Children's Medical Center Corporation

Other

Harvard College

Pharm-eco Laboratories, Inc.

Nuchem Pharmaceuticals Inc.

Ion Pharmaceuticals, Inc.

Richard John Lombardy

Adel M Moussa

Minghua Sun

Jose Alberto Halperin

Ying-Duo Gao

Yesh P Sachdeva

Carlo Brugnara

John J Clifford

Reem M Haidar

Eugene W Kelleher

Heather N Taft

Emile M Bellott

Rudolf Fluckiger

Mark Froimowitz

Emile M Bellot, Jr

Falguni M Kher

Reem M Haider

Michael H Zeldin

The present invention provides a class of chemical compounds useful as efficacious drugs in the treatment of sickle cell disease and diseases characterized by unwanted or abnormal cell proliferation, and in particular inflammatory diseases associated with unwanted cellular proliferation. The active compounds are substituted triaryl methane compounds or analogues thereof where one or more of the aryl groups is replaced with a heteroaryl, cycloalkyl or heterocycloalkyl group and/or the tertiary carbon atom is replaced with a different atom such as Si, Ge, N or P. the compounds inhibit mammalian cell proliferation, inhibit the Gardos channel of erythrocytes, reduce sickle erythrocyte dehydration and/or delay the occurrence of erythrocyte sickling or deformation.

Use of triaryl methane compounds for inhibiting unwanted cellular proliferation associated with inflammatory disease

The present invention provides substituted 3,3-diphenyl indole compounds, as well as analogues thereof, which are specific potent and safe inhibitors of mammalian cell proliferation. The compounds can be used to inhibit mammalian cell proliferation in situ as a therapeutic approach towards the treatment or prevention of diseases characterized by abnormal cell proliferation, such as cancer.

Substituted diphenyl indanone, indane and indole compounds and analogues thereof useful for the treatment or prevention of diseases characterized by abnormal cell proliferation

The present invention provides substituted 11-phenyl-dibenzazepine compounds which are specific, potent and safe inhibitors of mammalian cell proliferation. The compounds can be used to inhibit mammalian cell proliferation in situ as a therapeutic approach towards the treatment or prevention of diseases characterized by abnormal cell proliferation, such as cancer.

Substituted 11-phenyl-dibenzazepine compounds useful for the treatment or prevention of diseases characterized by abnormal cell proliferation

The present invention provides substituted 3,3-diphenyl indanone, indane and indole compounds, as well as analogues thereof, which are specific, potent and safe inhibitors of mammalian cell proliferation. The compounds can be used to inhibit mammalian cell proliferation in situ as a therapeutic approach towards the treatment or prevention of diseases characterized by abnormal cell proliferation, such as cancer.

Substituted diphenyl indanone, indane and indole compounds and analogues thereof useful for the treatment of prevention of diseases characterized by abnormal cell proliferation

The present invention provides substituted 11-phenyl-dibenzazepine compounds that are specific, potent and safe inhibitors of mammalian cell proliferation. The compounds can be used to inhibit mammalian cell proliferation in situ as a therapeutic approach towards the treatment or prevention of diseases characterized by abnormal cell proliferation, such as cancer.

Substitute 11-phenyl-dibenzazepine compounds useful for the treatment or prevention of diseases characterized by abnormal cell proliferation

The present invention provides a class of chemical compounds useful as efficacious drugs in the treatment of sickle cell disease and diseases characterized by unwanted or abnormal cell proliferation, and in particular inflammatory diseases associated with unwanted cellular proliferation. The active compounds are substituted triaryl methane compounds or analogues thereof where one or more of the aryl groups is replaced with a heteroaryl, cycloalkyl or heterocycloalkyl group and/or the tertiary carbon atom is replaced with a different atom such as Si, Ge, N or P, the compounds inhibit mammalian cell proliferation, inhibit the Gardos channel of erythrocytes, reduce sickle erythrocyte dehydration and/or delay the occurrence of erythrocyte sickling or deformation.

Disclosed is a three step synthesis of 11-aryl-5,6-dihydro-11H-dibenz&lsqb;b,e&rsqb;azepines from a 2-aminobenzophenone represented by the following structural formula:

Synthesis of 11-aryl-5,6-dihydro-11H-dibenz&lsqb;b,e&rsqb;azepines

Disclosed is a three step synthesis of 11-aryl-5,6-dihydro-11H-dibenz[b,e]azepines from a 2-aminobenzophenone represented by the following structural formula: ##STR1## and a starting material represented by the following structural formula: ##STR2## Phenyl Ring A, Phenyl Ring B and Phenyl Ring C are independently unsubstituted or substituted with one, two or three substituents. Each substituent on Phenyl Ring A, Phenyl Ring B and Phenyl Ring C is independently chosen. R is --H, a aliphatic group, a substituted aliphatic group, an aryl group, a substituted aryl group, --C(O)--R', --C(O)--H, --C(O)--NHR', --S(O).sub.2 R', --C(O)--C(O)--R', --C(O)--C(O)--H, --C(S)--R', --C(S)--H, --C(O)--OR', --C(S)--OR', --C(O)--SR', --C(S)--SR', --C(O)--NR'.sub.2 or --C(O)--C(S)--R'. R' is an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R.sub.1 is a leaving group. The present invention also includes novel compounds which are intermediates in the preparation of 11-aryl-5,6-dihydro-11H-dibenz[b,e]azepines.

Synthesis of 11-aryl-5,6-dihydro-11H-dibenz[b,e]azepines

The present invention provides a class of chemical compounds useful as efficacious drugs in the treatment of sickle cell disease and diseases characterized by unwanted or abnormal cell proliferation. The active compounds are substituted triaryl methane compounds or analogues thereof where one or more of the aryl groups is replaced with a heteroaryl, cycloalkyl or heterocycloalkyl group and/or the tertiary carbon atom is replaced with a different atom such as Si, Ge, N or P. The compounds inhibit mammalian cell proliferation, inhibit the Gardos channel of erythrocytes, reduce sickle erythrocyte dehydration and/or delay the occurrence of erythrocyte sickling or deformation.

Growing community of inventors

Littleton, MA, United States of America

Richard John Lombardy