193276-50-5

Upstream product

• 193276-48-1 (8-chloro-3,10-dibromo-6,11-dihydro-5H-benzo-<5,6>cyclohepta<1,2-b>pyridin-11-yl)-1-piperidine 
• 108-22-5 Isopropenyl acetate 
• 102096-25-3 2,2,2-trifluoroethyl isobutyrate 

Relevant academic research and scientific papers

Enzymatic kinetic resolution of piperidine atropisomers: Synthesis of a key intermediate of the farnesyl protein transferase inhibitor, SCH66336

The resolution of secondary amines via enzyme-catalyzed acylation is a relatively rare process. The kinetic resolution of a series of intermediates of SCH66336 (1), by either enzymatic acylation of the pendant piperidine (4, 5) or hydrolysis of the corresponding carbamate 3, was investigated. In the case of 4, the molecule exists as a pair of enantiomers due to atropisomerism about the exocyclic double bond. The enzymatic acylation of (±)-4 was optimized in terms of acylating agent, solvent, and moisture content. The use of lipase, Toyobo LIP-300, and trifluoroethyl isobutyrate as acylating agent resulted in isobutyrylation of the (+)-enantiomer, which is easily separated from the unwanted (-)-4. Hydrolysis of the isobutyramide 6c yielded the desired (+)-4 in high enantiomeric excess. (-)-4 may be recovered from the resolution step, racemized, and resubjected to enzymatic acylation to increase material throughput.

BENZO(5,6)CYCLOHEPTA(1,2B)PYRIDINE DERIVATIVES USEFUL FOR INHIBITION OF FARNESYL PROTEIN TRANSFERASE

Novel compounds of formula: (1.0) or a pharmaceutically acceptable salt or solvate thereof, wherein: a represents N or NO; R and R are the same or different and each represents halo; R and R are each independently selected from H and halo, provided that at least one of R and R is H; each dotted line (---) represents an optional bond; X is N, C when the optional bond to X is present, or CH when the optional bond to X is absent; T is a substituent selected from (A) or (B): Z represents O or S; R represents -C(O)N(R)2, -CH2C(O)N(R), -SO2R, -SO2N(R)2, -C(O)R, -C(O)-O-R, alkyl, aryl, aralkyl, cycloalkyl, heterocycloalkyl or heteroaryl; R represents alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, OR, NRH, SH, SR, SOR (where R is not H) or SO2R (where R is not H); and each R independently represents H, alkyl, aryl, or aralkyl; R is alkyl, aryl, aralkyl, heteroaryl, or heterocycloalkyl; R is selected from H, alkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, or heterocycloalkyl. Also disclosed are methods of inhibiting farnesyl protein transferase and methods for treating tumor cells.

BENZO(5,6)CYCLOHEPTA(1,2-B)PYRIDINE DERIVATIVES USEFUL FOR INHIBITION OF FARNESYL PROTEIN TRANSFERASE

Novel compounds of formula (1.0) are disclosed. In Formula (1.0) a represents N or NO, R and R are halo, R and R are independently H or halo provided that at least one is H, X is C, CH or N, and T represents a five or six membered heterocycloalkyl ring having one or two heteroatoms selected from S or O. Also disclosed are methods of inhibiting farnesyl protein transferase and methods for treating tumor cells.

COMPOUNDS USEFUL FOR INHIBITION OF FARNESYL PROTEIN TRANSFERASE

Novel compounds of formula (1.0) are disclosed. Compounds of formula (1.0) are represented by the compounds of formula (1.4) or (1.5) wherein R, R and R are each independently selected from halo. Also disclosed are methods of inhibiting farnesyl protein transferase and the growth of abnormal cells, such as tumor cells.

TRICYCLIC INHIBITORS OF FARNESYL PROTEIN TRANSFERASE

Novel compounds of formula (1.0) are disclosed. Compounds of formula (1.0) are represented by the compounds of formulas (1.4) or (1.5) wherein R, R and R are each independently selected from halo. Also disclosed are methods of inhibiting farnesyl