- Process development of the synthetic route to R116301
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We describe in this paper the synthesis of compound 1 (R116301), which was developed to prepare pilot scale quantities (20-50 kg) of drug substance. The synthesis involves the sBuLi deprotonation of Boc-protected piperidone acetal 2, followed b
- Guillaume, Michel,Cuypers, Jef,Dingenen, Jul
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- DIAZA-SPIRO-[4.4]-NONANE DERIVATIVES AS NEUROKININ (NK1) ANTAGONISTS
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This invention concerns substituted diaza-spiro-[4.4]-nonane derivatives having neurokinin antagonistic activity, in particular NK1 antagonist ic activity, their preparation, compositions comprising them and their use as a medicine, in particular for the
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Page/Page column 36
(2008/06/13)
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- SUBSTITUTED OXA-DIAZA-SPIRO-[5.5]-UNDECANONE DERIVATIVES AND THEIR USE AS NEUROKININ ANTAGONISTS
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This invention concerns substituted oxa-diaza-spiro-[5.5]-undecanone derivatives having neurokinin antagonistic activity, in particular an NK1 antagonistic activity, an NK3 antagonistic activity, a combined NK1/NK2/s
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(2010/11/23)
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- (2-BENZYL-4-{4-[1-(TETRAHYDROFURAN-3-CARBONYL)-PYRROLIDIN-3-YL]-PIPERAZIN-1-YL}-PIPERIDIN-1-YL)-(3,5-TRIFLUOROMETHYL-PHENYL))-METHANONE FOR THE TREATMENT OF SCHIZOPHRENIA
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This invention concerns the use of 2-benzyl-4-{4-[1-(tetrahydrofuran-3-carbonyl)-pyrrolidin-3-yl]-piperazin- l -yl}-piperidin-1-yl)-(3,5-trifluoromethyl-phenyl)-methanone and its derivatives having neurokinin antagonistic activity, in particular a combine
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- SUBSTITUTED DIAZA-SPIRO-[4.5]-DECANE DERIVATIVES AND THEIR USE AS NEUROKININ ANTAGONISTS
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This invention concerns substituted diaza-spiro-[4.5]-decane derivatives having neurokinin antagonistic activity, in particular NK1 antagonistic activity, a combined NK1/NK2 antagonist ic activity, a combined NK1/NK3 antagonist ic activity and a combined NK1/NK2/NK3 antagonistic activity, their preparation, compositions comprising them and their use as a medicine, in particular for the treatment and/or prophylaxis of schizophrenia, emesis, anxiety and depression, irritable bowel syndrome (IBS), circadian rhythm disturbances, pre-eclampsia, nociception, pain, in particular visceral and neuropathic pain, pancreatitis, neurogenic inflammation, asthma, chronic obstructive pulmonary disease (COPD) and micturition disorders such as urinary incontinence. The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1.
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(2008/06/13)
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- SUBSTITUTED DIAZA-SPIRO-[5.5]-UNDECANE DERIVATIVES AND THEIR USE AS NEUROKININ ANTAGONISTS
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This invention concerns substituted diaza-spiro-[5.5]-undecane derivatives having neurokinin antagonistic activity, in particular NK1 antagonistic activity, a combined NK1/NK2 antagonistic activity, a combined NK1/su
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Page/Page column 37
(2008/06/13)
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- SUBSTITUTED 4-ALKYL- AND 4-ALKANOYL-PIPERIDINE DERIVATIVES AND THEIR USE AS NEUROKININ ANTAGONISTS
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The invention concerns substituted 4-alkyl- and 4-alkanoyl-piperidine derivatives having neurokinin antagonistic activity, in particular NK1 antagonistic activity and a combined NK1/NK3 antagonistic activity, compositions
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(2010/02/14)
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- SUBSTITUTED 1,4-DI-PIPERIDIN-4-YL-PIPERAZINE DERIVATIVES AND THEIR USE AS NEUROKININ ANTAGONISTS
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The invention concerns substituted 1,4-di-piperidin-4-yl-piperazine derivatives having neurokinin antagonistic activity, in particular NK1 antagonistic activity, their preparation, compositions comprising them and their use as a medicine, in particular fo
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- SUBSTITUTED 1-PIPERIDIN-3-YL-4-PIPERIDIN-4-YL-PIPERAZINE DERIVATIVES AND THEIR USE AS NEUROKININ ANTAGONISTS
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This invention concerns substituted 1-piperidin-3-yl-4-piperidin-4-yl-piperazine derivatives having neurokinin antagonistic activity, in particular NK1 antagonistic activity, a combined NK1/NK3 antagonistic activity and a
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- SUBSTITUTED 1-PIPERIDIN-4-YL-4-AZETIDIN-3-YL-PIPERAZINE DERIVATIVES AND THEIR USE AS NEUROKININ ANTAGONISTS
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The invention concerns substituted 1-piperidin-4-yl-4-azefdin-3-yl-piperazine having neurokinin antagonistic activity, in particular NK1 and NK1/NK3- antagonistic activity, their preparation, compositions comprising them and their use as a medicine, in pa
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- SUBSTITUTED 1-PIPERIDIN-4-YL-4-PYRROLIDIN-3-YL-PIPERAZINE DERIVATIVES AND THEIR USE AS NEUROKININ ANTAGONISTS
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This invention concerns substituted I-piperidin-4-yl-4-pyrrolidin-3-yl-piperazine derivatives having neurokinin antagonistic activity, in particular NK1 antagonistic activity, a combined NK1/NK3 antagonistic activity and a combined NK1/NK2/NK3 antagonistic activity, their preparation, compositions comprising them and their use as a medicine, in particular for the treatment of schizophrenia, anxiety, depression, emesis and IBS. The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1. In view of their capability to antagonize the actions of tachykinins by blocking the neurokinin receptors, and in particular antagonizing the actions of substance P and Neurokinin B by blocking the NK1, NK2 and NK3 receptors, the compounds according to the invention are useful as a medicine, in particular in the prophylactic and therapeutic treatment of tachykinin-mediated conditions, such as, for instance CNS disorders, in particular schizoaffective disorders, depression, anxiety disorders, stress-related disorders, sleep disorders, cognitive disorders, personality disorders, eating disorders, neurodegenerative diseases, addiction disorders, mood disorders, sexual dysfunction, pain and other CNS-related conditions ; inflammation ; allergic disorders ; emesis ; gastrointestinal disorders, in particular irritable bowel syndrome (IBS); skin disorders ; vasospastic diseases ; fibrosing and collagen diseases ; disorders related to immune enhancement or suppression and rheumatic diseases and body weight control.
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- 1-(1,2-disubstituted pipeidinyl)-4-substituted piperidine derivatives
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The present invention concerns compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and stereochemically isomeric forms thereof, wherein n is 0, 1 or 2; m is 1 or 2, provided that if m is 2, then n is 1; p is 0, 1 or 2; ═Q is ═O or ═NR3; X is a covalent bond or a bivalent radical of formula —O—, —S—, —NR3—; R1is Ar1; Ar1C1-6alkyl or di(Ar1)C1-6alkyl, wherein each C1-6alkyl group is optionally substituted with hydroxy, C1-4alkyloxy, oxo or a ketalized oxo substituent of formula —O—CH2—CH2—O— or —O—CH2—CH2—CH2—O—; R2is Ar2; Ar2C1-6alkyl; Het or HetC1-6alkyl; R3is hydrogen or C1-6alkyl; R4is hydrogen; C1-4alkyl; C1-4alkyloxyC1-4alkyl; hydroxyC1-4alkyl; carboxyl; C1-4alkyloxycarbonyl or Ar3; R5is hydrogen; hydroxy; Ar3; Ar3C1-6alkyloxy; di(Ar3)C1-6alkyloxy; Ar3C1-6alkylthio; di(Ar3)C1-6alkylthio; Ar3C1-6alkylsulfoxy; di(Ar3)C1-6alkylsulfoxy; Ar3C1-6alkylsulfonyl; di(Ar3)C1-6alkylsulfonyl; —NR7R8; C1-6alkyl substituted with —NR7R8; or a radical of formula (a-1) or (a-2); R4and R5may also be taken together; R6is hydroxy; C1-6alkyloxy; C1-6alkyl or Ar3C1-6alkyl; Ar1, Ar2and Ar3are phenyl or substituted phenyl; Ar2is also naphtalenyl; and Het is an optionally substituted monocyclic or bicyclic heterocycle; as substance P antagonists; their preparation, compositions containing them and their use as a medicine.
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(2010/02/04)
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- 1- (1,2-disubstituted piperidinyl) -4-substituted piperazine derivatives
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This invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereoisomeric forms thereof, as substance-P antagonists; their preparation, compositions containing them and their use as a medicin
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- (Benzimidazolyl- and imidazopyridinyl) containing 1-(1,2-disubstituted piperidinyl) derivatives
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This invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n is 0, 1 or 2; m is 1 or 2, provided that if m is 2, then n is 1; X is a covalent
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