TW200819448A - Azaindole derivatives with a combination of partial nicotinic acetylcholine receptor agonism and dopamine reuptake inhibition - Google Patents

Azaindole derivatives with a combination of partial nicotinic acetylcholine receptor agonism and dopamine reuptake inhibition Download PDF

Info

Publication number: TW200819448A
Authority: TW; Taiwan
Prior art keywords: compound; pyrrolo; pyridine; ylmethyl; group
Prior art date: 2006-07-06

Application number

TW96124100A

Other languages

English (en)

Chinese (zh)

Inventor

Axel Stoit

Hein K A C Coolen

Der Neut Martina A W Van

Cornelis G Kruse

Original Assignee

Solvay Pharm Bv

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.)

2006-07-06

Filing date

2007-07-03

Publication date

2008-05-01

2007-07-03 Application filed by Solvay Pharm Bv filed Critical Solvay Pharm Bv

2008-05-01 Publication of TW200819448A publication Critical patent/TW200819448A/zh

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125000005334 azaindolyl group Chemical class N1N=C(C2=CC=CC=C12)* 0.000 title claims abstract description 6
102000019315 Nicotinic acetylcholine receptors Human genes 0.000 title abstract description 16
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230000005764 inhibitory process Effects 0.000 title abstract description 14
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238000000034 method Methods 0.000 claims abstract description 78
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 50
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 37
150000003839 salts Chemical class 0.000 claims description 32
-1 1-aza-bicyclo[2.2.2]oct-2-enyl Chemical group 0.000 claims description 31
208000035475 disorder Diseases 0.000 claims description 30
239000003814 drug Substances 0.000 claims description 25
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 24
125000000217 alkyl group Chemical group 0.000 claims description 22
MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 claims description 19
DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 claims description 16
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TW96124100A 2006-07-06 2007-07-03 Azaindole derivatives with a combination of partial nicotinic acetylcholine receptor agonism and dopamine reuptake inhibition TW200819448A (en)

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AR (1)	AR061808A1 (es)
MX (1)	MX2009000152A (es)
SA (1)	SA07280361B1 (es)
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UA (1)	UA97374C2 (es)

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MX2009000152A (es)	2009-03-25
AR061808A1 (es)	2008-09-24
UA97374C2 (ru)	2012-02-10
CN101484454A (zh)	2009-07-15
SA07280361B1 (ar)	2011-05-04

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