NO324700B1 - N-oksider, fremgangsmate for fremstilling av slike, anvendelse av slike for fremstilling av medikamenter for behandling av sykdom samt medikamenter inneholdende slike - Google Patents

N-oksider, fremgangsmate for fremstilling av slike, anvendelse av slike for fremstilling av medikamenter for behandling av sykdom samt medikamenter inneholdende slike Download PDF

Info

Publication number: NO324700B1
Authority: NO; Norway
Prior art keywords: methyl; tolyl; oxy; trifluoromethyl; bis
Prior art date: 2000-07-14

Application number

NO20030154A

Other languages

English (en)

Norwegian (no)

Other versions

NO20030154D0 (no

NO20030154L (no

Inventor

Patrick Schnider

Sonia Maria Poli

Torsten Hoffmann

Andrew Sleight

Original Assignee

Hoffmann La Roche

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.)

2000-07-14

Filing date

2003-01-13

Publication date

2007-12-03

2003-01-13 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

2003-01-13 Publication of NO20030154D0 publication Critical patent/NO20030154D0/no

2003-01-13 Publication of NO20030154L publication Critical patent/NO20030154L/no

2007-12-03 Publication of NO324700B1 publication Critical patent/NO324700B1/no

Links

238000000034 method Methods 0.000 title claims description 38
238000002360 preparation method Methods 0.000 title claims description 32
239000003814 drug Substances 0.000 title claims description 26
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 6
230000008569 process Effects 0.000 title claims description 4
201000010099 disease Diseases 0.000 title claims 3
150000001204 N-oxides Chemical class 0.000 title description 34
238000004519 manufacturing process Methods 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims description 99
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 22
239000011570 nicotinamide Substances 0.000 claims description 21
229960003966 nicotinamide Drugs 0.000 claims description 21
229940079593 drug Drugs 0.000 claims description 19
150000003839 salts Chemical class 0.000 claims description 15
-1 3,5-bis-trifluoromethyl-benzyl Chemical group 0.000 claims description 14
239000001257 hydrogen Substances 0.000 claims description 13
229910052739 hydrogen Inorganic materials 0.000 claims description 13
125000001424 substituent group Chemical group 0.000 claims description 12
229940047889 isobutyramide Drugs 0.000 claims description 11
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
102000002002 Neurokinin-1 Receptors Human genes 0.000 claims description 6
108010040718 Neurokinin-1 Receptors Proteins 0.000 claims description 6
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
239000002253 acid Substances 0.000 claims description 6
239000000654 additive Substances 0.000 claims description 6
229910052736 halogen Chemical group 0.000 claims description 5
150000002367 halogens Chemical group 0.000 claims description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
238000007254 oxidation reaction Methods 0.000 claims description 5
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
150000002431 hydrogen Chemical group 0.000 claims description 4
230000003647 oxidation Effects 0.000 claims description 4
229940044551 receptor antagonist Drugs 0.000 claims description 4
239000002464 receptor antagonist Substances 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
KVNIEWQWLOMTMV-UHFFFAOYSA-N n-[(2-chloro-5-methoxyphenyl)methyl]-n-methyl-4-(2-methylphenyl)-6-morpholin-4-ylpyridine-3-carboxamide Chemical compound COC1=CC=C(Cl)C(CN(C)C(=O)C=2C(=CC(=NC=2)N2CCOCC2)C=2C(=CC=CC=2)C)=C1 KVNIEWQWLOMTMV-UHFFFAOYSA-N 0.000 claims description 3
239000007800 oxidant agent Substances 0.000 claims description 3
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 3
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
125000003831 tetrazolyl group Chemical group 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
239000000243 solution Substances 0.000 description 59
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
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FMQPGFVLWDLWPR-UHFFFAOYSA-N n-methyl-n-[(2-methylnaphthalen-1-yl)methyl]-4-(2-methylphenyl)-6-morpholin-4-ylpyridine-3-carboxamide Chemical compound CC=1C=CC2=CC=CC=C2C=1CN(C)C(=O)C1=CN=C(N2CCOCC2)C=C1C1=CC=CC=C1C FMQPGFVLWDLWPR-UHFFFAOYSA-N 0.000 description 19
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STBYRSZXHDPASK-UHFFFAOYSA-N 1-(chloromethyl)-2-methylnaphthalene Chemical compound C1=CC=CC2=C(CCl)C(C)=CC=C21 STBYRSZXHDPASK-UHFFFAOYSA-N 0.000 description 10
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HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
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HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
OKBMCNHOEMXPTM-UHFFFAOYSA-M potassium peroxymonosulfate Chemical compound [K+].OOS([O-])(=O)=O OKBMCNHOEMXPTM-UHFFFAOYSA-M 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000011514 reflex Effects 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
238000003345 scintillation counting Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000004289 sodium hydrogen sulphite Substances 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
PODWXQQNRWNDGD-UHFFFAOYSA-L sodium thiosulfate pentahydrate Chemical compound O.O.O.O.O.[Na+].[Na+].[O-]S([S-])(=O)=O PODWXQQNRWNDGD-UHFFFAOYSA-L 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000010959 steel Substances 0.000 description 1
238000003860 storage Methods 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
108060008037 tachykinin Proteins 0.000 description 1
239000002466 tachykinin receptor agonist Substances 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
230000004797 therapeutic response Effects 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
239000005051 trimethylchlorosilane Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000003643 water by type Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

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- 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
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Pulmonology (AREA)
Immunology (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Psychiatry (AREA)
Addiction (AREA)
Urology & Nephrology (AREA)
Hospice & Palliative Care (AREA)
Dermatology (AREA)
Vascular Medicine (AREA)
Heart & Thoracic Surgery (AREA)
Ophthalmology & Optometry (AREA)
Cardiology (AREA)
Otolaryngology (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Pyridine Compounds (AREA)

NO20030154A 2000-07-14 2003-01-13 N-oksider, fremgangsmate for fremstilling av slike, anvendelse av slike for fremstilling av medikamenter for behandling av sykdom samt medikamenter inneholdende slike NO324700B1 (no)

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Application Number	Priority Date	Filing Date	Title
EP00115287		2000-07-14
PCT/EP2001/007850 WO2002006236A1 (en)	2000-07-14	2001-07-09	N-oxides as nk1 receptor antagonist prodrugs of 4-phenyl-pyridine derivatives

Publications (3)

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NO20030154D0 NO20030154D0 (no)	2003-01-13
NO20030154L NO20030154L (no)	2003-01-13
NO324700B1 true NO324700B1 (no)	2007-12-03

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US (4)	US6593472B2 (de)
EP (1)	EP1303490B1 (de)
JP (1)	JP3950044B2 (de)
KR (1)	KR100501608B1 (de)
CN (1)	CN1178917C (de)
AR (1)	AR029717A1 (de)
AT (1)	ATE400556T1 (de)
AU (1)	AU7061901A (de)
BR (1)	BRPI0112475B8 (de)
CA (1)	CA2415890C (de)
CY (1)	CY1108557T1 (de)
CZ (1)	CZ303639B6 (de)
DE (1)	DE60134749D1 (de)
DK (1)	DK1303490T3 (de)
EC (1)	ECSP034431A (de)
EG (1)	EG24968A (de)
ES (1)	ES2309075T3 (de)
GT (1)	GT200100137A (de)
HR (1)	HRP20030003B1 (de)
HU (1)	HU230316B1 (de)
IL (2)	IL153834A0 (de)
JO (1)	JO2372B1 (de)
MA (1)	MA26929A1 (de)
ME (1)	ME01311B (de)
MX (1)	MXPA03000366A (de)
MY (1)	MY154976A (de)
NO (1)	NO324700B1 (de)
NZ (1)	NZ523273A (de)
PA (1)	PA8522001A1 (de)
PE (1)	PE20020272A1 (de)
PL (1)	PL205207B1 (de)
PT (1)	PT1303490E (de)
RS (1)	RS50932B (de)
RU (1)	RU2266284C2 (de)
SI (1)	SI1303490T1 (de)
UY (1)	UY26839A1 (de)
WO (1)	WO2002006236A1 (de)
ZA (1)	ZA200210207B (de)

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2001
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Publication number	Publication date
HK1058198A1 (en)	2004-05-07
CN1441782A (zh)	2003-09-10
US6593472B2 (en)	2003-07-15
EP1303490B1 (de)	2008-07-09
ATE400556T1 (de)	2008-07-15
US6806370B2 (en)	2004-10-19
PL205207B1 (pl)	2010-03-31
MA26929A1 (fr)	2004-12-20
ES2309075T3 (es)	2008-12-16
UY26839A1 (es)	2002-01-31
PA8522001A1 (es)	2002-04-25
ZA200210207B (en)	2004-03-17
JP3950044B2 (ja)	2007-07-25
CA2415890A1 (en)	2002-01-24
MY154976A (en)	2015-08-28
HRP20030003B1 (en)	2011-01-31
HU230316B1 (hu)	2016-01-28
US20020045642A1 (en)	2002-04-18
HRP20030003A2 (en)	2003-02-28
SI1303490T1 (sl)	2008-10-31
NZ523273A (en)	2004-08-27
ECSP034431A (es)	2003-03-10
YU603A (sh)	2006-01-16
CZ303639B6 (cs)	2013-01-23
AR029717A1 (es)	2003-07-10
JO2372B1 (en)	2006-12-12
WO2002006236A1 (en)	2002-01-24
US20040048901A1 (en)	2004-03-11
HUP0301311A2 (hu)	2003-08-28
RU2266284C2 (ru)	2005-12-20
ME01311B (me)	2013-12-20
NO20030154D0 (no)	2003-01-13
EG24968A (en)	2011-03-14
US20030149039A1 (en)	2003-08-07
KR20030015387A (ko)	2003-02-20
CN1178917C (zh)	2004-12-08
PE20020272A1 (es)	2002-04-16
NO20030154L (no)	2003-01-13
JP2004504301A (ja)	2004-02-12
EP1303490A1 (de)	2003-04-23
CY1108557T1 (el)	2014-04-09
PT1303490E (pt)	2008-09-04
BR0112475A (pt)	2003-07-29
US20040014793A1 (en)	2004-01-22
US6897226B2 (en)	2005-05-24
BR0112475B1 (pt)	2013-10-15
KR100501608B1 (ko)	2005-07-18
IL153834A (en)	2008-11-03
MXPA03000366A (es)	2003-05-27
CA2415890C (en)	2009-04-07
BRPI0112475B8 (pt)	2021-05-25
IL153834A0 (en)	2003-07-31
AU7061901A (en)	2002-01-30
RS50932B (sr)	2010-08-31
PL365684A1 (en)	2005-01-10
DK1303490T3 (da)	2008-08-25
DE60134749D1 (de)	2008-08-21
US6747026B2 (en)	2004-06-08
GT200100137A (es)	2002-05-16

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Date	Code	Title	Description
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Publication	Publication Date	Title
NO324700B1 (no)	2007-12-03	N-oksider, fremgangsmate for fremstilling av slike, anvendelse av slike for fremstilling av medikamenter for behandling av sykdom samt medikamenter inneholdende slike
JP3399900B2 (ja)	2003-04-21	４−フェニル−ピリジン誘導体
CA2416874C (en)	2011-01-18	4-phenyl-pyridine derivatives as neurokinin-1 receptor antagonists
AU2001282005A1 (en)	2002-05-02	4-phenyl-pyridine derivatives as neurokinin-1 receptor antagonists
AU2001270619B2 (en)	2006-03-23	N-oxides as nk1 receptor antagonist prodrugs of 4-phenyl-pyridine derivatives
AU2001270619A1 (en)	2002-05-02	N-oxides as nk1 receptor antagonist prodrugs of 4-phenyl-pyridine derivatives