3,4-dihydrobenzopyran derivatives and medicinal uses thereof

Claim 2

A 3,4-dihydrobenzopyran derivative of the formula ##STR93## wherein R 1 and R 4 each represent a hydrogen atom or a lower alkyl group; R 2 represents a hydrogen atom, a halogen atom, a lower alkoxyl group or a lower alkenyloxy group; R 3 represents a hydrogen atom, a lower alkyl group or a lower alkoxyl group; R represents a group of the following formula (2) ##STR94## wherein n represents an integer of 0, 1 or 2; X 2 represents a methylene group or a carbonyl group; when X 2 represents a naphthylene group, R 6 represents a lower alkyl group or a lower alkyl group substituted by a hydroxyl group, ##STR95## and when X 2 represents a carbonyl group, R 6 represents ##STR96## where p and q each represent an integer of 0 to 4; X 3 represents a methylene group or a carbonyl group; Q 1 represents a nitrogen atom (═N--) a carbon atom ##STR97## where R 111 represents a hydrogen atom, a lower alkoxyl group, a halogen atom, a di-lower alkylamino group or a nitro group; R 71 , R 81 , R 91 and R 101 each represent a hydrogen atom or a lower alkoxyl group; Q 2 represents a nitrogen atom (═N--), a carbon atom ##STR98## where R 112 represents a hydrogen atom, a lower alkoxyl group, a halogen atom, a di-lower alkylamino group or a nitro group; and R 72 , R 82 , R 92 and R 102 each represent a hydrogen atom or a lower alkoxyl group; or a pharmacologically acceptable salt thereof.

Claim 3

The compound of claim 1, which is a 3,4-dihydrobenzopyran derivative of the formula ##STR99## wherein R 1 , R 2 , R 3 , R 4 and n have the same meanings as defined hereinbefore; R 61 represents ##STR100## where p, R 71 , R 81 , R 91 , R 101 , Q 1 and X 3 have the same meanings as defined hereinbefore or a pharmacologically acceptable salt thereof.

Claim 4

The compound of claim 2, which is a 3,4-dihydrobenzopyran derivative of the formula ##STR101## wherein R 11 , R 31 and R 41 each represent a lower alkyl group; R 21 represents a lower alkoxyl group; R 62 represents ##STR102## where p and X 3 have the same meanings as defined hereinbefore and R 14 , R 15 and R 16 each represent a lower alkoxyl group and are present in the 2,3,4- or 3,4,5-positions of the benzene ring or a pharmacologically acceptable salt thereof.

Claim 5

The compound of claim 1, which is a 3,4-dihydrobenzopyran derivative of the formula ##STR103## wherein R 1 , R 2 , R 3 , R 4 , X 2 and n have the same meanings as defined hereinbefore; when X 2 is a methylene group, R 63 represents a lower alkyl group or a lower alkyl group substituted by a hydroxyl group, ##STR104## and when X 2 is a carbonyl group, R 63 represents ##STR105## where g, R 71 , R 81 , R 91 , R 101 , Q 1 , R 72 , R 82 , R 82 , R 92 , R 102 and Q 2 have the same meanings as defined hereinbefore or a pharmacologically acceptable salt thereof.

Claim 6

The compound of claim 4, which is a 3,4-dihydrobenzopyran derivative of the formula ##STR106## wherein R 73 , R 83 and R 93 each represent a hydrogen atom or a methoxy group; when all of R 73 , R 83 and R 93 represent hydrogen atoms, either one of X 2 and X 3 represent a methylene group with the other group being a carbonyl group, all or R 12 , R 32 and R 42 represent hydrogen atoms and R 22 represents a chlorine atom, or all of R 12 , R 32 and R 42 represent methyl groups and R 22 represents a methoxy group; or when R 73 and R 83 each represent a methoxy group, R 93 represents a hydrogen atom, X 2 represents a methylene group or a carbonyl group and X 3 represents a methylene group, or when R 73 represents a hydrogen atom, R 83 and R 93 each represent a methoxy group, X 2 represents a methylene group and X 3 represents a carbonyl group, all of R 12 , R 32 and R 42 represent methyl groups and R 22 represents a methoxy group or all of R 12 , R 22 and R 42 represent hdyrogen atoms and R 32 represents a methoxy group; or a pharmacologically acceptable salt thereof.

Claim 7

The compound of claim 4, which is a 3,4-dihydrobenzopyran derivative of the formula ##STR107## wherein R 64 represents a lower alkyl group substituted by a hydroxyl group or a pharmacologically acceptable salt thereof.

Claim 8

The compound of claim 1 which is 3,4-dihydro-6-methoxy-2-[2-(piperazin-1-yl)ethyl]-2,5,7,8-tetramethyl-2H-benzopyran.

Claim 9

The compound of claim 1 which is 3,4-dihydro-6-methoxy-2-[2-[4-(3-methyl-2-butenyl)piperazin-1-yl]-ethyl]-2,5,7,8-tetramethyl-2H-benzopyran.

Claim 10

The compound of claim 1 which is 3,4-dihydro-6-methoxy-2-[2-[4-(3,7-dimethyl-2,6-octadienyl)piperazin-1-yl]ethyl]-2,5,7,8-tetramethyl-2H-benzopyran.

Claim 11

The compound of claim 1 which is 3,4-dihydro-6-methoxy-2-[2-[4-(3,7,11-trimethyl-2,6,10-dodecatrienyl)piperazin-1-yl]ethyl]-2,5,7,8-tetramethyl-2H-benzopyran.

Claim 12

The compound of claim 1 which is 3,4-dihydro-6-methoxy-2-[2-[4-(3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraenyl)piperazin-1-yl]ethyl]-2,5,7,8-tetramethyl-2H-benzopyran.

Claim 13

The compound of claim 1 which is 3,4-dihydro-6-methoxy-2-[2-[4-(3,4,5-trimethoxybenzoyl)piperazin-1-yl]ethyl]-2,5,7,8-tetramethyl-2H-benzopyran.

Claim 14

The compound of claim 1 which is 3,4-dihydro-6-methoxy-2-[2-[4-(3,4,5-trimethoxybenzyl)piperazin-1-yl]ethyl]-2,5,7,8-tetramethyl-2H-benzopyran.

Claim 15

The compound of claim 1 which is 1-[2-(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)ethyl]-4-(4-methoxybenzoyl)piperazine.

Claim 16

The compound of claim 1 which is 1-[2-(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)ethyl]-4-(4-dimethylaminobenzoyl)piperazine.

Claim 17

The compound of claim 1 which is 1-[2-(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)ethyl]-4-(4-nitrobenzoyl)piperazine.

Claim 18

The compound of claim 1 which is 1-[2-(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)ethyl]-4-(4-bromobenzoyl)piperazine.

Claim 19

The compound of claim 1 which is 1-[2-(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)ethyl]-4-(4-pyridylcarbonyl)piperazine.

Claim 20

The compound of claim 1 which is 1-[2-(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)ethyl]-4-(5,9,13-trimethyl-4,8,12-tetradecatrienoyl)piperazine.

Claim 21

The compound of claim 1 which is 1-[2-(3,4-dihydro-7-methoxy-2-methyl-2H-benzopyran-2-yl)ethyl]-4-(3,4,5-trimethoxybenzoyl)piperazine.

Claim 22

The compound of claim 1 which is 1-[2-(6-chloro-3,4-dihydro-2-methyl-2H-benzopyran-2-yl)ethyl]-4-(4-methoxybenzoyl)piperazine.

Claim 23

The compound of claim 1 which is 1-[3-(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)propyl]-4-(4-methoxybenzoyl)piperazine.

Claim 24

The compound of claim 1 which is 1-[(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)acetyl]-4-(2,3,4-trimethoxybenzyl)piperazine.

Claim 25

The compound of claim 1 which is 1-[(6-chloro-3,4-dihydro-2-methyl-2H-benzopyran-2-yl)acetyl]-4-(2,3,4-trimethoxybenzyl)piperazine.

Claim 26

The compound of claim 1 which is 1-[(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)carbonyl]-4-(2,3,4-trimethoxybenzyl)piperazine.

Claim 27

The compound of claim 1 which is 1-[2-(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)ethyl]-4-(2,3,4-trimethoxybenzyl)piperazine.

Claim 28

The compound of claim 1 which is 1-benzoyl-4-[2-(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)ethyl]piperazine.

Claim 29

The compound of claim 1 which is 1-[2-(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)ethyl]-4-methylpiperazine.

Claim 30

The compound of claim 1 which is 1-[2-(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)ethyl]-4-isopentylpiperazine.

Claim 31

The compound of claim 1 which is 1-[2-(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)ethyl]-4-(2-hydroxyethyl)piperazine.

Claim 32

The compound of claim 1 which is 1-[2-(3,4-dihydro-6-methoxy-2,5,7,8-tetramethyl-2H-benzopyran-2-yl)ethyl]-4-(3-hydroxypropyl)piperazine.

Claim 33

A pharmaceutical composition for the treatment of peptic ulcer, cough or sputum, said composition comprising an amount effective to treat peptic ulcer, cough or sputum of a 3,4-dihydrobenzopyran derivative of the formula ##STR108## wherein R 1 and R 4 each represent a hydrogen atom or a lower alkyl group; R 2 represents a hydrogen atom, a halogen atom, a lower alkoxyl group or a lower alkenyloxy group; R 3 represents a hydrogen atom, a lower alkyl group or a lower alkoxyl group; R represents a group of the following formula (2) ##STR109## wherein n represents an integer of 0, 1 or 2; X 2 represents a methylene group or a carbonyl group; when X 2 represents a methylene group, R 6 represents a lower alkyl group or a lower alkyl group substituted by a hydroxyl group, ##STR110## and when X 2 represents a carbonyl group, R 6 represents ##STR111## where p and q each represent an integer of 0 to 4; X 3 represents a methylene group or a carbonyl group; Q 1 represents a nitrogen atom (═N--), a carbon atom ##STR112## where R 111 represents a hydrogen atom, a lower alkoxyl group, a halogen atom, a di-lower alkylamino group or a nitro group; R 71 , R 81 , R 91 and R 101 each represent a hydrogen atom or a lower alkoxyl group; Q 2 represents a nitrogen atom (═N--), a substituted carbon atom ##STR113## where R 112 represents a hydrogen atom, a lower alkoxyl group, a halogen atom, a di-lower alkylamino group or a nitro group; and R 72 , R 82 , R 92 and R 102 each represent a hydrogen atom or a lower alkoxyl group; or a pharmacologically acceptable salt thereof and a pharmaceutically acceptable diluent or carrier.

Claim 34

A pharmaceutical composition for the treatment of peptic ulcer, cough or sputum, said composition comprising an amount effective to treat peptic ulcer, cough or sputum of a 3,4-dihydrobenzopyran derivative of the formula ##STR108## wherein R 1 and R 4 each represent a hydrogen atom or a lower alkyl group; R 2 represents a hydrogen atom, a halogen atom, a lower alkoxyl group or a lower alkenyloxy group; R 3 represents a hydrogen atom, a lower alkyl group or a lower alkoxyl group; R represents a group of the following formula (2) ##STR109## wherein n represents an integer of 0, 1 or 2; X 2 represents a methylene group or a carbonyl group; when X 2 represents a methylene group, R 6 represents a lower alkyl group or a lower alkyl group substituted by a hydroxyl group, ##STR110## and when X 2 represents a carbonyl group, R 6 represents ##STR111## where p and q each represent an integer of 0 to 4; X 3 represents a methylene group or a carbonyl group; Q 1 represents a nitrogen atom (═N--), a carbon atom ##STR112## where R 111 represents a hydrogen atom, a lower alkoxyl group, a halogen atom, a di-lower alkylamino group or a nitro group; R 71 , R 81 , R 91 and R 101 each represent a hydrogen atom or a lower alkoxyl group; Q 2 represents a nitrogen atom (═N--), a substituted carbon atom ##STR113## where R 112 represents a hydrogen atom, a lower alkoxyl group, a halogen atom, a di-lower alkylamino group or a nitro group; and R 72 , R 82 , R 92 and R 102 each represent a hydrogen atom or a lower alkoxyl group; or a pharmacologically acceptable salt thereof and a pharmaceutically acceptable diluent or carrier.

Claim 35

A pharmaceutical composition for the treatment of peptic ulcer which comprises an effective amount to treat peptic ulcer of a 3,4-dihydrobenzopyran derivative of the formula ##STR114## wherein R 1 and R 4 each represent a hydrogen atom or a lower alkyl group; R 2 represents a hydrogen atom, a halogen atom, a lower alkoxyl group or a lower alkenyloxy group; R 3 represents a hydrogen atom, a lower alkyl group or a lower alkoxyl group; n represents an integer of 0, 1 or 2; R 61 represents ##STR115## where p represents an integer of 0 to 4, X 3 represents a methylene group or a carbonyl group, Q 1 represents a nitrogen atom (═N--), a carbon atom ##STR116## where R 111 represents a hydrogen atom, a lower alkoxyl group, a halogen atom, a di-lower alkylamino group or a nitro group; R 71 , R 81 , R 91 and R 101 each represent a hydrogen atom or a lower alkoxyl group; or a pharmacologically acceptable salt thereof and a pharmaceutically acceptable diluent or carrier.

Claim 36

A pharmaceutical composition for the treatment of peptic ulcer which comprises an effective amount to treat peptic ulcer of a 3,4-dihydrobenzopyran derivative of the formula ##STR114## wherein R 1 and R 4 each represent a hydrogen atom or a lower alkyl group; R 2 represents a hydrogen atom, a halogen atom, a lower alkoxyl group or a lower alkenyloxy group; R 3 represents a hydrogen atom, a lower alkyl group or a lower alkoxyl group; n represents an integer of 0, 1 or 2; R 61 represents ##STR115## where p represents an integer of 0 to 4, X 3 represents a methylene group or a carbonyl group, Q 1 represents a nitrogen atom (═N--), a carbon atom ##STR116## where R 111 represents a hydrogen atom, a lower alkoxyl group, a halogen atom, a di-lower alkylamino group or a nitro group; R 71 , R 81 , R 91 and R 101 each represent a hydrogen atom or a lower alkoxyl group; or a pharmacologically acceptable salt thereof and a pharmaceutically acceptable diluent or carrier.

Claim 37

A pharmaceutical composition useful as an antitussive and/or expectorant which comprises as an active ingredient an amount effective as an antitussive and/or expectorant of 3,4-dihydrobenzopyran derivative of the formula ##STR117## wherein R 1 and R 4 each represent a hydrogen atom or a lower alkyl group; R 2 represents a hydrogen atom, a halogen atom, a lower alkoxyl group or a lower alkenyloxy group; R 3 represents a hydrogen atom, a lower alkyl group or a lower alkoxyl group; n-represents an integer of 0, 1 or 2; X 2 represents a methylene group or a carbonyl group; when X 2 represents a methylene group, R 63 represents a lower alkyl group or a lower alkyl group substituted by a hydroxyl group, ##STR118## and when X 2 represents a carbonyl group, R 63 represents ##STR119## where q represents an integer of 0 to 4, Q 1 represents a nitrogen atom (═N--), a carbon atom ##STR120## where R 111 represents a hydrogen atom, a lower alkoxyl group, a halogen atom, a di-lower alkylamino group or a nitro group; R 71 , R 81 , R 91 and R 101 each represent a hydrogen atom or a lower alkoxyl group; Q 2 represents a nitrogen atom (═N--), a carbon atom ##STR121## where R 112 represents a hydrogen atom, a lower alkoxyl group, a halogen atom, a di-lower alkylamino group or a nitro group; R 72 , R 82 , R 92 and R 102 each represent a hydrogen atom or a lower alkoxyl group; or a pharmacologically acceptable salt thereof and a pharmaceutically acceptable diluent or carrier.

Claim 38

A pharmaceutical composition useful as an antitussive and/or expectorant which comprises as an active ingredient an amount effective as an antitussive and/or expectorant of 3,4-dihydrobenzopyran derivative of the formula ##STR117## wherein R 1 and R 4 each represent a hydrogen atom or a lower alkyl group; R 2 represents a hydrogen atom, a halogen atom, a lower alkoxyl group or a lower alkenyloxy group; R 3 represents a hydrogen atom, a lower alkyl group or a lower alkoxyl group; n-represents an integer of 0, 1 or 2; X 2 represents a methylene group or a carbonyl group; when X 2 represents a methylene group, R 63 represents a lower alkyl group or a lower alkyl group substituted by a hydroxyl group, ##STR118## and when X 2 represents a carbonyl group, R 63 represents ##STR119## where q represents an integer of 0 to 4, Q 1 represents a nitrogen atom (═N--), a carbon atom ##STR120## where R 111 represents a hydrogen atom, a lower alkoxyl group, a halogen atom, a di-lower alkylamino group or a nitro group; R 71 , R 81 , R 91 and R 101 each represent a hydrogen atom or a lower alkoxyl group; Q 2 represents a nitrogen atom (═N--), a carbon atom ##STR121## where R 112 represents a hydrogen atom, a lower alkoxyl group, a halogen atom, a di-lower alkylamino group or a nitro group; R 72 , R 82 , R 92 and R 102 each represent a hydrogen atom or a lower alkoxyl group; or a pharmacologically acceptable salt thereof and a pharmaceutically acceptable diluent or carrier.