The present invention provides a compound having the structure wherein A is a ring structure, with or without substitution; X1 is C or N; X2 is N, O, or S; Y1 is H, -(alkyi), -(alkenyl), -(alkynyl), -(cycloalkyi), (haloalkyi), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y 2 is H, -(alkyi), -(alkenyl), -(alkynyl), -(cycloalkyi), (haloalkyi), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y3 is H-(alkyi), -(alkenyl), -(alkynyl), -(cycloalkyi), (haloalkyi), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y 4 is H-(alkyi), -(alkenyl), -(alkynyl), -(cycloalkyi), (haloalkyi), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y5 is H, -(alkyi), -(alkenyl), -(alkynyl), -(cycloalkyi), (haloalkyi), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); a and P are each present or absent and when present each is a bond.

The present disclosure describes a method to treat conditions, including cancer, using compounds that can target resistant cancer cells. The compounds of the invention can decrease the rate of proliferation of drug-resistant cancer cells, such as glioma, lung cancer, and uterine sarcoma.

The present disclosure describes a method to treat conditions, including cancer, using compounds that can target resistant cancer cells. The compounds of the invention can decrease the rate of proliferation of drug-resistant cancer cells, such as glioma, lung cancer, and uterine sarcoma.

A series of fused pentacyclic imidazole derivatives, being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders. In particular, the present invention is concerned with 6,7-dihydro-7,14-methanobenzimidazo[1,2-b][2,5]benzodiazocin-5(14H)-one derivatives and analogs thereof.

A series of fused pentacyclic imidazole derivatives, being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders. In particular, the present invention is concerned with 6,7-dihydro-7,14-methanobenzimidazo[1,2-b][2,5]benzodiazocin-5(14H)-one derivatives and analogs thereof.

The present invention provides a compound having the structure wherein A is a ring structure, with or without substitution; X1 is C or N; X2 is N, O, or S; Y1 is H, -(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y 2 is H, -(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y3 is H-(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y 4 is H-(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y5 is H, -(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); a and P are each present or absent and when present each is a bond.

The present invention provides a compound having the structure wherein A is a ring structure, with or without substitution; X1 is C or N; X2 is N, O, or S; Y1 is H, -(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y 2 is H, -(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y3 is H-(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y 4 is H-(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); Y5 is H, -(alkyl), -(alkenyl), -(alkynyl), -(cycloalkyl), (haloalkyl), -(alkyl)-O-(alkyl) or -(alkyl)-(cycloalkyl); a and P are each present or absent and when present each is a bond.

Described herein is (4R,7,S)-2-(3-(4-chlorophenyl)ureido)-9-methyl-5,6,7,8-tetrahydro-4H-4,7-epiminocyclohepta[b]thiophene-3-carboxamide mesylate, including crystalline forms and solvates thereof.

Described herein is (4R,7,S)-2-(3-(4-chlorophenyl)ureido)-9-methyl-5,6,7,8-tetrahydro-4H-4,7-epiminocyclohepta[b]thiophene-3-carboxamide mesylate, including crystalline forms and solvates thereof.

The present invention provides a compound having the structure:

##STR00001## wherein D, E and F are each independently NR.sub.1, CR.sub.2R.sub.3 or CR.sub.6R.sub.7, wherein one of D, E and F is NR.sub.1 and the remaining two are CR.sub.2R.sub.3 or CR.sub.6R.sub.7, wherein R.sub.1 is H or -(alkyl), and wherein R.sub.2, R.sub.3, R.sub.6 and R.sub.7 are each independently H, -(alkyl), -(alkenyl), -(alkynyl), -cycloalkyl, -alkylcycloalkyl, -aryl, heteroaryl or -alkylaryl; X.sub.1 is C or N; X.sub.2 is O, S, N, NR.sub.14 or CR.sub.15, wherein R.sub.14 is H, -(alkyl) or -cycloalkyl, wherein R.sub.15 is H, -(alkyl) or -cycloalkyl, and wherein X.sub.2 is other than N when X.sub.1 is N; α and β represent a bond that is present or absent, and wherein either α or β is present, wherein when α is present, then X.sub.1 is C and X.sub.2 is O, S or NR.sub.14, or when β is present, then X.sub.1 is N and X.sub.2 is N or CR.sub.15; R.sub.4, R.sub.5, R.sub.8 and R.sub.9 are each independently H, -(alkyl), -(alkenyl), -(alkynyl), -cycloalkyl, -alkylcycloalkyl, -aryl, heteroaryl, -alkylaryl, —OH, —O(alkyl), —OAc, —S(alkyl), —NH.sub.2, —NH(alkyl), —N(alkyl).sub.2, —COOH, —CO.sub.2(alkyl), —CONH.sub.2, —CONH(alkyl), —CON(alkyl).sub.2 or —CN, wherein when D is NR.sub.1 then R.sub.4 and R.sub.5 are each independently H, -(alkyl), -(alkenyl), -(alkynyl), -cycloalkyl, -alkylcycloalkyl, -aryl, heteroaryl or -alkylaryl, wherein when F is NR.sub.1 then R.sub.8 and R.sub.9 are each independently H, -(alkyl), -(alkenyl), -(alkynyl), -cycloalkyl, -alkylcycloalkyl, -aryl, heteroaryl or -alkylaryl or R.sub.1 and R.sub.4 together form a —(CH.sub.2).sub.m—, wherein m represents an integer from 2 to 4; and R.sub.10, R.sub.11, R.sub.12 and R.sub.13 are each independently H, halogen, -(alkyl), -(alkenyl), -(alkynyl), -cycloalkyl, -(aryl), -(heteroaryl), —OH, —OAc, —O(alkyl), —O-(alkenyl), —O-(alkynyl), —O-(aryl), —O-(heteroaryl), —SH, —S(alkyl), —S-(alkenyl), —S-(alkynyl), —S-(aryl), —S-(heteroaryl), —NH.sub.2, —NH-(alkyl), —NH-(alkenyl), —NH-(alkynyl), —NH-(aryl), —NH-(heteroaryl), —CO.sub.2(alkyl), —CONH.sub.2, —CN, —CF.sub.3, —CF.sub.2H, —OCF.sub.3 or NO.sub.2 or R.sub.10 and R.sub.11 together form a —O(CH.sub.2)O— or R.sub.11 and R.sub.12 together form a —O(CH.sub.2)O— or R.sub.12 and R.sub.13 together form a —O(CH.sub.2)O—; wherein when X.sub.1 is C, X.sub.2 is NR.sub.14, and D is CR.sub.2R.sub.3, E is NR.sub.1, F is CR.sub.6R.sub.7, then (i) R.sub.14 and at least two of R.sub.10, R.sub.11, R.sub.12 and R.sub.13 are other than hydrogen, or (ii) one of R.sub.2, R.sub.3, R.sub.6 and R.sub.7 i