The disclosure relates to USP30 Inhibitor Compounds, pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising same, and medical uses involving same.

Compounds, methods of use, and processes for making inhibitors of complement factor D or a pharmaceutically acceptable salt or composition thereof are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade. The inhibitors of factor D described herein reduce excessive activation of complement.

Compounds, methods of use, and processes for making inhibitors of complement factor D or a pharmaceutically acceptable salt or composition thereof are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade. The inhibitors of factor D described herein reduce excessive activation of complement.

A pharmaceutical intermediate including a first indole moiety which is associated with an optionally carboxylated hexahydroazepino moiety, an optionally carboxylated azonane moiety, or a second, optionally carboxylated indole moiety, having an alkyl, allyl, phenylallyl, cinnamyl, alkenyl, and/or alkyl-alkenyl substituent pendant from a nitrogen atom of the same.

A pharmaceutical intermediate including a first indole moiety which is associated with an optionally carboxylated hexahydroazepino moiety, an optionally carboxylated azonane moiety, or a second, optionally carboxylated indole moiety, having an alkyl, allyl, phenylallyl, cinnamyl, alkenyl, and/or alkyl-alkenyl substituent pendant from a nitrogen atom of the same.

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

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

The invention relates to chemical compounds and complexes that can be used in therapeutic and diagnostic applications.

The invention relates to chemical compounds and complexes that can be used in therapeutic and diagnostic applications.

The present invention relates to compounds of formula (I) and to pharmaceutical compositions containing them: ##STR00001##
wherein meanings of the substituents are indicated in the description. Such compounds for use in the treatment of cancer and other diseases related to altered angiogenesis, such as arthritic pathology, diabetic retinopathy, psoriasis and chronic inflammatory disease, are also within the scope of the present invention.