HRP20151073T1 - Postupak sinteze i kristalni oblik 4-{3-[cis-heksahidrociklopenta[c]pirol-2(1h)-il]propoksi}benzamid hidroklorida i njegove slobodne baze kao i farmaceutski pripravci koji ih sadrže - Google Patents
Postupak sinteze i kristalni oblik 4-{3-[cis-heksahidrociklopenta[c]pirol-2(1h)-il]propoksi}benzamid hidroklorida i njegove slobodne baze kao i farmaceutski pripravci koji ih sadrže Download PDFInfo
- Publication number
- HRP20151073T1 HRP20151073T1 HRP20151073TT HRP20151073T HRP20151073T1 HR P20151073 T1 HRP20151073 T1 HR P20151073T1 HR P20151073T T HRP20151073T T HR P20151073TT HR P20151073 T HRP20151073 T HR P20151073T HR P20151073 T1 HRP20151073 T1 HR P20151073T1
- Authority
- HR
- Croatia
- Prior art keywords
- formula
- compound
- accordance
- synthesis
- disease
- Prior art date
Links
- 230000015572 biosynthetic process Effects 0.000 title claims 21
- 238000003786 synthesis reaction Methods 0.000 title claims 19
- 238000000034 method Methods 0.000 title claims 14
- AFSVOZDCVFYWFG-KBGJBQQCSA-N 4-[3-[(3as,6ar)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]propoxy]benzamide;hydrochloride Chemical compound Cl.C1=CC(C(=O)N)=CC=C1OCCCN1C[C@H]2CCC[C@H]2C1 AFSVOZDCVFYWFG-KBGJBQQCSA-N 0.000 title claims 8
- 239000012458 free base Substances 0.000 title claims 2
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 48
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 11
- 208000035475 disorder Diseases 0.000 claims 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 6
- 201000011240 Frontotemporal dementia Diseases 0.000 claims 6
- 230000003542 behavioural effect Effects 0.000 claims 6
- 230000001149 cognitive effect Effects 0.000 claims 6
- 239000013078 crystal Substances 0.000 claims 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 4
- 238000005859 coupling reaction Methods 0.000 claims 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 4
- 208000024827 Alzheimer disease Diseases 0.000 claims 3
- 206010012289 Dementia Diseases 0.000 claims 3
- 206010067889 Dementia with Lewy bodies Diseases 0.000 claims 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 3
- 208000006264 Korsakoff syndrome Diseases 0.000 claims 3
- 201000002832 Lewy body dementia Diseases 0.000 claims 3
- 208000019022 Mood disease Diseases 0.000 claims 3
- 208000008589 Obesity Diseases 0.000 claims 3
- 208000002193 Pain Diseases 0.000 claims 3
- 208000018737 Parkinson disease Diseases 0.000 claims 3
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 3
- 201000004810 Vascular dementia Diseases 0.000 claims 3
- 230000032683 aging Effects 0.000 claims 3
- 210000004556 brain Anatomy 0.000 claims 3
- 230000006735 deficit Effects 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 229940079593 drug Drugs 0.000 claims 3
- 208000013403 hyperactivity Diseases 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- 230000004770 neurodegeneration Effects 0.000 claims 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims 3
- 235000020824 obesity Nutrition 0.000 claims 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims 3
- 238000000197 pyrolysis Methods 0.000 claims 3
- 230000002739 subcortical effect Effects 0.000 claims 3
- 208000011580 syndromic disease Diseases 0.000 claims 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 2
- 238000001237 Raman spectrum Methods 0.000 claims 2
- 229910021529 ammonia Inorganic materials 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 claims 2
- 230000000742 histaminergic effect Effects 0.000 claims 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims 2
- 238000006268 reductive amination reaction Methods 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- ZCALNZSERKKAGM-UHFFFAOYSA-N 4-(3,3-diethoxypropoxy)benzamide Chemical group CCOC(OCC)CCOC1=CC=C(C(N)=O)C=C1 ZCALNZSERKKAGM-UHFFFAOYSA-N 0.000 claims 1
- CKPWJBXTVZXVHS-UHFFFAOYSA-N 4-(3-chloropropoxy)benzamide Chemical compound NC(=O)C1=CC=C(OCCCCl)C=C1 CKPWJBXTVZXVHS-UHFFFAOYSA-N 0.000 claims 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 238000002441 X-ray diffraction Methods 0.000 claims 1
- 230000002378 acidificating effect Effects 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- -1 bicyclic amine Chemical class 0.000 claims 1
- 238000009739 binding Methods 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 239000003054 catalyst Substances 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
- 150000002576 ketones Chemical class 0.000 claims 1
- 230000003340 mental effect Effects 0.000 claims 1
- 229910052751 metal Inorganic materials 0.000 claims 1
- 239000002184 metal Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- 239000002798 polar solvent Substances 0.000 claims 1
- 229910000027 potassium carbonate Inorganic materials 0.000 claims 1
- 239000000843 powder Substances 0.000 claims 1
- 238000000634 powder X-ray diffraction Methods 0.000 claims 1
- 239000011541 reaction mixture Substances 0.000 claims 1
- 238000001953 recrystallisation Methods 0.000 claims 1
- 230000002829 reductive effect Effects 0.000 claims 1
- 239000007787 solid Substances 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
-
- 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
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/46—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/18—Radicals substituted by singly bound oxygen or sulfur atoms
- C07D317/22—Radicals substituted by singly bound oxygen or sulfur atoms etherified
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Claims (32)
1. Postupak za industrijsku sintezu spoja formule (I):
[image]
naznačen time, da spoj formule (II):
[image]
reagira s amonijakom pri temperaturi većoj od 100 °C, kako bi se dobio spoj formule (III):
[image]
koji se reducira, čime se dobije biciklički amin formule (IV):
[image]
taj spoj se zatim podvrgne
- ili reakciji povezivanja, u bazičnim uvjetima u polarnom mediju, sa spojem formule (V):
[image]
gdje Y predstavlja -CH2-Hal gdje Hal predstavlja halogen ili skupinu -CH2-OSO2-R pri čemu je R (C1-C6)alkil skupina ili -C6H4-CH3 skupina,
- ili reduktivnoj aminaciji, u kiselom mediju, sa spojem formule (V'):
[image]
pri čemu R' i R" predstavljaju, svaki neovisno jedan o drugom, (C1-C6)alkil skupinu ili R' i R" zajedno tvore skupinu -(CH2)n- pri čemu je n = 2-3 ili jedna od skupina R' i R" predstavljaju vodikov atom a druga predstavlja (C1-C6)alkil skupinu,
- ili reduktivnoj aminaciji sa spojem formule (V"):
[image]
da se dobije slobodna baza spoja formule (I), koji je podvrgnut prisutnosti HCl kako bi se dobio spoj formule (I), koji se izdvaja u obliku krutine.
2. Postupak za sintezu spoja formule (I), u skladu s patentnim zahtjevom 1, naznačen time, da se reakcijska smjesa dobivena na kraju reakcije spoja formule (II) s amonijakom podvrgava pirolizi.
3. Postupak za sintezu spoja formule (I), u skladu s patentnim zahtjevom 2, naznačen time, da se piroliza povoljno izvodi pri temperaturi većoj od ili jednakoj 200°C.
4. Postupak za sintezu spoja formule (I), u skladu s patentnim zahtjevom 2, naznačen time, da se piroliza povoljno izvodi pri temperaturi većoj od ili jednakoj 280°C.
5. Postupak za sintezu spoja formule (I), u skladu s patentnim zahtjevom 1, naznačen time, da se prevođenje spoja formule (III) u spoj formule (IV) provodi u prisutnosti vodika i metalnog katalizatora.
6. Postupak za sintezu spoja formule (I), u skladu s patentnim zahtjevom 1, naznačen time, da je spoj formule (V) 4-(3-kloropropoksi)benzamid.
7. Postupak za sintezu spoja formule (I), u skladu s patentnim zahtjevom 1, naznačen time, da se reakcija spajanja spoja formule (IV) sa spojem formule (V) provodi u prisutnosti karbonata, amina ili hidroksida.
8. Postupak za sintezu spoja formule (I), u skladu s patentnim zahtjevom 1, naznačen time, da se reakcija spajanja spoja formule (IV) sa spojem formule (V) provodi u prisutnosti kalijevog karbonata ili trietilamina.
9. Postupak za sintezu spoja formule (I), u skladu s patentnim zahtjevom 1, naznačen time, da se reakcija vezanja spoja formule (IV) sa spojem formule (V) provodi u polarnom mediju koji se sastoji od jednog ili više polarnih otapala izabranih između vode, alkohola, ketona, etera, amida, DMSO i acetonitrila.
10. Postupak za sintezu spoja formule (I), u skladu s patentnim zahtjevom 1, naznačen time, da se reakcija spajanja spoja formule (IV) sa spojem formule (V) provodi u mješavini voda/acetonitril ili voda/izopropanol.
11. Postupak za sintezu spoja formule (I), u skladu s patentnim zahtjevom 1, naznačen time, da se korak formiranje soli u prisutnosti HCl odvija u otapalu odabranom između vode, acetona i alkohola.
12. Postupak za sintezu spoja formule (I), u skladu s patentnim zahtjevom 1, naznačen time, da se korak formiranje soli u prisutnosti HCl odvija u acetonu ili izopropanolu.
13. Postupak za sintezu spoja formule (I), u skladu s jednim od patentnih zahtjeva 1 do 6, naznačen time, da je spoj formule (I) podvrgnut rekristalizaciji.
14. Spoj formule (V) u skladu s patentnim zahtjevom 1, pri čemu Y predstavlja skupinu -CH2-OSO2-R i pri čemu je R (C1-C6)alkil skupina ili -C6H4-CH3 skupina, naznačen time, da se koristi za uporabu kao međuprodukt u sintezi spoja formule (I).
15. Upotreba spoja formule (V) u skladu s patentnim zahtjevom 1 ili 14, naznačena time, da se koristi u sintezi spoja formule (I).
16. Spoj formule (V') u skladu s patentnim zahtjevom 1, naznačen time, da se koristi kao međuprodukt sinteze spoja formule (I).
17. Spoj formule (V'), u skladu s patentnim zahtjevom 16, naznačen time, da je to 4-(3,3-dietoksipropoksi)benzamid.
18. Upotreba spoja formule (V') u skladu s patentnim zahtjevom 16 ili 17, naznačena time, da se koristi u sintezi spoja formule (I).
19. Upotreba spoja formule (V") u skladu s patentnim zahtjevom 1, naznačena time, da se koristi u sintezi spoja formule (I).
20. Kristalni oblik I spoja formule (I) u skladu s patentnim zahtjevom 1:
[image]
naznačen time, da dijagram rendgenskog difraktograma praha ima sljedeće linije difrakcije (Braggov kut 2 theta, izražen u stupnjevima +/- 0.2 °): 16.97 °, 17.84 °, 18.90 °, 20.32 °, 23.87 °, 27.10 °, 27.86 ° i 30.34 °.
21. Kristalni oblik I spoja formule (I) u skladu s patentnim zahtjevom 20, naznačen time, da je karakteriziran dijagramom rendgenske difrakcije praha, mjereno uz pomoć PANalytical X'Pert Pro MPD difraktometrom s detektorom X'Celerator i izraženim položajem linije (Braggov kut 2 theta, izražen u stupnjevima +/- 0.2 °) i interplanarnom udaljenosti d (izraženo u Å):
[image]
22. Kristalni oblik I spoja formule (I) u skladu s patentnim zahtjevom 20 ili 21, naznačen time, da Ramanov spektar ima značajnu vršnu vrijednost na mjestima 1606 cm-1 ili 1676 cm-1.
23. Kristalni oblik I spoja formule (I) u skladu s bilo kojim od patentnih zahtjeva 20 do 22, naznačen time, da Ramanov spektar ima značajne vršne vrijednosti na mjestima 1676 cm-1, 1606 cm-1, 1564 cm-1, 1152 cm -1, 830 cm-1 i 296 cm-1.
24. Farmaceutski pripravak, naznačen time, da sadrži kao aktivni sastojak kristalni oblik I 4-{3-[cis-heksahidrociklopenta[c]pirol-2(1H)-il]propoksi}benzamid hidroklorida u skladu s jednim od patentnih zahtjeva 20 do 23, u kombinaciji s jednim ili više farmaceutski prihvatljivih, netoksičnih, inertnih nosača.
25. Farmaceutski pripravak u skladu s patentnim zahtjevom 24, naznačen time, da je namijenjen upotrebi u liječenju kognitivnih i psihičkih poremećaja ponašanja povezanih sa starenjem mozga i neurodegenerativnim bolestima te za liječenje poremećaja raspoloženja, sindroma poremećaja hiperaktivnosti i deficita pažnje, pretilosti i boli.
26. Farmaceutski pripravak u skladu s patentnim zahtjevom 24, naznačen time, da je namijenjen upotrebi u liječenju poremećaja kognitivnih i psihičkih poremećaja ponašanja povezanih s Alzheimerovom bolesti, Parkinsonovom bolesti, Pickovom bolesti, Korsakoffljevom bolesti, demencijom s Lewyjevim tijelima, frontalnom i subkortikalnom demencije, frontotemporalnom demencijom i vaskularnom demencijom.
27. Uporaba kristalnog oblika I 4-{3-[cis-heksahidrociklopenta[c]pirol-2(1H)-il]propoksi}benzamid hidroklorida u skladu s jednim od patentnih zahtjeva 20 do 23, naznačena time, da se koristi u proizvodnji lijeka za uporabu u tretmanu poremećaja histaminergičkog sustava.
28. Uporaba kristalnog oblika I 4-{3-[cis-heksahidrociklopenta[c]pirol-2(1H)-il]propoksi}benzamid hidroklorida u skladu s patentnim zahtjevom 27, naznačena time, da se koristi u proizvodnji lijeka namijenjenog liječenju kognitivnih i psihičkih poremećaja ponašanja povezanih sa starenjem mozga i neurodegenerativnim bolestima te za liječenje poremećaja raspoloženja, sindroma poremećaja hiperaktivnosti i deficita pažnje, pretilosti i boli.
29. Uporaba kristalnog oblika I 4-{3-[cis-heksahidrociklopenta[c]pirol-2(1H)-il]propoksi}benzamid hidroklorida u skladu s patentnim zahtjevom 27, naznačena time, da se koristi u proizvodnji lijeka namijenjenog liječenju kognitivnih i psihičkih poremećaja ponašanja povezanih s Alzheimerovom bolesti, Parkinsonovom bolesti, Pickovom bolesti, Korsakoffljevom bolesti, demencijom s Lewyjevim tijelima, frontalnom i subkortikalnom demencijom, frontotemporalnom demencijom i vaskularnom demencijom
30. Kristalni oblik I 4-{3-[cis-heksahidrociklopenta[c]pirol-2(1H)-il]propoksi}benzamid hidroklorida u skladu s bilo kojim od patentnih zahtjeva 20 do 23, naznačen time, da se koristi u liječenju poremećaja histaminergičkog sustava.
31. Kristalni oblik I 4-{3-[cis-heksahidrociklopenta[c]pirol-2(1H)-il]propoksi}benzamid hidroklorida u skladu s patentnim zahtjevom 30, naznačen time, da se koristi u liječenju kognitivnih i psihičkih poremećaja ponašanja povezanih sa starenjem mozga i neurodegenerativnim bolestima kao i za liječenje poremećaja raspoloženja, sindroma poremećaja hiperaktivnosti i deficita pažnje, pretilosti i boli.
32. Kristalni oblik I 4-{3-[cis-heksahidrociklopenta[c]pirol-2(1H)-il]propoksi}benzamid hidroklorida u skladu s patentnim zahtjevom 30, naznačen time, da se koristi u liječenju kognitivnih i psihičkih poremećaja ponašanja povezanih s Alzheimerovom bolesti, Parkinsonovom bolesti, Pickovom bolesti, Korsakoffljevom bolesti, demencijom s Lewyjevim tjelima, frontalnom i subkortikalnom demencijom, frontotemporalnom demencijom i vaskularnom demencijom.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR1101746A FR2976285B1 (fr) | 2011-06-08 | 2011-06-08 | Procede de synthese et forme cristalline du chlorhydrate de 4-{3-[cis-hexahydrocypenta[c]pyrrol-2(1h)-yl]propoxy}benzamide ainsi que les compositions pharmaceutiques qui la contiennent |
| EP12171118.8A EP2532651B1 (fr) | 2011-06-08 | 2012-06-07 | Procédé de synthèse et forme cristalline du chlorhydrate de 4-{3-[cis-hexahydrocyclopenta[c]pyrrol-2(1h)-yl]propoxy} benzamide ainsi que la base libre associée et les compositions pharmaceutiques qui les contiennent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20151073T1 true HRP20151073T1 (hr) | 2015-11-06 |
Family
ID=46172744
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20151073TT HRP20151073T1 (hr) | 2011-06-08 | 2015-10-09 | Postupak sinteze i kristalni oblik 4-{3-[cis-heksahidrociklopenta[c]pirol-2(1h)-il]propoksi}benzamid hidroklorida i njegove slobodne baze kao i farmaceutski pripravci koji ih sadrže |
Country Status (43)
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR3003466B1 (fr) * | 2013-03-22 | 2015-08-07 | Servier Lab | Utilisation du 4-{3-[cis-hexahydrocyclopenta[c]pyrrol-2(1h)-yl]propoxy}benzamide pour le traitement des douleurs neuropathiques |
| CN103601666B (zh) * | 2013-11-28 | 2015-09-02 | 遵义医学院 | 八氢环戊烷[c]吡咯的制备方法 |
| CN104387313B (zh) * | 2014-10-22 | 2015-12-30 | 滨海博大化工有限公司 | 一种1,2-环戊二甲酰亚胺的制备方法 |
| KR101966221B1 (ko) * | 2017-06-14 | 2019-04-12 | 최상근 | 유해가스 처리 장치 |
| CN115232058A (zh) * | 2022-08-01 | 2022-10-25 | 上海巽田科技股份有限公司 | 一种格列齐特中间体1,2-环戊二甲酰胺的合成方法 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US756120A (en) * | 1902-07-28 | 1904-03-29 | Krupp Gmbh | Recoil-gun with special devices for protecting the slide-tracks from dust. |
| NL132376C (hr) * | 1966-02-10 | |||
| US4895840A (en) * | 1987-06-10 | 1990-01-23 | A. H. Robins Company, Incorporated | N-(aryl-,aryloxy-,arylthio-arylsulfinyl-and arylsulfonyl-)alkyl-N,N'-(or n'n')alkylaminoalkyl ureas and cyanoguanidines |
| CN1314340A (zh) * | 2000-03-21 | 2001-09-26 | 山东省医药工业研究所 | 环戊烷酰亚胺的制备方法 |
| FR2866647B1 (fr) * | 2004-02-20 | 2006-10-27 | Servier Lab | Nouveaux derives azabicycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| CN100424077C (zh) * | 2005-06-07 | 2008-10-08 | 台州市四维化工厂 | 一种环戊烷1，2-二酰亚胺的制备方法 |
| FR2937251B1 (fr) * | 2008-10-16 | 2011-03-18 | Servier Lab | Utilisation du 4-{3-°hexahydrocyclopenta°c!pyrrol-2(1h)-yl! propoxy}benzamide pour l'obtention de medicaments destines au traitement des troubles du sommeil |
| AR074226A1 (es) * | 2008-11-26 | 2010-12-29 | Abbott Lab | Octahidrociclopenta[c]pirrol-4-aminas sustituidas como bloqueantes de los canales de calcio, composiciones farmaceuticas que las comprenden y el uso de las mismas para el tratamiento del dolor. |
| FR2953515B1 (fr) * | 2009-12-09 | 2011-12-23 | Servier Lab | Nouveaux derives du type hexahydrocyclopenta[b]pyrrole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR2974729B1 (fr) * | 2011-05-02 | 2013-04-19 | Servier Lab | Nouvelle association entre le 4-{3-[cis-hexahydrocyclopenta[c]pyrrol-2(1h)-yl]propoxy}benzamide et un inhibiteur de l'acetylcholinesterase et les compositions pharmaceutiques qui la contiennent |
-
2011
- 2011-06-08 FR FR1101746A patent/FR2976285B1/fr not_active Expired - Fee Related
-
2012
- 2012-05-22 PE PE2012000695A patent/PE20130046A1/es not_active Application Discontinuation
- 2012-05-22 IL IL219925A patent/IL219925A0/en unknown
- 2012-05-23 CR CR20120274A patent/CR20120274A/es unknown
- 2012-05-24 TN TNP2012000254A patent/TN2012000254A1/fr unknown
- 2012-05-24 AU AU2012203062A patent/AU2012203062B2/en not_active Expired - Fee Related
- 2012-05-24 SG SG2012038055A patent/SG186546A1/en unknown
- 2012-05-28 AP AP2012006280A patent/AP2012006280A0/xx unknown
- 2012-05-30 CA CA2779045A patent/CA2779045C/fr not_active Expired - Fee Related
- 2012-05-31 UY UY0001034110A patent/UY34110A/es unknown
- 2012-05-31 CU CU2012000087A patent/CU20120087A7/es unknown
- 2012-06-01 EC ECSP12011941 patent/ECSP12011941A/es unknown
- 2012-06-04 MA MA34937A patent/MA33883B1/fr unknown
- 2012-06-05 BR BRBR102012013573-6A patent/BR102012013573A2/pt not_active IP Right Cessation
- 2012-06-05 KR KR1020120060635A patent/KR20120136296A/ko active IP Right Grant
- 2012-06-05 GE GEAP201212735A patent/GEP20156395B/en unknown
- 2012-06-06 US US13/489,691 patent/US8664408B2/en not_active Expired - Fee Related
- 2012-06-06 CO CO12095647A patent/CO6580197A1/es unknown
- 2012-06-06 SV SV2012004237A patent/SV2012004237A/es unknown
- 2012-06-07 AR ARP120102010A patent/AR086848A1/es unknown
- 2012-06-07 JP JP2012129440A patent/JP5680022B2/ja not_active Expired - Fee Related
- 2012-06-07 MD MDA20120049A patent/MD4345C1/ro not_active IP Right Cessation
- 2012-06-07 PT PT121711188T patent/PT2532651E/pt unknown
- 2012-06-07 EP EP12171118.8A patent/EP2532651B1/fr active Active
- 2012-06-07 TW TW101120546A patent/TWI499584B/zh not_active IP Right Cessation
- 2012-06-07 RU RU2013158817/04A patent/RU2013158817A/ru not_active Application Discontinuation
- 2012-06-07 CL CL2012001500A patent/CL2012001500A1/es unknown
- 2012-06-07 ES ES12171118.8T patent/ES2554933T3/es active Active
- 2012-06-07 DK DK12171118.8T patent/DK2532651T3/en active
- 2012-06-07 HU HUE12171118A patent/HUE028050T2/en unknown
- 2012-06-07 PL PL12171118T patent/PL2532651T3/pl unknown
- 2012-06-07 SI SI201230309T patent/SI2532651T1/sl unknown
- 2012-06-07 RS RS20150642A patent/RS54279B1/en unknown
- 2012-06-07 ZA ZA2012/04183A patent/ZA201204183B/en unknown
- 2012-06-07 ME MEP-2015-148A patent/ME02346B/me unknown
- 2012-06-07 WO PCT/FR2012/051272 patent/WO2012168657A1/fr active Application Filing
- 2012-06-07 GT GT201200182A patent/GT201200182A/es unknown
- 2012-06-07 MX MX2012006525A patent/MX2012006525A/es not_active Application Discontinuation
- 2012-06-08 NI NI201200102A patent/NI201200102A/es unknown
- 2012-06-08 EA EA201200726A patent/EA022741B1/ru not_active IP Right Cessation
- 2012-06-08 CN CN201210189156XA patent/CN102816102A/zh active Pending
-
2013
- 2013-12-11 US US14/103,006 patent/US8952179B2/en not_active Expired - Fee Related
-
2014
- 2014-02-06 US US14/174,272 patent/US20140155453A1/en not_active Abandoned
- 2014-05-27 KR KR1020140063712A patent/KR20140079346A/ko not_active Application Discontinuation
- 2014-10-31 JP JP2014223181A patent/JP2015044840A/ja active Pending
-
2015
- 2015-10-02 CY CY20151100875T patent/CY1116739T1/el unknown
- 2015-10-09 HR HRP20151073TT patent/HRP20151073T1/hr unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HRP20151073T1 (hr) | Postupak sinteze i kristalni oblik 4-{3-[cis-heksahidrociklopenta[c]pirol-2(1h)-il]propoksi}benzamid hidroklorida i njegove slobodne baze kao i farmaceutski pripravci koji ih sadrže | |
| RU2544856C2 (ru) | НОВЫЕ ПРОИЗВОДНЫЕ 2,3,4,5-ТЕТРАГИДРО-1-ПИРИДО[4,3-b]ИНДОЛА И СПОСОБЫ ИХ ПРИМЕНЕНИЯ | |
| CA2457444A1 (en) | 1h-imidazole derivatives having cb1 agonistic, cb1 partial agonistic or cb1- antagonistic activity | |
| FI78691B (fi) | Foerfarande foer framstaellning av i position 3-substituerade pyridazinderivat, vilka inverkar pao det centrala nervsystemet. | |
| EA014244B1 (ru) | СПОСОБ ПОЛУЧЕНИЯ 1-Н-ИМИДАЗО[4,5-c]ПИРИДИНОВ И ИХ АНАЛОГОВ | |
| GB2048852A (en) | Derivatives of glycinamide | |
| RU2014145682A (ru) | Органические соединения | |
| CA2939835C (en) | Aminocarbonylcarbamate compounds | |
| CA2634008A1 (en) | Improved synthesis and preparations of duloxetine salts | |
| JP6203841B2 (ja) | カルバメート／尿素誘導体 | |
| WO2007054444A3 (en) | 3-aryl-isoxazole-4-carbonyl-benzofuran derivatives | |
| WO2011138625A1 (en) | Industrial process for the synthesis of ivabradine salts | |
| WO2002044142A2 (en) | Piperazine derivatives, their preparation and their use for treating central nervous system (cns) disorders | |
| WO2006028161A1 (ja) | セロトニン５－ｈｔ３受容体作動薬 | |
| JP2018506503A (ja) | Ｎ−［４−（１−アミノエチル）−フェニル］−スルホンアミド誘導体のキラル分割方法 | |
| MX2009010242A (es) | Compuestos de azetidina adecuados para el tratamiento de trastornos que responden a la modulacion del receptor de serotonina 5-ht6. | |
| CA2618636A1 (en) | Aminoaryl sulphonamide derivatives as functional 5-ht6 ligands | |
| JP2019501923A (ja) | 極性非プロトン性溶媒を用いたｎ−［４−（１−アミノエチル）−フェニル］−スルホンアミド誘導体のキラル分割方法 | |
| HRP20090523T1 (hr) | Novi piridinilaminoalkilen i piridiniloksialkilen ciklopropanamini, postupak njihove priprave i farmaceutski pripravci koji ih sadrže | |
| US9745264B2 (en) | Method for preparing silodosin and intermediate thereof | |
| AU2019300036A1 (en) | Inhibitors of histone deacetylase | |
| US20110034479A1 (en) | Deuterium-enriched alkyl sulfonamides | |
| US11166958B2 (en) | 4-pyrazin-2-ylmethyl-morpholine derivatives and the use thereof as medicament | |
| JP2014520785A5 (hr) | ||
| WO2014009964A1 (en) | Process for enantiomeric enrichment of 2 ', 6 ' - pipecoloxylidide |