Immunosuppressant compounds and compositions

The compound of claim 2 in which n is 0 or 1 and Z is chosen from:

• wherein the left and right asterisks of Z indicate the point of attachment between the —[C(R2)(R3)]n— group and A of Formula I, respectively;
• R7 is chosen from hydrogen and C1-6alkyl;
• and J1, J2 and J3 are independently methylene or a heteroatom selected from the group consisting of S, O and NR4;
• wherein R4 is hydrogen or C1-6alkyl;
• with the proviso that the number of heteroatoms are 2 or less.

A process for preparing a compound of Formula I:

• in which:
• n is 0, 1 or 2;
• R1 is chosen from C6-10aryl and C5-10heteroaryl;
• wherein any aryl or heteroaryl of R1 is optionally substituted by a radical chosen from C6-10arylC0-4alkyl, C5-6heteroarylC0-4alkyl, C3-8cycloalkylC0-4alkyl, C3-8heterocycloalkylC0-4alkyl or C1-10alkyl;
• wherein any aryl, heteroaryl, cycloalkyl or heterocycloalkyl group of R1 can be optionally substituted by one to five radicals selected from the group consisting of halo, C1-10alkyl, C1-10alkoxy, halo-substituted-C1-10alkyl and halo-substituted-C1-10alkoxy;
• and any alkyl group of R1 can optionally have a methylene replaced by a member of the group consisting of —S—, —S(O)—, —S(O)2—, —NR4— and —O—;
• wherein R4 is chosen from hydrogen or C1-6alkyl;
• R2 and R3 are independently chosen from hydrogen, C1-6alkyl, halo, hydroxy, C1-6alkoxy, halo-substituted C1-6alkyl and halo-substituted C1-6alkoxy;
• A is chosen from —X1C(O)OR4, —X1OP(O)(OR4)2, —X1P(O)(OR4)2, —X1P(O)OR4, —X1S(O)2OR4, —X1P(O)(R4)OR4 and 1H-tetrazol-5-yl;
• wherein X1 is a bond or
• C1-6alkylene and R4 is chosen from hydrogen and C1-6alkyl;
• W is chosen from a bond, C1-6alkylene and C2-6alkenylene;
• X is chosen from C2-4alkylene and C2-4alkenylene;
• wherein one methylene group of X can be replaced with an atom or group chosen from —O—, —S—, —S(O)—, —S(O)2— and —NR5—;
• wherein R5 is hydrogen, C1-6alkyl and —C(O)R6;
• wherein R6 is chosen from hydrogen and C1-6alkyl;
• wherein any alkylene or alkenylene of X can further be substituted by 1 to 3 radicals selected from the group consisting of halo, hydroxy, C1-6alkyl, C1-6alkoxy, halo-substituted C1-10alkyl and halo-substituted C1-10alkoxy;
• Y is chosen from C6-10aryl and C5-10heteroaryl, wherein any aryl or heteroaryl of Y can be optionally substituted with 1 to 3 radicals chosen from halo, hydoxy, nitro, C1-10alkyl, C1-10alkoxy, halo-substituted C1-10alkyl and halo-substituted C1-10alkoxy;
• Z is C1-6alkylene;
• wherein up to two methylene groups of Z can be replaced with divalent radicals chosen from —NR7—. C3-8cycloalkylene, C3-8heterocycloalkylene and phenylene;
• wherein R7 is chosen from hydrogen, C1-6alkyl and (CH2)1-2COOH;
• wherein Z may further be substituted by 1 to 3 radicals chosen from halo, hydroxy, C1-6alkyl, C1-6alkoxy, halo-substituted-C1-6alkyl and halo-substituted-C1-6alkoxy;
• or when a —NR7— replaces at least one methylene group of Z, R7 and Y together with the nitrogen atom to which R7 is attached, forms C8-14heteroarylene;
• which process comprises:
• (a) reacting a compound of formula 2:
• with a compound of formula 3:
• in which A, W, X, Y, Z, R1, R2, R3 and n are as defined for Formula I above;
• and
• (b) optionally converting a compound of the invention into a pharmaceutically acceptable salt;
• (c) optionally converting a salt form of a compound of the invention to a non-salt form;
• (d) optionally converting an unoxidized form of a compound of the invention into a pharmaceutically acceptable N-oxide;
• (e) optionally converting an N-oxide form of a compound of the invention to its unoxidized form;
• (f) optionally resolving an individual isomer of a compound of the invention from a mixture of isomers;
• (g) optionally converting a non-derivatized compound of the invention into a pharmaceutically acceptable prodrug derivative;
• and
• (h) optionally converting a prodrug derivative of a compound of the invention to its non-derivatized form.