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US 2001/0041714 A1Published application
5-HT7 receptor antagonists
AssigneeBristol-Myers Squibb Pharma Company
InventorsGary A. Cain, John F. McElroy
Life of this patent
Estimating the term…
Abstract
The present invention relates to compounds having pharmacological activity toward the 5-HT7 receptor. Pharmaceutical compositions and methods for their use in the treatment of CNS disorders are described.
Claims19
A compound of formula (I):
- 52
- or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:
- R1 is selected from a C6-10 carbocyclic aromatic residue substituted with 1-3 R1a, and a 5-10 membered aromatic heterocyclic system containing from 1-4 heteroatoms selected from N, O and S, substituted with 0-2 R1a;
- R1a is independently selected at each occurrence from halo, —NO2, —CN, —CF3 and —CF2CF3;
- X is selected from —S(O)p—, —C(O)—, —O—, —CH(OH)—, —NR4a—, —CH(OC(O)CH3)—, —S(O)2NR4— and a five membered saturated, partially saturated or unsaturated ring containing 0-2 heteroatoms selected from O and N;
- with the proviso that when X is a five membered saturated, partially saturated or unsaturated ring containing 0-2 heteroatoms selected from O and N, R1 may be an unsubstituted C6-10 carbocyclic aromatic residue;
- R4 is selected from hydrogen and C1-6 alkyl;
- R4a is taken together with R1 to form a 5 or 6-membered fused heterocyclic ring containing 1-2 heteroatoms selected from O and N, substituted with 1 or 2 carbonyl groups;
- Y is C1-3 alkylene;
- A is selected from a 5 or 6 membered saturated, partially saturated or unsaturated ring which contains from 0-1 heteroatoms selected from N, O and S, substituted with 0-3 R5, napthyl substituted with 0-3 R5, and napthyl fused with ring B substituted with 0-3 R5;
- R5 is selected from C1-5 alkyl, halo and —OCH3;
- n is selected from 1, 2, and 3;
- and
- p is selected from 0, 1, and 2.
11 more elements
A compound of formula (II):
- 53
- or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:
- R1 is selected from a C6-10 carbocyclic aromatic residue substituted with 1-3 R1a, and a 5-10 membered aromatic heterocyclic system containing from 1-4 heteroatoms selected from N, O and S, substituted with 0-2 R1a;
- R1a is independently selected at each occurrence from (CH2)rOR1d, halo, C1-4 alkyl, (CH2)r—C3-6 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, —CN, —NO2, —OCF3, (CH2)rNR1bR1c, (CH2)rSO2R1d, (CH2)rC(O)OH, (CH2)rC(O)OR1d, (CH2)rOC(O)R1d, (CH2)rC(O)R1d, (CH2)rNR1b C(O)R1c, (CH2)rC(O)NR1bR1c, (CH2)rSR1d, (CH2)rCH(═NR1b)NR1bR1c, (CH2)rSO2NR1bR1c, (CH2)rSO2NR1bR1c, (CH2)r(CF2)rCF3 and (CH2)r-phenyl substituted with 0-3 R1e;
- R1b and R1c are independently selected at each occurrence from hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl and (CH2)r-phenyl substituted with 0-3 R1e;
- R1d is independently selected at each occurrence from C1-6 alkyl and (CH2)r-phenyl substituted with 0-2 R1e;
- R1e is independently selected at each occurrence from H, —(CH2)rOR1f, halo, C1-4 alkyl, CN, NO2, and —CF3;
- R1f is selected from hydrogen and C1-5 alkyl;
- R1g is C1-5 alkyl;
- X is selected from —CR6R7—, —CR2R3—, —C(O)—, —O—, —S(O)2—, —S(O)2NR4— and NR4a;
- R4 is selected independently at each occurrence from hydrogen, C1-6 alkyl, (CH2)r-C3-7 cycloalkyl, (CH2)r-aryl, and (CH2)r-heteroaryl;
- R4a is taken together with R1 to form a 5 or 6-membered fused heterocyclic ring containing 1-2 heteroatoms selected from O or N substituted with 1 or 2 carbonyl groups;
- R6 is selected independently at each occurrence from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, (CH2)r—C3-6 cycloalkyl, (CH2)r-phenyl, —OH, —OC(O)R6a, C(O)R6a and C(O)OR6a;
- R6a is selected independently from C1-6 alkyl, phenyl and benzyl;
- R7 is selected from hydrogen and C1-5 alkyl;
- A is selected from a 5 or 6 membered saturated, partially saturated or unsaturated ring which contains from 0-1 heteroatoms selected from N, O and S, substituted with 0-3 R5, napthyl substituted with 0-3 R5, and napthyl fused with ring B substituted with 0-3 R5;
- R5 is selected independently at each occurrence from (CH2)rOR5d, halo, C1-4 alkyl, (CH2)r—C3-6 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, —CN, —NO2, —OCF3, (CH2)rNR5bR5c, (CH2)rSO2R5d, (CH2)rC(O)OH, (CH2)rC(O)OR5d, (CH2)rOC(O)R5d, (CH2)rC(O)R5b, (CH2)rNR5bC(O)R5c, (CH2)rC(O)NR5bR5c, (CH2)rSR5d, (CH2)rCH(═NR5b)NR5bR5c, (CH2)rSO2NR5bR5c, (CH2)rSO2NR5bR5c, (CH2)r(CF2)rCF3 and (CH2)r-phenyl substituted with 0-3 R5e;
- R5b and R5c are independently selected at each occurrence from hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, (CH2)r-phenyl;
- R5d is independently selected at each occurrence from C1-6 alkyl, phenyl substituted with 0-2 R5e, and benzyl substituted with 0-2 R5e;
- R5e is independently selected at each occurrence from hydrogen, —(CH2)rOR5f, halo, C1-4 alkyl, CN, NO2, and —CF3;
- R5f is selected from hydrogen and C1-5 alkyl;
- R5g is C1-5 alkyl;
- n is selected from 1, 2, and 3;
- r is selected from 0, 1, and 2.
21 more elements
A compound of formula (III):
- 54
- or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:
- R1 is selected from a C6-10 carbocyclic aromatic residue substituted with 1-3 R1a, and a 5-10 membered aromatic heterocyclic system containing from 1-4 heteroatoms selected from N, O and S, substituted with 0-2 R1a;
- R1a is independently selected at each occurrence from (CH2)rOR1d, halo, C1-4 alkyl, (CH2)r—C3-6 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, —CN, —NO2, —OCF3, (CH2)rNR1bR1c, (CH2)rSO2R1d, (CH2)rC(O)OH, (CH2)rC(O)OR1d, (CH2)rOC(O)R1d, (CH2)rC(O)R1d, (CH2)rNR1bC(O)R1c, (CH2)rC(O)NR1bR1c, (CH2)rSR1d, (CH2)rCH(═NR1b)NR1bR1c, (CH2)rSO2NR1bR1c, (CH2)rSO2NR1bR1c, (CH2)r(CF2)rCF3 and (CH2)r-phenyl substituted with 0-3 R1e;
- R1b and R1c are independently selected at each occurrence from hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl and (CH2)r-phenyl substituted with 0-3 R1e;
- R1d is independently selected at each occurrence from C1-6 alkyl and (CH2)r-phenyl substituted with 0-2 R1e;
- R1e is independently selected at each occurrence from H, —(CH2)rOR1f, halo, C1-4 alkyl, CN, NO2, and —CF3;
- R1f is selected from hydrogen and C1-5 alkyl;
- R1g is C1-5 alkyl;
- R4 is selected independently at each occurrence from hydrogen, C1-6 alkyl, (CH2)r-C3-7 cycloalkyl, (CH2)r-aryl, and (CH2)r-heteroaryl;
- R4a is taken together with R1 to form a 5 or 6-membered fused heterocyclic ring containing 1-2 heteroatoms selected from O or N substituted with 1 or 2 carbonyl groups;
- R6 is selected independently at each occurrence from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, (CH2)r-C3-6 cycloalkyl, (CH2)r-phenyl, —OH, —OC(O)R6a, C(O)R6a and C(O)OR6a;
- R6a is selected independently from C1-6 alkyl, phenyl and benzyl;
- R7 is selected from hydrogen and C1-5 alkyl;
- Y is C1-3 alkylene;
- A is selected from a 5 or 6 membered saturated, partially saturated or unsaturated ring which contains from 0-1 heteroatoms selected from N, O and S, substituted with 0-3 R5, napthyl substituted with 0-3 R5, and napthyl fused with ring B substituted with 0-3 R5;
- R5 is selected independently at each occurrence from (CH2)rOR5d, halo, C1-4 alkyl, (CH2)r-C3-6 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, —CN, —NO2, —OCF3, (CH2)rNR5bR5c, (CH2)rSO2R5d, (CH2)rC(O)OH, (CH2)rC(O)OR5d, (CH2)rOC(O)R5d, (CH2)rC(O)R5b, (CH2)rNR5bC(O)R5c, (CH2)rC(O)NR5bR5c, (CH2)rSR5d, (CH2)rCH(═NR5b)NR5bR5c, (CH2)rSO2NR5bR5c, (CH2)rSO2NR5bR5c, (CH2)r(CF2)rCF3 and (CH2)r-phenyl substituted with 0-3 R5e;
- R5b and R5c are independently selected at each occurrence from hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, (CH2)r-phenyl;
- R5d is independently selected at each occurrence from C1-6 alkyl, phenyl substituted with 0-2 R5e, and benzyl substituted with 0-2 R5e;
- R5e is independently selected at each occurrence from hydrogen, —(CH2)rOR5f, halo, C1-4 alkyl, CN, NO2, and —CF3;
- R5f is selected from hydrogen and C1-5 alkyl;
- R5g is C1-5 alkyl;
- n is selected from 1, 2, and 3;
- r is selected from 0, 1, and 2;
- and
- m is selected from 1, 2, and 3.
23 more elements
Dependencies are inferred from the claim text.