2-Aminomethyl benzimidazole derivatives

The present invention relates to novel derivatives of 2-aminomethyl benzimidazole, their process of preparation and their therapeutic application.
The novel compounds according to the present invention correspond to the general formula: ##EQU4## in which: Ar represents a phenyl ring optionally substituted by one or more halogen atoms, by one or more alkyl radicals containing from 1 to 4 carbon atoms or by one or more alkoxy groups which each contain up to 4 carbon atoms; and
R.sub.1 and R.sub.2 each represent an alkyl radical containing from 1 to 4 carbon atoms, or form together with the nitrogen atom to which they are attached, a heterocyclic radical selected from piperidino, pyrrolidino, morpholino and hexamethyleneimino.
The process according to the present invention comprises condensing a derivative of 2-chloromethyl benzimidazole of the general formula: ##EQU5## with an amine of the general formula: ##EQU6## in which the symbols, R.sub.1, R.sub.2 and Ar have the same significance as in formula (I).
The derivatives of formula (II) are themselves obtained by the reaction of a derivative of 2-hydroxymethyl benzimidazole of the general formula: ##EQU7## in which Ar has the same significance as in formula (I), with thionyl chloride of formula:
SOCl.sub.2 (V)
the derivatives of formula (IV) resulting from the reaction, in a hydroalcoholic medium maintained under reflux, of the hydrochloride of a derivative of piperidinomethylacetophenone of the general formula: ##EQU8## in which Ar has the same significance as in formula (I), with 2-methanol benzimidazole of formula:

The following preparations are given by way of example to illustrate the present invention.
EXAMPLE 1
1-(2'-benzoylethyl)-2-dimethylaminomethyl benzimidazole (Code No: 72 522)
1st stage: 1-(benzoylethyl)-2-hydroxymethyl benzimidazole (Code No: 72 337)
A mixture of 0.06 mol of 2-hydroxymethyl benzimidazole, 0.06 mol of piperidinomethyl acetophenone hydrochloride, 48 ml. of methanol and 72 ml of water is maintained under reflux for 2 hours. After cooling to ambient temperature, the desired compound precipitates out, is filtered and recrystallised from 30 ml. of ethanol.
Melting point = 149.degree.C
Yield = 66%
Empirical formula = C.sub.17 H.sub.16 N.sub.2 O.sub.2
Elementary analysis: C H N______________________________________Calculated % 72.84 5.75 9.99Found % 72.68 5.85 10.00______________________________________
2nd stage: 1-(2' -benzoylethyl)-2-chloromethyl benzimidazole (Code No: 72 370)
A solution of 0.95 mol of thionyl chloride in 270 c.c. of chloroform is added, at 15.degree.C over a period of 1 hour, to a suspension of 0.62 mol of 1-(2'-benzoylethyl)-2-methanol benzimidazole in 480 c.c. of chloroform. After contact for 2 hours at ambient temperature, the excess thionyl chloride is evaporated and the methanolic solution of hydrochloride is neutralised with sodium bicarbonate. After filtration and evaporation, the crude base is recrystallised from ethyl acetate.
Melting point = 109.degree.C
Yield = 67%
Empirical formula = C.sub.17 H.sub.15 ClN.sub.2 O
Elementary analysis: C H N______________________________________Calculated % 68.34 5.06 9.38Found % 68.14 5.18 9.24______________________________________
3rd stage: 1-(2'-benzoylethyl)-2-dimethylaminomethyl benzimidazole (Code No. 72 522)
0.13 mol of 1-(2'-benzoylethyl)-2-chloromethyl benzimidazole obtained from the preceding stage and 0.26 mol of dimethylamine are dissolved in 300 c.c. of benzene.
The solution is maintained at 50.degree.C for 3 hours. After cooling the dimethylamine hydrochloride formed is filtered off, and the benzene is evaporated. The base is crystallised from petroleum ether.
Melting point = 90.degree.C
Yield = 70%
Empirical formula = C.sub.19 H.sub.21 N.sub.3 O
Elementary analysis: C H N______________________________________Calculated % 74.24 6.89 13.67Found % 74.18 6.87 13.52______________________________________
EXAMPLE 2
1-(2'-benzoylethyl maleate)-2-diethylaminomethyl benzimidazole (Code No. 72 573)
0.1 mol. of 1-(2'-benzolyethyl)-2-chloromethyl benzimidazole obtained by the procedure of stage 2 according to Example 1, and 0.2 mol. of diethylamine are dissolved in 300 c.c. of benzene.
The solution is maintained at 40.degree.C for 3 hours. After filtration of the diethylamine hydrochloride formed, the benzene is evaporated off. The crude base is salified in 200 c.c. of acetone with the aid of 0.1 mol. of maleic acid.
Melting point = 108.degree.C
Yield = 43%
Empirical formula = C.sub.25 H.sub.29 N.sub.3 O.sub.5
Elementary analysis: C H N______________________________________Calculated % 66.50 6.47 9.31Found % 66.50 6.55 9.51______________________________________
The compounds listed in the following Table I have been prepared by the method of operation of the first stage according to Example 1, whilst the compounds listed in Table II have been prepared by the method of operation of stage 3 according to Example 1 or by the method of operation of Example 2, following the synthesis of the crude base, or its salt.
TABLE I__________________________________________________________________________ O .parallel. --CH.sub.2 --CH.sub.2 --C--Ar(II) Melting Elementary AnalysisCode Empirical Molecular point Yield Calculated % Found %No. Ar. Formula Weight (.degree.C) % C H N C H N__________________________________________________________________________72316 C.sub.17 H.sub.14 Cl.sub.2 N.sub.2 O 333.21 130 80 61.27 4.24 8.41 61.03 4.28 8.2172336 C.sub.17 H.sub.14 ClFN.sub.2 O 316.75 118 42 64.46 4.46 8.84 64.20 4.46 8.7072411 C.sub.21 H.sub.23 ClN.sub.2 O.sub.2 370.87 80 58 68.01 6.25 7.55 68.00 6.27 7.4772294 C.sub.18 H.sub.17 ClN.sub.2 O 312.78 139 51 69.11 5.48 8.96 69.03 5.60 8.8572335 C.sub.19 H.sub.19 ClN.sub.2 O 326.81 90 57 69.82 5.86 8.57 69.99 5.85 8.4372346 C.sub.19 H.sub. 19 ClN.sub.2 O.sub. 358.81 138 60 63.60 5.34 7.81 63.45 5.57 7.6172379 C.sub.20 H.sub.21 ClN.sub.2 O.sub. 388.84 135 50 61.77 5.44 7.21 61.97 5.39 7.07__________________________________________________________________________
TABLE II__________________________________________________________________________ O .parallel. --CH.sub.2 --CH.sub.2 --C--Ar(I)Code R Empirical Mole- Melt- Yield Elementary AnalysisNo. Ar. --N.angle. Form Formula cular ing (%) C H N R.sub.2 weight point (.degree.C)__________________________________________________________________________ %72493 base C.sub.21 H.sub.23 N.sub.3 O 333.42 97 74 Calculated 75.64 6.95 12.60 Found 75.79 7.04 12.4172491 base C.sub.22 H.sub.25 N.sub.3 O 347.44 136 53 Calculated 76.05 7.25 12.10 Found 75.98 7.28 12.1372494 --NO base C.sub.21 H.sub.23 N.sub.3 O.sub.2 349.42 111 71 Calculated 72.18 6.64 6.57 Found 72.00 6.57 12.0772451 base C.sub.23 H.sub.27 N.sub.3 O 358.45 110 58 Calculated 76.42 7.53 11.63 Found 76.23 7.58 11.8372479 N(CH.sub.3).sub.2 base C.sub.19 H.sub.20 ClN.sub.3 O 341.83 123 65 Calculated 66.76 5.90 12.29 Found 66.76 5.75 12.1272390 N(C.sub.2 H.sub.5).sub.2 base C.sub.21 H.sub.24 ClN.sub.3 O 369.88 111 67 Calculated 68.19 6.54 11.36 Found 68.36 6.65 11.43 %72366 base C.sub.21 H.sub.22 ClN.sub.3 O 367.87 135 73 Calculated 68.56 6.03 11.42 Found 68.57 6.16 11.4772389 base C.sub.22 H.sub.24 ClN.sub.3 O 381.89 156 57 Calculated 69.19 6.33 11.00 Found 68.99 6.26 11.0172359 --NO base C.sub.21 H.sub.22 ClN.sub.3 O.sub. 383.87 131 78 Calculated 65.70 5.78 10.95 Found 65.63 5.77 10.8072418 base C.sub.23 H.sub.26 ClN.sub.3 O 395.92 121 30 Calculated 69.77 6.62 10.61 Found 69.83 6.44 10.4972663 --N(CH.sub. 3).sub.2 maleate C.sub.23 H.sub.24 FN.sub.3 O.sub.5 441.45 152 50 Calculated 62.57 5.48 9.52 Found 62.44 5.58 9.5772568 --N(C.sub. 2 H.sub.5).sub.2 maleate C.sub.25 H.sub.28 FN.sub.3 O.sub. 469.50 130 32 Calculated 63.95 6.01 8.95 Found 63.75 6.08 8.8372708 base C.sub.21 H.sub.22 FN.sub. 3 O 351.41 81 77 Calculated 71.77 6.31 11.96 Found 71.80 6.46 11.8472487 base C.sub.22 H.sub.24 FN.sub.3 O 365.44 114 71 Calculated 72.30 6.62 11.50 Found 72.28 6.68 11.4772526 --NO maleate C.sub.25 H.sub.26 FN.sub.3 O.sub.6 483.48 135 61 Calculated 62.10 5.42 8.69 Found 62.20 5.43 8.8872488 base C.sub.23 H.sub.26 FN.sub.3 O 379.46 104 68 Calculated 72.80 6.91 11.07 Found 72.79 7.03 10.9872524 --N(CH.sub.3).sub.2 base C.sub.23 H.sub.29 N.sub. 3 O.sub.2 379.49 84 86 Calculated 72.79 7.70 11.07 Found 72.68 7.63 10.9472727 --N(C.sub.2 H.sub.5).sub.2 base C.sub.25 H.sub.33 N.sub.3 O.sub. 407.54 84 50 Calculated 73.67 8.16 10.31 Found 73.46 8.16 10.2372465 base C.sub.25 H.sub.31 N.sub.3 O.sub. 405.52 113 69 Calculated 74.04 7.71 10.36 Found 74.14 7.73 10.5272464 base C.sub.26 H.sub.33 N.sub.3 O.sub.2 419.55 130 73 Calculated 74.43 7.93 10.02 Found 74.23 7.80 10.19 %72523 --NO base C.sub.25 H.sub.31 N.sub.3 O.sub. 421.52 127 72 Calculated 71.23 7.41 9.97 Found 71.15 7.27 10.1172463 base C.sub.27 H.sub.35 N.sub.3 O.sub.2 433.57 100 60 Calculated 74.79 8.14 9.69 Found 74.94 8.25 9.8972457 --N(CH.sub.3).sub.2 base C.sub.20 H.sub.23 N.sub.3 O 321.41 106 75 Calculated 74.73 7.21 13.07 Found 74.82 7.21 12.8772574 --N(C.sub. 2 H.sub.5).sub.2 maleate C.sub.26 H.sub.31 N.sub.3 O.sub.5 465.53 99 55 Calculated 67.08 6.71 9.03 Found 66.90 6.81 9.0372476 base C.sub.22 H.sub.25 N.sub.3 O 347.44 122 63 Calculated 76.05 7.25 12.10 Found 75.89 7.14 12.0372477 base C.sub.23 H.sub.27 N.sub.3 O 361.47 155 82 Calculated 76.42 7.53 11.63 Found 76.21 7.33 11.4472478 --NO base C.sub.22 H.sub.25 N.sub.3 O.sub. 363.44 135 70 Calculated 72.70 6.93 11.56 Found 72.70 6.79 11.50 %72483 base C.sub.24 H.sub.29 N.sub. 3 O 375.50 99 56 Calculated 76.76 7.78 11.19 Found 76.61 7.85 11.1372712 --N(CH.sub.3).sub.2 base C.sub.21 H.sub.25 N.sub.3 O 335.43 135 54 Calculated 75.19 7.51 12.53 Found 75.24 7.50 12.4472736 --N(C.sub.2 H.sub.5).sub.2 maleate C.sub.27 H.sub.33 N.sub.3 O.sub.5 479.56 107 48 Calculated 67.62 6.94 8.76 Found 67.65 7.00 8.6872446 base C.sub.23 H.sub.27 N.sub.3 O 361.47 118 63 Calculated 76.42 7.53 11.63 Found 76.62 7.58 11.4572540 base C.sub.24 H.sub.29 N.sub.3 O 375.50 132 76 Calculated 76.76 7.78 11.19 Found 76.86 7.79 11.2772447 --NO base C.sub.23 H.sub.27 N.sub.3 O.sub. 377.47 116 53 Calculated 73.18 7.21 11.13 Found 73.04 7.23 11.06 3/472603 base C.sub.25 H.sub.31 N.sub.3 OH.sub.2 O 403.04 72 46 Calculated 74.50 8.28 10.43 Found 74.44 8.19 10.55 %72490 --N(CH.sub.3).sub.2 base C.sub.21 H.sub.25 N.sub.3 O.sub. 367.40 95 76 Calculated 68.64 6.86 11.44 Found 68.67 6.88 11.2472692 --N(C.sub.2 H.sub.5).sub.2 maleate C.sub.27 H.sub.33 N.sub.3 O.sub.7 511.56 123 41 Calculated 63.39 6.50 8.21 Found 63.19 6.54 8.2672617 base C.sub.23 H.sub.27 N.sub. 3 O.sub. 393.47 82 60 Calculated 70.20 6.92 10.68 Found 70.00 7.01 10.5872377 base C.sub.24 H.sub.29 N.sub.3 O.sub.3 407.49 101 85 Calculated 70.73 7.17 10.31 Found 70.93 7.29 10.1972391 --NO base C.sub.23 H.sub.27 N.sub.3 O.sub. 409.47 150 65 Calculated 67.46 6.65 10.26 Found 67.47 6.68 10.1472398 base C.sub.25 H.sub.31 N.sub.3 O.sub. 421.52 100 57 Calculated 71.23 7.41 9.97 Found 71.04 7.47 9.8172534 --N(CH.sub.3).sub.2 base C.sub.22 H.sub.27 N.sub.3 O.sub.4 397.46 164 86 Calculated 64.48 6.85 10.57 Found 66.26 6.87 10.51 %72539 --N(C.sub.2 H.sub.5).sub.2 base C.sub.24 H.sub.31 N.sub. 3 O.sub.4 425.51 167 50 Calculated 67.74 7.34 9.88 Found 67.91 7.28 9.9772414 base C.sub.24 H.sub.29 N.sub.3 O.sub. 423.50 154 71 Calculated 68.06 6.90 9.92 Found 67.86 6.92 9.7572413 base C.sub.25 H.sub.31 N.sub.3 O.sub. 437.52 143 60 Calculated 68.63 7.14 9.61 Found 68.43 7.06 9.4572525 --N O maleate C.sub.28 H.sub.33 N.sub.3 O.sub.9 555.57 154 74 Calculated 60.53 5.99 7.56 Found 60.72 5.89 7.6372412 base C.sub.26 H.sub.33 N.sub.3 O.sub. 451.55 136 55 Calculated 69.15 7.37 9.31 Found 69.35 7.48 9.11__________________________________________________________________________
The compounds of formula (I) have been tested on animals in the laboratory and have been shown to possess analgesic, antihypertensive, gastric antisecretory, anti-inflammatory, antiobronochoconstrictive and anticholinergic, spasmolytic, sedative, antiulcerous, vasodilatatory, stimulants for the central nervous system, antiarythmic, diuretic and antihistaminic properties.
1. Analgesic properties
The compounds of formula (I), administered by oral means to the mouse, are capable of reducing the number of painful stretchings caused by the intraperitoneal injection of acetic acid.
By way of example, the following Table III lists the results obtained by administration of 100 mg/Kg/p.o. of different compounds of formula (I).
TABLE III______________________________________Code No. of Percentage reductioncompound tested of number of painful stretchings - (%)______________________________________72 491 6572 523 4572 391 6072 617 7072 487 8072 663 6072 603 5072 708 6072 574 45______________________________________
2. Antihypertensive properties
The compounds of formula (I), administered by oral means to a rat suffering from high blood pressure, are capable of lowering the systolic arteriel pressure.
By way of example, there is provided in the following Table IV the results obtained by administration of different compounds of formula (I).
TABLE IV______________________________________Code No. of Dose administered Percentage ofcompound tested (mg/Kg/p.o.) rats with high blood pressure whose systolic arteriel pressure is returned to normal (%)______________________________________72 491 200 5072 414 150 7572 525 200 5072 526 100 7572 568 200 5072 479 200 5072 457 200 50______________________________________
3. Gastric antisecretory properties
Administered by intraduodenal means to a rat, the compounds of formula (I) are capable of reducing the gastric secretion measured after Shay ligature.
By way of example, the following Table V gives the results obtained by administration of 50 mg/Kg/i.d. of different compounds of formula (I).
TABLE V______________________________________Code No. of Percentage reductions in volumecompound tested of gastric secretion - (%)______________________________________72 493 2572 494 2572 523 2572 487 40______________________________________
4. Antiinflammatory properties
These properties are shown by a diminution of the local oedema caused by the sub-plantar injection of a phlogogenic agent, such as carraghenin, in the rat following the oral administration of compounds of formula (I).
The following Table VI lists, by way of example, the percentage reduction of the oedems caused by the sub-plantar injection of carraghenin, resulting from the administration of 100 mg/Kg/p.o. of different compounds of formula (I).
TABLE VI______________________________________Code No. of Percentage reduction ofcompound tested sub-plantar oedema (%)______________________________________72 494 4072 488 5072 526 5572 447 4072 366 6072 712 7072 390 60______________________________________
5. Antibronchoconstrictive and anticholinergic properties.
Injected by intraveinous or intraduodenal means, the compounds of formula (I) are capable of opposing the bronchoconstriction provoked in the guinea-pig by the itraveinous injection of acetylcholine by the Konzett method.
By way of example, the following Table VII lists the results obtained by the administration of different compounds of formula (I)
TABLE VII______________________________________Code No. of Dose Percentagecompound tested Administered inhibition of bronchoconstriction (%)______________________________________72 573 5 mg/kg/i.v. 10072 412 100 mg/kg/i.d. 8072 414 100 mg/kg/i.d. 5072 525 100 mg/kg/i.d. 8072 534 100 mg/kg/i.d. 5072 391 100 mg/kg/i.d. 10072 398 100 mg/kg/i.d. 10072 487 100 mg/kg/i.d. 6072 526 100 mg/kg/i.d. 7572 447 100 mg/kg/i.d. 5072 540 100 mg/kg/i.d. 5072 603 100 mg/kg/i.d. 5072 708 100 mg/kg/i.d. 9072 457 100 mg/kg/i.d. 8072 736 10 mg/kg/i.v. 9072 727 100 mg/kg/i.d. 100______________________________________
6. Spasmolytic properties
The compounds of formula (I), introduced in the conserving medium are capable of opposing the contractural action of barium chloride on the isolated duodenum of the rat. This activity is evaluated by taking papaverine as standard.
Thus, the compounds of Code Nos. 72 573, 72 708, and 72 736 presents an equivalent spasmolytic actvity to that of papaverine.
7. Sedative properties
The compounds of formula (I), administered by oral means to the mouse, reduce the number of explorations in the escape enclosure.
By way of example, the following Table VIII lists the results obtained by the administration of 100 mg/Kg/p.o. of different compounds of formula (I).
TABLE VIII______________________________________Code No. of Percentage reduction of numbercompound tested of explorations in the escape enclosure (%)______________________________________72 464 3072 377 3072 391 5072 663 3072 540 3072 603 3072 712 4072 692 30______________________________________
8. Antiulcerous properties
The compounds of formula (I) administered by intraduodenal means reduce the extent of gastric ulcers, provoked in a rat by tying of the pylorus (Shay ulcers).
By way of example, there is listed in the following Table IX, the results obtained by the administrations of 50 mg/Kg/i.d. of different compounds of formula (I).
TABLE IX______________________________________Code No. of Percentage reduction ofcompound tested Shay ulcers - (%)______________________________________72 377 5572 398 2572 490 3072 488 2572 526 4072 447 3572 603 3572 359 3572 366 4072 712 5572 708 3072 390 4072 479 3072 457 3072 574 4572 736 30______________________________________
9. Vasodilatatory properties
The compounds of formula (I) are capable of augmenting the flow of the coronary vessels of the isolated heart of a guinea-pig when said compounds are added in the perfusion liquid of said organ.
By way of example, there can be found in the following Table X, the percentage augmentation of the flow of the isolated heart of a guinea-pig by adding different compounds of formula (I) to the perfusion liquid, in a concentration of 1 .mu.g/ml.
TABLE X______________________________________Code No. of Percentage augmentations of flowcompound tested of isolated heart of a guinea-pig (%)______________________________________72 490 14072 479 8072 478 5072 692 60______________________________________
10. Central nervous system stimulating properties
The compounds of formula (I), administered by oral means to the mouse, provoke an augmentation of the number of excursions into the escape enclosure.
Thus, following the administration of 100 mg/Kg/p.o. of the compounds of Code Nos. 72 457 and 72 736, an augmentation of 30% in the number of excursions in the escape test, is observed.
11. Antiarythmic properties
Administered by intraperitoneal means, the compounds of formula (I) are capable of protecting the mouse against the ventricular fibrillations provoked by the inhalation of chloroform.
By way of example, the compounds of Code Nos. 72 488, 72 568 and 72 479 present a DE 50 of 200 mg/Kg/i.p.
12. Diuretic properties
The compounds of formula (I), administered by oral means to the mouse, simultaneously with a volume of 1 ml. of an isotonic solution of sodium chloride per 25 g of the corporeal weight of the mouse, are capable of provoking an augmentation of the volume of urine emitted by reference to control animals, the volume being measured for 6 hours following administration.
By way of example, the following Table XI lists the results obtained by the administration of 25 mg/Kg/p.o. of different compounds of formula (I).
TABLE XI______________________________________Code No. of Percentage augmentationcompound tested of urinary elimination (%)______________________________________72 447 7072 603 4572 457 4572 692 70______________________________________
13. Antihistaminic properties
The compounds of formula I, introduced in the conserving medium, are capable of opposing the contractural action of histamine on the isolated ileum of the guinea-pig. This activity is evaluated by taking promethazine as standard.
By way of example, the compound of Code No. 72 366 presents an equivalent activity to that of promethazine.
As a result of a comparison between the pharmacologically active doses mentioned above and the lethal doses listed in the following Table XII, the difference between said doses is sufficiently great to permit the utilisation of the compounds of formula (I) in therapeutics.
TABLE XII______________________________________Code No. of Dose administered Percentagecompound tested (mg/Kg/p.o.) mortality (%)______________________________________72 491 2 000 072 493 2 200 .perspectiveto.572 573 1 250 .perspectiveto.5072 494 2 000 072 464 2 000 072 523 2 000 072 412 2 000 072 414 1 800 .perspectiveto.5072 525 2 000 .perspectiveto.1072 534 2 000 072 377 2 000 072 391 2 000 072 398 2 000 072 490 1 800 .perspectiveto.5072 617 2 600 .perspectiveto.5072 487 1 825 .perspectiveto.5072 488 2 000 072 526 1 400 .perspectiveto.5072 568 1 425 .perspectiveto.5072 663 1 800 .perspectiveto.5072 447 2 000 072 540 2 000 072 603 2 000 072 359 2 000 072 366 2 000 072 712 2 000 072 708 1 600 .perspectiveto.5072 390 2 000 072 479 2 000 072 457 2 000 072 478 2 000 072 574 2 200 .perspectiveto.5072 692 1 400 .perspectiveto.5072 736 2 000 .perspectiveto.1072 727 2 000 O______________________________________
The compounds of formula (I) are useful in the treatment of gastro-duodenal ulcers, visceral spasms, asthma, anxiety, nervousness, painful inflammations, diverse originating pains, circulatory insufficiencies, cardiac arythmies, hypertension, oedemas, allergies and asthenia.
They may be administered by oral means in the form of tablets, gelules and dragees containing 10 to 400 mg of active ingredient (1 to 6 times per day), or suspensions containing 0.5 to 5% of active ingredient (1 to 6 spoonfuls per day), by parenteral means in the form of injectable ampoules containing 5 to 50 mg of active ingredient (1 to 3 times per day) and by rectal means in the form of suppositories containing 10 to 200 mg of active ingredient (1 to 3 times per day).
Accordingly, the present invention also relates to a therapeutic composition comprising a compound of the general formula (I) together with a therapeutically acceptable carrier.

2-Aminomethyl benzimidazole derivatives

Information

Patent Number

Date Filed

Date Issued

Inventors

Original Assignees

Examiners

Agents

CPC

US Classifications

Field of Search

US

International Classifications

Abstract

Description

Claims

Priority Claims (1)

US Referenced Citations (1)

Foreign Referenced Citations (1)