Method of producing 3-/2-(dimethylamino)-ethyl/-n-methyl-1n-invol-5-methane sulfonamide or its salts

专利摘要:
A compound of formula (I) <IMAGE> (I) and its physiologically acceptable salts and solvates are described as useful in treating and/or preventing pain resulting from dilatation of the cranial vasculature in particular migraine. The compound (I) may be prepared, for example, by cyclizing a compound of formula (II) <IMAGE> (II)
公开号:SU1498386A3
申请号:SU853935745
申请日:1985-08-01
公开日:1989-07-30
发明作者:Вильям Оксфорд Александр
申请人:Глэксо Груп Лимитед (Фирма)；
IPC主号:

专利说明:

This invention relates to a process for the preparation of a novel (dimethylamino) -til methyl-N-methyl-1H-indol-5-methanol-n-amide of formula
CHjllH-SOiCHt-roYQj-CHiCHiU (CH3) 2
or its salts, or solvates, which have a vasoconstrictive effect and can be used in medicine.
The lleJibHj of the invention is the development, based on the well-known method of the method for the use of new compounds, possessing the vessel-imaginary system.
Example I. Send t PHHoe connection with ntlr) cyglot (111 (l: 1).
A solution of 2 g of 3- (2-amino: thyl) -N-Methyl-1H-indole-5-methanesulfonamide and 0.564 g of sodium cyanoborohydride in 37.5 ml of methanol and 2.246 g of acetic acid are treated at approximately 1-2 C with a solution ( Zb / -w / ov) aqueous formaldehyde (1.25 ml) in 8.85 ml of methanol. The resulting solution was stirred for 2 hours at 22 ° C, after which 6.5 ml of 2N sodium hydroxide solution and 0.1 g of sodium borohydride were added. To the reaction sms, 7 ml of 2N hydrochloric acid was added, the methanol was evaporated, and drains up to 25 ml. Yat achieve rp 7 cob.plip solid potassium carbonate, ii.iriiop washed with ethyl acetate p-i rifi jet weaves
;about
00 oo
00
about:
 cm
i1 / 4H
pprm (.tweld. Aqueous gdc and washables | b-), feeds, saturate the carbohydrate cell line and extract with 1-ttyl ethyl acetate; ctl (1 | e of tcsthm cyiUtiT over magnesium sulphate and evaporate to obtain 1, 8 g of solid residue. G residue is recrystallized ich 16.7 ml of ittotropanol to obtain 1.307 g of crystalline base, 1.297 g of which is dissolved in 13 ml of PtMC and treated with a hot solution of 0.518 g of succinic acid in 1 3 ml of liMC, Leaks. 1 solution is cooled, the precipitated precipitate is filtered off and dried, yielding 1.737 g of salt 3- 2- (d1-methylamino) -ethyl j-N-methyl-1H-yndol-5-methanesulfonamide with succinic acid (1: 1),
m.p. 165-168 S.
Example 2 about the proposed connection ..
A solution of 7.1 g of sodium borohydride in water and 50 ml of formalin (36% May, //), in 50 ml of methanol is added to a solution of 10 g of 3- (2-amino-ethyl) -N-methyl-1H-indole-5 -methanesulfonamide in 200 ml of methanol at 15-2l s for 0.75 h. Then 75 ml of 2H hydrochloric acid are added and the mixture is evaporated in vacuo to 150 ml. "60 g of potassium carbonate is added to the mixture and extracted with ethyl acetate ( 2x150 ml) The combined extracts are dried over magnesium sulphate and concentrated in vacuo to give 10.7 g of (di-methylamino) -ethyl-methyl-1H-indole-5-methanesulphonamide, ToPL, 169-171 °; PRI me R 3. The proposed connection with fumaric acid (2: 1).
A hot solution of 590.8 mg of the product of example 2 in 7 ml of IC is treated with one portion of a hot solution of 128 mg of fumaric acid in 8 ml of 1-IMC, after which the mixture is cooled to 25 ° C. The resulting suspension is stirred for 30 minutes under ice cooling and then filtered Filter cake Washed with 2 ml ICD and dried under vacuum to give 619 mg of the compound, m.p. 204.5-206 ° С (with decomp.)
Found,%: C 54.1; H 6.7; N 7.
C C,
Calculated, C 54,4; H 6.6; R 11.9 ..
PRI me R 4. The proposed connection with benzoic acid (1: 1).
Hot solution 590,8 mg product. of example 3 in 7 ml of IMG coated with
Q 5
0
5 0 C 0

0
one (111 portions of hot acTB ipa 244 fn-benchoic acid in 2 ml of No. 1 C. pvl | lt 0.5 mp IM (and dried in B.iKywie to obtain 633 mg of the compound with mp. 173-175 C.
Paidrno, / :: C 60.3; H 6.6; N 9.9.
, -; -c, 11, oh,
Calculated: C 60.4; H 6, S; N .0, L
ll p ume r 5. The proposed compound with methanesulfone laL.Jiu-one (1: 1 |.
A warm solution of 0.213 g of methanolic background acid in 3 ml of IfMC added kp when moving to a solution of 0.597 g of the product g; p1-guml 3n 9 gsh hot PMS Paul}, silt neiU MeiinTB.jeMbiii solution is cooled to room temperature for one hour, cooled 20 mi / in an ice bath and then filtered. Salt obtained in the solid solid form at 0.642 g, so pl. 186-188,5 p.
Found,%: C 46; H 6.6; N 10.6.
C ,, H ,, N, 0, r-. STiOZP
In 1 number,%: C 46; H 6.4; N 10.7,
PRI me R 6. A compound with succinic acid and ethanol was proposed.
A hot clarified solution, 2h g of succinic acid in 10 ml of IC, is added to a stirred clarified solution of 3.14 of the product of Example 3 in 60 ml of IC at 70 ° C. The crystallization of the solid begins almost immediately and the mixture is cooled} until the stirred mixture is continued to cool for 45 minutes in an ice-bath. The solid is removed, filtered, washed with 36 ml of cold ethanol and dried under vacuum to obtain 4.17 g of the compound, t „ square 164-165 C. The product contains 5.52 wt.% / Maso ethanol (0.52 mol).
Found,%: C 51.7; H 6.95; N 9.8.
C H JJOJS. 0.5
Calculated,%: C, 52.25; H 6.95; N 9.6 „
Example 7 “Proposed compound with X.PORITE hydrogen (1: 1). To a stirred solution of 504 m of the product of example 3 in 4 ml of IC was added at 65 C 0.18 ml of concentrated hydrochloric acid, Then the solution was cooled to 2.i ° C, while observing fS, 8; N 12.6 H 6.7;
Р1Г.Я К1П1гт lipipi of taperl | 1st stage Continue to cool on the panel with HILT-ICE, taty solid Liltrovaprm is collected. The precipitate on the filter is washed (({((x1 ml) and s.utag at p. Nizhenzh M preslelia with a 517 mg compound, so pl./mi-215 C.
Found,%: C 50.75; one
C ,, H2, N, 0, / .NP1
Vmsisleno, / ;: С iO, 5; N 12.7,
Toxicological data
The following trials were carried out using the 3-f G salt: -C dimethylmino) -iTmi} -M-methyl-1P-indole-5-methanesulfonamide. with ampere h) acid (l: lj, introduction of pillboxes are triggered by the weight of the free base and
The compound administered orala to the group but ten rats each in up to 2 g / kg, In each group, half of the animals are followed in 3 days, and the remaining part is drawn in 14 days. During the periods of the survey, half
Determination of efficacy following intraduodenal injection.
The compound is administered intraduodenally to 5 anesthetized beagle dogs at a single dose equivalent to
lOxCDr. (measured, trace inside
The introduction of the vein as described in the vagina ;,
and carotid blood flow is measured using an electromagnetic flow test about
t5
20
 25
animals survived.
LD
50
2 g / kg.
The test is also carried out with intravenous administration of the compound at doses of 32 mg / kg. During the same period of examination of the basement, 1a of the animals emerged. LD (32 mg / kg
Biological tests of the compound were performed, showing its vasoconstrictive effect. The comparison was carried out with 3- (2-aminotthyl) -K-methyl-1H-indole-5-methanesulfonamide. Comparison data is given in the table,
The reduction of carotid blood no-G about the bed in dogs.
SP score, i.e. The cumulative dose required to achieve 5P7, from the maximum increase in carotid weight resistance, is determined in the hutrivepny administration of the compound to anesthetized beagle dogs at 15 min intervals, starting with a dosage of 1 µg / kg followed by the introduction of progressively increasing doses up to cum a dose of 300 µg / kg when the maximum increase in carotid vascular resistance is reached. Carotid blood flow is measured by means of an electromagnetic flow test, with a peak increase in kprotid vascular blood (resistance at each dose) recorded.
Connection: Suggested
35.8
More than 78
345
63
More than 80 134
0
five
0
3- (2-amino-ethyl) -N-methyl-1H-indole-5-methanesulfonamide
23
Criterion for progression to next test.
Less than 50
125 72 63 22
More than 39 34 33
More than 50
The table shows the advantages of the proposed compound ({for effective and stable absorption from the gastrointestinal tract.) Besides 1 (.) Th, the connection does not show
 ) ARA i8b
t any irblagoiri timh ..SNz
In the course of IGSPDOALYY on CHJ.
, N-S07C l - f vr7 T CHj
mutagenicity of OL X .MJ
T Chkim way. Connection nro tshch-, e7 vasoconstriction activity and can
to find application in medicine for le-or its salts, or solvates, for the pain caused by the violation of l and h for in and with the fact that 3- (2-nd vascular system, in particular amino-ethyl) -N-methyl -l H-indpl-5-metangchgreni, and other similar kara-IQ sulfonamide, undergo interaction with formaldehyde and borohydride

权利要求:
Claims (1)
[1]
Claims of the invention or sodium cyanoborohydride with the following method of preparation (discharging of the desired product
mino) -ethylJ-N-metRf -1 AND-indole-5-me-in the common species, or as a salt,
tansulfonamida formula 15 or solvate,

类似技术:

---

公开号 | 公开日 | 专利标题

---

SU1498386A3|1989-07-30|Method of producing 3-/2-|-ethyl/-n-methyl-1n-invol-5-methane sulfonamide or its salts or solvates

---

US3769286A|1973-10-30|Trialkoxy quinazolines

---

SU1428199A3|1988-09-30|Versions of method of producing derivatives of 2,2,3-iminobisethanol or acid-additive salts thereof,or stereochemical isomeric forms thereof

---

CA2087606C|2001-10-23| quinoxaline derivatives and methods for using same

---

US3793365A|1974-02-19|Amino acid derivatives

---

US4349549A|1982-09-14|Anti-hypertensive 1-substituted spiro|s

---

US4181729A|1980-01-01|Phenyl or phenoxy substituted spiro-imidazolidinedione derivatives

---

US4283539A|1981-08-11|Isoquinoline acetic acids

---

US4732916A|1988-03-22|Novel guanidinomethylbenzoic acid derivatives

---

US3678092A|1972-07-18|3-hydroxycyclopentyl-alkanoic acids

---

JP2013177462A|2013-09-09|Pharmaceutical composition

---

EP0171702A1|1986-02-19|Benzoxazinone derivatives, preparation and use

---

US5198442A|1993-03-30| quinoxaline derivatives and methods for using same

---

US4111962A|1978-09-05|Certain substituted 2-phenylnaphtho[1,2-b]furane and -[2,1-b]furane

---

US4314943A|1982-02-09|Heterocyclic substituted aryloxy 3-indolyl-tertiary butylaminopropanols

---

US4229464A|1980-10-21|Aminopropanol substituted indole compounds and compositions for the treatment of cardiac and circulatory diseases

---

US4382936A|1983-05-10|Cerebral vasodilator eburnane derivatives

---

SU1620049A3|1991-01-07|Method of producing derivatives of 4-|-pyperidine butanamide or their stereo isomers, or pharmaceutically acceptable acid-additive salts

---

US3890318A|1975-06-17|Derivatives of triiodo aminobenzenecarboxylic acids and the preparation thereof

---

IE62014B1|1994-12-14|Castanospermine esters in the inhibition of tumor metastasis

---

US4209527A|1980-06-24|Benzimidazolone derivatives

---

US3888983A|1975-06-10|Derivatives of thiazolino-pyrimidin-6-ones, in inducing analgesia

---

US5912261A|1999-06-15|Carboxyalkyl heterocyclic derivatives

---

US3925412A|1975-12-09|Cycloamidines

---

US4275192A|1981-06-23|Bis|dihydrazone derivatives and pharmacologically acceptable salts thereof

同族专利:

---

公开号 | 公开日

---

IS3034A7|1986-02-02|

---

JPH0623197B2|1994-03-30|

---

PL146005B1|1988-12-31|

---

AU573878B2|1988-06-23|

---

IE851918L|1986-02-01|

---

SE8503680D0|1985-08-01|

---

ES8700234A1|1986-10-16|

---

ES8801204A1|1987-12-16|

---

KE3858A|1989-06-02|

---

PT80900A|1985-09-01|

---

AU4568985A|1986-02-06|

---

PH22850A|1989-01-19|

---

JO1379B1|1986-11-30|

---

NO164653C|1990-11-07|

---

NO853046L|1986-02-03|

---

AT386196B|1988-07-11|

---

LU88266I2|1994-02-03|

---

US5037845A|1991-08-06|

---

IS1430B6|1990-07-16|

---

LU86032A1|1986-02-18|

---

ES552047A0|1987-12-16|

---

DE3527648C2|1993-08-26|

---

CZ404191A3|1993-04-14|

---

ES557480A0|1988-02-16|

---

JPS6147464A|1986-03-07|

---

HK33289A|1989-04-28|

---

UA6329A1|1994-12-29|

---

NL930065I2|1993-10-01|

---

DK351185A|1986-02-02|

---

ES8801788A1|1988-02-16|

---

FI78466B|1989-04-28|

---

SK404191A3|1995-09-13|

---

SK277952B6|1995-09-13|

---

DK158942B|1990-08-06|

---

BE903006A|1986-02-03|

---

SE8503680L|1986-02-02|

---

EG17283A|1992-06-30|

---

FI78466C|1989-08-10|

---

ES557482A0|1988-03-01|

---

FR2568571A1|1986-02-07|

---

FR2568571B1|1988-09-23|

---

ZW12485A1|1986-02-26|

---

NZ212948A|1989-05-29|

---

MX14221A|1993-10-01|

---

NO1994023I1|1994-11-09|

---

MX159672A|1989-08-02|

---

IL75986D0|1985-12-31|

---

PT80900B|1987-12-30|

---

DK158942C|1991-01-21|

---

IE58122B1|1993-07-14|

---

NL8502171A|1986-03-03|

---

NL930065I1|1993-09-01|

---

PL254800A1|1986-10-21|

---

ECSP941096A|1995-01-16|

---

ES557481A0|1988-02-16|

---

NL188642C|1992-08-17|

---

CH666026A5|1988-06-30|

---

PH24117A|1990-03-05|

---

IT1207325B|1989-05-17|

---

HU201738B|1990-12-28|

---

DK351185D0|1985-08-01|

---

FI852969L|1986-02-02|

---

KR860001788A|1986-03-22|

---

ES557483A0|1988-02-16|

---

DOP1989004759A|1999-02-06|

---

FI852969A0|1985-08-01|

---

ES545810A0|1986-10-16|

---

KR930003759B1|1993-05-10|

---

DE3527648A1|1986-02-13|

---

CZ280530B6|1996-02-14|

---

ES8801790A1|1988-02-16|

---

IL75986A|1989-02-28|

---

ES8801900A1|1988-03-01|

---

ZA855818B|1986-04-30|

---

SE452460B|1987-11-30|

---

NO164653B|1990-07-23|

---

GB8419575D0|1984-09-05|

---

ES8801789A1|1988-02-16|

---

ATA226685A|1987-12-15|

---

CA1241004A|1988-08-23|

---

MA20499A1|1986-04-01|

---

GR851850B|1985-11-26|

---

IT8548435D0|1985-08-01|

---

HUT40077A|1986-11-28|

引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

DE311728C|

---

US3322787A|1964-09-25|1967-05-30|Merck & Co Inc|Alpha-hydrazino-beta- alkanoic acid derivatives|

---

IT1036004B|1968-05-21|1979-10-30|Abc Ist Biolog Chem Spa|ACIDT 3 INDOLYL ADETOHYDROXAMICS|

---

US4283410A|1978-06-15|1981-08-11|Miles Laboratories, Inc.|3-Amino or amido-2- propanoic acid derivatives|

---

ZA795239B|1978-10-12|1980-11-26|Glaxo Group Ltd|Heterocyclic compounds|

---

ZW19381A1|1980-08-12|1983-03-09|Glaxo Group Ltd|Heterocyclic compounds|

---

AU548467B2|1980-08-12|1985-12-12|Glaxo Group Limited|Tryptamines and their isoindolylethyl derivatives|

---

DE3131752C2|1980-08-12|1992-04-23|Glaxo Group Ltd., London, Gb|

---

GR79215B|1982-06-07|1984-10-22|Glaxo Group Ltd|

---

GB8332434D0|1983-12-06|1984-01-11|Glaxo Group Ltd|Production of chemical compounds|

---

GB8332435D0|1983-12-06|1984-01-11|Glaxo Group Ltd|Chemical compounds|US5270333A|1986-01-28|1993-12-14|Glaxo Group Limited|Indole derivatives|

---

US5935925A|1990-05-08|1999-08-10|Synaptic Pharmaceutical Corporation|Methods of treating migraine and compounds useful for such methods|

---

US5155218A|1990-05-08|1992-10-13|Neurogenetic Corporation|Dna encoding human 5-ht1d receptors|

---

GB9013845D0|1990-06-21|1990-08-15|Glaxo Group Ltd|Process|

---

GB9022250D0|1990-10-12|1990-11-28|Glaxo Group Ltd|Medicaments|

---

GB9102579D0|1991-01-24|1991-03-27|Glaxo Group Ltd|Compositions|

---

GB9101592D0|1991-01-24|1991-03-06|Glaxo Group Ltd|Compositions|

---

CZ283018B6|1991-02-01|1997-12-17|Merck Sharp And Dohme Limited|Imidazole, triazole and tetrazole derivatives, process of their preparation, their use and pharmaceuticals based thereon|

---

GB9104890D0|1991-03-08|1991-04-24|Glaxo Group Ltd|Compositions|

---

AT399870B|1991-06-06|1995-08-25|Vita Invest Sa|Process for the preparation of 3-ethyl)- N-methyl-1H-indole-5-methanesulphonamide|

---

GB9209882D0|1992-05-07|1992-06-24|Glaxo Lab Sa|Compositions|

---

ES2059236B1|1992-06-18|1995-06-16|Imidex S A|PROCEDURE FOR THE SYNTHESIS OF 3-ETIL) -N-METHYL-1H-INDOL-5-METHANOSULFONAMIDE.|

---

ES2055651B1|1992-07-20|1995-03-01|Vita Invest Sa|PROCEDURE FOR THE OBTAINING OF NEW AMIDINES DERIVED FROM 3-AMINOETILINDOLES.|

---

IL106445A|1992-07-30|1998-01-04|Merck Sharp & Dohme|4-substituted 1, 2, 4-triazole derivatives, their preparation and pharmaceutical compositions containing them|

---

AT399871B|1993-02-15|1995-08-25|Vita Invest Sa|Process for the preparation of 2-carboxy-3-ethyl)-N-methyl-1H-indole-5-methanesulphonamide and its lower alkyl esters|

---

US5807571A|1993-05-06|1998-09-15|Lts Lohmann Therapie-Systeme Gmbh|Transdermal therapeutic systems for administering indole serotonin agonists|

---

GB9401436D0|1994-01-26|1994-03-23|Wellcome Found|Therapeutic heterocyclic compounds|

---

ES2084560B1|1994-03-09|1997-01-16|Almirall Lab|EL INDOL DERIVATIVES PREPARATION PROCEDURE.|

---

ES2079323B1|1994-06-21|1996-10-16|Vita Invest Sa|DERIVATIVES OF INDOL USEFUL FOR THE TREATMENT OF THE MIGRAINE, COMPOSITION AND CORRESPONDING USE.|

---

EP0804434A1|1994-08-02|1997-11-05|MERCK SHARP &amp; DOHME LTD.|Azetidine, pyrrolidine and piperidine derivatives|

---

US5521197A|1994-12-01|1996-05-28|Eli Lilly And Company|3-<1-alkylenearyl>-4-<1,2,3,6-tetrahydropyridinyl>-and 3-<1-alkylenearyl>-4-piperidinyl-1h-indoles: new 5-HT1F agonists|

---

US8022095B2|1996-08-16|2011-09-20|Pozen, Inc.|Methods of treating headaches using 5-HT agonists in combination with long-acting NSAIDs|

---

AU4074897A|1996-09-18|1998-04-14|Eli Lilly And Company|A method for the prevention of migraine|

---

AU4652697A|1996-10-08|1998-05-05|Eli Lilly And Company|New serotonin 5-ht1f agonists|

---

GB9714383D0|1997-07-08|1997-09-10|Pfizer Ltd|Improved process|

---

US6416472B1|1997-11-06|2002-07-09|Edus Inc.|Method and device for measuring cognitive efficiency|

---

US6066092A|1997-11-06|2000-05-23|Cady; Roger K.|Preemptive prophylaxis of migraine device and method|

---

US7189753B1|1997-11-06|2007-03-13|Cady Roger K|Preemptive prophylaxis of migraine|

---

JP4625637B2|2002-02-22|2011-02-02|シャイアエルエルシー|Active substance delivery system and method for protecting and administering an active substance|

---

AT500063A1|1999-11-23|2005-10-15|Sandoz Ag|COATED TABLETS|

---

CA2442281C|2001-03-27|2010-06-08|GalenLimited|Intravaginal drug delivery devices for the administration of an antimicrobial agent|

---

WO2003032983A1|2001-06-05|2003-04-24|Ronald Aung-Din|Transdermal migraine therapy|

---

FR2827287B1|2001-07-13|2003-10-31|Servier Lab|NOVEL BENZENE SULFONAMIDE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM|

---

US20060106227A1|2002-06-13|2006-05-18|Dr Reddy's Laboratories Limited|3-'2- ethyl!-n-methyl-1h-indole-5-methanesulfonamide and the succinate thereof|

---

US20040068000A1|2002-10-02|2004-04-08|Mintong Guo|Compression coated tablets|

---

CN1176649C|2002-10-16|2004-11-24|上海医药工业研究院|Inhalant of Shumaputan dry-powder and its preparation method|

---

EP1572647B1|2002-12-20|2016-09-21|Basf Se|Synthesis of amines and intermediates for the synthesis thereof|

---

US20080213363A1|2003-01-23|2008-09-04|Singh Nikhilesh N|Methods and compositions for delivering 5-HT3 antagonists across the oral mucosa|

---

WO2004076403A1|2003-02-24|2004-09-10|Transform Pharmaceuticals, Inc.|Sumatriptan crystalline forms, pharmaceutical compositions and methods|

---

US20070054953A1|2003-05-12|2007-03-08|Potluri Ramesh B|A novel process for preparation of indole derivatives|

---

US20070184109A1|2003-06-06|2007-08-09|Floyd Alison G|Compositions comprising triptans and nsaids|

---

US20070065463A1|2003-06-20|2007-03-22|Ronald Aung-Din|Topical therapy for the treatment of migranes, muscle sprains, muscle spasms, spasticity and related conditions|

---

GB2407498B|2003-10-30|2008-06-11|Cipla Ltd|Oral formulations for 5-HT receptor agonists with reduced degradation of active ingredient|

---

CA2569964A1|2004-06-10|2005-12-29|Duramed Pharmaceuticals, Inc.|Formulations of sumatriptan for absorption across biological membranes, and methods of making and using the same|

---

MX2007012818A|2005-04-13|2008-01-14|Neuraxon Inc|Substituted indole compounds having nos inhibitory activity.|

---

WO2007070504A2|2005-12-13|2007-06-21|Morton Grove Pharmaceuticals, Inc.|Stable and palatable oral liquid sumatriptan compositions|

---

US7989447B2|2006-04-13|2011-08-02|Neuraxon, Inc.|1,5 and 3,6-substituted indole compounds having NOS inhibitory activity|

---

JP2010507585A|2006-10-19|2010-03-11|オースペックス・ファーマシューティカルズ・インコーポレイテッド|Substituted indole|

---

US20090076121A1|2007-09-14|2009-03-19|Protia, Llc|Deuterium-enriched sumatriptan|

---

CN101910157B|2007-11-16|2014-05-07|纽尔亚商股份有限公司|Indole compounds and methods for treating visceral pain|

---

EP2219449A4|2007-11-16|2010-10-27|Univ Arizona State|Methods for treating visceral pain|

---

WO2009062318A1|2007-11-16|2009-05-22|Neuraxon, Inc.|3,5-substituted indole compounds having nos and norepinephrine reuptake inhibitory activity|

---

WO2009128089A2|2008-02-11|2009-10-22|Matrix Laboratories Limited|Novel solvate form of sumatriptan succinate and process for preparing sumatriptan salt employing the same|

---

US20090252791A1|2008-04-02|2009-10-08|Venkata Nookaraju Sreedharala|Pharmaceutical compositions comprising a triptan and a nonsteroidal anti-inflammatory drug|

---

KR101517415B1|2008-05-14|2015-05-07|에스케이바이오팜 주식회사|Transnasal anticonvulsive pharmaceutical composition comprising poorly soluble anticonvulsant|

---

WO2010005507A1|2008-06-30|2010-01-14|Afgin Pharma, Llc|Topical regional neuro-affective therapy|

---

JP2012506404A|2008-10-22|2012-03-15|ノバルティスアーゲー|Combination for migraine treatment|

---

US8329734B2|2009-07-27|2012-12-11|Afgin Pharma Llc|Topical therapy for migraine|

---

KR101646079B1|2009-09-25|2016-08-12|닥터 레디스 레보러터리즈 리미티드|Formulations comprising triptan compounds|

---

JP5660817B2|2010-07-21|2015-01-28|高田製薬株式会社|Internal solution containing sumatriptan succinate|

---

CN102432520B|2011-11-21|2013-10-09|山东新华制药股份有限公司|Preparation method for 3-[2-ethly]-N-methylindole-5-methyl sulfonylamine succinate|

---

US10383816B2|2015-03-02|2019-08-20|Afgin Pharma, Llc|Topical regional neuro-affective therapy with cannabinoid combination products|

---

MX2017011280A|2015-03-02|2018-06-27|Afgin Pharma Llc|Topical regional neuro-affective therapy with cannabinoids.|

---

US20180049994A1|2016-08-16|2018-02-22|Afgin Pharma, Llc|Topical regional neuro-affective therapy with caryophyllene|

法律状态:

优先权:

---

申请号 | 申请日 | 专利标题

---

GB848419575A|GB8419575D0|1984-08-01|1984-08-01|Chemical compounds|

---