Abstract: Indanyloxy compounds having 2-alkynyl substituents which exhibit diuretic, saluretic, and uricosuric activity are described. The compounds are obtained according to a process involving selective etherification of a 5-hydroxyindanone followed by alkynylation with a silylated alkynyl bromide to provide novel silylated intermediates which are hydrolyzed to indanyloxy compounds such as (6,7-dichloro-1-oxo-2-phenyl-2-propargyl-5-indanyloxy)acetic acid.

Abstract: A process for preparing 9-cyclohexyl-2-alkoxy-9H-adenine derivatives such as 9-cyclohexyl-2-n-propoxy-9H-adenine from 7-amino-5-(methylthio)[1,2,5]oxadiazolo[3,4-d]pyrimidine and 7-amino-5-(methylthio)[1,2,5]thiadiazolo[3,4-d]pyrimidine is described. Other aspects of the invention are directed to novel intermediates such as the compound 4-amino-6-(cyclohexylamino)-5-(formylamino)-2-(methylthio)pyrimidine.

Abstract: A bronchodilating process employing purine derivatives "9-cyclohexyl-9H-adenine er 9-benzyl-2-n-propoxy-9H-adenine" is disclosed.

Abstract: Adenine derivatives with 2-alkylthio and 9-(2-cyclohexenyl or cyclohexyl) substituents having non-adrenergic bronchodilating properties and use in the treatment or prophylaxis of broncho-constriction in mammals are disclosed.

Abstract: Styrylamidines are prepared by treating styrylsulfonylamidines with base. The styrylamidines are effective in the prevention of aggregation of blood platelets and as analgesics. Compounds of the invention are also useful as anticonvulsants, diuretics, and antihypertensive agents. The styrylsulfonylamidines of the invention which serve as precursors to the styrylamidines also have analgesic properties. Illustrative of the styrylamidines of the present invention are 4-amino-N-(4-aminostyryl)benzamidine and N-(3,4-dichlorostyryl)acetamidine. An example of a styrylsulfonylamidine is N-(styrylsulfonyl)acetamidine.

Abstract: N-Phenyl amidines which have diuretic, antithrombogenic, smooth muscle relaxant, anti-inflammatory and antiarrhythmic properties have been discovered. They are prepared by reacting a substituted aniline with a carboxamide selected from the group consisting of amides and lactams in the presence of phosphorus oxychloride. Typical examples of substituted N-phenyl amidines thus obtained are 5-methyl-2-(N-phenylbenzylamino)-1-pyrroline, 2-(N-phenylbenzylamino)-1-pyrroline, 3-[(N-1-pyrrolin-1-yl-p-anisidino)methyl]indole and 4,5,6,7,8,9-hexahydro-2-(N-phenylphenethylamino)-3H-azonine. Indole substituted N-phenyl amidines can be arranged to provide iminopyrrolinidinylindoles which are useful as diuretic, antithrombogenic and smooth muscle relaxant agents. In the case of 3-[(N-1-pyrrolin-2-yl-p-anisidino)methyl]indole, the rearranged product is 3-[[2-p-methoxyphenylimino)-1-pyrrolidinyl]methyl]indole.

Abstract: Indanyloxy compounds having 2-alkynyl substituents which exhibit diuretic, saluretic, and uricosuric activity are described. The compounds are obtained according to a process involving selective etherification of a 5-hydroxyindanone followed by alkynylation with a silylated alkynyl bromide to provide novel silylated intermediates which are hydrolyzed to indanyloxy compounds such as (6,7-dichloro-1-oxo-2-phenyl-2-propargyl-5-indanyloxy)acetic acid.

Abstract: A new class of alkylthiophenoxypropanolamine derivatives and methods for preparation are described. The compounds have vasodilating and antispasmodic activity, inhibit blood platelet aggregation and are substantially free of beta-adrenergic blocking effects. They are particularly valuable in the treatment of disease states responsive to vasodilation such as obstructive peripheral vascular diseases and cerebral vascular deficiencies. A representative and preferred embodiment of the invention consists of 1-[4-(1-methylethylthio)phenoxy]-3-(octylamino)-2-propanol.

Abstract: New 2-substituted-6-amino-9-tetrahydropyran-2-yl purine derivatives are disclosed. They are orally active bronchodilators with relatively little cardiovascular side effects. A representative and preferred embodiment of this invention is 2-n-propoxy-9-(tetrahydropyran-2-yl)-9H-adenine.

Abstract: 2-Aminothiophene-3-carboxamides are converted to oxamates or fumaramides by acylation of the amino group. Cyclization yields thieno[2,3-d]pyrimidines which may also be prepared from the corresponding oxazines. Compounds illustrative of those having inhibitory action on the immediate hypersensitivity reaction in mammals are N-[3-(aminocarbonyl)-4,5,6,7-tetrahydrobenzo[b]thien-2-yl]oxamic acid, ethyl 5,6,7,8-tetrahydro-4-oxo-4H-benzothieno[2,3-d][1,3]oxazine-2-carboxylate, and ethyl 3,4-dihydro-6-ethyl-4-oxothieno[2,3-d]pyrimidine-2-carboxylate.

Abstract: 1-Phenoxy-3-[(3-indolyl)-tert.-butyl]amino-2-propanols and related 1-aryloxy compounds are antihypertensive agents having vasodilator and adrenergic .beta.-receptor blocking action. Preferred compounds bear an ortho-substituent in the phenoxy group, and most preferably the cyano group.

Abstract: Improved processes for preparing 2'-alkoxy-2,5-di-substituted-9-oxo-6,7-benzomorphans from benz[e]indolines and synthesis of the benz[e]indoline intermediates are described. A representative example involves synthesis of 9b-allyl-8-methoxy-3-methyl-5,9b-dihydrobenz[e]indoline and bromination thereof to 9b-allyl-4-bromo-8-methoxy-2,4,5,9b-tetrahydro-1H-benz[e]indole methylbromide which is then hydrolyzed with a weak base such as ammonium bicarbonate to provide 5-allyl-2'-methoxy-2-methyl-9-oxo-6,7-benzomorphan.

Abstract: A novel crystalline monohydrate of 7-[D-.alpha.-amino-.alpha.-(p-hydroxyphenyl)acetamido]-3-methyl-3-cephem-4 -carboxylic acid is prepared and found to be a stable useful form of the cephalosporin antibiotic especially advantageous for pharmaceutical formulations.

Abstract: New orally active bronchodilating 6-amino-purine derivatives substituted in the two position with alkylamino or cyclohexylamino and in the nine position with 2-cyclohexenyl or cyclohexyl are disclosed.

Abstract: Styrylamidines are prepared by treating styrylsulfonylamidines with base. The styrylamidines are effective in the prevention of aggregation of blood platelets and as analgesics. Compounds of the invention are also useful as anticonvulsants, diuretics, and antihypertensive agents. The styrylsulfonylamidines of the invention which serve as precursors to the styrylamidines also have analgesic properties. Illustrative of the styrylamidines of the present invention are 4-amino-N-(4-aminostyryl)benzamidine and N-(3,4-dichlorostyryl)acetamidine. An example of a styrylsulfonylamidine is N-(styrylsulfonyl)acetamidine.

Abstract: N-substituted-14-hydroxy-3-substituted-morphinan derivatives have been found to possess potent narcotic agonist or antagonist activity. In particular, the compound N-Cyclobutylmethyl-3,14-dihydroxymorphinan has been found to possess potent agonist/antagonist activity as a non-narcotic analgesic. A new and efficient total synthesis of these compounds is described herein from the starting material 2-(p-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline.

Abstract: N-Phenyl amidines which have diuretic, antithrombogenic, smooth muscle relaxant, anti-inflammatory and antiarrhythmic properties have been discovered. They are prepared by reacting a substituted aniline with a carboxamide selected from the group consisting of amides and lactams in the presence of phosphorus oxychloride. Typical examples of substituted N-phenyl amidines thus obtained are 5-methyl-2-(N-phenylbenzylamino)-1-pyrroline, 2-(N-phenylbenzylamino)-1-pyrroline, 3-[(N-1-pyrrolin-]-yl-p-anisidino)methyl]indole and 4,5,6,7,8,9-hexahydro-2-(N-phenylphenethylamino)-3H-azonine. Indole substituted N-phenyl amidines can be rearranged to provide iminopyrrolinidinyl-indoles which are useful as diuretic, antithrombogenic and smooth muscle relaxant agents. In the case of 3-[(N-1-pyrrolin-2-yl-p-anisidino)methyl]indole, the rearranged product is 3-[[2-(p-methoxyphenylimino)-1-pyrrolidinyl]methyl]indole.

Abstract: A series of 2,6-diamino-4-tertiary-amino-pyridine 1-oxides is disclosed. Substituents in the 4-position include diethylamino, pyrrolidinyl, piperidino, morpholino, thiomorpholino, and N-methylpiperazino. Novel oxadiazolones such as 5-amino-7-(1-piperidinyl)-2H-[1,2,4]-oxadiazolo[2,3-a]pyridine-2-one which are useful in the preparation of the pyridine 1-oxides are also disclosed. The compounds of this invention lower blood pressure in normotensive and hypertensive mammals and are particularly useful in the treatment of hypertensive conditions in mammals. 2,6-Diamino-4-(1-piperidinyl)pyridine 1-oxides is a prepresentative embodiment of the invention.

Abstract: A mucolytic process is disclosed which comprises contacting N-(2-hydroxyethyl)mercaptoacetamidobenzamides or mercaptoacylamidobenzoic acids, mercaptoacetylsulfanilic acids and alkanoylthio derivatives thereof with mucus. Illustrative of compounds useful in the mucolytic process of the present invention are 4-(2-mercaptoacetamido)benzoic acid and N-(2-mercaptoacetyl)sulfanilic acid.

Abstract: A series of novel 4-amino-2-(thiadiazole-carbonyl piperazinyl)-6,7-dimethoxyquinazolines is disclosed having antihypertensive properties. The thiadiazole substituent may be optionally substituted with alkyl or lower alkoxy carbonylamino groups. A representative embodiment of the invention is 4-amino-6,7-dimethoxy-2-[4-(5-ethoxy-carbonylamino-1,2,3-thiadiazole-4-car bonyl)-piperazin-1-yl]-quinazoline.