FI68609B - FRAMEWORK FOR THERAPEUTIC TREATMENT OF THERAPEUTIC ACTIVATING BENSOFENONDERIVAT - Google Patents
FRAMEWORK FOR THERAPEUTIC TREATMENT OF THERAPEUTIC ACTIVATING BENSOFENONDERIVAT Download PDFInfo
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- FI68609B FI68609B FI760999A FI760999A FI68609B FI 68609 B FI68609 B FI 68609B FI 760999 A FI760999 A FI 760999A FI 760999 A FI760999 A FI 760999A FI 68609 B FI68609 B FI 68609B
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- ethyl
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- general formula
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- bensofenonderivat
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/32—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups
- C07C65/40—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups containing singly bound oxygen-containing groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/46—Friedel-Crafts reactions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/54—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition of compounds containing doubly bound oxygen atoms, e.g. esters
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
- C07C49/82—Ketones containing a keto group bound to a six-membered aromatic ring containing hydroxy groups
- C07C49/83—Ketones containing a keto group bound to a six-membered aromatic ring containing hydroxy groups polycyclic
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
ΓΒΊ ηη KUULUTUSJULKAISU / Cl ίΓ) QΓΒΊ ηη ANNOUNCEMENT / Cl ίΓ) Q
B '' UTLÄGG NINGSSKRIFT O O O U..7 • C (45) rat-3r.lli ayonnotty 10 10 1935 ^eddolat (51.) Kv.lk.*/lnt.CI.4 C 07 C 49/82, ^9/76 (21) Patenttihakemus — Patentansökning 760999 (22) Hakemispäivä — Ansöknlngsdag 13*04.76 (Fl) (23) Alkupäivä — Giltighetsdag 13*04.76 (41) Tullut |ulkiseksi — Blivit offentllg 1 8.1 0.76B '' UTLÄGG NINGSSKRIFT OOO U..7 • C (45) rat-3r.lli ayonnotty 10 10 1935 ^ eddolat (51.) Kv.lk. * / Lnt.CI.4 C 07 C 49/82, ^ 9 / 76 (21) Patent application - Patentansökning 760999 (22) Filing date - Ansöknlngsdag 13 * 04.76 (Fl) (23) Starting date - Giltighetsdag 13 * 04.76 (41) Becoming external - Blivit offentllg 1 8.1 0.76
Patentti- ja rekisterihallitus (44) Nähtäväkslpanon Ja kuul.|ulkaisun pvm. — 28.06.85National Board of Patents and Registration (44) Date of publication and hearing. - 28.06.85
Patent- och registerstyrelsen v ' Ansökan utlagd och utl.skrlften publicerad (32)(33)(31) Pyydetty etuoikeus—Begärd prioritet 17*04.75 Englanti-England(GB) 15805/75 (71) Lilly Industries Limited, Henrietta House, Henrietta Place, London W.1, Englant i-England(GB) (72) John Christopher Saunders, Maidenhead, Berkshire, William Robert Nigel Williamson, Slough, Buckinghamshire, Englanti-England(GB) (74) Oy Kolster Ab (54) Menetelmä uusien, terapeuttisesti aktiivisten bentsofenon i joiulann.i i st r>n valmistamiseksi - Förfarande för f ramstä 1 I n f ng av nya let ap«.'ui i ski aktiva bensofenonderivat Tämä keksintö koskee menetelmää uusien bentsofenonijohdannaisten valmistamiseksi. Keksinnön mukaisesti valmistetut yhdisteet ovat terapeuttisesti käyttökelpoisia ja sopivat varsinkin allergisten tilojen hoitamiseen.Patent and registration authorities in the United States of America (32) (33) (31) Privilege claimed — Begärd priority 17 * 04.75 England-England (GB) 15805/75 (71) Lilly Industries Limited, Henrietta House, Henrietta Place, London W.1, England i-England (GB) (72) John Christopher Saunders, Maidenhead, Berkshire, William Robert Nigel Williamson, Slough, Buckinghamshire, England-England (GB) (74) Oy Kolster Ab (54) Method The present invention relates to a process for the preparation of new benzophenone derivatives. The present invention relates to a process for the preparation of new benzophenone derivatives. The compounds according to the invention are therapeutically useful and are particularly suitable for the treatment of allergic conditions.
Kirjallisuutta, jossa käsitellään bentsofenoneja, niiden valmistusta ja niiden käyttöä on olemassa runsaasti. Tätä ennen ei kuitenkaan ole huomioitu, että o-hydroksibentsofenoneja ja niiden johdannaisia voidaan käyttää allergisten tilojen hoitamiseen.There is a wealth of literature on benzophenones, their preparation and their use. However, it has not previously been considered that o-hydroxybenzophenones and their derivatives can be used to treat allergic conditions.
Keksinnön kohteena on menetelmä uusien terapeuttisesti aktiivisten bentsofenoni johdannaisten valmistamiseksi, joiden yleinen kaava on 2 68609 R1 2 ^-\ /-^ (X’n ’ -fl-<σΓ / \ O (I)The invention relates to a process for the preparation of new therapeutically active benzophenone derivatives of the general formula 2 68609 R1 2 ^ - \ / - ^ (X'n '-fl- <σΓ / \ O (I)
RJ OHRJ OH
12 3 jossa R , R ja R merkitsevät vetyä tai etyyliä, jolloin ainakin yksi niistä on etyyli, (X)n tarkoittaa 1 tai 2 substituenttia, nimittäin klooria, fluoria tai metyyliä, edellyttäen, että 13 2 (i) kun R ja R ovat vetyjä ja R on etyyli, niin (X)n ei tarkoita pelkästään klooria tai fluoria; ja 1 2 3 (ii) kun R on etyyli ja R ja R ovat vetyjä, niin (X)n ei ole 4-kloori, 2,4- tai 3,4-dikloori, 2- tai 3-kloori, 4-fluori tai 3-metyyli.12 3 wherein R, R and R represent hydrogen or ethyl, at least one of which is ethyl, (X) n represents 1 or 2 substituents, namely chlorine, fluorine or methyl, provided that 13 2 (i) when R and R are hydrogen and R is ethyl, then (X) n does not mean chlorine or fluorine alone; and 1 2 3 (ii) when R is ethyl and R and R are hydrogen, then (X) n is not 4-chloro, 2,4- or 3,4-dichloro, 2- or 3-chloro, 4-fluoro or 3-methyl.
FI-patenttijulkaisusta 48 462 tunnetaan kaavan I mukaisia yhdisteitä lähellä olevia bentsofenoksiimeja, joilla ei kuitenkaan ilmoiteta olevan lääkekäyttöä. Rakenteeltaan läheisesti kaavan I mukaisia yhdisteitä muistuttavia yhdisteitä on esitetty myös SE-patenttijulkaisussa 424 325. Myöskään niillä ei ole ilmoitettu olevan lääkekäyttöä.FI patent publication 48 462 discloses benzophenoximes close to the compounds of the formula I, which, however, are not reported to have medicinal use. Compounds closely resembling compounds of formula I are also disclosed in SE patent publication 424 325. They are also not reported to have medicinal use.
Keksinnön mukaiselle menetelmälle on tunnusomaista, että yhdiste, jolla on yleinen kaavaThe process according to the invention is characterized in that the compound of the general formula
R3 OHR3 OH
12 3 jossa R , R ja R merkitsevät samaa kuin edellä, saatetaan reagoimaan Friedel-Crafts-asylointiolosuhteissa karboksyylihapon kanssa, jonka yleinen kaava on °—?—<cr ”«« o jossa (X)n merkitsee samaa kuin edellä ja Q on OH tai halogeeni.12 3 wherein R, R and R are as defined above are reacted under Friedel-Crafts acylation conditions with a carboxylic acid of the general formula ° -? - <cr ”« «o wherein (X) n is as defined above and Q is OH or halogen.
68609 368609 3
Kun kaavan (III) mukaisessa yhdisteessä Q on halogeeni, reaktio voidaan suorittaa käyttämällä katalysaattorina Lewis-hap-poa kuten esim. aluminiumhalogenidia (esim. kloridia) sopivassa inertissä liuottimessa kuten esim. 1,1,2,2-tetrakloorietaanissa tai rikkihiilessä.When Q in the compound of formula (III) is halogen, the reaction may be carried out using a Lewis acid such as e.g. aluminum halide (e.g. chloride) as a catalyst in a suitable inert solvent such as 1,1,2,2-tetrachloroethane or carbon disulphide.
Kun Q on hydroksyyli, booritrifluoridi tai (CF^CO^O ovat ensisijaisia katalysaattoreita, ja reaktio suoritetaan sopivassa liuottimessa tai ilman liuotinta.When Q is hydroxyl, boron trifluoride or (CF 2 CO 2 O) are the preferred catalysts, and the reaction is carried out in a suitable solvent or without a solvent.
Ei toivotun isomeerin tai ei toivottujen isomeerien määrää voidaan pienentää valitsemalla sopivat reaktio-olosuhteet, joissa lämpötilan säätö on erityisen tärkeätä. Sopiva reaktiolämpötila on 20°C:n ja kiehumislämpötilan välillä ja edullisesti 80°C:n ja kiehumislämpötilan välillä.The amount of undesired isomer or undesired isomers can be reduced by selecting appropriate reaction conditions in which temperature control is particularly important. A suitable reaction temperature is between 20 ° C and the boiling point, and preferably between 80 ° C and the boiling point.
Kuten edellä on esitetty, o-hydroksiryhmien asyylijohdannaisten valmistus voidaan suorittaa erilaisin menetelmin, esimerkiksi käsittelemällä o-hydroksibentsofenonia tai emäksisessä liuoksessa (esim. pyridiinissä tai alkalimetallihydroksidin kuten natrium- tai kaliumhydroksidin vesiliuoksessa) happoanhydridillä tai halogeenilla (lähinnä kloridi) tai asyloivan hapon liuoksella hap-poanhydridin ja katalysaattorin (esim. 70-%:inen perkloorihappo) läsnäollessa tai keittämällä palautusjäähdyttäen o-hydroksibentso-fenonin asyloivan hapon kanssa.As indicated above, the preparation of acyl derivatives of o-hydroxy groups can be carried out by various methods, for example by treatment with o-hydroxybenzophenone or an acid anhydride or halogen (mainly chloride) in an alkaline solution (e.g. pyridine or aqueous alkali metal hydroxide such as sodium or potassium hydroxide) and in the presence of a catalyst (e.g. 70% perchloric acid) or by refluxing with an acylating acid of o-hydroxybenzophenone.
Tämän keksinnön mukaisten o-hydroksibentsofenonien ja niiden johdannaisten on osoitettu olevan aktiivisia yhdessä tai useammassa neljästä kokeesta, joita tavallisesti käytetään antiallergi-sen aktiivisuuden toteamiseen. Mainituista kokeista kaksi on in vivo-kokeita - marsun ja ihmisen keuhkoleikekokeet - ja niihin sisältyy mediaattorien, histamiinin ja anafylaksian yhteydessä hitaasti reagoivan aineen (SRS-A), joita on osoitettu vapautuvan astmaattisen ihmisen keuhkoissa, suora määritys. Tämän keksinnön mukaisen yhdisteen katsotaan olevan aktiivinen, jos SRS-A:n vapautumista voidaan ehkäistä marsun keuhkoleikekokeessa ainakin 30 % annoksen ollessa 10 yug/ml tai pienempi. Kokeissa käytettävän lääkkeen absorptiosta, jakautumisesta ja metaboliasta riippuen tämän tasoinen aktiivisuus keuhkoleikekokeessa merkitsee, että in vi-vo-annos suun kautta annettuna on noin 0,5 - 100 mg/kg.The o-hydroxybenzophenones of this invention and their derivatives have been shown to be active in one or more of the four assays commonly used to detect antiallergic activity. Two of these experiments are in vivo experiments - guinea pig and human lung section experiments - and involve the direct determination of mediators, histamine and anaphylaxis slow-acting substance (SRS-A), which have been shown to be released in the lung of asthmatic humans. A compound of this invention is considered active if the release of SRS-A can be inhibited in a guinea pig lung section test at a dose of at least 30% at a dose of 10 μg / ml or less. Depending on the absorption, distribution and metabolism of the drug used in the experiments, this level of activity in the lung section experiment means that the in vivo oral dose is about 0.5 to 100 mg / kg.
* 68609* 68609
Muut kaksi koetta ovat in vivo-kokeita - Herxheimer-koe ja rotan vatsakalvoanafylaksia-koe - ja heijastuvat suun kautta annettuna kahta erilaista vaikutustapaa. Herxheimer-kokeessa altistetut marsut saadaan suojatuksi antigeeni-aerosolilla aiheutettuna keuhkoputkien koristusta vastaan, kun sensijaan rotilla vatsa-kalvoanafylaksia-kokeessa mitataan suoraan vapautunut SRS-A. Kokeiltaessa aktiivisia yhdisteitä näissä in vivo-kokeissa, vaikutus saavutettiin tavallisesti annoksilla 300 mg/kg tai alle.The other two trials are in vivo trials - the Herxheimer trial and the rat peritoneal anaphylaxis trial - and are reflected in two different modes of action when administered orally. Guinea pigs exposed in the Herxheimer experiment are protected by antigen aerosol induction of bronchial decoration, whereas instead of directly measured SRS-A in rats in the peritoneal membrane anaphylaxis experiment. When testing active compounds in these in vivo experiments, the effect was usually achieved at doses of 300 mg / kg or less.
Tämän keksinnön yhdisteillä ilmenee aktiivisuutta yhdessä tai useammassa edellä esitetyistä kokeista (laajin vaikutusspekt-ri on yhdisteillä, joilla on anti-allerginen vaikutus kaikissa neljässä kokeessa), ja ne ovat sen vuoksi käyttökelpoisia annettaessa ennalta ehkäisevää ja terapeuttista hoitoa äkillisissä yliherkkyyssairauksissa, astma mukaan luettuna, ja lievitettäessä status asthmaticus-tilaa. Eräissä tapauksissa yhdisteiden on todettu olevan käyttökelpoisia sairauksissa, joissa vapautuu ylimäärin prostaglandiineja, ja hengityselinten stimulanttina. Yhdisteiden myrkyllisyys on alhainen.The compounds of this invention exhibit activity in one or more of the above experiments (the broadest spectrum of activity is of compounds having anti-allergic activity in all four experiments) and are therefore useful in the prophylactic and therapeutic treatment of acute hypersensitivity diseases, including asthma, and in relieving status asthmaticus. In some cases, the compounds have been found to be useful in diseases in which excess prostaglandins are released and as a respiratory stimulant. The toxicity of the compounds is low.
Keksintöä kuvaavat edelleen seuraavat esimerkit:The invention is further illustrated by the following examples:
Esimerkki 1 2^41-dikloori-3-etyyli-2-hydroksibentsofenoniExample 1 2- [4-Dichloro-3-ethyl-2-hydroxybenzophenone
Aluminiumkloridia (26,7 g) lisättiin erinä sekoitettuun seokseen, jossa oli 2-etyylifenolia (12,2 g) ja 2,4-diklooribentso-yylikloridia (23,1 g) 1,1,2,2,-tetrakloorietaanissa (100 ml), ja sen jälkeen seosta kuumennettiin palautusjäähdyttäen 21 tuntia. Jäähtynyt liuos kaadettiin jäillä (200 g) jäähdytettyyn väkevään suolahappoon (100 ml). Orgaaninen fraktio erotettiin ja yhdistettiin kahden muun vesifraktiota pesemällä saadun klorofarmierän kanssa, ja sen jälkeen orgaaninen liuos pestiin kahdesti 10-prosentti-sella natriumkarbonaatin vesiliuoksella, kuivattiin magnesium-sulfaatti-monohydraatilla ja haihdutettiin tummaksi viskoosiseksi öljyksi (30,0 g). Tämä öljy tislattiin vakuumissa, jolloin ensimmäinen fraktio (156-172°C/0,06 mmHg) sisälsi 85 % haluttua tuotetta. (Ferrikloridiliuoksella käsiteltäessä muodostui purppuran-väristä liuosta, mikä osoitti, että läsnä oli o-hydroksiketonia). Ketonituote puhdistettiin kromatografoimalla piioksidi-kolonnissa, n22 = 1,6163.Aluminum chloride (26.7 g) was added portionwise to a stirred mixture of 2-ethylphenol (12.2 g) and 2,4-dichlorobenzoyl chloride (23.1 g) in 1,1,2,2-tetrachloroethane (100 ml). ), and then the mixture was heated to reflux for 21 hours. The cooled solution was poured into ice-cold concentrated hydrochloric acid (100 ml) (200 g). The organic fraction was separated and combined with the other two portions of chloroform obtained by washing the aqueous fraction, then the organic solution was washed twice with 10% aqueous sodium carbonate solution, dried over magnesium sulphate monohydrate and evaporated to a dark viscous oil (30.0 g). This oil was distilled in vacuo, the first fraction (156-172 ° C / 0.06 mmHg) containing 85% of the desired product. (Treatment with the ferric chloride solution gave a purple solution, indicating the presence of o-hydroxyketone). The ketone product was purified by chromatography on a silica column, n22 = 1.6163.
5 686095 68609
Esimerkki 2Example 2
Keksinnön mukaiselle menetelmälle analoginen menetelmä: 4-klooribentsoyylikloridia (1,35 g, 0,0077 moolia) lisättiin tiputtamalla liuokseen, jossa oli 4-etyylifenolia (0,86 g, 0,0070 moolia) 2,5-n natriumhydroksidin vesiliuoksessa (5,6 ml). Seosta ravisteltiin voimakkaasti 15 minuutin ajan, jolloin siitä erottui vaaleanruskeata kiinteätä ainetta. Seos laimennettiin vedellä (10 ml) ja kiinteä aine suodatettiin erilleen, pestiin vedellä (3 x 20 ml) ja kuivattiin. Kiinteä aine kiteytettiin uudelleen kahdesti n-heksaanista, jolloin saatiin vaaleanruskeita 4-etyylifenyyli-4-klooribentsoaatti-kiteitä, sp. 66,5-67°C.A method analogous to the process of the invention: 4-chlorobenzoyl chloride (1.35 g, 0.0077 mol) was added dropwise to a solution of 4-ethylphenol (0.86 g, 0.0070 mol) in aqueous 2.5 N sodium hydroxide solution (5, 6 ml). The mixture was shaken vigorously for 15 minutes to give a light brown solid. The mixture was diluted with water (10 mL) and the solid was filtered off, washed with water (3 x 20 mL) and dried. The solid was recrystallized twice from n-hexane to give light brown 4-ethylphenyl-4-chlorobenzoate crystals, m.p. 66.5 to 67 ° C.
Edellä mainittua esteriä (2,6 g) lämmitettiin aluminiumklo-ridin (1,33 g) kanssa tetrakloorietaanissa 6 tuntia 125°C:ssa. Tämän ajan jälkeen otettu näyte lisättiin laimeaan suolahappoon ja orgaaninen aine uutettiin kloroformiin. Kaasukromatografia-analyysi osoitti, ettei liuoksessa ollut esteriä, ja vertaamalla autenttiseen näytteeseen tuote todettiin 41-kloori-5-etyyli-2-hydroksi-bentsofenoniksi.The above ester (2.6 g) was heated with aluminum chloride (1.33 g) in tetrachloroethane for 6 hours at 125 ° C. After this time, the sample was added to dilute hydrochloric acid, and the organic matter was extracted with chloroform. Gas chromatographic analysis showed no ester in the solution, and by comparison with an authentic sample, the product was found to be 41-chloro-5-ethyl-2-hydroxybenzophenone.
Tällä menetelmällä valmistettiin myös keksinnön piiriin kuuluvat: 5-etyyli-2-hydroksi-4'-metyylibentsofenoni, sp. 49-51°C ja 4'-kloori-3,5-dietyyli-2-hydroksibentsofenoni, kp. 188°C/1,4 mmHg.By this method, the following were also prepared: 5-ethyl-2-hydroxy-4'-methylbenzophenone, m.p. 49-51 ° C and 4'-chloro-3,5-diethyl-2-hydroxybenzophenone, b.p. 188 ° C / 1.4 mmHg.
Claims (1)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB15805/75A GB1549171A (en) | 1975-04-17 | 1975-04-17 | Pharmaceutical formulations containing hydrocy bezophenonederivatives |
GB1580575 | 1975-04-17 |
Publications (3)
Publication Number | Publication Date |
---|---|
FI760999A FI760999A (en) | 1976-10-18 |
FI68609B true FI68609B (en) | 1985-06-28 |
FI68609C FI68609C (en) | 1985-10-10 |
Family
ID=10065798
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FI760999A FI68609C (en) | 1975-04-17 | 1976-04-13 | FRAMEWORK FOR THERAPEUTIC ACTIVATION OF THERAPEUTIC ACTIVATION |
Country Status (35)
Country | Link |
---|---|
JP (1) | JPS51128950A (en) |
AR (1) | AR217399A1 (en) |
AT (2) | AT347430B (en) |
AU (1) | AU502015B2 (en) |
BE (1) | BE840826A (en) |
BG (1) | BG33275A3 (en) |
CA (1) | CA1055041A (en) |
CH (1) | CH617654A5 (en) |
CS (1) | CS196305B2 (en) |
DD (1) | DD123596A5 (en) |
DE (2) | DE2546738C2 (en) |
DK (1) | DK146476A (en) |
EG (1) | EG12255A (en) |
ES (1) | ES446993A1 (en) |
FI (1) | FI68609C (en) |
FR (1) | FR2307524A1 (en) |
GB (1) | GB1549171A (en) |
GR (1) | GR59849B (en) |
HU (1) | HU176276B (en) |
IE (1) | IE42968B1 (en) |
IL (1) | IL49280A (en) |
LU (1) | LU74773A1 (en) |
MX (1) | MX3394E (en) |
NL (1) | NL7604164A (en) |
NO (1) | NO146022C (en) |
NZ (1) | NZ180379A (en) |
OA (1) | OA05301A (en) |
PH (1) | PH11507A (en) |
PL (1) | PL103084B1 (en) |
PT (1) | PT65015B (en) |
RO (1) | RO71258A (en) |
SE (1) | SE7604426L (en) |
SU (2) | SU644372A3 (en) |
YU (1) | YU97176A (en) |
ZA (1) | ZA761737B (en) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2377202A2 (en) * | 1977-01-12 | 1978-08-11 | Pharmascience Lab | PHARMACEUTICAL COMPOSITIONS CONTAINING HEXAHYDROXY-2,3,4,3 ', 4', 5'-BENZOPHENONE |
JPS6197240A (en) * | 1984-10-16 | 1986-05-15 | Sankyo Kasei Kk | Preparation of polyhydroxybenzophenone |
GB8603578D0 (en) * | 1986-02-13 | 1986-03-19 | Ici Plc | Aromatic ketone |
LU86387A1 (en) * | 1986-04-04 | 1987-12-07 | Oreal | AROMATIC COMPOUNDS, THEIR PREPARATION PROCESS AND THEIR USE IN HUMAN AND VETERINARY MEDICINE AND IN COSMETICS |
FR2649975B1 (en) * | 1989-07-19 | 1991-11-22 | Inst Nat Rech Chimique | NOVEL ACETYLENIC DERIVATIVES, THEIR PREPARATION PROCESS, NOVEL ACETYLENIC POLYMERS AND THEIR APPLICATIONS |
CA2133587C (en) * | 1992-04-22 | 2008-11-18 | Marcus F. Boehm | Compounds having selectivity for retinoid x receptors |
US5780676A (en) * | 1992-04-22 | 1998-07-14 | Ligand Pharmaceuticals Incorporated | Compounds having selective activity for Retinoid X Receptors, and means for modulation of processes mediated by Retinoid X Receptors |
US7655699B1 (en) | 1992-04-22 | 2010-02-02 | Eisai Inc. | Compounds having selective activity for retinoid X receptors, and means for modulation of processes mediated by retinoid X receptors |
US5962731A (en) * | 1992-04-22 | 1999-10-05 | Ligand Pharmaceuticals Incorporated | Compounds having selective activity for retinoid X receptors, and means for modulation of processes mediated by retinoid X receptors |
WO1994015901A1 (en) * | 1993-01-11 | 1994-07-21 | Ligand Pharmaceuticals Inc. | Compounds having selectivity for retinoid x receptors |
GB9620202D0 (en) * | 1996-09-27 | 1996-11-13 | Rhone Poulenc Agriculture | New herbicides |
GB2446397A (en) * | 2007-02-06 | 2008-08-13 | Gharda Chemicals Ltd | Improved processes for the production of poly(ether ketone) - PEK - and its monomer |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1060855A (en) * | 1963-09-20 | 1967-03-08 | Ici Ltd | Substituted aromatic ketones |
CH510395A (en) * | 1969-07-17 | 1971-02-15 | Ciba Geigy Ag | Use of 2-hydroxybenzophenones for antimicrobial finishing or for protecting textile materials against harmful microorganisms |
CH515871A (en) * | 1969-07-25 | 1971-11-30 | Sandoz Ag | Process for the preparation of new 2-hydroxy-3,5-tert-butyl-benzophenones |
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1975
- 1975-04-17 GB GB15805/75A patent/GB1549171A/en not_active Expired
- 1975-10-18 DE DE2546738A patent/DE2546738C2/en not_active Expired
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1976
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- 1976-03-30 DK DK146476A patent/DK146476A/en not_active IP Right Cessation
- 1976-04-01 NZ NZ180379A patent/NZ180379A/en unknown
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- 1976-04-09 DE DE19762615487 patent/DE2615487A1/en not_active Withdrawn
- 1976-04-12 AR AR262848A patent/AR217399A1/en active
- 1976-04-12 OA OA55796A patent/OA05301A/en unknown
- 1976-04-12 CH CH459876A patent/CH617654A5/en not_active IP Right Cessation
- 1976-04-13 ES ES446993A patent/ES446993A1/en not_active Expired
- 1976-04-13 FI FI760999A patent/FI68609C/en not_active IP Right Cessation
- 1976-04-13 CA CA250,199A patent/CA1055041A/en not_active Expired
- 1976-04-13 RO RO7685607A patent/RO71258A/en unknown
- 1976-04-13 FR FR7610788A patent/FR2307524A1/en active Granted
- 1976-04-14 PH PH18332A patent/PH11507A/en unknown
- 1976-04-14 PL PL1976188773A patent/PL103084B1/en unknown
- 1976-04-14 SE SE7604426A patent/SE7604426L/en not_active Application Discontinuation
- 1976-04-14 MX MX000173U patent/MX3394E/en unknown
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- 1976-04-15 BE BE6045444A patent/BE840826A/en not_active IP Right Cessation
- 1976-04-15 AT AT278676A patent/AT347430B/en not_active IP Right Cessation
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- 1976-04-16 SU SU762345332A patent/SU644372A3/en active
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- 1976-04-17 EG EG76217A patent/EG12255A/en active
- 1976-04-17 JP JP51044159A patent/JPS51128950A/en active Pending
- 1976-04-20 AU AU13154/76A patent/AU502015B2/en not_active Expired
- 1976-04-20 NL NL7604164A patent/NL7604164A/en not_active Application Discontinuation
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1977
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Legal Events
Date | Code | Title | Description |
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MM | Patent lapsed |
Owner name: LILLY INDUSTRIES LIMITED |