Patent GB-1514572-A (GB)
Title: 2,5-methanobenzo(g)quinolines
IPC: A61K31/435
Filed: 1975-05-19
Abstract: 1514572 Methanobenzoquinolines STERLING DRUG Inc 19 May 1975 [20 May 1974 12 May 1975] 27040/77 Divided out of 1514571 Heading C2C Novel methanobenzoquinolines of the general Formula II wherein R 1  is hydrogen, C 1-7 -alkyl, C 3-7 -alkenyl, C 3-7 -alkynyl, halo-C 3-7 -alkenyl, C 3-6 -cycloalkyl, C 3-6 -cycloalkyl-C 1-7 -alkyl, 2- or 3-furyl-methyl, or such 2- or 3-furylmethyl substituted on the unsubstituted ring carbon atoms by from one to three methyl groups, phenyl C 1-7 -alkyl, or phenyl-C 1-7 -alkyl substituted in the phenyl ring by from one to two members selected from halogen, C 1-7 -alkyl, hydroxy, C 1-4 -alkanoyloxy, C 1-7 -alkoxy, C 1-7 -alkylmercapto, trifluoromethy, amino and C 1-4 -alkanoylamino or a single methylenedioxy attached to adjacent carbon atoms; R 2 , R 2 <SP>1</SP> and R 2 <SP>11</SP> are each hydrogen, or two of them are hydrogen and the other is halogen, C 1-7 -alkyl, hydroxy, C 1-4 -alkanoyloxy, C 1-7  - alkoxy, C 1-7  - alkylmercapto, trifluoromethyl, nitro, amino, C 1-4 -alkanoylamino, C 1-7 - alkoxycarbonylamino or phenyl, or one is hydrogen and the remaining R 2  and R 2 <SP>1</SP> or R 2  and R 2 <SP>11</SP> together are methylenedioxy; R 3  is hydrogen or C 1-7 -alkyl; R 4  is hydrogen, C 1-7 - alkyl, C 1-7 -alkoxy-C 1-7 -alkyl, hydroxy-C 1-7 -alkyl C 1-7  - alkylthio - C 1-7  - alkyl, C 1-7  - alkylsulfinyl- C 1-7  - alkyl, phenylthio - C 1-7  - alkyl, phenylsulfinyl - C 1-7  - alkyl, C 3-7  - alkenyl or halo- C 1-7 -alkyl, or R 3  and R 4  together are divalent alkylene, -(CH 2 ) n -, where n is one of the integers 3 or 4; R 8  is hydrogen or C 1-7 -alkyl (only in the #-configuration); and Y is carboxy, cyano, carbo-C 1-7 -alkoxy, COR 5 , COO -C 1-4 - alkylene - C 3-6  - cycloalkyl, COO - C 1-4  - alkylenephenyl, or a group of the formula where R 5  and R 6  are each hydrogen, C 1-7 -alkyl, phenyl or phenyl-C 1-7 -alkyl except that R 5  cannot be hydrogen in COR 5  ; and R 7  is hydrogen, C 1-4 -alkanoyl, benzoyl or benzoyl substituted by one to three members selected from C 1-7 - alkyl, C 1-7 -alkoxy, hydroxy, halogen and trifluoromethyl, and acid addition salts thereof are prepared by subjecting to an acid-catalysed cyclization an azabicyclooctene of the Formula IV wherein Y<SP>1</SP> is carboxy, cyano, carbo-C 1-7 - alkoxy, COO - C 1-4  - alkylene - cycloalkyl, COO-C 1-4 -alkylene-phenyl or COR 5  where R 5  is C 1-7 -alkyl to prepare a compound of the Formula IIB where Y corresponds to Y<SP>1</SP>, if desired, reacting a compound of the Formula IIB obtained with a strong base followed by treatment with an acid or with a C 1-7 -alkyl ester of a strong mineral acid to obtain the corresponding compound of Formula IIA wherein R 8  is hydrogen or C 1-7 -alkyl, respectively, if desired, reacting a compound of the Formula II obtained wherein Y is carboxy with an appropriate esterifying agent to obtain the corresponding ester where Y is carbo-C 1-7 - alkoxy, COO-C 1-4 -alkylene-C 3-6 -cycloalkyl or COO-C 1-4 -alkylenephenyl, if desired, hydrolysing a compound obtained wherein Y is cyano to the corresponding compound wherein Y is carboxy, if desired, reacting one mole of a compound obtained wherein Y is carboxy with two moles of an organo lithium R 5 Li (where R 5  is other than hydrogen) to prepare a corresponding compound wherein Y is COR 5 , if desired, reacting one mole of a compound wherein Y is carbo- C 1-7  - alkoxy, COO - C 1-4  - alkylene - C 3-6 - cycloalkyl or COO - C 1-4  - alkylene - phenyl with two moles of R 5 Li or R 6 Li to give the corresponding compound wherein Y is where R 5  and R 6  are the same and are other than hydrogen and R 7  is hydrogen, if desired, reacta compound obtained where Y is COR 5  where R 5  is other than hydrogen with R 6 Li to give the corresponding compound wherein Y is where R 5  and R 6  are the same or different and are other than hydrogen, if desired, reducing a compound obtained wherein Y is COR 5  or carbo - C 1-7  - alkoxy, COO - C 1-4  - alkylene- C 3-6  - cycloalkyl or COO - C 1-4  - alkylene - phenyl ester with an alkali metal aluminium hydride or an alkali metal borohydride to obtain the corresponding compound wherein Y is and R 6  and R 7  are each hydrogen and R 5  is other than hydrogen (from the ketone) or hydrogen (from the ester), if desired, esterifying a compound of the Formula II obtained wherein Y is -CR 5 R 6 -OR 7  and R 7  is hydrogen to obtain the corresponding compound wherein R 7  is C 1-4 -alkanoyl, benzoyl or substituted benzoyl and, if desired, converting a basic compound obtained to an acid-addition salt thereof.  Azabicyclooctenes of the general Formula IV are prepared by reacting compounds of the Formulµ VI and VII wherein Hal is halogen, followed by treatment with CH 2  = CHY<SP>1</SP>. Ethyl 1 - methyl - 5α - vinyl - 1,2,3,4,4a,5,10,- 10a - octahydro - 2,5 - methanobenzo[g]quinoline- 3#-carboxylate hydrochloride is prepared by distilling the corresponding 5α-[2-(phenyl sulphinyl)ethyl] under reduced pressure and treating the product with HCl. Pharmaceutical compositions having analgesic activity comprise, as active ingredient, a methanobenzoquinoline of the Formula II, together with a suitable carrier.