EA019747B1 - Лактамные соединения и их применение в качестве фармацевтических препаратов - Google Patents

Лактамные соединения и их применение в качестве фармацевтических препаратов Download PDF

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Publication number: EA019747B1
Authority: EA; Eurasian Patent Office
Prior art keywords: diazaspiro; trans; hydroxycyclohexyl; oxo; compound
Prior art date: 2004-11-10

Application number

EA200701036A

Other languages

English (en)

Russian (ru)

Other versions

EA200701036A1 (ru

Inventor

Вэньцин Яо

Чуньхун Хэ

Цзиньцун Чжо

Мэйчжун Сюй

Колин Чжан

Дин-Цюань Цянь

Дэвид Бернс

Брайан В. Меткаф

Original Assignee

Инсайт Корпорейшн

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.)

2004-11-10

Filing date

2005-11-09

Publication date

2014-06-30

2005-11-09 Application filed by Инсайт Корпорейшн filed Critical Инсайт Корпорейшн

2007-12-28 Publication of EA200701036A1 publication Critical patent/EA200701036A1/ru

2014-06-30 Publication of EA019747B1 publication Critical patent/EA019747B1/ru

Links

-1 Lactam compounds Chemical class 0.000 title claims description 166
239000003814 drug Substances 0.000 title claims description 10
150000001875 compounds Chemical class 0.000 claims abstract description 705
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 56
201000010099 disease Diseases 0.000 claims abstract description 42
230000000694 effects Effects 0.000 claims abstract description 39
PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 claims abstract description 35
PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 claims abstract description 35
229960002478 aldosterone Drugs 0.000 claims abstract description 35
238000011282 treatment Methods 0.000 claims abstract description 19
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
238000000034 method Methods 0.000 claims description 639
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 103
125000000217 alkyl group Chemical group 0.000 claims description 65
125000003118 aryl group Chemical group 0.000 claims description 58
125000001072 heteroaryl group Chemical group 0.000 claims description 43
150000003839 salts Chemical class 0.000 claims description 40
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 39
125000000753 cycloalkyl group Chemical group 0.000 claims description 36
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 36
208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 30
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 28
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235000020824 obesity Nutrition 0.000 claims description 28
125000000714 pyrimidinyl group Chemical group 0.000 claims description 28
206010020772 Hypertension Diseases 0.000 claims description 27
125000005843 halogen group Chemical group 0.000 claims description 27
125000004076 pyridyl group Chemical group 0.000 claims description 27
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208000001145 Metabolic Syndrome Diseases 0.000 claims description 24
201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 24
125000003710 aryl alkyl group Chemical group 0.000 claims description 24
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 22
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 19
208000032928 Dyslipidaemia Diseases 0.000 claims description 16
208000017170 Lipid metabolism disease Diseases 0.000 claims description 16
125000003545 alkoxy group Chemical group 0.000 claims description 16
230000006378 damage Effects 0.000 claims description 16
201000001421 hyperglycemia Diseases 0.000 claims description 16
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 15
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 15
125000001624 naphthyl group Chemical group 0.000 claims description 15
208000024172 Cardiovascular disease Diseases 0.000 claims description 14
125000002541 furyl group Chemical group 0.000 claims description 14
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 13
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 13
125000004306 triazinyl group Chemical group 0.000 claims description 13
206010012601 diabetes mellitus Diseases 0.000 claims description 12
201000005577 familial hyperlipidemia Diseases 0.000 claims description 12
125000001188 haloalkyl group Chemical group 0.000 claims description 12
125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 12
238000004519 manufacturing process Methods 0.000 claims description 12
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
125000001544 thienyl group Chemical group 0.000 claims description 11
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 10
206010012289 Dementia Diseases 0.000 claims description 10
230000002526 effect on cardiovascular system Effects 0.000 claims description 10
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 10
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
208000010412 Glaucoma Diseases 0.000 claims description 9
206010019280 Heart failures Diseases 0.000 claims description 9
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229910052739 hydrogen Inorganic materials 0.000 claims description 9
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 9
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125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 8
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150000002367 halogens Chemical class 0.000 claims description 8
239000001257 hydrogen Substances 0.000 claims description 8
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125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 8
125000000335 thiazolyl group Chemical group 0.000 claims description 8
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229910052736 halogen Inorganic materials 0.000 claims description 7
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208000017169 kidney disease Diseases 0.000 claims description 7
229910052700 potassium Inorganic materials 0.000 claims description 7
206010052895 Coronary artery insufficiency Diseases 0.000 claims description 6
208000002705 Glucose Intolerance Diseases 0.000 claims description 6
208000006011 Stroke Diseases 0.000 claims description 6
125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
125000005553 heteroaryloxy group Chemical group 0.000 claims description 6
125000005842 heteroatom Chemical group 0.000 claims description 6
229910052757 nitrogen Inorganic materials 0.000 claims description 6
125000002971 oxazolyl group Chemical group 0.000 claims description 6
125000005476 oxopyrrolidinyl group Chemical group 0.000 claims description 6
230000002093 peripheral effect Effects 0.000 claims description 6
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ALZXWOFBWMNTEE-IWZNKUOBSA-N CC1=CC(C(F)(F)F)=CC(N2CC3(C(N([C@@H]4CC[C@@H](O)CC4)CC3)=O)CCC2)=N1 Chemical compound CC1=CC(C(F)(F)F)=CC(N2CC3(C(N([C@@H]4CC[C@@H](O)CC4)CC3)=O)CCC2)=N1 ALZXWOFBWMNTEE-IWZNKUOBSA-N 0.000 claims description 5
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
210000000056 organ Anatomy 0.000 claims description 5
230000008816 organ damage Effects 0.000 claims description 5
125000002098 pyridazinyl group Chemical group 0.000 claims description 5
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 claims description 4
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 4
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 4
125000004438 haloalkoxy group Chemical group 0.000 claims description 4
208000020346 hyperlipoproteinemia Diseases 0.000 claims description 4
XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims description 4
125000003226 pyrazolyl group Chemical group 0.000 claims description 4
125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 claims description 3
YPRGYYBHIYWKHG-UHFFFAOYSA-N 4-[1-oxo-9-[4-(trifluoromethyl)phenyl]-2,9-diazaspiro[4.5]decan-2-yl]cyclohexane-1-carbonitrile Chemical compound C1=CC(C(F)(F)F)=CC=C1N1CC2(C(N(C3CCC(CC3)C#N)CC2)=O)CCC1 YPRGYYBHIYWKHG-UHFFFAOYSA-N 0.000 claims description 3
KYEGQDHSGKTXDU-UHFFFAOYSA-N 4-[1-oxo-9-[5-(trifluoromethyl)pyridin-2-yl]-2,9-diazaspiro[4.5]decan-2-yl]cyclohexane-1-carbonitrile Chemical compound N1=CC(C(F)(F)F)=CC=C1N1CC2(C(N(C3CCC(CC3)C#N)CC2)=O)CCC1 KYEGQDHSGKTXDU-UHFFFAOYSA-N 0.000 claims description 3
MKJLUDHYOWNPML-UHFFFAOYSA-N 4-[9-(3,5-dichloropyridin-2-yl)-1-oxo-2,9-diazaspiro[4.5]decan-2-yl]cyclohexane-1-carbonitrile Chemical compound ClC1=CC(Cl)=CN=C1N1CC2(C(N(C3CCC(CC3)C#N)CC2)=O)CCC1 MKJLUDHYOWNPML-UHFFFAOYSA-N 0.000 claims description 3
AWULZLWAYLIPEH-UHFFFAOYSA-N 4-[9-(6-fluoropyridin-2-yl)-1-oxo-2,9-diazaspiro[4.5]decan-2-yl]cyclohexane-1-carbonitrile Chemical compound FC1=CC=CC(N2CC3(C(N(C4CCC(CC4)C#N)CC3)=O)CCC2)=N1 AWULZLWAYLIPEH-UHFFFAOYSA-N 0.000 claims description 3
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PQUVDNNEXQWBEU-SKIQCWHVSA-N COC1=CC=CC(N2CC3(C(N([C@@H]4CC[C@@H](O)CC4)CC3)=O)CCC2)=N1 Chemical compound COC1=CC=CC(N2CC3(C(N([C@@H]4CC[C@@H](O)CC4)CC3)=O)CCC2)=N1 PQUVDNNEXQWBEU-SKIQCWHVSA-N 0.000 claims description 3
NPARPJUFLZELGO-SKIQCWHVSA-N COC1=CC=NC(N2CC3(C(N([C@@H]4CC[C@@H](O)CC4)CC3)=O)CCC2)=C1 Chemical compound COC1=CC=NC(N2CC3(C(N([C@@H]4CC[C@@H](O)CC4)CC3)=O)CCC2)=C1 NPARPJUFLZELGO-SKIQCWHVSA-N 0.000 claims description 3
DKOYLJVAKAFBTB-DVUVRWKGSA-N ClC1=CC(Cl)=CN=C1N1CC2(C(N([C@@H]3CC[C@@H](CC#N)CC3)CC2)=O)CCC1 Chemical compound ClC1=CC(Cl)=CN=C1N1CC2(C(N([C@@H]3CC[C@@H](CC#N)CC3)CC2)=O)CCC1 DKOYLJVAKAFBTB-DVUVRWKGSA-N 0.000 claims description 3
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125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 3
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Classifications

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Also Published As

Publication number	Publication date
CA2585797C (en)	2015-01-06
KR20070085944A (ko)	2007-08-27
CN102731499A (zh)	2012-10-17
EP1812005B1 (en)	2015-09-16
IL182876A (en)	2015-10-29
IL182876A0 (en)	2007-08-19
EP1812005A4 (en)	2009-09-30
AU2005304560A1 (en)	2006-05-18
WO2006053024A2 (en)	2006-05-18
BRPI0518022A (pt)	2008-10-21
JP5202954B2 (ja)	2013-06-05
TWI400239B (zh)	2013-07-01
SG161261A1 (en)	2010-05-27
US20060116382A1 (en)	2006-06-01
CN102731499B (zh)	2016-01-13
AU2005304560C1 (en)	2013-05-09
NZ554906A (en)	2011-01-28
GEP20125565B (en)	2012-07-10
EP2450351A1 (en)	2012-05-09
TW200621763A (en)	2006-07-01
CA2585797A1 (en)	2006-05-18
WO2006053024A3 (en)	2007-07-05
JP2008519765A (ja)	2008-06-12
HK1113305A1 (zh)	2008-10-03
ZA200703754B (en)	2008-01-08
MX2007005527A (es)	2007-07-09
EP1812005A2 (en)	2007-08-01
NO20072322L (no)	2007-07-19
ES2547724T3 (es)	2015-10-08
KR101368228B1 (ko)	2014-02-27
NO340365B1 (no)	2017-04-10
EA200701036A1 (ru)	2007-12-28
AU2005304560B2 (en)	2012-05-03

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