US2876222A - 1,2,3,4-tetrahydroquinolyl and 1, 2, 3, 4-tetrahydroisoquinolyl derivatives of 1, 3-diazacyclohexene-2 - Google Patents
1,2,3,4-tetrahydroquinolyl and 1, 2, 3, 4-tetrahydroisoquinolyl derivatives of 1, 3-diazacyclohexene-2 Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/06—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D239/08—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms directly attached in position 2
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Description
1,2;3,4-TETRAHYDRO UINOLYL AND 1,25,4- TETRAHYDROISOQUINOLYL DERIVATIVES F 1,3-DIAZ ACYCLOHEXENE-2 Barry M. Bloom; Jackson Heights, N. Y., assignor to jChas. Pfizer & 'Co., Inc., New York, N. Y., a corporation of Delaware No Drawing, Application October 18,1956. Serial No. 616,594
Claims. (Cl. 260256.4)
This invention is concerned with new and highly effective therapeutic agents. In particular it is concerned with substituted and unsubstituted -1,2,3,4-tetrahydro- .quinolyl-l,3 diaZacycIoheXene-Z, 1 ,2,3,4 tetra'hydroisoquinolyl-l,3 diazacyclohexene 2 and their' pharmaceutically acceptable acid" addition salts. 1 4
Inmy copending and concurrently filedpatent application Serial. No. 616,639, entitled. Therapeutic Agents,
'1. describe certain 1,2,3,4-tetrahydroquinolyl-1,3ediazacyclopentener2, 1,2, 3 ,4,-tetrahydroisoquinolyl-1 ,3-diazacyclopentene-Z and their pharmaceutically acceptable acid addition salts. These agents are potent. regulators of United States Patent 0 the cardiovascular system having the special property of functioning as hypotensive agents.
I have now unexpectedly discovered that when the diazacyclopentene ring of the above described therapeutic agents is replaced with a diaaacyclohexene ring the resulting products, while still functioning as regulators of the cardiovascular system, have a special property opposite in nature to the 5-membered ring compounds, that is, they arepressor amines.
' The term, pressor arninehas a definite meaning to one'skilled in the art. -It refers to an organic amine which has the physiological eflect of vasoconstriction and other epinephrine like properties. These materials-cause constriction of the blood vessel-walls thereby decreasing the volume of the blood vesselsand increasing the blood pressure. They are used topically to causeconstriction .ofthe blood vessels of the nose in treatment of allergic rhinitis,- sinusitis, acutecoryzaand hay fever.
The compounds of the present invention are-diazacyclo: hexenes wherein the numbertwo carbon atom ofsaid diazacyclohexenes is attached to the heterocyclic nitrogen atomof. a tetrahydroquinolyl' or tetrahydroisoquinolyl ring. Both substituted and unsubstituted compounds of the instant invention arefound to possess pressor amine activity. The substituents on a substitutedlpressor' amine may be divided into classes according to whether they are on the aromatic ring of the tetrahydroquinoline or tetrahydroisoquinoline moieties, the partially reduced ring of these moieties or the carbon atoms of the diazacycloalkene 'rmga Thearomatic ring of the tetrahydroquinoline and tetrahydroisoquinoline moieties maybe substituted .With halogen atoms, that is, chlorine; bromine and iodine, alkoxy and alkyl groups containing up to four carbon atoms and ihydroxyl groups. The substituents on the partially reduced ring include alkyl groups containing up to four carbon atoms. a a
The substituents on the number four and six carbon atoms of the diazaeyclohexene ring' are alkyl 'groupsconitaining up to four carbon atoms, .In addition to alkyl groups containing up to four carbon atoms, the number five carbon atom of the diazacyclohexene ring may be substituted with a hydroxyl group. I
' The; following list is illustrative of thecompounds Within th'efpur'view of thisinvention. a I
di-n-propyl-1,3-diazacyclohexene-2. (7) 2-(1,2,3',4'-tetrahydro-6',7'- dibromol quinolyl)- 4-isopropyl-1,3-diazacyclohexene-2. V (8) 2-(1',2,3',4'-tetrahydro-5'- chloro-l'- quinolyl)-4,5-, dimethyl-l,3-diazacyclohexene-2. (9) 2-(1',2',3,4- tetrahydro-8'- iodo-1'- quinolyl)-5-hydroxy-1,3-diazacyclohexene-2. 7 (l0) 2-(1,2',3,4' tetrahydro-Z'- isoquinolyl)-l,3 diazacyclohexene-2.
(11) 2-(1",2,3',4- tetrahydro-l-methyl 2'- isoquinolyl) 1,3-diazacycloheXene-2.
(12) 2-(1',2,3',4f-tetrahydro 3'- ethyl-2- isoquinolyl)-4- ethyl-1,3-diazacycloheXene-2. 7 (l3) 2-(1,2,3',4'-tetrahydro 6',7'- di n-butyl 2'- isoquinolyl) -4,5 -di-n-butyl- 1,3 -diazacyclohexene-2.
(14) 2 (1',2,3,4 tetrahydro 3',4 diethyl 2' isoquinolyl)-4,5-diethyl-1,3-diazacyclohexene-2.
(l5) 2-( l,2',3 ,4-tetrahydro-8-bromo-2-isoquinolyl)-4- methyl-1,3-diazacycloheXene-2.
(16) 2-(1,2,3,4-tetrahydro-6'-hydroxy-2- isoquinolyl 1,3 -diazacycloheXene-2.
(17) 2-( 1,2',3.,4'- tetrahydro-2- isoquinolyD-S-hydroxy- 1,3-diazacyclohexene-2. (l8) 2-(1',2',3 ',4-tetrahydro-2'- isoquinolyl) 4,6-diethyl- 1,3-diazacyclohexene-2.
varalltylhalid'eor sulfate and an N-thiocarbamido--1,2,'3,4-
tetrahydroquinoline or N-thiocarbamido-l ,2,3',4-tetrahydroisoquinoline, the quinolyl and isoquinolyl rings being substituted or unsubstituted in: conformance with the description given above. I
The'synthesis applied to an isoquinolyl compound of the present invention is illustrated below.
. HzN-CHz N-og, I '0Ht-11x'+ RSII+ NHi IIIL-C z I Eor the preparation otag-quinolyl compound theiso:
quinolylisothiouronium salt of the aboveequation would be replaced with a quinolyl isothiouronium salt.
aqueous solution.
. sponse of the particular patient.
By reference to the above equation it can be seen that they size of the alkyl or aralkyl group, here represented by R, in the halide or sulfate used to form the isothiouroniurn salt is of no consequence as far as the final structure of the active compounds of my invention is concerned since it is ultimately removed in the form of a mercaptan. It is, however, convenient to use low molecular-weight alkyl halides or sulfates such as methyl iodide or dimethyl sulfate since the mercaptans which are ultimately formed from these types of compounds are relatively volatile and easily removed.
The symbol X in the above equation refers to a chloride, bromide, iodide or sulfate ion which together with the active cation forms a pharmaceutically acceptable acid addition salt. Other pharmaceutically acceptable acid addition salts such as, for example, succinate, maleate, .tartrate, citrate and glycolate can be formed from the halides or sulfates. They can be formed, for example, by converting the halide or sulfate to the free base and treating the free base with the chosen acid in Other methods of obtaining these valuable pharmaceutically acceptable acid addition salts are known to those skilled in the art.
The diaminoalkanes of the above reaction include diaminoalkanes such as, 1,3-diaminopropane and alkyl substituted derivatives wherein the alkyl group and/ or groups which replace the hydrogen and/ or hydrogens on various carbon atoms contain up to four carbon atoms. Also included are the above 1,3-diaminopropanes in which the carbon atom between the two carbon atoms which carry amino groups is substituted with a hydroxyl group. Compounds of this latter type give rise to S-hydroxy-substituted 1,3-diazacyclohexenes-2.
The acid addition salt which is obtained by carrying out the reactions illustrated in the equations given above is converted to the free base by dissolving it in water and neutralizing the acid with a suitable alkaline reagent such as sodium carbonate. The base can be isolated from the water by extraction with an immiscible organic solvent preferably one of low volatility such as methylene chloride or benzene.
More specific directions for the preparation of these valuable compounds can be obtained by reference to the appended examples or by reference to the aforesaid patent application, Synthesis of l,3-diazacycloalkene-2.
The compounds of this invention may be administered alone but are generally administered as a composition with a pharmaceutical carrier selected on-the basis of the chosen route of administration and standard pharmaceutical practice. For example, they may be administered orally in the form of tablets containing such excipients as starch, milk sugar, certain types of clay, etc. They may be administered in capsules either alone .or in admixture with the same or equivalent excipients. They may also be administered orally in the form of elixirs or oral suspensions which may contain flavoring or coloring agents. They may be injected .parenterally, that is, for example, intramuscularly or subcutaneously. For parenteral admisistration they are best used in the form of a sterile aqueous solution which may contain other solutes, for example, enough saline or glucose to make the solution isotonic.
The physician will determine the dosage which will be most suitable for an individual patient and it will vary with the form of administration, the age, weight and re Dosage units containing from 0.1 mg. to 100 mg. are useful. Those dosage unit forms which are prepared for subcutaneous administration will usually contain the lowest concentration of the active ingredient. Dosage forms for intramuscular administration will 'besornewhat higher and those dosage forms intended for oral administration, for example, elixirs, tablets or capsules will contain still more of the active ingredient. I
As might be expected, certain of these compounds are more active than others. For example, better activity is found if substituted alkyl groups which are present are no larger than ethyl or are a combination of ethyl and methyl groups with the majority of them being methyl groups. With alkoxy groups better activity is found if there are no more than two carbon atoms attached to the oxygen. It is better to have no more than two hydroxyl groups on a quinolyl or isoquinolyl group and the preferred halogen substituents are chlorine and bromine with no more than three chlorine atoms'or two bromine atoms on any given compound.
As noted above the compositions of this invention may take a variety of forms. Various diluents may be employed and the percentage of active ingredient may be varied. It is necessary that the active ingredient constitute a proportion of the composition such that a suitable dosage form will be obtained. Obviously several dosage unit forms may be administered at about the same time. Although compositions with less than 0.05% by weight of active ingredients are suitable, it is preferred to use compositions containing at least 0.05% of the active agent. Activity increases with the concentration of the active agent. The percentage by weight of active agent may be 10, 50, 75, or even higher. Dosage unit forms may be prepared with a minor proportion of a carrier and a major proportion of active materials.
The following examples are given solely for the purpose of illustration and are not to be construed as limitations of this invention, many variations of which are possible without departing from the spirit or scope thereof.
EXAMPLE I 2 (1,2,3,4 tetrahydro I quinolyl) 1,3 diazacyclohexene-Z N-thiocarbamido-1,2,3,4-tetrahydroquinoline (50 g.) and 20 ml. of methyl iodide are refluxed in 200 ml. of methanol for one hour. The solution is cooled and most of the solvent removed in vacuo to give a heavy precipitate of the isothiouronium salt which is recovered by filtration. The salt is taken up in an equimolar methanol solution of 1,3-diarninopropane and heated under reflux for ten hours. The solvent is partially removed in vacuo and the acid addition salt recovered by filtration.
The free base is obtained by treating an aqueous solution of the acid addition salt with aqueous potassium carbonate, extracting the aqueous solution with benzene and removing the organic solvent in vacuo.
EXAMPLE 11" 2 (1,2,3',4' tetrahydro I quinolyl) 4(or methyl-1,3-diazacyclohexene-2 N-thiocarbamido-l,2,3,4-tetrahydroquinoline (50 g.) and 20 ml. of methyl iodide are refluxed in 200 ml. of methanol for one hour. The solution is cooled and most of the solvent removed in vacuo to give a heavy precipitate of the isothiouronium salt which is recovered by filtration. The salt is taken up in an equimolar methanol solution of 1,3-diaminobutane and heated under reflux for ten hours. The solvent is partially removed in vacuo and the acid addition salt recovered by filtration.
The free base is obtained by treating an aqueous solution of the acid addition salt with aqueous potassium carbonate, extracting the aqueous solution with benzene and removing the organic solvent in vacuo.
EXAMPLE III 2 (1',2,3',4 tetrtzhydro 6',7' dimethoxy 2' isoquinolyl) -1 ,3-diazacyclohexene-2 salt which is recovered byfiltration. The salt is taken up m an-"equimolar methanol solution of 1-,3-d'iaminop'ro pane and heated under reflux for ten hours. The solvent is partially "removed in vacuo and the acid additions'alt recovered byfiltration. i r i The 'free base 'is obtained by treating an aqueoussolution of the acid additionsalt with aqueous" potassium carbonate, extracting the aqueous solution with benzene and removing the organic solvent in vacuo.
EXAMPLE 1v 2 (1',2,3,4' tetrahy dro 2' isoquinolyl) 1,3 diazacyclohexene-Z N-thiocarbarnido-1,2,3,4 tetrahydroisoquinoline (50 g.) and;2 Q ml. of v methyl bromide are refluxed in 200 ml. of methanol for one hour. The solution is-cooled and most oi the solvent removed invacuo to give a heavy precipitate of the isothiouronium salt which is recovered b filt at nh s'alt s ken P, in n equ m a r e hr anol solution of 1,3 diaminopropane and,v heated under reflux for ten. hours. The solvent ispartially removed in vacuo and the-acid addition san'rec 'verea by"'filtration.
The free base is obtainedby treating an" aqueous solu tion of the acid additionsalt with aqueouspotas'sium cai bonate, extracting the aqueous solution with benzene and removing the organic solvent in vacuo.
EXAMPLE v.
partially removed in vacuo and the acid addition salt re-- covered by filtration. "'Thefree base isobtained by treating an'aqueous solu: tion of the acid addition salt) with aqueous potassium carbonate, extracting the aqueous] solution with benzene and removing the organic solvent in vacuo.
iEXAMRLE I.
N thiocarbamido 6 methoxy 1,2,3,4 tetrahydroquinoline.v(50..g.) and.20. ml. of. benzyl bromide are re fli'ixecLinlOO mLofmethanolfor onehour. The solution is .cooledandmost .of, th e solvent removed in vacuo to give a heavy precipitate of the isothiouronium "salt 'which is recovered by filtration. The salt is taken up in an equimolar methanol solution of 1,3- diaminopropane andhjeated under reflux for-ten hours. The solvent is partially removed in vacuo and theacid additionsaltiecovered by filtration. i i
The free base is obtained'by treating an aqueous solution of the acid addition' salfwith aqueous potassium carbonate, extracting the aqueous solution withbenzene aiidj'removingfthe" organic solvent in vacuo.
EXAMPLE VII N thiocarbamido 6 chloro 1,2,3,4 tetrahydroisoquinoline (50 g.) and,,20,ml. of methyl. iodidefare ,refluxed ,in 200' ml. of ,methanolfor onehour, The solutionis cooled and most of the solvent removed in'vacuo to give a L heavy precipitatej'off the isothiouronium "salt which is recovered;by filtration. -The"sal t is taken up 3253 1 quinolyly and heated under reflux for ten hours.
of methanol for one hour.
EXAMPLE.
2 (1,2',3-,4 tetrahydro methoxy 2' isoquilto lyl) ,3 dia zqcyclohexene 2 N thiocarbamido 6 methoxy 1,2,3,4 tetrahydroisoquinoline (50 g.) and 20 ml. of methyl iodide are refiuxed in 200 ml. of methanol for one hour. The solution is cooled and most of the solvent removed in vacuo to give a heavy precipitate of the isothiouronium salt which is recovered by-filtration. The salt is taken up in an equimolar methanol solution of 1,3-diaminopropane The solvent is partially removed in vacuo and the acid addition salt recoveredby filtration.
The freejbase is obtained by treating an aqueous solution of the acid addition salt with'aqueous potassium car bonate, extracting the aqueous solution With benzene and removing the organic solvent in vacuo.
EX' AMI LE IX 2 (1 ,2',3',4 tetrahydro 1 qu inolyl) 5 hydroxy- 1,3-diazacyclohexenc-2 N thiocarbamido 1,2,3,4 tetrahydroquinoline (50 g.) and-20 m1. 'of methyl-iodide are refluxed in 20.0 ml. The solution is cooled and most of'the solvent removed in vacuo to give a heavy precipitate of the isothiouronium salt which is recovered by filtration; The salt is taken up in an equimolar methanol solution of 1,3-diamino-2-hydroxy propane and heated: under reflux for ten hours. The solvent is partially removed in vacuo and the acid addition salt ree covered by filtration. The free base is obtained by treating an aqueousv solu-. tion of the acid addition salt with aqueous potassium carbonate, extracting the aqueous solution with benzene and removing the organic solvent in vacuo.
EXAMPLE X 2 (1',2',3',4' tetrahydro 6 ,7 diethyl 1' quinolyl)- 1,3-ditzzacycloheicen-2 N thiocarbamido 6,7 diethyl 1,2,3,4 tetrahydro: quinoline (50 g.) and 20 ml. of methyl iodide'afe refluxd in 200 m1. of methanol for one 'hour. The solu' tion 'is cooled and most of the solvent removed in vacuo to giv e a heavy precipitate of the isothiouronium salt which'is recovered by filtration. The salt is taken 'up iii anequimolar methanol solution of'1,3-diaminopr'opane and heated under reflux for ten hours. The solvent is partially removed in vacuo and the acid addition salt re covered by filtration. The free base is obtained by treating an aqueous solution of the acid addition salt with aqueous potassium carbonate, extracting the aqueous solution with benzene and removing the organic solvent in vacuo.
EXAM XI The EXAMPLE X11 2 (1,2,3',4 tetrahydro 6', 7 dichloro 2 isoquinolyl)-1 ,3-diazacyclhexene-2 N thiocarbamido 6,7 dichloro 1,2,3,4 tetrahydroisoquinoline (50 g.) and 20 ml. of methyl iodide are refluxed in 200 ml. of methanol for one hour. The solution is cooled and most of the solvent removed in vacuo to. give a heavy precipitate of the isothiouronium salt which is recovered by filtration. The salt is taken up in an equimolar methanol solution of 1,3-diaminopropane and heated under reflux for ten hours. The solvent is partially removed in vacuo and the acid addition salt recovered by filtration.
The free base is obtained by treating an aqueous solution of the acid addition salt with aqueous potassium carbonate, extracting the aqueous solution with benzene and removing the organic solvent in vacuo.
EXAMPLE XIII 2 (1,2,3,4 tetrahydro 1' quinolyl) 4,5,6 triethyl-I ,3-diazacyclohexene-2 heated under reflux for ten hours. The solvent is partially removed in vacuo and the acid addition salt recovered by filtration.
The free base is obtained by treating an aqueous solution of the acid addition salt with aqueous potassium carbonate, extracting the aqueous solution with benzene 'and removing the organic solvent in vacuo.
EXAMPLE XIV V 2 (1' -,2',3',4' tetrahydro 2',3' dimethyl 1 quinolyl) 1 ,3 -diazacyclohexene-2 N thiocarbamido 2,3 dimethyl 1,2,3,4:tetrahydroquinoline (50 g.) and 20 ml. of methyl iodide are refluxed in 200 ml. ofmethanol for one hour. The solution is cooled and most of the solvent removed in vacuo to give a heavy precipitate of the isothiouronium salt which is recovered by filtration. The salt is taken up in an equimolar methanol solution of 1,3-diaminopropane and heated under reflux for ten hours. The solvent is partially removed in vacuo and the acid addition salt recovered by filtration.
The free base is obtained by treating an aqueous solution of the acid addition salt with aqueous potassium carbonate, extracting the aqueous solution with benzene and removing the organic solvent in vacuo.
EXAMPLE XV N-thiocarbamido-3 -.ethyll,2, 3,4-tetrahydroisoquinoline (50 g.) and 20, ml. of'n-butyl bromide are refluxed in 200" ml. of methanol for one hour. The solution is cooled and most of the solvent removed in vacuo to give aheavy precipitate of the isothiouronium salt which is recovered by filtration. The salt is taken up in an equimolar methanol solution of 1,3-diaminopropane and heated under reflux for ten hours. The solvent is partially 8 removed in vacuo and the acid addition salt recovered by filtration.
The free base is obtained by treating an aqueous solution of the acid addition salt withv aqueous potassium carbonate, extracting the aqueous solution with benzene and removing the organic solvent in vacuo.
EXAMPLE XVI 2-(1',2',3',4'-tetrahydr0-2'-ethyl-is0quinolyl) -1,3-dia-zacyclohexene-Z-glycolate EXAMPLE XVII A tablet base is prepared by blending the following ingredients in the proportion by weight indicated.
Sucrose U. S. P 82.0 Tapioca starch 13.6 Magnesium stearate 4.4
Into this tablet there is blended a sufiicient amount of 2-(1',2,3,4'-tetrahydro-6,7 dimethoxy-2-isoquinolyl)- 1,3-diazacyclohexene-2 to provide tablets each containing 50 mg. of active ingredient.
EXAMPLE XVIII Into the table base of Example XVII there is blended a sufiicient amount of the hydro-iodide salt of 2-(1',2',3',4'- tetrahydro-6-chloro-1'-quinolyl) 1,3-diazacyclohexene-2 to provide tablets each containing 0.5 mg. of active ingredient.
EXAMPLE XIX V A tablet base is prepared by blending the following ingredients in the proportion by weight indicated.
Sucrose U. S. P 80.3 Tapioca starch 13.2 Magnesium'stearate-.. 6.5
Intothis base there is blended a suflicient amount of 2-(1',2,3,4'-tetrahydro 6'-methoxy-1'-quinolyl)-1,3-diazacyclohexene-Z to provide tablets each containing 75 mg. of active ingredient.
EXAMPLE XX Into the tablet base of Example XIX there is blendeda suflicient amount of the hydrobromide salt of 2-(l',2',3', 4-tetrahydro 6'-chloro 2-isoquinolyl)-l,3 diazacyclohexene-Z to provide tablets each containing 0.1 mg. of active ingredient.
EXAMPLE XXI Ten liters of distilled water for injection, U. S; P. are poured into a 20 l. Pyrex glass bottle. To this water is added sufi'icient 2-(1',2',3',4-tetral1ydro-6'-methoxy-2'- isoquinolyl)-l,3-diazacyclohexene-2 hydrobromide to provide a 0.1 percent solution by weight.
9 EXAMPLE xxn A blend is prepared containing the following ingredients:
2-(1,2,3,4'-tetrahydro 1'-quinolyl) 1,3 diazacyclohexene-2 4.00 Magnesium stearate A 0.80 Magnesium stearate B 0.32
This blend is divided and formed into tablets each containing 5 mg. of active ingredient.
What is claimed is:
1. A compound selected from the group consisting of and the pharmaceutically acceptable acid addition salts thereof wherein R and R are each selected from the group consisting of hydrogen, chloro, bromo, iodo, hy-
droxy and alkyl and alkoxy containing up to 4 carbon atoms; R R R and R, are each selected from the group consisting of hydrogen and alkyl containing up to 4 carbon atoms; and R is selected from the group consisting of hydrogen, hydroxy and alkyl containing up to 4 carbon atoms.
2. 2-(l,2',3',4'-tetrahydro 1'-quino1y1) 1,3 diazacyclohexene-2.
3. 2-(1',2',3',4-tetrahydro 2'-isoquinoly1) 1,3-diazacyclohexene-Z.
4. 2-(1,2',3',4'-tetrahydro-ch1oro 2-isoquinoly1)-1,3- diazacyclohexene-Z.
5. 2-(1,2',3,4'-tetrahydro 6'-ch1oro- 2'-isoquinolyl)- 1,3-diazacyclohexene-2.
6. 2-(1,2,3,4'-tetrahydro-alkoxy 2'-isoquinolyl)-1,3- diazacyclohexene-Z wherein the alkoxy group contains up to four carbon atoms.
7. 2-(1',2',3',4'-tetrahydro-6-methoxy -2'-isoquinolyl)- 1,3-diazacyclohexene-2.
8. 2-(1,2,3,4' tetrahydro 6',7' dimethoxy 2'-isoquinolyl)-1,3-diazacyclohexene-2.
9. 2-(1,2',3',4' tetrahydro bromo 2' isoquinoly1)- 1,3-diazacyclohexene-2.
10. 2-(1',2,3,4'-tetrahydro iodo 2'-isoquinolyl)-1,3- diazacyclohexene-Z.
References Cited in the file of this patent Urech et al.: Helvetica Chimica Acta, vol. 33, No. 182, pp. 1386-1407.
Richters Organic Chemistry, volume IV, pp. 4-7 (1947).
' UNITED STATES PATENT OFFICE Certificate of Correction Patent No. 2,876,222 March 3, 1959 Barry M. Bloom It is hereby certified that error appears in the printed specification of the above numbered patent requlrmg correction and that the said Letters Patent should read as corrected below.
Column 9, claim 1, after the formula appearing between lines 20 and 29, insert the following additional formula:
Signed and sealed this 21st day of July 1959.
[smAL] Attest:
KARL H. AXLINE, ROBERT C. WATSON, Attestz'ng Oyficer. aommz'ssz'oner of Patents.
Claims (1)
1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3288805A (en) * | 1966-11-29 | Amino-eviid azoline | ||
US3314963A (en) * | 1962-07-23 | 1967-04-18 | Pfizer & Co C | Azabenzocycloalkane-n-carboxamidines |
US3466286A (en) * | 1958-05-28 | 1969-09-09 | Sandoz Ag | Pyrimidine dyestuffs |
US3549640A (en) * | 1967-11-03 | 1970-12-22 | Mallinckrodt Chemical Works | N-alkylsulfinylalkyl- and sulfonylalkyl-1,2,3,4-tetrahydroisoquinolines |
US3882126A (en) * | 1972-03-21 | 1975-05-06 | Smithkline Corp | 2-amino(and 2-aminomethyl)-2-quinolylthioacetamides |
-
1956
- 1956-10-18 US US616594A patent/US2876222A/en not_active Expired - Lifetime
Non-Patent Citations (1)
Title |
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None * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3288805A (en) * | 1966-11-29 | Amino-eviid azoline | ||
US3466286A (en) * | 1958-05-28 | 1969-09-09 | Sandoz Ag | Pyrimidine dyestuffs |
US3314963A (en) * | 1962-07-23 | 1967-04-18 | Pfizer & Co C | Azabenzocycloalkane-n-carboxamidines |
US3549640A (en) * | 1967-11-03 | 1970-12-22 | Mallinckrodt Chemical Works | N-alkylsulfinylalkyl- and sulfonylalkyl-1,2,3,4-tetrahydroisoquinolines |
US3882126A (en) * | 1972-03-21 | 1975-05-06 | Smithkline Corp | 2-amino(and 2-aminomethyl)-2-quinolylthioacetamides |
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