US4235919A
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US
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1-(Indol-4-yloxy)-3-(2-substituted amino)-2-propanols and pharmaceutical use thereof
Assignee: Fidelity Union Bank
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Filing: 1978-07-17
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Granted: 1980-11-25
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Expires: 1998-07-17
Abstract
Abstract The compounds of formula I <IMAGE> I wherein R is a group <IMAGE> wherein A is alkylene of 2 to 5 carbon atoms, X is a bond, oxygen or sulfur, R3 is hydrogen, hydroxy, alkoxy of 1 to 4 carbon atoms, halogen of atomic member of from 9 to 35, cyano, carbamoyl or a group NHCORd, wherein Rd is alkyl of 1 to 4 carbon atoms, and R4 is hydrogen and, when R3 is alkoxy of 1 to 4 carbon atoms, R4 additionally may be alkoxy of 1 to 4 carbon atoms or, when R3 is halogen of atomic number of from 9 to 35, R4 additionally may be halogen of atomic number of from 9 to 35 either (i) R1 is hydrogen or methyl and R2 is cyano, CONRaRb, COORc or CH2ORe, wherein Ra, Rb, Rc and Re independently are hydrogen or alkyl of 1 to 4 carbon atoms, or (ii) either R1 is methyl and R2 is halogen of atomic number of from 17 to 35 or R1 is halogen of atomic number of from 17 to 35 and R2 is hydrogen or methyl, with the provisos that (a) X is separated from the nitrogen atom of the 3-amino-2-hydroxypropoxy chain by at least 2 carbon atoms, (b) when X is a bond, R3 is other than hydrogen and (c) when R2 is cyano, R additionally may be alkyl of 3 to 7 carbon atoms, are useful as alpha - and beta -adrenoceptor blocking, antiarrhythmic and antihypertensive agents and as inhibitors of metabolic effects of emotional stress.
Inventors
- 👤 Richard Berthold
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-06 14:07
CPC Classifications
C; C07; C07D; C07D209/00; C07D209/02; C07D209/04; C07D209/10; C07D209/12; C07D209/30; C07D209/42
Claims Analysis
Total Claims: 40
Claim 1
Independent Claim
274 words
A compound of formula I ##STR52## wherein R is a group ##STR53## wherein A is alkylene of 2 to 5 carbon atoms, X is a bond, oxygen or sulfur, R 3 is hydrogen, hydroxy, alkoxy of 1 to 4 carbon atoms, halogen of atomic member of from 9 to 35, cyano, carbamoyl or a group NHCOR d , wherein R d is alkyl of 1 to 4 carbon atoms, and R 4 is hydrogen and, when R 3 is alkoxy of 1 to 4 carbon atoms, R 4 additionally may be alkoxy of 1 to 4 carbon atoms or, when R 3 is halogen of atomic number of from 9 to 35, R 4 additionally may be halogen of atomic number of from 9 to 35 either (i) R 1 is hydrogen or methyl and R 2 is cyano, CONR a R b , COOR c or CH 2 OR e , wherein R a ,R b ,R c and R e independently are hydrogen or alkyl of 1 to 4 carbon atoms, or (ii) either R 1 is methyl and R 2 is halogen of atomic number of from 17 to 35 or R 1 is halogen of atomic number of from 17 to 35 and R 2 is hydrogen or methyl, with the provisos that (a) X is separated from the nitrogen atom of the 3-amino-2-hydroxypropoxy chain by at least 2 carbon atoms, (b) when X is a bond, R 3 is other than hydrogen and (c) when R 2 is cyano, R additionally may be alkyl of 3 to 7 carbon atoms, in free form or in pharmaceutically acceptable salt form.
Claim 2
Dependent Claim
274 words
A compound of formula I ##STR52## wherein R is a group ##STR53## wherein A is alkylene of 2 to 5 carbon atoms, X is a bond, oxygen or sulfur, R 3 is hydrogen, hydroxy, alkoxy of 1 to 4 carbon atoms, halogen of atomic member of from 9 to 35, cyano, carbamoyl or a group NHCOR d , wherein R d is alkyl of 1 to 4 carbon atoms, and R 4 is hydrogen and, when R 3 is alkoxy of 1 to 4 carbon atoms, R 4 additionally may be alkoxy of 1 to 4 carbon atoms or, when R 3 is halogen of atomic number of from 9 to 35, R 4 additionally may be halogen of atomic number of from 9 to 35 either (i) R 1 is hydrogen or methyl and R 2 is cyano, CONR a R b , COOR c or CH 2 OR e , wherein R a ,R b ,R c and R e independently are hydrogen or alkyl of 1 to 4 carbon atoms, or (ii) either R 1 is methyl and R 2 is halogen of atomic number of from 17 to 35 or R 1 is halogen of atomic number of from 17 to 35 and R 2 is hydrogen or methyl, with the provisos that (a) X is separated from the nitrogen atom of the 3-amino-2-hydroxypropoxy chain by at least 2 carbon atoms, (b) when X is a bond, R 3 is other than hydrogen and (c) when R 2 is cyano, R additionally may be alkyl of 3 to 7 carbon atoms, in free form or in pharmaceutically acceptable salt form.
Claim 3
Dependent Claim
31 words
A pharmaceutical composition useful in treating vasoconstriction, arrhythmia, hypertension, and myocardial infarction comprising a therapeutically effective amount of a compound of claim 1, in association with a pharmaceutical carrier or diluent.
Claim 4
Dependent Claim
61 words
A method of treating diseases related to an adrenergic vasoconstriction, or coronary diseases, or diseases related to an inhibition of bowel motility, or arrhythmies, or hypertension, or lipolysis in the blood, hyperglycemia, appetite or myocardial infarction induced by emotional stress, which comprises administering to an animal in need of such treatment a therapeutically effective amount of a compound of claim 1.
Claim 5
Dependent Claim
235 words
A compound of claim 1 of formula Ix ##STR54## wherein R x is a group ##STR55## wherein A is as defined above, either (i) X x is oxygen or sulfur and R 1 x to R 4 x have the significances indicated above for R 1 to R 4 or (ii) X x is a bond and either (j) R 3 x is alkoxy of 1 to 4 carbon atoms or halogen of atomic number of from 9 to 35, R 4 x is hydrogen and, when R 3 x is alkoxy of 1 to 4 carbon atoms, R 3 x additionally may be alkoxy of 1 to 4 carbon atoms or, when R 3 x is halogen of atomic number of from 9 to 35, R 4 x additionally may be halogen of atomic number of from 9 to 35, R 1 x is hydrogen or methyl and R 2 x is CONR a R b , wherein R a and R b are as defined above, or (jj) R 3 x is hydroxy, cyano, carbamoyl or NHCOR d , wherein R d is as defined above, R 4 x is hydrogen and R 1 x and R 2 x have the significances indicated above for R 1 and R 2 , with the proviso, that X x is separated by at least 2 carbon atoms from the nitrogen atom of the 3-amino-2-hydroxypropoxy chain.
Claim 6
Dependent Claim
63 words
A compound of claim 1 of formula Ix' ##STR56## wherein A is as defined above, X x' is oxygen or sulfur and R 1 x' to R 4 x' have the significances indicated above for R 1 to R 4 , with the proviso, that X x' is separated by at least 2 carbon atoms from the nitrogen atom of the 3-amino-2-hydroxypropoxy chain.
Claim 7
Dependent Claim
110 words
A compound of claim 1 of formula Iu, ##STR57## wherein R u is a group ##STR58## wherein A is as defined above, R 1 u , R 2 u and R 4 u have the significances indicated above for R 1 , R 2 and R 4 and R 3 u with the exception of hydrogen has the significances indicated above for R 3 , with the provisos, that (a) the phenyl ring is separated by at least two carbon atoms from the nitrogen atom of the 3-amino-2-hydroxypropoxy chain and (b) when R 2 u is cyano, R 1 u additionally may be alkyl of 3 to 7 carbon atoms,
Claim 8
Dependent Claim
224 words
A compound of claim 1 of formula Iu', ##STR59## wherein R u' is a group ##STR60## wherein A is as defined above, R 3 u' of 1 to 4 carbon atoms or halogen of atomic number of from 9 to 35, R 4 u' is hydrogen and, when R 3 u' is alkoxy of 1 to 4 carbon atoms, R 4 u' additionally may be alkoxy of 1 to 4 carbon atoms or, when R 3 u' is halogen of atomic number of from 9 to 35, R 4 u' additionally may be halogen of atomic number of from 9 to 35, either (i) R 1 u' is hydrogen or methyl and R 2 u' is cyano, COOR c or CH 2 OR e , wherein R c and R e are as defined above, or (ii) either R 1 u' is methyl and R 2 u' is halogen of atomic number of from 17 to 35 or R 1 u' is halogen of atomic number of from 17 to 35 and R 2 u' is hydrogen or methyl, with the provisos, that (a) the phenyl ring is separated by at least 2 carbon atoms from the nitrogen atom of the 3-amino-2-hydroxypropoxy chain and (b) when R 2 u' is cyano, R 1 u' additionally may be alkyl of 3 to 7 carbon atoms.
Claim 9
Dependent Claim
17 words
A compound according to claim 1 which is 1-(3-chloro-2-methylindol-4-yloxy)-3-(2-phenoxyethylamino)-2-propanol, or a pharmaceutically acceptable acid addition salt thereof.
Claim 10
Dependent Claim
30 words
A compound of claim 1 wherein R is --C(CH 3 ) 3 , R 1 is H and R 2 is CN, or a pharmaceutically acceptable acid addition salt thereof.
Claim 11
Dependent Claim
26 words
A compound of claim 1 wherein R is ##STR61## R 1 is H, and R 2 is CN, or a pharmaceutically acceptable acid addition salt thereof.
Claim 12
Dependent Claim
26 words
A compound of claim 1 wherein R is ##STR62## R 1 is H, and R 2 is CN, or a pharmaceutically acceptable acid addition salt thereof.
Claim 13
Dependent Claim
26 words
A compound of claim 1 wherein R is ##STR63## R 1 is H, and R 2 is CN, or a pharmaceutically acceptable acid addition salt thereof.
Claim 14
Dependent Claim
28 words
A compound of claim 1 wherein R is ##STR64## R 1 is H, and R 2 is CONH 2 , or a pharmaceutically acceptable acid addition salt thereof.
Claim 15
Dependent Claim
28 words
A compound of claim 1 wherein R is ##STR65## R 1 is H, and R 2 is CONH 2 , or a pharmaceutically acceptable acid addition salt thereof.
Claim 16
Dependent Claim
28 words
A compound of claim 1 wherein R is ##STR66## R 1 is H, and R 2 is CONH 2 , or a pharmaceutically acceptable acid addition salt thereof.
Claim 17
Dependent Claim
28 words
A compound of claim 1 wherein R is ##STR67## R 1 is H, and R 2 is CONH 2 , or a pharmaceutically acceptable acid addition salt thereof.
Claim 18
Dependent Claim
28 words
A compound of claim 1 wherein R is ##STR68## R 1 is H, and R 2 is CONH 2 , or a pharmaceutically acceptable acid addition salt thereof.
Claim 19
Dependent Claim
26 words
A compound of claim 1 wherein R is ##STR69## R 1 is H, and R 2 is ##STR70## or a pharmaceutically acceptable acid addition salt thereof.
Claim 20
Dependent Claim
30 words
A compound of claim 1 wherein R is ##STR71## R 1 is CH 3 , and R 2 is CONH 2 , or a pharmaceutically acceptable acid addition salt thereof.
Claim 21
Dependent Claim
30 words
A compound of claim 1 wherein R is ##STR72## R 1 is H, and R 2 is COOCH(CH 3 ) 2 , or a pharmaceutically acceptable acid addition salt thereof.
Claim 22
Dependent Claim
30 words
A compound of claim 1 wherein R is ##STR73## R 1 is H, and R 2 is COOCH(CH 3 ) 2 , or a pharmaceutically acceptable acid addition salt thereof.
Claim 23
Dependent Claim
32 words
A compound of claim 1 wherein R is ##STR74## R 1 is CH 3 , and R 2 is COOCH 2 CH 3 , or a pharmaceutically acceptable acid addition salt thereof.
Claim 24
Dependent Claim
28 words
A compound of claim 1 wherein R is ##STR75## R 1 is CH 3 , and R 2 is Cl, or a pharmaceutically acceptable acid addition salt thereof.
Claim 25
Dependent Claim
28 words
A compound of claim 1 wherein R is ##STR76## R 1 is Cl, and R 2 is CH 3 , or a pharmaceutically acceptable acid addition salt thereof.
Claim 26
Dependent Claim
28 words
A compound of claim 1 wherein R is ##STR77## R 1 is CH 3 , and R 2 is Br, or a pharmaceutically acceptable acid addition salt thereof.
Claim 27
Dependent Claim
28 words
A compound of claim 1 wherein R is ##STR78## R 1 is Cl, and R 2 is CH 3 , or a pharmaceutically acceptable acid addition salt thereof.
Claim 28
Dependent Claim
28 words
A compound of claim 1 wherein R is ##STR79## R 1 is H, and R 2 is CONHCH 3 , or a pharmaceutically acceptable acid addition salt thereof.
Claim 29
Dependent Claim
30 words
A compound of claim 1 wherein R is ##STR80## R 1 is H, and R 2 is CH 2 OCH 3 , or a pharmaceutically acceptable acid addition salt thereof.
Claim 30
Dependent Claim
30 words
A compound of claim 1 wherein R is ##STR81## R 1 is H, and R 2 is CH 2 OCH 3 , or a pharmaceutically acceptable acid addition salt thereof.
Claim 31
Dependent Claim
33 words
A compound of the formula ##STR82## wherein R p is alkyl of 3 to 7 carbon atoms, and R 1 p is hydrogen or methyl, or a pharmaceutically acceptable acid addition salt thereof.
Claim 32
Dependent Claim
33 words
A compound of the formula ##STR82## wherein R p is alkyl of 3 to 7 carbon atoms, and R 1 p is hydrogen or methyl, or a pharmaceutically acceptable acid addition salt thereof.
Claim 33
Dependent Claim
142 words
A compound of the formula ##STR83## wherein R 1 p is as defined in claim 30, A is alkylene of 2 to 5 carbon atoms, R 3 p is hydroxy, alkoxy of 1 to 4 carbon atoms, halogen of atomic number from 9 to 35, cyano, carbamoyl or acetamido, and R 4 p is hydrogen and, when R 3 p is alkoxy of 1 to 4 carbon atoms, R 4 p additionally may be alkoxy of 1 to 4 carbon atoms, or when R 3 p is halogen of atomic number of from 9 to 35, R 4 p additionally may be halogen of atomic number of from 9 to 35, with the proviso that the phenyl ring is separated by at least 2 carbon atoms from the nitrogen atom of the 3-amino-2-hydroxypropoxy moiety, or a pharmaceutically acceptable acid addition salt thereof.
Claim 34
Dependent Claim
74 words
A compound of the formula ##STR84## wherein A, R 1 p , R 3 p and R 4 p are as defined in claim 10, and R a and R b are, independently, hydrogen or alkyl of 1 to 4 carbon atoms, with the proviso that the phenyl ring is separated by at least 2 carbon atoms from the nitrogen atom of the 3 -amino-2-hydroxypropoxy moiety, or a pharmaceutically acceptable acid addition salt thereof.
Claim 35
Dependent Claim
139 words
A compound of the formula ##STR85## wherein A, R 1 pd and R 2 pd are as defined in claim 34, R 3 p is hydroxy, alkoxy of 1 to 4 carbon atoms, halogen of atomic number of from 9 to 35, cyano, carbamoyl or acetamido, and R 4 p is hydrogen and, when R 3 p is alkoxy of 1 to 4 carbon atoms, R 4 p additionally may be alkoxy of 1 to 4 carbon atoms, or when R 3 p is halogen of atomic number of from 9 to 35, R 4 p additionally may be halogen of atomic number of from 9 to 35, with the proviso that the phenyl ring is separated by at least 2 carbon atoms from the nitrogen atom of the 3-amino-2-hydroxypropoxy moiety, or a pharmaceutically acceptable acid addition salt thereof.
Claim 36
Dependent Claim
127 words
A compound of the formula ##STR86## wherein A is as defined in claim 31, either (i) R 1 pd is halogen of atomic number of from 17 to 35 and R 2 pd is hydrogen or methyl or (ii) R 1 pd is methyl and R 2 pd is halogen of atomic number of from 17 to 35, R 3 pd is hydrogen or has the significance defined above for R 3 p in claim 31, R 4 pd is as defined in claim 31 for R 4 p , and X p is oxygen or sulfur, with the proviso that X p is separated by at least 2 carbon atoms from the nitrogen atom of the 3-amino-2-hydroxypropoxy moiety, or a pharmaceutically acceptable acid addition salt thereof.
Claim 37
Dependent Claim
74 words
A compound of the formula ##STR87## wherein A is alkylene of 2 to 5 carbon atoms, X p is oxygen or sulfur, R 1 p is hydrogen or methyl, and R 3 pd and R 4 pd are as defined in claim 34, with the proviso that the phenyl ring is separated by at least 2 carbon atoms from the nitrogen atom of the 3-amino-2-hydroxypropoxy moiety, or a pharmaceutically acceptable acid addition salt thereof.
Claim 38
Dependent Claim
76 words
A compound of the formula ##STR88## wherein A, X p , R 1 p , R 3 pd and R 4 pd are as defined in claim 35, and R a and R b are, independently, hydrogen or alkyl of 1 to 4 carbon atoms, with the proviso that the phenyl ring is separated by at least 2 carbon atoms from the nitrogen atom of the 3-amino-2-hydroxypropoxy moiety, or a pharmaceutically acceptable acid addition salt thereof.
Claim 39
Dependent Claim
83 words
A compound of the formula ##STR89## wherein A, X p , R 1 p , R 3 pd and R 4 pd are as defined in claim 35, and R 2 pe is CH 2 OH or COOR c wherein R c is hydrogen or alkyl of 1 to 4 carbon atoms, with the proviso that the phenyl ring is separated by at least 2 carbon atoms from the nitrogen atom of the 3-amino-2-hydroxypropoxy moiety, or a pharmaceutically acceptable acid addition salt thereof.
Claim 40
Dependent Claim
60 words
A compound of the formula ##STR90## wherein A, R 1 p , R 2 pe , R 3 pd and R 4 pd are as defined in claim 37, with the proviso that the phenyl ring is separted by at least 2 carbon atoms from the nitrogen atom of the 3-amino-2-hydroxypropoxy moiety, or a pharmaceutically acceptable acid addition salt thereof.
References Cited (Backward Citations)
US3340266A
Cited
US3432545A
Cited
GB1129072A
Cited
GB1269776A
Cited
US3696121A
Cited
US3696120A
Cited
US3705907A
Cited
US3699123A
Cited
US3751429A
Cited
GB1493006A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1983-11-25 | 1984-05-26 | 1984-11-25 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1987-11-25 | 1988-05-26 | 1988-11-25 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1991-11-25 | 1992-05-26 | 1992-11-25 | $7700.00 | Window Closed / Lapsed |