CA1123842A - Amino 4,5,6,7-tetrahydro-1h (ou 2h) - indazoles - Google Patents

Amino 4,5,6,7-tetrahydro-1h (ou 2h) - indazoles

Info

Publication number: CA1123842A
Authority: CA; Canada
Prior art keywords: tetrahydro; indazole; formulae; amino; compounds
Prior art date: 1979-01-22
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.): Expired

Application number

CA385,099A

Other languages

English (en)

Inventor

Nicholas J. Bach

Edmund C. Kornfeld

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Eli Lilly and Co

Original Assignee

Eli Lilly and Co

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.)

1979-01-22

Filing date

1981-09-02

Publication date

1982-05-18

1979-03-15 Priority claimed from US06/020,559 external-priority patent/US4276300A/en

1981-09-02 Application filed by Eli Lilly and Co filed Critical Eli Lilly and Co

1981-09-02 Priority to CA385,099A priority Critical patent/CA1123842A/fr

1982-05-18 Application granted granted Critical

1982-05-18 Publication of CA1123842A publication Critical patent/CA1123842A/fr

Status Expired legal-status Critical Current

Links

125000003277 amino group Chemical group 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 39
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238000005903 acid hydrolysis reaction Methods 0.000 claims abstract description 3
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract 2
238000000034 method Methods 0.000 claims description 14
238000004519 manufacturing process Methods 0.000 claims description 3
239000000126 substance Substances 0.000 claims 1
150000003839 salts Chemical class 0.000 abstract description 15
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108010057464 Prolactin Proteins 0.000 abstract description 13
229940097325 prolactin Drugs 0.000 abstract description 13
239000002253 acid Substances 0.000 abstract description 11
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract description 7
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 abstract description 7
206010034010 Parkinsonism Diseases 0.000 abstract description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 6
150000001350 alkyl halides Chemical class 0.000 abstract description 3
150000008064 anhydrides Chemical class 0.000 abstract description 3
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 abstract description 2
239000003112 inhibitor Substances 0.000 abstract description 2
238000006722 reduction reaction Methods 0.000 abstract description 2
238000005932 reductive alkylation reaction Methods 0.000 abstract description 2
125000002485 formyl group Chemical class [H]C(*)=O 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
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UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
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AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 13
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239000011541 reaction mixture Substances 0.000 description 8
238000001704 evaporation Methods 0.000 description 7
230000008020 evaporation Effects 0.000 description 7
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 6
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239000012299 nitrogen atmosphere Substances 0.000 description 4
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BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
239000007858 starting material Substances 0.000 description 4
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DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 2
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101150041968 CDC13 gene Proteins 0.000 description 2
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229910010084 LiAlH4 Inorganic materials 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
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VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
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QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
230000002152 alkylating effect Effects 0.000 description 2
229940043376 ammonium acetate Drugs 0.000 description 2
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ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
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230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
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239000012280 lithium aluminium hydride Substances 0.000 description 2
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BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 2
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HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
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238000002329 infrared spectrum Methods 0.000 description 1
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238000001819 mass spectrum Methods 0.000 description 1
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238000005649 metathesis reaction Methods 0.000 description 1
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WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
IZYBEMGNIUSSAX-UHFFFAOYSA-N methyl benzenecarboperoxoate Chemical compound COOC(=O)C1=CC=CC=C1 IZYBEMGNIUSSAX-UHFFFAOYSA-N 0.000 description 1
229940095102 methyl benzoate Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
XCVNDBIXFPGMIW-UHFFFAOYSA-N n-ethylpropan-1-amine Chemical group CCCNCC XCVNDBIXFPGMIW-UHFFFAOYSA-N 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
KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
229940049953 phenylacetate Drugs 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
229950009215 phenylbutanoic acid Drugs 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
229940080818 propionamide Drugs 0.000 description 1
WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229940116351 sebacate Drugs 0.000 description 1
CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 1
239000007787 solid Substances 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
238000010998 test method Methods 0.000 description 1
230000009466 transformation Effects 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
238000005303 weighing Methods 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

CA385,099A 1979-01-22 1981-09-02 Amino 4,5,6,7-tetrahydro-1h (ou 2h) - indazoles Expired CA1123842A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA385,099A CA1123842A (fr)	1979-01-22	1981-09-02	Amino 4,5,6,7-tetrahydro-1h (ou 2h) - indazoles

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
US506479A	1979-01-22	1979-01-22
US5,064		1979-01-22
US06/020,559 US4276300A (en)	1979-01-22	1979-03-15	Amino-substituted-4,5,6,7-tetrahydro-1H (or 2H)-indazoles
US20,559		1979-03-15
CA000330568A CA1120932A (fr)	1979-01-22	1979-06-26	Amino-subst. 4,5,6,7-tetrahydro-1h (ou 2h)-indazoles
CA385,099A CA1123842A (fr)	1979-01-22	1981-09-02	Amino 4,5,6,7-tetrahydro-1h (ou 2h) - indazoles

Publications (1)

Publication Number	Publication Date
CA1123842A true CA1123842A (fr)	1982-05-18

Family

ID=27426166

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA385,099A Expired CA1123842A (fr)	1979-01-22	1981-09-02	Amino 4,5,6,7-tetrahydro-1h (ou 2h) - indazoles

Country Status (1)

Country	Link
CA (1)	CA1123842A (fr)

1981
- 1981-09-02 CA CA385,099A patent/CA1123842A/fr not_active Expired

Legal Events

Date	Code	Title	Description
1999-05-18	MKEX	Expiry

Publication	Publication Date	Title
PL122153B1 (en)	1982-06-30	Process for preparing novel octahydropyrazolo-/3,4-g/ quinolinesnov
EP0618905A1 (fr)	1994-10-12	Derives d'imidazolyle-alkyle-piperazine et diazepine utilises comme agonistes antagonistes de l'histamine h3.
CA1123842A (fr)	1982-05-18	Amino 4,5,6,7-tetrahydro-1h (ou 2h) - indazoles
CA1128951A (fr)	1982-08-03	Amino 4,5,6,7-tetrahydro-ih(ou 2h)-indazoles
CA1120932A (fr)	1982-03-30	Amino-subst. 4,5,6,7-tetrahydro-1h (ou 2h)-indazoles
EP0109815B1 (fr)	1986-05-28	Tétrahydronaphtalènes substitués
EP0207696A1 (fr)	1987-01-07	Dialkylaminotétrahydrobenzothiazoles et -oxazoles
US4322430A (en)	1982-03-30	Amino-substituted 4,5,6,7-tetrahydro-1H (or 2H)-indazoles
US4322540A (en)	1982-03-30	Substituted 4,5,6,7-tetrahydro-1H (or 2H)-indazoles
KR880001430B1 (ko)	1988-08-08	옥타하이드로-옥사졸로[4,5-g]퀴놀린 유도체
KR830000708B1 (ko)	1983-04-06	아미노-치환된 4,5,6,7-테트라하이드로-1h(또는 2h)-인다졸의 제조방법
US4235776A (en)	1980-11-25	Tetrahydro-2H-benzo[c]pyrroles
FI78091C (fi)	1989-06-12	Analogifoerfarande foer framstaellning av saosom dopaminoagonister anvaendbara pyrimido/4,5-g/kinolinderivat.
US4367231A (en)	1983-01-04	Method of using octahydro pyrazolo[3,4-g]quinolines
EP0014792B1 (fr)	1982-12-01	Tétrahydro-2H-benzo(c)pyrroles, leur préparation, compositions pharmaceutiques les contenant et les composés utilisables contenant que médicaments
US4264622A (en)	1981-04-28	Tetrahydro-2H-benzo[c]pyrroles to inhibit prolactin secretion
CA1133487A (fr)	1982-10-12	Octahydropyrazolo (3,4,g) quinolines
KR830000326B1 (ko)	1983-03-04	옥타하이드로 피라졸로[3,4-g] 퀴놀린의 제조방법
US4783464A (en)	1988-11-08	N-substituted ergoline- and 9,10-didehydro-ergoline-8-carboxamide-and-8-aminomethyl-derivatives, their production and their pharmaceutical composition
CA1136141A (fr)	1982-11-23	Octahydropyrazolo (3,4,g) quinolines
US4622398A (en)	1986-11-11	Dialkylaminotetrahydroquinazoline
JPS6242897B2 (fr)	1987-09-10
CA1136144A (fr)	1982-11-23	Octahydropyrazolo (3,4,g) quinolines
CA1136629A (fr)	1982-11-30	Octahydropyrazolo (3,4,g) quinolines
CA1234112A (fr)	1988-03-15	Pyrimido(4,5-g)quinolines et produits intermediaires