ES2580759T3 - Compuestos orgánicos - Google Patents
Compuestos orgánicos Download PDFInfo
- Publication number
- ES2580759T3 ES2580759T3 ES09830742.4T ES09830742T ES2580759T3 ES 2580759 T3 ES2580759 T3 ES 2580759T3 ES 09830742 T ES09830742 T ES 09830742T ES 2580759 T3 ES2580759 T3 ES 2580759T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- methyl
- aryl
- optionally substituted
- halo
- 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.)
- Active
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- 150000002894 organic compounds Chemical class 0.000 title description 2
- -1 1-hydroxypropan-2-yl Chemical group 0.000 claims abstract description 228
- 150000001875 compounds Chemical class 0.000 claims abstract description 204
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 85
- 125000003118 aryl group Chemical group 0.000 claims abstract description 72
- 150000003839 salts Chemical group 0.000 claims abstract description 53
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 49
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 49
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 46
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 45
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 44
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 36
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims abstract description 34
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 34
- 239000011737 fluorine Substances 0.000 claims abstract description 34
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 33
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 30
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 29
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 27
- 239000000460 chlorine Substances 0.000 claims abstract description 26
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 26
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims abstract description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 25
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 24
- 150000002367 halogens Chemical class 0.000 claims abstract description 24
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 23
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 claims abstract description 23
- 125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 22
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 22
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims abstract description 21
- 125000002720 diazolyl group Chemical group 0.000 claims abstract description 20
- 125000001425 triazolyl group Chemical group 0.000 claims abstract description 20
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 18
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 18
- 125000001113 thiadiazolyl group Chemical group 0.000 claims abstract description 18
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims abstract description 17
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 16
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims abstract description 16
- 125000003831 tetrazolyl group Chemical group 0.000 claims abstract description 16
- 125000004512 1,2,3-thiadiazol-4-yl group Chemical group S1N=NC(=C1)* 0.000 claims abstract description 14
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims abstract description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 14
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 14
- 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 13
- RGTBLCLLSZPOKR-UHFFFAOYSA-N 5-methyl-1,2,4-oxadiazole Chemical compound CC1=NC=NO1 RGTBLCLLSZPOKR-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 12
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 10
- 125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 claims abstract description 10
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims abstract description 9
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 9
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 8
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims abstract description 8
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims abstract description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims abstract description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 8
- 125000004429 atom Chemical group 0.000 claims abstract description 7
- 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 abstract description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 6
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 5
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims abstract description 4
- 239000004305 biphenyl Substances 0.000 claims abstract description 4
- 235000010290 biphenyl Nutrition 0.000 claims abstract description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims abstract description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 72
- 125000005843 halogen group Chemical group 0.000 claims description 50
- 238000011282 treatment Methods 0.000 claims description 46
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 claims description 41
- 208000028017 Psychotic disease Diseases 0.000 claims description 23
- 239000000186 progesterone Substances 0.000 claims description 20
- 229960003387 progesterone Drugs 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 17
- 201000003631 narcolepsy Diseases 0.000 claims description 14
- 208000018737 Parkinson disease Diseases 0.000 claims description 11
- 229940011871 estrogen Drugs 0.000 claims description 11
- 239000000262 estrogen Substances 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 208000010412 Glaucoma Diseases 0.000 claims description 10
- 206010057671 Female sexual dysfunction Diseases 0.000 claims description 9
- 206010026749 Mania Diseases 0.000 claims description 9
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 9
- 201000000980 schizophrenia Diseases 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- 230000009529 traumatic brain injury Effects 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 8
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 7
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 7
- 208000020925 Bipolar disease Diseases 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 7
- 208000028698 Cognitive impairment Diseases 0.000 claims description 6
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 6
- 208000010877 cognitive disease Diseases 0.000 claims description 6
- 230000004406 elevated intraocular pressure Effects 0.000 claims description 6
- 208000024254 Delusional disease Diseases 0.000 claims description 5
- 208000005793 Restless legs syndrome Diseases 0.000 claims description 5
- 208000020186 Schizophreniform disease Diseases 0.000 claims description 5
- 208000003532 hypothyroidism Diseases 0.000 claims description 5
- 230000002989 hypothyroidism Effects 0.000 claims description 5
- 230000009245 menopause Effects 0.000 claims description 5
- 208000002851 paranoid schizophrenia Diseases 0.000 claims description 5
- 208000022610 schizoaffective disease Diseases 0.000 claims description 5
- 208000024891 symptom Diseases 0.000 claims description 5
- 201000000736 Amenorrhea Diseases 0.000 claims description 4
- 206010001928 Amenorrhoea Diseases 0.000 claims description 4
- 206010003805 Autism Diseases 0.000 claims description 4
- 208000020706 Autistic disease Diseases 0.000 claims description 4
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- 208000023105 Huntington disease Diseases 0.000 claims description 4
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 4
- 208000016620 Tourette disease Diseases 0.000 claims description 4
- 231100000540 amenorrhea Toxicity 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 201000006828 endometrial hyperplasia Diseases 0.000 claims description 4
- 208000000509 infertility Diseases 0.000 claims description 4
- 231100000535 infertility Toxicity 0.000 claims description 4
- 230000036512 infertility Effects 0.000 claims description 4
- 239000000583 progesterone congener Substances 0.000 claims description 4
- 210000002307 prostate Anatomy 0.000 claims description 4
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 4
- 208000037853 Abnormal uterine bleeding Diseases 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 201000005670 Anovulation Diseases 0.000 claims description 3
- 206010002659 Anovulatory cycle Diseases 0.000 claims description 3
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
- 206010012289 Dementia Diseases 0.000 claims description 3
- 208000012661 Dyskinesia Diseases 0.000 claims description 3
- 208000001914 Fragile X syndrome Diseases 0.000 claims description 3
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 claims description 3
- 206010020772 Hypertension Diseases 0.000 claims description 3
- 206010027339 Menstruation irregular Diseases 0.000 claims description 3
- 208000016285 Movement disease Diseases 0.000 claims description 3
- 208000001132 Osteoporosis Diseases 0.000 claims description 3
- 206010036595 Premature delivery Diseases 0.000 claims description 3
- 206010036618 Premenstrual syndrome Diseases 0.000 claims description 3
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 3
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 3
- 206010044565 Tremor Diseases 0.000 claims description 3
- 201000010105 allergic rhinitis Diseases 0.000 claims description 3
- 231100000552 anovulation Toxicity 0.000 claims description 3
- 230000036506 anxiety Effects 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 230000001363 autoimmune Effects 0.000 claims description 3
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 3
- 206010013663 drug dependence Diseases 0.000 claims description 3
- 229960005309 estradiol Drugs 0.000 claims description 3
- 229930182833 estradiol Natural products 0.000 claims description 3
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
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- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 3
- 208000019116 sleep disease Diseases 0.000 claims description 3
- 208000011117 substance-related disease Diseases 0.000 claims description 3
- PROQIPRRNZUXQM-UHFFFAOYSA-N (16alpha,17betaOH)-Estra-1,3,5(10)-triene-3,16,17-triol Natural products OC1=CC=C2C3CCC(C)(C(C(O)C4)O)C4C3CCC2=C1 PROQIPRRNZUXQM-UHFFFAOYSA-N 0.000 claims description 2
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 claims description 2
- YFGHCGITMMYXAQ-UHFFFAOYSA-N 2-[(diphenylmethyl)sulfinyl]acetamide Chemical compound C=1C=CC=CC=1C(S(=O)CC(=O)N)C1=CC=CC=C1 YFGHCGITMMYXAQ-UHFFFAOYSA-N 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 239000000935 antidepressant agent Substances 0.000 claims description 2
- 229940005513 antidepressants Drugs 0.000 claims description 2
- PROQIPRRNZUXQM-ZXXIGWHRSA-N estriol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 PROQIPRRNZUXQM-ZXXIGWHRSA-N 0.000 claims description 2
- 229960001348 estriol Drugs 0.000 claims description 2
- 229960001165 modafinil Drugs 0.000 claims description 2
- 208000020685 sleep-wake disease Diseases 0.000 claims description 2
- SJZRECIVHVDYJC-UHFFFAOYSA-M 4-hydroxybutyrate Chemical compound OCCCC([O-])=O SJZRECIVHVDYJC-UHFFFAOYSA-M 0.000 claims 1
- 201000009030 Carcinoma Diseases 0.000 claims 1
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- 239000002269 analeptic agent Substances 0.000 claims 1
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- 125000003545 alkoxy group Chemical group 0.000 abstract description 2
- 125000001475 halogen functional group Chemical group 0.000 abstract 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 39
- 238000001819 mass spectrum Methods 0.000 description 35
- 229940121836 Phosphodiesterase 1 inhibitor Drugs 0.000 description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
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- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 22
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- 102100024318 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B Human genes 0.000 description 16
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- ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 description 16
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- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 14
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 14
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- 125000001424 substituent group Chemical group 0.000 description 12
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- 238000011321 prophylaxis Methods 0.000 description 11
- ICISSZBYTVZMRU-UHFFFAOYSA-N 2-[4-(chloromethyl)phenyl]pyridine Chemical compound C1=CC(CCl)=CC=C1C1=CC=CC=N1 ICISSZBYTVZMRU-UHFFFAOYSA-N 0.000 description 10
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-
2009
- 2009-12-07 WO PCT/US2009/006437 patent/WO2010065147A1/en not_active Ceased
- 2009-12-07 BR BRPI0922809A patent/BRPI0922809A2/pt not_active IP Right Cessation
- 2009-12-07 CN CN2009801483001A patent/CN102238873A/zh active Pending
- 2009-12-07 EP EP09830742.4A patent/EP2367428B1/en active Active
- 2009-12-07 ES ES09830742.4T patent/ES2580759T3/es active Active
- 2009-12-07 US US13/133,147 patent/US8927556B2/en active Active
- 2009-12-07 MX MX2011005935A patent/MX2011005935A/es not_active Application Discontinuation
- 2009-12-07 EA EA201170768A patent/EA201170768A1/ru unknown
- 2009-12-07 MA MA33970A patent/MA32939B1/fr unknown
- 2009-12-07 CA CA2740385A patent/CA2740385A1/en not_active Abandoned
- 2009-12-07 JP JP2011539518A patent/JP5710492B2/ja not_active Expired - Fee Related
- 2009-12-07 PE PE2011001168A patent/PE20110834A1/es not_active Application Discontinuation
- 2009-12-07 KR KR1020117013107A patent/KR20110098730A/ko not_active Withdrawn
- 2009-12-07 AU AU2009322899A patent/AU2009322899A1/en not_active Abandoned
-
2011
- 2011-05-17 TN TN2011000244A patent/TN2011000244A1/fr unknown
- 2011-05-17 ZA ZA2011/03630A patent/ZA201103630B/en unknown
- 2011-06-02 IL IL213316A patent/IL213316A0/en unknown
- 2011-06-06 CR CR20110311A patent/CR20110311A/es unknown
- 2011-06-06 DO DO2011000171A patent/DOP2011000171A/es unknown
- 2011-06-29 CO CO11081319A patent/CO6390080A2/es active IP Right Grant
- 2011-07-05 EC EC2011011185A patent/ECSP11011185A/es unknown
-
2015
- 2015-01-05 US US14/589,602 patent/US20150353556A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EA201170768A1 (ru) | 2012-05-30 |
| ZA201103630B (en) | 2013-05-29 |
| CO6390080A2 (es) | 2012-02-29 |
| CN102238873A (zh) | 2011-11-09 |
| JP5710492B2 (ja) | 2015-04-30 |
| BRPI0922809A2 (pt) | 2018-05-29 |
| CA2740385A1 (en) | 2010-06-10 |
| EP2367428A1 (en) | 2011-09-28 |
| EP2367428B1 (en) | 2016-04-06 |
| US8927556B2 (en) | 2015-01-06 |
| KR20110098730A (ko) | 2011-09-01 |
| ECSP11011185A (es) | 2011-10-31 |
| DOP2011000171A (es) | 2011-10-31 |
| JP2012510991A (ja) | 2012-05-17 |
| CR20110311A (es) | 2011-11-10 |
| EP2367428A4 (en) | 2012-06-06 |
| MX2011005935A (es) | 2011-12-16 |
| IL213316A0 (en) | 2011-07-31 |
| PE20110834A1 (es) | 2011-12-14 |
| WO2010065147A1 (en) | 2010-06-10 |
| US20150353556A1 (en) | 2015-12-10 |
| TN2011000244A1 (en) | 2012-12-17 |
| US20120136013A1 (en) | 2012-05-31 |
| AU2009322899A1 (en) | 2010-06-10 |
| MA32939B1 (fr) | 2012-01-02 |
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