Superacid cyclodehydration of ketones in the production of tricyclic antihistamines

Schumacher, Doris P.; Murphy, Bruce L.; Clark, Jon E.; Tahbaz, P.; Mann, Thomas A.

doi:10.1021/jo00270a041

Cited by 34 publications

(18 citation statements)

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“…The pH of the reaction mixture was adjusted to 7, and then the mixture was extracted with CH2Cl2. The organic phase was dried over (12). Tricyclic amine 5 (0.5 g, 1.12 mmol) was dissolved in 11 mL of dilute H2SO4 (10%, v/v) at room temperature.…”

Section: -[8-chloro-3-(thiocyano)-56-dihydro-11h-benzo[56]-cyclohementioning

confidence: 99%

Structure−Activity Relationship of 3-Substituted N-(Pyridinylacetyl)-4- (8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)- piperidine Inhibitors of Farnesyl-Protein Transferase: Design and Synthesis of in Vivo Active Antitumor Compounds

Fg¹,

Vibulbhan²,

Df³

et al. 1997

J. Med. Chem.

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Novel tricyclic Ras farnesyl-protein transferase (FPT) inhibitors are described. A comprehensive structure-activity relationship (SAR) study of compounds arising from substitution at the 3-position of the tricyclic pyridine ring system has been explored. In the case of halogens, the chloro, bromo, and iodo analogues 19, 22, and 28 were found to be equipotent. However, the fluoro analogue 17 was an order of magnitude less active. Whereas a small alkyl substituent such as a methyl group resulted in a very potent FPT inhibitor (SCH 56580), introduction of bulky substituents such as tert-butyl, compound 33, or a phenyl group, compound 29, resulted in inactive FPT inhibitors. Polar groups at the 3-position such as amino 5, alkylamino 6, and hydroxyl 12 were less active. Whereas compound SCH 44342 did not show appreciable in vivo antitumor activity, the 3-bromo-substituted pyridyl N-oxide amide analogue 38 was a potent FPT inhibitor that reduced tumor growth by 81% when administered q.i.d. at 50 mpk and 52% at 10 mpk. These compounds are nonpeptidic and do not contain sulfhydryl groups. They selectively inhibit FPT and not geranylgeranyl-protein transferase-1 (GGPT-1). They also inhibit H-Ras processing in COS monkey kidney cells and soft agar growth of Ras-transformed cells.

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Section: -[8-chloro-3-(thiocyano)-56-dihydro-11h-benzo[56]-cyclohementioning

confidence: 99%

Structure−Activity Relationship of 3-Substituted N-(Pyridinylacetyl)-4- (8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)- piperidine Inhibitors of Farnesyl-Protein Transferase: Design and Synthesis of in Vivo Active Antitumor Compounds

Fg¹,

Vibulbhan²,

Df³

et al. 1997

J. Med. Chem.

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“…Cyclodehydration has been used to prepare the antihistamine precursor 80 under superacid conditions 315 The related transformation of 1-phenyl-2-propen-1-ones 81 (a Nazarov-type cyclization) [Eq. (5.121)] has also been studied by Shudo and co-workers.…”

Section: Cyclialkylationmentioning

confidence: 99%

Superacid‐Catalyzed Reactions

Oláh¹,

Prakash²,

Molnár³

et al. 2008

Superacid Chemistry

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“…Recognising this, Schumacher et al 10 later (Scheme 2) devised an improved route to Claritin 1 in which the lithiated pyridyl amide 8 was initially alkylated to give 9, a precursor for the nitrile 6.…”

Section: Introductionmentioning

confidence: 99%

Ozonolysis of some 8-alkoxyquinolines, and synthesis of a precursor to the non-sedating antihistamine Claritin

Eichler¹,

Grayson²

2014

Arkivoc

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3-Formyl-2-methoxycarbonylpyridine and isopropyl 3-formylpyridine-2-carboxylate have each been efficiently accessed in one step via the ozonolyses of 8-methoxy-or of 8-isopropoxyquinoline under near-ambient conditions. The compounds can be utilized as intermediates for syntheses of the tricyclic ketone 8-chloro-6,11-dihydro-5H-benzo [5,6]cyclohepta[1,2-b]pyridin-11-one, a precursor to the important non-sedating antihistamine Claritin.

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Superacid cyclodehydration of ketones in the production of tricyclic antihistamines

Cited by 34 publications

References 0 publications

Structure−Activity Relationship of 3-Substituted N-(Pyridinylacetyl)-4- (8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)- piperidine Inhibitors of Farnesyl-Protein Transferase: Design and Synthesis of in Vivo Active Antitumor Compounds

Structure−Activity Relationship of 3-Substituted N-(Pyridinylacetyl)-4- (8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)- piperidine Inhibitors of Farnesyl-Protein Transferase: Design and Synthesis of in Vivo Active Antitumor Compounds

Superacid‐Catalyzed Reactions

Ozonolysis of some 8-alkoxyquinolines, and synthesis of a precursor to the non-sedating antihistamine Claritin

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