US3891652A - Antianginal aryldecahydropyrrolo{8 3,4-f{9 quinolines - Google Patents

Antianginal aryldecahydropyrrolo{8 3,4-f{9 quinolines Download PDF

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US3891652A
US3891652A US374593A US37459373A US3891652A US 3891652 A US3891652 A US 3891652A US 374593 A US374593 A US 374593A US 37459373 A US37459373 A US 37459373A US 3891652 A US3891652 A US 3891652A
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Frederic Peter Hauck
Joseph E Sundeen
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ER Squibb and Sons LLC
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Priority to FR7422485A priority patent/FR2350841A1/en
Priority to JP49074922A priority patent/JPS5040595A/ja
Priority to DE2431201A priority patent/DE2431201A1/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D211/74—Oxygen atoms
    • C07D211/76—Oxygen atoms attached in position 2 or 6

Definitions

  • ABSTRACT 4-Ary1-2,3,3a,4,5,6,7,8,9,9b-decahydro-Il-I-pyrrolo- [3,4-f1quinolines, 4-aryl2,3,3a,4,5.7,8,9,9a,9bdecahydro-1-I-l-pyrr0lo[3,4-f]quinolinium salts, intermediates for their preparation and methods for their preparation are disclosed.
  • This invention relates to blood pressure lowering agents, anti-inflammatory agents, antianginal and antiarrhythmic agents of the following general formula wherein Aryl is selected from the group consisting of phenyl, naphthyl, and substituted phenyl or naphthyl, wherein said substituent is selected from the group consisting of lower alkyl, lower alkoxy, di(lower alkyl- )amino, halogen and trifluoromethyl, and R and R are selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, aryl, aryl-lower alkyl and aryllower alkenyl, and acid addition salts (la) thereof which have the formula
  • This invention also relates to the useful intermediates of the formulae:
  • the term lower alkyl is intended to mean a straight or branched chain alkyl group of from one to eight carbon atoms.
  • lower alkoxy is intended to mean a straight or branched chain alkyl group of from one to eight carbon atoms linked directly to an oxygen atom.
  • aryl is intended to mean phenyl, naphthyl and substituted phenyl or naphthyl.
  • substituted when applied to aryl or phenyl is intended to encompass one or two substituents which may be alike or different and are selected from the following group: lower alkyl, lower alkoxy, halogen, trifluoromethyl, and di(lower alkyl)amino.
  • acid addition salts is intended to encompass the salts formed upon the addition of an acid to the compounds of this invention.
  • monoor di-salts of this invention may be formed by the addition of such acids as hydrochloric acid, phosphoric acid, sulfuric acid, perchloric acid, acetic acid, citric acid, etc.
  • the preferred acids are those which form pharmaceutically acceptable acid addition salts although other salts may be of use in purifying and storing the compounds of this invention.
  • the salt form is best described by formula la.
  • the compounds of the present invention may exist in a number of isomeric forms such as steroisomeric forms, endo and exo forms, etc. All of these isomers are intended to be within the scope of the present invention.
  • Compounds of the formula VIIl are then added to compounds of the formula VII to give compounds of the formula ll.
  • Compounds of the formula ll are generally converted to compounds of the formula ill utilizing a dehydrating agent, such as ptoluene sulfonic acid or its monohydrate.
  • the dehydration reactions and Diels-Alder reactions are generally carried out from about 15 to about 80 in a lower alkyl anhydride solvent, such as acetic anhydride, for periods of from 1 hour to 24 hours.
  • a lower alkyl anhydride solvent such as acetic anhydride
  • the compounds of formula V are converted into the compounds of this invention by a reduction reaction utilizing LiAll'l in an ethereal solvent, preferably tetrahydrofuran.
  • the compounds of formula I may be converted to their salts by reaction with acids, such as sulfuric acid, perchloric acid, hydrochloric acid, etc.
  • acids such as sulfuric acid, perchloric acid, hydrochloric acid, etc.
  • the resultant compounds are best represented by formula Xl /N A H -B R 2X v
  • the compounds of this invention and their non-toxic pharmaceutically acceptable salts have thus been found to be useful as antiinflammatory, antianginal and anti-arrhythmic agents and to reduce blood pressure in mammals when administered in amounts ranging from about 2 mg. to about 25 mg. per kg. of body weight per day.
  • a preferred dosage regimen for optimum results would be from about l0 mg. to about 20 mg. per kg. of body weight per day, and such dosage units are employed that a total of from about 500 mg. to about 1,000 mg. of active ingredient for a subject of about 70 kg. body weight are administered in a 24 hour period.
  • the compounds of the present invention in the described dosages are intended to be administered orally; however, other routes such as rectally, intraperitoneally, subcutaneously, intramuscularly or intravenously may be employed.
  • the active compounds of the present invention are orally administered, for example, with an inert diluent or with an assimilable edible carrier, or they may be enclosed in hard or soft gelatin capsules, or they may be compressed into tablets, or they may be incorporated directly with the food of the diet.
  • the active compounds of this invention may be incorporated with excipients and used in the form of tablets, troches, capsules, elixirs, suspensions, syrups, wafers, chewing gum, and the like.
  • Such compositions and preparations should contain at least 0.1 percent of active compound.
  • the percentage in the compositions and preparations may, of course, be varied and may conveniently be between about 5 to about percent or more of the weight of the unit.
  • the amount of active compound in such therapeutically useful compositions of preparations is such that a suitable dosage will be obtained.
  • Preferred compositions or preparations according to the present invention are prepared so that an oral dosage unit form contains between about 10 and 200 milligrams of active compound.
  • the tablets, troches, pills, capsules and the like may also contain the following: a binder such as gum tragacanth, acacia, corn starch or gelatin; an excipient such as dicalcium phosphate, a disintegrating agent such as corn starch, potato starch alginic acid and the like; a lubricant such as magnesium stearate; and a sweetening agent such as sucrose, lactose or saccharin may be added or a flavoring agent such as peppermint, oil of Wintergreen, or cherry flavoring.
  • a binder such as gum tragacanth, acacia, corn starch or gelatin
  • an excipient such as dicalcium phosphate, a disintegrating agent such as corn starch, potato starch alginic acid and the like
  • a lubricant such as magnesium stearate
  • a sweetening agent such as sucrose, lactose or saccharin may be added or a flavoring agent such as peppermint, oil
  • any material used in preparing any dosage unit form should be pharmaceutically pure and substantially non-toxic in the-amounts employed.
  • EXAMPLE 6 6-BenZyl-2,3 ,3a,4,5 ,7,8,9,9a,9b-Decahydro-2-methyl- 4-phenyl-lll-pyrrolo[3,4-f]quinolinium chloride hydrochloride.
  • Example ld Substituting benzylamine for methylamine in the procedure of Example l-c yields the corresponding imide lactam which is then reduced as in Example ld,e to the title compound.
  • Example 1c Substituting aniline for methylamine in the procedure of Example 1c yields the corresponding imide lactam which is then reduced as in Example 1d,e to the title compound.
  • Aryl is selected from the group consisting of phenyl, naphthyl, substituted phenyl and substituted naphthyl, wherein said substituent is selected from the group consisting of lower alkyl, lower alkoxy, di(lower all yl)amino, halogen and trifluoromethyl, and R and R are selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, aryl-lower alkyl and styryl, and acid addition salts thereof having the formula:
  • aryl is selected from the group consisting of phenyl and pmethoxyphenyl and R and R are lower alkyl.
  • aryl is pmethoxyphenyl and R and R are methyl 4.
  • aryl is phenyl and citrate salts.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Hydrogenated Pyridines (AREA)

Abstract

4-Aryl-2,3,3a,4,5,6,7,8,9,9b-decahydro-1H-pyrrolo-(3,4f)quinolines, 4-aryl-2,3,3a,4,5,7,8,9,9a,9b-decahydro-1-Hpyrrolo(3,4-f)quinolinium salts, intermediates for their preparation and methods for their preparation are disclosed. In addition, pharmaceutical compositions containing said compounds and methods for using said compositions as antiflammatory, antianginal and anti-arrhythmic agents and to reduce blood pressure are reported.

Description

United States Patent [191 Hauck et a].
[4 1 June 24, I975 I 1 ANTIANGINAL ARYLDECAHYDROPYRROLO[ 3,4- F ]QUINOLINES [75] Inventors: Frederic Peter Hauck, Somerville;
Joseph E. Sundeen, Trenton, both of NJ.
[73] Assignee: E. R. Squibb & Sons, llnc.,
Princeton, NJ.
22 Filed: June 28,1973
21 Appl.l lo.z374,593
[52] U.S. Cl 260/288 R; 424/258; 260/240 D [51] Int. Cl C07d 33/52 [58] Field of Search 260/240 D, 288 R [56] References Cited OTHER PUBLICATIONS Luhan et al., Chem. Abstracts, Vol. 77, Abst. No. l524l9w (I972).
Wagner-lauregg et al., Helv. Chim. Acta Vol. 56, pgs. 440 to 449, (Jan. 31, 1973, copy received POSL 4/27/73).
Primary E.\'aminerJohn D. Randolph Attorney, Agent, or FirmLawrence S. Levinson; Merle J. Smith; Stephen B. Davis [57] ABSTRACT 4-Ary1-2,3,3a,4,5,6,7,8,9,9b-decahydro-Il-I-pyrrolo- [3,4-f1quinolines, 4-aryl2,3,3a,4,5.7,8,9,9a,9bdecahydro-1-I-l-pyrr0lo[3,4-f]quinolinium salts, intermediates for their preparation and methods for their preparation are disclosed.
5 Claims, No Drawings ANTIANGINAL ARYLDECAHYDROPYRROLOB,4-F]QUINOLINES This invention relates to blood pressure lowering agents, anti-inflammatory agents, antianginal and antiarrhythmic agents of the following general formula wherein Aryl is selected from the group consisting of phenyl, naphthyl, and substituted phenyl or naphthyl, wherein said substituent is selected from the group consisting of lower alkyl, lower alkoxy, di(lower alkyl- )amino, halogen and trifluoromethyl, and R and R are selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, aryl, aryl-lower alkyl and aryllower alkenyl, and acid addition salts (la) thereof which have the formula This invention also relates to the useful intermediates of the formulae:
ArylCH=0H l l HO ArylCH=CH l 0 II III 0 Aryl R I l R O t 2 The term lower alkyl is intended to mean a straight or branched chain alkyl group of from one to eight carbon atoms.
The term lower alkoxy is intended to mean a straight or branched chain alkyl group of from one to eight carbon atoms linked directly to an oxygen atom.
The term aryl is intended to mean phenyl, naphthyl and substituted phenyl or naphthyl.
The term substituted" when applied to aryl or phenyl is intended to encompass one or two substituents which may be alike or different and are selected from the following group: lower alkyl, lower alkoxy, halogen, trifluoromethyl, and di(lower alkyl)amino.
The term acid addition salts is intended to encompass the salts formed upon the addition of an acid to the compounds of this invention. Thus monoor di-salts of this invention may be formed by the addition of such acids as hydrochloric acid, phosphoric acid, sulfuric acid, perchloric acid, acetic acid, citric acid, etc. The preferred acids are those which form pharmaceutically acceptable acid addition salts although other salts may be of use in purifying and storing the compounds of this invention. The salt form is best described by formula la.
The compounds of the present invention may exist in a number of isomeric forms such as steroisomeric forms, endo and exo forms, etc. All of these isomers are intended to be within the scope of the present invention.
The compounds of this invention are prepared from the readily available compounds of the formulae ArylCH=CHha l ide VI VII Vlll the preferred halide is the bromide, by reaction with magnesium turnings in an ethereal solvent, such as ether, tetrahydrofuran, dioxane, diglyme, etc., at from room temperature to about C. for 15 minutes to about 24 hours. Compounds of the formula VIIl are then added to compounds of the formula VII to give compounds of the formula ll. Compounds of the formula ll are generally converted to compounds of the formula ill utilizing a dehydrating agent, such as ptoluene sulfonic acid or its monohydrate. Since compounds of the formula Ill tend to dimerize readily, the dehydration is usually carried out in the presence of a dienophile of the formula lX wherein Z is -O- or to give compounds of the formula IV or V. When compounds of the formula IX, wherein Z is O, are employed, compounds of the formula IV are obtained which are converted to compounds of the formula V by reaction with a compound of the formula X.
The dehydration reactions and Diels-Alder reactions are generally carried out from about 15 to about 80 in a lower alkyl anhydride solvent, such as acetic anhydride, for periods of from 1 hour to 24 hours.
The compounds of formula V are converted into the compounds of this invention by a reduction reaction utilizing LiAll'l in an ethereal solvent, preferably tetrahydrofuran.
The compounds of formula I may be converted to their salts by reaction with acids, such as sulfuric acid, perchloric acid, hydrochloric acid, etc. The resultant compounds are best represented by formula Xl /N A H -B R 2X v The compounds of this invention and their non-toxic pharmaceutically acceptable salts have thus been found to be useful as antiinflammatory, antianginal and anti-arrhythmic agents and to reduce blood pressure in mammals when administered in amounts ranging from about 2 mg. to about 25 mg. per kg. of body weight per day. A preferred dosage regimen for optimum results would be from about l0 mg. to about 20 mg. per kg. of body weight per day, and such dosage units are employed that a total of from about 500 mg. to about 1,000 mg. of active ingredient for a subject of about 70 kg. body weight are administered in a 24 hour period.
The compounds of the present invention in the described dosages are intended to be administered orally; however, other routes such as rectally, intraperitoneally, subcutaneously, intramuscularly or intravenously may be employed.
The active compounds of the present invention are orally administered, for example, with an inert diluent or with an assimilable edible carrier, or they may be enclosed in hard or soft gelatin capsules, or they may be compressed into tablets, or they may be incorporated directly with the food of the diet. For oral therapeutic administration, the active compounds of this invention may be incorporated with excipients and used in the form of tablets, troches, capsules, elixirs, suspensions, syrups, wafers, chewing gum, and the like. Such compositions and preparations should contain at least 0.1 percent of active compound. The percentage in the compositions and preparations may, of course, be varied and may conveniently be between about 5 to about percent or more of the weight of the unit. The amount of active compound in such therapeutically useful compositions of preparations is such that a suitable dosage will be obtained. Preferred compositions or preparations according to the present invention are prepared so that an oral dosage unit form contains between about 10 and 200 milligrams of active compound.
' The tablets, troches, pills, capsules and the like may also contain the following: a binder such as gum tragacanth, acacia, corn starch or gelatin; an excipient such as dicalcium phosphate, a disintegrating agent such as corn starch, potato starch alginic acid and the like; a lubricant such as magnesium stearate; and a sweetening agent such as sucrose, lactose or saccharin may be added or a flavoring agent such as peppermint, oil of Wintergreen, or cherry flavoring. When the dosage unit form is a capsule, it may contain in addition to materials of the above type a liquid carrier such as a fatty oil. Various other materials may be present as coatings or to otherwise modify the physical form of the dosage unit, for instance, tablets, pills or capsules may be coated with shellac, sugar or both. A syrup or elixir may contain the active compounds, sucrose as asweetening agent, methyl and propyl parabens as preservatives, a dye and a flavoring such as cherry or orange flavor. Of course, any material used in preparing any dosage unit form should be pharmaceutically pure and substantially non-toxic in the-amounts employed.
The invention will be described in greater detail in conjunction with the following specific examples.
EXAMPLE 1 2,3,3a,4,5,7,8,9,9a,9b-Decahydro-2,6-dimethyl-4- phenyl-lH-pyrrolo[3,4-f]quinolinium chloride hydrochloride a. l-methyl-2-styryl-2-hydroXy-6-piperidone The Grignard reagent prepared in 300 ml of THF from 24 g (1.0 mole) of magnesium and 42 g (0.30 mole) of fl-bromostyrene is decanted from excess metal and added dropwise under nitrogen to a solution of 27 g (0.21 moles) of N-methyl glutarimide-at-35. After l /i hrs. at room temperature, the mixture is treated with 250 ml of saturated NH.,Cl solution with cooling. The separated aqueous layer is reextracted and the combined THF extracts washed with salt, dried over MgSO, and freed of solvent. Product is extracted into hot ether and crystallized on cooling to yield white crystals, mp 108l 129C.
b. l-methyl-7-phenyl-3,4,5,6,7,8-hexahydro-2-1H- quinolone-S,6-dicarboxylic acid anhydride A slurry of 0.8 g (2.6 mmole) of the above adduct in 12 ml of acetic anhydride is treated with 0.4 g (4.1 mmole) of maleic anhydride and 10 mg of toluenesulfonic acid hydrate. After standing overnight, the mixture is taken up in ether and seeded to yield the title compound as a crystalline solid, mp 20l-204.
c. 2,3,3a,4,5,6,7,8,9,9b-Decahydro-2,6-dimethyl-4 phenyll H-pyrrolo[ 3 ,4-flquinolinel ,3 ,7-trione The anhydride (0.55g, 1.3 mmole) is taken up in 10 ml of 40 percent aqueous methylamine and the temperature raised slowly to where it is held for 10 minutes in vacuo. Cooling leaves the title compound as a glass having an ir consistent with the product.
d. 2,3,3a,4,5,6,7',8,9,9b-Decahydro-2,6-dimethyl-4- phenyl-l H-pyrrolo[3,4-f]quinoline The above imide lactam (0.4 g, 1.0 mmole) in ml of 1:1 ether: methylene chloride is treated with 0.5 g of lithium aluminum hydride in portions,. then heated under reflux for 2 hrs. After decomposition with water. the mixture is filtered and the salts washed with methylene chloride. Evaporation gives 0.3 g of tacky yellow oil.
e. 2,3,3a,4,5.7.8,9,94.5,7,8.9,99h-Decahydro-2.6- dimethyl-4-phenyl-lH-pyrrolo[3,4-f1quinolinium chloride hydrochloride The above product is dissolved in isopropanol-ether and treated with excess HCl. The crude salt is recrystallized from isopropanol-acetone-ether to yield a solid of mp 165175.
Anal. Calcd. for C, 64.22; H. 7.94; N, 7.88; Cl, 19.35. Found C, 64.37; H, 8.24; N, 7.69; Cl, 20.19
EXAMPLE 2 2,3,3a,4,5,7,8,9,9a,9b-Decahydro-2,6-dimethyl-4pmethoxyphenyl-l lHl-pyrrolo[3 ,4-f1quinolinium chloride hydrochloride Substituting p-methoxy-B-bromostyrene for B-bromostyrene in the procedure of Example la yields the corresponding substituted piperidone which is converted by the same sequence as Example 1 to the title compound.
EXAMPLE 3 2,3,3a,4,5,7,8,9,9a,9b-Decahydro-2,6-dimethyl-4-ptolyl-lllll-pyrrolo-[3,4-f]quinolinium chloride hydrochloride Substituting p-methyl-B-bromostyrene for B-bromostyrene in the procedure of Example la yields the corresponding substituted piperidone which is converted by the same sequence as Example 1 to the title compound.
EXAMPLE 4 2,3,3a,4,5,7,8,9,9a,9b-Decahydro-2,6-dimethyl-4-pdimethylaminophenyll l-ll-pyrrolo-[3,4-f1quinolinium chloride hydrochloride.
Substituting p-dimethylamino-B-bromostyrene for B-bromostyrene in the procedure of Example la yeilds the corresponding substituted piperidone which is converted by the same sequence as Example 1 to the title compound.
EXAMPLE 5 2,3,3a,4,5,7,8,9,9a,9b-Decahydro-2,6-dimethyl-4-pfluorophenyl- 1 l-ll-pyrrolo-[ 3,4-f]quinolinium chloride hydrochloride.
Substituting p-fluoro-B-bromostyrene for ,B-bromostyrene in the procedure of Example la yields the corresponding substituted piperidone which is converted by the same sequence as Example 1 to the title compound.
EXAMPLE 6 EXAMPLE 7 6-BenZyl-2,3 ,3a,4,5 ,7,8,9,9a,9b-Decahydro-2-methyl- 4-phenyl-lll-pyrrolo[3,4-f]quinolinium chloride hydrochloride.
Substituting N-benzylglutarimide for N-methylglutarimide in the procedure of Example In yields the corresponding piperidone which is converted by the same sequence as Example 1 to the title compound.
EXAMPLE 8 2-Benzyl-2,3,3a.4.5,7.8,9,9a.9b-Decahyclro-6-methyl- 4-phenyllH-pyrrolo[3,4-f]quinolinium chloride hydrochloride.
Substituting benzylamine for methylamine in the procedure of Example l-c yields the corresponding imide lactam which is then reduced as in Example ld,e to the title compound.
EXAMPLE 9 2,3,3a,4,5,7,8,9,9a,9b-Decahydro-6-methyl-2,4- diphenyl-lH-pyrrolo[3,4-f]quinolinium chloride hydrochloride.
Substituting aniline for methylamine in the procedure of Example 1c yields the corresponding imide lactam which is then reduced as in Example 1d,e to the title compound.
EXAMPLE 1O 2,3.3a.4,5.7,8,9,9a,9b-Decahydro-2-ethyl-6-methyl-4- phenyl-lll-ll-pyrrolo[3,4-f]quinolinium chloride hydrochloride.
Substituting N-ethylmaleimide for maleic anhydride in the procedure of Example lb and raising the reaction temperature to 80 yields 2,3,3a,4,5,6,7,8,9,9bdecahydro-Z-ethyl-6-methyl-4-phenyl-1l-l-pyrrolo[3 ,4- f]quinoline-1,3,7-trione directly which is then converted by the procedure of Example 1-d,e to the title compound.
What is claimed is:
11. A compound of the formula wherein Aryl is selected from the group consisting of phenyl, naphthyl, substituted phenyl and substituted naphthyl, wherein said substituent is selected from the group consisting of lower alkyl, lower alkoxy, di(lower all yl)amino, halogen and trifluoromethyl, and R and R are selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, aryl-lower alkyl and styryl, and acid addition salts thereof having the formula:
Aryl
2. The compound of claim 1 wherein aryl is selected from the group consisting of phenyl and pmethoxyphenyl and R and R are lower alkyl.
3. The compound of claim 2 wherein aryl is pmethoxyphenyl and R and R are methyl 4. The compound of claim 2 wherein aryl is phenyl and citrate salts.
UNITED STATES PATENT OFFICE QETIFICATE ()F CORRECTION Patent No. 3,891,652 Dated June 24, 1975 Inventods) Frederic Peter Hauck et a1.
It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:
Column 4, line 3, "of" should read or Column 5, line 8, "2,3,3a,4,5,7,8,9,94,5,7,8,9,99b" should read 2,3,2a,4,5,7,8,9,9a,9b
Column 5, line 42, "veilds" should read yields Signed and Scaled this sixteenth D 3) 0f September 1975 [SEAL] Arrest:
RUTH C. MASON C. MARSHALL DANN Arresting Officer (ummixsimwr ojlatenls and Trademarks

Claims (5)

1. A COMPOUND OF THE FORMULA
2. The compound of claim 1 wherein aryl is selected from the group consisting of phenyl and p-methoxyphenyl and R and R1 are lower alkyl.
3. The compound of claim 2 wherein aryl is p-methoxyphenyl and R1 and R2 are methyl.
4. The compound of claim 2 wherein aryl is phenyl and R1 and R2 are methyl.
5. The compound of claim 1 wherein said acid addition salt is selected from the group consisting of the hydrochloride, phosphate, sulfate, perchlorate, acetate, and citrate salts.
US374593A 1973-06-28 1973-06-28 Antianginal aryldecahydropyrrolo{8 3,4-f{9 quinolines Expired - Lifetime US3891652A (en)

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US374593A US3891652A (en) 1973-06-28 1973-06-28 Antianginal aryldecahydropyrrolo{8 3,4-f{9 quinolines
GB2721474A GB1477734A (en) 1973-06-28 1974-06-19 Quinolines
FR7422485A FR2350841A1 (en) 1973-06-28 1974-06-27 ARYLDECAHYDROPYRROLO (3,4-F) ANTI-ANGINOUS QUINOLEINES
JP49074922A JPS5040595A (en) 1973-06-28 1974-06-28
DE2431201A DE2431201A1 (en) 1973-06-28 1974-06-28 4-ARYLDECAHYDRO-1H-PYRROLO SQUARE BRACKET ON 3,4 SQUARE BRACKET FOR QUINOLINE DERIVATIVES, METHOD OF THEIR MANUFACTURING AND MEDICINAL PRODUCTS
US05/549,581 US3963724A (en) 1973-06-28 1975-02-13 Intermediates useful in the preparation of aryldecahydropyrrolo[3,4-f]quinolines

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DE (1) DE2431201A1 (en)
FR (1) FR2350841A1 (en)
GB (1) GB1477734A (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4235909A (en) * 1979-04-19 1980-11-25 Eli Lilly And Company Octahydro-2H-pyrrolo[3,4-g]quinolines
US4282362A (en) * 1979-04-19 1981-08-04 Eli Lilly And Company Octahydro-2H-pyrrolo[3,4-g]quinolines
US4311844A (en) * 1980-04-18 1982-01-19 Eli Lilly And Company Octahydro-2H-pyrrolo[3,4,-g]quinolines

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE895842A (en) * 1982-02-12 1983-08-08 Sandoz Sa NOVEL ERGOPEPTIDE ALKALOIDS, THEIR PREPARATION AND THEIR USE AS MEDICAMENTS
JP2005222832A (en) * 2004-02-06 2005-08-18 Sumitomo Electric Ind Ltd Manufacturing method and manufacturing device of cable

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
luhan et al., Chem. Abstracts, Vol. 77, Abst. No. 152419w (1972). *
Wagner-Jauregg et al., Helv. Chim. Acta Vol. 56, pgs. 440 to 449, (Jan. 31, 1973, copy received POSL 4/27/73). *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4235909A (en) * 1979-04-19 1980-11-25 Eli Lilly And Company Octahydro-2H-pyrrolo[3,4-g]quinolines
US4282362A (en) * 1979-04-19 1981-08-04 Eli Lilly And Company Octahydro-2H-pyrrolo[3,4-g]quinolines
US4311844A (en) * 1980-04-18 1982-01-19 Eli Lilly And Company Octahydro-2H-pyrrolo[3,4,-g]quinolines

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FR2350841B1 (en) 1978-12-29
JPS5040595A (en) 1975-04-14
FR2350841A1 (en) 1977-12-09
GB1477734A (en) 1977-06-22
DE2431201A1 (en) 1975-01-16

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