American Home Products Corporation

Dong H Kim

Ronald J McCaully

Stanley Charles Bell

Arthur Attilio Santilli

Disclosed herein are 4-phenyl-tetrahydro-isoxazolo[5,4-b]-pyridine-5-carboxylic acid esters of Formula I: ##STR1## wherein Ar is phenyl or phenyl substituted by a halogen, nitro, or trifluoromethyl group; R.sup.1 is C.sub.1-3 alkyl; and R.sup.2 is C.sub.1-5 alkyl, (C.sub.1-5) alkoxy (C.sub.1-3)-alkyl, or mono- or di(C.sub.1-5) alkylamino (C.sub.1-3)alkyl; or physiologically acceptable acid addition salts thereof. The compounds of the invention exhibit calcium antagonist and antihypertensive properties in standard pharmacological procedures.

3A,4,7,7a-tetrahydro-3,6,7a-trimethyl-4-substituted

Disclosed herein is a process for obtaining indoline-2-carboxylic acid ester tin complexes directly from o-nitropyruvic acids using metallic tin and dry hydrogen chloride gas in a lower alkanol solvent, at atmospheric pressures.

Tin complexes of indoline-2-carboxylic acids and esters prepared from

Disclosed herein are 2,3-dihydro-1H-indole-2-carboxylic acids substituted on the nitrogen with 3-mercapto-2-alkyl-1-oxoalkyl, 3-phosphoryl-2-alkyl-1-oxopropyl, or 2-amino-2-alkyl-1-oxoalkyl derivatives which act as inhibitors of angiotensin converting enzyme and as antihypertensive agents. The compounds of the invention (excluding disclosed intermediates) have the general formula: ##STR1## wherein: n is 1 or 0;

N-(2-Substituted-1-oxoalkyl)-2,3-dihydro-1H-indole-2-carboxylic acid

Disclosed herein are 2,3-dihydro-1H-indole-2-carboxylic acids substitued on the nitrogen with 3-mercapto-2-alkyl-1-oxoalkyl, 3-phosphoryl-2-alkyl-1-oxopropyl, or 2-amino-2-alkyl-1-oxoalkyl derivatives which act as inhibitors of angiotensin converting enzyme and as antihypertensive agents. The compounds of the invention (excluding disclosed intermediates) have the general formula: ##STR1## wherein: n is 1 or 0;

N-[2-Substituted-1-oxoalkyl]-2,3-dihydro-1H-indole-2-carboxylic acid

Disclosed herein are .alpha.-[(alkylamino)methyl]-.beta.-aryloxy-benzeneethanols exhibiting antiarrhythmic activity and having the following formula: ##STR1## wherein R is hydrogen, halogen, lower alkyl, or lower alkoxy; X is phenyl, 1-naphthyl, or a phenyl group substituted by a halogen, a lower alkyl group, or a lower alkoxy group; R.sub.1 is lower alkyl; and pharmacologically acceptable acid addition salts thereof. Also disclosed is a process for the addition of an aryloxy group at the 3-position of a 3-phenyl-2-oxiranecarboxamide to produce an .alpha.-hydroxy-.beta.-aryloxy-benzenepropanamide, said process comprising contacting an alkali metal aryloxide with said 3-phenyl-2-oxiranecarboxamide in the presence of a crown ether. Such .alpha.-hydroxy-.beta.-aryloxy-benzenepropanamides may then be reduced to produce the compounds of the invention.

Process for preparing

Disclosed herein are N-(3-mercapto-2-alkyl-1-oxopropyl)-2,3-dihydro-1H-indole-2-carboxylic acids and derivatives thereof which act as inhibitors of angiotensin converting enzyme and as anti-hypertensive agents. Derivatives include those in which the 3-mercapto group is substituted with phosphate derivatives or is replaced by a variously substituted amino group. The compounds of the invention (excluding disclosed intermediates) have the general formula: ##STR1## wherein: n is 1 or 0;

1,1'-[Dithiobis(2-alkyl-1-oxo-3,1-propanediyl)]-bis[2,3-dihydro-1H-indole

Disclosed herein are N-(3-mercapto-2-alkyl-1-oxopropyl)-2,5-dihydro-1H-indole-2-carboxylic acids and derivatives thereof which act as inhibitors of angiotensin converting enzyme and as anti-hypertensive agents. Derivatives include those in which the 5-mercapto group is substituted with phosphate derivatives or is replaced by a variously substituted amino group. The compounds of the invention (excluding disclosed intermediates) have the general formula: ##STR1## wherein: n is 1 or 0;

10,10a-Dihydro-1H-thiozino[4,3-a,]-indole-1,4(3H)-diones

Disclosed herein are 3[[(2,3-dihydro-1H-indole-2-yl)carbonyl]thio]propanoic (and acetic) acids of the general formula: ##STR1## wherein: n is 1 or 0;

3-[[(2,3-Dihydro-1H-indol-2-yl)carbonyl]thio]propanoic (and acetic)

Disclosed herein are .alpha.-[(alkylamino)-methyl]-.beta.-aryloxy-benzeneethanols exhibiting antiarrhythmic activity and having the following formula: ##STR1## wherein R is hydrogen, halogen, lower alkyl, or lower alkoxy; X is phenyl, 1-naphthyl, or a phenyl group substituted by a halogen, a lower alkyl group, or a lower alkoxy group; R.sub.1 is lower alkyl; and pharmacologically acceptable acid addition salts thereof. Also disclosed is a process for the addition of an aryloxy group at the 3-position of a 3-phenyl-2-oxiranecarboxamide to produce an .alpha.-hydroxy-.beta.-aryloxy-benzenepropanamide, said process comprising contacting an alkali metal aryloxide with said 3-phenyl-2-oxiranecarboxamide in the presence of a crown ether. Such .alpha.-hydroxy-.beta.-aryloxy-benzenepropanamides may then be reduced to produce the compounds of the invention.

.alpha.-[(Alkylamino)-methyl]-.beta.-aryloxy-benzeneethanols exhibiting

1H,5H-[1,4]Thiazepino[4,3-a]indole-1,5-diones

The invention is directed to 4-amino-2-phenyl-6-thiopyrimidine compounds having the formula ##SPC1## Where R.sup.1 -R.sup.3 are as defined in the specification. The compounds have pharmacodynamic activity as central nervous system depressants. That is, they produce a calming effect in the host.

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Wayne, PA, United States of America

Dong H Kim