JP2009537542A - ヒスタミン−３アンタゴニストとしてのｎ−ベンゾイルピロリジン−３−イルアミンおよびｎ−ベンジルピロリジン−３−イルアミン - Google Patents
ヒスタミン−３アンタゴニストとしてのｎ−ベンゾイルピロリジン−３−イルアミンおよびｎ−ベンジルピロリジン−３−イルアミン Download PDFInfo
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- JP2009537542A JP2009537542A JP2009511057A JP2009511057A JP2009537542A JP 2009537542 A JP2009537542 A JP 2009537542A JP 2009511057 A JP2009511057 A JP 2009511057A JP 2009511057 A JP2009511057 A JP 2009511057A JP 2009537542 A JP2009537542 A JP 2009537542A
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- Prior art keywords
- dimethylamino
- phenyl
- carbonyl
- pyrrolidin
- benzoyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
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- FAVZGMWROXRERG-UHFFFAOYSA-N n-pyrrolidin-3-ylbenzamide Chemical compound C=1C=CC=CC=1C(=O)NC1CCNC1 FAVZGMWROXRERG-UHFFFAOYSA-N 0.000 title abstract description 5
- 239000005557 antagonist Substances 0.000 title description 4
- NFLXIAUKMQBTMN-UHFFFAOYSA-N n-benzylpyrrolidin-3-amine Chemical compound C=1C=CC=CC=1CNC1CCNC1 NFLXIAUKMQBTMN-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 120
- -1 N-benzylpyrrolidin-3-ylamine compound Chemical class 0.000 claims abstract description 34
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 238000011282 treatment Methods 0.000 claims abstract description 21
- 102000004384 Histamine H3 receptors Human genes 0.000 claims abstract description 17
- 108090000981 Histamine H3 receptors Proteins 0.000 claims abstract description 17
- 208000015114 central nervous system disease Diseases 0.000 claims abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims description 35
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 14
- 208000024827 Alzheimer disease Diseases 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 12
- 125000000304 alkynyl group Chemical group 0.000 claims description 11
- 208000010877 cognitive disease Diseases 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 7
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 201000000980 schizophrenia Diseases 0.000 claims description 7
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 6
- 208000019116 sleep disease Diseases 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 6
- SQKQXYJHTKDETF-SFHVURJKSA-N (4-phenoxyphenyl)-[(3s)-3-pyrrolidin-1-ylpyrrolidin-1-yl]methanone Chemical compound N1([C@H]2CCN(C2)C(=O)C=2C=CC(OC=3C=CC=CC=3)=CC=2)CCCC1 SQKQXYJHTKDETF-SFHVURJKSA-N 0.000 claims description 5
- 125000004122 cyclic group Chemical group 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- WAQUETNOOMBFBP-UHFFFAOYSA-N n-[4-[3-(dimethylamino)pyrrolidine-1-carbonyl]phenyl]quinoline-2-carboxamide Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC(=O)C1=CC=C(C=CC=C2)C2=N1 WAQUETNOOMBFBP-UHFFFAOYSA-N 0.000 claims description 4
- 208000012239 Developmental disease Diseases 0.000 claims description 3
- LUVDFJBSHAGGKE-UHFFFAOYSA-N [3-(dimethylamino)pyrrolidin-1-yl]-[4-[(2-phenylquinazolin-4-yl)amino]phenyl]methanone Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=NC2=CC=CC=C12 LUVDFJBSHAGGKE-UHFFFAOYSA-N 0.000 claims description 3
- IFQUMLVBMNTRID-UHFFFAOYSA-N [4-(1-benzothiophen-3-ylamino)phenyl]-[3-(dimethylamino)pyrrolidin-1-yl]methanone Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=CSC2=CC=CC=C12 IFQUMLVBMNTRID-UHFFFAOYSA-N 0.000 claims description 3
- JSNWCXLSYPAWMD-UHFFFAOYSA-N [4-(2,1,3-benzothiadiazol-4-ylamino)phenyl]-[3-(dimethylamino)pyrrolidin-1-yl]methanone Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=CC=CC2=NSN=C12 JSNWCXLSYPAWMD-UHFFFAOYSA-N 0.000 claims description 3
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 3
- DMULPHWOFFXUNA-UHFFFAOYSA-N 3-chloro-n-[4-[3-(dimethylamino)pyrrolidine-1-carbonyl]phenyl]-1-benzothiophene-2-carboxamide Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C2=CC=CC=C2S1 DMULPHWOFFXUNA-UHFFFAOYSA-N 0.000 claims description 2
- GCCRIUBIPIFWEY-IBGZPJMESA-N 4-[4-[(3s)-3-pyrrolidin-1-ylpyrrolidine-1-carbonyl]phenoxy]benzonitrile Chemical compound N1([C@H]2CCN(C2)C(=O)C=2C=CC(OC=3C=CC(=CC=3)C#N)=CC=2)CCCC1 GCCRIUBIPIFWEY-IBGZPJMESA-N 0.000 claims description 2
- SYHQFYLFEOBBCN-UHFFFAOYSA-N 6-chloro-n-[4-[3-(dimethylamino)pyrrolidine-1-carbonyl]phenyl]-2h-chromene-3-carboxamide Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC(=O)C1=CC2=CC(Cl)=CC=C2OC1 SYHQFYLFEOBBCN-UHFFFAOYSA-N 0.000 claims description 2
- 208000020358 Learning disease Diseases 0.000 claims description 2
- 208000012902 Nervous system disease Diseases 0.000 claims description 2
- XVMBEFQCSIKAQZ-IBGZPJMESA-N [(3s)-3-pyrrolidin-1-ylpyrrolidin-1-yl]-(4-quinolin-4-yloxyphenyl)methanone Chemical compound N1([C@H]2CCN(C2)C(=O)C=2C=CC(OC=3C4=CC=CC=C4N=CC=3)=CC=2)CCCC1 XVMBEFQCSIKAQZ-IBGZPJMESA-N 0.000 claims description 2
- RNYXSJGBMGKIBA-UHFFFAOYSA-N [3-(dimethylamino)pyrrolidin-1-yl]-[4-(1h-indol-5-ylamino)phenyl]methanone Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=CC=C(NC=C2)C2=C1 RNYXSJGBMGKIBA-UHFFFAOYSA-N 0.000 claims description 2
- JQPUUYMBIYTUQT-UHFFFAOYSA-N [3-(dimethylamino)pyrrolidin-1-yl]-[4-(7h-purin-6-ylamino)phenyl]methanone Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=NC2=C1N=CN2 JQPUUYMBIYTUQT-UHFFFAOYSA-N 0.000 claims description 2
- FAFBJBCVAFXQHO-UHFFFAOYSA-N [3-(dimethylamino)pyrrolidin-1-yl]-[4-(isoquinolin-1-ylamino)phenyl]methanone Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC2=CC=CC=C12 FAFBJBCVAFXQHO-UHFFFAOYSA-N 0.000 claims description 2
- QEVDRWFDZMXCDJ-UHFFFAOYSA-N [3-(dimethylamino)pyrrolidin-1-yl]-[4-(pyridin-2-ylamino)phenyl]methanone Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=CC=CC=N1 QEVDRWFDZMXCDJ-UHFFFAOYSA-N 0.000 claims description 2
- APPDICQYWHQOBV-UHFFFAOYSA-N [3-(dimethylamino)pyrrolidin-1-yl]-[4-(pyrimidin-2-ylamino)phenyl]methanone Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=CC=N1 APPDICQYWHQOBV-UHFFFAOYSA-N 0.000 claims description 2
- AXAGRBLKRVZYNW-UHFFFAOYSA-N [3-(dimethylamino)pyrrolidin-1-yl]-[4-(quinolin-5-ylamino)phenyl]methanone Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=CC=CC2=NC=CC=C12 AXAGRBLKRVZYNW-UHFFFAOYSA-N 0.000 claims description 2
- VKPWZZOPZNLDQJ-UHFFFAOYSA-N [3-(dimethylamino)pyrrolidin-1-yl]-[4-(thieno[3,2-d]pyrimidin-4-ylamino)phenyl]methanone Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=NC2=C1SC=C2 VKPWZZOPZNLDQJ-UHFFFAOYSA-N 0.000 claims description 2
- GFSZGLWVDJWVLE-UHFFFAOYSA-N [3-(dimethylamino)pyrrolidin-1-yl]-[4-[(7-methylthieno[3,2-d]pyrimidin-4-yl)amino]phenyl]methanone Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=NC2=C1SC=C2C GFSZGLWVDJWVLE-UHFFFAOYSA-N 0.000 claims description 2
- UFTOVKRNMRDBFT-UHFFFAOYSA-N [3-(dimethylamino)pyrrolidin-1-yl]-[4-[[5-(trifluoromethyl)pyridin-2-yl]amino]phenyl]methanone Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=CC=C(C(F)(F)F)C=N1 UFTOVKRNMRDBFT-UHFFFAOYSA-N 0.000 claims description 2
- YKTYDJHPZQEINO-UHFFFAOYSA-N [4-(1,3-benzodioxol-5-ylamino)phenyl]-[3-(dimethylamino)pyrrolidin-1-yl]methanone Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=CC=C(OCO2)C2=C1 YKTYDJHPZQEINO-UHFFFAOYSA-N 0.000 claims description 2
- UZYSZFYBZBIYEY-UHFFFAOYSA-N [4-(2,3-dihydro-1,4-benzodioxin-6-ylamino)phenyl]-[3-(dimethylamino)pyrrolidin-1-yl]methanone Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=CC=C(OCCO2)C2=C1 UZYSZFYBZBIYEY-UHFFFAOYSA-N 0.000 claims description 2
- ZEMFLUOFZVCRDI-SFHVURJKSA-N [4-(2-chloro-4-methylphenoxy)phenyl]-[(3s)-3-pyrrolidin-1-ylpyrrolidin-1-yl]methanone Chemical compound ClC1=CC(C)=CC=C1OC1=CC=C(C(=O)N2C[C@H](CC2)N2CCCC2)C=C1 ZEMFLUOFZVCRDI-SFHVURJKSA-N 0.000 claims description 2
- HDMCVNKJGBLMGK-IBGZPJMESA-N [4-(2-methylphenoxy)phenyl]-[(3s)-3-pyrrolidin-1-ylpyrrolidin-1-yl]methanone Chemical compound CC1=CC=CC=C1OC1=CC=C(C(=O)N2C[C@H](CC2)N2CCCC2)C=C1 HDMCVNKJGBLMGK-IBGZPJMESA-N 0.000 claims description 2
- CCZGBCCDZHTUEX-INIZCTEOSA-N [4-(3-chloro-4-fluorophenoxy)phenyl]-[(3s)-3-pyrrolidin-1-ylpyrrolidin-1-yl]methanone Chemical compound C1=C(Cl)C(F)=CC=C1OC1=CC=C(C(=O)N2C[C@H](CC2)N2CCCC2)C=C1 CCZGBCCDZHTUEX-INIZCTEOSA-N 0.000 claims description 2
- XESZKIFDWRZDHB-SFHVURJKSA-N [4-(3-fluorophenoxy)phenyl]-[(3s)-3-pyrrolidin-1-ylpyrrolidin-1-yl]methanone Chemical compound FC1=CC=CC(OC=2C=CC(=CC=2)C(=O)N2C[C@H](CC2)N2CCCC2)=C1 XESZKIFDWRZDHB-SFHVURJKSA-N 0.000 claims description 2
- MTYKYSGFMAMMOQ-SFHVURJKSA-N [4-(3-methoxyphenoxy)phenyl]-[(3s)-3-pyrrolidin-1-ylpyrrolidin-1-yl]methanone Chemical compound COC1=CC=CC(OC=2C=CC(=CC=2)C(=O)N2C[C@H](CC2)N2CCCC2)=C1 MTYKYSGFMAMMOQ-SFHVURJKSA-N 0.000 claims description 2
- YBVCXYYJJQZRNW-IBGZPJMESA-N [4-(3-methylphenoxy)phenyl]-[(3s)-3-pyrrolidin-1-ylpyrrolidin-1-yl]methanone Chemical compound CC1=CC=CC(OC=2C=CC(=CC=2)C(=O)N2C[C@H](CC2)N2CCCC2)=C1 YBVCXYYJJQZRNW-IBGZPJMESA-N 0.000 claims description 2
- WAKKURBHPPTSHC-IBGZPJMESA-N [4-(4-chloro-2-methylphenoxy)phenyl]-[(3s)-3-pyrrolidin-1-ylpyrrolidin-1-yl]methanone Chemical compound CC1=CC(Cl)=CC=C1OC1=CC=C(C(=O)N2C[C@H](CC2)N2CCCC2)C=C1 WAKKURBHPPTSHC-IBGZPJMESA-N 0.000 claims description 2
- HHPVZMYBDRHDTL-SFHVURJKSA-N [4-(4-chlorophenoxy)phenyl]-[(3s)-3-pyrrolidin-1-ylpyrrolidin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1OC1=CC=C(C(=O)N2C[C@H](CC2)N2CCCC2)C=C1 HHPVZMYBDRHDTL-SFHVURJKSA-N 0.000 claims description 2
- UCKCZZXZNYMBCG-IBGZPJMESA-N [4-(4-fluoro-2-methylphenoxy)phenyl]-[(3s)-3-pyrrolidin-1-ylpyrrolidin-1-yl]methanone Chemical compound CC1=CC(F)=CC=C1OC1=CC=C(C(=O)N2C[C@H](CC2)N2CCCC2)C=C1 UCKCZZXZNYMBCG-IBGZPJMESA-N 0.000 claims description 2
- PFFXQLLETABCOE-SFHVURJKSA-N [4-(4-fluorophenoxy)phenyl]-[(3s)-3-pyrrolidin-1-ylpyrrolidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1OC1=CC=C(C(=O)N2C[C@H](CC2)N2CCCC2)C=C1 PFFXQLLETABCOE-SFHVURJKSA-N 0.000 claims description 2
- MOQGWEWITCELLN-SFHVURJKSA-N [4-(4-methoxyphenoxy)phenyl]-[(3s)-3-pyrrolidin-1-ylpyrrolidin-1-yl]methanone Chemical compound C1=CC(OC)=CC=C1OC1=CC=C(C(=O)N2C[C@H](CC2)N2CCCC2)C=C1 MOQGWEWITCELLN-SFHVURJKSA-N 0.000 claims description 2
- YBZTVABBMXYECK-IBGZPJMESA-N [4-(4-methylphenoxy)phenyl]-[(3s)-3-pyrrolidin-1-ylpyrrolidin-1-yl]methanone Chemical compound C1=CC(C)=CC=C1OC1=CC=C(C(=O)N2C[C@H](CC2)N2CCCC2)C=C1 YBZTVABBMXYECK-IBGZPJMESA-N 0.000 claims description 2
- DFPMBTDQUIPMCK-QFIPXVFZSA-N [4-[3-(3-fluorophenoxy)phenoxy]phenyl]-[(3s)-3-pyrrolidin-1-ylpyrrolidin-1-yl]methanone Chemical compound FC1=CC=CC(OC=2C=C(OC=3C=CC(=CC=3)C(=O)N3C[C@H](CC3)N3CCCC3)C=CC=2)=C1 DFPMBTDQUIPMCK-QFIPXVFZSA-N 0.000 claims description 2
- RTRPSRRXGSCHKD-QFIPXVFZSA-N [4-[4-(4-fluorophenoxy)phenoxy]phenyl]-[(3s)-3-pyrrolidin-1-ylpyrrolidin-1-yl]methanone Chemical compound C1=CC(F)=CC=C1OC(C=C1)=CC=C1OC1=CC=C(C(=O)N2C[C@H](CC2)N2CCCC2)C=C1 RTRPSRRXGSCHKD-QFIPXVFZSA-N 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 201000003723 learning disability Diseases 0.000 claims description 2
- SXUXCCXSTJNPTR-UHFFFAOYSA-N n-[4-[3-(dimethylamino)pyrrolidine-1-carbonyl]phenyl]-1,2,3,4-tetrahydronaphthalene-2-carboxamide Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC(=O)C1CC2=CC=CC=C2CC1 SXUXCCXSTJNPTR-UHFFFAOYSA-N 0.000 claims description 2
- HDGCAAKEVPXROM-UHFFFAOYSA-N n-[4-[3-(dimethylamino)pyrrolidine-1-carbonyl]phenyl]-1-benzothiophene-2-carboxamide Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC(=O)C1=CC2=CC=CC=C2S1 HDGCAAKEVPXROM-UHFFFAOYSA-N 0.000 claims description 2
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- QRZKOBIUSAZZPI-UHFFFAOYSA-N n-[4-[3-(dimethylamino)pyrrolidine-1-carbonyl]phenyl]-4-methoxyquinoline-2-carboxamide Chemical compound N=1C2=CC=CC=C2C(OC)=CC=1C(=O)NC(C=C1)=CC=C1C(=O)N1CCC(N(C)C)C1 QRZKOBIUSAZZPI-UHFFFAOYSA-N 0.000 claims description 2
- KLUDPWOLVUXGDO-UHFFFAOYSA-N n-[4-[3-(dimethylamino)pyrrolidine-1-carbonyl]phenyl]-4-phenoxybenzamide Chemical compound C1C(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1=CC=CC=C1 KLUDPWOLVUXGDO-UHFFFAOYSA-N 0.000 claims description 2
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- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
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- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
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- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- XQOIBQBPAXOVGP-UHFFFAOYSA-N n-ethyl-2-methylpropan-2-amine Chemical compound CCNC(C)(C)C XQOIBQBPAXOVGP-UHFFFAOYSA-N 0.000 description 1
- GNVRJGIVDSQCOP-UHFFFAOYSA-N n-ethyl-n-methylethanamine Chemical compound CCN(C)CC GNVRJGIVDSQCOP-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
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- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 239000012057 packaged powder Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
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- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- WFVMVMAUXYOQSW-UHFFFAOYSA-N quinoline-2-carbonyl chloride Chemical compound C1=CC=CC2=NC(C(=O)Cl)=CC=C21 WFVMVMAUXYOQSW-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 210000003370 receptor cell Anatomy 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000016978 synaptic transmission, cholinergic Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- GVIJJXMXTUZIOD-UHFFFAOYSA-N thianthrene Chemical compound C1=CC=C2SC3=CC=CC=C3SC2=C1 GVIJJXMXTUZIOD-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000000858 thiocyanato group Chemical group *SC#N 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Chemical group 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000004034 viscosity adjusting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D413/12—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 linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US80190506P | 2006-05-19 | 2006-05-19 | |
| PCT/US2007/011765 WO2007136668A2 (en) | 2006-05-19 | 2007-05-16 | N-benzoyl-and n-benzylpyrrolidin-3-ylamines as histamine-3 antagonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009537542A true JP2009537542A (ja) | 2009-10-29 |
| JP2009537542A5 JP2009537542A5 (https=) | 2010-07-08 |
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| JP2009511057A Withdrawn JP2009537542A (ja) | 2006-05-19 | 2007-05-16 | ヒスタミン−３アンタゴニストとしてのｎ−ベンゾイルピロリジン−３−イルアミンおよびｎ−ベンジルピロリジン−３−イルアミン |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US7842715B2 (https=) |
| EP (1) | EP2027086B1 (https=) |
| JP (1) | JP2009537542A (https=) |
| CN (1) | CN101432261A (https=) |
| AR (1) | AR061015A1 (https=) |
| AT (1) | ATE533744T1 (https=) |
| AU (1) | AU2007254232A1 (https=) |
| CA (1) | CA2649913A1 (https=) |
| MX (1) | MX2008014743A (https=) |
| PE (1) | PE20080371A1 (https=) |
| TW (1) | TW200811165A (https=) |
| WO (1) | WO2007136668A2 (https=) |
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| BRPI0709612A2 (pt) * | 2006-03-15 | 2011-07-19 | Wyeth Corp | composto de fórmula i; método para o tratamento de um distúrbio no sistema nervoso central relacionado ou afetado pelo receptor histamina-3 em um paciente que necessita deste tratamento; método para a inibição do receptor h3; composição farmacêutica; e processo para a preparação de um composto de fórmula i |
| TW200823204A (en) * | 2006-10-17 | 2008-06-01 | Arena Pharm Inc | Biphenyl sulfonyl and phenyl-heteroaryl sulfonyl modulators of the histamine H3-receptor useful for the treatment of disorders related thereto |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| EP2242745A1 (de) * | 2008-02-07 | 2010-10-27 | Sanofi-Aventis | Neue phenyl-substituierte imidazolidine, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| US8236792B2 (en) * | 2008-05-23 | 2012-08-07 | Janssen Pharmaceutica Nv | Substituted pyrrolidine amides as modulators of the histamine H3 receptor |
| AU2009291783A1 (en) * | 2008-09-10 | 2010-03-18 | Alcon Research, Ltd | Aminopyrimidine inhibitors of histamine receptors for the treatment of disease |
| EP2635554A2 (en) * | 2010-11-01 | 2013-09-11 | Neurotune AG | Novel neurotrypsin inhibitors |
| EP2683705B1 (de) | 2011-03-08 | 2015-04-22 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| US8871758B2 (en) | 2011-03-08 | 2014-10-28 | Sanofi | Tetrasubstituted oxathiazine derivatives, method for producing them, their use as medicine and drug containing said derivatives and the use thereof |
| US8828995B2 (en) | 2011-03-08 | 2014-09-09 | Sanofi | Branched oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof |
| WO2012120052A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2683699B1 (de) | 2011-03-08 | 2015-06-24 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| CN102784146A (zh) * | 2011-05-19 | 2012-11-21 | 复旦大学 | N-苯基喹唑啉-4-胺类衍生物的药用用途 |
Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
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| GB1416872A (en) * | 1972-03-10 | 1975-12-10 | Wyeth John & Brother Ltd | 4-aminoquinoline derivatives |
| US3933829A (en) * | 1974-08-22 | 1976-01-20 | John Wyeth & Brother Limited | 4-Aminoquinoline derivatives |
| US4159331A (en) * | 1978-05-05 | 1979-06-26 | The Upjohn Company | Antihypertensive 4-aminoquinolines |
| US4166853A (en) * | 1978-05-05 | 1979-09-04 | The Upjohn Company | Antihypertensive 7-trifluoromethyl-4-aminoquinolones |
| DK111387A (da) | 1986-03-05 | 1987-09-06 | Otsuka Pharma Co Ltd | Carbostyrilderivater og salte deraf, laegemiddel indeholdende saadanne derivater samt fremgangsmaade til fremstilling af derivaterne |
| ATE219766T1 (de) | 1993-04-07 | 2002-07-15 | Otsuka Pharma Co Ltd | N-acylierte 4-aminopiperidin derivate als aktive bestandteile von peripher gefässerweiternden wikstoffen |
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-
2007
- 2007-05-16 EP EP07777110A patent/EP2027086B1/en not_active Not-in-force
- 2007-05-16 CN CNA2007800155388A patent/CN101432261A/zh active Pending
- 2007-05-16 MX MX2008014743A patent/MX2008014743A/es not_active Application Discontinuation
- 2007-05-16 WO PCT/US2007/011765 patent/WO2007136668A2/en not_active Ceased
- 2007-05-16 JP JP2009511057A patent/JP2009537542A/ja not_active Withdrawn
- 2007-05-16 AU AU2007254232A patent/AU2007254232A1/en not_active Abandoned
- 2007-05-16 CA CA002649913A patent/CA2649913A1/en not_active Abandoned
- 2007-05-16 AT AT07777110T patent/ATE533744T1/de active
- 2007-05-16 PE PE2007000590A patent/PE20080371A1/es not_active Application Discontinuation
- 2007-05-17 TW TW096117605A patent/TW200811165A/zh unknown
- 2007-05-18 US US11/804,686 patent/US7842715B2/en not_active Expired - Fee Related
- 2007-05-18 AR ARP070102147A patent/AR061015A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| TW200811165A (en) | 2008-03-01 |
| AU2007254232A1 (en) | 2007-11-29 |
| CA2649913A1 (en) | 2007-11-29 |
| WO2007136668A9 (en) | 2008-03-27 |
| US20070270440A1 (en) | 2007-11-22 |
| WO2007136668A2 (en) | 2007-11-29 |
| EP2027086A2 (en) | 2009-02-25 |
| PE20080371A1 (es) | 2008-04-09 |
| MX2008014743A (es) | 2008-12-01 |
| ATE533744T1 (de) | 2011-12-15 |
| AR061015A1 (es) | 2008-07-30 |
| CN101432261A (zh) | 2009-05-13 |
| EP2027086B1 (en) | 2011-11-16 |
| US7842715B2 (en) | 2010-11-30 |
| WO2007136668A3 (en) | 2008-01-24 |
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