AU2315401A - Oxamides as IMPDH inhibitors - Google Patents

Description

S&FRef: 540258

AUSTRALIA

PATENTS ACT 1990 COMPLETE SPECIFICATION FOR A STANDARD PATENT

ORIGINAL

Name and Address of Applicant: Actual Inventor(s): Address for Service: Invention Title: F. Hoffmann-La Roche AG 124 Grenzacherstrasse CH-4070Basel Switzerland Michael John Broadhurst, Christopher Huw Hill, David Nigel Hurst, Philip Stephen Jones, Paul Brittain Kay, Ian Reginald Kilford, Robert Murray McKinnell Spruson Ferguson St Martins Tower,Level 31 Market Street Sydney NSW 2000 Oxamides as IMPDH Inhibitors The following statement is a full description of this invention, including the best method of performing it known to me/us:- 5845c Oxamides as IMPDH Inhibitors Case 20611 The present invention relates to novel oxamide derivatives, a process for their manufacture, pharmaceutical preparations containing these derivatives, and the use of these derivatives as medicaments. In particular, the present invention relates to novel oxamide derivatives which are inhibitors of inosine monophosphate dehydrogenase

(IMPDH).

Inosine monophosphate dehydrogenase (IMPDH) is an enzyme involved in the de novo synthesis of guanine nucleotides. The enzyme catalyses the NAD-dependent oxidation of (IMP) to xanthosine-5'-monophosphate which is the rate limiting step in the synthesis of guanine nucleotides. As a result of the key role of the enzyme in guanine nucleotide biosynthesis, the enzyme represents an important target for the development of inhibitors which would have utility as therapeutic agents in the treatment of IMPDH related processes.

o The de novo synthesis of guanine nucleotides is particularly important in B- and T- Slymphocytes to provide sufficient levels of nucleotides to support a proliferative response to mitogen or antigen [Wu, Persp. in Drug Discovery and Design., 2, 185-204, (1994)]. IMPDH inhibition is thus an attractive target for selectively inhibiting the immune system. Inhibitors of IMPDH are known [Pankiewicz, Exp. Opin. Ther.

20 Patents., 9, 55-65, (1999)], and the uncompetitive inhibitor mycophenolic acid (MPA) has been demonstrated to inhibit the response of B-and T-cells to mitogen or antigen [Allison, A.C. and Eugui, Transplant. Proc., 25, 8-18, (1993)]. MPA has therefore been utilised as an immunosuppressant.

It is also recognised that IMPDH plays a role in other rapidly proliferating cells such as tumour cell lines, indicating that IMPDH inhibition is a target for anti-cancer chemotherapy Nagai, M. et al., 51, 3886-3890, (1990)].

RAU/21.12.2000 -2- IMPDH inhibition has also been shown to play a role in viral replication in some cell lines which support virus replication [Pankiewicz, Exp. Opin. Ther. Patents., 9, 55-65, (1999)]. Ribavirin, for example, is a broad spectrum antiviral agent which has been approved by the U.S. Food and Drug Administration for use as an aerosol for infants with serious respiratory infections due to respiratory syncytial virus and is also in use as an agent for the treatment of patients infected with Hepatitis C virus when used in combination with interferon Patterson, J.L. and Fernandez-Larsson, Rev. Infect. Dis., 12, 1139- 1146, (1990); McHutchison, J.G. et al., New. Engl. J.Med., 339, 1549-1550, (1998)].

Ribavirin is converted in cells to ribavirin 5' monophosphate which is an inhibitor of

IMPDH.

Additionally, the IMPDH inhibitors ribavirin and MPA have been shown to inhibit the replication of yellow fever virus (a RNA virus) whilst MPA has been demonstrated to inhibit Hepatitis B virus replication (a DNA virus) in vitro supporting the broad range antiviral activity of these inhibitors Neyts, J. et al., Antiviral Res., 30, 125-132, (1996); Gong, Z.J. et al., J. Viral Hepatitis., 6, 229-236, (1999)]. Furthermore, MPA has also been shown to potentiate the antiviral effects of nucleoside analogues both in vitro and in animal models [Neyts, J. and De Clercq, Inter. Antiviral News., 7, 134-136, (1999)].

Together these observations indicate that IMPDH inhibitors have utility as broad spectrum 20 antiviral agents.

.t 'i IMPDH inhibitors would therefore have therapeutic potential as immunosuppressants, anti-cancer agents and anti-viral agents. Specifically, such compounds may be used in the treatment of transplant rejection, the treatment of cancer and as antiviral agents in the treatment of viral diseases such as retroviral infections and hepatitis C virus infections (either alone or in combination with other antiviral agents such as interferon or derivatives ~thereof, such as conjugates with polyethylene glycol).

The novel oxamide derivatives provided by the present invention are compounds of the general formula -3- R6

NNR

4

R

8

I

R

5 R

O

wherein R' represents heterocyclyl;

R

2 represents hydrogen, unsubstituted lower alkyl, lower alkoxy, halo, hydroxy or cyano; 10 R 3 represents hydrogen, unsubstituted lower alkyl, lower alkoxy, halo, or cyano;

R

4 represents hydrogen, lower alkyl, lower cycloalkyl, aryl, or heterocyclyl;

R

5 represents hydrogen, unsubstituted lower alkyl, lower alkoxy, halo, or cyano;

R

6 represents hydrogen, unsubstituted lower alkyl, lower alkoxy, halo, or cyano;

R

7 represents hydrogen, or unsubstituted lower alkyl; 15 R 8 represents hydrogen, or unsubstituted lower alkyl; or R 4 and R 8 together with the nitrogen atom to which they are attached represent heterocyclyl; and pharmaceutically acceptable salts thereof.

The oxamide derivatives provided by the present invention are inhibitors of the O enzyme inosine monophosphate dehydrogenase (IMPDH). They can be used as medicaments, especially for treating immune mediated conditions or diseases, viral diseases, bacterial diseases, parasitic diseases, inflammation, inflammatory diseases, hyperproliferative vascular diseases, tumours, and cancer. They can be used alone or in combination with other therapeutically active agents, for example, an immunosuppressant, a chemotherapeutic agent, an anti-viral agent, an antibiotic, an antiparasitic agent, an anti-inflammatory agent, an anti-fungal agent and/or an anti-vascular hyperproliferation agent.

(1 In particular, compounds of the present invention and compositions containing the same are useful as chemotherapeutic agents, inhibitors of viral replication and modulators of the immune system, and can be used for the treatment of viral diseases such as retroviral infections and hepatitis C virus infections (either alone or in combination with other antiviral agents such as interferon or derivatives thereof, such as conjugates with is polyethylene glycol), inflammatory diseases such as osteoarthritis, acute pancreatitis, chronic pancreatitis. asthma, and adult respiratory distress syndrome, hyperproliferative vascular diseases such as restenosis, stenosis and artherosclerosis, cancer, for example lymphoma and leukaemia, and as immunosupressants in the treatment of autoimmune diseases, graft versus host diseases and transplant rejection.

2. 20 Compounds of the present invention which have antiviral effects and/or immunosupressive properties are particularly useful for treating HCV infection.

A second aspect of the present invention provides a process for the manufacture of compounds of the formula I as defined above, and their pharmaceutically acceptable salts which process comprises the general reaction scheme A as set out below.

A third aspect of the present invention provides a process for the manufacture of .9 compounds of the formula IX as defined below and their pharmaceutically acceptable salts which process comprises the general reaction Scheme B as set out below.

A fourth aspect of the present invention provides a process for the manufacture of 9 compounds of the formula I as defined above and their pharmaceutically acceptable salts, which process comprises the general reaction scheme: I \I)AYLIB\LIBA]036)9 doc:nss i, Coupling, and ii, Optional R2 O Modification R2 R /R 3

NR

4

R

8 R R 3 S+ HO 0

R

6 5 NR 0 R 6

NNR

4

R

8 R R 7 O (11)

(I)

wherein R' to R 8 are defined as in claim 1, and optionally, converting the compound of formula into a pharmaceutically acceptable salt.

A fifth aspect of the present invention provides compounds produced by any one of the process of the second to fourth aspects of the present invention.

A sixth aspect of the present invention provides a pharmaceutical composition comprising a compound of formula I as defined above or its pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier, diluent or adjuvant, and, optionally, one or more additional therapeutically active substance(s).

A seventh aspect of the present invention provides a process for the production of a medicament, which process comprises bringing a compound of formula I as defined above, or a pharmaceutically acceptable salt thereof into a galenical administration form S. together with a pharmaceutically acceptable carrier, diluent or adjuvant and, optionally, S 15 one or more additional therapeutically active substance(s).

An eighth aspect of the present invention provides a method of treating an immune mediated condition or disease, a viral disease, a bacterial disease, a parasitic disease, inflammation an inflammatory disease, a hyperproliferative vascular disease, a tumour, or cancer in a subject, comprising the step of administering to the subject a therapeutically effective amount of a compound of formula I as defined above or its pharmaceutically acceptable salt or a pharmaceutical composition of the sixth aspect of the invention.

A ninth aspect of the present invention provides a method of treating an immune mediated condition or disease, a viral disease, a bacterial disease, a parasitic disease, inflammation, an inflammatory disease, a hyperproliferative vascular disease, a tumour, or cancer in a subject, comprising the steps of(a) administering to the subject a therapeutically effective amount of a compound of formula I as defined above or its pharmaceutically acceptable salt or a pharmaceutical composition of the sixth aspect of the invention and concurrently or sequentially administering to the subject one or more additional therapeutically active substance(s).

II:\DIAYLIB\LIBA]03699.doc:nss A tenth aspect of the present invention provides a method of treating or preventing I MPDH mediated diseases, comprising the step of administering to a subject an effective amount of a compound of formula I as defined above or a pharmaceutical composition of the sixth aspect of the present invention.

An eleventh aspect of the present invention provides the use of an effective amount of a compound of formula I as defined above or its pharmaceutically acceptable salt for the manufacture of a medicament for the treatment or prevention of IMPDH mediated diseases.

A twelfth aspect of the present invention provides the use of an effective amount of a compound of formula I as defined above or its pharmaceutically acceptable salt, in combination with, an effective amount of one or more additional therapeutically active substance(s), for the manufacture of a medicament for the treatment of an immune mediated condition or disease, a viral disease, a bacterial disease, a parasitic disease, inflammation, an inflammatory disease, a hyperproliferative vascular disease, a tumour, or cancer.

A thirteenth aspect of the present invention provides the use of an effective amount ofla compound of formula I as defined above or its pharmaceutically acceptable salt, for the manufacture of a medicament for the treatment of an immune mediated condition or disease, a viral disease, a bacterial disease, a parasitic disease, inflammation, an inflammatory disease, a hyperproliferative vascular disease, a tumour, or cancer.

:A fourteenth aspect of the invention provides an effective amount of a compound of formula I as defined above or its pharmaceutically acceptable salt or an effective amount !of a pharmaceutical composition of the sixth aspect of the present invention when used for the treatment of an immune mediated condition or disease, a viral disease, a bacterial disease, a parasitic disease, inflammation an inflammatory disease, a hyperproliferative P vascular disease, a tumour, or cancer in a subject.

A fifteenth aspect of the invention provides an effective amount of a compound of formula I as defined above or its pharmaceutically acceptable salt or an effective amount of a pharmaceutical composition of the sixth aspect of the present invention when used for the treatment or prevention of IMPDH mediated diseases As used herein, the term "lower alkyl", means a straight-chain or branched-chain alkyl group containing up to 10 carbon atoms, preferably from 1 to 8 carbon atoms, more preferably from 1 to 6 carbon atoms, e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.butyl, tert-butyl, n-pentyl, n-hexyl and 1,1-dimethylethyl; and which is optionally I I.\I)AYLIB\LIBA]O3699.doc:nss 4c substituted by e.g. one or more of cyano, halo, carboxyl, hydroxyl, lower alkoxy, lower S celo alkoxy, aryloxy, heterocyclyloxy, heterocyclyl (lower alkoxy)-aryl-amino-oxalyloxy. lower alkoxy-carbonyl, C C

C

C.

CC

C.

C

a C. C C C

CC

CC

[I\[)AYLIB\IIBA]03'699.doc nss aryl, aryl-carbonyl-amino-aryl, lower alkyl-carbonyl-amino-aryl, heterocyclyl, lower alkyl-heterocyclyl, lower cycloalkyl, lower alkenyl, lower alkynyl, amino, mono- or di-(lower alkyl) amino, lower cycloalkyl amino, aryl amino, heterocyclylamino, lower alkyl-aryl-lower alkyl-amino, lower alkoxy-carbonyl-amino, lower alkenylcarbonyl-amino, lower alkyl-carbonyl-amino, di-(aryl)-lower alkyl-carbonyl-amino, lower alkyl-sulphonyl-lower alkyl-carbonyl-amino, lower cycloalkyl-lower alkyl-carbonyl-amino, heterocyclyl-lower alkyl-carbonyl-amino, lower alkoxy-lower alkyl-carbonyl-amino, diaryl-lower alkyl-carbonyl-amino, aryl-carbonyl-amino, lower alkyl-aryl-carbonyl-amino, tri-(lower alkyl)-aryl-carbonyl-amino, mono- or di-(lower alkoxy)- aryl-carbonyl-amino, di-(lower alkyl)-amino-aryl-carbonyl-amino, lower alkyl-carbonyl-amino-aryl-carbonylamino, heterocyclyl-aryl-carbonyl-amino, lower cycloalkyl-carbonyl-amino, mono- or tetra-(lower alkyl)-lower cycloalkyl-carbonyl-amino, heterocyclyl-carbonyl-amino, monoor di-(lower alkyl)-heterocyclyl-carbonyl-amino, tri-(lower alkyl)-aryl-oxalyl-amino, lower alkyl-carbamoyl, or aryl-carbamoyl, thio, lower alkyl thio, lower cycloalkyl thio, aryl thio, heterocyclyl thio, lower alkyl sulphonyl, lower cycloalkyl sulphonyl, aryl sulphonyl, heterocyclyl sulphonyl.

Where there is more than one substituent, each substituent may be the same or different, for example tri-fluoromethyl, triphenylmethyl, 1-[1-methyl- [methylformyl] -2-phenyl] ethyl, or 2-[1-hydroxyl-3-cyclohexyl].

The term "unsubstituted lower alkyl" means an alkyl group as defined above where no substituents are present.

*25 The term "lower alkenyl" means an alkenyl group containing from 2 to 7 carbon atoms, e.g.

allyl, vinyl and butenyl.

The term "lower alkynyl" means an alkynyl group containing from 2 to 7 carbon atoms, e.g.

propargyl or butynyl.

-6- The term "lower cycloalkyl", alone or in combination as in "lower cycloalkyl-lower alkyl", means a cycloalkyl group containing 3 to 10 carbon atoms, preferably 3 to 7 carbon atoms, e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and adamantyl, and which may be optionally substituted by e.g. one or more of lower alkyl, carboxyl, hydroxyl or aryl or optionally be benz-fused e.g. to aryl. Where there is more than one substituent, each substituent may be the same or different. Cyclopropylmethyl, 2-cyclobutyl-ethyl and 3cyclohexyl-propyl are examples of lower cycloalkyl-lower alkyl groups.

The term "halo" denotes fluorine, chlorine, bromine or iodine.

The term "lower alkoxy" denotes an optionally substituted lower alkyl group as defined hereinbefore, which is bonded via an oxygen atom, e.g. methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert.-butoxy and the like. Suitable substituents are those applicable for "lower alkyl".

The term "aryl", alone or in combination as in "aryl-lower alkyl", means phenyl or naphthyl, optionally benz-fused, for example benz-fused to a lower cycloalkyl ring, and/or optionally substituted by e.g. one or more of halo, 20 cyano, carboxyl, lower alkyl-thio, nitro, oxo, hydroxyl, lower alkoxy, lower cycloalkyloxy, aryloxy, heterocyclyl oxy lower alkyl-heterocyclyl, heterocyclyl, S"lower alkoxy-carbonyl, lower alkyl-carbonyl, heterocyclyl-carbonyl, lower alkylheterocyclyl-carbonyl, sulphamoyl, lower alkyl- sulphamoyl, thio, lower alkyl thio, lower cycloalkyl thio, aryl thio, heterocyclyl thio, -7lower alkyl-sulphonyl, lower cycloalkyl sulphonyl, aryl sulphonyl, heterocyclyl-sulphonyl, amino, mono- or di-(lower alkyl) amino, lower alkyl-sulphonyl-amino, di-(lower alkyl)heterocyclyl-amino, lower alkyl-carbonyl-amino, (lower alkyl-carbonyl)(lower alkyl)amino, lower alkoxy-carbonyl-amino, aryl-carbonyl-amino, mono- or di-(lower alkyl)-carbamoyl, aryl-carbamoyl, lower alkyl, aryl-lower alkyl, amino-lower alkyl, heterocyclyl-lower alkyl, lower alkoxycarbonyl-lower alkyl, lower alkyl- sulphamoyl-lower alkyl, aryl-sulphonyl-amino-lower alkyl, lower alkyl-sulphonyl-amino-lower alkyl, lower alkoxy-carbonyl-amino-lower alkyl, heterocyclyl-oxy-carbonyl-amino-lower alkyl, aryloxy-carbonyl-amino-lower alkyl, lower alkyl-carbonyl-amino-lower alkyl, lower alkoxy-carbonyl-(lower alkyl)-amino-lower alkyl, lower alkyl-carbamoyl-lower alkyl, lower alkyl-aryl-carbonyl-amino-lower alkyl, arylcarbamoyl-lower alkyl, lower cycloalkyl-carbonyl-amino-lower alkyl, heterocyclylcarbonyl-amino-lower alkyl, or aryl-carbonyl-amino-lower alkyl. Where there is more than one substituent, each substituent may be the same or different, for example 1-(3methoxy-4-oxazolyl)phenyl, 1-(3-chloro-4-methoxy)phenyl, 1-(3-chloro-4-methyl) phenyl and 1-(3-fluoro-4-methyl)phenyl.

The same substituents as listed above apply for all terms containing the phrase "optionally Ssubstituted phenyl S The term "aryloxy" denotes an aryl group as defined hereinbefore, which is bonded via an oxygen atom, e.g. phenoxy, and the like.

As used herein, the term "heterocyclyl", alone or in combination as in "heterocyclyl-lower alkyl", means a saturated, unsaturated or partially saturated monocyclic or bicyclic ring system which contains one or more hetero atoms selected from nitrogen, sulphur and oxygen; and which is attached to the rest of the molecule via a carbon atom (C-linked), or a nitrogen atom (N-linked) in the ring system, and which is optionally substituted in the same manner as the aryl group defined hereinbefore and/or by oxido. Where there is more than one substituent, each substituent may be the same or different.

-8- Examples of heterocyclyl groups are oxazolyl, isoxazolyl, furyl, tetrahydrofuryl, 1,3- O dioxolanyl, dihydropyranyl, thienyl, pyrazinyl, isothiazolyl, isoquinolinyl, indolyl, indazolyl, quinolinyl, dihydrooxazolyl, pyrimidinyl, benzofuranyl, tetrazolyl, pyrrolidinonyl, (N-oxide)-pyridinyl, pyrrolyl, triazolyl e.g. 1,2,4-triazolyl, pyrazolyl, benzotriazolyl, piperidinyl, morpholinyl, thiazolyl, pyridinyl, dihydrothiazolyl, imidazolidinyl, pyrazolinyl, benzothienyl, piperazinyl, imidazolyl, thiadiazolyl e.g. 1,2,3thiadiazolyl, and benzothiazolyl.

Any functional reactive) group present in a side-chain may be protected, with the protecting group being a group which is known per se, for example, as described in "Protective Groups in Organic Synthesis", 2nd Ed., T.W. Greene and P.G.M. Wuts, John Wiley Sons, New York, NY, 1991. For example, an amino group can be protected by a tert.-butoxycarbonyl, formyl, trityl, benzyloxycarbonyl, 9-fluorenylmethyloxycarbonyl (Fmoc), trifluoroacetyl, 2-(biphenylyl)isopropoxy-carbonyl or isobornyloxycarbonyl group or in the form of a phthalimido group; or a hydroxyl group can be protected by a tert.-butyldimethylsilyl, tetrahydropyranyl, 4-methoxybenzyl, or benzyl; or a carboxyl group can be protected in the form of an ester, for example as a methyl or tert.butyl ester.

The protecting group may be retained in the final compound or optionally removed by techniques known in the art.

The compounds of this invention may contain one or more asymmetric carbon atoms and may therefore occur as racemates and racemic mixtures, single enantiomers, diastereomeric mixtures and individual diastereomers. Furthermore, where a compound of the invention contains an olefinic double bond, this can have the or (Z) 25 configuration. Also, each chiral centre may be of the R or S configuration. All such isomeric forms of these compounds are embraced by the present invention.

Examples of compounds of formula are shown below in Table la and b: Examples of compounds of formula are shown below in Table la and Ib: h i -2 0 L 0210 J1 00 6T q 0 00 00 00 0 z 0 0 -0 N3r 0 0o 00 0 3f 0 0= o 0 z 0= Z--o God. 9 0 0* 0 I1I- I. 12 0

S

S

S.

S. S S5 S CS 13 1ONjf 0 0

NN

0~N N Nj~N 0-

NN

N.N

I"A

N u 0 00 e 0 0 000 0 0006 000 0000 0.00 4* 006 0 000 00 0 6 0 0 6 00 00 0 06 0* 0 00 0 0 0 0 0000 0* 006 0* 0 0 0 6 0 0 000 0 6 0*6 0 000 060 00 006 00 15

S

@OSO

0O 0 S

S

500050 0 S. @5 0

S

55 S S S 55 0

OOSO

0 0000 0~ 0 S S 5.5.

S

5055 055e 5.55 0e S 05 S @0 16- 17 18 4N 0 0 I 1 S S S S 55 S S S S S S S 555 S S S S S S S S S S S S 555 5 5 S 555 5.5 55 555 55 20 table lb Name Structure MS(ES) Ex No

(M+H)

t Benzyl 4-{2-[[[3-methoxy-4-(5oxazolyl)phenylamino] oxalyl.] a5342 mino]I -2-methyipropyll -1I-5342 piperidinecarboxylate N-[3-Methoxy-4-(5-oxazolyl) phenyl] [1,l1-dimethyl-2-0 (phenylthio) ethyl] oxalamide 42 422C N- 2- (I -Acetyl-4-piperidinyl)

O

1,1-dimethylethyl] [3methoxy-4-( 5-oxazolyl)phenyl] O~ ~443 423 oxalamide 21 N-(2-Cyclohexyl-1,1-CF dimethylethyl)-N'- [3-methoxy- K-NSf N 0 CH'c 400 424 N- [3-Methoxy-4- (5-oxazolyl) 0- 'H phenyl] [1,1-dimethyl-2-(N- N0 methylanilino) ethyl] oxalamide o HC c 2342 1,2,3,4-Tetrahydro-1-I quinolyl)-1,1-dimethylethyl] 0 NrIt NYN4942 [3-methoxy-4-(5-oxazolyl) N 4402 phenyl] oxalamide o N- (4-Hydroxyphenylthio N1 1, 1-dim ethylethyl] [3-0 _&4247 methoxy-4-( oxalamide N-[3-(4-Hydroxyphenyl)-1,1- 010 OH dimethyipropyl] 42 59 methoxy-4-(5-oxazolyl)phenyl] HCo4259 oxalamide N- [3-Methoxy-4- (5-oxazolyl) 0 NNJ~~y phenyl] 1-dimethyl-2- (Cl A 0A9 oxido-4-pyridyl)carboxamido] N4559 ethyl] oxalamide

CH

N- [2-(4-Acetylbenzamido)-1,1- c dimethylethyl] [3-methoxy- 0I 4- (5-oxazolyl)phenyl] oxalamide 479.1 600 07H, N-j13-Methoxy-4-(5-oxazolyl) 0 N',-C phenyl]-N'-[3-[(4- 8 0 methylbenzamido)methyl] pheny48.60 1] oxalamide 22 N-[3-[(2-Methoxybenzamido) 1. N0 methyl]phenyl]-N'-[3-methoxy- o 4- (5-oxazolyl)phenyl] oxalamide 501.1 602 N-[3-[(4-Chlorobenzmido)

I,

methyllphenyl]-N'-[3-rnethoxy- 00. 0 4- (5-oxazolyl)phenyl] oxalamide50.63 o0 N-[3-[[(1,3-Benzodioxol-5- o yl)carboxamido]methyllphenyll [3-methoxy-4-( 5-oxazolyl) 515.2 604 phenyl] oxalamide N- (2,3-Dihydro-1I-indolyl) N YQ H 1, 1-dimethylethyl] 43o0 methoxy-4- (5-oxazolyl)phenyl] N45 0 oxalamide N-[2-(3,4-Dihydro-6-methyl- C N 2H-quinol-1-yl)- 1,1- oa oILQQ..

dimethylethyl] [3-methoxy- V"i 463 606 4- (5-oxazolyl)phenyl] oxalamide N- 1-(3-Benzofuranyl)- 1- cr, methylethyl] [3-methoxy-4-4260 (5-oxazolyl)phenyl] oxalamide ~c 2 0 N- [3-Methoxy-4- phenyl] 1, 1 -dimethyl-3-(4- P Ci 50O60 phenoxypiperidino)propyl] oxala5068 mide N- 1-Butyryl-4-piperidinyl)- 1,1-dimethylethyll]-N'- [3-4760 methoxy-4-( 5-oxazolyl)phenyl] l 7 0 oxalamide N- [1-(Methanesulfonyl)-4- f00 piperidinyl] -1,1-dimethylethyl] -4761 [3-methoxy-4-(5-oxazolyl) CG 7 1 23 phenyl] oxalamide N- [1 -(Benzenesulfonyl)-4-£ piperidinyl] 1,1 -dimethylethyl] -5461 3-methoxy-4- (5-oxazolyl)5461 phenyl] oxalamide N- -Isobutyryl-4-

OC

piperidinyl)- 1,1 -dirnethylethyl] [3-methoxy-4-(5-oxazolyl) 0 t N471 612 phenyl] oxalamide tert-Butyl 4- [3-II[3-methoxy-4- I l oxalyl] %00 amino] -3-methylbutyl] 1- 515 613 piperidinecarboxylate CI- 0 a- N- [3-Methoxy-4-(5-oxazolyl) I <R phenyl]-N'-[1,1-dimethyl-3-(4- N piperidinyl)propyl I oxalamide 0415 614 Preferred compounds of formula are those where at least one of R 2, R 3, R 5and R 6 is not hydrogen.

Furthermore, preferred compounds of formula are those where R 1 represents an optionally substituted oxazole ring.

In particular, preferred compounds of formula are those according to the general formula: -24- R6 NRR

(IX)

RR

N

wherein

R

2 to R 8 are defined as above; and,

R

9 is hydrogen, lower alkyl, aryl-lower alkyl;

R

O is hydrogen.

More particularly, preferred compounds of formula are those according to the general formula wherein

R

2 is methoxy or chloro; 10 R 3 is hydrogen;

R

4 is heterocyclyl, aryl, or optionally substituted branched chain lower alkyl;

R

5 is hydrogen;

R

6 is hydrogen;

R

7 is hydrogen;

R

8 is hydrogen;

R

9 is hydrogen;

R

1 0 is hydrogen.

In particular, preferred compounds of formula are also those according to the general formulas: XI a XI b wherein R 2

R

3

R

5

R

6

R

7

R

9 and R'O are defined as above 5 R" and R 13 is H or lower alkyl, m=l to 5 and

R

12 is heterocyclyl or aryl, with the proviso that R 12 does not stand for 4-fluorophenyl.

Particularly preferred compounds of formula (XIa or XIb) are those wherein

R

2 is methoxy, R 3

R

5

R

6

R

9

RI',R

11 and R 13 are hydrogen and wherein R 12 is optionally substituted phenyl and optionally substituted heteroaryl, with the proviso that R 12 does not stand for 4-fluorophenyl.

Examples of such compounds are listed in table 1c -26 table Ic

S

S

S S Name Structure MS(ES) Ex No N-[3-Methoxy-4-(5oxazolyl)phenyl]-N'- [1,1-dimethyl- MtN'( j 0O,408 302 methylphenyl) ethyl]I oxalamide

CHCM

methylphenyl) ethyl]I-N'- -1 0 H, 408 303 oxazolyl)phenyl] oxalamide N-[3-Methoxy-4-(5- II- r oxazolyl)phenyl] 1-dimethyl-N 2- (3 -pyridyl)ethyll oxalamide 0 ~cC N 395 304 N-[3-Methoxy-4-(5- N 0 0'* oxazolyl) phenyl]-N'- 1- dimethyl 111N( CM 0 CM, ac 408 305 methyiphenyl) ethyl] oxalamide N- [3-Methoxy-4-(5-

OC

oxazolyl)phenyll-N'- [1,1-dimethyl- s 2- (2-thienyl) ethyl] oxalamide 400 306 00".

N- [2-(4-Benzyloxy-phenyl)- 1,1 dimethyl- ethyl] methoxy-4- 5037 oxazol- 5-yl-phenyl) -oxalamide5037 N- [2-(4-Hydroxy-phenyl)-1,1- N r dimethyl- ethyl]I-N'- (3 -methoxy-4- -410 308

-CN

N-(3-Methoxy-4-oxazol-5-yl-

N

p he nyl) 2 -m eth oxyp h enyl) 1- dim ethyl -ethyl] 424 309 oxalamide 27 9*9* 9.

9 9 .9 99 9 9 9 9. 9 9.

9.

9 9999 9 9999 9* 9 .9 9.

9 9999 999 9 999* 9 99 99 N- (2-Hydroxy-phenyl)- 1,1- FvO -6 dimethyl- ethyl] (3 -methoxy-4- 410 310 -oxalamide v0 o-o1 N- (1,1 -Dimethyl-2-phenyl- I

H

propyl)-N-(3-methoxy-4-oxazol- 408 311 -oxalamide N- [2-(3-Hydroxy-phenyl)- 1,1dimethyl-ethyl] -N'-(3-methoxy-4- 41 312I oxazol- 5-yl-phenyl)-oxalamide4132 N-(3-Methoxy-4-oxazol-5-yl-N phenyl)-N'- [2-(3-methoxy-4231 phenyl)- 1,1 -dimethyl-ethyl] -4231 oxalamide N- [4-(Cyanomethoxy)phenyl] //0 1, 1-dimethylethyl] [3-methoxy-- 4- (5-oxazolyl)phenyljoxalamide4931 2- [[[3-Methoxy-4-(5-N

N

oxazolyl)anilino] oxalyl] amino] -2-N)YX S 468 315 methyipropyl] phenoxy] acetic acid 2- [2-[[[3-Methoxy-4-(5-N oxazolyl) anilino] oxalyl] amino] -2methyipropyl] phenoxy] acetic acid4643 2- [2-[[[3-Methoxcy-4-(5oxazolyl)anilino] oxalyl] amino] -2methylpropyl] phenoxy] acetic acid 468 439 N- [3-Methoxy-4-(5- I I% oxazolyl)phenyl]-N'-[ 1,1-dimethyl- 0 -oxido-4- o 411 440 pyridyl) ethyl] oxalamide N-[3-Methoxy-4-(5- N~ /0 oxazolyl)phenyl] -dimethyl- 411-4 2-(1-oxido-3-4141 28 6 0 0* 0 0* 0 0 ~0 0 *0 0* *0 pyridyl) ethyl] oxalamide N-[3-Methoxy-4-(5- N//-0rCH S 0 oxazolyl)phenyl] 1,1 -dimethyl- N N -oxido-2- 0c a CC 411 442 pyridyl) ethyl] oxalamide 2- [3-Methoxy-4-(5- oxazolyl)anilino] oxalyl)] amino] -2methylpropyl ]phenoxy] acetic acid 468 443 IN-12-(2-Benzofuranyl)-II-

N

dimethylethyl] [3-methoxy-4- ,JiN 0 6-6C OH, oxalamide C -3 4 N- [3-Methoxy-4-(5- N- ,C oxazolyl)phenyl]-N'-[1,1-dimethyl- 0 9 2-(3-methyl-2- -448 445 b enzofuranyl) ethyl] oxalamide N- (7-Methoxy-2-benzofuranyl)- N

F

1, 1-dimethylethyl] [3-meth o)y_ 0 N60 4- (5-oxazolyl)phenyl] oxalamide C -X 464 446 N-[2-(5-Methoxy-2-benzofuranyl)- 1,1 -dimethylethyl] -[3-methoxyoxalamide 464 447 N- [2-(6-Methoxcy-2-benzoftiranyl)- N~ 'c 0 1,1-dimethylethyl] [3-methoxy- 0, F 4- (5-oxazolyl)phenyl] oxalamide -464 448 Benzyl 4- [2-[[[3-methoxy-4-(5- oxazolyl)anilino] oxalyl] amino] j J) methyipropyll benzoate 528 449 4-[2-[[[3-Methoxy-4-(5-N oxazolyl) anilino] oxalyl] amino] -S methylpropyllbenzoic acid o438 450 29 Benzyl 3- ([3-methoxy-4-(5oxazolyl)anilino] oxalyl] amino] -2methyipropyl] benzo ate 3- [3-Methoxy-4-(5oxazolyl)anilino] oxalyl] amino] -2methylpropyllbenzoic acid N- [2-(3-Benzofuranyl)-1,1dimethylethyl] [3-methoxy-4oxalamide Benzyl [3-methoxy-4-(5oxazolyl)anilino] oxalyl] amino] -2methyipropyl] benzofurancarboxylate 2- [3-Methoxy-4-(5oxazolyl)anilino] oxalyl] amino] -2- 0000 methyipropyl] .00 benzofurancarboxylic acid N- [3-Methoxy-4-(5- :oxazolyiphenyl]I 1- pyridyl)methyH -1- 00996:cyclopentyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] -oxido- :0.:*4-pyridyl)methyl] -1cyclopentyl] oxalamide 0 0 0 N- 2- (4-Methoxy-2-benzofuranyl) 1,1 -dimethylethyl] -[3-methoxy- 4- (5-oxazolyl)phenyl] oxalamide [3-Methoxy-4-(5-oxazolyl) phenyl] [2-(2,6-dimethyl-4pyridyl)- 1,1 -dimethylethyl] oxalamide 30 .0.

600 0*0 0 .o N- [3-Methoxy-4-(5- 0NW0 oxazolyl)phenyl]-N'- L1,1-dimethyl- NJ 2-(2,6-dimethyl-l1-oxido-4-pyridyl) 43. ethyl] oxalamide N- [3-Methoxy-4-(5-oxazolyl) 0 .N )cI -IV phenyl]-N'-[1-[(4-pyridyl)methyl]- a0 (I 393 655 1 -cyclopropyl] oxalamide N N- [3-Methoxy-4-(5-oxazolyl) 0 N phenyl] [1I- (1 -oxido-4- (\I409 656 pyridyl)methyl] -1-N cyclopropyl]I oxalamide N- [3-Methoxy-4-(5-oxazolyl) 0 N Yu N_ K X.I 407 657 1 -cyclobutyl] oxalamide N N- [3-Methoxy-4-(5-oxazolyl) 0 N -0J phenyl] f 1- 1-oxido-4- 0a pyridyl)methyl] -1-cyclobutyl] N~ 421 658 oxalamide N-[3-Methoxy-4-(5-oxazolyl) 0 N~LQc~ phenyl] [1-[(4-pyridyl)methyl] ok <\435 659 1 -cyclohexyl] oxalamide N N- [3-Methoxy-4-(5-oxazolyl) 0~ Ny phenyl] 1-oxido-4- <x\1 451 660 pyridyl) methyl]

N

cyclohexyl] oxalamide

NINXK~N

phenyl]-N'- [1,1-dimethyl-2-(2- a 0 methyl-4-pyridyl) ethyl]I oxalamide N 409 661 N- [3-Methoxy-4-(5-oxazolyl) 0 Ny r;I"Y*C0 phenyl]-N'- [1,1-dimethyl-2-(2- a0 0 methyl-i -oxido-4- 42N6 pyridyl) ethyl] oxalamide -31 2- [3-Methoxy-4-(5- N~~ oxazolyl) anilino] oxalyl] amino] ~N AN y S methyipropyl] 0H 44 6 benzothiophenecarboxylic acid Particularly preferred compounds of formula are also those according to the general formula wherein R 2

R

6 R' and R 10 are defined as above,

R

11 R 1 3 ,R1 4 R1 5 R1 6 R'1 7 and R'1 8 are H or lower alkyl and R1 9 is alkyl, cycloalkyl, heterocyclyl alkyl or aryl alkyl.

Particularly preferred compounds of formula (XII) are those wherein

R

2 is methoxy and R R R 6

R

9

R'

0 and R' are hydrogen.

Examples of such compounds are listed in table I d below 32 Name N- [3-Methoxy-4- (5-oxazolyl)phenyl] 1,1-dimethyl-2- pyridinyl)methylamino] phenyll ethyl] oxala mide N- [3-Methoxy-4-(5-oxazolyl)phenyl] 1,1-dimethyl-2-[4- pyridyl)methylamino] phenyl] ethyl] oxalam ide N- [4-(2-Furfurylamino)phenyl] 1,1 dimethylethyl] [3-methoxy-4- oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5-oxazolyl)phenyl] 1 -Dimethyl- 2 (2 :thenylamino)phenyl] ethyl] oxalamide N- [3-Methoxcy-4-(5-oxazolyl)phenyl] [1,1-dimethyl-2-[4-(2,2dimethylpropylamino)phenyl] ethyl] oxalam ide N- 1H-Imidazol-2- :yl)methylaminol phenyl] 1,1 dimethylethyl] -methoxy-4- oxazolyl)phenyl] oxalamide N- [3-Methoxcy-4-(5-oxazolyl)phenyl] [1,1-dimethyl-2-[4-[(4pyridyl)methylaminolphenyl] ethyl] oxalam ide i 0 0- C, 0 JI 33 N- [3-Methoxy-4-(5-oxazolyl)phenyl] 1-dimethyl-2- thiazolyl) methylamino] phenyl] ethyl] oxala 506.1 323 mide N-[2-[4-(3-Furfurylamino)phenyl]-1,1- N O dimethylethyl] [3-methoxy-4-(5- .0 48.02 oxazolyl)phenyl]I oxalamide48. 32 N 2 4 5-(Hydroxymethyl) 2- o' fu rfu rylamino]I phenyl] 1 dimethylethyl I 0I51. 2 [3-methoxy-4-(5-51. 32 oxazolyl)phenyl] oxalamide N 2- (4 -B en zylaminophenyl) 1, 1 Ck 0O dimethylethyl] [3-methoxy-4-(5- 0 oxazolyl)phenyl] oxalamide J,499.1 326 N- 2- (2-Hydroxybenzylamino)phenyl] C0.

1, 1 -dimethylethyl] 3-methoxy-4- oxazolyl)phenyl Ioxalamide 515.1 327 N- 2- (3-Cyanobenzylamino)phenyl] 1, 1 -dimethylethyl] 3-methoxy-4- oxazolyl)phenyl]I oxalamide52. 38 N- [3-Methoxy-4-( 5-oxazolyl)phenyl] 0 o0~c O [1,1-dimethyl-2- pyridyl)benzylamino] phenyl] ethyl] oxalami 576.2 329 de N- (2-Fluorobenzylamino)phenyl]

CH

1, 1-dimethylethyl] [3-methoxy-4-(5- o 51.F3 oxazolyl)phenyl]I oxalamide ,51. Particularly preferred compounds of formula are also those according to general formula 34 X111 wherein R R R R R R 9 and R" 0 are defined as above,

R

11 R1 3 'R1 4 R1 5 R1 6 R 1 7 and R 18 are H or lower alkyl and R 20 is alkyl, cycloalkyl, aryl, heterocyclyl.

Particularly preferred compounds of fromula (XIII) are those wherein Ris methoxy and R R R 6

R

9 R'O,Rlland R' are hydrogen.

Examples of such compounds are listed in table le below Table le Name Structure MS(ES) Ex No

(M+H)

t (Cyclopropylcarboxamido)phenyl] 47.03 1,1 -dimethylethyl] [3-methoxy-4-47.31 (5-oxazolyl)phenyl] oxalamide N- (Cyclobutylcarboxamido) Ct 0jA~r p henyl] 1 di methyl ethyl] 3 r0-0 methoxy-4- (5-oxazolyl)phenyl 9. 3 oxalamide N-1{3-Methoxcy-4- (5-oxazolyl)phenylI C, 1 0 N -N'-[1,1-dimethyl-2-(4- 49.03 pivalamidophenyl) 1, 1 4 9.3 dimethylethyl] oxalamide 35 N- [3-Methoxy-4- (5-oxazolyl)phenyl] j IrD 1,1-dimethyl-2- 1H-pyrrol- 0. 3 2-yl)carboxamido] phenyl] ethyl]50. 34 oxalamide N- [(2-Furyl) c carboxamido] phenyl] 50.o3 dimethylethyl] [3-methoxy-4-(5-50. oxazolyl)phenyll oxalamide N- [(3-Furyl) o N carboxamido] phenyl] 1,1 503. 33 dimethylethyl] [3-methoxy-4-(5-50. 36 oxazolyl)phenyl] oxalamide N- H-Irnidazol-4-yI) carboxamido] phenyl] -1,1l- o 50.N3 dimethylethyl] [3-methoxy-4-(5- 0. 3 oxazolyl)phenyl] oxalamide N- [(Tetrahydro-2 (RS) -furyl) j carboxamido] phenyl] 1, 1- 50.2 33 dimethylethyl 3-methoxy-4- (5-50. 38 oxazolyl)phenyl] oxalamide N- 3 -Methoxy-4- oxazolyl) o -o phenyl] 1, 1 -dimethyl-2 4- o 1. 3 pyridyl) carboxamido phenyl ethyl ox51. 39 alamide 1, 1 dimethyl-2 (4-pyridyl) o oo carboxamido] phenyl] ethyl] oxalamide 514. 34 N- [3-Methoxy-4- (5-oxazolyl)phenyl]

N-

[1,1-dimethyl-2- [(2-thienyl) 519.1 341 carboxamido] phenyl] ethyl] oxalamide N N- [3-Methoxy-4-(5-oxazolyl)phenyl] P NY [1,1 -dimethyl-2- [(3-thienyl) N N

N

N*

N.

36 carboxamido] phenyl] ethyl] oxalamide 519.1 342 N- [4-(2-Cyclopentylacetamido)

N

phenyl] 1,1 -dimethylethyl] 0 methoxy-4- (5-oxazolyl)phenyl] 519.2 343 oxalamide N- [3-Methoxy-4-(5-oxazolyl) phenyl] -N'-[1,1-dimethyl-2- 0 2. 4 methylbenzamido)phenyl] ethyl] oxala mide N- [3-Methoxy-4- (5-oxazolyl)phenyl] I1 0, 1-dimethyl-2- (4-52.34 methylbenzamido)phenyl] ethyl] oxala J52. 34 mide N- 2- Cycloheptylcarboxamido) l 0 phenyl] 1-dimethylethyl] I-c 53.N4 methoxy-4- (5-oxazolyl)phenyl] 3. 4 oxalamide 0- N- [(5-Isoxazolyl) carboxamidol %P NYphenyl] -1,1-dimethylethyl] -N50.1 34 methoxy-4- (5-oxazolyl)phenyl] 0. 4 oxalamide N- (Cyclopentylcarboxamido)

YD

phenyl] 1,1 -dimethylethyl] 0 0.4 methoxy-4- (5-oxazolyl)phenyl] 0. 4 oxalamide N- [2-f 4- [(Tetrahydro-3(RS)-furyl)

C

carboxamido] phenyl] -1,1-50.34 dimethylethyl] [3-methoxy-4-(5-50. 34 oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5-oxazolyl)phenyl] [1,1-dimethyl-2- [(1-methyl- N_0 51. 1 H-pyrrol-2-yl) carboxamido] phenyl] I51. 0.

37 ethyl] oxalamide N- [3-Methoxy-4- (5-oxazolyl)phenyl] c 1,1-dimethyl-2- 52.31 thiadiazol-4-yl)carboxamido] phenyl]52. 31 ethyl] oxalamide [4-(3-Fluorobenzamido)phenyl] o 0K -1,1-dimethylethyl]-N'-[3-methoxy- .0i 5-oxazolyl)phenyll oxalamide 531.1 352 N- (4-Fluorobenzamido)phenyl] I -1dimethylethyl]-N'-[3-methoxy-0 4-oxazolyl)phenyl oxalamide j53. 33 N- [4-(2-Clrbnaio Cl% 0 Mehxbaiophenyl-1,1-diehlty]N-3 i 0 diehlty]-' 3methoxy-4- (5-oxzllNhnl 547.1 355 oxazllpyoxlamide N- [4-(3-Chlorobenzamido) C. 0 phenyl] -1,1 -dimethylethyl] 547.1 methoxy-4- (5-oxazolyl)phenyl] 4. oxalamide N- [4-(4-Chlorobenzamido) 0 phenyl 1,1-dimethylethyl] 0 methoxy-4- (5-oxazolyl)phenyl] l547.1 357 oxalamide N- [(41-Ihorndol--y /l o phnl dimethylethyl] [3-me0N-(0 38 N- [3-Methoxy-4- [1,1-dimethyl-2- [4-56. 39 (dimethylamino)benzamido] phenyl] e56. 39 thyloxalamide N-[3-Methoxy-4-(5-oxazolyl)phenyl] 0' HPI -N'-[1,1-dimethyl-2-[4-(3,3dimethylbutyramido)]I phenyl] ethyl] o 507.1 360 xalamide N- [3-Methoxy-4- (5-oxazolyl)phenyl] 1, 1-dimethyl-2- (1 tetrazolyl)acetamido] phenyl] ethyl] ox51. 36 alamide N- [3 -Methoxy-4- (5-oxazolyl)phenyl] 0- (\Chiral 1,1-dimethyl-2- [(5-oxo-2(S) pyrrolidinyl)carboxamido] phenyl] eth52. 36 yl] oxalamide N- 3-Methoxy-4- (5-oxazolyl)phenyl]5c ,ko 1-dimethyl-2-{4-[f(5-oxo-2 -o pyrrolidinyl)carboxamido] phenyl] eth 520.1 363 yl] oxalamide N- [3-Methoxy-4- (5-oxazolyl)phenyl] K 1-dimethyl-2- o6. 6 naphthyl)carboxamido] phenyl] ethyl] oxalamide N- [(6-Cyano-3-pyridyl) c~

-H

carboxamidojphenyl}- 1,1- N k o dimethylethyl] [3-methoxy-4-(5- 580.1 365 oxazolyl)phenyl] oxalamide

(M+H+

ACN)

N-[2-[4-(3-Methoxybenzamido) 0 phenyl] -1,1 -dimethylethyl] [3methoxy-4- (5-oxazolyl)phenyl] _j543.1 366 -39oxalamide N- [4-(3,5-Difluorobenzamido) phenyl] 1,1 -dimethylethyl] 04. 6 methoxy-4- oxalamide N- 1H-Indol-5-yl) 0 carboxamido] phenyl] -1,1-I dimethylethyl] -N'-[3-methoxy-4-(5- 01552.1 368 oxazolyl)phenyl] oxalamide (2-Butenamido)phenyl] 1,1 -dimethylethyl] [3-methoxy-4 J(47. 6 oxalamide47.36 0 r 1 N- (2-Methoxyacetamido) zi phenyl] -1,1 -dimethylethyl] 48. 37 methoxy-4-( 5-oxazolyl)phenyl] 8. 7 oxalamide N-[3-methoxy-4-(5-oxazolyl)phenyl]-

N

1,1-dimethyl-2- [(2-methyl-3- 51. 37 furyl)carboxamido] phenyl] ethyl] oxal51. 37 amide N- [3-Methoxy-4-(5-oxazolyl)phenyl] 1,1-dimethyl-2- [(5-methyl-4- I 51.37 isoxazolyl)carboxamido] phenyl] ethyl] 51.N7 oxalamide 9* a a a. a a N- [3-Methoxy-4- (5-oxazolyl)phenyl] 1,-dimethyl-2- [(3-methyl-4isoxazolyl)carboxamido] phenyl] ethyl] oxalamide 0"~ 0 0

(\I

518.1 t -r N- 3-Methoxy-4-(5-oxazolyl)phenyl] 1, 1-dimethyl-2- (5-methyl-3isoxazolyl)carboxamido] phenyl] ethyl] oxalamide

(\I

518.1 374 40 N- 3-Methoxy-4- (5-oxazolyl)phenyl] yQ 1,1 -dimethyl-2- -oxido-3- o pyridyl)carboxamido] phenyl] ethyl] ox53. 37 alamide N- [3-Methoxy-4- (5-oxazolyl)phenyl] C -N'-[1,1-dimethyl-2-[4-[(1-oxido-4- 53. 7 pyridyl) carb oxamido]I phenyl]J ethyl ox alamide N 3- Methoxy- 4 -oxazolyl.)phenyl] opc [1,1 -dimethyl-2- orY oc dimethyl-2-furyl)carboxamido] 531.1 377 phenyl]I ethyl] oxalamide

,CH.

N- [3-Methoxcy-4- (5-oxazolyl)phenyl] occ 1,1-dimethyl-2- o~f~YJ dimethyl-2H-pyrazol-3-yl) 531.1 378 carboxamido] phenyl] -1,1dim ethylethyl] oxalamide N- [3-Methoxy-4-(5-oxazolyl)phenyl] 1,1-dimethyl-2- [(3-methyl-2- -53.37 thienyl)carboxamido] phenyl] ethyl] ox53. 37 alamide N- 3 -Methoxy-4- oxazolyl) phenyl] NXa 1, 1 -dimethyl- 2 2 thienyl) acetamido phenyl ethyl]J oxala 533.1 380 mide N- 3-Methoxy-4- oxazolyl)phenyl] I -N'-[1,1-dimethyl-2-[4-[(4-methyl-2- o 3. 8 thienyl)carboxamido] phenyl] ethyl] ox53. 38 alamide N- [3-Methoxy-4-(5-oxazolyl)phenyl] [1,1 -dimethyl-2- [(4-methyl- 0 1 ,2,3-thiadiazol-5- 55382 yl)carboxamido] phenyl] ethyl] oxalami____ S 41 4** (4-Acetamidobenzamido) 'YC-e phenyl] -1,1-dimethylethyl] 0570.1 383 methoxiy-4- oxalamide N- (3,4-Dimethoxybenzamido) phenyl] 1-dimethylethyl] 0 methoxy-4- (5-oxazolyl)phenyl] 7. 8 oxalamide N-[2-[4-(4-Chloro-2- a, 0o 00, -C methoxybenzamido)phenyl]-I,1- 0 57.o8 dimethylethyl] [3-methoxy-4- N57. 38 oxazolyl)phenyl] oxalamide N-[2-[4-(2,6-Dichlorobenzamido)a phenyl]-1,1-dimethylethyl]-N'-[3- 0 c %i581 386 oxalamide N- [(Bicyclo[4.2.O]octa- 1 a o N N triene-7(RS)-yl)carboxamido] o539.1 387 phenyl] 1,1-dimethylethyl] [3methoxy-4- oxalamide N- [3-Methoxy-4-(5-oxazolyl)phenylI 1,1-dimethyl-2- [4-(2-oxo-2- 54. 38 phenylacetamido )phenyl] ethyl] oxala N54.38 mide N- [2-14- 2- (2-Fluorophenyl) acetaniido]phenyll-1,1-5438 dimethylethyl]-N'- [3-methoxy-4-(5-5438 oxazolyl)phenyl] oxalamide 42 N- [2-(4-Fluorophenyl) acetamido]phenyl}- 1,1dirnethylethyl)-N'- [3-methoxy-4-(5oxazolyl)phenyl] oxalamnide N- [3-Methoxcy-4-(5-oxazolyl)phenyl] (4-methoxy-3-thienyl) carboxamido] phenyll -1,1dimethylethyl] oxalamide N- (4-Acetylbenzamido) phenyl] 1,1-dimethylethyl] [3methoxy-4- oxalamide N- ,3-Benzodioxol-5-yl) carboxamido] phenyl] -1,1ldimethylethyl] [3-methoxy-4- oxazolyl)phenyl] oxalamide N- [2-(2-Chlorophenyl) acetamido] phenyl] 1,1dimethylethyll [3-methoxy-4- oxazolyl)phenyl] oxalamide N- [2-(4-Chlorophenyl) acetamido Iphenyl] -1,1dimethylethyl] -N'-[3-methoxy-4-(5oxazolyl)phenyl] oxalamide :tert-Butyl 4- [3-methoxy-4oxalyl] amino] -2methyipropyll phenyl] carbamnoyl) benz oate [3-Methoxy-4-(5-oxazolyl) anilino] oxalyl] amino] -2methyipropyl] phenyl] carbamnoyllbenz oic acid i 0 -43- Particularly preferred compounds of formula are also those according to general formula

R

9 N R

XVIII

Ro 1"R 3 O R R 12 R O CH) Z R o

R

wherein R 2 R R, R 6

R

6

R

9 and R'O are defined as above, R" and R 1 3 are H or lower alkyl, n= 0 or 1,

R

a Rb are lower alkyl or Ra and Rb taken together with the carbon atom to which they are 10 attached form a 3 to 7 member carbocycle, and

R

12 is heterocyclyl, aryl or lower cycloalkyl and Z is O, S or NR 2 8 wherein R 28 is H or lower alkyl.

Further preferred compounds of formula XVIII are those according to general formulas: 15 Further preferred compounds of formula XVIII are those according to general formulas: 44 XIVa (CH) R 1 2 XIVb @000 *000 0* 0 0 00*00 0 *0 00 0 0 0 R 0 N: CH(CH 2 R 1 2 RN R11 0 R wherein R 2 R 3

R

5 R' and R' 0 are defined as above R" and R 1 3 is H or lower alkyl, n= 0 or 1, m=1 to 5 and, 10 R 1 2 is heterocyclyl, aryl or lower cycloalkyl.

Particularly preferred compounds of formula (XIV) are those wherein R 2 is methoxy and R 3 R 5 R 6

R

9

R'

0 and R 1 3 are hydrogen.

*0 V 0* 0900 0 @000 00 0 0* Examples of such compounds are listed in table 1f' below 45 table le' Name Structure MS(ES) Ex No

(M+H)

t N- [3-(4-Hydroxy-phenoxy)-l,11-

OC

dimethyl-propyl] -N'-(3-methoxcy- 44 396 N- [3-Methoxy-4-(5-oxazolyl) T= F methoxyphenoxy)- 1,1- CHI39 dimethyipropyl]I oxalamide N- [3-Methoxy-4- (5-oxazolyl) oo phenyl] [1,1-dimethyl-3-(4-I nitrophenoxy)propyl] oxalamide 4609 N- (2-Hydroxyphenoxy)- 1, 1- I dimethylpropyl] [3-methoxy-4oxalamide 0 CHH U 440 399 N- (4-Amino-phenoxy)- 1, 1- NO oCH dimethyl-propyl] (3-methoxy- 0I 4-oxazol-5-yl-phenyl)-oxalamide C K 3940 N- 3- (4-Acetylamino-phenoxy) 1,1-dimethyl-propyl] methoxy-4-oxazol-5-yl-phenyl)- 0~ 'O.R,41 0 oxalamide N-[3-Methoxy-4-(5-oxazolyl) N1 pyridyloxy) propyl] oxalamide 0N4240 N-[3-(3-Hydroxyphenoxy)-1,1- N N N--r dimethyipropyl] [3-methoxy-4- -oxazolyl) phenyl I oxalamide 0 440 403 0SO 0 SO aO 00 0000 0: 999* 500 0 46 N- [3-Methoxy-4-(5-oxazolyi) N 170 0 phenyll-N'-[3-(3- l methoxyphenoxcy)- 1, 1- 0 454 404 dimethyipropyll oxalamide N- j3-Methoxy-4-(5-oxazoly1) 0~ Q phenyll f 1,1-dimethyl-3-(3- CN'YN,--aN0 nitrophenoxy)propyl]I oxalamide 0 469 405 N- [3-(3-Aminophenoxcy)- 1, 1- N "O 0dimethylpropyl] [3-methoxy-4- iNf,-,ON oxalamide04346 4-1[3- [[3-Methoxy-4- (5-oxazolyl)

N

anilinol oxalyll amino] 0C%-y 6 3 methylbutoxcylbenzoic acid4643 2- [3-[[3-Methoxy-4-(5-oxazolyl) 0~Oo anilino] oxalyl] amino] 0- P6 0' 6 3 methylbutoxcy] benzoic acido4643 [[3-Methoxy-4-(5-xzll oxllanilinol oxalyll amino] o methylbutoxy]bpenoy]eic acid 498 436 2- [[3-Methoxy-4-(5-[_ oxazolyl)anilinol oxalyUl amino] -3 4903 methylbutoxcy] phenoxy] acetic acid4943 [[3-Methoxy-4-(5- "OO oxazolyl)phnl]-no '-(1,1-daino]h-444 3-phenboxyppyoxylacic cdoe9 3 N-[3-Methoxy-4-(5-oxazolyl) SOo" phenyl] [1,1-dimethyl-3-(I 1-c

W

oxido-3-pyridyloxy)propyl] 441 543 47 oxalamide N- [3-(3,4-Dihydroxyphenoxcy)- 1, 1 v"q0-C dimethylpropyl] -N'-[(3-methoxy-4- 0Yt 01 5K4 oxalamide4554 N- [3-Methoxy-4- phenyl]-N'-[1,1-dimethyl-3-[4- 0 Iy0 (methylcarbamoyl)phenoxy] propyl 481 545 I oxalamide N-[3-Methoxy-4-(5-oxazolyl) 0.a phenyl] dimethoxyphenoxy) 1, 1 c 8 4 dimethyipropyl] oxalamide N- [(2-Hydroxyethyl) carbamoyllphenoxy]-1,1-dimethyl- I propyl] [3-methoxy-4-(5- 511 547 oxazolyl)phenyl] oxalamide fl N-[3-(3-Chlorophenoxy)-1,1- dimethylpropyl]-N'-[3-methoxy-4- C 5 4 (5-oxazolyl)phenyl] oxalamide 0i 5 4 CH 0 i N-13-Methoxy-4-(5-oxazolyl) 10 N "Z 0 ,OJIN phenyl]-N'-[1,1-dimethyl-3-(3- 00pyridyloxcy)propyl] oxalamideN4259 N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N'-[1,1-dimethyl-3-(2-Ipyridyloxy)propyl]I oxalamide 0NCcl 425 550 2-[4-[3-I1[[3-Methoxy-4-(5oxazolyl) anilino] oxalyl] amino] oc methylbutoxy] phenyl] acetic acid 482 551 2- [3-Methoxy-4-(5- //o0 oxazolyl)anilino] oxalyl] amino] Il-<o 482 552 -48methylbutoxy] phenyl] acetic acid 4-[2-[[[3-Methoxy-4-(5-oxazolyl)I anilinol oxalyll amino] 0 methylpropoxylbenzoic acid4553 4- [[3-Methoxy-4-(5-oxazolyl) anilino] oxalyll amino] 00, -f methylbutoxy] -2-methylbenzoic 482 554 acid 3- [3-Methoxy-4-(5oxazolyl)anilino] oxalyl] amino] C., methylbutoxy] phenyl] propionic 496 555 acid 3-[4-[3-[[[3-Methoxcy-4oxalyll amino] 09 556 3-methylbutoxyiphenyl] propionic acid 3-[2-[3-[[[3-Methoxy-4-(5- N' 0 O-Cl oxazolyl)anilinol oxalyl] amino] 'a 9 methylbutoxy] phenyl] propionic acid 2-[3-[3-[[[3-Methoxy-4-(5- 'FIc 0 0 oxazolyl)anilino] oxalylj amino] t methylbutoxy] phenoxyl acetic acid 498 558 anilino Ioxalyl Ia min o-3 methylbutoxy] -3-methylbenzoic 0482 559 acid N-[3-(4-Cyano-2- Ni I H methoxyphenoxy)-1,1- 479 56 dimethypropyl [3 -methoxy-4- Ni4756 oxalamide 49 N- [3-(3-Cyanophenoxy)- 1,1- Z- I dimethyipropyl] [3-methoxy-4oxalamide 449.6 561 N- [4-(4-Acetyl- I-piperazinyl) phenoxy] -1,1-dimethyipropyl] [3-methoxy-4- (5-oxazolyl) phenyl] 550.4 562 oxalamide N-[3-Methoxy-4-(5-

CH

oxazolyl)phenyl] [1,1 -dimethyl- 53.4 56 3- (2-morpholinophenoxcy)propyll 3. 6 oxalamide (M Na) t N- [3-Methoxy-4- (5-oxazolyl) Ny,) 5 C a phenyl]-N'-[1,1-dimethyl-3-[3- (dimethylamino)phenoxy] 489.6 564 (M Na)+ propyl] oxalamide N-[3-(1,3-Benzodioxol-5-yloxy)- o 1,1 -dimethylpropyll [3methoxy-4- (5-oxazolyl)phenyl] J 468.4 565 oxalamide N- [3-Methoxcy-4-(5-oxazolyl) N o 0-l phenyl 3 0loc'R trimethoxyphenoxy) 1, 1- 0514.4 566 dimethyipropyl oxalamide N- 3-Methoxy-4- (5-oxazolyl) N

H

phenyl]-N'-[3-(3,5- 50o6 dimethoxyphenoxy) 1, 1-5056 dimethyipropyl] oxalamicle (M Na) t N- [3-(5,6,7,8-Tetrahydro-5-oxo-2- c" OHC naphthyloxy)- 1,1-dimethylpropyl] o 492.4 568 [3-methoxy-4-(5oxazolyl)phenyl] oxalamide 4 5~ 4

S

S

N* S S

S.

S.

SS

S.

0

*.SS

50 o I N-[3-(2-Acetamido-5- t t 0 methylphenoxy)-1,1- 0 <Y~ dimethyipropyl] 3-methoxy-4- 0517.6 569 oxalamide (M Na) t 3-Acetamidophenoxcy) -1,1 dimethyipropyl] [3-methoxy-4- (,31 (5-oxaz1l1lnhnyl1 oxalamide 503.6 570 (M Na)t dimethyipropyl] [3-methoxy-4- oxalamide ,485.2 571 (M Na) t

F

OH 0cCH c N- [3-(2-Fluoro-6-

I

methoxyphenoxy)-1,1- (\pa II0 47. 572F dimethyipropyl] -methoxy-4- N47. 52 oxalamide N- [3-Methoxy-4-(5-oxazolyl) 0 p henyl]-N'- 1 -dim ethyl- 3 KN oxo-2H- 1 -benzopyran-7- 492.4 573 yloxy)propyll oxalamide N- (4-Acetyl-3-methylphenoxy)- IF r N c- 1,1 -dimethylpropyl] 48. 57 methoxy-4- (5-oxazolyl)phenyl] 8. 7 oxalamide (E)-N-[3-Methoxy-4-(5-oxazolyI) C o,%c0 oxo-l1-butenyl)phenoxy] propyl] 9. 7 oxalamide N- [3-(3-Acetylphenoxcy)-1,1- C N Cs dimethyipropyl] [3-methoxy-4- J146. 7 -oxazolyl) phenyl oxalamide464 57 -51 N- [3-(4-Acetylphenoxy)- 1,1-CH 0I H o dimethylpropyl] [3-methoxy-4- I oxalamide ,466.2 577 OC o~l N> O N- [3-(4-Acetamido-2- Y1&x, chiorophenoxcy)- 1,1- yN dimethylpropyl]-N'- [3-methoxcy-4- 515.6 578 oxalamide N-[3-Methoxcy-4-(5-o oxazolyl)phenyl]-N'-[1,1-dimethyl-- 3-(4-pyridyloxcy)propyl] oxalamide o a~t Z N 425 579 NI 0 N- 13-Methoxy-4-(5-oxazolyl) phenyl]-N'-[1,1-dimethyl-3-(1- 44 580 oxido-4- pyridyloxy)propyl]41 58 oxalamide w+-0o -c N-[3-Methoxy-4-(5-oxazolyl) o- phenyl] [1,1-dimethyl-3-(2,6- Iy dimethyl-4-pyridyloxy)propyll at453 581 oxalamide N-[3-Methoxy-4-(5-oxazolyl)

-H

phenyl]-N'-[1,1-dimethyl-3-(2,6- dimethyl-l-oxido-4-pyridyloxy) GA469 582 propyl] oxalamide 0F o c N-[2-(4-Cyanophenoxy)-1,1- 0l NN,0 dimethylethyl] [3-methoxy-4- <I (5-oxazolyl)phenyll oxalamide N435 583 N-[3-Methoxcy-4-(5-oxazolyl) phenyl] (2-methoxcy-4- 455 584-xpyridyloxcy)- 1,1-dimethyipropyl] 5 8 oxalamide o' 0c" N- [3-Methoxy-4-(5-oxazolyl) 0 N& Z N phenyl] [1,1 -dimethyl-2- V, (1 H-tetrazol- S-yl )phenoxy] ethyl] 478 585

V

V

V. V 52 oxalamide N- (4-Cyanophenoxcy)- 1,1 dimethyipropyl]I 3-methoxy-4-4958 oxalamide 449 586 N- [2-(3-Cyanophenoxy)- 1, 1- 0-1 dimethylethyl] [3-methoxy-4- N4758 -oxazolyl) phenyl oxalamide4758 N 3 -Methoxy- 4-(5 -oxazolyl) o- N T1<v phenyl 1 -dimethyl -2 (1I H -tetrazol 5 -yl) phenoxy]I ethyl] 478 588 oxalamide C tN N- [3-Methoxcy-4-(5-oxazolyl) CK 0 I pheyl 1, -imehy-3-[4 0492 589 propyl] oxalamide Benzyl 4- [[3-methoxy-4-(5oxazolyl)anilino] oxalyl] amino] -1I-57.59 cyclobutyl] ethoxy]benzoate57. 59 Benzyl 4- [1-[[[3-methoxy-4-(5-0 oxazolyl)anilino] oxalyl] amino] 1- J cyclopentyl] ethoxy]benzoate 584.3 591 Benzyl 4- [1-[[[3-methoxy-4-(5- -i oxazolyl)anilino] oxalyl] amino] 1- 0, cyclohexyl] ethoxy]benzoate 598.3 592 [[3-Methoxy-4-(5oxazolyl)anilinoloxalyl] amino] I 494.2 593 cyclopentyl] ethoxcy]benzoic acid N 0 4- [[3-Methoxy-4-(5- G oxazolyl)anilinol oxalyl] amino] -1 0. 9 cyclohexyl] ethoxy] benzoic acid50. 59 53 [3-Methoxy-4-(5- N 0 oxazolylanilino] oxalyl)amino -1I- 0-c 0 cyclobutyl] ethoxylbenzoic acid 480.2 595 Benzyl 2-methoxy-4- oxazolyl) an ilino] oxalyl amino] 588 635 methylbutoxy] benzoate

OC

3-Chloro-4-[3-[[[3-methoxy-4-(5- oxazolyl) an ilino ]oxalyl ]amino-3 RVC' methylbutoxy] benzoic acid 0502 636 2-Methoxy-4- [[3-methoxy-4- "i oxazolyl)anilino] oxalyl] amino] 0l 45-'0 o 3-methylbutoxylbenzoic acid 0 498 637 3-Methoxy-4- [3-methoxy-4- N 0 No oxalyl] amino] -1 3-methylbutoxylbenzoic acid 0 498 638

N,

4 2 -M eth oxy- 4 oN oxazolyl)anilino] oxalyl] amino] -1I-I cyclopropyllethoxy]benzoic acid OH466 639 2-Chloro-4- [3-[[[3-methoxy-4- o oxazolyl)anilino] oxalyl] amino] '-Iv2I~O methylbutoxy] benzoic acid o 502 640 4- [3-Methoxy-4- (5-oxazolyl) o anilino] oxalyl] amino] oo methylbutoxy] NI519 641 quinolinecarboxylic acid S. (cis/trans)-4- [[3-Methoxy-4oxalyll amino] 3-methylbutoxy] -1cyclohexanecarboxylic acid NQ y 0 )a,,AyNf--O 0 0 54 (cis/trans)-4- [2-[[[3-Methoxy-4- 0 Yk 0 0 0-0- OH oxalyl] amino] Na 2-methyipropoxyl 460 643 cyclohexanecarboxylic acid 3-Fluoro-4- [3-methoxy-4-(5- 9- 0 oxazolyl)anilino] oxalyl] amino] methylbutoxylbenzoic acid 0 486 644 3-Acetamido-4- [3-jj[3-methoxy-4- 0~ H oxalyl] amino] 0 f1-OIC%OH 3-methylbutoxylbenzoic acid 0 525 645 3- (Methanesulfonamido) Q Q [[[3-methoxy-4-(5- -kI NttN OH oxazolyl) anilino] oxalyl] amino] 0 561 646 methylbutoxylbenzoic acid [[3-Methoxy-4-(5-oxazolyl) N N -~y anilino] oxalyl] amino] O methylbutoxy] 0 496 647 dimethylbenzoic acid 3- 3-Methoxy-4-(5-oxazolyl) NO9 0 OH anilino] oxalyl] amino] methylbutoxy] 469 648 pyridinecarboxylic acid 8- [[3-Methoxy-4-(5-oxazolyl) N IO 0'0O anilino] oxalyl] amino] kNrf,-,1964 methylbutoxyl -2-05164 quinolinecarboxylic acid 5-[(3-[[3-Methoxy-4-(5-oxazolyl)

L

anilinol oxalyll amino] 0 o 0 methylbutoxy] -2-indolecarboxylic acid 55 Further preferred compounds of formula XVIII are those according to general formula R9 2 N R'

XIX

IR

3

R

N (C 2 s wherein R R 6 R R 9 and R" 0 are defined as above, R" and R 1 3 are H or lower alkyl, n=0orl1, R a, R b are lower alkyl or R a and R b taken together with the carbon atom to which they are attached form a 3 to 7 member carbocycle, and R'1 2 is heterocyclyl, aryl or lower cycloalkyl.

Particularly preferred compounds of formula (XIX) are those wherein R 2 ismethoxy and R 3

R

9

R'

0 R" and R 13 are hydrogen.

Examples of such compounds are listed in table Ife below: Name Structure MS(ES) Ex No

(M+H)

t N- [3-Methoxy-4-(5-oxazolyl)

ON"

phenyl] [1,1-dimethyl-2- (phenylthio) ethyl Ioxalamide 0~ t U 426 615 N- 2- (4-Hydroxyphenylthio) 1, 1 0"0O 0' dimethylethyl] methoxy-4- 0 oxalamide 0442 616 N- [3-Methoxy-4-(5-oxazolyl) N--0 a0C phenyl] 1, 1-dimethyl-2-

SC

(phenylthio) ethyl] oxalamide Ut440 617 56 N- [3-Methoxy-4- (5-oxazolyl) NN phenyl] [1,1 -dimethyl-2-(2- pyridylthio) ethyl Ioxalamide 0 t F 427 618 N- [3-Methoxy-4- (5-oxazolyl)NO r 0~ phenyl] 1-dimethyl-3-(2- STN pyridylthio)propylj oxalamide 0 at 441 619 N-[3-Methoxcy-4-(5-oxazolyl) N'-O OC" phenl]-N-[I,-dimthyl3-(S thienylthio)propyljoxalamide 0 CH 446 620 N-[3-Methoxy-4-(5-oxazolyl) Ni pyrimidylthio)propyl] oxalamide 0 at 442 621 N-[3-Methoxy-4-(5-oxazolyl)Ni phenyl]-N'-[1,1-dimethyl-3-(4-- NCH pyridylthio)propyl] oxalamide 0 C~ 441 622 N-[3-Methoxy-4-(5-oxazolyl) 0' phenl]-N-[1,-dimthyl3-(S thiazolylthio)propyl]I oxalamide 0 C%447 623 N -o0 O'% N- [3-(4-Hydroxyphenylthio)- 11 dimethyipropyl] methoxy-4- 0 c oxalamide 456 624 N-[3-Methoxy-4-(5-oxazolyl) phenyl] [1,1-dimethyl-3-(5- I methyl-i ,3,4-thiadiazol-2 -ylthio) oi m -Ct462 625 propyl] oxalamide N- [3-(2-Benzooxazolylthio)- 1, 1 0 dimethyipropyl] [3-methoxy-4- OHJ /\&'rb48 2 (5-oxazolyl)phenyl] oxalamide-4862 N- [3-(2-Benzothiazolylthio)- 1, 1

C,

dimethyipropyl] [3 -methoxy-4- o \Cl 9 2 oxalamide-4962 57 0H OCH, Methyl 4-[2-[I[3-methoxy-4-(5- oxazolyl)anilino] oxalyll amino] it methylpropylthio Ibenzoate 484 628 tert-Butyl 6- [3-methoxy-4-(5- oxazolyl)anilinol oxalyllamnino] I 4 2 methylbutyithiol -3-5462 pyridinecarboxylate anilinol oxalyl]amino] -3-I methylbutylthio] 0 485 630 pyridinecarboxylic acid trifluoro acetate (1:1) 3-Mehoxy4-(5oxazlyl anilinol oxalyl] amino] -3methylbutylthio]benzoic acid 484 631 N- (4-Benzyloxyphenylthio)- 1,1 Wdimethylethyl] [3-methoxy-4- Nj-±SOOf -oxazolyl) phenyl oxalamide 0532 664 N 2- (4 -Benzyloxyphenylthio) 1, 1 dimethyipropyl] [3-methoxy-4- 0 4 6 (5 -oxazolyl) phenyl oxalamide5465 2 3 [3 -Methoxy- 4-(5 -oxazolyl)

I

anilino Joxalyl ]amin o]3 O A 525 666 methylbutylthio] -52566 benzoxazolecarboxylic acid dimethyipropyl] [3-methoxy-4 1 0 (5-oxazolyl)phenyl] oxalamide 0 ND 430 667 F 0 2- [[3-Methoxy-4- (5-oxazolyl) N'YY Fr anilino] oxalyl] amino] Fll 0 N methylbutylthio] OH4868 pyridinecarboxylic acid -58trifluoroacetate (1:1) 4-[2-[[[3-methoxy-4-(5- 0 oxazolyl)anilino] oxalyl] amino] I methylpropylthio]benzoic acid 470 669 2- [3-Methoxy-4-(5-oxazolyl) anilino] oxalyl] amino]-3- 525 670 methylbutylthio]-6- 525 670 benzoxazolecarboxylic acid Further preferred compounds of formula (XVIII) are those according to general formula

R

9 2R 3 a N R X X Sein RR 0 R Rb 12 6(CH2)n

N"

R

6 N R 1 3 I1 R28 3 5 7

R

13 and R 28 are H or lower alkyl, Sattached form a 3 to 7 number carbocycle, and

*R

2 is heterocyclyl, aryl or lower cycloalkyl.

Particuarly preferred compounds of formula (XX) are those wherein R 2 is methoxy and R 3 R R 6

R

9 Ro, R R and R 13 are hydrogen and R 28 is hydrogen or methyl.

Examples of such compounds are listed in table 1f 3 below.

59 Name Structure MS(ES) Ex No N- [3-Methoxy-4-(5-oxazolyl) O2 phenyl]-N'-[1,1-dimethyl-2-(N- 0 methylanilino) ethyl] oxalamide 0H'C CH 423 632 N- (3-Anilino- 1,1-dimethyipropyl) N0 1CH [3-methoxy-4- (5-oxazolyl) N phenyl] oxalamide hydrochloride H -f423 633 1) anilino] oxalyl] amino]l-3--

I

methylbutylamino]benzoic acid 467 634 Particularly preferred compounds of formula are also those according to general formula 21

NJ

wherein R 2 R 3 R 5 R 6 k 7

R

9 and R1 0 are defined as above, R" and R 1 3 is H or lower alkyl, n 0 or 1 60 R 2 1 is optionally substituted alkyl, cycloalkyl,phenyl, heterocyclyl, optionally substituted cycloalkyl alkyl, phenyl alkyl or heterocyclyl alkyl, optionally substituted alkyl carbonyl, cycloalkyl carbonyl, phenyl carbonyl, heterocyclyl carbonyl, optionally substituted alkyl sulphonyl, cycloalkyl sulphonyl, phenyl sulphonyl, heterocyclyl suiphonyl.

Particularly preferred compounds of formula (XV) are also those wherein R 2 is methoxy, R 6

R

9

R'

0 and R 1 3 are hydrogen.

Examples of such compounds are listed in table 1g below

S.

S S

S

*0 S S

S

S S 555555

S

0 S. S

S*

S

*S.S

55 S S Name Structure MS(ES) Ex No N- [3-Methoxy-4-(5- oxazolyl)phenyl] [1,1-dimethyl-2- CaiC 0 j 7 0 (4-phenyl-l-4740 piperazinyl)ethyl] oxalamide N- [3-Methoxcy-4-(5- 0 oxazolyl)phenyll NY N methoxyphenyl) 1 -piperazinyl 1- '0508 408 dimethylethyl] oxalamide N- [3-Methoxy-4-(5-

NOI

oxazolyl)phenyl] Ik-N, methoxyphenyl)- I-piperazinyl] 1, 1- N-j50840 61 dimethylethyll oxalamide N-[3-Methoxy-4-(5- Ooxazolyl)phenyl] Li1, 1 -dimethyl-3- 0 492 410 (4-phenyl- 1-04941 piperazinyl)propyl] oxalamide N- [3-Methoxy-4-(5- 0 'N9 oxazolyl)phenyl] I N'A.NYN..) -o methoxy-phenyl)- 1 -piperazinyl] 1, 1- 0C,0508 411 dimethyl ethyl] oxalamide N- (4-Benzyl- 1 -piperazinyl) 1,1 -0 dimethylethyl] 3-methoxy-4- oxazolyl)phenyl] oxalamide4941 N- (Benzenesulfonyl) 1 q piperazinyl] 1, 1 -dimethylethyl] c,~JsMJJ 5 1 [3-methoxy-4-(5- 45N1 oxazolyl)phenyl] oxalamide 0 dimthyethl]-N'- [3-methoxy-4-(5- Ir NY&Nl-'0 0 1 oxazolyl)phenyl] oxalamide N5041 (Trifluoromethyl)phenyl 1 -I piperazinyl] -1,1-dimethylethyl] 5449 [3-methoxy-4-(5oxazolyl)phenyl]I oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] 1,1 -dimethyl- 2- [4-(2-methylphenyl)- 1- 0o 492 460 pip erazinyl] ethyl] oxalamide

S

Sees 0eOS

SS

5 S 0

S

.5 S 0 *S S 5*

S

S S

S.

5e5e

S

5.55 .5*

S

.555 5* 6 5* *5 [4-(2-Fluorophenyl)-1piperazinyl] -1,1-dimethylethyl] [3-methoxy-4-(5- 06 496 62 oxazolyl)phenyl] oxalamide N- [4-(4-Fluorophenyl)- 1- ,1 0 piperazinyl 1, 1-dimethylethyl] 4946 [3-methoxy-4-(5-4946 oxazolyl)phenyl]I oxalamide N- [3-Methoxcy-4-(5- 0~ o oxazolyl)phenyl]-N'-[2- [4-(2-0C%5846 methoxyphenyl) -1I -piperazinyl] 1, 1 -5046 dimethylethyl] oxalamide N- [3-Methoxy-4-(5- 3.

oxazolyl)phenyl]I-N'- 1-dimethyl-2- 54 464 kj (2-thiophenesulfonyl)-l 1-846 pip erazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5- o oxazolyl)phenyl] [1,1 -dimethyl-2- 0 r~ (2,4,6-trimethylbenzenesulfonyl) -58.46 1 -piperazinyl] ethyl] oxalamide N- [4-(4-Fluorobenzenesulfonyl)- A 1 -piperazinyl] -1,1-dimethylethyl] J560.1 466 [3-methoxy-4-(5oxazolyl)phenyl] oxalamide N- (Trifluoromethanesulfonyl) F~ I-piperazinyl] 1-dimethylethyl] 0 o-.a53446 [3-methoxy-4-(5- N 3 oxazolyl)phenyl)]I oxalamide N- 2- 4- (Isopropylsulfonyl) 1 piperazinyl] 1-dimethylethyl] 0 [3-methoxy-4-(5- 508.1 468 oxazolyl)phenyl) oxalamide [3-Methoxy-4-(5c 00,0r j oxazolyl)phenyl] [1,1-dimethyl-2- 00 568.1 469 [4-(styrylsulfonyl)- 1- 63 piperazinyl] ethyl] oxalamide N- [4-(Ethanesulfonyl)-1-

A

piperazinyl] -1,1-dimethylethyl] >rxJijo [3-methoxy-4- 494.1 470 oxazolyl )phenyl] oxalamide N-[3-Methoxy-4-(5oxazolyl)phenyl]-N'- [1,1-dimethyl-2- ~Q% [4-(propanesulfonyl)- 1- 508.1 471 piperazinyl] ethyl] oxalamide N- [4-(3-Chloropropanesulfonyl) 0 C 1 -piperazinyl 1, 1-dimethylethyl] -54.47 [3-methoxy-4-(5-54. 47 oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5-

\P

oxazolyl)phenyl] [1,1 -dimethyl-2- I i 56.1 47 [4-(o-toluenesulfonyl)-l 1-561 7 piperazinyll ethyl] oxalamide N- 4- Fluorobenzenesulfonyl) 1 -piperazinyl] 1, 1 -dimethylethyl] -N 1 56.47 [3-methoxy-4-(5-v56. 47 oxazolyl)phenyl] oxalamide N- [4-(2-Cyanobenzenesulfonyl)- I1-piperazinyl] 1, 1-dirnethylethyl] 0 [3-methoxy-4-(5- 567.1 475 oxazolyl)phenyl] oxalaniide N- [3-Methoxy-4-(5- o oxazolyl)phenyl] 2- 561.1 476 dimethyl-4-isoxazolylsulfonyl)-l 1-,56.

piperazinyll -1,1 -dimethylethyl] oxalamide N- [4-(5-Fluoro-2methylbenzenesulfonyl)- 1 piperazinyl] -1,1 -dimethylethyl] 64 [3-methoxy-4-(5- 574.1 477 oxazolyl)phenyl] oxalamide N- Difluorobenzenesulfonyl)- 1piperazinyl] -1,1-dimethylethyl] 578.1 478 [3-methoxy-4-(5oxazolyl)phenyl] oxalamide N- [3-Methoxcy-4-(5- 1 c 0 k)Q %)F oxazolyl)phenyl] 1,1 -dimethyl-2- 0 4. 7 (1-methyl- 1H-imidazole-4-54. 47 sulfonyl)-1piperazinyll ethyl] oxalamide N-

F

Difluorobenzenesulfonyl) -1-I57. 48 piperazinyl] -1,1-dimethylethyl] 57.-8 [3-methoxy-4-(5oxazolyl)phenyl] oxalamide N- Difluorobenzenesulfonyl) -1piperazinyl] -1,1 -dimethylethyll 578.1 481 [3-methoxy-4-(5oxazolyl)phenyl] oxalamide (Cyclohexylmethanesulfonyl)-1 56. 48 pip erazinyl 1- 1, 1 -dimethylethyl] 56.-8 [3-methoxy-4-(5oxazolyl)phenyl]I oxalamide N- [3-Methoxy-4-(5- l oxazolyl)phenyl] 1, 1 -dimethyl-2- 57. 8 [4-(2-phenylethanesulfonyl)- 1 -57. 48 pip erazinyl] ethyl] oxalamide 65 N- [3-Methoxy-4-(5- oxazolyl)phenyl] 0C. 4 oU dimethoxyphenyl)- 1-piperazinyl] 538 484 1, 1 -dimethylethyl] oxalamide N- [3-Methoxy-4-(5- o oxazolyl)phenyl] [1,1 -dimethyl-2- 0jNkN~~ [4-(4-methylphenyl)-1- 492 485 pip erazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5- 'N 00,> oxazolyl)phenyl] [1,1-dimethyl-2- oII [4-(2,4-dimethylphenyl)-1- 506 486 piperazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] 1 __c dimethoxyphenyl)-l1-piperazinyl] 16538 487 1, 1 -dimethyl ethyl] oxalamide N- (4-Cyclohexyl- 1 -piperazinyl) 1,1 -dimethylethyl] [3 -methoxy-4- 0 oxalamide 484.4 488 N- (Cyclohexylmethyl)- 1 piperazinyl] 1 dimethylethyl] 0 [3-methoxy-4-(5- 498.2 489 oxazolyl)phenyl]I oxalamide N- [4-(2-Methoxybenzyl)- 1piperazinyl] -1,1 -dimethylethyl] 522.1 490 [3-methoxy-4-(5oxazolyl)phenyl] oxalamide N- [4-(2-Hydroxybenzyl) 1

D

piperazinyl] 1, 1 -dimethylethyl] (~-T581 9 [3-methoxy-4-(5- f57 9 oxazolyl)phenyl] oxalamide 66 N- [3-Methoxy-4-(5oxazolyl)phenyl] 1, 1 -dimethyl-2- ~~Y (2-methylbenzyl)- 1 piperazinyl] ethyl] oxalamide N- [3-Methoxcy-4-(5oxazolyl)phenyl] 1,1 -dimethyl-2- [4-(2-thenyl)- 1piperazinyll ethyl] oxalamide N- [3-Methoxcy-4-(5oxazolyl)phenyll 1, 1 -dimethyl-2- (2(RS) -phenylpropyl)- 1 piperazinyl] ethyl] oxalamide N- [3-methoxcy-4-(5oxazolyl)phenyl] ,1-dimethyl-2- (4-pivaloyl- 1piperazinyl) ethyl]I oxalamide N- [4-(2-Furoyl)- 1 -piperazinyl] 1,1-dirnethylethyl] [3-methoxy-4- :(5-oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] [1,1 -dimethyl-2- [4-(2-thenoyl)- 1piperazinyl] ethyl] oxalaniide N- [3-Methoxy-4-(5- :oxazolyl) phenyl] 1, 1-dimethyl-2 [4-(3-thenoyl)- 1piperazinyl]I ethyl oxalamide N 2- 4 Cyclopentylacetyl) 1 piperazinyl] 1, 1 -dimethyl- ethyl] [3-methoxcy-4-(5oxazolyl)phenyl) ]oxalamide 4 67 N- (Cyclohexylcarbonyl) -1 piperazinylhl,ldimethylethyl] 0-1"' [3-methoxy-4-(5- 512.1 500 oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5- 0 oxazolyl)phenyl] [1,1-dimethyl-2- J_ ,_520.1 501 [4-(2-methylbenzoyl)- 1piperazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5- jli oxazolyl)phenyl] 1, 1 -dimethyl-2- 0-'0 [4-(4-methylbenzoyl)- 1 520.1 502 piperazinyl] ethyl] oxalamide N- (Cycloheptylcarbonyl) piperazinyl] 1, 1 -dimethylethyl] -N [3-methoxy-4-(5- 526.2 503 oxazolyl)phenyl] oxalamide N- [3-Methoxcy-4-(5oxazolyl)phenyl] 1, 1 -dimethyl-2- N-rY 1H-pyrazol-4-yl)carbonyl] (\f496.1 504 pip erazinyl] ethyl] oxalamide N- [4-(Cyclopentylcarbonyl)- 1 piperazinyl] 1,1 -dimethylethyl] [3-methoxy-4-(5- 40 0498.1 505 oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl]-N'-[1,1-Dimethyl- N 2- 1-methyl- 1H-pyrrol-2-50. 56 yl)carbonyl] -1piperazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl]-N'-[1,1-dimethyl-2- I 1,2,3-thiadiazol-4-yl)carbonyl] 514.1 507 1-pip erazinyl] -ethyl] oxalamide

S

S

S.

68 N- [4-(3-Fluorobenzoyl)- 1 piperazinyl] 1,1 -dimethylethyl] [3-methoxy-4- oxazolyl)phenyll oxalamide N- [4-(4-Fluorobenzoyl)- 1piperazinyl] 1,1 -dimethylethyl] [3-methoxy-4-(5oxazolyl)phenyl] oxalamide N- [4-(Cyclopropylcarbonyl)- 1piperazinyl] 1, 1 -dimethylethyl] [3-methoxy-4- oxazolyl)phenyll oxalamide N- [4-(2-Cyclohexylacetyl)- 1 piperazinyl] 1, 1 -dimethylethyl] [3-methoxy-4-(5oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] dimethylbutyryl) -1 -piperazinyl] 1,1 dimethylethyl] oxalamide N- [4-(3-Hydroxy-2,2dimethyipropionyl)-l1-piperazinyl] 1,1 -dimethylethyl] [3-methoxy-4- -oxazolyl) phenyl oxalamide [3-Methoxy-4-(5oxazolyl)phenyl] [1,1 -dimethyl-2- [4-(3-methyl-2-furoyl)- 1piperazinyl]I ethyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] -dimethyl-2- [4-(2-methyl-3-furoyl)- 1piperazinyl] ethyl] oxalamide 0 N.

69 N- [3-Methoxy-4-(5- oNC oxazolyl)phenyl] [1,1 -dimethyl-2- 1. 1 (5-methyl- 1H-pyrazol-3-51. 56 yl)carbonyl] -1pip erazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] 1 -dimethyl-2- ri [4-[(5-methyl-4- 511.1 517 isoxazolyl) carb onyl] 1 piperazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5oxazolyl) phenyl]I 1, 1 dimethyl -2 -r" [(5-methyl-3- 511.1 518 isoxazolyl) carb onyl -1 piperazinyl]I ethyl oxala mide N 2- 4- (4 -Amin oben zoyl) 1-

C'

piperazinylll-1,1-dimethylethyl]-N'- I- [3-methoxcy-4-(5- v521.1 519 oxazolyl)phenyl] oxalamide N-[2-[4-(2-Hydroxybenzoyl)-1piperazinyl] -1,1 -dimethylethyl] 1_ 2 2 [3-methoxy-4-(5-52. oxazolyl)phenyl]I oxalamide N- [2-[(4-(4-Hydroxcybenzoyl)- 1- piperazinyl] 1,1 -dimethylethyl] j'''52.51 [3-methoxy-4-(5- 52. 51 oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl 1, 1 -dimethyl- 2- 0j54. 2 (2,5-dimethyl-2H-pyrazol-3- 52. 52 yl)carbonyl-1pip erazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl]-N'-II1,1-dimethyl-2- [4-(3-methyl-2-thenoyl)- 1piperazinyl] ethyl] oxalamide N-[3-Methoxy-4-(5- o~a oxazolyl)phenyl] [1,1 -dimethyl-2- I [4-(4-methyl-2-thenoyl)- 1pip erazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5- c oxazolyl)phenyl] 1-dimethyl-2 [(2,2,3,3-tetramethyl- 1cyclopropyl)carbonyl] -1piperazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5-LA oxazolyl)phenyl] [1,1 -dimethyl-2- i [(4-methyl-1,2,3-thiadiazol-5yl)carbonyl] -1piperazinyl] ethyl] oxalamide 2- (3 -Cyanobenzoyl) 1 [3-methoxy-4-(5- *.:oxazolyl)phenyl] oxalamide N- [(Bicyclo[4.2.0] octa- 1(6),2,4-trien-7-yl)carbonyl] 0 piperazinyl] -1,1-dim ethylethyl] [3-methoxy-4-(5oxazolyl)phenyl] oxalamide N- 2- 4- (3 -Hydroxybenzoyl) 1

NO~

*piperazinyl 1 -dimethylethyl]I [3-methoxy-4-(5oxazolyl)phenyl] oxalamide 71 N- (2-Ethylbutyl)- 1 -o C% piperazinyl] 1, 1 -dimethylethyl] I8. 3 [3-methoxy-4-(5-48. 53 oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5- 0 1 oxazolyl)phenyl] 1, 1 -dimethyl-2-502 53 (2-phenylethyl)- 1 -50. 53 pip erazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] 1-dimethyl-2- [3-(methylthio)propyl] 490.1 532 piperazinyl] ethyl] oxalamide N- [2-[4-(2,6-Difluorobenzyl)- 1piperazinyl 1-1,1-dimethylethyl] 52.53 [3-methoxy-4-(5-52. 53 oxazolyl)phenyl] oxalamide N- [4-(3-Furfuryl)- I-piperazinyl] -o 1,1 -dimethylethyl] [3-methoxy-4- Y7 (5-oxazolyl)phenyl] oxalamide 482.1 534 N- [(2-Benzofuranyl)methyl] o HP 73"J 1 -piperazinyl] -1,1-dimethylethyll -53.55 [3-methoxy-4-(5-N oxazolyl)phenyl) ]oxalamide N-[2-[4-(2-Cyanobenzyl)-1piperazinyl] -1,1-dimethylethyl] 51.1 53 [3-methoxy-4-(5-51. 53 oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5-0 oxazolyl)phenyl] [4-(3,3-48.53 dimethylbutyl) -1-piperazinyl] -1,1-48. 53 dimethylethyl]I oxalamide 4 a 72 N- [3-Methoxy-4-(5- oxazolyl)phenyl] [1,1-dimethyl-2-54.53 [(2-quinolinyl)methyl] -1-54. 53 piperazinyl] ethyl] oxalamide tert-Butyl 4- [2-[[3-methoxy-4- (5-0 l oxazolyl)anilino] oxalyl] amino] -2methyipropyl] -1I -piperazineacetate 516 539 4- [2-[[[3-Methoxy-4-(5- o r-Xi oxazolyl) anilino] oxalyl] amino] 460 54 methyipropyl] -1-piperazineacetic4650 acid trifluoroacetate (1:1) N- [2-[4-(Cyclopropylmethyl)-- 1piperazinyl] -1,1-dimethylethyl] N4551 [3-methoxy-4-(5-N4551 oxazolyl)phenyl] oxalamide tert-Butyl 4- 3-methoxy-4oxalyl] amino] -2methyipropyl] 1-piperazinyl] 578 651 benzoate 4- [[3-Methoxy-4-(5-oxazolyl) O anilino] oxalyl] amino]

N-

methyipropyl] 1-piperazinyllbenzoic 0 ~H 522 652 acid trifluoroacetate 1:1) In particular preferred compounds of formula are also those according to the general formula 73 0

XV'

wherein R R R R 6

,R',R

9

,R'

0 and R' are defined as above R 22 R 23 R 24 R 25 and R 26 are H or lower alkyl R 27 is alkyl, aryl or heterocyclyl, alkoxy, aryloxy, heterocyclyl oxy Particularly preferred compounds of formula (XVI) are those wherein Ris methoxy, R R R R 9

R

10

,R'

3 AR, R 23

R

24

R

2 and R 2 are hydrogen.

Examples of such compounds are listed in table lh below: Name Structure ME(ES) Ex No Phenyl oxazolyl) anilino] oxalyll amino] benzyl] 48741 carbamnate

N

IF 489 [3-methoxy-4-(5- 416 74 oxazolyl)phenyl] oxalamide Chlorobenzamido)methyll phenyl] I5041 0 00 N[3-methoxy-4-(5- 0 ,Or j 501. 418 oxazolyl)phenyl] oxalamide \l Dmethoxybenzamido)methyl] phenyl] 7 CN -N'-[3-methoxy-4-(5- oo 53.41 oxazolyl)phenyl] oxalamide Cyantobenzamido)methylphenyl]'- 0 9. 2 -[3-methoxy-4-(5- y C'y 3. 1 oxazolyl)phenyl] oxalamide In particular preferred compounds of formula are also those according to the general formula 0 @000 0*0* 00 0 000 0 0 0 *0 0

S

00 0 0* 000000 0 0000 0 *500 00 0 0 0 00 0000 0 0000 *000 0 *000 *0 0 0* 0 00

XVII

5wherein R 2 R 3 R 5 R 6 R' and W' 0 are defined as above

R'

1 and R 13 is H or lower alkyl and 75 R 1 2 is heterocyclyl, aryl or lower cycloalkyl.

Particularly preferred compounds of formula (XVII) are those wherein R2 3 312 Ris methoxy, R R R R 1 and R' are hydrogen and wherein R is optionally substituted phenyl or 21 wherein R 2 1 is as above.

S

0SSO 0* 0O S SoS 0 *05555 *S SO S S 0 @0 05

S

50555* 0 50(0

C

5055 5* 9 *9

S.

0500

S

*005 000S

S

0~*S @0 0 00 50 Examples of such compounds are listed in table I i below: Name Structure MS(ES) Ex No N-[3-Methoxy-4-(4- N oxazolyl)phenyl]-N'-[1,1-dimethyl- 0 47 428K 2-(4-phenyl- 1-4742 piperazinyl) ethyl] oxalamide N- (4-Benzyloxyphenyl)- 1,1 dimethylethyl] [3-methoxy-4- I (4-oxazolyl)phenyl] oxalamide 500 429 76 N- [2-(4-Hydroxyphenyl)- 1,1- g01 ii dimethylethyl] [3-methoxy-4- 0 CH (4-oxazolyl)phenyl] oxalamide \-N410 430 N-[3-Methoxy-4-(4oxazolyl)phenyl] I l methoxyphenyl)- 1-piperazinyl]- 50-3 1,1 -dimethylethyl] oxalamide N- [3-Methoxy-4-(2-methyl-4oxazolyl)-phenyl] (4methoxyphenyl)-1-piperazinyl]- rN522.4 432 1,1 -dimethylethyl] oxalamide The compounds of formula (IV) and (VIII) which are intermediates in the foregoing processes are novel and are also provided by the present invention.

Reaction Scheme A R3+Me O)0 (CI Coupling

NR

7 H0 Hydrolysis iCoupling, and ii, Optional modification NR 4

R

8 HNR 4 R 8

(V

-77- With reference to Reaction Scheme A, the first step comprises the coupling of a compound O of formula (II) with an activated oxalyl derivative, such as methyl chlorooxoacetate, to give a compound of formula (III). The reaction may be carried out in a conventional manner, suitably in an organic solvent which is inert under the reaction conditions and in the presence of an organic base at about 0°C to about room temperature. Suitable solvents include halogenated hydrocarbons, e.g. dichloromethane. Pyridine and tri(lower alkyl)amines, e.g. triethylamine, can be mentioned as examples of suitable organic bases which can be used.

Subsequent hydrolysis of the compound of formula (III) to give the acid compound of formula (IV) may be carried out by treatment with a solution of an alkali metal hydroxide, such as sodium hydroxide, in a suitable solvent system, such as aqueous methanol.

Alternatively, a compound of formula (II) may be coupled with tert.butyl chlorooxoacetate, followed by treatment with acid to remove the tert.butyl group, to give a compound of formula (IV).

The compound of formula (IV) is then coupled with an amine compound of formula (V) using standard peptide coupling reagents, such as hydroxybenzotriazole in the presence of 1- 20 ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, to give the oxamide h compound of formula After this coupling step, the R groups of the resulting compound may be further modified by techniques known in the art, for example, functional groups may be altered, and/or *25 connected to further groups Reaction Scheme B -78-

O

0+ II Coupling MeO 1

R

o 7 0

R

3 0 OMe

R

5

O

Hydrolysis

R

9 i, Coupling, and R N/ R 2 ii, Optional N R 2 R1 0 R3 Modification RO O R N,>NR HNF 4

R

8 R H (IX) R 5

R

7 (Vll) R 6 R Referring to Reaction Scheme B, the first step comprises the coupling of a compound of formula (VI) with an activated oxalyl derivative, such as methyl chlorooxoacetate, to give a compound of formula (VII). The reaction is carried out in the manner described above for the formation of a compound of formula (III) from a compound of formula (II).

10 Subsequent hydrolysis of the compound of formula (VII) to give the acid compound of formula (VIII) is then carried out as described above for the hydrolysis of a compound of formula (III).

Alternatively, a compound of formula (VI) may be coupled with tert.butyl chlorooxoacetate, followed by treatment with acid to remove the tert.butyl group, to give a compound of formula (VIII).

The compound of formula (VIII) is then coupled with an amine compound of formula (V) to give the oxamide compound of formula under the conditions described above for the coupling of a compound of formula (IV) with a compound of formula -79- After this coupling step, the R groups of the resulting compound may be further modified by techniques known in the art, for example, functional groups may be altered, and/or connected to further groups Reaction Scheme C i, Coupling, and ii, Optional 8 Modification R 1 NR4R 8

NR

4

R

8 10 Alternatively, compounds of formula are made by the coupling of a compound of formula (II) with an oxalamic acid compound of formula using standard peptide coupling reagents, such as hydroxybenzotriazole in the presence of 1-ethyl-3-(3dimethylaminopropyl) carbodiimide hydrochloride, to give the oxamide compound of formula After this coupling step, the R groups of the resulting compound may be further modified by techniques known in the art, for example, functional groups may be altered, and/or connected to further groups As mentioned above, the compounds of formula and salts thereof are inhibitors of IMPDH enzyme both in vitro and in vivo, and can be used in the control or prevention of IMPDH mediated conditions or diseases.

IMPDH activity can be assayed using an adaptation of the method reported by Carr [S.

Carr et al., J. Biol. Chem. 268, p.

2 72 8 6 (1993)], the disclosure of which is herein incorporated by reference. IMPDH activity was measured spectrophotometrically, by monitoring the increase in absorbance at 340nm due to the formation of NADH (E340 is 6220 M-l cm-1) from the reduction of NAD. The IMPDH reaction mixture contained 0.1M Tris pH8.0, 0.1M KC1, 1mM DTT, 3mM EDTA, 100mM IMP and 100mM NAD.

The reaction was initiated by the addition of IMPDH (human type II) to a final concentration in the assay of between InM and 5nM with respect to the IMPDH tetramer.

The initial rate is measured by following the linear increase in absorbance at 340nm at 370 C for 45 minutes. The reading was conducted using a Spectromax 190 (Molecular Devices) spectrophotometer in a 96 well plate format with a final reaction volume of 200pl.

For inhibitor assay analysis, the compound is dissolved in DMSO to a final concentration of 10mM and added to the initial reaction mixture as 5gl to give final DMSO concentration of The enzyme reaction is initiated by the addition of IMPDH and the initial rates measured as above. IC 50 determinations are made by measuring the initial rates in the presence of 10 concentrations of inhibitor and fitting the data using the 4 parameter curve fit from the Softmax pro software (Molecular Devices).

*o Preferred compounds of the invention tested in the above assay have an ICso value up to 500nM i.e. 0.5 gM.

Specific examples of IC 50 values for preferred compounds of formula are set out below in Table 2: o. Table 2 Compound of Formula IC 50 81 (jiM) tert-Butyl [3-[[[3-methoxy-4-(5- 0.036 oxazolyl) o c anilino] oxalyl] amino] benzyl] carbamnate 0 N-tert-Butyl-N'- [3-methoxy-4-(5- 0.037 oxazolyl)phenylloxalamide [3-Methoxy-4- (5-oxazolyl)anilino] 0.044 oxalyl] amino] benzyl] carbamic acid tetrahydro-3 -furyl ester yolN- [3-(Benzamidomethyl)phenyl] 0.013 6- :)ymethoxy-4- oxazolyl)phenyl] oxalamide Cu Isopropyl [[3-methoxy-4-(5- 0.033 0 oxazolyl) anilino] oxalyl] amino] benzyl] carbamnate N-[3-Methoxy-4-(5-oxazolyl)phenyl]- 0.03 0 -methyl- I -phenylethyl)oxalamide M0 N-(1,1-Dimethylpropyl)-N'- 0.031

HC

0 0N oxazolyl)phenyl] oxalamide H3 CH N N- [3-Methoxy-4-(5-oxazolyl)phenyl] 0.034 0 HC 0 H,C 0,oxazolyl)phenylloxalamide 82 N' N-(2-Hydroxy- 1,1-dimethylethyl)-N'- 0.072 I [3-methoxy-4-(5- 0 C %oxazolyl)phenylloxalamide N' l,1-Dimethyl-2-phenylethyl)-N'- 0.0 oxazolyl)phenyl]I oxalamide Phenyl (5-oxazolyl)anilino] 0.011 2' oxalyl] amino] benzyl] carbamnate N- [3-Methoxy-4- (5-oxazolyl)phenyl] 0.035 )~fN N'-[13-[(phenylcarbamoyl)methyl] phenyl] oxalamide 0 tert-Butyl [2-[[[3-methoxcy-4-(5- 0.075 I ~o o cs oxazolyl)anilino] oxalyl] amino] -2- N methyipropyl] carbamnate 0 N, N-(2-Amino- 1, 1-dimethylethyl) 0.097 F N oxazolyl)phenyl] oxalamide trifluoro acetate (1:1) N- [3-Methoxy-4- (5-oxazolyl)phenyl] 0.010 [1,1 -dimethyl-2-(4-nitrophenyl) ethyl] oxalamide F N- 3- (Aminomethyl)phenyl] 0.233 I oxazolyl)phenylloxalamide trifluoroacetate (1:1) Methyl [3-[[[3-methoxy-4-(5- 0.121 o oxazolyl)anilino] oxalyl] amino] benzyl] ca rbamnate -83- SN- [3-Methoxy-4-(5-oxazolyl)phenyl]- 0.277 o N'-(3-pyridyl)oxalamide 0.125 [(Benzenesulfonamido)methyl] phenyl] LI N'-[3-methoxy-4-(5oxazolyl)phenyl] oxalamide cX CH, N-(2-Dimethylamino-1,1- 0.17 HC N o Io dimethylethyl)-N'-[3-methoxy-4-(5oxazolyl)phenyl] oxalamide hydrochloride (1:1) o N-[3-Methoxy-4-(5-oxazolyl)phenyl]- 0.199 0 0 [1-methyl-1xN c (methylcarbamoyl) ethyl] oxalamide N-tert-Butyl-N'-[3-chloro-4-(5- 0.169 o oxazolyl)phenyl]oxalamide HK0 N N-tert-Butyl-N'-[3-methoxy-4-(4- 0.46 0 oxazolyl)phenyl] oxalamide Compounds of formula which are acidic can form pharmaceutically acceptable salts with bases such as alkali metal hydroxides, e.g. sodium hydroxide and potassium hydroxide; alkaline earth metal hydroxides, e.g. calcium hydroxide, barium hydroxide and magnesium hydroxide, and the like; with organic bases e.g. N-ethyl piperidine, dibenzylamine, and the like. Those compounds of formula which are basic can form pharmaceutically acceptable salts with inorganic acids, e.g. with hydrohalic acids such as hydrochloric acid and hydrobromic acid, sulphuric acid, nitric acid and phosphoric acid, and the like, and with organic acids, e.g. with acetic acid, tartaric acid, succinic acid, fumaric acid, maleic acid, malic acid, salicylic acid, citric acid, methanesulphonic acid and p-toluene sulphonic acid, and the like. The formation and isolation of such salts can be carried out according to methods known in the art.

-84- W The oxamide derivatives provided by the present invention the compounds of formula and their pharmaceutically acceptable salts), can be used as medicaments, for example in the form of pharmaceutical preparations. The pharmaceutical preparations can be administered enterally, such as orally, in the form of tablets, coated tablets, drag~es, hard and soft gelatine capsules, solutions, emulsions or suspensions, or nasally, e.g. in the form of nasal sprays. They can also be administered rectally, e.g. in the form of suppositories, or parenterally, intramuscularly, intravenously, or subcutaneously), for example, in the form of injection solutions.

For the manufacture of pharmaceutical preparations the oxamide derivatives can be formulated with therapeutically inert, inorganic or organic carriers. Lactose, corn starch or derivatives thereof, talc, stearic acid or its salts can be used, for example, as such carriers for tablets, coated tablets, drag~es and hard gelatine capsules. Suitable carriers for soft gelatine capsules are, for example, vegetable oils, waxes, fats, semi-solid and liquid polyols and the like. Depending on the nature of the active ingredient no carriers are, however, generally required in the case of soft gelatine capsules. Suitable carriers for the manufacture of solutions and syrups are, for example, water, polyols, sucrose, saccharose, invert sugar, glucose and the like. Suitable carriers for the manufacture of injection solutions are, for 20 example, water, saline, alcohols, polyols, glycerine, vegetable oils and the like. Natural or hardened oils, waxes, fats, semi-liquid or liquid polyols and the like are suitable carriers for the manufacture of suppositories. The pharmaceutical preparations of the present invention may also be provided as sustained release formulations or other appropriate formulations.

ee The pharmaceutical preparations can also contain preservatives, solubilizers, stabilizers, wetting agents, emulsifiers, sweeteners, colourants, flavourants, salts for adjustment of the osmotic pressure, buffers, masking agents or antioxidants. They may also contain other therapeutically active substances, such as an immunosuppressant, a chemotherapeutic agent, an anti-viral agent, an antibiotic, an anti-parasitic agent, an anti-fungal agent, an anti-inflammatory agent and/or an anti-vascular hyperproliferation agent. A preferred agent that may be used with the compounds of the present invention is interferon or derivatives thereof, such as conjugates with polyethylene glycol.

M Medicaments containing compounds of formula or salts thereof and a therapeutically acceptable carrier, as well as a process for the manufacture of such medicaments are also objects of the present invention. This process comprises bringing a compound of formula or a pharmaceutically acceptable salt thereof into a galenical administration form together with a therapeutically inert carrier material and, if desired, one or more additional therapeutically active substances.

A further object of the invention comprises the use of the oxamide derivatives provided by the invention in the treatment of an immune mediated condition or disease, a viral disease, a bacterial disease, a parasitic disease, inflammation, an inflammatory disease, a hyperproliferative vascular disease, a tumour, or cancer. The dosage can vary within wide limits and will, of course, be adjusted to the individual requirements in each particular case. Dosage levels of between about 0.01 and about 100 mg/kg body weight per day (preferably 0.5 75 mg/kg/day) in monotherapy and/or in combination therapy are preferred, administered from about 1 -5 times per day. The active ingredient may be combined with a carrier material. A typical preparation will contain from about 5% active compound (preferably from about 20% 80% active compound). The daily *dosage can be administered as a single dosage or in divided dosages.

The compounds and compositions of the present invention may be for use in monotherapy and/or combination therapy, i.e. the treatment may be in conjunction with the administration of one or more additional therapeutically active substance(s). When the treatment is combination therapy, such adminstration may be concurrent or sequential with respect to that of the oxamide derivatives of the present invention. Thus, concurrent administration, as used herein, includes administration of the agents in conjunction or combination, together, or before or after each other.

It will be understood that references herein to treatment extend to prophylaxis as well as to treatment of existing conditions. Treatment of a disease or condition, as used herein, also includes preventing, inhibiting, regressing, reversing, alleviating or relieving the disease or condition, or the clinical symptoms thereof. The term "subject" as used herein refers to animals, including humans and other mammals.

The following Examples illustrate the present invention.

-86- With regard to the starting materials that are known compounds some of these may be purchased from commercial suppliers. Other starting materials that are known and their analogues can be prepared by methods well known in the art. Examples of compounds available from commercial suppliers, and citations to the synthesis of other compounds and their analogues are provided in the following: Compounds of formula (II) and the compounds of formula (VI) are obtained from commercial suppliers 4-(5-oxazolyl)aniline, Maybridge catalogue number DFP 00120), or prepared by adaptation of the methods disclosed in published patent application WO 974002, or prepared by adaptation of the methods provided in Palacz et al., FEBS Lett., 1984, 176(2), 365-370.

The compounds of formula are obtained from commercial suppliers tert-butylamine, Aldrich catalogue number B8,920-5; Cumylamine, TCl-US catalogue number C1293), or prepared by adaptation of the methods provided in Kazuo Achiwa et al., Chem.Pharm.Bull., 1998,46(4), 697-670.

S

The compounds of formula are prepared by adaptation of the methods provided in Minisci et al., J. Org. Chem., 1995, 60(17), 5430-5433.

Examples of commercially available reagents include those used in Examples 7, 10 and 11, (2methoxy-4-nitrobenzoic acid, Aldrich catalogue number 42,291-6; tert-butylacetic acid, Aldrich catalogue number B8,840-3; and p-tolualdehyde, Aldrich catalogue number T3,560-2, respectively).

Where indicated, the NMR spectra were recorded on a Bruker DRX 400 MHz spectrometer with the probe temperature set at 300 K.

Where indicated by mass spectra were recorded under electron impact conditions on a THERMOQUEST MAT95 S with a source temperature of 200'C.

Other mass spectra were recorded under electrospray ionisation spectra (ESI) conditions, on one of the following machines: 87 a) THERMOQUEST SSQ 7000 [Solvent 0.085% TFA in 90% Acetonitrile/water; flow rate 100 microliters/minute; capillary 250'C; spray voltage 5KV; sheath gas 80 psi], or b) LC-MS system (liquid chromatograph coupled to mass spectrum) THERMOQUEST TSQ 7000 ELECTROSPRAY or MICROMASS PLATFORM ELECTROSPRAY [Solvent 50.1% TFA in water or 0.085% TFA in 90% acetonitrile/ water or 0.085% TFA in acetonitrile].

Unless otherwise indicated, the mass spectroscopy values recorded in the MS(ES) column refer to values, apart from the ones shown as (M t

;EI).

Example 1 N-Tert-butvl-N'- [3-methoxcv-4- (5-oxazolvl )tDhenvll oxalamide Me

N.NH

2

CIOCCO

2 Me EtN!

'~NHOCCO

2 Me Me SNHOCOONF(Bu N~NHOCC0 2

H

t-BuNH 2

EDAC

HOAt Example 1, Alternative synthesis

HO

2 CCONq t Bu

EDAC-

HOAt

NH

2 'NHOCCONH t Bu -88- A solution of 26 mg (0.1 mmol) of N-[3-methoxy-4-(5-oxazolyl)phenyl]oxalamic acid, 15 mg (0.2 mmol) of tertiary butylamine, 28 mg (0.15 mmol) of 1-(3dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 15 mg (0.11 mmol) of 1hydroxy-7-azabenzotriazole in 1 ml of dimethylformamide was stirred at room temperature for 4 hours then diluted with ethyl acetate and washed with 2M hydrochloric acid, saturated sodium bicarbonate and water. The resulting solution was dried over magnesium sulphate and evaporated to dryness. The residue was triturated with diethyl ether/petrol and collected by filtration to give 11 mg of N-tert-butyl-N'-[3-methoxy- 4-(5-oxazolyl)phenyl]oxalamide as a white solid. MS: m/e 318.0 [M+H] The starting material was prepared as follows: i) 5.7 g (30 mmol) of 3-methoxy-4-(5-oxazolyl)aniline and 3.33 g (33 mmol) of triethylamine were dissolved in 50 ml of dichloromethane and the solution was cooled to 0 0 C. A solution of 3.86 g (31.5 mmol) of methyl oxalyl chloride in 10ml of dichloromethane was added dropwise and the resulting mixture was stirred for 1 hour then washed with 2M hydrochloric acid. The precipitated solid was collected by filtration and washed with dichloromethane and water to give 6.2 of methyl N-[3-methoxy-4-(5oxazolyl)phenyl]oxalamate as a yellow solid. 'H NMR (400 MHz, DMSO-d 6 8: 3.88 3.94 7.48 7.58 (1H,dd), 7.65 7.68 8.39 10.92 (1H,s).

*o ii) 6.2 g (22.46 mmol) of methyl N-[3-methoxy-4-(5-oxazolyl)phenyl]oxalamate and 1.2 g (30 mmol) of sodium hydroxide were refluxed in 240 ml of methanol/water for 2 hours then cooled, filtered and acidified with 2M hydrochloric acid. The precipitated solid was collected by filtration and washed with water, acetone and diethyl ether to give 5.1 g of N-[3-methoxy-4-(5-oxazolyl)phenyl]oxalamic acid as a pale yellow solid. MS: m/e 262.9 -89- Alternatively N-tert-butyl-N'- [3-methoxy-4-(5-oxazolyl)phenyl]oxalamide can be prepared as follows: A solution of 95 mg (0.5 mmol) of 3-methoxy-4-(5-oxazolyl)aniline, 73 mg (0.5 mmol) of N-tert-butyloxalamic acid, 134 mg (0.7 mmol) of 1-(3-dimethylaminopropyl)-3ethylcarbodiimide hydrochloride and 75 mg (0.55 mmol) of 1-hydroxy-7-azabenzotriazole in 4 ml of dichloromethane was stirred a room temperature for 18 hours. The resulting mixture was washed with 2M hydrochloric acid and saturated sodium bicarbonate, dried over magnesium sulphate and evaporated to dryness. The residue was triturated with petrol and collected by filtration to give 128 mg of N-tert-butyl-N'-[3-methoxy-4-(5oxazolyl)phenyl]oxalamide as a pale yellow solid. MS: 318 Example 2 Tert-butyl F [3-methoxy-4-(5-oxazolyl)anilinol oxalyl] aminol benzyll carbamate NHBoc

NO

Me MeEDAC S+ HOAt

NHOCCO

2 H NH 2 N OMe NHBoc .i")OO~eNr S.i

NHOCCON

A mixture of 2.04 g (7.79 mmol) of N-(3-methoxy-4-(5-oxazolyl)phenyl]oxalamic acid, prepared as described above in Example 1 above, 1.9 g (8.56 mmol) of tert-butyl (3aminobenzyl)carbamate, 1.8 g (9.4 mmol) of 1-(3-dimethylaminopropyl)-3ethylcarbodiimide hydrochloride and 1.3 g (9.6 mmol) of 1-hydroxy-7-azabenzotriazole in ml of dimethylformamide was stirred for 20 hours at room temperature. The resulting 90 precipitate was collected by filtration and washed with dichloromethane to give 1.8 g of tert-butyl 3- [3 -methoxy-4- 5-oxazolyl)anilino] oxalyl] amino]I benzyl] carbamnate as a white solid. MS: m/e 466 Example 3 N- (Aminomethyiphenyl] r 3-methoxcy-4-(5-oxazolyl)phenyl] oxalamide trifluoroacetate 0NHBoc

TFA

Me

NH

2

NHOCCONH

.TFA

15 mg (0.032 mmol) of tert-butyl [[3-methoxy-4-(5oxazolyl) anilino] oxalyl] amino] benzyl] carbamnate, prepared as described in Example 2 above, were dissolved in 1 ml of dichloromethane and 1 ml of trifluoroacetic acid at room temperature for 5 minutes. The solution was evaporated to dryness, the residue triturated with diethyl ether and collected by filtration to give 11 mg of N- [3-(aminomethylphenyl] N'-[3-methoxy-4-(5-oxazolyl)phenyl]oxalamide trifluoroacetate as a white solid. MS: m/e 408 [M-iH+MeCN]+.

Example 4 -91- N-[3-(Benzamidomethyl)phenyll-N'-[3-methoxy-4-(5-oxazolyl)phenyll oxalamide

.NH

PhCOCI Et 3

N

.TFA

NHOCPh 29 mg (0.21 mmol) of benzoyl chloride were added to a solution of 100 mg (0.21 mmol) of N-[3-(aminomethyl)phenyl]-N'- [3-methoxy-4-(5-oxazolyl)phenyl] oxalamide trifluoroacetate, prepared as described in Example 3 above, and 46 mg (0.46 mmol) of triethylamine in a mixture of 2 ml of dimethylformamide and 5 ml of 10 dichloromethane, and stirred at room temperature for 18 hours. The solution was washed with 2M hydrochloric acid and saturated sodium bicarbonate then dried over magnesium sulphate and evaporated to dryness. The residue was chromatographed on silica gel using ethyl acetate/petrol for the elution. After trituration with diethyl ether there was obtained 45 mg of N-[3-(benzamidomethyl)phenyl]-N'-[3-methoxy-4-(5- 15 oxazolyl)phenyl]oxalamide as a white solid. MS: m/e 471.0 Example 92 N- [3-f (Benzenesulphonamido)methyll phenyl [3-methoxcy-4-( phenyll oxalamide

NH

2 PhSO 2

CI

Et 3

N

.TFA

In an analogous manner to that described in Example 4 but replacing benzoyl chloride with phenylsulphonyl chloride there was obtained N- [3- [(benzenesulphonamido) methyl] phenyl] [3-methoxy-4- (5-oxazolyl)phenyl] oxalamide as a white solid. MS: m/e 507 Example 6 *see Methyl [F3-methoxv-4- (5-oxazolyv)anilinol oxazolvH aminobenzyl 1carbamate acqrvle

EI

3

N

-N 0N1-cQDi

.TFA

93 In an analogous manner to that described in Example 4 but replacing benzoyl chloride with methyl chloroformate there was obtained methyl [3-methoxy-4-(5oxazolyl)anilinol oxalyll amino] benzyl] carbamnate as a white solid. MS: m/e 425 [M+H] t Example 7 N-Tert-butyl-N'- r3-metho~c-4-(4-oxazolyl)p2henyl1 oxalamide

NO

2 OMe C0 2

H

Me HNMe.HQ~i

EDAC

NO

2 'NOMe CONOMe Me

NH

2 SnCI 2 'NOMe CONMe H02CCONH tBu

EDAC

NHOCCONH t

BU

'NOMe CONOMe Me NHOCCONH t Bu MeMgBr

I

'NOMe

OCH

3 NHOCCONH t Bu

PTMAT

'NOMe

OCH

2 Br IHOCCONH t Bu

HCOONH

4

HCOOH

-94- A mixture of 371 mg (1 mmol) of N-[4-(bromoacetyl)-3-methoxyphenyl]-N'-tertbutyloxalamide and 315 mg (5 mmol) of ammonium formate was refluxed in 10 ml of formic acid for 4 hours then cooled and evaporated to dryness. The residue was dissolved in ethyl acetate, washed with 2M sodium hydroxide and dried over magnesium sulphate.

The solution was evaporated to dryness and the residue chromatographed on silica gel using ethyl acetate/petrol (7:18) for the elution. There was obtained after trituration with diethyl ether/petrol 65 mg of N-tert-butyl-N'-[3-methoxy-4-(4oxazolyl)phenyl]oxalamide as a white solid. MS: m/e 318 [M+H] t The starting material was prepared as follows: i) A mixture of 3.94 g (20 mmol) of 2-methoxy-4-nitrobenzoic acid, 3.9 g (40 mmol) of N,O-dimethylhydroxylamine hydrochloride, 5.73 g (29.92 mmol) of 1-(3dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 3.37 g (22 mmol) of 1hydroxybenzotriazole hydrate and 5.06 g (44 mmol) of N-ethylmorpholine in 50 ml of dichloromethane was stirred at room temperature for 3 hours then washed with 2M hydrochloric acid and saturated bicarbonate. The resulting solution was dried over 2 magnesium sulphate, evaporated to dryness and the residue triturated with diethyl ether and collected by filtration to give 3.95 g of N,O-dimethyl 2-methoxy-4nitrobenzohydroxamate as a white solid. 'H NMR (400 MHz, CDC13) 6: 3.37 3.48 3.97 7.45 7.80 7.91 (1H,dd).

ii) A mixture of 1.2 g (5 mmol) of N,O-dimethyl 2-methoxy-4nitrobenzohydroxamate and 4.75 g (25 mmol) of tin(II) chloride in 40 ml of ethanol was heated at 80 0 C for 30 minutes then cooled and evaporated to dryness. The residue was dissolved in dichloromethane, washed with 2M sodium hydroxide and the organic phase dried over magnesium sulphate and evaporated to dryness to give 960 mg of N,O-dimethyl 4-amino-2-methoxybenzohydroxamate as an off-white solid. 'H NMR (400 MHz, CDC1 3 8: 3.25 3.62 3.79 6.22 6.28 (1H,dd), 7.09 (1H,d).

iii) A mixture of 700 mg (3.33 mmol) of N,O-dimethyl 4-amino-2methoxybenzohydroxamate, 483 mg (3.33 mmol) of N-tert-butyloxalamic acid, 600 mg (3.92 mmol) of 1-hydroxybenzotriazole hydrate and 960 mg (5.01 mmol) of 1-(3dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in 15 ml of dichloromethane was stirred at room temperature for 3 hours then washed with 2M hydrochloric acid and saturated sodium bicarbonate. The organic phase was dried over magnesium sulphate, evaporated to dryness and the residue chromatographed on silica gel using ethyl acetate/petrol for the elution to give 960mg of N,O-dimethyl 4-[[(tertbutylamino)oxalyl] amino]-2-methoxybenzohydroxamate as a white solid. 'H NMR (400 MHz, CDC 3 6: 1.46 3.25-3.4 3.45-3.65 3.89 7.08 (1H,dd), 7.29 7.44 7.53 9.40 (1H,s).

iv) 3.1 ml (4.34 mmol) of 1.4M methylmagnesium bromide in tetrahydrofuran were added in portions over 1 hour to a solution of 337 mg (1 mmol) of N,O-dimethyl 4- [(tertbutylamino)oxalyl]amino]-2-methoxybenzohydroxamate in 10 ml of anhydrous tetrahydrofuran. The resulting solution was diluted with diethyl ether and washed with 2M hydrochloric acid. The organic phase was dried over magnesium sulphate, evaporated to dryness and the residue chromatographed on silica gel using ethyl acetate/petrol (3:7) for the elution to give 255 mg of N-(4-acetyl-3-methoxyphenyl)-N'-tert-butyloxalamide as 20 a white solid. 'H NMR (400 MHz, CDCl 3 8: 1.45 2.61 3.96 7.03 (1H,dd), 7.43 7.64 7.82 9.47 (1H,s).

v) 320 mg (0.85 mmol) of phenyltrimethylammonium tribromide were added in portions over 10 minutes to a stirred solution of 247 mg (0.85 mmol) of N-(4-acetyl-3- 25 methoxyphenyl)-N'-tert-butyloxalamide in 5 ml of anhydrous tetrahydrofuran. After

S.

15 minutes a further 100 mg (0.26 mmol) of phenyltrimethylammonium tribromide were added. The resulting suspension was diluted with diethyl ether, washed with water and the organic phase was dried over magnesium sulphate. Evaporation gave a gum which was chromatographed on silica gel using firstly 0.5% methanol in dichloromethane then 1% methanol in dichloromethane for the elution. The product was dissolved in diethyl ether/petrol and the resulting crystals were collected by filtration to give 135 mg of N- [4-(bromoacetyl)-3-methoxyphenyl]-N'-tert-butyloxalamide as a white solid. 'H NMR (400 MHz, CDC1 3 1.44 3.99 4.61 7.06 (1H,dd), 7.42 7.68 7.93 9.51 (1H,s).

96 Examples 8-11 Coupling NHBoc NH 2 o S0 N N~ 0-sok _0 Example Acid Deprotection Coupling0 0 N-e-N 0 Example 9 Example Reductive Amination H 0

Y

Example 11 Example 8 Tert-butvl[2- r 3-methoxv-4- (5-oxazolvlanilinol oxaIv1]amino1 -2methyipropyl I carbamnate 77mg (0.87 mmol) of tert-butyl (2-amino-2-methylpropyl)carbamate 207 mg (1.05 mmol) of 1- (3 -dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, 166 mg (1.08 mmol) of 1-hydroxy-7-azabenzotriazole and 200 mg (0.76 mmol) of N-[3-methoxy- 4-(5-oxazolyl)phenyl]oxalamic acid were dissolved in 5 ml of dichloromethane and 5 ml of dimethylformamide and stirred for 16 hours at room temperature. The mixture was then -97diluted with 50 ml of dichloromethane and washed with a 10% solution of citric acid and brine. The organic layer was then dried with anhydrous magnesium sulphate, filtered and evaporated to dryness. The residue was chromatographed on silica gel using 30% ethyl acetate in hexane for the elution to give 165 mg of tert-butyl [2-[[[3-methoxy-4-(5oxazolyl)anilino]oxalyl]amino]-2-methylpropyl]carbamate as a yellow solid, 'H NMR (400MHz, d6 DMSO) 6: 1.35 6H), 1.45 9H), 3.25 2H), 3.95 3H), 7.25 1H), 7.55 7.70 2H), 7.80 8.25 1H), 8.50 1H), 10.8 1H).

Example 9 N-(2-Amino- 1,1-dimethylethyl)-N'- [3-methoxy-4-(5-oxazolyl)phenyl] oxalamide trifluoroacetate (1:1) 26 mg (0.29 mmol) of tert-butyl [3-methoxy-4-(5oxazolyl)anilino]oxalyl]amino]-2-methylpropyl]carbamate was dissolved and stirred in ml of a 1:1 mixture of 1,1,1-trifluoroacetic acid and dichloromethane. After 1 hour the solvent mixture was co-evaporated with toluene three times and dichloromethane twice.

The resulting gum was then triturated with 40-60 petroleum ether to give 124 mg of N-(2amino-1,1 -dimethylethyl)-N'- [3-methoxy-4-(5-oxazolyl)phenyl] oxalamide .see*: 20 trifluoroacetate as a yellow solid, 'H NMR (400MHz, d6 DMSO) 6: 1.40 3.20 3.90 3H), 7.50 7.60-7.74 2H), 7.80 1H), 7.90 3H), 8.30 8.40 10.80(s,1H).

*.e The previously described trifluoroacetic acid salt was partitioned between a 25 saturated sodium hydrogencarbonate solution and ethyl acetate. The organic layer was then dried with magnesium sulphate, filtered and evaporated to give the free base used in Example *oo o Example -98- N-(3-Methoxy-4-(5-oxazolyl)phenyll [2-(3,3-dimethylbutyramido)- 1, 1-dimethylethylloxalamide mg (0.09 mmol) of N-(2-amino- 1,1 -dimethyl-ethyl)-N'-(3-methoxy-4-oxazol- 5-yl-phenyl)-oxalamide, 52 mg (0.45 mmol) of tert-butylacetic acid, 86 mg (0.45 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 69 mg of HOAt were dissolved and stirred in 2 ml of dimethylformamide. After stirring for 16 hours the mixture was diluted with 10 ml of dichloromethane and washed with 10% citric acid solution in water, saturated sodium hydrogen carbonate solution and brine. The organic solution was then dried with solid magnesium sulphate, filtered and evaporated to give N-(3-methoxy- 4-(5-oxazolyl)phenyl]-N'-[2-(3,3-dimethylbutyramido)-1,1-dimethylethyl]oxalamide as a pale yellow solid, MS: m/e 431.3 Example 11 N- 13-Methoxy-4-(5-oxazolyl)phenyll-N'-[2-(4-methylbenzylamino)- 1,1dimethylethyll oxalamide 0:00 mg (0.09 mmol) of N-(2-amino- 1,1 -dimethyl-ethyl)-N'- (3-methoxy-4-oxazol- 20 5-yl-phenyl)-oxalamide, 11.3 mg (0.095 mmol) of 4-methylbenzaldehyde and 30 mg :(0.14 mmol) of sodium triacetoxyborohydride were dissolved in 2ml of a 5% acetic acid dichloromethane mixture for 16 hours. The reaction mixture was then diluted with 8 ml of dichloromethane and washed with water, saturated sodium hydrogen carbonate and brine.

The resulting organic solution was then dried with magnesium sulphate, filtered and evaporated to give N- [3-methoxy-4-(5-oxazolyl)phenyl]-N'- [2-(4-methylbenzylamino)- 1,1-dimethylethyl]oxalamide as a yellow solid MS: m/e 437.3 Example 12 99 2-f[F 3-Methoxy-4- (5-oxazolyl) anilino 1 oxalyl 1 amino] -2-methyipropionic acid 0~ OMe

NHOCCQNHXCO

2 Me W OMe NHOCCON HX C 2

H

A mixture of 161 mg (0.446 mmol) of methyl 2-[[3-methoxcy-4-(5oxazolyl)anflinooxalyl] amino] -2-methylpropionate and 56 mg (1.33 mmol) of lithium hydroxide hydrate in 3 ml of methanol and 0.5 ml of water was heated at 50'C for 2 hours then diluted with water and washed with diethyl ether. The aqueous phase was acidified to pH2 with 2M hydrochloric acid and extracted twice with ethyl acetate. The combined organic extracts were dried over magnesium sulphate and evaporated to dryness. The residue was chromatographed on silica gel using dichioromethane/methanol/acetic acid/water (120:15:3:2) for the elution. After trituration with ether there was obtained mg of 2- [3-methoxy-4- (5-oxazolyl)anilino] oxalyl] amino] -2-methyipropionic acid as a white solid. MS: m/e 247.9 *set 0. 0.

Example 13 N 3 -Methoxcy-4- oxazolyl) phenyl]I methyl- I- (phenylcarbamoyl) ethyl]I oxalamide PhNH 2 NHOCCONHXC0 2

H

Me

EDAC

HOAt NHOCCONHX<CONHPh -100- A solution of 30 mg (0.086 mmol) of 2-[[[3-methoxy-4-(5oxazolyl)anilino]oxalyl]amino]-2-methylpropionic acid, 16 mg (0.172 mmol) of aniline, 18 mg (0.132 mmol) of 1-hydroxy-7-azabenzotriazole and 25 mg (0.131 mmol) of 1-(3dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in 2 ml of dimethylformamide was stirred at room temperature for 18 hours then diluted with ethyl acetate and washed with 2M hydrochloric acid and saturated sodium bicarbonate. The organic phase was dried over magnesium sulphate and after evaporation the residue was triturated with diethyl ether and collected by filtration to give 20 mg of N-[3-methoxy-4-(5oxazolyl)phenyl] -N'-[1-methyl-1- (phenylcarbamoyl)ethyl] oxalamide as a white solid. MS: m/e 423.0 Example 14 N- [3-Methoxy-4-(5-oxazolyl)phenyll 1-methyl-I -(methylcarbamoyl)ethyll oxalamide N O W OMe

EDAC

I~ MeNH, ED MeN 2 HOAt

NHOCCONHXCO

2 H .HCI NEM .0 OMe NHOCCONHXCONHMe sea* A mixture of 30 mg (0.086 mmol) of 2-[[[3-methoxy-4-(5oxazolyl)anilino] oxalyl] amino] -2-methylpropionic acid, 12 mg (0.178 mmol) of methylamine hydrochloride, 18 mg (0.132 mmol) of 1-hydroxy-7-azabenzotriazole, 25 mg (0.131 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 22 mg (0.218 mmol) of triethylamine in 2 ml of dimethylformamide was stirred at room temperature for 18 hours then diluted with ethyl acetate and washed with 2M hydrochloric 101acid and saturated sodium bicarbonate. The organic solution was dried over magnesium sulphate, evaporated to dryness and the residue chromatographed on silica gel using dichloromethane/methanol (24:1) for the elution. After trituration with ether there was obtained 17 mg of N-[3-methoxy-4-(5-oxazolyl)phenyl] -N'-[1-methyl-1- (methylcarbamoyl)ethyl]oxalamide as a white solid. MS: m/e 361.0 [M+H] Example 2- 3-Methoxy-4-(5-oxazolyl)anilinol oxalyll amino] phenyl] acetic acid :OMe LiOH 0 *000 0000

S

05 0 0

S

S

00 O

S

*S0SS p* 0 A solution of 740 mg (1.81 mmol) of methyl 2-[3-[[[3-methoxy-4-(5oxazolyl)anilino]oxalyl]amino]phenyl]acetate and 152 mg (3.62 mmol) of lithium hydroxide hydrate in 10 ml of methanol, 10 ml of 1,4-dioxane and 5 ml of water was stirred at room temperature for 18 hours. The solvent was removed by evaporation and the residue dissolved in water. The aqueous solution was washed with diethyl ether and acidified with citric acid solution. The solid which precipitated was collected by filtration and washed with water, ethanol and diethyl ether to give 414 mg of [3-methoxy-4- (5-oxazolyl)anilino]oxalyl]amino]phenyl]acetic acid as a white solid. MS: m/e 396.0 102 Example 16 N- [3-Methoxv-4- (5-oxazolvl)phenyll -N [(phenylcarbamoyl)methyl] p2henyll oxalamide i) CICO 2 iBu,NEMii) PhNH 2 -CONHPh 0 *.0 0 0 .0* 0.* 011.

*0.

0 o A solution of 30 mg (0.076 mmol) of [[3-methoxy-4-(5oxazolyl)anilino] oxalyl] amino] phenyl] acetic acid and 11 mg (0.096 mmol) of N- 10 ethylmorpholine in 1 ml of dimethylformamide was cooled to 0 0 C and a solution of 12 mg (0.088 mmol) of isobutyl chloroformate in 1 ml of dichioromethane was added. The resulting mixture was stirred for 30 minutes at 0 0 C then a solution of 7 mg (0.075 mmol) of aniline in 1 ml of dichloromethane was added and stirring was continued for a further hour at 0 0 C. After 18 hours at room temperature the mixture was evaporated to dryness 15 and the residue chromatographed on silica gel using dichloromethane/methanol (19: 1) for the elution. There was obtained 3 mg of N-[3-methoxy-4-(5-oxazolyl)phenyl]-N'-[3- [(phenylcarbamoyl)methyl]phenylloxalamide as a white solid MS: m/e 471.0 103 Example 17 N- [3-Methoxcy-4-(5-oxazolyl)phenyl] -[3-[(methylcarbamoyl)methyl] p2henyll oxalamide 'C0 2

H

MN.HCI,EDAC

HOBt,NEM 0 *.0 0 0 0* o 0* 6o.e.

o.

A mixture of 30 mg (0.076 mmol) of 2- [3-methoxy-4-(5oxazolyl)anilino] oxalyl] amino] phenyl] acetic acid, 22 mg (0.115 mmol) of 1-(3dimethylaminopropyl)-3-ethylacrbodiimide hydrochloride, 14 mg (0.092 mmol) of Ihydroxybenzotriazole hydrate, 26 mg (0.385 mmol) of methylamine hydrochloride and 52 mg (0.452 mmol) of N-ethylmorpholine in 1 ml of dimethylformamide was stirred at room temperature for 18 hours. The solvent was removed by evaporation and the residue chromatographed on silica gel using dichloromethane/methanol (1:19) for the elution.

15 There was obtained 15 mg of N-[3-methoxy-4-(5-oxazolyl)phenyl]-N'-[3-[(methy carbamoyl)methyllphenylloxalamide as a white solid. MS: m/e 409 104 Example 18 N- (3-Aminophenl)-N'- r3-metho~cv-4- (5-oxazolvl)phenvll oxalamide trifluoroacetate

TFA

.TFA

mg (0.043 mmol) of tert-butyl [3-[[[3-methoxy-4-(5-oxazolyl) anilino] oxalyl] amino] phenyl] carbamnate were dissolved in a mixture of 1 ml of dichioromethane and 1 ml of trifluoroacetic acid at room temperature for 10 minutes. The 10 solvent was removed by evaporation and the residue triturated with diethyl ether. The resulting solid was collected by filtration to give 18 mg of N-(3-aminophenyl)-N'-[3trifluoroacetate as a white solid. MS: m/e 394.0 [M±H+MeCN] 15 Example 19 N- Benzamido)p2henyll -[3-methoxy-4- (5-oxazolyl)phenyl 1oxalamide 105 MeNH 2 N" 0 Me

HC

SPhCO 2 H,NEM NHOCCON EDAC,HOBtI NHOCCON~bNHOCCONb

.TFA

A mixture of 30 mg (0.064 mmol) of N-(3-aminophenyl)-N'-[3-methoxy-4-(5oxazolyl)phenyl]oxalamide trifluoroacetate, 9 mg (0.074 mmol) of benzoic acid, 15 mg (0.078 mmol) of 1- (3-dimethylaminopropyl) ethylcarbodiimide hydrochloride, 15 mg (0.096 mmol) of 1-hydroxybenzotriazole hydrate and 22 mg (0.19 mmol) of Nethylmorpholine in 0.5 ml of dimethylformamide was stirred at room temperature for 18 hours then diluted with ethyl acetate and washed with 10% citric acid solution, saturated sodium bicarbonate and water. The organic phase was dried over magnesium sulphate, evaporated to dryness and the residue chromatographed on silica gel using dichioromethane/methanol (19:1) for the elution. There was obtained after trituration with diethyl ether/petrol 12 mg of N-[3-(benzamidophenyl]-N'-[3-methoxy-4-(5oxazolyl)phenyll oxalamide as a white solid. MS: m/e 457.0 Exml Exmle2 N Me.

NH Me.02~ N-[3 Mehaeulhoaid~peyl 3-ehoy--( MoaoeS)penl2Cxaamd N NHOCCON NEt 3

NI

.TFA

106- 12 mg (0.011 mmol) of methanesulphonyl chloride were added to a solution of mg (0.011 mmol) of N-(3-aminophenyl)-N'-[3-methoxy-4-(5oxazolyl)phenyl]oxalamide trifluoroacetate and 32 mg (0.317 mmol) of triethylamine in 0.5 ml of dimethylformamide. The resulting solution was left at room temperature for 18 hours then diluted with ethyl acetate and washed with 10% citric acid solution, saturated sodium bicarbonate and water. The organic phase was dried over magnesium sulphate, evaporated to dryness and the residue chromatographed on silica gel using ethyl acetate/petrol for the elution. There was obtained 5 mg of N-[3- (methanesulphonamido)phenyl]-N'-[3-methoxy-4-(5-oxazolyl)phenyl]oxalamide as a white solid. MS: m/e 431.0 Example 21 N- [2-(4-Aminophenyl)- 1,1-dimethylethyll-N'- [3-methoxy-4-(5oxazolyl)phenylloxalamide

NO

NO

2 SnCI 2

NHOCCONH

OMe

NNH

NHOCCONH

A mixture of 44 mg (0.1 mmol) of N-[3-methoxy-4-(5-oxazolyl)phenyl]-N'-[1,1dimethyl-2-(4-nitrophenyl)ethyl]oxalamide and 90 mg (0.5 mmol) of tin(II) chloride were dimethyl-2- (4-nitrophenyl) ethyl] oxalamide and 90 mg (0.5 mmol) of tin(II) chloride were 107 stirred and heated at 85'C in 2 ml of ethanol and 1 ml of 1,4-dioxane for 5 hours. The resulting solution was cooled, diluted with ethyl acetate and washed with 2M sodium hydroxide. The organic phase was dried over magnesium sulphate, evaporated to dryness and the residue chromatographed on silica gel using ethyl acetate/petrol for the elution. After trituration with petrol there was obtained 31mg of N-[2-(4-aminophenyl)- 1,1 -dimethylethyl] -methoxy-4- (5-oxazolyl) phenyl] oxalamide as a white solid. MS: m/e 409 Example 22 N- 4-Benzamidophenyl)- 1.1 -dimethylethyl] r 3-methoxcy-4- (5-oxazolyl)p2henylI oxalamide *0* 0*00 0 OMe

SNH

2

NHOCCONH

PhCO 2

H

EDAC

HOBt N0OMe SNHOCPh NHOCCONH~x A mixture of 30 mg (0.074 mmol) of N-[2-(4-aminophenyl)-1,1-dimethylethyl] [3-methoxy-4-(5-oxazolyl)phenyl]oxalamide, 10 mg (0.082 mmol) of benzoic acid, 14 mg (0.092 mmol) of 1-hydroxybenzotriazole hydrate, 21 mg (0.11 mmol) of 1-(3dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 18 mg (0.16 mmol) of Nethylmorpholine in 2 ml of dichloromethane was stirred at room temperature for 18 hours 108then diluted with dichloromethane and washed with 2M hydrochloric acid and saturated sodium bicarbonate. The organic phase was dried over magnesium sulphate, evaporated to dryness and the residue chromatographed on silica gel using ethyl acetate/petrol for the elution. There was obtained 9 mg of N-[2-(4-benzamidophenyl)-l,l-dimethylethyl]- N'-[3-methoxy-4-(5-oxazolyl)phenyl]oxalamide as a white solid. MS: m/e 513 Example 23 N-[2-(4-Acetamidophenyl)-1,1-dimethylethyl]-N'-[3-methoxy-4-(5-oxazolyl)phenyl] oxalamide

NH

2

NHOCCONH

OMe S NHAc NHOCCONH> A mixture of 30 mg (0.074 mmol) of N-[2-(4-aminophenyl)-1,1-dimethylethyl]-N'- [3-methoxy-4-(5-oxazolyl)phenyl]oxalamide, 8 mg (0.078 mmol) of acetic anhydride and 17 mg (0.15 mmol) of N-ethylmorpholine in 1 ml of dichloromethane was stirred at room temperature for 2 hours. The solvent was removed by evaporation and the residue triturated with diethyl ether and collected by filtration to give 14 mg of acetamidophenyl)-l,l-dimethylethyl]-N'-[3-methoxy-4-(5-oxazolyl) phenyl]oxalamide as a white solid. MS: m/e 451 109- Example 24 N2-[ 3-Methoxy-4-(5-oxazolvl)anilino]oxalvll-N1,3-dimethyl-L-valinamide N O Me NHOCCONH CO 2 Me N 0 Me NaOHHCOH O NNHOCCONH

CO

2

H

290mg (0.75 mmol) of N-[[3-methoxy-4-(5-oxazolyl)anilino]oxalyl]-3-methyl-Lvaline methyl ester in 3 ml of methanol and 1 ml of 1M aqueous sodium hydroxide were warmed gently and the resulting solution left at room temperature for 18 hours. The mixture was diluted with water, washed with diethyl ether and the aqueous phase acidified S• with 2M hydrochloric acid. The solution was extracted with ethyl acetate and the organic 15 phase dried over magnesium sulphate, evaporated to dryness and the residue chromatographed on silica gel using ethyl acetate/acetic acid (99:1) for the elution. After trituration with diethyl ether there was obtained 110 mg of N2-[[3-methoxy-4-(5- S oxazolyl)anilino]oxalyl]-N1,3-dimethyl-L-valinamide as a white solid. MS: m/e 376.0 Example Tert-butyl 4-(5-oxazolyl)anilinol oxalyll aminolbenzyll carbamate 110- NHBoc NHBoc MeO 2 CCOCI Et3N_

NH

2

NHOCCO

2 Me NHBoc N O NaOH

EDAC_

NHOCCO

2 H NH 2 N 0O NHBoc SNHOCCON In an analogous manner to that described in Example 1 but replacing 3-methoxy-4with 4-(5-oxazolyl)aniline and N-tert-butyloxalamic acid with N-[3- [(tert-butoxyformamido)methyl]phenyl]oxamic acid there was obtained tert-butyl [3n [[[4-(5-oxazolyl)anilino] oxalyl]amino]benzyl]carbamate as a white solid. 'H NMR (400 MHz, DMSO) 6: 1.4 4.1 7.02 7.32 7.40 7.63 (1H,s), 7.69 7.70-7.79 (3H,m, 7.97 8.43 10.82 10.99 (1H,s).

The starting material was prepared as follows: i) 586 mg (4.78 mmol) of methyl oxalyl chloride were added to a solution of 1 g (4.5 mmol) of tert-butyl (3-aminobenzyl)carbamate and 508 mg (5.03 mmol) of triethylamine in 10 ml of dichloromethane. The resulting solution was stirred at room temperature for 30 minutes then washed with 5% citric acid solution and saturated sodium bicarbonate. The organic phase was dried over magnesium sulphate and the solvent removed by evaporation to give 1.5 g of methyl N-[3- [(tert-butoxyformamido)methyl]phenyl]oxamate as a viscous gum. iH NMR (400 MHz, CDC13) 8: 1.43 3.96 4.31 (2H,d) 4.9-5.0 (br.s, 1H), 7.11 7.33 7.51 7.52 8.86 (br.s. 1H).

111 ii) A mixture of 1.232 g (4 mmol) of methyl N-[3-[(tert-butoxy formamido)methyl] phenyl]oxamate and 0.24 g (6 mmol) of sodium hydroxide in 15 ml of methanol/water was stirred at room temperature for 2 hours. The solvent was removed by evaporation and the residue dissolved in water and diethyl ether. The aqueous layer was acidified with citric acid and washed twice with ethyl acetate. The combined organic solutions were dried over magnesium sulphate and the solvent removed by evaporation to give 670 mg of N-[3-[(tert-butoxyformamido)methyl] phenyl]oxamic acid as a white solid. 'H NMR (400 MHz, DMSO) 6: 1.48 4.17 7.09 7.36 (1H,t), 7.49 (1H, 7.64 7.74 10.75 (1H,s).

Example 26 0*@S Tert-butyl 4-(5-oxazolyl)anilino] oxalyl] amino]benzyl carbamate N' 0 NHBoc N 0

NHOCCO

2 H EDAq EDANHNHOCCO2H NHOCCON o NH 2 NHBoc In an analogous manner to that described in Example 25 but replacing N-[3-[(tertbutoxyformamido)methyl]phenyl]oxamic acid with N-[2-[tertbutoxyformamido)methyl]phenyl]oxamic acid there was obtained tert-butyl So: oxazolyl)anilino]oxalyl]amino]benzyl]carbamate as a white solid MS: m/e 437.0 [M+H] Example 27 112- Tert-butyl 4- 5-oxazolyl)anilino I oxalyl I amino Ibenzyl I carbamnate N HBoo NHOCC0 2

H

In an analogous manner to that described in Example 25 but replacing N- [(tertbutoxyformamido)methyl] phenyl] oxamic acid with N- [tert-butoxyformamido) methyllphenyl]oxamic acid there was obtained tert-butyl oxazolyl)anilino] oxalyl] amino]benzyl] carbamnate as a white solid. MS: m/e 436.6 Example 28 N-Tert-butyl-N'- (5-oxazolyl)p2henyl] oxalamide tBuNHOCCO 2 H EDAQ.L

NH

2 SNHOCCONH t Bu 113- In an analogous manner to that described in Example 1 but replacing 3-methoxy-4with 4-(5-oxazolyl)aniline there was obtained oxazolyl)phenyl]oxalamide as a pale yellow solid. MS: m/e 329.0 [M+H+MeCN] Example 29 N-[3-(Aminomethvlphenvl -N'-[4-(5-oxazolvl)phenvl oxalamide trifluoroacetate .NHBoc .NH2

TFA

.TFA

In an analogous manner to that described in Example 3 but replacing tert-butyl [3- [[[3-methoxy-4-(5-oxazolyl)anilino]oxalyl]amino]benzyl]carbamate with tert-butyl [3- [[[4-(5-oxazolyl)oxalyl]amino]benzyl]carbamate there was obtained N-[3- 15 (aminomethylphenyl]-N'-[4-(5-oxazolyl)phenyl]oxalamide trifluoroacetate as a white solid. MS: m/e 336 [M] Examples 30-193 In a manner analogous to that described in Example 1, starting with N-[3oxalamic acid (prepared as described in Example 1, parts (i) and and the appropriate amine the compounds shown in Table 3 were also prepared: Table 3 -114- Example Structure

MS(ES)

338.0 31. 0. r

N.

0 362.9 32. 0 0 395.0 33. NN

N

y 352.0

N

34. 00 466

(M

t

;EI)

0 352.0 115 -116- 44.

0

N

0 338.9 46. I NiN NO 0 380.0 N0 Oj/ 332.0 48.

N

0 374.0 49. 1O' N 0 0- 362.0 50. N N N 317.9 51. N 332.0 52. ~Y k ,CNIX

N

53. N.N N

(N<

N~1 389.9 117- 54.~ 0 328.0 4 N0 N

I-I

346.0 56. N 0 0 289.9 57. N 0 318.0 58. 7 0 304.0 59.N 0 333.9 NNy j 394.0 118 119 4 120 75.0 N N N

N

346.8

H

76.1 395.8 77. N N K- 0 332.4 78.0

N

332.4 79.

N

316.2

NF

N

0 F 344.0 81. 0 N \0 A 0 NY 317.8 82. 0 NN 1 IA 0 328.2 121 0 0

K~I

0 0 122 .*00 0 o000 0000.

*.go 123 97. 0 374.0 98. 0 NN (0 0 299.8 99. 0 N N' 0 0 302.2 100.0 N 316.2 101.0 N 372.0 102.0 N0 N-iN 319.8 103.0 N N

N-N

332.4 9 .9.

.9 9 9* *9.

.00.

6 90 124 p 0 *600 *0 @0 0 060 0 0@*000 0 SO 00 0 0

S

S. S @5 00 Oe Os 0 0050 .00 S *6 t 0@ 0*0S

S

500 @560 0050 00 0 S S 0* 104. 0 N 0 332.4 105.

N

336.6 106. N NV N 01

N

342.0 107.N o0~ 0 308.0 108.NN o0 345.8 109.

0 0 402.0 110. 0 N 405.2 0 0 N- 356.0 125 112. 0 N 0O 0 113. 0 N- 358.2 114. 0 N o 0 I 359.2 115. 0 N 374.0 116. O i N 372.0 117.1 0

N

I 389.2 118. 0 NjN- Y (\Ow 389.4 119. 0 N ~JI 276.0 120. 0 N F 0 0 FF N 394

(M*;EI)

126- 127 130.0 N<NIN N 378.4 131.

NO

03

N

423 132.

(0 0

N

389.4 133.

0 1 N N'1hIo 0 0 I338.2

N

134. 0 0 N0 363.4 135.0N 0 ~-0 356

N

136.

0 N 'nNNN 0 -0 370

N

137.

0) N )KNa i 0 371.8 ci 138.

0 N N <0 -0 \Ir 406.2 -128- 139.

0 0

N

402.2 140. I I 386.2 0NJN aCi o0 0

N

141. A c, 406.2 142. 1 I la N N I Y NC

N

1r43N 384 144.01 N Q 12 380.2 0\ 0 0, N 143.

146.0 N 0 0 NI 366.2 147.

\N I 366.2 148.

\0 0F N 368.2 129- 151.

0 395 152. N, 0NN- i 383.2 153.

NO

0, NyZ,, 0 409.4

<N

154.

N

0 0

N

380.8 155. 0 0 .NZ 368.2 <Na 156.

N 424.2 157.

0 N

N

Oi 0 'Na 354.2 130 131

S.

132 .9 9 9 *t9 9 99999 9 99 .9 99 9 9 99 9 .9 *9 999999 9 99*.

9 9999 99 9 9.

99 99.9 9 9 99.9 99 9 .9 9.

175.

F

F

0 j~ -0

N

406.2 176.0o0 0

N

406.2 177. 0 N~I o1 0 N\ 394.2 178.

u

NJ(I

407 179.I N UO~i N iN N 4 N 0

N

507.2 180. 0 NNAK N 473.2 181. 0N~~YN

N

451.2 182.N 0 0

N

405.2 133- 0*.

0 SO S

S

5* 0

S

S.

a S *005 134- 0 NJ-', -0 I 409.4

N

192. i 0 0 445.2 0 193. e N~N~ (0 -0

N

464 Examples 194- 214 In a manner analogous to that described in Example 4, starting with N- [3- (aminomethyl)phenyl] methoxy-4- (oxazolyl)phenyl] oxalamide trifluoroacetate (prepared as descibed in Example 3) and the appropriate carboxylic acid derivative the compounds shown in Table 5 also were prepared: Table 135- 136 206.I 472.1 207. I 0 N

N

0 0 0 N 472.0 208. I-NN yo

N

o 00 473.0 209.NN N' 477.0 210. NN <N 477.0 211. NN 477.2 212.

0 477.2 213. 0. N N' N o 00 485.1 214.

N.N

N 485.2 Examples 215 301 137 In a manner analogous to that described in Example 10, starting with N- [2-amino- 1,1 -dimethylethyl) (3-methoxy-4-oxazol- 5-ylpbenyl)oxalamide (prepared as described in Example 9) and the appropriate carboxylic acid the compounds shown in table 4 were also prepared: Table 4 Example Structure MS(ES) 215. N o 0 0 0 N\ 401.0 216. 0 NLKN~I I) 0 0 415.0 217.

I

o 0 0 N 417.0 218. N

N

:426.0 219.

0 0427.0 *220 0 220 N-LMN 0 0 221.42.

UIN YLN

D

0 c 0 0 431.0

N

138 0 438.0 224. 0 N o 0 0 0- 439.0

N-

225.

0 0 Wil 443.0 226. IS\ NJ 443.0 227. I1XI N ~443.1 228.

0 0 0443.1 229. N0 C o 0 0451.0 230.

,0 0 0451.0 Ni 231.

0 0 N-il 457.1 232. N< 0 0 462.0 0 233 11.X 0 0 0 482.0 iK 139 9 140 141 142 0* 143 144- 145 :0.

00* Examples 302-315 438-458 and 653-663 Typical methods used for the preparation of compounds of table 1c are described below: Example 440 N- f 3-Methox 5-oxazolyl)phenylI [l l,-dimethyl-2-( 1-oxido-4pyridyl)ethyl] oxalamide mg (0.1 mmol) of 60% 3-chloroperoxybenzoic acid were added to a stirred 146solution of 20 mg (0.051 mmol) of N- [3-methoxy-4-(5-oxazolyl)phenyl] [1,1dimethyl-2-(4-pyridyl)ethyl]oxalamide in 1 ml of dichloromethane. The mixture was stirred for 1 hour then diluted with ethyl acetate, washed with sodium bisulphite solution, sodium bicarbonate solution and brine. The organic solution was dried over magnesium sulphate, evaporated to dryness and the residue triturated with diethyl ether to give 13 mg of N- [3-methoxy-4-(5-oxazolyl)phenyl]-N'- 1,1-dimethyl-2-( -oxido-4pyridyl)ethyl]oxalamide as an off-white solid. MS: m/e 411 The starting material was prepared as follows: i) A solution of 17.4 g (0.115 mol) of alpha, alpha-dimethyl-4-pyridineethanol in 115 ml of acetic acid was added dropwise to a mixture of 115 ml of acetic acid, 58 ml of concentrated sulphuric acid and 6.8 ml (0.126 mmol) of acetonitrile with cooling in an ice/salt bath. The resulting mixture was stirred for 2 hours at room temperature and the pH raised to 10 by the addition of 6M sodium hydroxide solution with ice cooling. The slurry was filtered, washed with ethyl acetate and the aqueous filtrate extracted twice with ethyl acetate. The combined organic extracts were dried over magnesium sulphate, evaporated to dryness and the residue chromatographed on silica gel using ethyl acetate/methanol and (3:17) for the gradient elution. There was obtained 1.87 20 g of N-[1,1-dimethyl-2-(4-pyridyl)ethyl]acetamide as an orange oil. 'H NMR (400 MHz to**:

CDC

3 8: 1.29 1.91 3.11 5.10 7.07 8.50(2H,d).

ii) A solution of 1.8 g (9.3 mmol) of 1,l-dimethyl-2-(4-pyridyl)ethyl]acetamide, 2.66 g (9.3 mmol) of titanium (IV) isopropoxide and 2.56 g (14 mmol) of diphenylsilane in 25 10 ml of tetrahydrofuran was stirred at room temperature for 20 hours. The resulting mixture was chromatographed on silica gel using dichloromethane/methanol/acetic acid/water (60:18:2:3) for the elution. The product was dissolved in 20 ml of concentrated hydrochloric acid and 50 ml of methanol and evaporated to dryness. The residue was evaporated with toluene five times to give 620 mg of alpha, alpha-dimethyl-4pyridineethylamine hydrochloride as a pale brown solid. 'H NMR (400 MHz DMSO) 8: 1.31 3.26 8.02 8.4-8.6 (3H,br.s), 8.88 (2H,d).

iii) A mixture of 100 mg (0.45 mmol) of alpha, alpha-dimethyl-4-pyridineethylamine hydrochloride 120 mg (0.45 mmol) of N-[3-methoxy-4-(5-oxazolyl)phenyl]oxalamic acid, 105 mg (0.68 mmol) of 1-hydroxybenzotriazole hydrate, 105 mg (0.54 mmol) of 1-(3dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 127 mg (1.1 mmol) of N- 147ethylmorpholine in 4 ml of dichloromethane was stirred for 20 hours at room temperature then diluted with ethyl acetate and washed with water and brine. The organic solution was dried over magnesium sulphate, evaporated to dryness and the residue chromatographed on silica gel using ethyl acetate/methanol (19:1) for the elution. After trituration with diethyl ether there was obtained 32 mg of N-[3-methoxy-4-(5-oxazolyl)phenyl]-N'-[1,1dimethyl-2-(4-pyridyl)ethyl]oxalamide as a white solid. MS: m/e 395 Example 455 2- 3-Methoxy-4-(5-oxazolyl)anilinoloxalyl] amino] -2-methylpropyl] benzofurancarboxylic acid A solution of 68 mg (0.12 mmol) of benzyl 2-[2-[[[3-methoxy-4-(5oxazolyl)anilino]oxalyl] amino]-2-methylpropyl]-5-benzofurancarboxylate in 10 ml of tetrahydrofuran was hydrogenated with 20 mg of 10% palladium on carbon for 4 hours.

The resulting suspension was filtered, evaporated to dryness and the residue triturated with diethyl ether to give 41 mg of 2-[2-[[[3-methoxy-4-(5oxazolyl)anilino] oxalyl] amino]-2-methylpropyl]-5-benzofurancarboxylic acid as a white solid. MS: m/e 477.9 [M+H] The starting material was prepared as follows: o00 *0 i) A solution of 1.976 g (22.46 mmol) of isobutyric acid in 8 ml of anhydrous tetrahydrofuran was added to a stirred suspension of 1.078 g (26.95 mmol) of 60% sodium hydride and 2.268 g (22.46 mmol) of diisopropylamine in in 40 ml of anhydrous tetrahydrofuran under a nitrogen atmosphere and the mixture heated to reflux for minutes. After cooling to 0°C a solution of 14.04 ml (22.46 mmol) of 1.6M butyllithium in hexanes was added maintaining the temperature at 0-5 0 C. After 5 minutes at 0°C the mixture was warmed to 30-35 0 C for 20 minutes, cooled to 0°C and a solution of 5.3 g (22.46 mmol) of 2-(bromomethyl)-5-benzofurancarbonitrile in 15 ml of anhydrous tetrahydrofuran was added maintaining the temperature at 0°C. The suspension was 148stirred for 5 minutes at 0°C then warmed to 30-35 0 C for 20 minutes before being cooled to and quenched by the careful addition of 50 ml of water and diluted with 50 ml of diethyl ether. The aqueous phase was separated, acidified with concentrated hydrochloric acid and extracted with diethyl ether. The organic phase was dried over magnesium sulphate, evaporated to dryness and the residue chromatographed on silica gel using ethyl acetate/petrol for the elution. There was obtained 670 mg of 5-cyano-alpha, alphadimethyl-2-benzofuranpropionic acid as a white solid. 'H NMR (400 MHz CDC13) 8: 1.23 3.01 6.46 7.38 7.42 7.75 (1H,s).

ii) A mixture of 652 mg (2.68 mmol) of 5-cyano-alpha, alpha-dimethyl-2benzofuranpropionic acid, 732 mg (2.68 mmol) of diphenylphosphoryl azide and 269 mg (2.66 mmol) of triethylamine in 8 ml of tert-butanol was refluxed for 8 hours then evaporated to dryness and the residue dissolved in ethyl acetate and washed with saturated sodium bicarbonate solution. The organic phase was dried over magnesium sulphate, evaporated to dryness and chromatographed on silica gel using ethyl acetate/petrol (2:3) for the elution to give 225 mg of white solid which was suspended in 10 ml of 2M sodium hydroxide solution and stirred and refluxed for 20 hours. The resulting suspension was cooled, evaporated to dryness and 5 ml of ethylene glycol and 400 mg of potassium hydroxide were added. After heating at 190 0 C for 20 minutes 2 ml of water were added and after a further 20 minutes another 15 ml of water were added and heating continued for minutes until a thick paste remained which was cooled and dissolved in 20 ml of water.

Concentrated hydrochloric acid was added to bring the pH to 2 then 25 ml of dioxan, 3 g (21.74 mmol) of potassium carbonate and 1.5 g (6.88 mmol) of di-tert-butyl dicarbonate were added and the mixture stirred for 24 hours. The solvent was removed by evaporation 25 and the residue dissolved in diethyl ether and water. The aqueous phase was separated, acidified with 2M hydrochloric acid and extracted with diethyl ether. The organic phase was dried over magnesium sulphate and evaporated to dryness to give 106 mg of 2-[2- (tert-butoxyformamido)-2-methylpropyl] -5-benzofurancarboxylic acid as a colourless gum.

iii) A mixture of 105 mg (0.32 mmol) of2-[2-(tert-butoxyformamido)-2acid, 80 mg (0.53 mmol) ofbenzyl bromide, and 200 mg (1.45 mmol) of potassium carbonate in 4 ml of dimethylformamide was stirred at 149room temperature for 1 hour then diluted with diethyl ether and water. The organic phase O was washed twice with water, dried over magnesium sulphate, evaporated to dryness and the residue chromatographed on silica gel using ethyl acetate/petrol for the elution.

There was obtained 104 mg of benzyl 2- [2-(tert-butoxyformamido)-2-methylpropyl]-5benzofurancarboxylate as a colourless gum. 'H NMR (400 MHz CDC13) 8: 1.39 (6H,s), 1.50 3.23 4.49 5.41 6.52 7.34-7.52 8.02 8.30 (1H,s).

iv) 103 mg (0.24 mmol) of benzyl 2- [2-(tert-butoxyformamido)-2-methylpropyl] benzofurancarboxylate were dissolved in 5 ml of trifluoroacetic acid/dichloromethane (1:1) for 10 minutes then evaporated to dryness and the residue dissolved in 1 ml of dimethylformamide and added to a stirred solution of 66 mg (0.25 mmol) of N-[3acid, 115 mg (1 mmol) of N-ethylmorpholine, mg (0.29 mmol) of 1-hydroxybenzotriazole hydrate and 70 mg (0.37 mmol) of 1-(3dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in 2 ml of dimethylformamide and the resulting mixture stirred at room temperature for 18 hours. After dilution with ethyl acetate the organic solution was washed with 2M hydrochloric acid, saturated sodium bicarbonate solution and water, dried over magnesium sulphate, evaporated to dryness and the residue chromatographed on silica gel using ethyl acetate/petrol (45:55) for the elution.

20 After trituration with diethyl ether there was obtained 81 mg of benzyl 2-[2-[[[3-methoxy- 4-(5-oxazolyl)anilino] oxalyl]amino]-2-methylpropyl] -5-benzofurancarboxylate as a white solid. MS m/e 568 oo Example 443 [3-Methoxy-4-(5-oxazolyl)anilino] oxalyl)]amino]-2methylpropyl]phenoxy] acetic acid A solution of 45 mg (0.081 mmol) of benzyl 2-[3-[[[3-methoxy-4- (5-oxazolyl)anilino]oxalyl]amino]-2-methylpropyl] phenoxy] acetate in 5 ml of ethanol/tetrahydrofuran was hydrogenated with 4 mg of palladium on carbon catalyst for 5 hours. The resulting suspension was filtered, evaporated to dryness and triturated with diethyl ether to give 29 150 mg of 2- [3-methoxy-4-(5-oxazolyl)amino]-2methylpropyl]phenoxy] acetic acid as a white solid. MS: m/e 468 [M+H] The starting material was prepared as follows: i) 8 mg (0.2 mmol) of 60% sodium hydride were added to a stirred solution of 85 mg (0.2 mmol) of N-[2-(3-hydroxyphenyl)-1,1dimethylethyl]-N'- [3-methoxy-4-(5-oxazolyl)phenyl] oxalamide in 1 ml of dimethylformamide. After 10 minutes 55 mg (0.24 mmol) of benzyl bromoacetate were added and the mixture stirred at room temperature for 4 hours. The resulting solution was diluted with ethyl acetate, washed twice with water, dried over magnesium sulphate and evaporated to dryness. The residue was chromatographed on silica gel using ethyl acetate/petrol (2:1) for the elution. There was obtained 51 mg ofbenzyl 2-[3-[2-[[[3-methoxyoxalyl] amino] -2-methylpropyl] phenoxy]acetate as a white solid. MS: m/e 558 In a manner analogous to that described in Example 1, starting with N-[3methoxy-4-(5-oxazoyl)phenyl oxalamic acid, prepared as described in Example 1, parts (i) and and the appropriate amine, additional compounds shown in table Ic were also prepared.

table Ic Name Structure MS(ES) Ex No

(M+H)

N-[3-Methoxy-4-(5- 'Cq oxazolyl)phenyl]-N'-[ 1,1-dimethyl-

N

o 408 302 methylphenyl)ethyl] oxalamide 151 N- 1,1-Dimethyl-2-(2methylphenyl) ethyl I [3oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] 1,1 -dimethyl- 2-(3-pyridyl)ethyl] oxalamide C C.

0 408 303 304 N-[3-Methoxy-4-(5- N -CO oxazolyl)phenyl]-N'-[1,1-dimethyl- _r.NS(CM 0 CM, 408 305 methylphenyl) ethyl] oxalamide N- [3-Methoxy-4-(5- 0 oxazolyl)phenyl] 1, 1 -dimethyl- 2 (2 -thi enyl) ethyl]J oxal am id e s/400 306 N- (4-Benzyloxy-phenyl)- 1,1dimethyl-ethyl] (3-methoxy-4- 5037 oxazol-5-yl-phenyl) -oxalamide N- [2-(4-Hydroxy-phenyU- 1,1-

CC

dimethyl- ethyl] (3 -methoxy-4-

N

oxazol-5-yl-phenyl)-oxalamide CH 410 308 N-(3-Methoxy-4-oxazol-5-yl- phenyl)-N'- [2-(4-methoxy-Iphenyl) 1-dimethyl- ethyl] 424 309 oxalamide N- (2-Hydroxy-phenyl)- 1,1- v0O't0

C

dimethyl- ethyl]I- (3 -methoxy-4- 41 310' oxazol-5-yl-phenyl) -oxalamide o M 1 1 propyl)-N'-(3-methoxy-4-oxazol- 408i 311 CI4031 152 N-[2-(3-Hydroxy-phenyl)-1,1- 0a dimethyl-ethyl] (3-methoxy-4oxazol- 5-yl-phenyl) -oxalamide4132 N-(3-Methoxy-4-oxazol-5-yl-N phenyl)-N'-[2-(3-methoxy-04231 phenyl) 1, 1 -dimethyl- ethyl] 42431 oxalamide N-[2-[4-(Cyanomethoxy)phenyl]- 1,1-dimethylethyl]-N'-[3-n-ethoxy- 4931 5-oxazolyl)phenyl] oxalamide4931 [[3-Methoxcy-4-(5

CH,

oxazolyl)anilino] oxalyl] amino] S- 468 315 methyipropyl] phenoxy] acetic acid 2- [2-[I[3-Methoxy-4-(5-N' oxazolyl)anilino] oxalyl] amino] -2methyipropyl] phenoxy] acetic acid O~468 438 2- [2-[[[3-Methoxy-4-(5- I C N oxazolyl) anilino] oxalyl] amino] oy1.

methylpropyl Iphenoxy] acetic acid 468 439 0- N- [3-Methoxy-4-(5- OI I oxazolyl)phenyl] [1,1 -dimethyl- 1-oxido-4- 0 ,411 440 pyridyl) ethyl] oxalarnide N-[3-Methoxy-4-(5-

F

N oxazolyl)phenyl] [1,1 -dimethyl- K- 1-oxido-3- 0 4,C C1 411 441 pyridyl)ethyl] oxalamide CH,

N.H

N-[3-Methoxcy-4-(5- N oxazolyl)phenyl] 1, 1 -dimethyl- N -oxido-2- O FC ai, 411 442 pyridyl) ethyl I oxalamide 153 [[3-Methoxy-4-(5oxazolyl) anilino] oxalyl) ]amino] -2methylpropyll phenoxyl acetic acid 468 443 N- [2-(2-Benzofuranyl)- 1,1dimethylethyll-N'-[3-methoxy-4- N,)yN oxalamide4344 N- [3-Methoxy-4-(5-N6 oxazolyl)phenyl] [1,1-dimethyl- A<~ 2-(3-methyl-2- -P 448 445 benzofuranyl) ethyl]I oxalamide N- 2- (7-Methoxy-2-benzofuranyl)- N" CH 4- (5-oxazolyl)phenyl] oxalamide-4646 N- (5-Methoxy-2-benzofuranyl)-o 1,1-dimethylethyl] [3-methoxy- oxalamide 464 447 N- (6-Methoxcy-2-benzofuiranyl)- ,c 1,1 -dimethylethyl] [3-methoxy- &N)x o 4- (5-oxazolyl)phenyl] oxalamide -464 448 Benzyl 4- [2-[[[3-rnethoxy-4-(5oxazolyl)anilino] oxalyl] amino] N methyipropyl] benzoate c528 449 4- [2-[I[3-Methoxy-4-(5- oxazolyl) anilino] oxalyl] amino] -2 -Sr o methyipropyl] benzoic acid 0438 450 Benzyl 3- [[3-methoxy-4-(5- o oxazolyl)anilino] oxalyl] amino] o 2 methyipropyl] benzoate5241 oxazolyl) anilino oxalyl] amino] 438 452 methylpropyl]benzoic acid H I4345 154 N- [2-(3-Benzofuranyl)- 1,1- N dimethylethyl] [3-methoxy-4-N N oxalamide o~ 434 453 Benzyl 2- [2-I[[3-methoxcy-4-(5oxazolyl)anilino] oxalyl] amino] -2methyipropyl] 568 454 benzofurancarboxylate oxazolyl)anilino] oxalyl] amino] -2-47. methyipropyl] 47.05 benzofurancarboxylic acid N- [3-Methoxy-4-(5- PN/- 0'H oxazolylphenyl] N0 pyridyl)methyl] 0421 456 cyclopentyloxalamide

CH

N- [3-Methoxy-4-(5- N.

oxazolyl)phenyl] -oxido- IJ-r1 §C1- 3745 4-pyridyl)methyl] -1-4345 cyclopentyl] oxalamide N- [2-(4-Methoxy-2-benzofuranyl)- Nr0o 1,1-dimethylethyl] [3-methoxy- 4- (5-oxazolyl)phenyl] oxalamide NC0464 458 C"l [3-Methoxcy-4-(5-oxazolyl) Coi CH phenyl]-N'-[2-(2,6-dimethyl-4- 0 423.22 653 pyridyl)- 1,1 -dimethylethyl]N oxalamide N- [3-Methoxy-4-(5- 0 Nt±0 oxazolyl)phenyl]-N'-[1,1-dimethyl-

X.A,

o 0 439.3 654 2-(2,6-dimethyl- 1-oxido-4-pyridyl) N ethyl] oxalamide 155 N- [3-Methoxy-4-(5-oxazolyl) 0~L.~Z phenyl] [(4-pyridyl)methyl] -a 1-cyclopropyll oxalamide N 393 655 N- [3-Methoxy-4-(5-oxazolyl) IN~~Z~ phenyl] [1I- (1 -oxido-4- 0 pyridyl)methyl] N~ 409 656 cyclopropyl] oxalamide N- [3-Methoxy-4-(5-oxazolyl) phenyl]-N'-[1-[(4-pyridyl)methyl]- -a 1 -cyclobutyl] oxalamide N 0 N- 3-Methoxy-4- (5-oxazolyl) I N' phenyl] [1I- -oxido-4- 0 pyridyl)methyl] -1I -cyclobutyll N~ 421 658 oxalamide N- 3-Methoxy-4- (5-oxazolyl) 0NJjQ.III phenyl] 1- (4-pyridyl)methyl] 1 -cyclohexyl]I oxalamide N 3 N- [3-Methoxy-4-(5-oxazolyl)

ON-

0

NJNQ

phenyl] 1-oxido-4- 0 1 pyridyl)methyl]-1- N 1 451 660 cyclohexyl] oxalamide N- [3-Methoxy-4-(5-oxazolyl) Nj phenyl] [1,1 -dimethyl-2-(2- 0 methyl pyridyl) ethyl] oxalamnide N409 661 N- [3-Methoxy-4-(5-oxazolyl) 0 NJ >J2~ phenyl] [1,1-dimethyl-2-(2- 0 methyl-i -oxido-4- N425 662 pyridyl) ethyl I oxalamide 2- 3-Methoxy-4-(5- Na& J0 oxazolyl)anilino] oxalyl] amino] -2-N y S methyipropyl] OH 4406 benzothiophenecarboxylic acid S. 156 000.

0.

Exam-ples 3 16-330: In a manner analogous to that described in Example 11 starting with N- (4aminophenyl) -1,1 -dimethylethyl] [3-methoxy-4- (5-oxazolyl)phenyl] oxalamide, prepared as described in example 21, and the appropriate aldehyde compounds shown in table Id were also prepared.

table I d Name Structure MS(ES) Ex No N- [3-Methoxy-4- (5-oxazolyl)phenyl] H 0% [1,1-dimethyl-2-[4-[(2-0 pyridinyl) methylamino] phenyl] ethyl] oxala "500.1 316 mide N- [3-Methoxy-4- (5-oxazolyl)phenyl] -N'-CH [1,1-dimethyl-2- 50.1 31 pyridyl) methylamino] phenyl] ethyl] oxalam50. 31 ide N- [4-(2-Furfurylamino)phenyl]-1,1dimethylethyl] [3-methoxy-4- -031 oxazolyl)phenyl] oxalamide48. 31 N- [3-Methoxy-4- (5-oxazolyl)phenyl] 5. j [l,1-Dimethyl-2-[4-(2- 50.1 31 thenylamino)phenyl] ethyl] oxalamide50. 31 N- [3-Methoxy-4- 5-oxazolyl)phenyl] CA 0i [1,1-dimethyl-2- 47.32 dimethyipropylamino )phenyl] ethyl] oxalam J47. 32 ide 157 4* N-[2-[4-[(1H-Imidazol-2- H yl)methylamino]phenyl] 1,1-oN dimethylethyl] [3-methoxy-4-(5- 489.1 321 oxazolyl)phenyl] oxalamide N- [3-Methoxy-4- (5-oxazolyl)phenyl] c. 0H [1,1-dimethyl-2-[4-[(4-o pyridyl)methylamino] phenyl] ethyl] oxalam N 500.1 322 ide N- [3-Methoxy-4- (5-oxazolyl)phenyl] ND [1,1-dimethyl-2-[4-[(2- <050.1 32 thiazolyl)methylaminol phenyl] ethyl] oxala N3 0. 2 mide N- 2- Furfurylamino)phenyl 1, 1- c% o KjjANJI~ dimethylethyl] 3-methoxy-4- o 8. 2 oxazolyl)phenyl] oxalamide48. 32 N-[2-[4-[5-(Hydroxymethyl)-2-0 furfurylamino] phenyl] -1,1-dimethylethyll (0 [3-methoxy-4-(5- S51. 32 oxazolyl)phenyl] oxalamide N- [2-(4-Benzylaminophenyl)-1,1- t o% dimethylethyl]-N'-[3-methoxy-4-(5- o~ 9. 2 oxazolyl)phenyl] oxalamide49. 32 N- (2-Hydroxybenzylamino)phenyl]-

H

1,1 -dimethylethyl] [3-methoxy-4- <\151 2 oxazolyl)phenyl] oxalamide a51. 32 N- [4-(3-Cyanobenzylamino)phenyl] o 1,1 -dimethylethyl] [3-methoxy-4- oxazolyl)phenyl] oxalamide 524.1 328 N- [3-Methoxy-4-(5-oxazolyl)phenyl] 1-dimethyl- 2- 1 pyridyl)benzylamino ]phenyl] ethyl ]oxalami (17a576.2 329 de 158 N- (2-Fluorobenzylamino)phenyl] 1, 1-dimethylethyl] [3-rnethoxy-4- 51. 3 oxazolyl)phenyl] oxalamide51. Exam-ples 33 1-395 and 596-597: In a manner analogous to that described in Example 22 starting from N- (4aminophenyl) 1 -dimethylethyl] 3-methoxy-4- (5-oxazolyl)phenyl] oxalamide, prepared as described in example 2 1, and the appropriate carboxylic acid compounds shown in table le were also prepared.

4g..

Table 1le Name Structure MS(ES) Ex No

(M+H)

t (Cyclopropylcarboxamido)phenyl] 0 1, 1-dimethylethyl] [3-methoxy-4- 477.1 331 oxalamide N- 2- (Cyclobutylcarboxamido) t 0 phenyl] 1, 1 -dimethylethyl] rI methoxy-4-( 5-oxazolyl)phenyl 491.1 332 oxalamide N- {3-Methoxy-4- (5-oxazolyl)phenyl] It [1,1-dimethyl-2-(4- 0 9. 3 pivalamidophenyl) 1, 1 -49.

159 dimethylethyl] oxalamide

S

S

S. *S S. S

S

S.

S

S.

S

*5

S

*SS*

S

S S

S.

N- [3-Methoxy-4-(5-oxazolyl)phenylI 1-dimethyl-2 [(I1H -pyrrol 50.34 2-yl)carboxamidojphenyl] ethyl]50. 34 oxalamide N- [(2-Furyl) carboxamido] phenyl] 1, 1- 503. 335 dlimethylethyl] [3-methoxy-4-(5-50. oxazolyl)phenyl]I oxalamide N- [(3-Furyl) c% o336 carboxamido] phenyl] -1,1-50.

dimethylethyl] [3-methoxy-4- (5-50.

oxazolyl)phenyl] oxalamide N- 2- H-Imidazol-4-yl) carboxamido] phenyl] 1, 1- I 031 3 dimethylethyl] [3-methoxy-4- (5-50. 37 oxazolyl)phenyl] oxalamide N- [(Tetrahydro-2(RS)-furyl) carboxamido] phenyl] 1,1- 507.2 338 dimethylethyll [3-methoxy-4- N oxazolyl)phenyl] oxalamide N- [3-Methoxy-4- (5-oxazolyl) c N phenyl] f 1, 1-dimethyl-2- Ilr-,Y-c pyridyl)carboxamido] phenyl] ethyl] ox51. 39 alamide N- [3-Methoxy-4-(5-oxazolyl)phenyl]

K

[1,1-dimethyl-2- [(4-pyridyl) o I k carboxamido] phenyl] ethyl] oxalamide 514.1 340 N- [3-Methoxy-4- (5-oxazolyl)phenyl] N Y -0J~ 1-dimethyl-2- [(2-thienyl) o-59. 4 carboxamido] phenyl] ethyl] oxalamide 51.N4 160 N- [3-Methoxy-4-(5-oxazolyl)phenyl] I 0N 1,1 -dimethyl-2- t4- (3-thienyl 0 1. 4 carboxamido] phenyl] ethyl] oxalamide P51. 34 N- [4-(2-Cyclopentylacetamido) o VcaY 0 phenyl 1,1 -dimethylethyl] [3methoxy-4- (5-oxazolyl)phenyl] 519.2 343 oxalamide 1,1 -dimethyl-2- I zn a methylbenzamido)phenyl] ethyl] oxala52. 34 mide N-[t3-Methoxy-4-(5-oxazolyl)phenyl] I -rC t1,1 -dimethyl-2- methylbenzamido)phenyl] ethyl] oxala J 2. 4 mide N- (Cycloheptylcarboxamido) phenyll -1,1 -dimethylethyl] 9-D 53.o4 methoxy-4-( 5-oxazolyl)phenyl] ,53. 4 oxalamide N- [(5-Isoxazolyl) carboxamido] c phenyl] -1,1-dimethylethyl] (I041 4 methoxy-4-( 5-oxazolyl)phenyl] 0. 4 oxalamide N- (Cyclopentylcarboxamido) phenyl] ,1-dimethylethyl] 0. 4 methoxy-4-( oxalamide N-[2-{4-[(Tetrahydro-3(RS)-furyl)

C

carboxamido]phenyl]- 1,1- 50.34 dimethylethyl] [3-methoxy-4-(5-50. 34 oxazolyl)phenyll oxalamide

OC**

C.

C C

C

C

C.

C C

C

et C

C

C.

C

C. C C

C

C

C. C C C

C.

161

S

*000

S.

S S

S

S

0 S. 06 S 0 5 @0 S 4* 4 45 0 0000 @0

S

~S1.

S

*00* 0

S.

S..

0005

S

*000 500

S

@405 00 0 0@ @5 N-[3-Methoxcy-4-(5-oxazolyl)phenyl] 0 -N'-[1,1-dimethyl-2-[4-[(1-methyl- I0 0 1. 1H-pyrrol-2-yl)carboxamidolphenylI ethyl] oxalamide N- [3-Methoxy-4-(5-oxazolyl)phenyl] -N'-(1,1-dimethyl-2-[4-[(1,2,3-52. 31 thiadiazol-4-yl)carboxamidojphenyl 2. ethyl] oxalamide N- (3-Fluorobenzamido)phenyl] CN 0 AP, -1 -dimethylethyl] [3-methoxy- 4- (5-oxazolyl)phenyl] oxalamide53. 32 N- (4-Fluorobenzamido)phenyl] cl F -,-dimethylethyl] 3 -methoxy- 4- (5-oxazolyl)phenyl] oxalamide 531.1 353 dimethylethyl] 3-methoxy-4- 543.2 354 oxazolyl)phenyl]I oxalamide [4-(2-Chlorobenzamido) 050 Y phenyl]-1,1-dimethylethyl]-N'-[3-I-54. methoxy-4-( 5-oxazolyl)phenyl] 4. oxalamide N-[2-[4-(3-Chlorobenzamido) cN' phenyl] -1,1-dimethylethyl] [3methoxy-4- (5-oxazolyl)phenyl] _j oxalamide N- (4-Chlorobenzamido)Cy phenyl]-1,1-dimethylethyl]-N'-[3- Nk.0 4. methoxy-4- (5-oxazolyl)phenyl] 4.

oxalamide N- (H-Indol-2-yl) carboxamido] phenyl] 1, 1 dimethylethyl] [3-methoxy-4- (5 N 162 oxazolyl)phenyl] oxalamide 552.1 358 N- [3-Methoxy-4-(5-oxazolyl)phenyl] [1,1-dimethyl-2- [4-56.39 (dimethylamino)benzamidolphenyl]e e5. thyl] oxalamide N- [3-Methoxcy-4- (5-oxazolyl)phenyl] l 1, 1-dimethyl-2- (3,3dimethylbutyramido) phenyl] ethyl] o 507.1 360 xalamide N- [3-Methoxy-4- (5-oxazolyl)phenyl] l 0 1-dimethyl-2- (1 tetrazolyl)acetamido] phenyl] ethyl] ox51. 36 alamide N- [3-Methoxcy-4-(5-oxazolyl)phenylI t o -N'--[1,1-dimethyl-2- [(5-oxo-2(S)-o52. 36 pyrrolidinyl)carboxamido] phenyl] eth52.36 yl]I oxalamide N- [3-Methoxy-4- (5-oxazolyl)phenyl] N Y 1,1-dimethyl-2-{4- 52.36 pyrrolidinyl)carboxamido]phenyl] eth52.36 yI] oxalamide N- [3-Methoxy-4- (5-oxazolyl)phenyl] cK 1, 1-dimethyl-2- 56.o6 naphthyl)carboxamido] phenyl] ethyl] S53. 6 oxalamide N- [2-14- [(6-Cyano-3-pyridyl)c carboxamido] phenyl}- 1, 1 X dimethylethyl] [3-methoxy-4-(5- ~!-580.1 365 oxazolyl)phenyl] oxalamide

(M+H+

ACN)

163 N- [4-(3-Methoxybenzamido) 1 phenyl]-1,1-dimethylethyl]-N'-[3methoxy-4- (5-oxazolyl)phenyll 543.1 366 oxalamide N- [4-(3,5-Difluorobenzamido) phenyl]-1,1-dimethylethyl]-N'-[3- 54. 3675OI~ methoxy-4- oxalamide N- 1H-Indol-5-yl) carboxamido] phenyll -1,1dimethylethyl] [3-methoxy-4- 552.1 368 oxazolyl)phenyl]I oxalamide [4-(2-Butenamido)phenyl] 0 1,1 -dimethylethyl] [3-methoxy-4- I oxalamide 477.1 369 N- (2-Methoxyacetamido) phenyl] ,1-dimethylethyl] m eth oxy 4- (5 -oxa zolyl) ph en yl 481.2 370 oxalamide N 3 -meth oxy- 4 oxa zolyl) phe nyl] 1, 1 -di methyl -2 4- (2 -m ethyl -3 0 517. 37 fu ryl) carb oxam ido p he nyllI ethyl oxal51. 37 amide N- [3-Methoxcy-4-(5-oxazolyl)phenyl] I ~ro 1, 1-dimethyl- 2- [(5-methyl-4- 51.37 isoxazolyl)carboxamido] phenyl] ethyl] 51. 7 oxalamide N- [3-Methoxy-4-(5-oxazolyl)phenyl] JIo 1,1-dimethyl-2- [(3-methyl-4- 0 518.1 373 isoxazolyl)carboxamidol phenyl] ethyl] oxalamide

N

N. N N

N

N. N

N

N.

N

164 N- [3-Methoxy-4-(5-oxazolyl)phenyl] N0 -N'-[1,1-dimethyl-2-[4-[(5-methyl-3- I

Y

isoxazolyl)carboxamido] phenyl] ethyl] 518.1 374 oxalamide N- [3-Methoxy-4-(5-oxazolyl)phenyl] I 1,1-dimethyl-2- l-oxido-3- I-53.37 pyridyl)carboxamido] phenyl] ethyl] ox53. 37 alamide N- [3-Methoxy-4-(5-oxazolyl)phenyl] I 1,1 -dimethyl-2- 1-oxido-4pyridyl) carboxamido] phenyl] ethyl] ox I 3. 7 alamide N- [3-Methoxy-4- (5-oxazolyl)phenyl] I Oc [1,1-dimethyl-2- 0JX dimethyl-2-furyl)carboxamido] 531.1 377 phenyl]I ethyl] oxalamide N- [3-Methoxy-4-(5-oxazolyl)phenyl] 1, 1 -dimethyl-2- oNlI1Q 2 0% dimethyl-2H-pyrazol-3-yl) N531.1 378 carboxamido] phenyl]-1,1 dimethylethyl]I oxalamide N- [3-Methoxy-4-(5-oxazolyl)phenyl] 1,1-dimethyl-2- [(3-methyl-2- o 3. 7 thienyl)carboxamido] phenyl] ethyl] ox53. 37 alamide N- [3-Methoxy-4-(5-oxazolyl)phenyl] o [1,1-dimethyl-2- 0 thienyl)acetamido] phenyl] ethyl] oxala53. 38 mide N- [3-Methoxy-4-(5-oxazolyl)phenyl] N5 l(O 0 [1,1 -dimethyl-2- [(4-methyl-2- 3. 8 thienyl)carboxamido]phenyl] ethyl] ox<I53. 38 alamide 165 N- [3-Methoxy-4-(5-oxazolyl)phenyl] -i 1,-dimethyl-2- [(4-methyl- 38 1 ,2,3-thiadiazol-5-5338 yl)carboxamidolphenyl] ethyl] oxalami de N- (4-Acetamidobenzamido) phenyl] -1,1-dimethylethyl] -o570.1 383 methoxy-4- oxalamide N- [4-(3,4-Dimethoxybenzamido) phenyl] -1,1-dimethylethyl] 573.1 3841I methoxy-4- (5-oxazolyl)phenyl] 7. 8 oxalamide N- [4-(4-Chloro-2- -11I dimethylethyl] [3-methoxy-4-(5- N'578.2 385 oxazolyl)phenyl] oxalamide N- [4-(2,6-Dichlorobenzamido) o phenyl] 1,1 -dimethylethyl] o c, methoxy-4-( 5-oxazolyl)phenyl] 581 386 oxalamide N- [(Bicyclo octa- o NY~ triene-7(RS) -yl)carboxamido] phenyl] ,1-dimethylethyl] W,539.1 387 methoxcy-4- oxalamide N-[3-Methoxy-4-(5-oxazolyl)phenylI c,% -N'-[1,1-dimethyl-2-[4-(2-oxo-2-o54. 38 phenylacetamido)phenyl] ethyl] oxala54.38 mide N- [2-(2-Fluorophenyl)I yyi' acetamido ]phenyl}-1, 1- 54 8 dimethylethyl] [3-methoxy-4-(5- V 4 8 166oxazolyl)phenyl] oxalamide N- [2-14- [2-(4-Fluorophenyl) acetarnidol phenyl 1,1 -5439 dimethylethyl) 3-methoxy-4- (5-39 oxazolyl)phenyl] oxalamide N- [3-Methoxy-4- (5-oxazolyl)phenyl] TIo y -N-[2-{4-[(4-methoxy-3-thienyl) (0 o carboxamido] phenyll -1,1-5439 dimethylethyl]I oxalamide N- [4-(4-Acetylbenzamido)phenyl 1, 1-dimethylethyl] 55.39 methoxy-4- (5-oxazolyl)phenyl] IJ55. 9 oxalamide N- [(1,3-Benzodioxol-5-yl) o carboxamido] phenyl] -1,1 -o57. 39 dimethylethyl] -methoxy-4- (5-57. 39 oxazolyl)phenyl] oxalamide N- [2-(2-Chlorophenyl) nc acetamido] phenyl 1, 1 -56. 39 dimethylethyl] [3-methoxy-4- (5-56. 39 oxazolyl)phenyl] oxalamide N- [2-(4-Chlorophenyl)0 acetamido]phenyl]-1,1dimethylethyl] [3-methoxy-4- 561.1 395 oxazolyl)phenyl] oxalamide tert-Butyl [2-[[[3-methoxy-4- IA oxalyl] amino] -2methyipropyl] phenyl] carbamnoyl) benz 613 596 oate 167- [3-Methoxy-4-(5-oxazolyl) anilino] oxalyl] amino]-2- 557 597 methylpropyl]phenyl]carbamoyl]benz oic acid Examples 396-406; 433-437;542-595 and 635-650 Typical methods used for the preparation of the compounds of tables If', lf 2 and if are described below: Example 398.

N-[3-Methoxy-4-(5-oxazolyl)phenyll-N'-[1,1-dimethyl-3-(4nitrophenoxy)propyl] oxalamide S(i) A mixture of 0.5g (3.94 mmol) of 2,4,4-trimethyl-5,6-dihydro-1,3(4H)oxazine and 1. 0.5g (3.6 mmol) of 4-nitrophenol were heated at 180C under a nitrogen atmosphere for 6 15 hours. The resulting mixture was cooled and purified by chromatography on silica gel using ethyl acetate for the elution. There was obtained 524 mg of N-[1,1-dimethyl-3-(4- :nitrophenoxy)propyl] acetamide.

(ii) 693 mg (2.61 mmol) of N-[1,1-dimeyhyl-3-(4-nitrophenoxy)propyl]acetamide, 815 mg(2.87 mmol) of titanium isopropoxide and 719 mg (3.91mmol) of diphenylsilane were dissolved in 8 ml of tetrahydrofuran and left at room temperature for 18 hours. The resulting solution was dissolved in ethyl acetate and saturated sodium bicarbonate solution, filtered and the organic phase extracted twice with 2M hydrochloric acid. The combined acid extracts were basified with 2M sodium hydroxide solution, extracted with ethyl acetate and the organic extracts dried over magnesium sulphate, filtered and evaporated to dryness to give 266 mg of 1,1-dimethyl-3-(4-nitrophenoxy)propylamine.

The 1,1-dimethyl-3-(4-nitrophenoxy)propylamine was then coupled to N-[3-methoxy-4oxalamic acid by a procedure analogous to that described in example 1 -168to give N-[3-methoxy-4-(5-oxazolyl)phenyl]-N'- [1,1-dimethyl-3-(4nitrophenoxy)propyl]oxalamide as a pale yellow solid. MS: m/e 469 Example 433 4- [3-Methoxy-4-(5-oxazolyl)anilino] oxalyll amino] -3-methylbutoxvybenzoic acid.

A solution of 650 mg (1.17 mmol) of benzyl 4- [3-methoxy-4-(5oxazolyl)anilino]oxalyl] amino]-3-methylbutoxy]benzoate in 20 ml of tetrahydrofuran was hydrogenated with 65 mg of 10% palladium on charcoal catalyst for 48 hours, a further mg of catalyst being added after 24 hours and again after 44 hours. The resulting suspension was filtered, evaporated to dryness and the residue triturated with diethyl ether to give 415 mg of 4- [3-methoxy-4-(5-oxazolyl)anilino]oxalyl]amino]-3methylbutoxy]benzoic acid as a white solid. MS: m/e 468 The starting material was prepared as follows: i) A mixture of 1.14 g (5 mmol) of benzyl 4-hydroxybenzoate and 800 mg (6.3 mmol) of 2,4,4-trimethyl-5,6-dihydro-1,3(4H)-oxazine was stirred and heated at 180 0 C for 3 hours. A further 600 mg (4.72 mmol) ofoxazine were added and heating was continued for 21 hours. The resulting mixture was cooled and chromatographed on silica gel using ethyl acetate/petrol for the elution. There was obtained 1.52 g ofbenzyl 4-(3acetamido-3-methylbutoxy) benzoate as a white solid. 'H NMR (400 MHz CDCl 3 8: 1.43 1.94 2.26 4.14 5.36 5.65 6.91 7.35- 7.52 8.05 (2H,d).

a ii) A solution of 1.5 g (4.23 mmol) of benzyl 4-(3-acetamido-3-methylbutoxy) benzoate, 1.166 g (6.35 mmol) of diphenylsilane and 1.2 g (4.23 mmol) of titanium(IV) isopropoxide in 4 ml of tetrahydrofuran was stirred at room temperature for 6 hours. The resulting mixture was diluted with diethyl ether/2M sodium hydroxide solution, filtered and the organic phase extracted twice with 2M hydrochloric acid. The combined aqueous -169extracts were basified with 2M sodium hydroxide solution and extracted with ether. The organic extract was dried over magnesium sulphate and evaporated to dryness to give 1.16 g of benzyl 4-(3-amino-3-methylbutoxy) benzoate as a pale coloured gum. 'H NMR (400 MHz CDC1 3 8:1.22 1.92 4.08 5.36 6.90 7.33-7.48 8.05 (2H,d).

iii) A solution of 873 mg (3.33 mmol) of N-[3-methoxy-4-(5oxazolyl)phenyl]oxalamic acid, 500 mg (3.27 mmol) of 1-hydroxybenzotriazole hydrate, 1.2 g (3.83 mmol) of benzyl 4-(3-amino-3-methylbutoxy) benzoate and 1 g (5.22 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in 10 ml of dimethylformamide was stirred at room temperature for 24 hours. The resulting mixture was diluted with ethyl acetate and washed with 2M hydrochloric acid, saturated sodium bicarbonate solution and water then dried over magnesium sulphate, evaporated to dryness and chromatographed on silica gel using ethyl acetate/petrol for the elution.

After trituration with diethyl ether there was obtained 765 mg ofbenzyl oxalyl] amino]-3-methylbutoxy]benzoate as a white solid.

MS: m/e 558 [M+H] o* Example 434 2- 3- [3-Methoxy-4-15-oxazolvl)anilinoIoxalylI aminol-3-methylbutoxylbenzoic acid.

In an analogous manner to that described in Example 433 but replacing benzyl 4- 25 [[3-methoxy-4-(5-oxazolyl)anilino oxalyl] amino -3-methylbutoxy]benzoate with Sbenzyl 2- [3-methoxy-4-(5-oxazolyl)anilino]oxalyl]amino]-3-methbeylbutox enzoate there was obtained [3-methoxy-4-(5-oxazolyl)anilino] oxalyl] amino]-3methylbutoxy]benzoic acid as a white solid. MS: m/e 468 The starting material was prepared as follows: 170w i) A solution of 917 mg (3.5 mmol) of N- [3-methoxy-4-(5-oxazolyl)phenyl]oxalamic acid, 650 mg (4.66 mmol) of 3-amino-3-methyl-1-butanol hydrochloride 612 mg (4 mmol) of 1-hydroxybenzotriazole hydrate, 690 mg (6 mmol) of N-ethylmorpholine and 960 mg (5 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in ml of dimethylformamide was stirred at room temperature for 20 hrs. The resulting mixture was diluted with ethyl acetate and washed with 2M hydrochloric acid, saturated sodium bicarbonate solution and water then dried over magnesium sulphate, evaporated to dryness and chromatographed on silica gel using ethyl acetate/petrol for the elution. There was obtained 410 mg of N-(3-hydroxy-1,l-dimethylpropyl)-N'-[3as a pale yellow solid. MS: m/e 348 ii) A solution of 48 mg (0.276 mmol) of diethyl azodicarboxylate in 2 ml of tetrahydrofuran was added to a mixture of 72 mg (0.275 mmol) of triphenylphosphine, 57 mg (0.25 mmol) of benzyl salicylate and 87 mg (0.25 mmol) of N-(3-hydroxy-1,1dimethylpropyl)-N'- [3-methoxy-4-(5-oxazolyl)phenyl] oxalamide and left at room temperature for 1 hour. The resulting mixture was chromatographed twice on silica gel using first ethyl acetate/petrol then methanol/dichloromethane (1:49) for the elutions. There was obtained 29 mg of benzyl [3-methoxy-4-(5- 20 oxazolyl)anilino]oxalyl]amino]-3-methylbutoxy]benzoate as a colourless gum. MS: m/e 558 [M+H] t Example 435 25 3- 3- [3 3-Methoxy-4-(5-oxazolvyl)anilinol oxalyll aminol -3-methylbutoxy]benzoic acid.

In an analogous manner to that described in Example 433 but replacing benzyl 4hydroxybenzoate with benzyl 3-hydroxybenzoate there was obtained 3-[3-methoxy-4-(5oxazolyl)anilino]oxalyl] amino] -3-methylbutoxy]benzoic acid as a white solid. MS: m/e 468 171 W Example 553 4- [2-If 3-Methoxcy-4-( 5-oxazolyl)anilinol oxalylI amino] -2-methylpropox ylbenzoic acid.

In an analogous manner to that described in Example 433 but replacing benzyl 4- [3-methoxy-4- (5-oxazolyl)anilino] oxalyl] amino] -3-methylbutoxy]benzoate with benzyl 4- [3-methoxy-4- (5-oxazolyl)anilino] oxalyl] amino] -2methyipropoxy] benzoate there was obtained 4- [3-methoxy-4- oxazolyl)anilino]oxalyll amino] -2-methylpropoxylbenzoic acid as a white solid. MS: m/e 454 The starting material was prepared as follows: (i A ouino .8 4mo)o ,-ietyaiiie(ars .A.Ce.Sc 191 63 871.n 4 ml fbny -ydoyezaei 0m fclrfr wt lrmehe Ah solution ofs 0.280d gw4io)of22dm thaMiridie (Cair, d s.om.Che.ioc.

194012:3:87) anode9g(4d)o benzyl 4-(2-aio2- ehyroxybenzoate n30g ofchoor was) heTe unerrelue f-(-aio- 3 hr mThrctonxturne was loed to oo an[dlue 2wihdormethoane. Thensoluton asi ashd ith mae snoodum hydoxiade sluionfo chromatogr33, aphy ofii the reide usngyldich2-loromethnomthno- aetc (240:12:3:)afforded bezyflio 4(an-2-methylpropoxy~benzoa hte sol.30g m 172- Example 561 was prepared in a manner analogous to that described for example 433, parts and (ii) where the benzyl 4-hydroxybenzoate was replaced with 3-cyanophenol.

Examples 585, 588 and 589 were prepared from the compounds of examples 583, 587 and 586 respectively, by reacting the nitrile substituent with trimethylsilyl azide and dibutyl tin oxide according to the method of S.J. Wittenberger and B.G.J. Donner, J. Org. Chem., 1993,58,4139-4141.

For examples in table 1if' containing unprotected hydroxyl or amino groups suitable protecting groups were used, such as benzyl for hydroxyl and benzyloxycarbonyl for amino or similar groups, hereinbefore mentioned and well known in the art.

table if' Name Structure MS(ES) Ex No N- [3-(4-Hydroxy-phenoxy)- 1,1- 0 o dimethyl-propyl] -N'-(3-methoxy- 4 0 ot 4-oxazol-5-yl-phenyl)-oxalamide 440 396 N-[3-Methoxy-4-(5-oxazolyl) aphenyl]-N'-[3-(4methoxyphenoxy)-1,1dimethylpropyl] oxalamide N- [3-Methoxy-4-(5-oxazolyl) phenyl] [1,1 -dimethyl-3-(4nitrophenoxy)propyl] oxalamide -1- 173 N-[3-(2-Hydroxyphenoxy)-1,1-

N~

dimethylpropyll-N'-[3-methoxy-4- I- N oxalamide 0 CH, 440 399 N- (4-Amino-phenoxy)- 1, 1- N 0'CH dimethyl-propyl] -N'-(3-methoxy- oN 4-oxazol- 5-yl-phenyl) -oxalamide 0 CH 439 400 N- (4-Acetylamino-phenoxy) 1,1 -dimethyl-propyl] -N'-(3-04841 0 CH, oxalamide N-[3-Methoxy-4-(5-oxazolyl) V phenyl] 1,-dimethyl-3-(3- ANS(N pyridyloxcy)propyl] oxalamide oN 425 402 N- 3- (3-Hydroxyphenoxcy)- 1, 1- N -00 dimethyipropyl] 3-methoxy-4_ (5-oxazolyl)phenyl] oxalamide 0 440 403 N- [3-Methoxy-4- (5-oxazolyl) N1phenyl] 044404 methoxyphenoxy)-1,1 dimethyipropyl]I oxalamide N- [3-Methoxy-4-(5-oxazolyl)

Q.

phenyl] 1,1 -dimethyl-3-(3- iQN YNN nitrophenoxy)propyl] oxalamide 0469 405 N- [3-(3-Aminophenoxy)- 1, 1 O dimethyipropyl] [3-methoxy-4- OC<N (5-oxazolyl)phenyl] oxalamide 0439 406 4- [3-Methoxy-4- anilino] oxalyl] amino] 0 O- 46I3 methylbutoxy] benzoic acid 04643 2-[3-[[[3-Methoxy-4-(5-oxazolyl) 0 anilino] oxalyl] amino] 0 cl 468 434 174 methylbutoxy]benzoic acid 3-[3-[[[3-Methoxy-4-(5-oxazolyl) anilino] oxalyl] amino] CH6.

methylbutoxy]benzoic acid 468 435 [3-Methoxy-4-(5oxazolyl) anilino] oxalyl] amino] -3methylbutoxy] phenoxy] acetic acid 0 498 436 2-[2-[3-[[[3-Methoxy-4-(5oxazolyl)anilino] oxalyl] amino] -3methylbutoxy] phenoxy] acetic acid 4903 N-[3-Methoxy-4-(5-NO oxazolyl)phenyl]-N'-(1,1-dimethyl- C. 2 4 3 -phenoxypropyl)oxalamide 4252 N-[3-Methoxy-4-(5-oxazolyl) 0N phenyl] [1,1 -dimethyl-3-( 1oxido-3-pyridyloxy)propyl] 1 441 543 oxalamide N-[3-(3,4-Dihydroxyphenoxy)-1,1- V NgOC dimethylpropyl]-N'-[3-methoxy-4- 0 CH 1 oxalamide 0'456 544 N-[3-Methoxy-4-(5-oxazolyl)I phenyl] [1,1-dimethyl-3- 0 CH 48154 (methylcarbamoyl)phenoxy] propyl04855 oxalamide N- [3-Methoxy-4-(5-oxazolyl) phenyl]-N'-[3-(3,4-0 dimethoxyphenoxy) 1, 1 -4856 dimethylpropy1] oxalamide N- [(2-Hydroxyethyl) N carbamoyl] phenoxy] -1,1 -dimethyl- CH. I propyl]-N'- [3-methoxy-4-(5- 511 547 175 oxazolyl)phenyl] oxalamide N- [3-(3-Chlorophenoxy)- 1, 1- N dimethylpropyl] [3-methoxy-4- a 45 548a oxalamide C~K 5 4 N- [3-Methoxy-4-(5-oxazolyl) 10 N 0 I phenyl] 1-dimethyl-3- N pyridyloxy)propyl]I oxalamide\-N4259 N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N'-[1,1-dimethyl-3-(2-Ipyridyloxy)propyl] oxalamide O-C 0l 425 550 2-[4-[3-[[[3-Methoxy-4-(5-

W--

oxazolyl)anilino I oxalyl] amino] 0C methylbutoxy] phenyl] acetic acid 482 551 2- [3-Methoxy-4-(5oxazolyl)anilino] oxalyl] amino] -3methylbutoxy] phenyl] acetic acid 1 482 552 4-[2-[[L[3-Methoxy-4-(5-oxazolyl) 0 NLKO anilino] oxalyll amino] 0 methylpropoxy]benzoic acid4553 [[[3-Methoxy-4-(5-oxazolyl) NO anilino oxalyl amino] O methylbutoxy] -2-methylbenzoic CM OH. 482 554 acid 3 3 -Meth oxy- 4 L oxazolyl)anilino] oxalyl] amino] 0 methylbutoxy] phenyl] propionic 496 555 acid 3- [[3-Methoxy-4oxalyl] amino] 0 3-methylbutoxy] phenyl] propionic 0496 556 -176- S. *5 acid [[3-Methoxy-4-(5-

N

oxazolyl) anilino] oxalyl] am ino] o CH, 496 557 methylbutoxy] phenyl] propionic4957 acid 2- 3- 3- [[3-Methoxy-4- (5-o 01A0 oxazolyl) anilino] oxalyl] amino] -3methylbutoxy] phenoxy] acetic acid 498 558 4-[3-[[[3-Methoxy-4-(5-oxazolyl) N 0 anilinol oxalyl] amino] I~ c methylbutoxy] -3-methylbenzoic 48o5 acid

-N

N-[3-(4-Cyano-2- qI I 0 methoxyphenoxy)-1,1- o 479 56 dimethyipropyl] -N'-[3-methoxcy-4-4756 -oxazolyl) phenyl oxalamide N 3 -Cyanophenoxy) 1-

NY-

o dim ethyip ropyl] 3 -methoxy- 4- ,j49. 6 oxalamide49.56 N- 3- (4-Acetyl- 1 -piperazinyl) phenoxy] -1,1-dimethyipropyl] 550.4 562 methoxy-4- oxalamide N- [3-Methoxy-4-(5- I oxazolyl)phenyl]-N'-[1,1-dimethyl- (N314)6 3- (2-morpholinophenoxy)propyl] 3. 6 oxalamide (M +Na)+ N- [3-Methoxy-4-(5-oxazolyl) c c phenyl] [1,1-dimethyl-3- o (dimethylamino)phenoxy] 489.6 564 (M +Na)< 177propylloxalamide CH, 0 c N-[3-(1,3-Benzodioxol-5-yloxy)- -YvN:Y ,Ccoo> )a I'l-dimethylpropyll-N'-[3- -il

N

468.4 565 oxalamide N-[3-Methoxy-4-(5-oxazolyl) phenyl]-N'-[3-(3,4,5trimethoxypheno)cy) 1, 1 514.4 566 dimethylpropyl] oxalamide N- [3-Methoxy-4-(5-oxazolyl) oct o phenyl]-N'-[3-(3,5- o dimethoxyphenoxy) 1, 1 N-j 506 567 dimethylpropyl]oxalamide (M Na)' o N-[3-(5,6,7,8-Tetrahydro-5-oxo-2- cFj 0 H.C I-o naphthyloxy)-II-dimethylpropylI o N'-[3-methoxy-4-(5- 492.4 568 oxazolyl)phenyl I oxalamide ol N-[3-(2-Acetamido-5- Y t o tc al a 4 methylphenoxy)-II- 01 dimethylpropyl]-N'-[3-methoxy-4- o 517.6 569 oxalamide (M Na)-' N-[3-(3-Acetamidophenoxy)-1,1- o dimethylpropyl]-N'-[3-methoxy-4- '.-Jt oxalamide 503.6 570 (M Na)+ N-[3-(IH-Indol-4-yloxy)-1,1- cl o c cH c,-a L N dimethylpropyll-N'-[3-methoxy-4-

A

oxazolyl) phenyl oxalamide 1\1 jl 485.2 571 (M Na)+

F

CH. o N-[3-(2-Fluoro-6- I o N o"? methoxyphenoxy)-II- o o dimethylpropyl]-N'-[3-methoxy-4- I N 472.2 572 178 oxalamide N- [3-Methoxy-4-(5-oxazolyl) o phenyl] [1,1-dimethyl-3-(2oxo-2H- 1-benzopyran-7- 492.4 573 yloxy)propyl] oxalamide N- (4-Acetyl-3-methylphenoxy)- N~ oIcc 1,1-dimethylpropyl]-N'-[3- C, 480.2~." 57 methoxy-4- (5-oxazolyl)phenyl]48. 57 oxalamide [3-Methoxy-4-(5-oxazolyl) It oc m phenyl] 1,-dimethyl-3- o 49. 57 oxo-l1-butenyl)phenoxy] propyl] oxalamide N- [3-(3-Acetylphenoxy)- 1,1- N 0lo Isc dimethyipropyl] [3-methoxy-4- 466. 07 oxalamide46.57 N- [3-(4-Acetylphenoxy)- 1, 1 oHc\, o dimethyipropy] [3-methoxy-4- o 46. 7 (5-oxazolyl)phenyl] oxalamideN46.57 N- [3-(4-Acetamido-2- (HX-~ chlorophenoxy)-1,1- dimethyipropyl] methoxy-4- 515.6 578 oxalamide N-[3-Methoxy-4-(5- W'o~ oc" oxazolyl)pbenyl]-N'-[1,1-dimethyl--I 3-(4-pyridyloxy)propyl] oxalamide oH, 1 N 425 579 N 0 CH N- [3-Methoxy-4-(5-oxazolyl) phenyl] ,1-dimethyl-3-(l 1-HI41 8 oxido-4-pyridyloxy)propyl] 4 8 oxalamide 179 N- [3-Methoxy-4-(5-oxazolyl) S'No-~t I phenyl] 1,1 -dimethyl-3-(2,6- Iy dimethyl-4-pyridyloxy)propyl] Ci453 581 oxalamide N- 3-Methoxy-4- phenyl]-N'-[I,1-dimethyl-3-(2,6-0 dimethyl- 1-oxido-4-pyridyloxy) OA469 582 propyl] oxalamide N- (4-Cyanophenoxy) 1- 10 N 0 0 dimethylethyl] [3-methoxy-4- oxalamideN4358 N- [3-Methoxy-4-(5-oxazolyl) P phenyl] [3-(2-methoxy-4pyridyloxy)- 1,1 -dimethyipropyl] 5 584 oxalamide N-[3-Methoxy-4-(5-oxazolyl) 0 'kAa phenyl] 1, 1 -dimethyl-2-

N

(1 H-tetrazol-5-yl)phenoxy] ethyl] 478 585 oxalamide N- (4-Cyanophenoxy) -1,1 dimethyipropyll [3-methoxy-4-4958 oxalamide N- (3-Cyanophenoxy)- 1, 1- 0 _NA N dimethylethyl] f[3-methoxy-4- oK I' (5-oxazolyl)phenyl] oxalamide V476 587 fl,- 0 H N-N, N- [3-Methoxy-4-(5-oxazolyl) 0 N 'eN0 N N phenyl] 1-dimethyl-2- [3-CH (1 H-tetrazol- 5-yl)phenoxy] ethyl] 478 588 oxalamide N- [3-Methoxy-4- (5-oxazolyl) 1. 0 I phenyl] 1-dimethyl-3- (1 H-tetrazol-5-yl)phenoxy] propyl]4958

N

N N 180 oxalamide oxazolyl)anilino] oxalyl] amino] -1Icyclobutyl] ethoxylbenzoate 570.2 590 Benzyl 4- [1-[[[3-methoxy-4-(5oxazolyl)anilino] oxalyl] amino] -1Icyclopentyl] ethoxylbenzoate 584.3 591 Benzyl 4- [1-[[[3-methoxy-4- oxazolyl)anilino] oxalyl] amino] -1I- cyclohexyl] ethoxy] benzoate 598.3 592 4- [3-Methoxy-4- 01 oxazolyl)anilinol oxalyl] amino] I cyclopentyllethoxy]benzoic acid N/I 494.2 593 4- [3 M et oxy- c0 oxazolyl)anilino] oxalyl] amino] 0. 9 cyclohexyllethoxylbenzoic acid N50. 59 4- [[3-Methoxy-4-(5- C,oxazolyl) anilino ]oxalyl) amino 0 cyclobutyl] ethoxylbenzoic acid 480.2 595 Benzyl 2-methoxy-4- methoxy-4- (5-0 lla oxazolyl)anilino] oxalyl] amino] 0588 635 methylbutoxy] benzo ate /90 .,o 3-Chloro-4-[3-[[[3-methoxy-4-(5- N 0 oxazolyl)anilino] oxalyl] amino] 11 methylbutoxy] benzoic acid05263 2-Methoxy-4- [[3-methoxy-4- L- Nl I I oxalyl] amino] 0-yN+_ 3-methylbutoxy]benzoic acid 0 498 637 181 3-Methoxy-4- [[3-methoxy-4- N /1oxalyl] amino] Iv 3-methylbutoxylbenzoic acid 0%o 498 638 4-[2-[1-[[143-Methoxy-4-(5- I oxazolyl)anilino] oxalyl] amino] -1 1 cyclopropyllethoxylbenzoic acid 466 639 2-Chloro-4-[3-[ [[3-methoxy-4-(5- oxazolyl)anilino] oxalyl] amino] -3-o methylbutoxy]benzoic acid. 502 640 4-[3-[[[3-Methoxy-4-(5-oxazolyl) o.

anilino] oxalyl] amino] -3-o methylbutoxy] 519 641 quinolinecarboxylic acid (cis/trans)-4- [3-[[[3-Methoxy-4- 0 anilino] oxalyl] amino] 0 +-KO'[DOH 3-methylbutoxy] 0 474 642 cyclohexanecarboxylic acid (cis/trans)-4- [[3-Methoxy-4- 0 -ItA (5-oxazolyl)anilino] oxalyl] amino] 0 2-methyipropoxy] 460 643 cyclohexanecarboxylic acid 3-Fluoro-4- [3-[[[3-methoxy-4-(5- N7 9 0F oxazolyl)anilino] oxalyl] amino] 0O methylbutoxy] benzoic acid 0 486 644 3-Acetamido-4- [3-[[[3-methoxy-4- 0~ HN oxalyl] amino] 0 IbyO 3-methylbutoxy]benzoic acid 0 525 645 3-(Methanesulfonamido)-4- N-O 0- 9 [[[3-methoxy-4-(5- Il N oxazolyl)anilino] oxalyl] amino] 0 561 646 methylbutoxy] benzoic acid

C

C

182 4- [3-[[[3-Methoxy-4-(5-oxazolyl) Q~ anilino] oxalyl] amino] methylbutoxy] 0 496 647 dimethylbenzoic acid [3-Methoxy-4-(5-oxazolyl) YU 0 OH anilino] oxalyl] amino] KONNt ,O Z methylbutoxy] 469 648 pyridinecarboxylic acid 0 H ethoxy-4-(5-oxazolyl)

N'

1 0 anilino] oxalyl] amino] 'INI~yNj,-O methylbutoxy] 0519 649 quinolinecarboxylic acid [[3-Methoxy-4- (5-oxazolyl) N-Y0 anilino] oxalyl] amino] 0 H methylbutoxy] -2-indolecarboxylicH5060 acid Examples 615-63 1 and 664-670 Example 615 N- 3-Methoxy-4- oxazolyl)phenyl]j 1, 1 dimethyl-2 -(phenylthio) ethyl] oxalamide.

A mixture of 2g (17.7 mmol) of 2,4,4-trimethyl-2-oxazoline and 1.95 g (17.7 mmol) of thiophenol were heated at 120C for 18 hours. After cooling the resulting solid was triturated with diethyl ether/petrol and filtered off to give 2.55 g of 1,1dimethyl-2- (phenylthio) ethyl] acetamide as a white solid.

183- (ii) A solution of 2.5 g (11.2 mmol) of N-[1,1-dimethyl-2- (phenylthio)ethyl]acetamide, 3.18 g (11.2 mmol) of titanium isopropoxide and 3.09 g (16.8 mmol) of diphenylsilane in 12 ml of tetrahydrofuran were stirred at room temperature for 18 hours. The resulting mixture was chromatographed on silica gel using 6% and methanol in dichloromethane for the elution. There was obtained 2 g of 1,1-dimethyl-2- (phenylthio)ethylamine as a pale orange oil. The 1,1-dimethyl-2-(phenylthio)ethylamine was then coupled to N-[3-methoxy-4-(5-oxazoyl)phenyl oxalamic acid by a procedure analogous to that described in example 1 to afford N-[3-methoxy-4-(5-oxazolyl)phenyl]- [1,1-dimethyl-2-(phenylthio)ethyl] oxalamide. MS: m/e 426 Example 616 was prepared by an analogous method to that described for example 615 but using 4-benzyloxythiophenol in place of the thiophenol and removing the protecting group using a mixture of hydrogen bromide in acetic acid.

The additional compounds in table If 2 were prepared in an analogous manner to that described for example 615 by reaction of the appropriate i*" thiol with either 2,4,4-trimethyl-2-oxazoline or 2,4,4-trimethyl-5,6- 20 dihydro-1,3(4H)oxazine and, where necessary, removal of any protecting groups by conventional methods.

table If 2 *o• 184 N- [3-Methoxy-4-(5-oxazol Yl) 0 C phenyl] 1, 1-dimethyl-2- 1 0 Nl (phenylthio) ethyl] oxalamide 0 F C 426 615 N- (4-Hydroxyphenyhthio)- 1, 1- N'210' 0 dimethylethyl] [3-methoxy-4- -lNfS& oxalamide 0442 616 N- [3-Methoxcy-4-(5-oxazolyl) N; 0- 0-c phenyl] 1,1-dimethyl-2- K 'JlyN- sy0 (phenylthio) ethyl] oxalamide CF 440 617 N- [3-Methoxy-4-(5-oxazolyl) N ,C~ 0 N phenyl] [1,1-dimethyl-2-(2- 6 IY pyridylthio) ethyl Ioxalamide 0 C C 427 618 N- [3-Methoxy-4-(5-oxazolyl)

N~

phenyl] [1,1-dimethyl-3- N S__N pyridylthio)propyl] oxalamide 0 Q- l 441 619 N- [3-Methoxy-4-(5-oxazolyl)

C"

phenyl] [1,1-dimethyl-3-(2thienylthio)propyl] oxalamide 0 C%446 620 N-[3-Methoxy-4-(5-oxazolyl) N'-O G-C' phenyl]-N'-[1,1-dimethyl-3-(2- W N, pyrimidylthio)propyl] oxalamide 0 442 621 N- [3-Methoxcy-4-(5-oxazolyl)N"0o phenyl] 1-dimethyl-3-(4-I 0 N4162 pyridylthio)propyl] oxalamide0 +4162 N- [3-Methoxy-4-(5-oxazolyl) WN-o0-O" phenyl]-N'-[1,1-dimethyl-3-(2thiazolylthio)propylloxalamide 0 C%447 623 N-[3-(4-Hydroxyphenylthio)-1,1- N 0" dimethyipropyl] [3-methoxy-4- 0 "45I2 -oxazolyl) phenyl oxalamide4562 a a.

a a a a a a.

a 185 N- [3-Methoxy-4-(5-oxazolyl) phenyl] 1, 1-dimethyl-3-(5- Nr>Y'N methyl-i ,3,4-thiadiazol-2-ylthio) 0FCH,462 625 propyl] oxalamide N- (2-Benzooxazolylthio) 1, 1 //0O 0 dimethyipropyl] [3-methoxy-4- -oxazolyl) phenyl oxalamide4862 N 3- (2 Benzothiazolylthio) 1- 0-~ dimethylpropyl]-N'-[3-methoxy-4- *4962 -oxazolyl) phenyl oxalamide4962 M ethyl 4 -methoxy- 4 I oxazolyl)anilino] oxalyl] amino] 0 methyipropyithiol benzoate 484 628 tert-Butyl 6- L L[3-methoxy-4-(5- 2 oxazolyl)anilino]oxalyl] amino] 00l methylbutylthio] C 541 629 pyridinecarboxylate 6-[3-[[[3-Methoxy-4-(5-oxazolyl) 0F0 anilino] oxalyl] amino] oi methylbutylthio] 0 485 630 pyridinecarboxylic acid trifluoro acetate (1:1) [[3-Methoxy-4-(5-oxazolyl) c H anilino]oxalyl] amino] I ii:C methylbutylthiolbenzoic acid 0484 631 N- [2-(4-Benzyloxyphenylthio)- 1,1- dimethylethyl] [3 -methoxy-4oxalamide 0532 664 N- [2-(4-Benzyloxyphenylthio)- 1, 1 O0 dimethylpropyl] -[3-methoxy-4- 0N N Sc~ 4 6 oxalamide5465 186 anilino] oxalyll amino] n H methylbutylthio] o C525 666 benzoxazolecarboxylic acid 1H-Imidazol-2-ylthio)- 1,1- N Q dimehylropll-'- 0 N4367 F 0 2-[3-[[[3-Methoxy-4-(5-oxazolyl) 0 Fr' anilino] oxalyl] amino] N kNX_--SNl 0 ot '485 668 methylbutylthio]

O

pyridinecarboxylic acid trifluoroacetate (1:1)

H

[[3-methoxy-4-(5-

O

oxazolyl)anilino] oxalyll amino] ~N methylpropylthiolbenzoic acid 470 669 2-[3-[[[3-Methoxy-4-(5-oxazolyl) anilino] oxalyl] amino] 52 7 methylbutylthio] -6-5267 benzoxazolecarboxylic acid ExamPles 632-634 The compounds in table I e were prepared in an analogous manner to that described for example 398 in table lfe by replacing the 4-nitrophenol with the appropriate aniline and reaction with either 2,4,4-trimethyl- 2-oxazoline or 2,4,4-trimethyl- 5,6-dihydro- 1,3(4H)oxazine and, where necessary, removal of any protecting groups by conventional methods.

187 table I e Name Structure MS(ES) Ex No

(M+H)

t N- [3-Methoxy-4-(5-oxazolyl) /NJ- 0I0 phenyl]-N'-[1,1-dimethyl-2-(Nmethylanilino) ethyl] oxalamide 0H C%423 632 N- (3-Anilino- 1,1-dimethyipropyl) 0~ 0 "CF' [3-methoxy-4-(5-oxazolyl) phenyl] oxalamide hydrochloride 0 HH423 633 1) 4- 3-1 [3-Methoxy-4- (5-oxazolyl) 0'c anilino]oxalyll amino] iv C ICIO0 6 3 methylbutylamino]benzoic acid04663 ExamPles 407-414; 459-54 1 and 651-65 2 Typical methods used for the preparation of the compounds of table Ig are described below: 10 Example 408.

N- [3-Methoxy-4-(5-oxazolyl)phenyl] [4-(4-methoxyphenyl)- 1 -piperazinyl] 1,1dimethylethyl] oxalamide.

A stirred solution of 3.23 g (16.8 mmol) of 1-(4-methoxyphenyl)piperazine, 2.00 g (16.8 mmol) of 2-methyl-2-nitropropan-l-ol and 5.34 g (50.4 mmol) of sodium carbonate 188in 40ml of n-butanol was refluxed for 16h. The reaction mixture was allowed to cool and diluted with 100ml of dichloromethane. The solution was filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel using petroleum ether/ethyl acetate (10:1) for the elution to afford 1.86 g (6.34 mmol, 38%) of 1-(4methoxyphenyl)-4-(2-methyl-2nitropropyl)piperazine as a white solid.

(ii) A solution of 1.86 g (6.34 mmol) of 1-(4-methoxyphenyl)-4-(2-methyl-2nitropropyl)piperazine and 0.5 g of palladium on activated charcoal in 50 ml of ethanol was stirred at room temperature under an atmosphere of hydrogen for 48h. The reaction mixture was filtered and the filtrate concentrated in vacuo to afford 1.59 g (6.04 g mmol, 95%) of 2-[4-(4-methoxyphenyl)-piperazin-1-yl)-l,l-dimethylethylamine as a clear oil.

The 2- [4-(4-methoxyphenyl)-piperazin-1-yl)-1,1-dimethylethylamine was then coupled to N-[3-methoxy-4-(5-oxazoyl)phenyl oxalamic acid by a procedure analogous to that described in example 1 to afford N-[3-methoxy-4-(5-oxazolyl)phenyl]-N'- methoxyphenyl)-1-piperazinyl]-1,1-dimethylethyl]oxalamide as a white solid. MS: m/e 508 Examples 407, 409, 410, 411, 412 and similar structures were prepared by an analogous procedure by replacing the 1-(4-methoxyphenyl)piperazine with the 20 appropriately substituted piperazine.

Examples 413 and 414 were prepared by an analogous procedure by replacing the 1-(4-methoxyphenyl)piperazine with t-butyl-1-piperazinecarboxylate to give 4-(2-amino- 2-methylpropyl)piperazine- -carboxylic acid t-butyl ester which was then coupled to N- [3-methoxy-4-(5-oxazoyl)phenyl oxalamic acid. The resulting product could then be deprotected to give N- [3-Methoxy-4-(5-oxazolyl)phenyl]-N'-[1,1-dimethyl-2-(1piperazinyl)ethyl]oxalamide that could be used for the preparation of examples 413 414 and a variety of additional N-acyl and N-sulfonyl derivatives, such as those shown in table Ig, by using the appropriate acylating or sulfonylating reagent.

189- Example 489.

[4-(Cyclohexylmethyl)- -piperazinyl]-1,1-dimethylethyl]-N'-[3- A stirred solution of 48mg of N-[3-methoxy-4-(5-oxazolyl)phenyl]-N'- [1,1dimethyl-2-(1- piperazinyl)ethyl] oxalamide (1.2mmol) and 13mg of cyclohexanecarboxaldehyde (1.2mmol) in 1ml of a 5% acetic acid dichloromethane mixture was treated with a solution of 38mg of sodium triacetoxyborohydride (1.8mmol) in Iml of a 5% acetic acid dichloromethane mixture. After stirring overnight at room temperature the reaction mixture was diluted with 10ml of dichloromethane and washed with 8ml of a sodium bicarbonate solution followed by 8ml of water. The organic layer was then evaporated and purified using flash chromatography on a silica gel column eluting with 5% methanol dichloromethane to give after evaporation of the fractions 14.3mg (0.3 mmol, 25%) of N-[2-[4-(cyclohexylmethyl)- -piperazinyl]-1,1-dimethylethyl]-N'- [3in the form of a white solid. MS: m/e 498.2 9 20 Additional N-alkylated compounds shown in table Ig were prepared by analogous methods.

table g 9 9 9 190 N- [3-Methoxy-4-(5- lo 09" r1 oxazolyl)phenyl] [1,1-dimethyl-2- (4-phenyl- 1- %0478 407 piperazinyl) ethyl]I oxalamide N- [3-Methoxy-4-(5- 0 oxazolyl)phenyl] NQ N'N methoxyphenyl) -1 -piperazinyl] 1,1- 0508 408 dlimethylethyl] oxalamide N- [3-Methoxy-4-(5- ao oxazolyl)phenyl] 0)N N N 0 0 methoxyphenyl)- 1-pip erazinyl] 1,1- N4CNY5049 dimethylethyl]I oxalamide N-[3-Methoxy-4-(5- N- O0'rI oxazolyl)phenyl] -dimethyl-3 3 -j (4-phenyl- 1- 0492 410 pip erazinyl)propyll oxalamide N- [3-Methoxy-4-(5- 0y N)NtO oxazolyl)phenyl] 0- 58 1 methoxy-phenyl) -1-piperazinyl] -1,1dimethylethyl]I oxalamide N-[2-(4-Benzyl-1-piperazinyl)-1,1oxazolyl)phenyl] oxalamide N492 412 N- [4-(Benzenesulfonyl)- 1- %o i piperazinyl] 1, 1 -dimethylethyl] 0 5 1 oxazolyl)phenyl] oxalamide 0 N- [2-(4-Benzoyl- 1-piperazinyl)- 1, 1dimethylethyl] 3-methoxcy-4-(5- 0 ~NNJ 0 oxazolyl)phenyl]oxalamide N506 414 Is.. S

S

S. 55 S S S.

S

S

S.

S

A.

S

S. S S 191 0 (Trifluoromethyl)phenyl] -1Ipiperazinyl] 1, 1-dimethylethyl] [3-methoxy-4-(5oxazolyl)phenyl]I oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] 1, 1 -dimethyl-2- [4-(2-methylphenyl)- 1piperazinyl] ethyl] oxalamide N- (2-Fluorophenyl)- 1 piperazinyll 1-1, 1 -dimethylethyl] [3-methoxy-4-(5oxazolyl)phenyl] oxalamide N- (4-Fluorophenyl)- 1 piperazinyl] 1, 1 -dimethylethyl] [3-methoxy-4-(5oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] (000.0: methoxyphenyl) 1- piperazinyl] 1,1 00 :000*0dimethylethyl]I oxalamide o* 0 N- [3-Methoxy-4-(5oxazolyl)phenyl] -dimethyl-2- :00.0[4- (2 -thiophenesulfonyl) -1piperazinyl] ethyl] oxalamide 0 N- [3-Methoxy-4-(5- .000 oxazolyl)phenyl] 1, 1 -dimethyl-2- 0000[4- (2,4,6-trimethylbenzenesulfonyl) 0 0 01 -piperazinyl] ethyl] oxalamide N- [4-(4-Fluorobenzenesulfonyl)- 1 -piperazinyl] 1,1 -dimethylethyl] [3-methoxy-4-(5oxazolyl)phenyl] oxalamide

I

0

N

0

ILO

0 C-%

CI%

0 0 192 N- [4-(Trifluoromethanesulfonyl)- 1I -piperazinyl] 1,1 -dimethylethyl] [3-methoxcy-4-(5oxazolyl)phenyl) oxalamide N- (Isopropylsulfonyl)- 1 piperazinyl] 1,1 -dimethylethyl] [3-methoxy-4-(5oxazolyl)phenyl) ]oxalamide [3-Methoxy-4-(5oxazolyl)phenyl] 1,1 -dimethyl-2- [4-(styrylsulfonyl)- Ipiperazinyl] ethyl] oxalamide N- [4-(Ethanesulfonyl)- 1 piperazinyll -1,1 -dimethylethyl] [3-methoxy-4-(5oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] 1,1 -dimethyl-2- 4-(propanesulfonyl)- 1- A 0 a..:piperazinyl] ethyl] oxalamide N- [2-[4-(3-Chloropropanesulfonyl)- 1 -piperazinyl] -1,1-dimethylethyl] [3-methoxy-4-(5oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5- .oxazolyl)phenyl]I 1, 1 -dimethyl- 2- (o-toluenesulfonyl) 1 piperazinyl] ethyl] oxalamide N- [4-(2-Fluorobenzenesulfonyl)- 1 -piperazinyl] -1,1-dimethylethyl] [3-methoxcy-4-(5oxazolyl)phenyl] oxalamide

I

CIs i

I

193 N- [4-(2-Cyanobenzenesulfonyl)- 1 -piperazinyl] 1, 1 -dimethylethyll 0 1~ 56.N7 [3-methoxy-4-(5-56. 47 oxazolyl) phenyl]I oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] o 56. 47 dimethyl-4-isoxazolylsulfonyl) -1Ipiperazinyl] -1,1 -dimethylethyl] oxalamide N- [4-(5-Fluoro-2methylbenzenesulfonyl) 1 0 piperazinyl] 1, 1 -dimethylethyl] 57.-7 [3-methoxy-4-(5oxazolyl)phenyl]I oxalamide N- q Difluorobenzenesulfonyl) -1Ipiperazinyl] -1,1 -dimethylethyl]-N'- ~'578.1 478 [3-methoxy-4-(5oxazolyl)phenyl] oxalamide N-[3-Methoxy-4-(5oxazolyl)phenyl] 1 -dimethyl-2- <1 o 4. 7 (1 -methyl-1IH-imidazole-4-54. 47 sulfonyl)- 1piperazinyl] ethyl] oxalamide o 0 F Difluorobenzenesulfonyl)- 1 i o ~57. 8 piperazinyll -1,1 -dimethylethyll 57.-8 [3-methoxy-4-(5oxazolyl)phenyl] oxalamide o Difluorobenzenesulfonyl)-l 1- piperazinyl 1-1,1-dimethylethyl] vo o578.1 481 [3-methoxy-4-(5oxazolyl)phenyl] oxalamide @00* 0 000000 00 *0 0 0 0 00 0 0* 00 194- 0cC% 0 1 (Cyclohexylmethanesulfonyl)-- 56. 48 pip erazinyl] 1, 1 -dimethylethyl] 56.-8 [3-methoxy-4-(5oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5cl cov 1o oxazolyl)phenyl] [1,1-dimethyl-2- o o 570.1 483 [4-(2-phenylethanesulfonyl)- 1piperazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] dimethoxyphenyl)- 1-piperazinyl] 538 484 1,1 -dim ethylethyl] oxalamide N- [3-Methoxy-4-(5-j. o oxazolyl)phenyl] [1,1 -dimethyl-2- o [4-(4-methylphenyl)-l- N492 485 piperazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5- o a [4 -di methylph enyl) I- 506 486 pip erazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] dimethoxyphenyl)- I-piperazinyl] 538 487 1,1 -dimethylethyl] oxalamide N- [2-(4-Cyclohexyl- I-piperazinyl)- 1,1 -dimethylethyl] [3-methoxy-4- o oxalamide 484.4 488 *0e* 0 0 jO. 0 0 *4*000

N

0*

N

00 0 0

NO

[4-(Cyclohexylmethyl)-1piperazinyl] -1,1 -dimethylethyl] [3-methoxy-4-(5o 0~ 498.2 48 195 oxazolyl)phenyl] oxalamide N- [4-(2-Methoxybenzyl)-1Ipiperazinyl] 1, 1 -dimethylethyl] [3-methoxy-4-(5oxazolyl)phenyl] oxalamide N- (2-Hydroxybenzyl)- 1 piperazinyl] 1, 1 -dimethylethyl] [3-methoxy-4-(5oxazolyl)phenyl] oxalamide N- [3-Methoxcy-4-(5-.

oxazolyl)phenyl] 1, 1 -dimethyl-2- (2-methylbenzyl) 1 pip erazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] 1,1 -dimethyl-2- [4-(2-thenyl)- 1pip erazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] [1,1 -dimethyl-2- 0. (2 (RS) -phenylpropyl) I1piperazinyl]I ethyl] oxalamide N- [3-methoxy-4-(5oxazolyl) phenyl I 1, 1 dimethyl-2 (4-pivaloyl- 1piperazinyl) ethyl] oxalamide N- [4-(2-Furoyl)- 1-piperazinyl] 1,1 -dimethylethyl] -[3-methoxy-4- 0600 9 (5-oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] 1, 1 -dimethyl-2- [4-(2-thenoy)- 1piperazinyl] ethyl] oxalamide 196 N- [3-Methoxy-4-(5oxazolyl)phenyl] [1,1 -dimethyl-2- 5149 [4-(3-thenoyl)-l 512-9 pip erazinyl] ethyl] oxalamide N- (2-Cyclopentylacetyl)- Ipiperazinyl] 1, 1 dimethyl- ethyl] [3-methoxy-4-(5- 512.1 499 oxazolyl)phenyl)]Ioxalamide N- [4-(Cyclohexylcarbonyl)- 1- 0~ piperazinyl] -1,1-dimethylethyl] -N'-51.50 [3-methoxy-4-(5-51. oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl]-N'- 1,1-dimethyl-2-52.50 [4-(2-methylbenzoyl)- 1-52. piperazinyl] ethyl] oxalamide N- [3-Methoxcy-4-(5- [4-oyl phnl(4-[1 1-dmethylbezy) 1oxazoleylenyl 11-dmy- 520.1 502 pip erazinyl] ethyl] oxalamide N- [4-(Cycloheptylcarbonyl) 1 OC piperazinyl] 1,1 -dimethylethyl] 526.2 [3-methoxy-4-(5- C 2. 0 oxazo lyl)p h enyl]I oxal am id e N- [3-Methoxy-4-(5oxazolyl)phenyl]-N'-] 1,1-dimethyl-2- 4 H-pyrazol-4-yl)carbonyl] C o496.1 504 piperazinyl]I ethyl]I oxalamide N 2- 4 -(Cycl op en tyl ca rb onyl) 1 piperazinyl] 1, 1 -dim ethylethyl] [3-methoxy-4-(5- Co 0498.1 505 oxazolyl)phenyl] oxalamide 0 0000 OOee S0 0e 6

S

0

OSSSS@

S

OS OS S 0 S. 0 S S

S.

0500@@ 6 *550 5 S. S 0@ 50 0 555.

0005 0 00 0 05 55 197 N- [3-Methoxy-4-(5oxazolyl)phenyl]-N'-[1,1-Dimethyl- 2- [(1-methyl- 1H-pyrrol-2-50. 56 yl)carbonyl] -1piperazinyl] ethyl] oxalamide N-[3-Methoxy-4-(5- 0I oxazolyl)phenyl] 1, 1 -dimethyl-2- I51.50 (1 ,2,3-thiadiazol-4-yl)carbonyl] -51. 1-pip erazinyl] -ethyl] oxalamide N- [4-(3-Fluorobenzoyl)- 1piperazinyl] -1,1 -dimethylethyl] [3-methoxy-4-(5- 524.1 508 oxazolyl)phenyl] oxalamide N- (4-Fluorobenzoyl)- 1- N VC piperazinyl]- 1,1-dimethylethyl] -0521 59 [3-methoxy-4-(5-v52. oxazolyl)phenyl]I oxalamide N- (Cyclopropylcarbonyl)- 1piperazinyl] -1,1 -dimethylethyl] OT [3-methoxy-4-(5- 470.1 510 oxazolyl)phenyl] oxalamide N-[2-[4-(2-Cyclohexcylacetyl)-l- 52. 511 pip erazinyl] -1,1-dimethylethyl] [3-methoxy-4-(5-52. 51 oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] 2- 500.2 512 dimethylbutyryl) -1-piperazinyl 1-1,1 dimethylethyl] oxalamide N- 2- [4-(3-Hydroxy-2,2dimethyipropionyl)- 1-piperazinyl] -50.51 1,1 -dimethylethyl] -[3-methoxy-4-50. 51 oxalamide 198 N- [3-Methoxy-4-(5oxazolyl)phenyl] 1 -dimethyl-2- [4-(3-methyl-2-furoyl)- 1 piperazinyl]I ethyl]I oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] 1,1 -dimethyl-2- (2-methyl-3-furoyl)- 1 pip erazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] 1, 1 -dimethyl-2- (5-methyl- 1H-pyrazol-3yl)carbonyl] -1piperazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] 1 -dimethyl-2- [(5-methyl-4isoxazolyl)carbonyl] -1Ipiperazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl]-N'-[ 1,1-dimethyl-2- [(5-methyl-3isoxazolyl)carbonyl] -1pip erazinyl] ethyl] oxalarnide N 2- 4- (4-Aminobenzoyl) 1 piperazinyl 1 dimethylethyl] [3-methoxy-4-(5oxazolyl)phenyl] oxalamide (2-Hydroxybenzoyl) 1 piperazinyl] -1,1 -dimethylethyl] [3-methoxy-4-(5oxazolyl)phenyl] oxalamide 199 N- [4-(4-Hydroxybenzoyl)-1Ipiperazinyl]-1,1-dimethylethylH-N'- 0 1- [3-methoxy-4-(5- (1522.1 521 oxazolyl)phenyl]I oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] 1,1 -dimethyl-2-52.52 (2,5-dimethyl-2H-pyrazol-3-52. 52 yl)carbonyl] -1piperazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5-0 oxazolyl)phenyl] 1, 1 -dimethyl-2-52.53 (3-methyl-2-thenoyl)- 1 -52. 53 piperazinyl] ethyl] oxalamide N- [3-Methoxcy-4-(5oxazolyl)phenyl] [1,1-dimethyl-2- 0 [4-(4-methyl-2-thenoyl)- 1- 526.1 524 pip erazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl]-N'-[1,1-dimethyl-2-52. [4-[(2,2,3,3-tetramethyl-l 52.-52 cyclopropyl)carbonyl] -1piperazinyl] ethyl] oxalamide N- [3-Methoxy-4- P* oxazolyl)phenyl] 1, 1 -dimethyl-2- [(4-methyl-i ,2,3-thiadiazol-5- 528.1 526 yl)carbonyl] -1piperazinyl] ethyl] oxalamide N- [4-(3-Cyanobenzoyl)- 1- c piperazinyl] 1,1 -dimethylethyl] 52 [3-methoxy-4-(5-53. 52 oxazolyl)phenyl] oxalamide 200 N- [(Bicyclo [4.2.O]octa- 1 (6),2,4-trien-7-yl)carbonyl] 1- o piperazinyl] -1,1 -dimethylethyl] J,532.1 528 [3-methoxy-4-(5oxazolyl)phenyl] oxalamide 0 0 N- (3-Hydroxybenzoyl)- 1 NCC F J pip erazinyl] 1, 1 -dimethylethyl] 59 [3-methoxy-4-(5-52.59 oxazolyl)phenyl] oxalamide N- (2-Ethylbutyl)-1I-o cl piperazinyl] 1, 1 -dimethylethyl] [3-methoxy-4-(5- 486.1 530 oxazolyl)phenyl] oxalamide N- [3-Methoxcy-4-(5- c w 1 oxazolyl)phenyl] 1, 1 -dimethyl-2- (2-phenylethyl) 1 o2I1 506.2 531 piperazinyl]I ethyl] oxalamide N-[3-Methoxy-4-(5- oxazolyl)phenyl] 1-dimethyl-2- 49.53 [3-(methylthio)propyl] -1-49. 53 piperazinyl] ethyl] oxalamide N-[2-[4-(2,6-Difluorobenzyl)-1piperazinyl] -1,1 -dimethylethyl] [3-methoxy-4-(5- 528.1 533 oxazolyl)phenyl] oxalamide N-[2-[4-(3-Furfuryl)-1-piperazinyl]- 1,1 -dimethylethyl] [3-methoxy-4- O~' (5-oxazolyl)phenyl] oxalamide 482.1 534 N- (2-Benzofuranyl)methyl] N".o9 I 1 -piperazinyl] 1, 1 -dimethylethyl] jiO053.55 [3-methoxy-4-(5-53. oxazolyl)phenyl) ]oxalamide 201 N- [4-(2-Cyanobenzyl)- 1 piperazinyl] 1,1 -dimethylethyl] -N [3-methoxy-4-(5- 'I~517.1 536 oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5oxazolyl)phenyl] 53 dimethylb utyl) -1I pip erazinyl] 1 dimethylethyl] oxalamide N- [3-Methoxy-4-(5oxazolyl) phenyl 1 dimethyl 2- 543.2 538 4- (2 -quinolinyl) methyl]I -1Ipiperazinyl] ethyl] oxalamide tert-Butyl 4- [2-[[[3-methoxy-4- oxazolyl) anilino] oxalyl amino] i methyipropyl] -1-piperazineacetate 516 539 4-[2-[[[3-Methoxy-4-(5oxazolyl)anilino] oxalyl] amino] 4664 methyipropyl] -piperazineacetic4650 acid trifluoroacetate (1:1) N- (Cyclopropylmethyl)- 1 0N 0 F piperazinyl] 1, 1 -dimethylethyl] 0 C [3-methoxy-4-(5- N3 C 456 541 oxazolyl)phenyl] oxalamide tert-Butyl 4- 3-methoxy-4- O (5 -oxazolyl) anilino] oxalyl]I amino] N04ryA, N methyipropyl] I1-piperazinyl] 578 651 benzoate 4- [[3-Methoxy-4-(5-oxazolyl) OHr anilino] oxalyl] amino] N,YN methyipropyl] 1-piperazinyl] benzoic t-o FO 2 acid trifluoroacetate 1: 1) a 202 Exam-pies 4 15-420: In a manner analogous to that described in Example 4 starting with N- [3- (aminomethyiphenyl] [3-methoxy-4- 5-oxazolyl)phenyl] oxalamide and the appropriate carboxylic acid chloride compounds shown in table 1h were prepared.

table lh Name Structure ME(ES) Ex No Phenyl o oxazolyl)anilino] oxalyll amino] benzyl]-"4841 carbamnateN Fluorobenzamido)methyl]phenyl] I N [3-methoxy-4-(5- 004841 oxazolyl)phenyl] oxalamide Chlorobenzamido)methyllphenyl]-N'- 0 y J i [3-methoxy-4-(5- 0 0 505 417 oxazolyl)phenyl] oxalamide Methoxybenzamido)methyllphenyl]- 0 NY' N'-[3-methoxy-4-(5-0 051.48 oxazolyl)phenyl] oxalamide Dimethoxybenzamido)methyl] phenyl] 0 Ny NJIZ Y1 Iy 0 0 c 531.2 419 -N'-[3-methoxy-4-(5-j oxazolyl)phenyl]I oxalamide Cy n be z m do) m hy] phenyl] 49 420 [3-methoxy-4-(5- I\ 49I 2 -203oxazolyl)phenyl]oxalamide Examples 421-427 and 598-614: Typical methods used for the preparation of the compounds of table lb are described below: Examples 421 and 423 were prepared by reaction of N-[3-methoxy-4-(5oxazolyl)phenyl]-N'- [1,1-dimethyl-2- (4-piperidinyl)ethyl] oxalamide with the appropriate acylating reagent.

Example 424 was prepared in a manner analogous to that described in Example 1, starting with N-[3-methoxy-4-(5-oxazoyl)phenyl oxalamic acid, prepared as described in Example 1, parts and and the appropriate amine.

Example 422 N- [3-Methoxy-4-(5-oxazolyl)phenyl]-N'- [1,1-dimethyl-2-(phenylthio)ethyl] oxalamide.

A mixture of 2g (17.7 mmol) of 2,4,4-trimethyl-2-oxazoline and 1.95 g (17.7 mmol) of 2-(phenylthio)ethyl]acetamide as a white solid.

(ii) A solution of 2.5 g (11.2 mmol) of N- [1,1-dimethyl-2-(phenylthio)ethyl]acetamide, 3.18 g (11.2 mmol) of titanium isopropoxide and 3.09 g (16.8 mmol) of diphenylsilane in 12 ml of tetrahydrofuran were stirred at room temperature for 18 hours. The resulting mixture was chromatographed on silica gel using 6% and 10% methanol in -204dichloromethane for the elution. There was obtained 2 g of 1,1-dimethyl-2- (phenylthio)ethylamine as a pale orange oil. The 1,1-dimethyl-2-(phenylthio)ethylamine was then coupled to N-[3-methoxy-4-(5-oxazoyl)phenyl oxalamic acid by a procedure analogous to that described in example 1 to afford N-[3-methoxy-4-(5-oxazolyl)phenyl]- [1,1-dimethyl-2-(phenylthio)ethyl]oxalamide. MS: m/e 426 Example 427 was prepared by an analogous method to that described for example 422 but using 4-benzyloxythiophenol in place of the thiophenol and removing the protecting group using a mixture of hydrogen bromide in acetic acid.

Example 607 was prepared starting from benzofuran-3-acetic ethyl ester by alkylation iodomethane using potassium tertiary butoxide as base followed by alkaline hydrolysis, Curtius reaction, hydrolysis in ethylene glycol and water at 180 0 C. The resulting amine was then coupled to N-[3-methoxy-4-(5-oxazoyl)phenyl oxalamic acid as described in Example 1.

S Example 426 was prepared in a manner analogous to that described for example 408 in table Ig using tetrahydro quinoline in place of 1-(4-methoxyphenyl)piperazine.

Example 610 -205- 1 -(Methanesulfonyl)-4-piperidinyll -1,1-dimethylethyll-N'- [3-methoxy-4-(5oxazolyl)phenylloxalamide 14 mg (0.12 mmol) of methanesulphonyl chloride were added to a solution of 40 mg (0.1 mmol) of N-[3-methoxy-4-(5-oxazolyl)phenyl-N'-[l,1-dimethyl-2-(4piperidinyl)ethyl] oxalamide in 1 ml of dichloromethane followed by 17 mg (0.15 mmol) of N-ethylmorpholine and the mixture stirred at room temperature for 4 hours. The resulting solution was diluted with ethyl acetate, washed with 2M hydrochloric acid and saturated sodium bicarbonate solution, dried over magnesium sulphate, evaporated to dryness and the residue triturated with diethyl ether. There was obtained 23 mg of (methanesulfonyl)-4-piperidinyl]-l,l-dimethylethyl]-N'-[3-methoxy-4-(5oxazolyl)phenyl]oxalamide as an off-white solid. MS m/e 479 [M+H] The starting material was prepared as follows: i) A solution of 4.65 g (31 mmol) of alpha, alpha-dimethyl-4-pyridineethylamine, 15.6 g (0.154 mol) of triethylamine and 13.5g (61.9 mmol) of di-tert-butyl dicarbonate in 100 ml of methanol was stirred at room temperature for 2 days then evaporated to dryness. The residue was dissolved in ethyl acetate, washed with water, dried over magnesium sulphate, 20 evaporated to dryness and chromatographed on silica gel using ethyl acetate/petrol (2:1) for the elution. There was obtained 2.12 g of tert-butyl [l,1-dimethyl-2-(4pyridyl)ethyl]carbamate as a pale orange solid. 'H NMR (400 MHz CDC13) 8: 1.29 (6H,s), 1.49 3.04 4.30 (1H, br.s), 7.10 8.52 (2H,d).

ii) 2.1 g (8.4 mmol) of tert-butyl [1,1-dimethyl-2-(4-pyridyl)ethyl]carbamate, in 20 ml of methanol were hydrogenated with 400 mg of 10% palladium on carbon catalyst at 70 0

C

and 7 Bar for 6 days. The resulting suspension was filtered, evaporated to dryness and the residue triturated with diethyl ether/petrol to give 1.2 g oftert-butyl [1,1-dimethyl-2- (4-piperidinyl)ethyl]carbamate as a white solid. 'H NMR (400 MHz DMSO) 8: 1.18 1.28-1.41 1.37 1.52-1.69 1.75-1.83 2.74-2.84 3.12-3.21 6.40-6.48 (1H,br.s), 8.60-8.95 (1H,br.s).

-206iii) A solution of 1.2 g (4.68 mmol) oftert-butyl [1,1-dimethyl-2-(4- O piperidinyl)ethyl]carbamate, 945 mg (9.36 mmol) of triethylamine and 2.33 g (9.36 mmol) of N-(benzyloxycarbonyloxy)succinimide in 20 ml of dichloromethane was stirred at room temperature for 18 hours then washed with 10% citric acid solution and saturated sodium bicarbonate solution. The organic phase was dried over magnesium sulphate, evaporated to dryness and the residue chromatographed on silica gel using ethyl acetate/petrol (1:2) for the elution. There was obtained 1.89 g of benzyl 4-[2-(tert-butoxyformamido)-2methylpropyl]-1-piperidinecarboxylate. 'H NMR (400 MHz CDCl 3 6:1.15-1.32 (2H,m), 1.29 1.42 1.49-1.78 2.75-2.90 4.05-4.16 4.41 (1H,br.s), 5.12 7.27-7.42 iv) A solution of 1.79 g (4.6 mmol) ofbenzyl 4-[2-(tert-butoxyformamido)-2methylpropyl]-1-piperidinecarboxylate in 6 ml of trifluoroacetic acid/dichloromethane was stirred at room temperature for 5 minutes then evaporated to dryness. The residue was dissolved in 20 ml of dichloromethane along with 1.2 g (4.58 mmol) of N-[3acid, 1.1 g (5.74 mmol) of 1-(3dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 1.32g (11.5 mmol) of Nethylmorpholine and 1.1 g (6.9mmol) of 1-hydroxy-7-azabenzotriazole. After stirring overnight the solution was diluted with ethyl acetate, washed with 10% citric acid solution 20 and saturated sodium bicarbonate solution, dried over magnesium sulphate evaporated to dryness and chromatographed on silica gel using ethyl acetate/petrol for the elution.

*There was obtained 1.14 g of benzyl 4- [[[3-methoxy-4-(5oxazolyl)phenylamino]oxalyl]amino]-2-methylpropyl}-1-piperidinecarboxylate as a white foam. MS: m/e 535 [M+H] t v) A solution of 1.1 g (2.05 mmol) of benzyl 4-{2-[[[3-methoxy-4-(5oxazolyl)phenylamino]oxalyl]amino]-2-methylpropyl}-l-piperidinecarboxylate in 25 ml of methanol was hydrogenated with 100 mg of 10% palladium on carbon catalyst for 4 hours. The resulting suspension was filtered and evaporated to dryness to give 732 mg of N-[3-methoxy-4-(5-oxazolyl)phenyl]-N'-[1, -dimethyl-2-(4-piperidinyl)ethyl] oxalamide as an off-white solid. MS: m/e 401 [M+H] t Example 616 was prepared starting from benzofuran-3-acetic ethyl ester by alkylation -207iodomethane using potassium tertiary butoxide as base followed by alkaline hydrolysis, Curtius reaction, hydrolysis in ethylene glycol and water at 180 0 C. The resulting amine was then coupled to N-[3-methoxy-4-(5-oxazoyl)phenyl oxalamic acid as described in Example 1.

Example 619 N-[2-[1-(Methanesulfonyl)-4-piperidinyll -1,1-dimethylethyll-N'- [3-methoxy-4-(5oxazolyl)phenylloxalamide 14 mg (0.12 mmol) of methanesulphonyl chloride were added to a solution of 40 mg (0.1 mmol) of N- [3-methoxy-4-(5-oxazolyl)phenyl-N'- [1,1-dimethyl-2-(4piperidinyl)ethyl]oxalamide in 1 ml of dichloromethane followed by 17 mg (0.15 mmol) of N-ethylmorpholine and the mixture stirred at room temperature for 4 hours. The resulting solution was diluted with ethyl acetate, washed with 2M hydrochloric acid and saturated sodium bicarbonate solution, dried over magnesium sulphate, evaporated to dryness and the residue triturated with diethyl ether. There was obtained 23 mg of (methanesulfonyl)-4-piperidinyl]-l,l-dimethylethyl]-N'-[3-methoxy-4-(5- 20 oxazolyl)phenyl]oxalamide as an off-white solid. MS m/e 479 9 The starting material was prepared as follows: S• i) A solution of 4.65 g (31 mmol) of alpha, alpha-dimethyl-4-pyridineethylamine, 15.6 g (0.154 mol) of triethylamine and 1 3 .5g (61.9 mmol) of di-tert-butyl dicarbonate in 100 ml of methanol was stirred at room temperature for 2 days then evaporated to dryness. The residue was dissolved in ethyl acetate, washed with water, dried over magnesium sulphate, evaporated to dryness and chromatographed on silica gel using ethyl acetate/petrol (2:1) for the elution. There was obtained 2.12 g of tert-butyl [1,1-dimethyl-2-(4pyridyl)ethyl]carbamate as a pale orange solid. 'H NMR (400 MHz CDC1 3 1.29 (6H,s), 1.49 3.04 4.30 (1H, br.s), 7.10 8.52 (2H,d).

-208ii) 2.1 g (8.4 mmol) of tert-butyl [1,1-dimethyl-2-(4-pyridyl)ethyl]carbamate, in 20 ml of methanol were hydrogenated with 400 mg of 10% palladium on carbon catalyst at and 7 Bar for 6 days. The resulting suspension was filtered, evaporated to dryness and the residue triturated with diethyl ether/petrol to give 1.2 g oftert-butyl [1,1-dimethyl-2- (4-piperidinyl)ethyl]carbamate as a white solid. 'H NMR (400 MHz DMSO) 6: 1.18 1.28-1.41 1.37 1.52-1.69 1.75-1.83 2.74-2.84 3.12-3.21 6.40-6.48 (1H,br.s), 8.60-8.95 (1H,br.s).

iii) A solution of 1.2 g (4.68 mmol) of tert-butyl [1,1-dimethyl-2-(4piperidinyl)ethyl]carbamate, 945 mg (9.36 mmol) of triethylamine and 2.33 g (9.36 mmol) of N-(benzyloxycarbonyloxy)succinimide in 20 ml of dichloromethane was stirred at room temperature for 18 hours then washed with 10% citric acid solution and saturated sodium bicarbonate solution. The organic phase was dried over magnesium sulphate, evaporated to dryness and the residue chromatographed on silica gel using ethyl acetate/petrol (1:2) for the elution. There was obtained 1.89 g of benzyl 4-[2-(tert-butoxyformamido)-2methylpropyl]-l-piperidinecarboxylate. 'H NMR (400 MHz CDCl 3 1.15-1.32 (2H,m), 1.29 1.42 1.49-1.78 2.75-2.90 4.05-4.16 4.41 (1H,br.s), 5.12 7.27-7.42 iv) A solution of 1.79 g (4.6 mmol) of benzyl 4-[2-(tert-butoxyformamido)-2methylpropyl] -1 -piperidinecarboxylate in 6 ml of trifluoroacetic acid/dichloromethane was stirred at room temperature for 5 minutes then evaporated to dryness. The residue was dissolved in 20 ml of dichloromethane along with 1.2 g (4.58 mmol) of N-[3- 25 methoxy-4-(5-oxazolyl)phenyl]oxalamic acid, 1.1 g (5.74 mmol) of 1-(3- S dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 1.32g (11.5 mmol) of Nethylmorpholine and 1.1 g (6.9mmol) of 1-hydroxy-7-azabenzotriazole. After stirring .overnight the solution was diluted with ethyl acetate, washed with 10% citric acid solution o* and saturated sodium bicarbonate solution, dried over magnesium sulphate evaporated to dryness and chromatographed on silica gel using ethyl acetate/petrol for the elution.

There was obtained 1.14 g of benzyl [[3-methoxy-4-(5oxazolyl)phenylamino] oxalyl] amino]-2-methylpropyl}-l -piperidinecarboxylate as a white foam. MS: m/e 535 209 v) A solution of 1.1 g (2.05 mmol) of benzyl 4-{2-[[[3-methoxy-4-(5oxazolyl)phenylamino] oxalyl] amino] -2 -methylpropyll 1 -piperidinecarboxylate in 25 ml of methanol was hydrogenated with 100 mg of 10% palladium on carbon catalyst for 4 hours. The resulting suspension was filtered and evaporated to dryness to give 732 mg of N- methoxy-4- (5-oxazolyl)phenyl] 1 dimethyl- 2- (4-piperidinyl) ethyl] oxalamide as an off-white solid. MS: m/e 401 [M-iH] t The remaining examples in table lb were prepared by methods analogous to those described above, as appropriate to the structure, or by methods previously described for related structures.

table lb Name Structure MS(ES) Ex No.

(M H) Benzyl 4-f2-[[[3-methoxy-4-(5oxazoll)phenlamino] oxalyl] a mino] -2-methylpropyl}-1-5342 0. piperidinecarboxylate N- [3-Methoxy-4- (5-oxazolyl) //-0O'P pflenylJ-N-[1,1-cllmetflyl-2- 0Y N2642 (peylho ety I oxalamide N 426 422 N- 2- (1 -Acetyl-4-piperidinyl) 1, 1-dimethylethyl]I 3methoxy-4- oxalamide -4 210 N-(2-Cyclohexyl-1,1- N -t dimethylethyl) -methoxy- NN- 400 424 oxalamide K N- [3-Methoxy-4- (5-oxazolyl) 4 ,C;=O phenyl] [1,1-dimethyl-2-(N- N I6 0' methylanilino) ethyl] oxalamide o HC CNi 2 2 N- (1,2,3,4-Tetrahydro- 1quinolyl)- 1,1 -dimethylethyl] 0 k)Kii [3-methoxy-4-(5-oxazolyl) N0 4 2 phenyl] oxalamide N- 2- (4-Hydroxyphenylthio) N'10 0- N0 1, 1-dimethylethyl] 3 NAN methoxy-4- (5-oxazolyl)phenyl] 4 2 oxalamide N- 3 -(4-Hydroxyphenyl) 1, 1- N'

OH

dimethyipropyl]I 3-N OH ~424 598 oxalamide N- 3-Methoxy-4- (5-oxazolyl) 0 NNf'N phenyl]-N'- 1-dimethyl-2-[(I 1- 0 0 oxido-4-pyridyl)carboxamido] 5 9 ethyl] oxalamide 2 -(4-Acetylbenzamido) 1 -N dimethylethyl] [3-methoxy- I0 47. 4-(5-oxazolyl)phenyl] oxalamide47. N-[3-Methoxcy-4-(5-oxazolyl) 0 N YK0 _NJ: phenyl]-N'-[3-[(4-0 485. methylbenzamido)methyl] pheny48. 1] oxalamide 9* I. i. 1. -211- N- [(2-Methoxybenzamido) 0, N I'.

methyllphenyl] [3-methoxy- 4- (5-oxazolyl)phenyl] oxalamide 501.1 602 N- (4-Chlorobenzmido) 0 methyl]phenyl]-N'-[3-methoxy- <'55.,0 oxalamide _50. 63 N-[3-[[(1,3-Benzodioxol-5- Il oc-YDo yl)carboxamido]methyllphenyl] o( 51. 0 [3-methoxy-4-(5-oxazolyl)51.60 phenyl] oxalamide N-[2-(2,3-Dihydro-1-indolyl)-

NYILN)

1,1-dimethylethyl]-N'-[3- o 3 0 methoxy-4- (5-oxazolyl)phenyl] N4360 oxalamide N- (3,4-Dihydro-6-methyl- C 2H-quinol-1-yl)-1,1- 0 dimethylethyl]-N'-[3-methoxy- Vi463 606 4- (5-oxazolyl)phenyl] oxalamide N- 1- (3-Benzofuranyl)- I1-N methylethyl]-N'-[3-methoxy-4- 42 607l~ (5-oxazolyl)phenyl] oxalamide H4260 o~ 0, N- [3-Methoxy-4-(5-oxazolyl) N phenyl] [1,1-dimethyl-3- (4-5068 phenoxypiperidino)propyl] oxala5068 mide N- (1 -Butyryl-4-piperidinyl)- 1, 1-dimethylethyl] [3methoxy-4- (5-oxazolyl)phenyl] 471 609 oxalamide N- [1-(Methanesulfonyl)-4- piperidinyl] -1 ,-dimethyl ethyl] 479 610~ [3-methoxcy-4-(5-oxazolyl)4761 9 9..

9 9* 9 9* 9 '9 *9 .9 9 9* 9999 9 9* S

NN

212 phenyl] oxalamide N- 1 -(Benzenesulfonyl)-4-2 piperidinyl] 1,1 -dimethylethyl] -5461 [3-methoxy-4-( 5-oxazolyl)o'C5461 phenyl] oxalamide N- (1 -Isobutyryl-4piperidinyl) 1, 1 -dimethylethyl] 47 61 3-methoxy-4- (5-oxazolyl) C 4761 phenyl] oxalamide tert-Butyl 4- [3-methoxy-4- 0 N,

Y

anilino] oxalyl]0 H amino] -3-methylbutyl] -1I- 515 613 piperidinecarboxylate CK6 0 CHl N- [3-Methoxy-4-(5-oxazolyl)o N phenyl] 1-dimethyl-3-(4- 0 piperidinyl)propyl]I oxalamide 0415 614 Exam-ples 428-432: Examples 428, 431 and 432 of table 1i were prepared in a manner analogues to that described for example 408 in table Ig but using N- [3-methoxy-4-(4-oxazoyl)phenyl oxalamic acid or N- [3-methoxy-4-(2-methyl-4-oxazoyl)phenyl oxalamic acid in place of N-[3-methoxy-4-(5-oxazoyl)phenyl oxalamic acid for the coupling step.

Examples 429 and 430 of table I i were prepared by analogues procedures to those described for the preparation of the compounds of table If.

table 1i 213 Name Structure MS(ES) Ex No oxazolyl)phenyl] 1,1 -dimethyl- 0 l 2-(4-phenyl-1- 478 428 piperazinyl) ethyl] oxalamide N- (4-Benzyloxyphenyl)- 1,1dimethylethyll]-N'- [3-methoxy-4- l 0 2 (4-oxazolyl)phenyl] oxalamide5042 N- (4-Hydroxyphenyl)- 1,1 -0 dimethylethyl] [3-methoxy-4- 0-11 0 (4-oxazolyl)phenyl] oxalamide \-N410 430 N-[3-Methoxy-4-(4-

OJZJY

oxazolyl)phenyl]-N'-[2-[4-(4methoxyphenyl) -1-piperazinyl]- 508 431 1,1 -dimethylethyl] oxalamide N- [3-Methoxy-4-(2-methyl-4-N'V oxazolyl)-phenyl] 0 ~N 1N~N methoxyphenyl)- I-piperazinyl] rN522.4 432 1,1 -dimethylethyl] oxalamide

OSS*

9.

*9 9* 9 9 *99* 9*@g 9 99*9 .9 9 94 In the present specification "comprise" means "includes or consists of' and "comprising" means "including or consisting of'.

The features disclosed in the foregoing description, or the following claims, or the accompanying drawings, expressed in their specific forms or in terms of a means for performing the disclosed function, or a method or process for attaining the disclosed 214 result, as appropriate, may, separately, or in any combination of such features, be utilised for realising the invention in diverse forms thereof.

600@ 0e 9 S

S

S.

S S

S

OS S S S 9 9**S*S

P.S.

S. S

SS

9 .55.

55..

S

OS..

S. S 55

Claims (13)

1. Compounds of the general formula R 2 R1 R 3 6 I NR4R R 0 wherein R' represents heterocyclyl; 10 R 2 represents hydrogen, unsubstituted lower alkyl, lower alkoxy, halo, hydroxy or 0e cyano; o R 3 represents hydrogen, unsubstituted lower alkyl, lower alkoxy, halo, or cyano; R 4 represents hydrogen, lower alkyl, lower cycloalkyl, aryl, or heterocyclyl; R 5 represents hydrogen, unsubstituted lower alkyl, lower alkoxy, halo, or cyano; 15 R 6 represents hydrogen, unsubstituted lower alkyl, lower alkoxy, halo, or cyano; R 7 represents hydrogen, or unsubstituted lower alkyl; R 8 represents hydrogen, or unsubstituted lower alkyl; or R 4 and R 8 together with the nitrogen atom to which they are attached represent heterocyclyl; -216- and pharmaceutically acceptable salts thereof.

2. Compounds according to Claim 1 wherein at least one of R 2 R 3 R 5 and R 6 is not hydrogen.

3. Compounds according to Claim 1 or Claim 2 wherein R 1 represents an optionally substituted oxazole ring.

4. Compounds according to any one of the preceding claims wherein R' represents an optionally substituted oxazole ring, according to the general formula: R 9 N R2 R NR 4 R 8 R 5 0 (IX) wherein R 2 to R 8 are defined as in Claim 1, and R 9 represents hydrogen, lower alkyl, or aryl-lower alkyl; R' 1 represents hydrogen. Compounds according to Claim 4 wherein R 9 represents methyl, ethyl or benzyl.

6. Compounds according to Claim 4 wherein R 9 and R 1 0 are hydrogen. -217-

7. Compounds according to Claim 1 or Claim 2 wherein R' represents triazolyl.

8. Compounds according to any one of the preceding claims wherein R 2 is lower alkoxy.

9. Compounds according to claim 8 wherein R 2 is methoxy. Compounds according to any one of the preceding claims wherein R 4 represents a lower alkyl group which is branched.

11. Compounds according to any one of the preceding claims wherein R 7 is hydrogen.

12. Compounds according to any one of the preceding claims wherein R 8 is hydrogen. 15 13. A compound according to any one of claims 1, 2, 3,4, or 6, selected from:

218- tetrahydro-3 -furyl ester "p oCgt N-13- (Benzamidomethyl)phenyl] methoxy-4- oxazolyl)phenyl] oxalamide Isopropyl [3-11 13-methoxy-4-(5- 0 al. 0 oxazolyl) anilino] oxalyl] amino] benzyl] carbamnate ,6-y TN- [3-Methoxy-4-(5-oxazolyl)phenyl] UI 0~I (1-methyl-i -phenylethyl) oxalamide 0% 0 N- (1,1-Dimethylpropyl)-N'- [3-methoxy- 0 NCCH c 0 N- [3-Methoxy-4-(5-oxazolyl)phenyl] H3CN oH A (1,1 ,3,3-tetramethyl-butyl)oxalamide OICH N- (1)1-Dimethylpropargyl)-N'- 13- N OH, oxazolyl)phenyl] oxalamide 6010 N- (2-Hydroxy- 1, -dimethylethyl)-N'- 13- o oxazolyl)phenyl] oxalamide Phny [3[-oxazolyl)pey]oaaieno oxalyl] amino] benzyl carbamnate 219 N- [3-Methoxy-4- (5-oxazolyl)phenyl] 0 (phenylcarbamoyl)methyl] phenyl] oxalamide N N tert- Butyl 2- 3-methoxy-4- (5 0 0 CF oxazolyl)anilino] oxalyl] amino] -2- N ~methyipropyl]I carbamnate HCH~ N-(2-Amino- 1,1-dimethylethyl)-N'- [3- 0 N J' o -0 HO methoxcy-4- oxazolyl)phenyl] oxalamide trifluoroacetate 1: 1) N' N- [3-Methoxy-4-(5-oxazolyl)phenyl] o [1,1 -dimethyl-2- (4-nitrophenyl) ethyloxalamide N- [3-(Aminomethyl)phenyl] [3- methoxy-4- oxazolyl)phenyl] oxalamide trifluoroacetate (1:1) Methyl [3-[[[3-methoxy-4-(5- oxazolyl)anilino] oxalyl] amino] benzyl] car bamnate N- [3-Methoxy-4- (5-oxazolyl)phenyl] 0 (3-pyridyl)oxalamide [(Benzenesulfonamido) methyl] phenyl] [3-methoxcy-4-(5- oxazolyl)phenyl] oxalamide 220 N- (2-Dimethylamino- 1,1- oI~dimethylethyl) 3-methoxy-4- oxazolyl)phenyl] oxalamide hydrochloride 1) 0 3-Methoxy-4- (5-oxazolyl)phenyl]I ,6C4 [1-methyl-i- (m ethyl ca rbamoyl) ethyl oxal am id e N-tert-Butyl-N [3-chloro-4-(5- o~ oxazolyl)phenyl] oxalamide ~C4~ UN N~N-tert-Butyl-N'- [3-methoxy-4-(4- N, O, 0oxazolyl)phenyl] oxalamide 00 o o S. .o or a pharmaceutically acceptable salt thereof. 14. Compounds according to claim 1 of the formula XI a XI b -221- wherein R 2 R 3 R 5 R 7 R 9 and Ro are defined as above R" and R 13 is H or lower alkyl, m=l to 5 and R 1 2 is heterocyclyl or aryl, with the proviso that R 12 does not stand for 4-fluorophenyl. 15. Compounds according to claim 14 wherein R 2 is methoxy, R 3 R 5 R 6 R 9 R 1 0 R" and R 13 are hydrogen and wherein R 1 2 is optionally substituted phenyl and optionally substituted heteroaryl, with the proviso 15 that R 12 does not stand for 4-fluorophenyl. 16. Compounds according to claims 14 or 15 selected from table Ic Name Structure 222 N- [3-Methoxy-4-(5- oxazolyl)phenyl]-N'- 1,1-dimethyl- methylphenyl) ethyl]I oxalamide 'CI CH'NS 0' 01 N-[1,1-Dimethyl-2-(2- O0 methylphenyl)ethyl] N H methoxy-4- 0 CH, oxazolyl)phenyl] oxalamide N-[3-Methoxy-4-(5- N.cl oxazolyl)phenyl] 1, 1 -dimethyl- NN 2- (3 -pyridyl) ethyl] oxalamide 0 H~C CHI N-[3-Methoxy-4-(5- N -oO' oxazolyl)phenyl] 1-dimethyl- I iii CM' methylphenyl) ethyl]I oxalamide N- [3-Methoxcy-4-(5- OC oxazolyl)phenyl] 1, 1 -dimethyl- N 2- (2 -thienyl) ethyl] oxalamide N-[2-(4-Benzyloxy-phenyl)- 1,1-0 dimethyl- ethyl] (3 -methoxy-4- oxazol-5-yl-phenyl) -oxalamide N- (4-Hydroxy-phenyl) N2 C~ dimethyl-ethyl] -N'-(3-methoxy-4_ HI X oxazol- 5-yl-phenyl) -oxalamide N-(3-Methoxy-4-oxazol-5-yl- phenyl)-N'- [2-(4-methoxy- phenyl)- 1,1 -dimethyl- ethyl] oxalamide N- (2-Hydroxy-phenyl)- 1,1- dimethyl -ethyl]I- (3 -methoxy-4- -r1N( N CI 223 N-(1,1-Dimethyl-2-phenyl- d_ II H propyl)-N'-(3-methoxy-4-oxazol--CH -oxalamide C 0'O N-[2-(3-Hydroxy-phenyl)-1,1- dimethyl- ethyl] (3 -methoxy-4- IO;ON- -oxalamide N- (3-Methoxy-4-oxazol- phenyl)-N'- [2-(3-methoxy- phenyl) 1-dimethyl- ethyl]l 0 oxalamide N- 14-(Cyanomethoxy)phenyl] 1,1-dimethylethyl]-N'-[3-methoxcy-N N~ 2-[4-[2-[[[3-Methoxy-4-(5-N 9 oxazolyl)anilino] oxalyl] amino] methyipropyl Iphenoxy] acetic acid 2-[2-[2-[[[3-Methoxy-4-(5- -,yC oxazolyl) anilino] oxalyl] amino] N0- methyipropyl] phenoxy] acetic acid 2-[3-[2-[[[3-Methoxy-4-(5- N 6 Y oxazolyl)anilino] oxalyl] amino] N N methyipropyl] phenoxy] acetic acid N-[3-Methoxy-4-(5- oxazolyl)phenyl] 1, 1 -dimethyl- NI Y 2-(1-oxido-4- pyridyl) ethyl]I oxalamide N-[3-Methoxy-4-(5- N 0 oxazolyl)phenyl] 1, 1 -dimethyl- 1-oxido-3- pyridyl) ethyl]I oxalamide 224 N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1 -dimethyl- 2-(1-oxido-2- pyridyl)ethyl] oxalamide 2- [3-Methoxy-4-(5- oxazolyl)anilino] oxalyl) ]amino] -2- methyipropyl] phenoxy] acetic acid dimthyethll-N'- [3-methoxy-4- oxalamide N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1,1-dimethyl- 2-(3-methyl-2- benzofuranyl) ethyl]I oxalamide N- [2-(7-Methoxy-2-benzofuranyl)- 1,1 -dimethylethyl] [3-methoxy- 4-(5-oxazolyl)phenyl] oxalamide N- [2-(5-Methoxy-2-benzofuranyl)- 1,1-dimethylethyl] [3-methoxy- 4- (5-oxazolyl)phenyl] oxalamide OCqr 0 qC CH, 0* 0. N- [2-(6-Methoxy-2-benzofuranyl)- N"- 1,1 -dimethylethyl] [3-methoxy- A-Y 4- (5-oxazolyl)phenyl] oxalamide Benzyl 4- [2-[[[3-methoxy-4-(5- oxazolyl)anilino] oxalyl] amino] -2- methyipropyl] benzoate 2 r r3 -Meth oy- 4 oxazolyl)anilino] oxalyl] amino] -2--S methyipropyl] benzoic acid Benzyl 3- [J-methoxy-4-(5- No 0' 0 oxazolyl)anifino] oxalyl] amino] C 225 methyipropyl] benzoate 0e S S S S S S S S. S *.SS S. S S S *5S~ *0 S S S 3-[2-[[[3-Methoxy-4-(5- r O-l 0 0 oxazolyl)anilino] oxalyl] amino] 'N CH methylpropyljbenzoic acid N-[2-(3-Benzofuranyl)-1,1- dimethylethyl] [3-methoxy-4-- ~y Benzyl 2-[2-[[[3-methoxy-4-(5- -c0 oxazolyl)anilino] oxalyl] amino] methyipropyl] benzofurancarboxylate 0. 2- [2-[[[3-Methoxy-4-(5-k oxazolyl)anilino] oxalyl] amino] oY. methyipropyl] benzofurancarboxylic acid C N- [3-Methoxy-4-(5- oxazolylphenyl] pyridyl)methyl] -1- cyclopentyl]I oxalamide N-[3-Methoxy-4-(5- N 0,CH 0 4-pyridyl)methyl] -1- cyclopentyl] oxalamide N- [2-(4-Methoxcy-2-benzofuranyl)- Nf d 1,1-dimethylethyl] [3-methoXy_ s"c o 4- (5-oxazolyl)phenyl] oxalamideV0 [3-M ethoxy-4-(5-oxazolyl) FI OHC H IC phenyl] [2-(2,6-dimethyl-4- pyridyl)- 1,1 -dimethylethyl] oxalamide 226 N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1, 1 -dimethyl- 2- (2,6-dimethyl- 1 -oxido-4-pyridyl) ethyl] oxalamide 0 0 A1 N. NrJ UN N N- [3-Methoxy-4-(5-oxazolyl) phenyl] [1I- [(4-pyridyl)methyl] 1 -cyclopropyl] oxalamide 0 N (0 N k -0 I N- [3-Methoxy-4- (5-oxazolyl) phenyl] 1- -oxido-4- pyridyl)methyl] -1- cyclopropyl] oxalamide o N irJ N 0 0 'N N- [3-Methoxcy-4-(5-oxazolyl) phenyl] [1I- (4-pyridyl)methyl] 1 -cyclobutyl] oxalamide N *1- S *0 S *SS S IS S S S 0@ 0 S *5 S S.SS S *Se .555 *5 5 55 55*5 S 59e5 S .554 oc S S S 5@ N- [3-Methoxcy-4-(5-oxazolyl) phenyl] 1- [(1-oxido-4- pyridyl)methyl] 1-cyclobutyl] oxalamide o: N- 0 0 (31c N- [3-Methoxy-4-(5-oxazolyl) phenyl] 11I- [(4-pyridyl)methyl] 1 -cyclohexyl] oxalamide 0 N 0 0 <\N o N- [3-Methoxy-4-(5-oxazolyl) phenyl] [1I- (1-oxido-4- pyridyl)methyl] -1- cyclohexyl] oxalamide -N 4 N i N- [3-Methoxy-4-(5-oxazolyl) phenyl] 1,1 -dimethyl-2-(2- methyl- 4-pyridyl) ethyl] oxalamide o N Ny N>K 2 JN 0 0 N- [3-Methoxy-4-(5-oxazolyl) N.N'Kj1 phenyl] 1,1 -dimethyl-2-(2- 0-0 methyl-i -oxido-4-N pyridyl) ethyl]I oxalamide 227 2- [3-Methoxy-4-(5- oxazolyl)anilinolIoxalyl] amino] -2- methyipropyl] benzothiophenecarboxylic acid 17. Compounds according to claim 1 of the formula R 1 6 wherein R 2 ,R 3 ,R 5 R, R 7 R 9 and R' 0 are defined as above, R 11 R 13 ,R1 4 R1 5 R" 6 R 17 and R" are H olwealkyl and R1 9 is alkyl, cycloalkyl, heterocyclyl alkyl or aryl alkyl. 10 18. Compounds according to claim 17 wherein R2 3561 Ris methoxy and R R R R 9 R 10 and R' are hydrogen. 19. Compounds according to claim 17 or 18 selected from table Id 228 N- [3-Methoxy-4-(5-oxazolyl)phenyl] 1,l-dimethyl-2- pyridinyl)methylamino] phenyl] ethyl] oxala mide -,t 000. a *:o N- [3-Methoxy-4- (5-oxazolyl)phenyl] C. 0 [l,1-dimethyl-2-[4-[(3- <'O pyridyl)methylamino] phenyl] ethyl] oxalam ide N- (2-Furfurylamino)phenyl 1,1 5. H*C dimethylethyl] [3-methoxy-4-( oxazolyl)phenyl] oxalamide N- [3-Methoxy-4- (5-oxazolyl)phenyl] [1,l1-Dimethyl- 2- -Y0D, 0, thenylamino)phenyl] ethyl] oxalamide N- 3-Methoxy-4-(5-oxazolyl)phenyl] cj C 1-dimethyl-2- (2,2- dimethylpropylamino)phenyl] ethyl] oxalam ide N- [(lH-Imidazol-2- N yl)methylamino] phenyl] 1,1- 0. Q dimethylethyl] -N'-[3-methoxy-4-(5- oxazolyl)phenyl] oxalamide N- [3-Methoxy-4- (5-oxazolyl)phenyl] o pyridyl)methylamino] phenyl] ethyl] oxalam ide N- [3-Methoxcy-4- (5-oxazolyl)phenyl] -N'-N [1,l1-dimethyl-2- [(2-o thiazolyl)methylamino] phenyl] ethyl] oxala N mide N- [4-(3-FurfuLrylamino)phenyl] c% o dimethylethyll [3-methoxy-4-(5- -ao" 229 oxazolyl)phenyl] oxalamide N- [5-(Hydroxymethyl)-2- JT, furfurylamino] phenyl] -1,1-dimethylethyl]- Vy [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide N- [2-(4-Benzylaminophenyl)-1,1- cjJi~ dimethylethyl] [3-methoxy-4- oxazolyl)phenyl] oxalamideN N-[2-[4-(2-Hydroxybenzylamino)phenyl]- O~~ 1,1-dimethylethyl]-N'-[3-methoxy-4-(5-I oxazolyl)phenyl] oxalamide N- [4-(3-Cyanobenzylamino)phenyl] 1,1 -dimethylethyl] [3-methoxy-4- oxazolyl)phenyl]I oxalamide N- 3-Methoxy-4- (5-oxazolyl)phenyl pyridyl)benzylamino] phenyl] ethyl] oxalami de N- (2-Fluorobenzylamino)phenyl] N 1,1-imetyletyl]N'-[-metoxy--(5 oxazolyl)phenyl] oxalamideN Compounds according to claim 1 of the formula 230 X111 wherein R 2 R 6 R 9 and R' 0 are defined as above, R, ,R 13,R 14,R 15,R1 6 R 17 and R' 8 are Hor lower alkyl and R 20 is alkyl, cycloalkyl, aryl, heterocyclyl. .0* 0 21. Compounds according to claim 20 wherein Ris methoxy and R, R R R 9 R1 0 and R' are hydrogen. 22. Compounds according to claim 20 or 21 selected from table le C. 9 9a a Name Structure qq 0 (Cyclopropylcarboxamido)phenyl] -I 1, 1- dimethylethyl]I 3 -methoxy-4- oxalamide N- 2- (Cyclohutylcarboxamido) C' q.~f~lL phenyl] -1,1-dimethylethyl] 0 methoxy-4- 231 oxalamide N- 3-Methoxy-4- (5-oxazolyl)phenyl] C, '1 0 CO -N'-[1,1-dimethyl-2-(4-0 pivalamidophenyl) 1,1 dimethylethyl I oxalamide N- 3-Methoxy-4- 5-oxazolyl) phenyl]Nlj- 1, 1-dimethyl-2- 4- (IH -pyrrol- 2-yl)carboxamido]phenyl] ethyl] oxalamide N-[2-[4-[(2-Furyl)j% Np carboxamido]phenyl] dimethylethyl] [3-methoxy-4-(5-N oxazolyl)phenyl]I oxalamide N- [(3-Furyl) c carboxamido] phenyl] -1,1 dimethylethyl] -N'-[3-methoxy-4-(5- N oxazolyl)phenyl] oxalamide N- 1H-Imidazol-4-yl) carboxamido] phenyl] 1,1 dimethylethyl] -N'-[3-methoxy-4-(5- N oxazolyl)phenyl] oxalamide N- [(Tetrahydro-2(RS)-furyl)N dimethylethyl] -N'-[3-methoxy-4-(5- oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5-oxazolyl) o phenyl]-N'- [1,1-dimethyl-2- [(2-o pyridyl)carboxamido] phenyl] ethyl] ox alamide N- [3-Methoxy-4-(5-oxazolyl)phenyl] c [1,1-dimethyl-2- [(4-pyridyl) o o carboxamido] phenyl] ethyl] oxalamide 232 N-[3-Methoxy-4-(5-oxazolyl)phenyl] c ND 0 r 1,-dimethyl-2- [4-[(2-thienyl) 0 carboxaniido] phenyll ethyl] oxalamide N- [3-Methoxy-4-(5-oxazolyl)phenylI CH op 1, 1-dimethyl-2- [(3-thienyl) carboxamido] phenyl] ethyl] oxalamide N- (2-Cyclopentylacetamido) NQ K(O phenyl]-1,1-dimethylethyl]-N'-[3- methoxy-4- oxalamide N- [3-Methoxy-4- (5-oxazolyl) phenyl] oN N Y 1,1-dirnethyl-2- oI methylbenzamido)phenyl] ethyl] oxala N'a mide N- f[3-Methoxy-4- (5-oxazolyl)phenyl] N N [1,1-dimethyl-2- o o methylbenzamido)phenyl] ethyl] oxala N mide N- 2- (Cycloheptylcarboxamido) phenyl]- 1, 1-dimethylethyl] o ~NX.~ methoxcy-4- oxalamide N- (5-Isoxazolyl) carboxamido] cN phenyl 1, 1-dimethylethyl] C methoxy-4- oxalamide N- [4-(Cyclopentylcarboxamido) NP phenyl] -1,1-dimethylethyl] 'o methoxy-4- (5-oxazolyl)phenyl] N oxalamide N-[2-{4-[(Tetrahydro-3(RS)-fulryl) N o N carboxamido]phenyl] N :)XJr dimethylethyl] [3-methoxy-4-(5- N 233 oxazolyl)phenyl]I oxalamide N- [3-Methoxy-4-(5-oxazolyl)phenyl] y 1H-pyrrol-2-yl)carboxamicio]phenyl] ethyl] oxalamide N- [3-Methoxy-4-(5-oxazolyl)phenyl] l- -N'-(1,1-dimethyl-2- (I0 thiadiazol-4-yl)carboxamido] phenyl] ethyl] oxalamide N- (3-Fluorobenzamido)phenyl] l 0 -1,1 -dimethylethyl] -N'-[3-methoxcy- 'Io 4- (5-oxazolyl)phenyl] oxalamideN N- 2- (4-Fluorobenzamido)phenyll 1, 1 -dimethylethyl] 3-methoxcy- I-0 4- (5-oxazolyl)phenyl] oxalamide l N c Methoxybenzamido)phenyl]-1,l- dimethylethyl] [3-methoxy-4- N oxazolyl)phenyl] oxalamide N- [4-(2-Chlorobenzamido) C O H N r phenyl]-1,1-dimethylethyl]-N'-[3- methoxy-4- oxalamide N- [4-(3-Chlorobenzamido) 0 l% phenyl] 1,1 -dimethylethyl] IOv- methoxy-4-( oxalamide N- 44-Chlorobenzamido) 0l VC -a phenyl]-1,1-dimethylethyl]-N'-[3- N"j oI methoxy-4- (5-oxazolyl)phenyl] NJ oxalamide N N N NN N N N N N. N* 234 N- 1H-Indol-2-yl) carboxamido] phenyl] 1,1- dimethylethyl] [3-methoxy-4- oxazolyl)phenyl] oxalamide N- [3-Methoxy-4- (5-oxazolyl)phenyl] 1, 1-dimethyl-2- [4- (dimethylamino)benzamido] phenyl] e thyl] oxalamide 0 'n~c -c 0 S S S S S

555. S S N-[3-Methoxy-4-(5-oxazolyl)phenyl] YI 1,1-dimethyl-2- dimethylbutyramido) I phenyl] ethyl] o xalamide N- [3-Methoxy-4- -N'-[1,1-dimethyl-2-[4-[2-(1- tetrazolyl)acetamido] phenyl] ethyl] ox alamide N- [3-Methoxy-4- 1,1-dimethyl-2- [(5-oxo-2(S)- pyrrolidinyl)carboxamido] phenyl] eth yl] oxalamide N- [3-Methoxy-4- (5-oxazolyl)phenyl] Chial IN- 1,-dimethyl-2-{4- (5-oxo-2(R)- pyrrolidinyl)carboxamido] phenyl] eth yloxalamide N- [3-Methoxcy-4-(5-oxazolyl)phenyl] I cm 0 K. -N'-[l,1-dimethyl-2-[4-[(2-o naphthyl)carboxamido] phenyl] ethyl] oxalamide N- [(6-Cyano-3-pyridyl) oA~~f carboxamido] phenyll Q-YN-z dimethylethyl] [3-methoxy-4-(5- j 0 oxazolyl)phenyl] oxalamide 235 N ~CH, N- [4-(3-Methoxybenzamido) phenyl] 1,1 -dimethylethyl] [3- methoxy-4- oxalamide (IV- N- [4-(3,5-Difluorobenzamido) phenyl] 1,1 -dimethylethyl] [3- methoxy-4- oxalamide o o Y--r XJcr C: o N- carboxamido] phenyl] 1,1 dimethylethyl] [3-methoxy-4-(5- oxazolyl) phenyl] oxalamide 0 0 N. N N. N N. N N N. N N N. 2- 4- Butenamido)phenyl] 1,1 -dimethylethyl] [3-methoxy-4- oxalamide N-[2-[4-(2-Methoxyacetamido) A phenyl] 1,1 -dimethylethyl] [3- methoxy-4- oxalamide N- [3-methoxy-4-(5-oxazolyl)phenyl] 0 1,1 -dimethyl-2- (2-methyl-3- 0 N~Xif furyl)carboxamido] phenyl] ethyl] oxal N amide N- [3-Methoxy-4-(5-oxazolyl)phenyl] CHN 1,1 -dimethyl-2- (5-methyl-4- <I 0 N<N~ isoxazolyl)carboxamido] phenyl] ethyl]N oxalamide N- [3-Methoxy-4-(5-oxazolyl)phenyl] isoxazolyl)carboxamido] phenyl] ethyl] oxalamide 236 N- [3-Methoxy-4-(5-oxazolyl)phenyl] ,1-dimethyl-2- [4-[(5-methyl-3- isoxazolyl)carboxamidol phenyl] ethyl] oxalamide N-(3-Methoxy-4-(5-oxazolyl)phenyl] o pyridyl)carboxamido] phenyl] ethyl] ox alamide N- [3-Methoxcy-4- (5-oxazolyl)phenyl] [1,l-dimethyl-2- 1-oxido-4- pyridyl)carboxamido] phenyl] ethyl] ox alamide N- [3-Methoxy-4- [1,1-dimethyl-2- O~ dimethyl-2-furyl)carboxamido] phenyl] ethyl] oxalamide N- [3-Methoxy-4-(5-oxazolyl)phenyl] 1 1,1-dimethyl-2- dimethyl-2H-pyrazol-3-yl) carboxamido] phenyl] -1,1 dimethylethyl]I oxalamide N- [3-Methoxy-4- 1,1-dimethyl-2- [4-[(3-methyl-2- thienyl)carboxamido]phenyl] ethyl] ox alamide I y~t 0 F1 N- [3-Methoxcy-4-(5-oxazolyl)phenyl] o N. Xa ,1-dimethyl-2- thienyl)acetamido] phenyl] ethyl] oxala mide N- [3-Methoxcy-4-(5-oxazolyl)phenyl] 1,1-dimethyl-2- [(4-methyl-2- 0 thienyl)carboxamido] phenyl] ethyl] ox alamide 237 N- [3-Methoxy-4-(5-oxazolyl)phenyl] -N1- 1,1-dimethyl-2- [(4-methyl- 1 ,2,3-thiadiazol-5- yl) carboxamido phenyl ethyl oxalami de N- [4-(4-Acetamidobenzamido) phenyl] 1,1 -dimethylethyl] [3-o methoxy-4- oxalamide N- (3,4-Dimethoxybenzamido) phenyl] 1,1 -dimethylethyll o methoxy-4- oxalamide N-[2-[4-(4-Chloro-2- -1,1-RC dimethylethyl] -methoxy-4- oxazolyl)phenyl] oxalamide N- [4-(2,6-Dichlorobenzamido)- phenyl]-1,1-dimethylethyl]-N'-[3- -roo methoxy-4-(5-oxazolyl)phenyl] j oxalamide N- [(Bicyclo[4.2.O]octa- 1 (6),2,4-o triene-7(RS)-yl)carboxamido] phenyl] -1,1 -dimethylethyl] [3- methoxy-4- oxalamide 0 N-[3-Methoxy-4-(5-oxazolyl)phenyl] mc o _r i [1,1 -dimethyl-2- [4-(2-oxo-2-o phenylacetamido)phenyll ethyl] oxala mide N-[2-{4-[2-(2-Fluorophenyl) acetamidolphenyl}-1,1- dimethylethyl] [3-methoxy-4-(5- N N. *N N N N N N N. N N N. N. N NN N. 238 oxazolyl)phenyl] oxalamnide N- [2-14- [2-(4-Fluorophenyl) acetamido] phenyll 1,1 dimethylethyl)-N'- [3-methoxcy-4- oxazolyl)phenyl] oxalamnide 0 i N- [3-Methoxy-4-(5-oxazolyl)phenyl] [(4-methoxy-3-thienyl) carboxamido]phenyl}- 1,1- dimethylethyl] oxalamide N- [4-(4-Acetylbenzamnido) phenyl]-1,1-dimethylethyl] [3- methoxy-4- oxalamide N- ,3-Benzodioxol-5-yl) carboxarnido] phenyll -1,1- dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide N- [2-(2-Chlorophenyl) acetamido] phenyl] 1,1 dimethylethyl] [3-methoxy-4- oxazolyl)phenyl] oxalamnide 0" 0 t *N O 0 0oy (\I CNo Il o'Ia ('I -D 0 i *ee. *t N- [2-(4-Chlorophenyl) acetamido] phenyl] 1,1- dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalamnide (vi- tert-Butyl 4-[[4-[2-[[[3-methoxy-4- (5-oxazolyl)anilino] oxalyl] amino] -2- methyipropyl] phenyl] carbamoyl) benz oate c., 239 4- [3-Methoxy-4-(5-oxazolyl) anilino] oxalyl] amino] -2- methyipropyl] phenyl] carbamoyl]benz oic acid 04PO 23. Compounds according to claim 1 of the formula XVIII -C2)n _,R1 *4S. p p p p S p pp pp wherein R R R R R' and R1 0 are defined as above, R 11 and R 1 3 are H or lower alkyl, n= 0 or 1, R a, R b are lower alkyl or Ra and R b taken together with the carbon atom to which they are attached form a 3 to 7 member carbocycle, and R'1 2 is heterocyclyl, aryl or lower cycloalkyl and ZisO, Sor NR 2 too* *.wherein R 2 1 is H or lower alkyl. 24. Compounds according to claim 23 of the formulas: 240 XIVa XIVb ri- N0 1 (CH 2 R 1 2 N R 1 3 wherein R 2 R 3 R 5 R 6 R 9 and R 10 are defined as above 5 R" andR 13 is H or lower alkyl, n= 0 or 1 (CH 2 M=1 to 5 and, R 12 is heterocyclyl, aryl or lower cycloalkyl. Compounds according to claims 23 and 24 wherein R2 an are3 Ris methoxy adR R R 9 R' 0 and R ar hydrogen. 241 26. Compounds according to claim 23 to 25 selected from table Ife Name Structure N- 3- (4-Hydroxy-phenoxy) 1, 1- 'cit dimethyl-propyl] (3-methoxy- cH 4-oxazol- 5-yl-phenyl)-oxalamide 0 CN N- [3-Methoxy-4-(5-oxazolyl) phenyl]-N'-[3-(4-I- methoxyphenoxy) 1,1 dimethylpropyl] oxalamide N- [3-Methoxy-4- (5-oxazolyl) ol phenyl] ,1-dimethyl-3-(4- 1 nitrophenoxy)propyl] oxalamnideo t N-[3-(2-Hydroxyphenoxy)-1,1- dimethylpropyl]-N'-[3-methoxy-4- 00 oxalamnide0 N-[3-(4-Amino-phenoxy)-1,1- N'0 or, H, dimethyl-propyl]-N'-(3-methoxy-I 4-oxazol- 5-yl-phenyl)-oxalamide 0 CHF k N- [3-(4-Acetylamino-phenoxy)- -cN 1,1-dimethyl-propyl]-N'-(3- methoxy-4-oxazol- -lpey) N(4 oxalamide N-[3-Methoxy-4-(5-oxazolyl) N210 phenyl] ,1-dimethyl-3-(3- I -Nky+< ,O pyridyloxy)propyl] oxalamide 0N N-[3-(3-Hydroxyphenoxy)-i,i- N dimethylpropyl] [3-methoxy-4_ bNY~ oxalan-ide 242 N- [3-Methoxy-4-(5-oxazolyl) phenyl] methoxyphenoxy)-1,1 dimethyipropyl] oxalamide /7-0 0 0 C N- [3-Methoxy-4-(5-oxazolyl) Q. phenyl] [1,1-dimethyl-3- )N YN-OafN 0 nitrophenoxy)propyll oxalamnide N- [3-(3-Aminophenoxy)- 1, 1- N-'O 0' dimethyipropyl] -rethoxy-4- NN ,OtN oxalamide 4- [3-Methoxy-4- (5-oxazolyl) 26 yr anilino] oxalyl] amino] 0-r methylbutoxy] benzoic acid0 2- [[3-Methoxy-4-(5-oxazolyl) H anilino] oxalyl] amino] -3- methylbutoxylbenzoic acid0 t 3- [[3-Methoxy-4-(5-oxazolyl) 1 A anilino]oxalyl] amino] -3-N methylbutoxylbenzoic acid 2- [[3-Methoxy-4-(5- N oxazolyl)anilino] oxalyl] amino] -3-0 methylbutoxy] phenoxy] acetic acid 2- [3-Methoxy-4-(5- oxazolyl)anilino] oxalyl] amino] o methylbutoxy] phenoxcy] acetic acid N-[3-Methoxcy-4-(5- N'-O C oxazolyl)phenyl] (1,1 -dimethyl-- 3 -phenoxypropyl)oxalamide N- [3-Methoxy-4-(5-oxazolyl) N phenyl] 1,1-dimethyl-3-(I 1-c, oxido- 3-pyridyloxy)propyl] 243 oxalamide ,-o N-[3-(3,4-Dihyclroxyphenoxy)-1,1- dimethyipropyl] [3-methoxy-4-0CH oxalamide 0 N- [3-Methoxy-4-(5-oxazolyl) ZQK f phenyl]-N'-[1,1-dimnethyl-3- 0 C O (methylcarbamoyl)phenoxyl propyl oxalamide N- [3-Methoxy-4-(5-oxazolyl) dimethoxyphenoxy) 1,1 dimethyipropyl] oxalamide N- [(2-Hydroxyethyl) carbamoyl] phenoxy] -1,1-dimethyl- propyl]-N'- [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide N-[3-(3-Chlorophenoxy)-1,1-NO dimethylpropyl]-N'-1j3-methoxy-4- -W 0 04,z oxalamidle N-[3-Methoxy-4-(5-oxazolyl) 10 N'JN F0 phenyl]-N'-[1,1-dimethyl-3-(3- N pyridyloxy)propyl] oxalamide N-[3-Methoxy-4-(5-oxazolyl) r ll phenyl] 1,-dimnethyl-3-(2- N~~f pyridyloxy)propyl] oxalamide C l 2-[4-[3-[[[3-Methoxy-4-(5- oxazolyl)anilino] oxalyl] amino] -3-a methylbutoxy] phenyl] acetic acid [[3-Methoxy-4-(5- O oxazolyl)anilino] oxalyl] amino] HC 244 *0. methylbutoxy] phenyl] acetic acid a~ 0cvi 4- [3-Methoxy-4-(5-oxazolyl) 0 Ot0- anilino] oxalyl] amino] -2- methylpropoxy]benzoic acid anilino] oxalyl] amino] l methylbutoxy] -2-methylbenzoic O acid 3- [3-Methoxy-4- oxazolyl)anilino] oxalyl] amino] j O methylbutoxy] phenyll propionic acid 3- [3-[[[3-Methoxy-4- o anilino] oxalyl] amino] -H 3-methylbutoxy] phenyll propionic acid 3- [[3-Methoxy-4-(5-N0 oxazolyl)anilino] oxalyl] amino] Ir methylbutoxy] phenyl] propionic acid 2 3 -Methoxy- 4 oxazolyl)anilino] oxalyl] amino] t t methylbutoxyl phenoxy] acetic acid 4-[3-[[[3-Methoxy-4-(5-oxazolyl) NH;O anilino] oxalyl] amino] -,-PC methylbutoxy] acid N-[3-(4-Cyano-2- j, 0H CH methoxyphenoxy) 0 I' dimethyipropyl] [3-methoxy-4- oxalamide 245 N- [3-(3-Cyanophenoxy)- 1, 1- dimethyipropyl] [3-methoxy-4- oxalamide 0 0 0 c N- (4-Acetyl- I1-piperazinyl) phenoxy] 1, 1-dimethyipropyl] [3-methoxy-4- oxalamide KNO (~0 N-[3-Methoxy-4-(5- CIH oxazolyl)phenyl] [1,1-dimethyl- NCN 3- (2-morpholinophenoxcy)propyl] oxalamide N- [3-Methoxy-4- 0 phenyl]-N'- [1,1-dimethyl-3- [3- (dimethylamino)phenoxy] propyl] oxalamide N- [3-(1,3-Benzodioxol-5-yloxcy)- 0N 1,1-dimethylpropyl] [3- methoxy-4- oxalamide N- [3-Methoxy-4-(5-oxazolyl) 't phenyl] 0 CH, trimethoxyphenoxy) -1,1- dimethyipropyl]I oxalamide N- [3-Methoxy-4- phenyl]-N'-[3-(3,5- o I dimethoxyphenoxy) 1,1 dimethyipropyl] oxalamide 0 N 3 -Tetrahydro 5-oxo- 2- N' 0 C naphthyloxy) 1-dimethylpropyl] F 0 [3-methoxy-4-(5- oxazolyl)phenyl I oxalamide 246 N- [3-(2-Acetamido-5- methylphenoxy) -1,1- dim ethyipropyl] methoxy-4- oxalamide GI 0 go*. 0 04 S. N-[3-(3-Acetamidophenoxy)-1,1- I dimethyipropyl] [3 -methoxy-4- 1, -oxazolyl) phenyl oxalamide dimethylpropyl] 3 -methoxy-4- 0 oxalamide oIc c~ N- [3-(2-Fluoro-6- 0 methoxyphenoxy)-1,1- A00 N- dimethyipropyl] 3-methoxy-4- oxalamide N- [3-Methoxy-4-(5-oxazolyl) 0 a' ph enyl]-N'- 1 -d imethyl- 3 J, oxo -2 H- 1- b en zopyran -7 yloxy)propyl] oxalamide N- (4-Acetyl-3-methylphenoxy) Ai 0 C m 1, 1-dimethylpropyl] 0A0 methoxy-4- oxalamide [3-Methoxy-4- (5-oxazolyl) o, phenyl]-N'- 1,-dimethyl-3-[4-(3- 0 oxo-l1-butenyl)phenoxy] propyl] oxalamide N-[3-(3-Acetylphenoxy)-1,1- 0 n c dimethyipropyl] [3-methoxy-4- I~ oxalamide CH. N- (4-Acetylphenoxy)- 1, 1 C 0lc dimethylpropyl] [3-methoxy-4- Y-kA 0& oxalamide 247 O~ HC C' Ir N- [3-(4-Acetamido-2- N1 chiorophenoxy) I1 0C dimethyipropyl] -[3-methoxy-4- oxalamide N-[3-Methoxy-4-(5- FN-o oxazolyl)phenyl] [1,1 -dimethyl- I 3-(4-pyridyloxy)propyl] oxalamide N- [3-Methoxy-4-(5-oxazolyl)I phenyl] 1-dimethyl-3-( 1- 0 cm II, O oxido-4-pyridyloxy)propyl] oxalamide Pf -C N- [3-Methoxcy-4-(5-oxazolyl)N CH phenyl] 1-dimethyl-3-(2,6- 0 Cy IN dimethyl-4-pyridyloxy)propyl] 0 oxalamide N- [3-Methoxy-4-(5-oxazolyl) w- C phenyl]-N'-[1,1-dimethyl-3-(2,6- dimethyl- 1 -oxido-4-pyridyloxy) t propyl] oxalamide H, 0 CH, N- 2- (4-Cyanophenoxy) 1, 1- 0 0N dimethylethyl] [3-methoxy-4- XN oxalamide N- [3-Methoxy-4- (5-oxazolyl) N/ 'I phenyl] (2-methoxy-4- I 0~NC~>><N pyridyloxy) 1 -dimethyipropyl] oxalamide N- [3-Methoxy-4- (5-oxazolyl) 0 NWN phenyl] 1-dimethyl-2- N, (1 H-tetrazol-5-yl)phenoxy] ethyl] oxalamide N- [3-(4-Cyanophenoxy)- 1,1 dimethyipropyl] [3-methoxy-4- 248 oxalamide I N- [2-(3-Cyanophenoxy)- 1, 1- dimethylethyl] [3-methoxy-4- oxalamide N- [3-Methoxy-4-(5-oxazolyl) phenyl] 1,1-dimethyl-2- [3- ethyl] oxalamide 0N 001 0 C,~4 ID 0 C 6 N-N 0. N N N. N N-[3-Methoxy-4-(5-oxazolyl) o7 phenyl]-N'-[1,1-dimethyl-3-[4- Io propyl] oxalamide Benzyl 4-[2-[1-[[[3-methoxy-4-(5- oxazolyl)anilino] oxalyHl amino] -1I- cyclobutyl] ethoxy]benzoate Benzyl 4-[2-[1-[[[3-methoxy-4-(5- C' oxazolyl)anilino] oxalyl] amino] cyclopentyl] ethoxy]benzoate Benzyl 4- [3-methoxy-4- I oxazolyl)anilino] oxalyl] amino] -1I- cyclohexyl] ethoxylbenzoate o 4- [1-[[[3-Methoxcy-4-(5- c o oxazolyl)anilino] oxalyl] amino]-1I- I "e cyclopentyllethoxy]benzoic acid N 4- [3-Methoxy-4-(5- c GQ. o oxazolyl)anilinol oxalyl] amino] -1I- o oIN cyclohexyllethoxylbenzoic acid N 0 4-[2-[1-[[[3-Methoxy-4-(5- 01 oxazolyl) anilino Ioxalyl) amino] o cyclobutyl] ethoxylbenzoic acid 249 0 Benzyl 2-methoxy-4- methoxy-4- o N ClyN.-, oxazolyl)anilino] oxalyl] amino] -3- methylbutoxy] benzoate 3-Chloro-4- [[[3-methoxy-4- 7 ?0 oxazolyl)anilino] oxalyl] amino] Y- I methylbutoxylbenzoic acid0 2-Methoxy-4- [3-[[[3-methoxy-4- L-6 C, anilino] oxalyl] amino] 1IJ4O 0 0- 3-methylbutoxylbenzoic acid0 0-%0 3-Methoxy-4- [3-[[[3-methoxy-4- 0~ oxalyl] amino] -F 3-methylbutoxylbenzoic acid 0 4-[2-[l-1[[3-Methoxy-4-(5- c" oxazolyl)anilinol oxalyl]amino] -1I- 0Y o-y cyclopropyl] ethoxy]benzoic acid o H 2-Chloro-4-[3-[[[3-methoxy-4-(5- oxazolyl)anilino] oxalyl] amino] o methylbutoxylbenzoic acido [[3-Methoxy-4-(5-oxazoly) K" o I .P- anilino] oxalyl] amino] 0o~ methylbutoxy] -2- quinolinecarboxylic acid (cis/trans)-4- [3-Methoxy-4-0 (5-oxazolyl)anilino] oxalyl] amino] 0 O')IrH 0 3-methylbutoxy] -1- cyclohexanecarboxylic acid (cis/trans)-4- [3-Methoxy-4- N AN anilino] oxalyl] amino] 2-methyipropoxy] -1- cyclohexanecarboxylic acid N 250 3-Fluoro-4-[3-[[[3-methoxy-4-(5- N 0F oxazolyl)anilino] oxalyl] amino] 0 methylbutoxylbenzoic acid 3-Acetamido-4- [3-methoxy-4- N -0 HN anilino] oxalyl I amino] 0 yO 0 3-methylbutoxylbenzoic acid 3-(Methanesulfonamido)-4- QN 0 H9! [[[3-methoxy-4-(5- a -YN+-O0H oxazolyl)anilino] oxalyl] amino] 0 methylbutoxylbenzoic acid 4- [3-Methoxy-4- (5-oxazolyl) N' anilino] oxalyl] amino] 0 OH methylbutoxy] 0 dimethylbenzoic acid 3- [[3-Methoxy-4- (5-oxazolyl) NO 9 0 0OH anilino] oxalyl] amino] oNAN+-K07- methylbutoxy] -2- pyridinecarboxylic acid O OH 8- [3-[[[3-Methoxy-4-(5-oxazolyl) N.S 0 anilino] oxalyl] amino] -3-aN"NF 0 methylbutoxy] -2- quinolinecarboxylic acid 5- [3-Methoxy-4-(5-oxazolyl)0 anilino] oxalyl] amino] 0a ON H methylbutoxy] -2-indolecarboxylic acid a. 27. Compounds according to claim 23 of the formula 251 XIX ,C 2)n" S R1 2 3 56 9 wherein R R R R R7, R' and R 10 are defined as above, R" and R 1 3 are H or lower alkyl, n= 0 or 1, R a, R b are lower alkyl or R' and Rb taken together with the carbon atom to which they are attached form a 3 to 7 member carbocycle, R 12 is heterocyclyl, aryl or lower cycloalkyl. 28. Compounds according to claim 27 wherein 10 R 2is methoxy and R 9 R' 0 R" and R 1 3 are hydrogen. 29. Compounds according to claim 23, 27 and 28 selected from table lfe Name Structure N- [3-Methoxcy-4-(5-oxazolyl) /N&O OC phenyl]-N'-[1,1-dimethyl-2-I- (phenylthio) ethyl] oxalamide O FC 0" 252 N- (4-Hydroxyphenylthio)- 1,1 dimethylethyl] [3-methoxy-4- oxalamide N- [3-Methoxy-4-(5-oxazolyl) phenyl] 1,l1-dimethyl-2- (phenylthio) ethyl] oxalamide N- 3-Methoxy-4-(5-oiazoly1) phenyl] 1, 1-dimethyl-2- (2- pyridylthio) ethyl]I oxalamide N'-O 0' 0 Ay N-[3-Methoxy-4-(5-oxazolyl)N'O0 phenyl]-N'-[l,l-dimethyl-3-(2- I-~ pyridylthio)propyl] oxalamide N-[3-Methoxy-4-(5-oxazolyl) O CF phenyl] 1,-dimethyl-3-(2- i thienylthio)propyl] oxalamide0 l N- [3-Methoxy-4-(5-oxazolyl) NIIO1 O-C phenll 1 1 dimthy-3-2- 1 0 pyrimidylthio)propyl] oxalamide 0c N-[(3-Methoxy-4-(5-oxazolyl) N1"0 1 phenyl]-N'-[l,1-dimethyl-3-(4- -IyPS pyridylthio)propyll oxalamide 0 04~ K N- [3-Methoxy-4- (5-oxazolyl) WJ'0 0-C, phenyl]-N'- ,l-dimethyl-3-(2- 11-Y thiazolylthio)propyl] oxalamide 0 Cl N-[3-(4-Hydroxyphenylthio)- 1,1- L-1 I~ dimethyipropyl] [3-methoxy-4- 0 y4hsQ oxalamide N-[3-Methoxy-4-(5-oxazolyl) 0 phenyl] l,-dimethyl-3-(5- oq N CS,r, s methyl-i ,3,4-thiadiazol-2-ylthio) propyl] oxalamide 253 a a a a a a a a. N- [3-(2-Benzooxazolylthio)-1,1- O- dimethylpropyl]-N'- [3-methoxy-4- oxalamide N-[3-(2-Benzothiazolylthio)-1,1- dimethyipropyl] [3-methoxy-4- oxalamide Methyl 4- [2-[[[3-methoxy-4-(5- 0 N lS oxazolyl)anilino] oxalyl] amino] ~'0 methylpropylthio] benzoate oxazolyl)anilino] oxalyl] amino] 0". methylbutylthio] 01 pyridinecarboxylate F 0 anilino] oxalyl] amino] O__1 kc C O methylbutylthio] pyridinecarboxylic acid trifluoroacetate (1:1) 4- [3-Methoxy-4- (5-oxazolyl) 0 anilino ]oxalyl] amino] ,'PC 1 methylbutylthio]benzoic acid0 N- (4-Benzyloxyphenylthio) -1,1-N-Q 0 dimethylethyl] [3-methoxy-4- L I1NANt-SaoYI (5-oxazolyl)phenyl] oxalamide N- [2-(4-Benzyloxyphenylthio)- 1, 1 W dimethyipropyl] [3-methoxy-4-0 oxalamide 2- [[3-Methoxy-4- (5-oxazolyl) ~c anilino] oxalyl] amino] 3- Oj methylbutyithiol benzoxazolecarboxylic acid 254 N- 1H-Imidazol-2-ylthio)- 1,1 dimethyipropyl] -methoxy-4- oxalamide 2- [3-Methoxy-4- (5-oxazolyl) anilino] oxalyl] amino] -3- methylbutyithio] -3- pyridinecarboxylic acid trifluoroacetate (1:1) <0 o0 0 N F 0 0' 9 F OH 4-[2-[[[3-methoxy-4-(5- J 1 oxazolyl)anilino] oxalyl] amino] ANk N< 0 methylpropylthio]benzoic acid 2- [[3-Methoxy-4- anilinojoxalyl]amino] C methylbutylthio] -6- benzoxazolecarboxylic acid 30. Compound according to claim 23 of the formula N R'XX Ra Rb 12 R 0 NC 613N R 11 28 R'1 3 and R 2 are H or lower alkyl, n= 0 or 1, Ra, R b are lower alkyl. or Ra and Rb taken together with the carbon atom to which they are attached form a 3 to 7 memeber carbocycle, and R 1 2 is heterocyclyl, aryl or lower cycloalkyl. 255 31. Compound according to claim 30, wherein R 2is methoxy and R 3 R 5 R 6 R 9 R 10 ,R 1 and R'1 3 are hydrogen and R 28 is hydrogen or methyl. 32. Compounds according to claims 23, 30 and 31 selected from table I e Name Structure MS(ES) Ex No (Mi-H)+ N- [3-Methoxcy-4-(5-oxazolyl) phenyl]J 1, 1-dimethyl 0 methylanilino) ethyl] oxalamide 0HC C 4263 N'-[3-methoxy-4-(5-oxazolyl) WI y 4>_ phenyl] oxalamide hydrochloride 0 CHCj423 633 (1:1) anilino] oxalyl] amino] f-C methylbutylaminolbenzoic acid 467 634 33. Compounds according to claim 1 of the formula 256 R21 N wherein R R R R R R 9 and R1 0 are defined as above, R' 1 and R 1 3 is H or lower alkyl, n 0 or 1 %*9 *00.

942.5 R 2 1 is optionally substituted phenyl, optionally substituted phenyl alkyl, optionally substituted phenyl carbonyl, optionally substituted phenyl sulfonyl. 34. Compounds according to claim 33 wherein wherein R 2 is methoxy, R 3 R 6 R 9 R 10 ,R11 and R'1 3 are hydrogen. Compounds according to claims 33 or 34 selected from table I g 257 Name Structure N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1, 1 -dimethyl-2- 0or-0 (4-phenyl- 1- 0 piperazinyl) ethyl] oxalamide N- [3-Methoxy-4-(5- 0NI oxazolyl)phenyl] ,No methoxyphenyl)-1I-piperazinyl] 'L dimethylethyl] oxalamide N- [3-Methoxy-4-(5- KNa 0 o oxazolyl)phenyl] [2 0 fNYNyKNCD methoxyphenyl) -1I -piperazinyl] 1, 1- N dimethylethyl]I oxalamide N-[3-Methoxy-4-(5-N0- oxazolyl)phenyl] 1, 1-dimethyl- 3- I kNNY (4-phenyl- 1- piperazinyl)propyl] oxalamide N- [3-Methoxy-4-(5- (NI oxazolyl)phenyl] 0 N KK N N2, o methoxy-phenyl) -1 -piperazinyll 1, 1- <OY dimethylethyl] oxalamide N- 2- (4-Benzyl- 1 -piperazinyl)- 1, 1 0 y K C 1 dimethylethyl] -methoxy-4- (J1N NJ oxazolyl)phenyl]I oxalamide N- [4-(Benzenesulfonyl)- 1 c piperazinyl] 1, 1 -dimethylethyl] [3-methoxy-4-(5- N oxazolyl)phenyl] oxalamide N- (4-Benzoyl- 1 -piperazinyl) 1,1 dimethylethy1] [3-methoxy-4- -r oxazolyl)phenyl] oxalamideN .:Oo 000. 0 0 0 0 OVOO: :0.00. 0.0 0. :.oo* 0.000 O..o 0.00 ::*oo 258 (Trifluoromethyl)phenyl] -1 piperazinyl] 1,1 -dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide F F cN 0 0% N- [3-Methoxy-4-(5-I W~9 oxazolyl)phenyl] -dimethyl-2- 0 NYN -N, [4-(2-methylphenyl)-l- piperazinyl] ethyl] oxalamide [4-(2-Fluorophenyl)-l- C piperazinyl] 1 dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide N- 2- 4- (4-Fluorophenyl) 1 0lt pip erazinyl] -1,1-dimethylethyl] I 13 -methoxy-4- oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5- oxazolyl)phenyl]-N'-[2-[4-(2- methoxyphenyl)- 1-piperazinyl] -1,1- dimethylethyl] oxalamide N- [3-Methoxcy-4-(5- oxazolyl)phenyl] 1-dimethyl-2- [4-(2-thiophenesulfonyl)- 1- piperazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5-% oxazolyl)phenyl]-N'-[1,1-dimethyl-2- (2,4,6-trimethylbenzenesulfonyl) 1 -piperazinyl] ethyl] oxalamide N- (4-Fluorobenzenesulfonyl) 1 -piperazinyl] 1, 1 -dimethylethyl] -N'-j0 [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide 259 N- [4-(Trifluoromethanesulfonyl)- C% 0N 1 -piperazinyl] 1, 1 -dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl) I oxalamide N- (Isopropylsulfonyl)-l 1- N piperazinyl] -1,1-dimethylethyl] 14c [3-methoxy-4-(5- oxazolyl)phenyl) oxalamide [3-Methoxy-4- (5- oxazolyl)phenyl] [1,1-dimethyl-2- [4-(styrylsulfonyl)- 1- piperazinyl] ethyl] oxalamide N- [4-(Ethanesulfonyl)- 1 piperazinyl] 1, 1 -dimethylethyl] [3-methoxcy-4-(5- oxazolyl)phenyl] oxalamide 0 IC CF% yx y,- 0 0, ?HI N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1, 1 -dimethyl-2- (propanesulfonyl)- I1- piperazinyl] ethyl] oxalamide 0 0 0* N- [4-(3-Chloropropanesulfonyl)- 1 -piperazinyl] 1,1 -dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1,1 -dimethyl-2- [4-(o-toluenesulfonyl)- 1 piperazinyl] ethyl] oxalamide c 0l ('N 0 N- (2-Fluorobenzenesulfonyl)- 1-piperazinyl]-1,1-dimethylethyl] 0~ [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide 260 N- [4-(2-Cyanobenzenesulfonyl)- 1-piperazinyl 1,1-dimethylethyl] 0 [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide N- [3-Methoxcy-4-(5- oxazolyl)phenyl] dimethyl-4-isoxazolylsulfonyl)- 1 piperazinyl] 1, 1 -dimethyl- ethyl] oxalamide N- [4-(5-Fluoro-2- methylbenzenesulfonyl)- 1 piperazinyl] 1, 1 -dim ethylethyl] [3-methoxy-4-(5- oxazolyl) phenyl] oxalamide V R 01, CI% 0 lic _jI N- Difluorobenzenesulfonyl)- 1- piperazinyl] -1,1-dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1 -dimethyl-2- 1-methyl- 1H-imidazole-4- sulfonyl)- 1- piperazinyl]I ethyl] oxalamide N- Difluorobenzenesulfonyl)- 1 piperazinyl] 1,1 -dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide H% 0 Ic c~ 0 0 4 c(9 N- Difluorobenzenesulfonyl)- 1 CIo piperazinyl] -1,1 -dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide 261 (Cyclohexylmethanesulfonyl)-l- piperazinyl]I 1 dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5- oxazolyl) phenyl 1, 1 di methyl -2 4 -phenylethan es ulfo nyl) 1 p iperazinyllI ethyl oxalamide N- [3-Methoxy-4-(5- oxazolyl)phenyl] dimethoxyphenyl)- 1 -piperazinyl] 1, 1 -dirnethylethyl] oxalamide N- [3-Methoxy-4- orY oxazolyl)phenyl] 1, 1 -dimethyl-2-o [4-(4-methylphenyl)- 1 piperazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5- N o% [4-(2,4-dimethylphenyl)- 1- piperazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5- oxazolyl)phenyl]-N'-[2-[4-(3,4- r k dimethoxyphenyl)- 1-piperazinyl] 1,1 -dimethylethyl] oxalamide N- [2-(4-Cyclohexyl-1-piperazinyl)- 1,1-dimethylethyl]-N'-[3-methoxy-4- (5-oxazolyl)phenyll oxalamide J N- [4-(Cyclohexylmethyl)-1- ocl piperazinyl] -1,1 -dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide N 262 N- [4-(2-Methoxybenzyl)- 1- piperazinyl] 1,1 -dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide N- [4-(2-Hydroxybenzyl)- I1- piperazinyl] 1, 1 -dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalan-ide N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1,1 -dimethyl-2- [4-(2-methylbenzyl)- 1 piperazinyl] ethyl] oxalamide o b o 4- N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1, 1-dimethyl-2- [4-(2-thenyl)- 1- pip erazinyl] ethyl] oxalamide o o N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1, 1 -dimethyl-2- (2(RS)-phenylpropyl)- 1- piperazinyl] ethyl] oxalamide *N 0 jc O~ N N N- [3-methoxy-4-(5- oxazolyl)phenyl] [1,1-dimethyl-2- (4-pivaloyl- 1- pip erazinyl) ethyl] oxalamide 61C, i N- (2-Furoyl)- 1-piperazinyl] 1,1-dimethylethyl]-N'- [3-methoxy-4- (5-oxazolyl)phenyl] oxalamide 0 C,% 4 N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1, 1 -dimethyl-2- [4-(2-thenoyl)- 1- piperazinyl] ethyl] oxalamide 0~y I 263 N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1,1 -dimethyl-2- [4-(3-thenoyl)- 1- piperazinyl] ethyl] oxalamide N- (2-Cyclopentylacetyl)-1I- piperazinyl] 1, 1 -dimethyl- ethyl]I [3-methoxy-4-(5- oxazolyl)phenyl) ]oxalamide N- (Cyclohexcylcarbonyl)-1I- piperazinyll 1, 1 -dimethylethyl] [3-methoxcy-4-(5- oxazolyl)phenyl] oxalamide N- [3-Methoxcy-4- oxazolyl)phenyl] 1, 1 -dimethyl-2- [4-(2-methylbenzoyl)- 1 piperazinyl] ethyl] oxalamide o~o N- [3-Methoxy-4-(5- oxazolyl)phenyl] [1,1 -dimrethyl-2- [4-(4-rnethylbenzoyl)- 1- piperazinyl] ethyl] oxalamide N- (Cycloheptylcarbonyl)- 1 piperazinyl] 1, 1-dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1,1 -dimethyl-2- H-pyrazol-4-yl)carbonyl] -1I- piperazinyl] ethyl] oxalamide N- (Cyclopentylcarbonyl)- 1 piperazinyl] 1, 1 -dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide o~O 0 0 0 (~Ofl(> o 264 N- [3-Methoxy-4-(5- r.~ oxazolyl)phenyl] 1, 1 Dimethyl- 2- (1 -methyl- IH -pyrrol-2- yl)carbonyl] -1- piperazinyl] ethyl]I oxalamide N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1-dimethyl-2- 0-l~ (1,2,3 -thiadiazol-4-yl) carbonyl] I1-piperazinyl] -ethyl] oxalamide N- 2- 4- Fluorobenzoyl) 1 piperazinyl] -1,1-dimethylethyl] or [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide N- [4-(4-Fluorobenzoyl)- 1 cq piperazinyl] 1, 1 -dimethylethyl] i [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide N- (Cyclopropylcarbonyl)-1I- piperazinyl] 1, 1 -dimethylethyl] 1r [3-methoxy-4-(5-(" oxazolyl)phenyl] oxalamide N 2- 4- (2 -Cycl oh exylace tyl) -1I- p ip er azi nylI 1, 1 d imethyl ethyl -N'-o [3-methoxy-4-(5- oxazolyl)phenyl]I oxalamide N- [3-Methoxy-4-(5- oxazolyl)phenyl] dimetliylb utyryl) 1- pip erazinyl]-11 dimethylethyl] oxalamide N 2- 4 -Hydroxy- 2,2 dimethylpropionyl) pip erazinyl- 1, 1- dim ethylethyl]I 3- methoxy-4- oxalamide S S S. 265 N- [3-Methoxy-4-(5- oxazolyl)phenyl] [I 1,1 -dimethyl-2- [4-(3-methyl-2-furoyl)- 1- pip erazinyl] ethyl] oxalamide YL- 61". N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1,1 -dimethyl-2- (2-methyl-3-furoyl)- 1 piperazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5- oxazolyl)phenyll 1, 1 -dimethyl-2- O-f I (5-methyl- 1H-pyrazol-3- yl)carbonyl] -1- piperazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5- c oxazolyl)phenyl] 1 -dimethyl-2- (5-methyl-4- isoxazolyl)carbonyl] -1I- piperazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1, 1 -dimethyl-2- 0-r [(5-methyl-3- isoxazolyl) carbonyl] -1I- piperazinyl] ethyl] oxalamide N- (4-Aminobenzoyl)- I-0 piperazinyl]- l,1-dimethylethyl]-N'-- [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide N- 2- (2-Hydroxybenzoyl) 1 oF piperazinyl] -1,1 -dimethylethyl] [3-methoxy-4-(5- oxazolyl) phenyl]I oxalamide OS C C. C 0* S Ce -266- N- [4-(4-Hydroxybenzoyl)- 1- piperazinyl] 1,1 -dimethylethyl] -N [3-methoxy-4-(5- oxazolyl)phenyl]I oxalamide 0 KCOI. N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1,1 -dimethyl-2- [(2,5-dimethyl-2H-pyrazol-3- yl)carbonyl] -1- piperazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1, 1 -dimethyl-2- (3-methyl-2-thenoyl)- 1 piperazinyl] ethyl] oxalamide N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1, 1 -dimethyl-2- [4-(4-methyl-2-thenoyl)- 1 piperazinyl] ethyl] oxalamide 6 0 c a ANCOL. i N- [3-Methoxcy-4-(5- oxazolyl)phenyl] [1,1-dimethyl-2- [(2,2,3,3-tetramethyl-1- cyclopropyl)carbonyl] -1I- piperazinyl] ethyl] oxalarnide N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1, 1 -dimethyl-2- (4-methyl- 1,2,3-thiadiazol-5- yl)carbonyl] -1- piperazinyl] ethyl] oxalamide 0 0 4 N- (3-Cyanobenzoyl) -1I- piperazinyl] 1-dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide 267 oaf 0. 6 0 [(Bicyclo[4.2.O]octa- 1(6),2,4-trien-7-yl)carbonyl] -1- piperazinyl] -1,1-dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl]I oxalamide N- [2-[4-(3-Hydroxybenzoyl)- 1- piperazinyl] -1,1 -dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide ~Y~o i N- [4-(2-Ethylbutyl)- 1- piperazinyl] -1,1 -dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide i~i: ~yLI% N- [3-Methoxy-4-(5- oxazolyl)phenyl] [1,1 -dimethyl-2- [4-(2-phenylethyl)- 1- piperazinyl] ethyl] oxalamide I N- [3-Methoxy-4-(5- oxazolyl)phenyl] 1, 1 -dimethyl-2- 4- (methylthio)propyl] I1- piperazinyl]I ethyl] oxalamide N- (2,6-Difluorobenzyl) -1I- piperazinyl] 1,1 -dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide H6 01 or F I N- [4-(3-Furfuryl)- 1-piperazinyl] 0 1,1-dimethylethyl] [3-methoxy-4- oxalamide N- [(2-Benzofuranyl)methyl] Nc o (IT C-% I1-piperazinyl 1, 1-dimethylethyl] -N'-0 [3-methoxy-4-(5- oxazolyl)phenyl) Ioxalamide 268 N- [4-(2-Cyanobenzyl)- 1- piperazinyl] 1, 1 -dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5- oxazolyl)phenyl] (3 ,3- dimethylbutyl)-1-piperazinyl] -1,1- dimethylethyloxalamide N- [3-Methoxy-4-(5- oxazolyl)phenyl] [1,1-dimethyl-2- [(2-quinolinyl)methyl] -1- piperazinyl] ethyl] oxalamide tert -B utyl 2 -meth oxy- 4 oxazolyl) anilino] oxalyl] amino] methyipropyl] 1 -pip erazineacetate 4- [[([3-Methoxy-4-(5- C oxazolyl)anilino] oxalyl]amino] -2- methyipropyl] I1-piperazineacetic acid trifluoroacetate (1:1) N- [4-(Cyclopropylmethyl)- 1- I N ,t ICO piperazinyl] -1,1 -dimethylethyl] [3-methoxy-4-(5- oxazolyl)phenyl]I oxalamide tert-Butyl 4- 2- [3-methoxy-4- N O oxalyl] amino] 0 methyipropyl] -1I -piperazinyl] benzoate 4- [[[3-Methoxy-4-(5-oxazolyl) O anilino] oxalyl] amino] N04 N, methyipropyl] -1-piperazinyl] benzoic N- 0 O acid trifluoroacetate (1:1) 0* S 269 36. Compounds according to claim 1 of the formula 6\ N 13 R2'l R 7 0 R 0 wherein R, R R, R 6 ,R',R 9 ,R' 0 and R' are defined as above R 22 R 23 R 2 4 R 25 and R 26 are H or lower alkyl l0 R 2 1 is alkyl, aryl or heterocyclyl, alkoxy, aryloxy, heterocyclyl oxy. xv' (see 37. Compounds according to claim 36 wherein 2 3 5 10 13 22 23 24 256 15 R is methoxy, R R,R R9 ,R1,R ,R R R R 2 and R 2 are hydrogen. 38. Compounds according to claims 36 or 37 selected from table 1h 270 Phenyl 0- oxazolyl) anilino] oxalyl] amino] benzyl] 0- carbamnate N Fluorobenzamido)methyl]phenyl] 110 0:),Na [3-methoxy-4-(5-0 oxazolyl)phenyl] oxalamide Chlorobenzamido)methyl]phenyl]-N 01 0 [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide Methoxybenzamido)methyll phenyl] 0' 0 0 N'-[3-methoxy-4-(5- oxazolyl)phenyl] oxalamide N- Dimethoxybenzamido)methyllphenyl] ao -N'-[3-methoxy-4-(5-00 oxazolyl)phenyll oxalamide Cyanobenzamido)methyllphenyl] 0 F [3-methoxy-4-(5- oxazolyl)phenyl] oxalamide 39.. Compounds according to claim 1 of the formula xviI 271 wherein R R R R R 7 and R1 0 are defined as above R" and R" 3 is H or lower alkyl and R 1 2 is heterocyclyl, aryl or lower cycloalkyl. Compounds according to claim 39 wherein R 2 is methoxy, R 3 R 5 R 6 R 9 and 13 are hydrogen and wherein R 12is optionally substituted phenyl or R21 wherein R 2 1 is as above. 41. Compounds according to claims 39 or 40 selected from table Ii es.. N- [3-Methoxy-4-(4- oxazolyl)phenyl] [1,1-dimethyl- 2- (4-phenyl- 1- piperazinyl) ethyl I oxalamide o I 0 00O 272 N- [2-(4-Benzyloxyphenyl)- 1,1- dimethylethyl] [3-methoxy-4- 0. 0 (4-oxazolyl)phenyl] oxalamide N-[2-(4-Hydroxyphenyl)-1,1- C, UUJ0 1 dimethylethyl] [3-methoxy-4- 0" (4-oxazolyl)phenyl] oxalamide N-[3-Methoxy-4-(4- oxazolyl)phenyl] C methoxyphenyl) -1-piperazinyl] 1,1 -dimethylethyl] oxalamide N- [3-Methoxy-4-(2-methyl-4- oxazolyl)-phenyl] methoxyphenyl)- 1 -piperazinyl] 1,1 -dimethylethyl] oxalamide 42. Compounds according to claim 1 of the formula OSS* 9* table lb Name Structure Benzyl 4-12- [[3-methoxy-4-(5- oxazolyl)phenylamino] oxalyl] a mino] -2-methylpropyl} 1 piperidinecarboxylate N- [3-Methoxy-4- (5-oxazolyl) CN ji phenyl] 1, 1 -dimethyl-2- S (phenylthio) ethyl] oxalamide o fc CHN 273 N- 1-Acetyl-4-piperidinyl)- 1, 1-dimethylethyl] [3- methoxy-4- oxalamide O N-(2-Cyclohexyl-1,1- N~ .CN dimethylethyl)-N'- [3-methoxy- 'i:NY> 4- (5-oxazolyl)phenyl] oxalamide 0 CHM N-[3-Methoxy-4-(5-oxazolyl) F phenyl]-N'-[1,1-dimethyl-2-(N- 0 N;'N0 methylanilino) ethyl] oxalamide IY N- (1,2,3,4-Tetrahydro- I1- i- quinolyl) 1 -dimethylethyl] 0:a N 'JNN~ [3-methoxy-4-(5-oxazolyl) N. 0 phenyl] oxalamide k N- 12- (4-Hydroxyphenylthio)- N'O0' 0 1, 1-dimethylethyl] I -4 NIN~SQ methoxy-4- oxalamide N- [3-(4-Hydroxyphenyl)- 1, 1 tO dimethylpropyl] N i: N$(a methoxy-4- oxalamide N- [-Mehoxy4- 5-oazoll) .0 phenyl] 1-dimethyl-2- (o 0 oxido-4-pyridyl)carboxamido] N ethyl] oxalamide N- (4-Acetylbenzamido)- 0 dimethylethyl] [3-methoxy- 00 4- (5-oxazolyl)phenyl] oxalamide N- [3-Methoxy-4-(5-oxazolyl) 0 iK 00 phenyl]-N'-[3-[(4-W methylbenzamido)methyl] pheny 0 *000 *000 OS 00 0 000 0 *0**00 00 0 0 *0 0@ *0 0@0000 *00* C 000* *0 0 S S S. 5050 0 0050 00 0 SO OS -274- 1] oxalamide N- [(2-Methoxybenzamido) C, iiQ 0. 0 NI methyllphenyl]-N'-[3-methoxy- YO A 4- (5-oxazolyl)phenyl] oxalamide N 3 Chlorob enzmi do) methyllphenyl]-N'-[3-methoxy- I 4- (5-oxazolyl)phenyl] oxalamide cp0> N- [3-[[(1,3-Benzodioxol-5- O yl)carboxamido] methyll phenyll 0 [3-methoxy-4-(5-oxazolyl) phenyl]I oxalamide %c ccr- N-[2-(2,3-Dihydro-1-indolyl)- YUQ NQ 1,1-dimethylethyl]-N'-[3- 0 0 K <\Nl methoxy-4- (5-oxazolyl)phenyl] N oxalamide N- [2-(3,4-Dihydro-6-methyl- OHC a 2H-quinol-yl)- 1,1- '0'a 0 0% dimethylethyl]-N'-[3-methoxy- N 4- N-[1-(3-Benzofuranyl)-l- a methylethyl] [3-methoxy-4- A>~ -oxazolyl) phenyl oxalamide iC, N- [3-Methoxy-4-(5-oxazolyl) N phenyl] 1,1 -dimethyl-3-(4-rCI phenoxypiperidino)propyl] oxala mide N- (1 -Butyryl-4-piperidinyl)- 1, 1-dimethylethyl] [3- methoxy-4- oxalamide *000 *0O *0000 0 0 275 N- 1-(Methanesulfonyl)-4- pip eridinyl] 1, 1 -dimethyl ethyl] [3-methoxy-4- phenyl] oxalamide N- 1-(Benzenesulfonyl)-4- piperidinyll 1, 1-dimethylethyl] [3-methoxy-4- phenyl] oxalamide N- 2- (1 -Isobutyryl-4- piperidinyl)- 1, 1 -dimethylethyl] 3-methoxy-4- phenyl] oxalamide o". F- 0 K CM, 0 OH, tert-Butyl 4- 3-methoxy-4- oxalyl] amino] -3-methylbutyl] -1I- piperidinecarboxylate 0H CCH N-[3-Methoxcy-4-(5-oxazolyl) N 0 0CH phenyl] [1,1-dimethyl-3-(4- N ZT pip eridinyl)propyl] oxalamide 276 43. A compound of formula (I) R 2 R6 NR4R8 R O (I) wherein R represents heterocyclyl; R 2 represents hydrogen, unsubstituted lower alkyl, lower alkoxy, halo, hydroxy or cyano; R 3 represents hydrogen, unsubstituted lower alkyl, lower alkoxy, halo, or cyano; R 4 represents hydrogen, lower alkyl, lower cycloalkyl, aryl, or heterocyclyl; R 5 represents hydrogen, unsubstituted lower alkyl, lower alkoxy, halo, or cyano; R" represents hydrogen, unsubstituted lower alkyl, lower alkoxy, halo, or cyano; R 7 represents hydrogen, or unsubstituted lower alkyl; R" represents hydrogen, or unsubstituted lower alkyl; or R 4 and R 8 together with the nitrogen atom to which they are attached represent heterocyclyl; and pharmaceutically acceptable salts thereof, substantially as hereinbefore described with reference to any one of the Examples. 44. A process for the manufacture of the compounds of formula claimed in any 20 one of claims 1 to 43 and their pharmaceutically acceptable salts, which process comprises the general reaction scheme: I I:\I)AYLIB\LIBA]03690.doc:nss 277 R 2 R R 3 R 6 NR 7 H R 5 (IT) 0 Coupling R 2 SM Cl RR R 3 0 R 6 OMe R5 R 7 (III) 0 SNR 4 R 8 0 i, Coupling, and ii, Optional Modification HNR 4 R 8 Hydrolysis O 0 S (IV) vwherein R' to R 8 are defined as in claim 1, and, optionally, converting the compound of bormula into a pharmaceutically acceptable salt. A compound of formula as defined in claim 1 when produced by the process of claim 44. 46. Compounds of the general formula (IV) wherein R R R R R 6 an dR 7 are defined as in claim I. 47. A process for the manufacture of the compounds claimed in claim 4, and their is pharmaceutically acceptable salts, which process comprises the general reaction scheme: [I :\DAYLIB\LIBA]03699.doc nss 278 O R 3 +MeO R C M CI 'NHR7 Coupling R 10 (VI) (VII) Hydrolysis if i, Coupling, ii, Optional Modification ,3 O(V) (V) 0 OH o 7 (IX) (VII) wherein R 2 R 3 R 4 R S R 6 R 7 and R 8 are defined as in claim 1, and R 9 and R'i are defined as in claim 4, and, optionally, converting the compound of formula (IX) into a pharmaceutically acceptable salt. 48. Compounds of the general formula o. o o R' O 1 R6 OH R R7 R 0 (VIII) wherein R 2 R 3 R R and R 7 are defined in claim 1, and R 9 and R io are defined as in claim 4. 49. A process for the manufacture of the compounds of formula claimed in any one of claims 1 to 43 and their pharmaceutically acceptable salts, which process comprises the general reaction scheme: [I \DAYLIB\LIBA]03699.doc:nss 279 i, Coupling, and ii, Optional R2 Modification R2 R RNR 4 8 A 3 R R3 N IR R R6 R NRH 0 R6 N NR 4R R 5 R 5 R7 (II) (I) wherein R 1 to R 8 are defined as in claim 1, and optionally, converting the compound of formula into a pharmaceutically acceptable salt. 50. A compound of formula as defined in claim 1, when produced by the process of claim 49. 51. Compounds according to any one of claims 1 to 43 and their pharmaceutically acceptable salts, when manufactured according to the process claimed in claim 44 or claim 49. 52. Compounds according to claim 4, and their pharmaceutically acceptable salts, when manufactured according to the process claimed in claim 47. 53. A pharmaceutical composition comprising a compound according to any one of claims 1 to 43, 45, 50, 51 or 52, or its pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier, diluent or adjuvant, and, optionally, one or more additional therapeutically active substance(s). 54. A pharmaceutical composition according to claim 53, wherein the one or more additional therapeutically active substance(s) is an immunosuppressant, a chemotherapeutic agent, an anti-viral agent, an antibiotic, an anti-parasitic agent, an anti- lungal agent, an anti-inflammatory agent and/or an anti-vascular hyperproliferation agent. 2 0 55. A pharmaceutical composition according to claim 54, wherein the one or more additional therapeutically active substance(s) is interferon or a derivative thereof. S* 56. A compound according to any one of claims 43, 45, 50, 51 or 52 or its 0 pharmaceutically acceptable salt, or a composition according to any one of claims 53 to 55 when used in therapy. 25 57. A compound or composition when used according to claim 56 wherein said therapy is monotherapy. 58. A compound or composition when used according to claim 56 wherein said therapy is combination therapy. 1I \DAYLIIB\I.IBA]0369) doc:nss 280 59. A therapy method comprising administering to a patent in need an effective amount of a compound according to any one of claims 1 to 43, 45, 50, 51 or 52 or a composition according to any one of claims 53 to The method of claim 59 wherein said therapy is monotherapy. 6 I. The method of claim 59 wherein said therapy is combination therapy. 62. A process for the production of a medicament, which process comprises bringing a compound according to any one of claims 1 to 43, 45, 50, 51 or 52, or a pharmaceutically acceptable salt thereof into a galenical administration form together with a pharmaceutically acceptable carrier, diluent or adjuvant and, optionally, one or It more additional therapeutically active substance(s). 63. A process according to claim 62. wherein the one or more additional therapeutically active substance(s) is an immunosuppressant, a chemotherapeutic agent, an anti-viral agent, an antibiotic, an anti-parasitic agent, an anti-fungal agent, an anti- inflammatory agent and/or an anti-vascular hyperproliferation agent. 64. A process according to claim 63. wherein the one or more additional therapeutically active substance(s) is interferon or a derivative thereof. A medicament when produced by the process of any one of claims 62 to 64. 66. A method of treating an immune mediated condition or disease, a viral disease. a bacterial disease, a parasitic disease, inflammation an inflammatory disease, a hyperproliferative vascular disease, a tumour, or cancer in a subject, comprising the step of administering to the subject a therapeutically effective amount of a compound according to any one of claims 1 to 43, 45, 50, 51 or 52, or its pharmaceutically acceptable salt, or a pharmaceutical composition according to any one of claims 53 to 67. A method of treating an immune mediated condition or disease, a viral disease, a bacterial disease, a parasitic disease, inflammation, an inflammatory disease, a hyperproliferative vascular disease, a tumour, or cancer in a subject, comprising the steps of administering to the subject a therapeutically effective amount of a compound according to any one of claims 1 to 43. 45, 50, 51 or 52, or its pharmaceutically *i acceptable salt, or a pharmaceutical composition according to any one of claims 53 to and concurrently or sequentially administering to the subject one or more additional therapeutically active substance(s). 68. A method according to claim 67, wherein the one or more additional therapeutically active substance(s) is selected from the group consisting of an immunosuppressant, a chemotherapeutic agent, an anti-viral agent, an antibiotic, an anti- I :\DAYLIB\LIBA]03609 doc:nss 281 parasitic agent, an anti-fungal agent, an anti-inflammatory agent and an anti-vascular hyperproliferation agent. 69. A method according to claim 68, wherein the one or more additional therapeutically active substance(s) is interferon or a derivative thereof. s 70. A method of treating or preventing IMPDH mediated diseases, comprising the step of administering to a subject an effective amount of a compound according to any one of claims 1 to 43, 45, 50, 51 or 52 or its pharmaceutically acceptable salt, or a pharmaceutical composition according to any one of claims 53 to 71. The use of an effective amount of a compound according to any one of claims I to 43. 45, 50, 51 or 52, or its pharmaceutically acceptable salt for the manufacture of a medicament for the treatment or prevention of IMPDH mediated diseases. 72. The use of an effective amount of a compound according to any one of claims I to 43, 45, 50. 51 or 52, or its pharmaceutically acceptable salt, in combination with, an effective amount of one or more additional therapeutically active substance(s), for the manufacture of a medicament for the treatment of an immune mediated condition or disease, a viral disease, a bacterial disease, a parasitic disease, inflammation, an inflammatory disease, a hyperproliferative vascular disease, a tumour, or cancer. 73. The use according to claim 72 wherein the one or more additional therapeutically active substance(s) is selected from the group consisting of an immunosuppressant, a chemotherapeutic agent, an anti-viral agent. an antibiotic, an anti- parasitic agent, an anti-fungal agent, an anti-inflammatory agent and an anti-vascular hyperproliferation agent. 74. The use according to claim 73 wherein the one or more additional therapeutically active substance(s) is interferon or a derivative thereof. 25 75. The use of an effective amount of a compound according to any one of claims I to 43. 45, 50, 51 or 52 or its pharmaceutically acceptable salt, for the manufacture of a medicament for the treatment of an immune mediated condition or disease, a viral disease. a bacterial disease, a parasitic disease, inflammation, an inflammatory disease, a hyperproliferative vascular disease, a tumour, or cancer. o 76. The use according to claim 75. wherein the medicament is for concurrent or sequential administration with one or more additional therapeutically active substance(s). 77. The use according to claims 76 wherein the one or more additional therapeutically active substance(s) is selected from the group consisting of an immunosuppressant, a chemotherapeutic agent, an anti-viral agent, an antibiotic, an anti- 11 \DIAYLIB\LIBA]0360)9.doc:nss 282 parasitic agent, an anti-fungal agent, an anti-inflammatory agent and an anti-vascular O hyperproliferation agent. 78. The use according to claim 77 wherein the one or more additional therapeutically active substance(s) is interferon or a derivative thereof. 579. The method according to any one of claims 66 to 70, wherein said disease being treated is an immune mediated condition or disease, especially an autoimmune disease. a graft versus host disease, or transplant rejection. The use according to any one of claims 71 to 78, wherein said disease being treated is an immune mediated condition or disease, especially an autoimmune disease, a to graft versus host disease, or transplant rejection. 81. The use according to any one of claims 71 to 78, wherein said disease being treated is a viral disease, especially a viral disease wherein the virus is orthomyxovirus, paramyxovirus, herpesvirus, retrovirus, flavirus, pestivirus, hepatrophic virus, bunyavirus. Hantaan virus, Caraparu virus, human papilloma virus, encephalitis virus, arena virus, reovirus, vesicular stomatitis virus, rhinovirus, enterovirus, Lassa fever virus, togavirus, poxvirus, adenovirus, rubiola virus, rubella virus, or hepatitis virus. 82. The use according to claim 81, wherein the virus is hepatitis C. 83. The use according to claim 81, wherein the virus is HIV. 84. The use according to any one of claims 71 to 78 wherein said disease being treated is a hyperproliferative vascular disease, especially wherein the hyperproliferative vascular disease is restenosis, stenosis or artherosclerosis. 85. The use of any one of claims 71 to 78, for the treatment of inflammation or an inflammatory disease, especially an inflammatory disease wherein the inflammatory disease is osteoarthritis, acute pancreatitis, chronic pancreatitis, asthma, or adult respiratory distress syndrome. 86. The use according to any one of claims 71 to 78, for the treatment of a tumour or cancer, especially for the treatment of cancer wherein the cancer is lymphoma or leukaemia. 87. The method according to any one of claims 66 to 70 wherein said disease being treated is a viral disease, especially a viral disease wherein the virus is orthomyxovirus, paramyxovirus, herpesvirus, retrovirus, flavirus, pestivirus, hepatrophic virus, bunyavirus, Hantaan virus, Caraparu virus, human papilloma virus, encephalitis virus, arena virus, reovirus, vesicular stomatitis virus, rhinovirus, enterovirus, Lassa fever virus, togavirus, poxvirus, adenovirus, rubiola virus, rubella virus, or hepatitis virus. I:\DAYLIB\LIBA]03699.doc:nss 283 88. The method according to claim 87 wherein the virus is hepatitis C. 89. The method according to claim 87 wherein the virus is HIV. The method according to any one of claims 66 to 70 wherein said disease being treated is a hyperproliferative vascular disease, especially wherein the hyperproliferative vascular disease is restenosis, stenosis or artherosclerosis. 91. The method according to any one of claims 66 to 70 for the treatment of inflammation or an inflammatory disease, especially an inflammatory disease wherein the inflammatory disease is osteoarthritis, acute pancreatitis, chronic pancreatitis, asthma, or adult respiratory distress syndrome. 0 92. The method according to any one of claims 66 to 70 wherein for the treatment of a tumour or cancer, especially for the treatment of cancer wherein the cancer is lymphoma or leukaemia. 93. An effective amount of a compound according to any one of claims 1 to 43, 50, 51 or 52 or its pharmaceutically acceptable salt or an effective amount of a pharmaceutical composition according to any one of claims 53 to 55 when used for the treatment of an immune mediated condition or disease, a viral disease, a bacterial disease, a parasitic disease, inflammation an inflammatory disease, a hyperproliferative vascular disease, a tumour, or cancer in a subject. 94. A compound or composition when used according to claim 93 wherein a therapeutically effective amount of aid compound or composition is administered to said subject concurrently or sequentially with one or more additional therapeutically active substance(s). 9 A compound or a composition when used according to claim 94 wherein the one or more additional therapeutically active substance(s) is selected from the group s consisting of an immunosuppressant, a chemotherapeutic agent, an anti-viral agent, an antibiotic, an anti-parasitic agent, an anti-fungal agent, an anti-inflammatory agent and an anti-vascular hyperproliferation agent. 96. A compound or composition when used according to claim 95 wherein the one or more additional therapeutically active substance(s) is interferon or a derivative 30 thereof. 97. An effective amount of a compound according to any one of claims 1 to 43, 45. 50, 51 or 52 or its pharmaceutically acceptable salt or an effective amount of a pharmaceutical composition according to any one of claims 53 to 55 when used for the treatment or prevention of IMPDH mediated diseases. [I \DA YLIB\LIBA103699.doc:nss 284 98. A compound or composition when used according to any one of claims 93 to 97 wherein said disease being treated is an immune mediated condition or disease, especially an autoimmune disease, a graft versus host disease, or transplant rejection. 99. A compound or composition when used according to any one of claims 93 to S 97 wherein said disease being treated is a viral disease, especially a viral disease wherein the virus is orthomyxovirus, paramyxovirus, herpesvirus, retrovirus, flavirus, pestivirus, hepatrophic virus, bunyavirus, Hantaan virus, Caraparu virus, human papilloma virus. encephalitis virus, arena virus, reovirus, vesicular stomatitis virus, rhinovirus, enterovirus, Lassa fever virus, togavirus, poxvirus, adenovirus, rubiola virus, rubella virus, or hepatitis vir S. 100. A compound or composition when used according to claim 99 wherein the virus is hepatitis C. 101. A compound or composition when used according to claim 99 wherein the virus is HIV. 102. A compound or composition when used according to any one of claims 93 to 97 wherein said disease being treated is a hyperproliferative vascular disease, especially wherein the hyperproliferative vascular disease is restenosis, stenosis or artherosclerosis. 103. A compound or composition when used according to claim 102 for the treatment of inflammation or an inflammatory disease, especially an inflammatory disease wherein the inflammatory disease is osteoarthritis, acute pancreatitis. chronic pancreatitis. o asthma, or adult respiratory distress syndrome. 104. A compound or composition when used according to claim 102 for the treatment of inflammation or an inflammatory disease, especially an inflammatory disease Swherein the inflammatory disease is osteoarthritis, acute pancreatitis, chronic pancreatitis, C. 25 asthma, or adult respiratory distress syndrome. SDated 20 February, 2001 F. Hoffmann-La Roche AG Patent Attorneys for the Applicant/Nominated Person SPRUSON FERGUSON Cool o [I \),AYHII\LI BA]03(699.doc:nss