GB2070606A - 2(1h)-pyridinone derivatives their preparation and pharmaceutical compositions containing them - Google Patents

2(1h)-pyridinone derivatives their preparation and pharmaceutical compositions containing them Download PDF

Info

Publication number
GB2070606A
GB2070606A GB8106335A GB8106335A GB2070606A GB 2070606 A GB2070606 A GB 2070606A GB 8106335 A GB8106335 A GB 8106335A GB 8106335 A GB8106335 A GB 8106335A GB 2070606 A GB2070606 A GB 2070606A
Authority
GB
United Kingdom
Prior art keywords
compound
phenyl
formula
methyl
carbon atoms
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
GB8106335A
Other versions
GB2070606B (en
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sandoz AG
Original Assignee
Sandoz AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sandoz AG filed Critical Sandoz AG
Publication of GB2070606A publication Critical patent/GB2070606A/en
Application granted granted Critical
Publication of GB2070606B publication Critical patent/GB2070606B/en
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/73—Unsubstituted amino or imino radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C07D213/82—Amides; Imides in position 3

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The derivatives have the formula: (FORMULA) where R<s1>s and R<s2>s represent independently from one another hydrogen, an alkyl group or a monocyclic aryl group possibly substituted provided that a) at least R<s1>s or R<s2>s represents an aryl group b) if R<s2>s represents hydrogen, R<s1>s represents a non substituted pyridinyl group or 2-,3- or 4 - substituted by one or two low alkyl groups. The invention also concerns the salts. The derivatives have a cardiotonic action and can be used as medicines. They are obtained through amination.

Description

SPECIFICATION 2(1 H)-pyridinone Derivatives, Their Preparation and Pharmaceutical Compositions Containing Them The present invention relates to 2(1 H)-pyridone derivatives, their preparation and pharmaceutical compositions containing them.
In particular, the invention provides compounds of formula I,
wherein R, and R2 independently are hydrogen, alkyl or optionally substituted monocyclic aryl with the provisos that a) at least one of R, and R2 is aryl and b) when R2 is hydrogen, then R, is other than 2-, 3- or 4-pyridinyl, unsubstituted or substituted by one or two lower alkyl groups, hereinafter referred to as "the compounds of the invention".
It is to be appreciated that for the sake of simplicity the compounds of the inventions are defined with reference to the tautomeric form of formula I. However, the invention extends to all tautomeric forms of the compounds, e.g. the iminoi form.
As used herein, the term "monocyclic aryl" indicates a radical bonded through an unfused aromatic ring. The ring may be carbocyclic, such as phenyl, or heterocyclic containing up to 3 heteroatoms. As indicated, the radical may be substituted or unsubstituted.
In accordance with the invention, there are especially provided compounds of formula la,
wherein Rt and R2 independently are i) hydrogen or alkyl of 1 to 4 carbon atoms, ii) phenyl, phenyl monosubstituted by dialkylamino of independently 1 to 4 carbon atoms in each alkyl moiety or phenyl mono or independently disubstituted by alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halogen of atomic number of from 9 to 35 or iii) pyrrolyl, furanyl, thienyl, thiazolyl, imidazolyl, pyrazolyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl with the provisos that aa) at least one of R1 and R2 has the above significance ii) or iii) and bb) when Fl;; is hydrogen, then R, is other than 2-, 3- or 4-pyridinyl.
Alkyl of 1 to 4 carbon atoms and alkoxy of 1 to 4 carbon atoms preferably are of 1 or 2, especially 1 carbon atom. Halogen preferably is chlorine or bromine, especially chlorine. In dialkylamino the two alkyl moieties preferably are identical. Pyrrolyl preferably is 3-pyrrolyl. Furanyl preferably is 3-furanyl.
Thienyl preferably is 3-thienyl. Thiazolyl preferably is 4-thiazolyl. Imidazolyl preferably is 4-imidazolyl.
Pyrazolyl preferably is 3-pyrazolyl. Pyridinyl preferably is 2- or 4-, especially 4-pyridinyl. Pyrimidinyl preferably is 4-pyrimidinyl. Pyridazinyl preferably is 4-pyridazinyl. Pyrazinyl preferably is 2-pyrazinyl.
R, preferably is alkyl or has the above significance ii) or iii). Rr especially has significance ii). B; preferably has the above significance i), it especially is methyl. Significance i) preferably is alkyl.
Significance ii) preferably is unsubstituted or monosubstituted phenyl. When it is monosubstituted phenyl, the substituent preferably is in the m- or p-, especially in the p-position. When it is disubstituted phenyl, the substituents preferably are in the m- and p-positions. They preferably are identical. Preferred substituents of the phenyl group are alkoxy and halogen, especially alkoxy.
Significance iii) preferably is pyrrolyl, furanyl, thienyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl, especially furanyl, pyridinyl, pyrimidinyl or pyrazinyl, especially pyrimidinyl or pyridinyl, especially pyrimidinyl. Preferably one of R1 and R2 has significance i).
In one group of compounds of formula la R, and R2 are other than pyridinyl. In a subgroup they have a significance other than significance iii).
A preferred group of compounds of formula la is the compounds of formula laa,
wherein R,aa has significance ii) or iii) indicated above.
In one group of compounds of formula laa Rraa is other than pyridinyl. In a subgroup R,a has significance ii) indicated above.
A further group of compounds of formula la is the compounds of formula Ipa
wherein Rpa is i) phenyl, phenyl monosubstituted by dialkylamino of independently 1 to 4 carbon atoms in each alkyl moiety or phenyl mono- or independently disubstituted by alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halogen of atomic number of from 9 to 35, or ii) pyrrolyl, furanyl, thienyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl and B28 is alkyl of 1 to 4 carbon atoms.
A further group of compounds of formula la is the compounds of formula Ipb,
wherein R,b is hydrogen or alkyl of 1 to 4 carbon atoms and RP2b has the significance indicated above for R,Pa.
A further group of compounds of formula la is the compounds of formula Ipc,
wherein R,Pc with the exception of pyridinyl has the significance indicated above for B18.
In accordance with the invention, a compound of the invention may be obtained by a process comprising aminating a corresponding compound of formula II,
wherein R, and R2 are as defined above and Rx is a group capable of conversion to a primary amino group.
The amination process may be effected in conventional manner for the production of analogous 3-amino-2(1 H)-pyridinone derivatives. Rx may be a conventional radical used for conversion to a primary amino group, such as nitro and especially carbamoyl. For example, when Rx is carbamoyi, the reaction conditions of a Hofmann degradation may be used. The reaction preferably is effected under strong alkaline conditions, e.g. in the presence of an alkali metal hydroxide and bromine. Preferably water is used as a solvent. Suitable reaction temperatures may be from about 50 to about 1 000C, conveniently about 1 000C.
The compounds of formula I may be isolated from the reaction mixture and purified in a manner analogous to known methods.
The compounds of the invention may exist in free base form or in salt fprm. Free base forms may be converted into salt forms in conventional manner and vice-versa. Suitable acids for acid addition salt formation include hydrochloric, malonic, p-toluenesulfonic and methanesulfonic acid. Suitable bases for anionic salt formation include sodium and potassium hydroxide.
The starting materials may be obtained in known manner In particular, a compound of formula íl, wherein Bx is carbamoyl, may e.g. be obtained by partial hydrolysis of a corresponding compound of formula Ill,
wherein R, and R2 are as defined above, e.g. with sulfuric or phosphoric acid.
A compound of formula III may e.g. be obtained by reacting a corresponding compound of formula IV,
wherein R, and R2 are as defined above and Alk is lower alkyl, preferably methyl, with cyanacetamide.
The reaction may e.g. be effected in the presence of acetic acid, in which case a compound of formula II may be directly obtained.
A compound of formula IV may e.g. be obtained by reacting a corresponding compound of formula V,
wherein R1 and R, are as defined above, with an N,N-di(lower)alkyl formamide di(lower)alkyl acetal, preferably N,N-dimethylformamide dimethyl or diethyl acetal.
Insofar as the preparation of any particular starting material is not particularly described, this may be effected in conventional manner or in analogous manner to that described herein.
In the following Examples all temperatures are in degrees Centrigrade and are uncorrected.
Example 1 3-Amino-6-methyl-5-phenyl-2(1 H)-pyridinone 2.1 ml of bromine are added dropwise at 0 to a stirred solution of 8.4 g of sodium hydroxide in 125 ml of water. 7.3 g of 1,2-dihydro-6-methyí-2-oxo-5-phenyl-nicotinamide are then added and the mixture heated under stirring to 1000 for 3 hours. After cooling to room temperature the resultant solution is carefully acidified with 6N hydrochloric acid and stirring continued for 30 minutes. The resulting precipitate is filtered off under vacuum and recrystallized from methanol. The title compound is obtained (M.P. 260--263 0; M.P. of the mesylate salt form: 220222 [dec.]).
The starting material is obtained as follows: Benzylmethylketone and N,N-dimethylformamide dimethyl acetal are heated to 800 for 5 hours.
The so-obtained crude 4-dimethylamino-3-phenyl-3-buten-2-one is then reacted with cyanacetamide at boiling temperature in the presence of sodium ethoxide. The so-obtained 1 ,2-dihydro-6-methyl-2oxo-5-phenylpyridin-3-carbonitrile (M.P. 290-2940-from methanol) is then partially hydrolysed with 90% sulfuric acid at 1000 to give 1,2-dihydro-6-methyl-2-oxo-5-phenyl nicotinamide (M.P.
> 3000--from dimethylformamide).
The following compounds of formula I may be obtained by reaction of the appropriate compound of formula II, wherein Bx, is carbamoyl, in analogous manner to Example 1:
Example R1 R2 No. M.P. 2 m-tolyl Me b 245--250 (dec.) 3 p-CI-phenyl Me ms231-2340 4 p-Me0-phenyl Me b256-2600 5 m-,p-diMe0-phenyl Me b218-2200 6 phenyl Et b 1921940 7 o-tolyl Me b231-2320 8 Me phenyl b 174-1760 9 pyrimidin-4-yl H b 283287 10 phenyl H ch 240243 11 pyrazin-2-yl H b 262264 12 phenyl phenyl b296-2990 13 furan-2-yl Me b189--1910 14 pyridin-2-yi phenyl b 239242 1 5 m-Me0-phenyl Me b 244-2450 16 pyridin-4-yl Me b 290295 1 7 o-Me0-phenyl Me b 22'i 226
b=in free base form ch=in hydrochloride salt form ms=in mesylate salt form Et=ethyl Me=methyl MeO=methoxy dec.=decomposition The compounds of the invention possess pharmacological activity.
The compounds possess cardiotonic activity, as indicated by standard tests. For example, in the normotonic Numal anaesthetized dog, an increase in the contractile force of the left ventricle is observed upon intravenous administration of from about 0.02 to about 2 mg/kg.
The test method is as follows: Dogs of either sex weighing from 10 to 1 5 kg are used. Numal in a dosis of 65 mg/kg i.v. is used as an anaesthetic. The animal is attached in supine position on the operation table. After the usual preparations have been effected, a heparinized catheter is introduced along the Arteria carotis dextra into the left ventricle under radiological control and the transmission of the pressure is registered with a donor membrane (Gould Statham P 23 Gb). The increase in pressure as a function of time is computed and registered with an HSE-physiodifferentiator. The pressure increase in the left ventricle is a measure of the contractile force of the heart. The magnitude of the pressure differential is indicated in mm Hg/sec. A suitable body temperature (about 36 to 370C) is maintained constant.After a control period of about 40 minutes the test substance is injected into the Vena femoralis and its effect on the registered or computed parameters observed.
The compounds are therefore indicated for use as cardiotonic agents, e.g. for the treatment of heart insufficiency.
Preferred in this indication are the compounds of Examples 1 and 4, especially the compound of Example 1.
An indicated daily dose is from about 10 mg to about 500 mg, suitably administered, e.g. orally, in divided dosages of from about 2.5 mg to about 250 mg of the compounds two to four times daily, or in retard form. An example of a daily dosage is from 10 to 100 mg.
The compounds may be administered in pharmaceutically acceptable salt from, preferably acid addition salt form. Such salt forms exhibit the same order of activity as the free forms and are readily prepared in conventional manner. The present invention also provides a pharmaceutical composition comprising a compound of the invention in free form or in pharmaceutically acceptable salt form, in association with a pharmaceutical carrier or diluent. Such compositions may be in the form of, for example, a solution or a tablet.

Claims (33)

Claims
1. A process for the production of a compound of formula I,
wherein R1 and R2 independently are hydrogen, alkyl or optionally substituted monocyclic aryl with the provisos that a) at least one of R1 and R2 is aryl, b) when R2 is hydrogen, then R1 is other than 2-, 3- or 4-pyridinyl unsubstituted or substituted by one or two lower alkyl groups, which comprises aminating a corresponding compound of formula 11,
wherein R1 and R2 are as defined above and Bx is a group capable of conversion to a primary amino group.
2. A process for the production of a compound of formula la,
wherein R; and R2 independently are i) hydrogen or alkyl of 1 to 4 carbon atoms, ii) phenyl, phenyl monosubstituted by dialkylamino of independently 1 to 4 carbon atoms in each alkyl moiety or phenyl mono- or independently disubstituted by alkyl of 1 to 4 carbon atoms, alkoxy of from 1 to 4 carbon atoms or halogen of atomic number of from 9 to 35 or iii) pyrrolyl, furanyl, thienyl, thiazolyl, imidazolyl, pyrazolyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl with the provisos that aa) at least one of Rra and R2 has the above significance ii) or iii) and ba) when B;; is hydrogen, then Rla is other than 2-, 3- or 4-pyridinyl, which comprises aminating a corresponding compound of formula lla,
wherein R8l and R2 are as defined above and Rx is as defined in claim 1.
3. A process for the production of a compound as defined in claim 1, substantially as hereinbefore described with reference to any one of the Examples.
4. A compound of formula I, as defined in claim 1, whenever produced by a process according to claim 1.
5. A compound of formula I, as defined in claim 1.
6. A compound of formula la, as defined in claim 2.
7. A compound of claim 6 of formula la, as defined in claim 2, wherein Rla and R2 are other than pyridinyl.
8. A compound of claim 6 of formula laa,
wherein B818 has significances ii) or iii) indicated in claim 2.
9. A compound of claim 8 of formula laa, as defined in claim 8, wherein B818 is other than pyridinyl.
10. A compound of claim 6 of formula Ipa,
wherein Spa is i) phenyl, phenyl monosubstituted by dialkylamino of independently 1 to 4 carbon atoms in each alkyl moiety or phenyl mono- or independently disubstituted by alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or halogen of atomic number of from 9 to 35, or ii) pyrrolyl, furanyl, thienyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl and R2a is alkyl of 1 to 4 carbon atoms.
11. A compound of claim 6 of formula lpb,
wherein Rlpb is hydrogen or alkyl of 1 to 4 carbon atoms and B2Pb has the significance indicated above for Rip8.
12. A compound of claim 6 of formula Ipc,
wherein RlPC with the exception of pyridinyl has the significance indicated in claim 10 for RlPa.
13. The compound of claim 6, which is 3-amino-6-methyl-5-phenyl-2(1 H)-pyridinone.
14. The compound of claim 6, wherein R1 and R2 are, respectively, m-tolyl and methyl.
1 5. The compound of claim 6, wherein R1 and R2 are, respectively, p-CI-phenyl and methyl.
16. The compound of claim 6, wherein R1 and R2 are, respectively, p-Me0-phenyl and methyl.
17. The compound of claim 6, wherein R1 and R2 are, respectively, m-, p-diMeO-phenyl and methyl.
18. The compound of claim 6, wherein R1 and R2 are, respectively, phenyl and ethyl.
19. The compound of claim 6, wherein R1 and R2 are, respectively, o-tolyl and methyl.
20. The compound of claim 6, wherein R1 and R are respectively, methyl and
21. The compound of claim 6, wherein R1 and R2 are, respectively, pyrimidin-4-yl and hydrogen.
22. The compound of claim 6, wherein R1 and R2 are, respectively, phenyl and hydrogen.
23. The compound of claim 6, wherein R1 and R2 are, respectively, pyrazin-2-yl and hydrogen.
24. The compound of claim 6, wherein R1 and R2 are, respectively, phenyl and phenyl.
25. The compound of claim 6, wherein R1 and R2 are, respectively furan-2-yl and methyl.
26. The compound of claim 6, wherein R1 and R2 are, respectively, pyridin-2-yl and phenyl.
27. The compound of claim 6, wherein R1 and R2 are, respectively, m-Me0-phenyl and methyl.
28. The compound of claim 6, wherein R1 and R2 are, respectively, pyridin-4-yl and methyl.
29. The compound of claim 6, wherein R1 and R2 are, respectively, o-Me0-phenyl and methyl.
30. A compound according to any one of claims 4 to 29, in free base form.
31. A compound according to any one of claim 4 to 29, in salt form.
32. A compound according to any one of claims 4 to 29, in acid addition salt form.
33. A pharmaceutical composition comprising a compound of any one of claims 4 to 29 in free base form or in pharmaceutically acceptable salt form, in association with a pharmaceutical carrier or diluent
GB8106335A 1980-03-03 1981-02-27 2(1h)-pyridinone derivatives their preparation and pharmaceutical compositions containing them Expired GB2070606B (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CH166880 1980-03-03
CH166980 1980-03-03
CH571780 1980-07-25
CH794780 1980-10-24

Publications (2)

Publication Number Publication Date
GB2070606A true GB2070606A (en) 1981-09-09
GB2070606B GB2070606B (en) 1984-02-29

Family

ID=27428258

Family Applications (1)

Application Number Title Priority Date Filing Date
GB8106335A Expired GB2070606B (en) 1980-03-03 1981-02-27 2(1h)-pyridinone derivatives their preparation and pharmaceutical compositions containing them

Country Status (16)

Country Link
CA (1) CA1183533A (en)
CH (1) CH652395A5 (en)
DE (1) DE3106460A1 (en)
DK (1) DK94481A (en)
ES (1) ES8301469A1 (en)
FI (1) FI810558L (en)
FR (1) FR2477148A1 (en)
GB (1) GB2070606B (en)
IL (1) IL62246A (en)
IT (1) IT1142458B (en)
NL (1) NL8100964A (en)
NZ (1) NZ196385A (en)
PT (1) PT72596B (en)
SE (1) SE8101336L (en)
WO (1) WO1981002575A1 (en)
YU (1) YU51581A (en)

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0061774A2 (en) * 1981-03-30 1982-10-06 Sterling Drug Inc. 3-Amino-5-(substituted)-2 (1H) pyridinones and 3-cyano compounds useful as cardiotonics and preparation thereof
GB2121037A (en) * 1982-05-18 1983-12-14 Sandoz Ag 2(1h)-pyridinone derivatives their preparation and pharmaceutical compositions containing them
US4432979A (en) * 1981-10-26 1984-02-21 William H. Rorer, Inc. Pyridone compounds
EP0102227A2 (en) * 1982-08-23 1984-03-07 Warner-Lambert Company 2(1H)-pyridinones, useful as cardiotonic agents, and their production
US4465686A (en) * 1981-09-08 1984-08-14 Sterling Drug Inc. 5-(Hydroxy- and/or amino-phenyl)-6-(lower-alkyl)-2-(1H)-pyridinones, their cardiotonic use and preparation
EP0118528A1 (en) * 1982-08-23 1984-09-19 Rorer International (Overseas) Inc. 5-(bicyclic nitrogen-heteroaryl)pyrid-2-ones and their use for increasing cardiac contractility
EP0124090A1 (en) * 1983-04-29 1984-11-07 Merrell Dow Pharmaceuticals Inc. 5-Acyl-2-(1H)-pyridinones
EP0127756A1 (en) * 1983-04-20 1984-12-12 Fabrica De Productos Quimicos Y Farmaceuticos Abello, S.A. Process for the preparation of 5-pyridyl-pyridine-2(1H)-ones
US4503061A (en) * 1983-07-22 1985-03-05 Warner-Lambert Company Substituted phenyl-pyridinones as cardiotonic agents
US4514400A (en) * 1981-10-26 1985-04-30 William H. Rorer, Inc. Cardiotonic 5-heteroaryl-pyridone
US4515797A (en) * 1981-09-08 1985-05-07 Sterling Drug Inc. 3-Amino-5-(hydroxy- and/or aminophenyl)-6-(lower-alkyl)-2(1H)-pyridinones and cardiotonic use thereof
US4517192A (en) * 1983-01-31 1985-05-14 Sterling Drug Inc. 6-Alkyl-5-[4-(alkylsulfinyl or alkylsulfonyl)phenyl]-2(1H)-pyridinones and their use as cardiatonics
US4539321A (en) * 1981-10-26 1985-09-03 William H. Rorer, Inc. 5-Diaza-aryl-3-substituted pyridone compounds
US4593028A (en) * 1981-10-26 1986-06-03 William H. Rorer, Inc. 5-hetero aryl-substituted-2-pyridones useful as cardiotonic agents for treatment of congestive heart failure
EP0200024A2 (en) 1985-04-30 1986-11-05 ARZNEIMITTELWERK DRESDEN GmbH 3-Cyano-pyridines, process for their preparation and their pharmaceutical use
US4666913A (en) * 1985-11-22 1987-05-19 William H. Rorer, Inc. Hydroxy and aminothiazolyl-benzodiazinone compounds, cardiotonic compositions including the same, and their uses
AT384021B (en) * 1982-05-18 1987-09-25 Sandoz Ag Process for the preparation of novel 2(1H)-pyridinone derivatives and their salts
AU624536B2 (en) * 1989-10-13 1992-06-11 Smith Kline & French Laboratories Limited Substituted(2-alkoxy-phenyl)-2(1H)-pyridinones
US5254571A (en) * 1988-04-21 1993-10-19 Smith Kline & French Laboratories Ltd. Chemical compounds

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2529891A1 (en) * 1982-07-12 1984-01-13 Nativelle Sa Ets PYRIDYL-3 ALCOXY-5 PYRAZOLE DERIVATIVES, PREPARATION METHOD AND THERAPEUTIC APPLICATION
DE3406329A1 (en) * 1984-02-22 1985-08-22 Merck Patent Gmbh, 6100 Darmstadt PYRIDONE
US4785005A (en) * 1986-06-25 1988-11-15 Rorer Pharmaceutical Corporation 6-(6-alkylpyridone)-carbostyril compounds and their cardiotonic uses
GB8809481D0 (en) * 1988-04-21 1988-05-25 Smith Kline French Lab Chemical compounds

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3355278A (en) * 1961-03-13 1967-11-28 Hooker Chemical Corp Herbicidal composition and method
NL6816241A (en) * 1967-12-01 1969-06-03
FR2050940A5 (en) * 1969-06-30 1971-04-02 Rhone Poulenc Sa
US3666765A (en) * 1969-10-27 1972-05-30 Union Carbide Corp Synthesis of 2-pyridones and derivatives thereof
US3721676A (en) * 1969-11-12 1973-03-20 Merck & Co Inc Certain 3-amino-2(1h)pyridones
BE758759A (en) * 1969-11-12 1971-05-10 Merck & Co Inc ANTI-INFLAMMATORY PYRIDONES
US4038396A (en) * 1975-02-24 1977-07-26 Merck & Co., Inc. Anti-inflammatory oxazole[4,5-b]pyridines
US4072746A (en) * 1975-10-14 1978-02-07 Sterling Drug Inc. 3-Amino-5-(pyridinyl)-2(1H)-pyridinones

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0061774A3 (en) * 1981-03-30 1983-09-07 Sterling Drug Inc. 3-amino-5-(substituted)-2 (1h) pyridinones and 3-cyano compounds useful as cardiotonics and preparation thereof
EP0061774A2 (en) * 1981-03-30 1982-10-06 Sterling Drug Inc. 3-Amino-5-(substituted)-2 (1H) pyridinones and 3-cyano compounds useful as cardiotonics and preparation thereof
US4465686A (en) * 1981-09-08 1984-08-14 Sterling Drug Inc. 5-(Hydroxy- and/or amino-phenyl)-6-(lower-alkyl)-2-(1H)-pyridinones, their cardiotonic use and preparation
US4515797A (en) * 1981-09-08 1985-05-07 Sterling Drug Inc. 3-Amino-5-(hydroxy- and/or aminophenyl)-6-(lower-alkyl)-2(1H)-pyridinones and cardiotonic use thereof
US4514400A (en) * 1981-10-26 1985-04-30 William H. Rorer, Inc. Cardiotonic 5-heteroaryl-pyridone
US4432979A (en) * 1981-10-26 1984-02-21 William H. Rorer, Inc. Pyridone compounds
US4593028A (en) * 1981-10-26 1986-06-03 William H. Rorer, Inc. 5-hetero aryl-substituted-2-pyridones useful as cardiotonic agents for treatment of congestive heart failure
US4539321A (en) * 1981-10-26 1985-09-03 William H. Rorer, Inc. 5-Diaza-aryl-3-substituted pyridone compounds
GB2121037A (en) * 1982-05-18 1983-12-14 Sandoz Ag 2(1h)-pyridinone derivatives their preparation and pharmaceutical compositions containing them
AT384021B (en) * 1982-05-18 1987-09-25 Sandoz Ag Process for the preparation of novel 2(1H)-pyridinone derivatives and their salts
EP0118528A4 (en) * 1982-08-23 1985-09-09 Rorer Internat Overseas Inc 5-(bicyclic nitrogen-heteroaryl)pyrid-2-ones and their use for increasing cardiac contractility.
EP0118528A1 (en) * 1982-08-23 1984-09-19 Rorer International (Overseas) Inc. 5-(bicyclic nitrogen-heteroaryl)pyrid-2-ones and their use for increasing cardiac contractility
EP0102227A3 (en) * 1982-08-23 1985-10-30 Warner-Lambert Company 2(1h)-pyridinones, useful as cardiotonic agents, and their production
EP0102227A2 (en) * 1982-08-23 1984-03-07 Warner-Lambert Company 2(1H)-pyridinones, useful as cardiotonic agents, and their production
WO1984000685A1 (en) * 1982-08-23 1984-03-01 Rorer Int Overseas Pyridone compounds
US4517192A (en) * 1983-01-31 1985-05-14 Sterling Drug Inc. 6-Alkyl-5-[4-(alkylsulfinyl or alkylsulfonyl)phenyl]-2(1H)-pyridinones and their use as cardiatonics
EP0127756A1 (en) * 1983-04-20 1984-12-12 Fabrica De Productos Quimicos Y Farmaceuticos Abello, S.A. Process for the preparation of 5-pyridyl-pyridine-2(1H)-ones
EP0124090A1 (en) * 1983-04-29 1984-11-07 Merrell Dow Pharmaceuticals Inc. 5-Acyl-2-(1H)-pyridinones
US4503061A (en) * 1983-07-22 1985-03-05 Warner-Lambert Company Substituted phenyl-pyridinones as cardiotonic agents
EP0200024A2 (en) 1985-04-30 1986-11-05 ARZNEIMITTELWERK DRESDEN GmbH 3-Cyano-pyridines, process for their preparation and their pharmaceutical use
US4666913A (en) * 1985-11-22 1987-05-19 William H. Rorer, Inc. Hydroxy and aminothiazolyl-benzodiazinone compounds, cardiotonic compositions including the same, and their uses
US5254571A (en) * 1988-04-21 1993-10-19 Smith Kline & French Laboratories Ltd. Chemical compounds
AU624536B2 (en) * 1989-10-13 1992-06-11 Smith Kline & French Laboratories Limited Substituted(2-alkoxy-phenyl)-2(1H)-pyridinones

Also Published As

Publication number Publication date
YU51581A (en) 1983-12-31
DE3106460A1 (en) 1982-01-28
GB2070606B (en) 1984-02-29
FR2477148A1 (en) 1981-09-04
CH652395A5 (en) 1985-11-15
FR2477148B1 (en) 1983-09-02
ES499971A0 (en) 1982-12-01
CA1183533A (en) 1985-03-05
SE8101336L (en) 1981-09-04
WO1981002575A1 (en) 1981-09-17
IT8147920A0 (en) 1981-03-02
NZ196385A (en) 1983-12-16
DK94481A (en) 1981-09-04
FI810558L (en) 1981-09-04
IL62246A0 (en) 1981-05-20
ES8301469A1 (en) 1982-12-01
IT1142458B (en) 1986-10-08
PT72596B (en) 1982-07-13
NL8100964A (en) 1981-10-01
PT72596A (en) 1981-04-01
IL62246A (en) 1984-09-30

Similar Documents

Publication Publication Date Title
GB2070606A (en) 2(1h)-pyridinone derivatives their preparation and pharmaceutical compositions containing them
US3995039A (en) Pyrazolo [1,5-a] [1,3,5] triazines
GB1601195A (en) 4-acylamino-or 4-acylaminoalkyl-benzoic acids derivatives thereof and processes for their manufacture
SU999972A3 (en) Process for producing derivatives of pyrido-(1,2a)-pyrimidine or their pharmaceutically acceptable salts or their optically active isomers
HU193924B (en) Process for preparing substituted indeno-pyridazines and pharmaceutics comprising the same
CA1240330A (en) 2-(1h)-pyridinone derivatives, their preparation and pharmaceutical compositions containing them
KR900003368B1 (en) Process for preparing novel indenothiazole derivatives
GB1568398A (en) Triazolo pyridazine derivatives
UA6841A1 (en) METHOD OF PREPARATION OF PYRIDAZINONE DERIVATIVES OR THEIR WATER-SOLUBLE SALTS WITH A PHARMACEUTICALLY ACCEPTABLE ACID
EP0116628B1 (en) 1-acyl-3-pyridylmethylguanidines and their use as antihypertensive agents
US2786059A (en) Derivatives of 2-nu-methyl-1, 2, 3, 4-tetrahydro-gamma-carbolines
US3378564A (en) Certain pyridyl tetrazole derivatives
US3736326A (en) Isoxazolopyridine carboxylic acids and esters
US4183934A (en) 4-Hydroxy-7-(substituted)phenylpteridines
US3736327A (en) Isoxazolopyridine ketone derivatives
EP0074229B1 (en) Triazole gastric anti-secretory agents
JPS6049634B2 (en) Method for producing quinoxaline-1,4-dioxide derivative
CA1073905A (en) Pyrazolo (1,5-a) pyrido (3,2-e) pyrimidine-7-carboxylic acid derivatives
US3850940A (en) Intermediate pyrazolopyridine carbonitriles
JPS6051190A (en) Triazolo-pyrimidine derivative, manufacture and cardiac stimulant
US3903096A (en) New derivatives of sulfonyl-, sulfinyl- and sulfenyl-1H-pyrazolo {8 3,4-b{9 -pyridines
US2810725A (en) Pyridoxal derivatives of isonicotinic acid hydrazide
US3912737A (en) Isoxazolopyridine carboxylic acids and esters
US2807616A (en) Oxazolopyrimidines and method of preparing same
US3928348A (en) N-methyl-imidazole derivatives and their production

Legal Events

Date Code Title Description
PCNP Patent ceased through non-payment of renewal fee