Patent GB-1199768-A (GB)
Title: Nitrogen Heterocycles and process for their preparation
IPC: C07D217/22
Filed: 1967-10-27
Abstract: 1,199,768. Quinazoline, quinoline and isoquinoline derivatives. CHAS PFIZER & CO. Inc. 27 Oct., 1967 [31 Oct., 1966], No. 49047/67. Heading C2C. The invention comprises compounds of formula and their acid addition salts, wherein A and B are each OH, Me or C 1-5  alkoxy, or one of them is H, or A-B is benzo or C 1-4  alkylenedioxy; R<SP>1</SP> is H, C 1-6  alkyl (possibly halogenated) Ph, PhCH 2 , PhC 2 H 4  or substituted Ph; D<SP>1</SP> and D<SP>2</SP> are each N or one of them is CH; when D<SP>1</SP> and D<SP>2</SP> are both N, Y is NR<SP>2</SP>R<SP>3</SP>, where R<SP>2</SP>, R<SP>3</SP> are each H, alkyl, alkenyl, hydroxyalkyl or cycloalkyl (up to C 6 ), Ph or Ph-C 1-6 -alkyl, or R<SP>2</SP>R<SP>3</SP> complete with the N a saturated 4- or 5- membered ring, or Y is piperidino, morpholino or 4-R<SP>4</SP>-piperazino or -homopiperazino, R<SP>4</SP> being H, alkyl, alkylcarbonyl, MeSO 2 , PhSO 2 , alkoxycarbonyl, alkenyl or alkenyloxycarbonyl (up to C 6  in the alkyl or alkenyl groups), benzoyl, naphthoyl, aryl or aryloxycarbonyl (up to C 10  in the aryl group), or Y is 4-(JCR<SP>13</SP>R<SP>15</SP>CR<SP>5</SP>R<SP>14</SP>OCO)-piperazino or -homopiperazino, where each of R<SP>5</SP>, R<SP>13</SP>, R<SP>14</SP>, R<SP>15</SP> is H, C 1-4  alkyl or CH 2 OH or R<SP>5</SP>-C-C-R<SP>13</SP> is C 6-9  cycloalkyl, and J is H, Cl, Br, OH, C 1-5  acyloxy, C 1-5  alkoxy, C 1-5  acylamido, aryloxy, aroyloxy or aroylamido (up to C 10  in the aryl group), amino (possibly substituted by 1 or 2 C 1-4  alkyl or up to C 10  aryl groups) or a saturated C 4 N-C 7 N ring; when D<SP>1</SP> is CH and D<SP>2</SP> is N, Y is NR<SP>6</SP>R<SP>7</SP> where R<SP>6</SP>, R<SP>7</SP> are each H, C 1-6  alkyl, C 2 H 4 OH, up to C 10  aryl or aryl (up to C 7 )-C 1-3  alkyl (the aryl groups optionally bearing up to 3 substituents, which are halogen or C 1-4  alkoxy), or NR<SP>6</SP>R<SP>7</SP> is a saturated 4- to 8-membered ring, or Y is morpholino, thiamorpholino or 4-X-piperazino [where X is H, C 3-6  alkenylamino, up to C 6  acylamino, (C 1-6 -alkoxy) carbonylamino, (up to C 6 - alkenyloxy) carbonylamino, or arylamino, aroylamino or carbaryloxyamino (up to C 10  in the aryl group)]; or when either D<SP>1</SP> or D<SP>2</SP> is CH and the other is N, Y is 4-(JCR<SP>13</SP>R<SP>15</SP>CR<SP>5</SP>R<SP>14</SP>OCO)- piperazino as defined above. These compounds are prepared by standard methods. Starting materials and intermediates.-Details are given of the preparation of N-carbethoxy-6- aminoveratric acid, 4,5-dimethoxy-N-carbozy - anthranilic anhydride, 6-aminoveratramide, 6- propionamidoveratramide, 2 - ethyl - 6,7 - dimethoxy - 4(3H) - quinazolinone, 2 - ethyl- or methyl - 4 - chloro 6,7 - dimethoxyquinazoline, 6,7 - dimethoxy - 4 - (3H) - quinazolinone, 4 - chloro - 6,7 - dimethoxyquinazoline, phenyl 4 - (6,7 - dimethoxyquinazolin - 4 - yl) piperazine - 1 - thiolcarboxylate, N - carbethoxyhomoveratrylamine, 6,7 dimethoxy - 3,4 - dihydro - 1(2H) - isoquinolinone, 6,7 - dimethoxy - 1(2H) - isoquinolinone, 1 - chloro - 6,7 - dimethoxyisoquinoline and phenyl 4- (6,7 - dimethoxyisoquinolin - 1 - yl) - piperazine - 1-thiolcarboxylate. Therapeutic compositions for inhaling or oral, intravenous or intramuscular administration comprise compounds of the above formula, which are bronchodilators, antihypertensives and muscle relaxants, and inhibit the activity of phosphodiesterase.