178312-64-6

Upstream product

• 106-95-6 allyl bromide 
• 3218-49-3 3,4-dichloro-benzeneacetonitrile 
• 556-56-9 allyl iodid 
• 88641-55-8 tetrabutylammonium chloride monohydrate 

Downstream Products

• 173457-42-6 4-(3,4-dichlorophenyl)-4-formylbut-1-ene 
• 178312-12-4 (S)-5-Allyl-1-cyclohexylmethyl-5-(3,4-dichloro-phenyl)-piperidin-2-one 
• 178312-08-8 [(S)-1-Cyclohexylmethyl-3-(3,4-dichloro-phenyl)-6-oxo-piperidin-3-yl]-acetaldehyde 
• 194427-18-4 5(S)-5-Allyl-1-cyclohexyl-5-(3,4-dichlorophenyl)piperidin-2-one 
• 194427-23-1 [(S)-1-Cyclohexyl-3-(3,4-dichloro-phenyl)-6-oxo-piperidin-3-yl]-acetaldehyde 
• 178312-15-7 (S)-2-(3,4-Dichloro-phenyl)-2-[2-((S)-4-isopropyl-4,5-dihydro-oxazol-2-yl)-ethyl]-pent-4-enylamine 
• 480421-68-9 (R)-2-(3,4-Dichloro-phenyl)-2-[2-((S)-4-isopropyl-4,5-dihydro-oxazol-2-yl)-ethyl]-pent-4-enylamine 
• 480421-67-8 2-(3,4-Dichloro-phenyl)-2-[2-((S)-4-isopropyl-4,5-dihydro-oxazol-2-yl)-ethyl]-pent-4-enenitrile 
• 194427-17-3 Methyl 4(S)-4-(3,4-dichlorophenyl)-4-formylhept-6-enoate 
• 194427-16-2 4(S)-4-(3,4-Dichlorophenyl)-4-formylhept-6-enoic acid 
• 178312-14-6 5(S)-5-Allyl-5-(3,4-dichlorophenyl)-2(1H)-piperidone 

Relevant academic research and scientific papers

Discovery and SAR of 4-amino-2-biarylbutylurea MCH 1 receptor antagonists through solid-phase parallel synthesis

-4-Amino-2-arylbutylbenzamides such as 1 were identified as micromolar MCH 1 receptor (MCH1R) antagonists via screening using a scintillation proximity assay based on [125I]-MCH binding to recombinant, human MCH1R. Subsequent lead optimization

ARYL AND BIARYL COMPOUNDS HAVING MCH MODULATORY ACTIVITY

In one embodiment, this invention provides a novel class of compounds as antagonists of the MCH receptor, methods of preparing such compounds, pharmaceutical compositions containing one or more of the compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention or amelioration or one or more of diseases associated with the MCH receptor. An illustrative inventive compound is shown below:

Structure-activity relationships of 1-alkyl-5-(3,4-dichlorophenyl)-5-{2-[(3-substituted)-1-azetidinyl]ethyl} -2-piperidones. 1. Selective antagonists of the neurokinin-2 receptor

The design, synthesis, and pharmacological evaluation of a novel class of neurokinin-2 (NK2) antagonists 1-alkyl-5-(3,4-dichlorophenyl)-5-{2-[(3-substituted)- 1-azetidinyl]ethyl}-2-piperidones (5-44) are described. These compounds are formally derived from 2 by incorporating the metabolically vulnerable N-methylamide function into a more stable six-membered ring lactam 4, resulting in increased stability in human liver microsome (HLM) preparations relative to 2 (T1/2(HLM) of 30 min vs 2 receptor in the Rabbit pulmonary artery (RPA) assay (pA2 = 9.3) and increased in vitro metabolic stability (T1/2(HLM) = 70 min) relative to 4. Metabolic route identification studies revealed that N-benzyl oxidation was a major route in this relatively lipophilic lead (log D = 3.2). Further exploration of the N-lactam substituent SAR targeting reduced lipophilicity to attenuate P-450 metabolism revealed that incorporation of a cyclopropylmethyl group in this region of the molecule gave a balance of good potency and high metabolic stability. For example, the significantly less lipophilic analogue 29 (log D = 2.3) possessed both good functional potency (RPA, pA2 = 8. 1) and high in vitro metabolic stability (T1/2(HLM) = 120 min). Optimization in this N-cyclopropylmethyllactam series by modification of the nature of the azetidine 3-substituent as a strategy to further increase potency and moderate log D led to the identification of sulfamide analogue 33, which possessed both excellent metabolic stability in vitro (T1/2(HLM) > 120 min) and high potency in both RPA (pA2 = 8.9) and human bladder smooth muscle (pKb = 8.9) functional assays. In addition, NK2 antagonist 33 (IC50 = 4 nM) showed excellent selectivity over both the related human neurokinin receptors h-NK1 (IC50 = 7.9 μM) and h-NK3 (IC50 = 1.8 μM) in radioligand binding studies.

Quaternary ammonium compounds as tachykinin antagonists

The present invention provides a compound of formula (I) wherein R is phenyl, C3-C7cycloalkyl or heteroaryl, each of which being optionally benzo- or C3-C7cycloalkyl-fused and optionally substituted, including in the benzo- or C3-C7cycloalkyl-fused portion, by from 1 to 3 substituents each independently selected from C1-C4alkyl, fluoro(C1-C4)alkyl, C1-C4alkoxy, fluoro(C1-C4)alkoxy, phenoxy, C2-C4alkanoyl, halo, C1-C4alkoxycarbonyl, C3-C7cycloalkyl, —S(O)m(C1-C4alkyl), cyano, —NR2R3, —S(O)mNR2R3, —NR4(C1-C4alkanoyl) and —CONR2R3, or R is 2,3-dihydrobenzo[b]furanyl or chromanyl; R1is H or C1-C6alkyl; W is a direct link, methylene or ethylene; X is unbranched C2-C4alkylene; Y is phenyl, naphthyl, benzyl, pyridyl, thienyl or C3-C7cycloalkyl, each of which being optionally substituted by from 1 to 3 substituents each independently selected from C1-C4alkyl, fluoro(C1-C4)alkyl, C1-C4alkoxy, fluoro(C1-C4)alkoxy, halo and cyano; Ar is phenyl, naphthyl, benzyl, thienyl, benzo[b]thienyl or indolyl, each of which being optionally substituted by from 1 to 3 substituents each independently selected from C1-C4alkyl, fluoro(C1-C4)alkyl, C1-C4alkoxy, fluoro(C1-C4)alkoxy, halo and cyano, or Ar is 1,3-benzodioxolan-4 or 5-yl or 1,4-benzodioxan-5 or 6-yl; ZAis a pharmaceutically acceptable anion; with the proviso that when W is a direct link and R is optionally fused and optionally substituted heteroaryl, said heteroaryl is linked by a ring carbon atom to the carbonyl group. The compounds are tachykinin antagonists.

3-Azetidinylalkylpiperidines or -pyrrolidines as tachykinin antagonists

The present invention provides compounds of formula (I) and the pharmaceutically acceptable salts thereof. Such compounds and salts are tachykinin antagonists.

Piperidone tachykinin antagonists

The present invention provides compounds of formula (I) and the pharmaceutically acceptable acid addition salts thereof, wherein X is a direct link or C1-C4alkylene; and R is C3-C7cycloalkyl optionally substituted by 1 or 2 substituents each independently selected from fluoro and C3-C7cycloalkyl: with the proviso that X is not methylene when R is cyclopropyl, together with processes for the preparation of, intermediates used in the preparation of, compositions containing and uses of, such compounds. These compounds are useful as tachykinin antagonists.

(Azetidin-1-ylalkyl) lactams as tachykinin antagonists

The present invention provides compounds of formula (I) and the pharmaceutically acceptable salts thereof, wherein R is C3 -C7 cycloalkyl, aryl or C1 -C6 alkyl, said C1 -C6 alkyl, said C1 -C6 alkyl being optionally substituted by fluoro, COOH, --COO(C1 -C4 alkyl), C3 -C7 cycloalkyl, adamantyl, aryl or het1, and said C3 -C7 cycloalkyl being optionally substituted by 1 or 2 substituents each independently selected from C1 -C4 alkyl, C3 -C7 cycloalkyl, C1 -C4 alkoxy, hydroxy, fluoro, fluoro (C1 -C4) alkyl and fluoro (C1 -C4) Alkoxy; R1 is phenyl, naphthyl, thienyl, benzothienyl or indolyl, each optionally substituted by 1 or 2 substituents each independently selected from C1 -C4 alkyl, C1 -C4 alkoxy, halo and trifluormethyl; R2 is --CO2 H, --CONR3 R4, --CONR5 (C3 -C7 cycloalkyl), --NR5 (C2 -C5 alkanoyl), --NR3 R4, --NR5 CONR5 R6, (C3 -C7 cycloalkyl-C1 -C4 alkyl)R5 N--, --NR5 COCF3, --NR5 SO2 CF3, --NR5 (SO2 C1 -C4 alkyl), --NR5 SO2 NR5 R6, --NR5 (SO2 aryl), --N(aryl) (SO2 C1 -C4 alkyl), --OR5, --O(C3 -C7 cycloalkyl), --SO2 NR5 R6, het3 or a group of formulas: (a), (b), (c), (d), (e), (f), (g) or (h); X is C1 -C4 alkylene; X1 is a direct link or C1 -C6 alkylene; X2 is a direct link, CO, SO2, or NR5 CO; and m is 0, 1 or 2; together with intermediates used in the preparation of compositions containing and the use as tachykinin angatonists of such derivatives. STR1

3-aza and 3-oxa piperidone tachykinin antagonists

Compounds of the formula: STR1 wherein: X is O, NH or NR1 ; R1 is C1 -C6 alkyl, C3 -C7 cycloalkyl, C3 -C7 cycloalkyl(C1 -C4)alkyl, aryl or aryl (C1 -C4)alkyl; wherein the C1 -C6 alkyl group is optionally substituted by fluorine and the C3 -C7 cycloalkyl or C3 -C7 cycloalkyl(C1 -C4 )alkyl group is optionally substituted in the cycloalkyl ring by up to two substituents each independently selected from halo, C1 -C4 alkoxy or halo(C1 -C4)alkoxy; R2 is phenyl optionally substituted with one or two halo substituents, indolyl or thienyl; R3 is NH2, --NR4 SO2 (C1 -C6 alkyl), --NR4 SO2 aryl, --NR4 CO(C1 -C6 alkyl), --NR4 CO aryl or a 5 to 7-membered N-linked cyclic group incorporating W in the ring wherein W is O, NR5, CH(OH), CHCO2 H, CHN(R4)2, CHF, CF2, C=O or CH2 ; R4 is H or C1 -C6 alkyl; R5 is H, C1 -C6 alkyl, C3 -C7 cycloalkyl, C3 -C7 cycloalkyl(C1 -C6)alkyl, C2 -C6 alkanoyl, C4 -C8 cycloalkanoyl, C3 -C7 cycloalkyl(C2 -C6)alkanoyl, aryl CO--, C1 -C6 alkyl SO2 --, C3 -C7 cycloalkyl SO2 --, C3 -C7 cycloalkyl(C1 -C6)alkyl SO2 --, aryl-SO2 -- or (R6)2 NSO2 --, wherein each R6 is independently H or C1 -C4 alkyl or the two groups may be joined to form with the nitrogen atom to which they are attached, a pyrrolidinyl, piperidino, morphlino or piperazinyl group; m is 0, 1 or 2 with the proviso that m is not 0 when W is NR5, C=O, or O; and n is an integer of from 1 to 4; are neurokinin receptor antagonists of utility in the treatment of a variety of medical conditions including urinary incontinence, asthma and related conditions.