereof.
3. The compound according to claim 1 in which
R1A represents hydrogen, methyl or ethyl,
R1B represents hydrogen,
R2A represents hydrogen, methyl, trifluoromethyl, ethyl or n-propyl,
R2B represents hydrogen or methyl,
or
R2A and R2B are attached to one another and together with the carbon atom to which they are attached form a cyclic group of the formula
in which
n represents the number 1 or 2, and
R1A and R1B have the meanings mentioned above,
R3 represents hydrogen,
R4 represents fluorine, chlorine or methyl,
R5A represents methyl,
R5B represents trifluoromethyl,
or
R5A and R5B are attached to one another and together with the carbon atom to which they are attached form a difluoro-substituted cyclopentyl ring of the formula
R6 represents fluorine, chlorine, methyl, trifluoromethyl, ethyl, 1,1-difluoroethyl, 2,2,2-trifluoroethyl, isopropyl, tert-butyl, 1,1,1-trifluoro-2-methylpropan-2-yl, vinyl, 1-fluorovinyl, cyclopropyl, 2,2-difluorocyclopropyl, cyclobutyl or 3,3-difluorocyclobutyl,
and
R7 represents hydrogen, fluorine, chlorine or methyl,
or a salt, solvate or solvate of a salt thereof.
4. The compound according to claim 1, wherein the compound is
(+)-3-(3-{(2S,3R)-2-(4-tert-butylphenyl)-4,4,4-trifluoro-3-methylbutanoylamino}-4-chlorophenyl)propanoic acid;
3-4-Chloro-3-({4,4,4-trifluoro-3-methyl-2-4-(2,2,2-trifluoroethyl)phenylbutanoyl}amino)phenylpropanoic acid;
3-(4-chloro-3-{(2S,3R)-2-(4-ethylphenyl)-4,4,4-trifluoro-3-methylbutanoylamino}phenyl)butanoic acid;
(3S)-3-(4-chloro-3-{(4-chlorophenyl)(2,2-difluoro-cyclopentyl)acetylamino}phenyl)butanoic acid;
(+)-3-(4-Chloro-3-{(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoylamino}phenyl)propanoic acid;
(+)-(2S)-3-(4-Chloro-3-{(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoylamino}phenyl)-2-methylpropanoic acid;
(+)-1-(3-{(2S,3R)-2-(4-Chlorophenyl)-4,4,4-trifluoro-3-methylbutanoylamino}-4-fluorophenyl)-cyclopropylacetic acid;
1-(4-Chloro-3-{(3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoylamino}phenyl)cyclobutylacetic acid;
(+)-(2S)-2-(4-Chloro-3-{(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoylamino}benzyl)butanoic acid;
3-(3-{(3R)-2-(4-Chlorophenyl)-4,4,4-trifluoro-3-methylbutanoylamino}-4-fluorophenyl)-2-methylpropanoic acid;
threo-3-(3-{(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoylamino}-4-fluorophenyl)-2-methylbutanoic acid;
2-(3-{(2S,3R)-2-(4-Chlorophenyl)-4,4,4-trifluoro-3-methylbutanoylamino}-4-fluorophenyl)-trans-cyclopropanecarboxylic acid;
(+)-2-(4-Chloro-3-{(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoylamino}benzyl)-2-methylbutanoic acid;
3-(4-Chloro-3-{(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoylamino}phenyl)hexanoic acid;
(+)-3-(4-Chloro-3-{(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoylamino}phenyl)hexanoic acid;
(+)-3-(4-Chloro-3-{(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoylamino}phenyl)-4,4,4-trifluorobutanoic acid;
(+)-3-(4-Chloro-3-{(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoylamino}phenyl)pentanoic acid;
3-(4-chloro-3-{(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoylamino}phenyl)-2,2-dimethylpropanoic acid;
1-(4-chloro-3-{(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoylamino}-phenyl)cyclobutylacetic acid;
1-(4-chloro-3-{(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoylamino}-phenyl)cyclopropylacetic acid;
(2S)-3-4-chloro-3-({4,4,4-trifluoro-3-methyl-2-4-(2,2,2-trifluoroethyl)phenylbutanoyl}amino)phenyl-2-methylpropanoic acid;
(2S)-3-4-chloro-3-({(2S,3R)-2-4-(3,3-difluorocyclobutyl)phenyl-4,4,4-trifluoro-3-methylbutanoyl}amino)phenyl-2-methylpropanoic acid;
1-(4-chloro-3-{(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoylamino}phenyl)-3,3-difluorocyclobutylacetic acid; or
(2S)-3-(4-Chloro-3-{(4-chlorophenyl)(3,3-difluorocyclopentyl)acetylamino}phenyl)-2-methylpropanoic acid.
5. A process for preparing a compound according to claim 1, wherein
(a) a carboxylic acid of the formula (II)
in which R5A, R4B, R6 and R7 have the meanings given in claim 1
is coupled with an amine of the formula (III)
in which R1A, R1B, R2A, R3B, R1 and R4 have the meanings given in claim 1
and
T1 represents (C1-C4)-alkyl or benzyl,
to give a carboxamide of the formula (IV)
in which R1A, R1B, R2A, R2B, R3, R4, R5A, R5B, R6, R7 and T1 have the meanings given above,
(b) the ester radical T1 is removed to give the compound of formula (I), and
(c) the compound of formula (I) is optionally separated into its enantiomers andor diastereomers, andor optionally reacted with one or more (i) solvents andor (ii) bases to give a solvate, salt andor solvate of a salt thereof.
6. The process according to claim 5, wherein step (a) is performed via a carbonyl chloride intermediate in the presence of a base.
7. The process according to claim 5, wherein in step (b) the ester radical T1 is removed by basic or acidic solvolysis and, if T1 represents benzyl, also by hydrogenolysis.
8. A pharmaceutical composition comprising a compound according to claim 1 and an inert, non-toxic, pharmaceutically suitable excipient.
9. A pharmaceutical composition comprising a compound according to claim 2 and an inert, non-toxic, pharmaceutically suitable excipient.
10. A pharmaceutical composition comprising a compound according to claim 3 and an inert, non-toxic, pharmaceutically suitable excipient.
11. A pharmaceutical composition comprising a compound according to claim 4 and an inert, non-toxic, pharmaceutically suitable excipient.
12. A pharmaceutical composition comprising a compound according to claim 1 in combination with one or more further active compounds selected from the group consisting of organic nitrates, NO donors, cGMP-PDE inhibitors, stimulators of guanylate cyclase, agents having antithrombotic activity, agents lowering blood pressure, and agents altering lipid metabolism.
13. A pharmaceutical composition comprising a compound according to claim 2 in combination with one or more further active compounds selected from the group consisting of organic nitrates, NO donors, cGMP-PDE inhibitors, stimulators of guanylate cyclase, agents having antithrombotic activity, agents lowering blood pressure, and agents altering lipid metabolism.
14. A pharmaceutical composition comprising a compound according to claim 3 in combination with one or more further active compounds selected from the group consisting of organic nitrates, NO donors, cGMP-PDE inhibitors, stimulators of guanylate cyclase, agents having antithrombotic activity, agents lowering blood pressure, and agents altering lipid metabolism.
15. A pharmaceutical composition comprising a compound according to claim 4 in combination with one or more further active compounds selected from the group consisting of organic nitrates, NO donors, cGMP-PDE inhibitors, stimulators of guanylate cyclase, agents having antithrombotic activity, agents lowering blood pressure, and agents altering lipid metabolism.
16. A method for the treatment andor prevention of heart failure, angina pectoris, hypertension, pulmonary hypertension, ischemias, vascular disorders, impaired microcirculation, thromboembolic disorders or arteriosclerosis comprising administering to a human or animal in need thereof an effective amount of a compound according to claim 1.
17. A method for the treatment andor prevention of heart failure, angina pectoris, hypertension, pulmonary hypertension, ischemias, vascular disorders, impaired microcirculation, thromboembolic disorders or arteriosclerosis comprising administering to a human or animal in need thereof an effective amount of a compound according to claim 2.
18. A method for the treatment andor prevention of heart failure, angina pectoris, hypertension, pulmonary hypertension, ischemias, vascular disorders, impaired microcirculation, thromboembolic disorders or arteriosclerosis comprising administering to a human or animal in need thereof an effective amount of a compound according to claim 3.
19. A method for the treatment andor prevention of heart failure, angina pectoris, hypertension, pulmonary hypertension, ischemias, vascular disorders, impaired microcirculation, thromboembolic disorders or arteriosclerosis comprising administering to a human or animal in need thereof an effective amount of a compound according to claim 4.
20. The process according to claim 5, wherein step (a) is performed in the presence of an inert solvent with the aid of a condensing agent.