AU637406B2 - Oxabicyclo ethers. - Google Patents

Description

TITLE B HERBICIDAL OXABICYCLO ETHERS CROSS-REFERENCE TO RELATED APPLICATION A-8812-B This application is a continuation-in-part of copending application U.S. Serial No. 07/431,734 filed September 11, 1989.

Field of the Invention The present invention relates to novel oxabicyclo ether derivative compounds, to compositions containing these ether derivative compounds, and to methods of using these compounds or compositions to control the growth of undesired vegetation. More particularly, the present invention relates to a variety of compounds, compositions, and methods of using them which are herbicidally active on a wide variety of weed species and exhibit safety to rice, cereals and broadleaf crops.

Background of the Invention Payne et al., U.S. Patent 4,567,283 and Payne et al., U.S. Patent 4,670,041 disclose a variety of herbicidal bicyclic ethers of the Formula

"I

I c 1!' r' S~iss'nUufs~re8ru la GB-A-2,188,931 discloses compounds of the following structure:

I

Hal OCH2-

S

wherein Y is a single bond or -CH2-; U.S. 4,798,621 discloses a method-of-use for the following compounds: sz~l-;U7~ B~iE~i' WO 91/03464 PCT/US90/04953 2 U.S. 4,798,621 and WO 8,902,219 both disclose bicyclic ethers and their method-of-use in rice.

U.S. 4,486,219 discloses bicyclic ethers of the formula:

CH

2

W

R

It is an object of the present invention to provide compounds and compositions which exhibit herbicidal activity on a variety of economically important weed species. It is a further object of the present invention to provide compounds and compositions that are herbicidally safe to rice, cereals and broadleaf crops. It is a feature of the present invention to furnish novel oxabicyclo ethers that exhibit useful herbicidal activity. These and other objects, features and advantages will become apparent with respect to the following description of the invention.

SUMMARY OF THE INVENTION The present invention comprises compounds of the formulas selected from the group consisting of: WO 91/03464 I'CT/US9O/04953 3 01 I

I

x y go 0 WO 91/03464 PCT/i 9/45 JS90/04953 Vill and stereoisorners thereof, wherein X and Y are independently H or C(R 3

)(R

4

OR

5 Z is C(R 3

)(R

4

OR

5

R

1 is H or a straight-chain Cl-C 3 alkyl; WO 91/03464 pCU/ US9O/04953

R

2 is H, Cl-C 6 alkyl, C 2

-C

4 alkenyl, C 2

-C

4 alkynyl, phenyl Or Cl-C 4 alkyl substituted by Ph, OH, CN, OR 8 S0 2 RB, PhSO 2

N

3 C0 2

R

8 or CO 2

H;

R

3

R

4

R

9 and R 10 are independently H, C 1

-C

4 alkyl, C 2

-C

4 alkenyl, C 2

-C

4 alkynyl or lC alkyl substituted with OCH 3 or OCH 2

CH

3

R

5 is C 1

-C

3 alkyl, C 2

-C

4 alkenyl, C 3

-C

4 alkynyl, benzyl or C 1

-C

4 alkyl substituted with OR 8

OCF

3

R

8 is C 1

-C

3 alkyl; Q is WCH 2 or

R

W is phenyl optionally substituted with 1-3 substituents selected from F, Cl, Br, Cl-C 3 alkyl, CI-C 3 alkoxy, OH, CN, Cl-C 3 haloalkyl, Cl-C 3 haloalkoxy, Cl.-C 3 alkylthio, C 2

-C

4 aikenyl and C 2

-C

4 alkynyl, or W is a 5 or 6-membered heterocyclic ring containing 0-2 nitrogens, 0-2 oxygens or 0-2 sulfurs, each ring optionally substituted with 1-2 substituents selected from F, Cl, Br, CH 3 and OCH 3 WO 91/03464 PCT/US90/04953 6

Z

1 is CH 2 NRa, O, S or may be taken to form a double bond with an adjacent carbon;

R

a is H or C 1

-C

3 alkyl;

R

6 is H, halogen, R 8

OR

8

SR

8 or CN;

R

7 is H, F, Cl, CH 3

OCH

3 OH or OR 8 q 1 is 0, 1 or 2; and q is 0, 1 or 2.

provided that 1) at least one of X and Y is C(R 3

)(R

4 )0R 5 2) R 3

R

4

R

9 and R 10 each contains no more than four carbon atoms; 3) in Formula II, if R 1 is H then X is

C(R

3

)(R

4

)OR

5 and Y is H; 4) the sum of q and q 1 is 0, 1 or 2; and if the sum of q and ql is 0 then Z 1 is CH 2 A representative exemplification of the aforementioned heterocycles includes but is not limited to pyrrole, furan, thiophene, tetrahydropyran, tetrahydrofuran, isoxazole, oxazole, pyrazole, imidazole, thiazole, pyridine and pyrazines; Preferred compounds of the invention for either their biological activity or ease of synthesis are: 1. Compounds of Formulas I, II, III, IV, V, VI, VII, or VIII wherein: W is phenyl optionally substituted by 1-2 substituents selected from F, Cl, Br, CH 3 and OCH 3 or W is tetrahydropyran, tetrahydrofuran, thiophene, isoxazole, pyridine or pyrazine, each ring optionally substituted with 1-2 substituents selected from F, Cl, Br, CH 3 and OCH 3 pCT/US90/04953 WO 91/03464 Q is Q-1 Q2 R C9 pCT/US90/04953 WO 91/03464 eS9/45

POQA.

Q-1 0 Re Rd Q-1 2

Q-

1 .1 Q-3 Q-1 4 Ris H or C 1

-C

3 alkyl; and

R

5 is other than benzyl.

2. Compounds of Preferred-1 wherein

R

2 is H, Cl-C 3 alkyl, C 2

-C

3 alkenyl

C

2

-C

3 alkynyl.

3. Compounds of Preferred 2 wherein

R

3 is H, C 1

-C

3 alkyl., C 3

-C

4 alkenyl

C

3

-C

4 alkynyl;

R

4 is H, Cl-C 3 alkyl, C 3

-C

4 alkenyl

C

3

-C

4 alkynyl;

R

5 is H, Cl-C 3 alkyl, C 3

-C

4 alkenyl

C

3

-C

4 alkyny.;

I

WO 91/03464 PCT/US90/04953 9

R

9 is H, C 1

-C

3 alkyl, C 3

-C

4 alkenyl or

C

3

-C

4 alkynyl;

R

10 is H, C 1

-C

3 alkyl, C 3

-C

4 alkenyl or

C

3

-C

4 alkynyl; 4. Compounds of Preferred 3 wherein Q is Q-l, Q-3, Q-6, Q-7 or Compounds of Preferred 4 wherein the compound is of Formula I.

6. Compounds of Preferred 4 wherein the compound is of Formula II.

7. Compounds of Preferred 4 wherein the compound is of Formula III.

8. Compounds of Preferred 4 wherein the compound is of Formula IV.

9. Compounds of Preferred 4 wherein the compound is of Formula V.

Compounds of Preferred 4 wherein the compound is of Formula VI.

11. Compounds of Preferred 4 wherein the compound is of Formula VII.

12. Compounds of Preferred 4 wherein the compound is of Formula VIII.

Specifically Preferred for its biological activity and/or ease of synthesis is the compound of Preferred 5 which is: 2-(l-ethyl-l-methoxypropyl)-6-(phenylmethoxy)-7oxabicyclo[22.2.l]heptane, (2-exo, 6-exo); and the compound of Preferred 7 which is: 2-(ethoxymethyl)-5-methyl-4-(phenylmethoxy)-6oxabicyclo[3.2.1]occane, (2-endo, 4-endo).

WO 91/03464 PC/US90/04953 Al 1 my- p-r-ef-er-ably- beseeeted-f-r-mthe consisting of pyrrole, furan, th tetrahydropyran, tetdra rran, isoxazole, oxazole, pyrazole, Compounds of Formula I-VIII that have the group Syn with respect to the oxygen-containing bridge are usually more herbicidally active than the anti form. The present invention contemplates all of the herbicidally active forms resulting from synthesis and from deliberately created mixtures.

The compounds of the invention are prepared by treating the appropriately substituted oxabicycloalkanol (Ia-VIIIa) with a compound of the formula

WCH

2 X in which X is a halogen atom or a mesyloxy, tosyloxy group or the like. This reaction is carried out, as shown in Scheme 1, in the presence of a strong base, such as an alkali metal hydride, in an inert solvent, such as ethers, aromatic hydrocarbons, dimethyformamide and the like. Suitable temperatures for the reaction are preferably from 20 0 C to 100 0

C.

The product ethers are recovered and isolated by conventional techniques.

Compositions suitable for controlling the growth of undersired vegetation are also contemplated as within the scope of this invention. Such compositions comprise an effective amount of any of the compounds disclosed herein and at least one of the following: surfactant, solid, or liquid diluent.

Methods for controlling the growth of undesired vegetation are similarly considered to be within the scope of the invention. These methods comprise applying to the locus to be protected an effective amount of any of the compounds disclosed herein. Of particular importance is the method wherein the locus to be protected is rice.

1.

WO 91/03464 pC/US90/04953 11 Scheme 1

WCH

2

X

Ia-VIIIa I-VIII base The alkylating agents WCH 2 X are prepared in the conventional manners known to those skilled in the art from the alcohols WCH 2

OH.

The alcohols, WCH20H, are generally known in the art and are most conveniently prepared through metal hydride sodium borohydride) reduction of the corresponding bicyclic ketones which can be derived by Friedel-Crafts type cyclization of derivatives of phenylalkylcarboxylic acid, phenoxyalkylcarboxylic acids, phenylthioalkylcarboxylic acids, benzyloxyalkylcarboxylic acids, and benzylthioalkylcarboxylic acids. Details may be found in a) T. Laird in.Comprehensive Organic Chemistry, D. Barton and W. D. Ollis, ed., Vol. 1, pp. 1165-1168, Pergamon Press, New York (1979); b) M. H. Palmer and N. M. Scollick, J. Chem. Soc.. C., (1968), 2833; c) C. E. Dalgliesch and Mann, J. Chem.

Soc., (1945), 893; d) C. D. Hurd and S. Hayao, J. Am.

Chem. Soc., (1954), 76, 4299 and 5056; and e) R. Lesser, Chem. Ber., (1923), 56, 1642.

Alternatively, the compounds of Formulas I-VIII may be prepared by the coupling procedure described in Scheme 2, which is used in cases where the standard Williamson ether synthesis proves problematic. This procedure uses a Lewis acidic metal oxide wherein the metal can remove the halide 1 -II WO 91/03464 pCT/US90/0495 3 12 ion by forming an insoluble precipitate. For example, Silver oxide can be used and the silver halide is the co-product. Alternative metal oxides that may be used are HgO, CaO, MgO. N,N-Dimethylformamide and ethereal solvents, such as diethyl ether, tetrahydrofuran, dioxane, or 1,2-dimethoxyethane are the preferred solvents. Other solvents likely to provide good yields include dipolar aprotic solvents like dimethyl sulfoxide, acetone and N,N'-dimethylpropyleneurea.

Scheme 2 Hal la-VIIIa I-VIII+ MHal

Z'

R' q n is 1 or 2 The oxabicycloalkanols (Ia-VIIIa) can be obtained generally by one or more of the following routes: directly by a) epoxidation-cyclization of unsaturated cyclic alcohols, with or without isolation of the epoxy alcohol intermediates; indirectly by b) Diels-Alder reactions of furans with dienophiles; or by c) Diels-Alder reactions of other dienes with dienophiles.

i_~LII/ WO 91/03464 PCT/US90/04953 13 Non-limiting illustrations of the preparation of representative compounds follow.

The compounds of Formula Ia are synthesized through the sequence shown in Scheme 3. Diels-Alder adducts are formed from readily available furans and from dienophiles including acrylate esters, acrolein, acryloyl chloride, and the like (see Murai et al., J. Chem. Soc., Chem. Comm. 221 (1981); and Kotsuki et al., Bull. Chem. Soc. Jpn., 57, 3339 (1984); and Laszlo et al., Tet. Let., 25, 4387 (1984) for Diels-Alder methodology). For example, the Diels-Alder adduct is prepared from furan and acryloyl chloride. Treatment of with alcohol and base at 0°C to ambient temperature produces the corresponding ester. This intermediate is treated with the appropriate Grignard reagent or reducing agent lithium aluminum hydride) as shown in Equation 3b. Optionally, treatment with an alkyl halide or alkyl sulfonate and a base sodium hydride) in an inert solvent, such as tetrahydrofuran or N,N-dimethylformamide at ambient temperature to 150 0 C produces Alcohol (4a) or ether (4b) is oxidized with a peroxide, such as hydrogen peroxide or m-chloroperbenzoic acid, in a suitable solvent, such as methylene chloride, to yield an epoxide.

This intermediate is treated with a reducing agent, such as lithium triethylborohydride or lithium aluminum hydride, to reductively open the epoxide to produce alcohol la, using the method of Krishnamurthy et al., J. Amer. Chem. Soc., 95., 8486 (1973), as shown in Equation 3c.

L~

pci-iUS9O/04953 WO 91/03464 BShernea 8) R -1 C\ I~i~~cacJ~ ocJ- I 0 1 R3 b) (2) 1 ROE. biaso 2) R 3

M

3) PR X, base a: R b: R5 H i 1. M WO 91/03464 PC/US90/04953

R

1

R

3 1) peroxide c) (4) 2) reducing agent Alternatively, compounds of Formula Ia may be synthesized through the sequence shown in Scheme 4, in which groups R 3 and R 4 may be varied independently. The Diels-Alder adducts prepared from furan and a vinyl carbonyl are treated with the appropriate Grignard reagent or reducing agent to produce alcohol Alcohol Ia can then be prepared via the routes previously described in Equations 3b and 3c or modifications thereof.

Scheme 4 RI 0 rl-"R 3 C3) (6) s I 1.

'1 PCrIUS9/04953 WO 91/03464

R'M

b) 1) R'X, base 2) peroxide c) (7) 3) reducing agent Compounds of Formula Ia, especially where R 3 and/or R 4 are allylic or vinylic can be prepared through the sequence shown in Scheme 5. The Diels-Alder adducts are treated with a peroxide as described in Equation 3c. This intermediate is treated with the appropriate Grignard reagent such as vinyl magnesium halide or allyl magnesium halide, to produce alcohol Alcohol la can be prepared via the routes previously described in Equations 3b and 3c, or modifications thereof.

WO 91/03464 WO 9103464PCT/ US9O/04953 a)RI 0 Y= OR, R3 1) peroxide b) (8) 2) R'4M Rl OH 0 0 O C) (9) 1 R5 X, bas e 2) reducing agent WO 91/03464 PTU9/45 PCT/US90/04953 18 Compounds of Formula Ia can also be synthesized through the sequence shown in Scheme 6. Diels-Alder adducts (10) are formed from furan and a dicarbonyl dienophile, such as maleic anhydride, using the methods of Hanessian et al., TeLett.L, 27, 5071 (1986) or Woodward et al., J.Ae, hm So. 70, 1161 (1948). Alcohol Ia can be prepared via the routes shown previously in Equations 4b and 4c or 5b and 5c or modifications thereof.

R R2 I 1 0 1

Y

0 R 2 0 Y= OR, R' 1) R'M 2) P5X, base.

b) (10) ior 3) peroxide 4) reducing agent 1) peroxide 2) R'M 3) R 5 X, base 4) reducing agent M- i i PCr/S90/04953 WO 91/03464 19 Compounds of Formula IIa can be prepared by the method described in Scheme 7 or modifications thereof. Cyclohexene (11) can be prepared via a Diels-Alder reaction using the methods of Alder et al., Chem. Ber., a, 1312 (1953). Treatment of the diester with a Grignard reagent or a reducing agent yields the diol derivative. Monoalkylation, using methods described earlier, yield a mixture of ethers Treatment of (12) with peroxide and acid, as taught in U.S. Patent Serial No. 4,542,244, yields alcohol IIa.

In situations where the endo form is desired, it can be obtained by oxidation of the 2-exo-IIa to the corresponding ketone, followed by reduction of the ketone with a reducing agent, such as sodium borohydride.

Scheme 7 R' R' a) R heat MOC 2) ROH acid

R

2

C

2

R

(11) PCr/US9/04953 WO 91/03464 1) RM b) (1 1) 2) IRX, base (12) 1) peroxide 2) acid c) (12) Compounds of Formula liIa can be prepared by the method described in Scheme 8 or modifications thereof. Cyclohexene (13) can be prepared via a Diels-Alder from readily available dienophiles, such as maleic anhydride, and a diene component, such as isoprene or butadiene, using the methods of Fieser et al., J. Amer. Chem. Soc., A6, 802 (1942). Treatment of (13) with a Grignard reagent or reducing agent yields the diol derivative. Monoalkylation using WO 91/03464 PCT/US90/04953 21 methods described earlier yields ether (14).

Treatment of (14) with peroxide and acid as taught in U.S. Patent Ser. No. 4,542,244 yields IIIa.

In situations where the endo form is desired, it can be obtained by oxidation of the 2-exo-IIIa to the corresponding ketone, followed by reduction of the ketone with a reducing agent, such as sodium borohydride.

Scheme 8 1) R4M 2) RX, base 3 R3

OH

Y= R, OR (13) (14)

A

WO 91/03464 PCT/US90/0495 3 22

OR

1) peroxide 3 2) acid b) (14) R p 3 0

R

4 IIIa Compounds of Formula IIIa can also be prepared by the method described in Scheme 9 or modifications thereof. Cyclohexene (15) can be prepared via a Diels-Alder from diene (16) and a readily available dienophile, such as methylacrylate. Treatment of with a Grignard reagent or reducing agent yields the diol derivative. Monoalkylation using methods described earlier yields ether Treatment of (17) with peroxide and acid, as described earlier, yields IIIa. In situations where the endo form is desired, it can be obtained by oxidation of the 2-exo-IIIa to the corresponding ketone, followed by reduction of the ketone with a reducing agent, such as sodium borohydride.

WO 91/03464 WO 9103464PCY/US9O/04953

I

02 R 16 15) 1) R 3 M 2) R 5 H (17) 1) peroxide (17) 2) acid I Ia WO 91/03464 PCT/US90/04953 24 Compounds of Formula IV can be prepared by the method described in Scheme 10. Hydroxylation of with a catalytic amount of osmium tetroxide and trimethylamine oxide as stoichiometric oxidant, adapted from a literature procedure [Ray et al., Tet. Lett,, 21, 449 (1980)], followed by Williamson ether coupling reaction with the appropriate alkylating agent WCH 2 X, as described previously, yields ether Oxidation of this alcohol using Jones reagent, as described by Heap et al. J. Chem. Soc. B, 164 (1966), yields ketone (19), which is alkylated with an appropriately substituted ketone using an amide base under conditions known in the art. Treatment of the resulting alcohol with an alkyl halide in the presence of a strong base, as described previously, yields Addition of an appropriate Grignard reagent or reducing agent (such as sodium borohydride) to the carbonyl group produces alcohol which is cyclized to yield the desired ether IVa by means of the alkoxymercuration/ demurcuration sequence [Bordwell et al., J. Amer.

Chem. Soc., 8E, 993 (1966)].

Scheme i i k SOH

OCHW

1) s 0 4 2) WCH 2 X base (1B) WO 91/03464 WO 91/3464riUS90/04953 Jones oxidation b) (18) 0 OCH 2

W

1 )MNR 2 2) R 3 R'(C=0) C) (l9) 3) R 5 X, base R4R30 OCH2W

RO

1 R 1

M

R4 R OH Pl 0C.

2

W

d) C20) (21)

A

WO 91/03464 PCT/US90/04953 26

R

3 R' OCH 2

W

1) g(COAc) 2 o e) (21) R1)(0c) 0 2) NaBH 4 IVa Compounds of Formula VIIa (where X H) and VIa can be prepared by the method described in Scheme 11 or modifications thereof. Diesters (22) and (23) can be prepared via a Diels-Alder reaction such as described by Ruden et al. Amer. Chem. Soc., 92, 6892 (1975)) using readily available diene components, such as isoprene or butadiene and a dialkylketomalonate. Treatment of the esters with a Grignard reagent or a reducing reagent, as described earlier, yields the diols (24) and Monoalkylation, using methods described earlier, followed by treatment with peroxide and acid, as described earlier, yield alcohols VIIa and VIa. In situations where the endo alcohol is desired, it can be obtained by oxidation of the exo-VIIa or exo-VIa to the corresponding ketone followed by reduction of the ketone with a reducing agent, such as sodium borohydride.

PCT/US90/04953 WO 91/03464 Schem 11 (a)t 0C2 (22) (23) and (23)-

R

3

OH

OH 3 HR3 (24) WO 91/03464 PCT/US90/04953 28 SRp'0 1) RX, base 0 3

R

Cc)(24) and (25) 2) peroxide R 1 R3 0- -3OR' 3) acid 3 R3

R

3 VIIa VIa Compounds of Formula Vila (where Y H) and of Formula Va can be prepared by the method described in Scheme 12 or modifications thereof. Diene (26) can be prepared from the corresponding diene ester by addition of a Grignard reagent or a reducing agent such as described by Corey et al. (Tet. Let., 3Q, 2537 (1975), followed by alkylation of the resulting alcohol. Diels-Alder reaction of (26) with glyoxylate using methods similar to Jurczak et al., J. Oro. Chem., AA, 3347 (1979) yields (27) and (28).

Treatment of (27) and (28) with a Grignard reagent or a reducing agent yields alcohols (29) and i 30 Treatment with peroxide and acid as described earlier yields alcohols Vila and Va. The endo alcohol can be obtained as described in Scheme 11.

PCT/US90/0495 3 WO 91/03464 Schaeme12 R C0 2

CH

3 3

R

3 R ,_R 1 .R 3 m 2) R 5 X, baeig (26) 99R R5 0

R'

0 (28) (26) (27)

R

3 m (27) (28) (29) WO 91/03464 WO 9103464PCU/US90/04953

H

5

H

0

R

1) peroxide H R3 R3RHO RHz C29) (30) OR~ 2) acid R 1

H

VIle Va Compounds of Formula VIII can be prepared by the method described in Scheme 13. Treatment of compound with a trialkylamine N-oxide and catalytic osmium tetroxide yields triol (31).

Alkylation of (31) with a QX (such as benzyl bromide), followed by treatment with R 5 X and a strong base, yields VIII.

R R 3 1 R H 3 0 OH 0504 H

HO

N

R

(31) WO 91/03464 PCT/US90/04953 31

R

1

R

3 3 1) QX, base Q R (31 0 2) RX, base R 5 0

R

2

VIII

EXAMPLE 1 StpA: 7-oxabicyclo[2.2.1]hept-5-ene-2-carboxylic acid, 1,4-dimethyl-, methyl ester, (endo and exo, racemic) Acryloyl chloride (32.8 ml, 0.40 mol) was cooled to 0°C in an ice-water bath under a nitrogen atmosphere. Aluminum chloride (1.60 g, 0.012 mol) was added in 0.5 g portions with stirring. The mixture was stirred at 5 0 C for 10 minutes, then was cooled to -65 0 C with an isopropanol-dry ice bath.

2,5-Dimethylfuran (38.4 g, 0.40 mol) was added dropwise at -65 0 C to -50 0 C over 1.5 hours. After addition was complete, the mixture was stirred for 1 hour. Methylene chloride (250 ml) was added to the mixture. The mixture was then cannulated to a stirring mixture of triethylamine (48.4 g, 0.48 mol) and methanol (60 ml) at -55 0 C to -40 0 C over

M

WO 91/03464 PCT/US90/04953 32 minutes. The mixture was stirred at -65 0 C for 1.25 hours, then was allowed to warm to ambient temperature. The mixture was poured into 500 ml water. The phases were separated and the aqueous layer was extracted two times with methylene chloride. The combined organic layers were washed with saturated sodium bicarbonate and brine solutions, dried over magnesium sulfate and concentrated in vacuo to leave 35.12 g of a yellow oil. Flash chromatography in 3:1 hexanes:ether on 800 g of silica gel yielded 17.34 g of the endo isomer and 11.82 g of the exo isomer.

NMR (CDC1 3 endo isomer: 6.22 1H), 6.03 1H), 3.61 3H), 2.88 (dd, 1H), 1.91 (ddd, 1H), 1.80 (ddd, 1H), 1.70 3H), 1.56 3H).

NMR (CDC1 3 exo isomer: 6.18 1H), 6.12 1H), 3.69 3H), 2.52 (dd, 1H), 2.0 (dd, 1H), 1.66 (dd, 1H), 1.62 3H), 1.50 3H).

Step B: 7-oxabicyclo[2.2.1]hept-5-ene-2-methanol, 1,4-dimethyl-, exo-, (racemic-) Lithium aluminum hydride (2.3 g, 60.0 mmol) was added under a nitrogen atmosphere to 100 ml dry tetrahydrofuran. The mixture was heated at reflux for 15 minutes, then cooled to 0°C. A solution of 7-oxabicyclo[2.2.l]hept-5-ene-2-carboxylic acid, 1,4-dimethyl-, methyl ester, (exo, racemic) (14.3 g, 78.6 mmol) in 100 ml tetrahydrofuran was added dropwise over 1.5 hours. The mixture was then allowed to warm to ambient temperature and stirred for another 4.0 hours. The mixture was cooled to 5 0

C

in an ice-water bath and 2.3 ml of water, 2.3 ml of sodium hydroxide, and 2.3 ml of water were added

I

t WO 91/03464 PCT/US90/04953 33 The solids were removed by suction filtration and washed with 40 ml of cold tetrahydrofuran. The filtrate was concentrated in vacuo to yield 9.5 g of a colorless oil.

NMR (CDC1 3 6.22 1H), 6.12 1H), 3.83 (m, 1H), 3.74 1H), 2.17 (dd, 1H), 1.86 1H), 1.68 (dd, 1H), 1.59 3H), 1.58 3H), 1.51 (dd, 1H).

IR (CH 2 C12): 3620, 3480, 1385, 1330, 1190, 1140, 1120, 1075, 1035, 975, 365 cm- 1 MS 155 137, 109, 107, 96, 95, 93.

Step C: 7-oxabicyclo[2.2.1]hept-2-ene, 1,4-dimethyl- 2-[(phenyl methoxy)methyl]-, (exo-, racemic) Sodium hydride (1.54 g, 3.85 mmol of a 60% oil dispersion) was washed with hexanes, decanted, and suspended in 20 ml of dimethylformamide. A solution of 4.75 g (30.8 mmol) of 7-oxabicyclo[2.2.1]hept-5ene-2-methanol, 1,4-dimethyl-, exo (racemic) in 40 ml dimethylformamide was added dropwise at 200 over minutes. The mixture was stirred 45 minutes at ambient temperature. Benzyl bromide (6.05 g, 35.4 mmol) was added dropwise in 30 ml dimethylformamide over 30 minutes. The mixture was stirred 20 hours at ambient temperature. The mixture was poured into 350 ml of water and extracted three times with methylene chloride. The combined extracts were washed with brine, dried over magnesium sulfate and concentrated in vacuo to yield 7.83 g of a yellow oil. Flash chromatography in 3:1 hexanes:ether on 400 g of silica gel yielded 3.77 g of a light yellow oil.

WO 91/03464 PCr/US9O/04953 34 NMR (CDCl 3 7.40-7.26 (in, 5H), 6.12 2H), 4.51 (dq, 2H), 3.60 (dd, 1H), 3.43 (dd, 1H), 1.97 (in, 1H), 1.70 (dd, 1H), 1.56 3H), 1.53 3H), 1.18 (dd, 1H).

IR (CH 2 Cl 2 1595, 1450, 1380, 1360, 1330, 1195, 1140, 1120, 1090, 1035, 1025, 860.

Anal. Calcd. for C 1 6

H

2 0 0 2 C, 78.69; H, 8.20.

Found: C, 78.80; H, 8.37.

Step D: 3,B-dioxatricycloll3.2.1.0 sup2, sup4]octane, 1,5-dimethyl-6-[ (phenylmethoxy)methyl]-, (exo, racernic-) To a stirring soluti.on of 3.60 g (15.0 mxnol) of 7-oxabicyclo[2.2.1]hept-2-ene, 1,4-dimethyl-2- [(phenylmethoxy)methyl]- (exo, raceinic) in 50 ml methylene chloride was added 3.56 g (16.5 innol) of 80% technical m-chloroperbenzoic acid at 0 0 C to 0 C. The mixture was stirred at 0 0 C to 10 0 C for 1 hour, then at amibient temperature. After 20 hours at ambient temperature, the mixture was cooled to 0 0

C

for 0.5 hour, filtered, and washed with cold methylene chloride. The filtrate was washed with sodium sulfite, sat. sodium bicarbonate, and brine and dried over magnesium sulfate and concentrated in vacuo to yield 4.05 g of a light yellow oil. Flash chromatography in 1:1 hexane:ether on 150 g of silica gel yielded 3.30 g of a colorless liquid.

NMR (CDCl 3 7.40-7.26 (mn, 5H), 4.48 (dq, 2H), 3.52 (dd, 1H), 3.26 (dd, 1H), 3.17 (dq, 2H), 2.10-1.98 (in, 1H), 1.85 (dd, 1H), 1.47 3H), 1.46 3H), 1.18 (dd, 1H).

WO 91/03464 PCT/US90/04953 IR (CH 2 C1 2 1451, 1400, 1380, 1362, 1308, 1218, 1192, 1120, 1090, 1025, 968, 915, 880, 870, 830, 810 cm 1 MS 261 183, 181, 169, 153, 139, 91.

Step E: 7-oxabicyclo[2.2.1]heptan-2-ol, 1,4-dimethyl- 6-[(phenylmethoxy)methyl]-, (exo, racemic), mixed with isomer To a stirring 1M solution of lithium triethylborohydride (25.4 ml) in tetrahydrofuran was added 3.30 g (12.7 mmol) of 3,8-dioxatricyclo[3.2.1.0 sup2, sup4]octane,1,5-dimethyl-6-[(phenylmethoxy)methyl]-, (exo, racemic) in 10 ml tetrahydrofuran at ambient temperature. After 3 hours at reflux, the mixture was cooled to 0°C and 10.2 g of a 10% sodium hydroxide solution was added dropwise. The mixture was warmed to ambient temperature and 8.64 g of hydrogen peroxide (76.2 mmol) was added dropwise.

The mixture was stirred at 40 0 C for 30 minutes, then was saturated with potassium carbonate crystals. The mixture was poured into 100 ml ether and the organic layer was separated. The aqueous layer was extracted with ether three times. The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated in vacuo to yield 4.45 g of a light yellow oil. Flash chromatography in 3:1 ether: hexanes on 150 g of silica gel yielded 2.04 g of colorless oil containing a 2:1 mixture of the 6-(phenylmethoxy) methyl isomer.

WO 91/03464 PCT/US90/04953 36 NMR (CDC1 3 7.32 5H), 4.48 2H), 3.77 (m, 1H), 3.54 1H), 3.20 1H), 2.20 1H), 1.90 1H), 1.75 1H), 1.66 1H), 1.45, 1.43, 1,41 and 1.38 6H, total), 1.30 1H), 1.12 1H).

IR(CH

2 C12): 3580, 3460 1452, 1380, 1363, 1203, 1090, 1070, 1027, 860 cm 1 Step F: 7-oxabicyclo[2.2.1]heptane, 1,4-dimethyl-2- (phenylmethoxy)-6-[(phenylmethoxy)methyl]-, 2:1 with the isomer, (exo, exo, racemic) Sodium hydride (0.39 g, 9.73 mmol) was washed with hexanes, decanted, and suspended in 10 ml of dimethylacetamide. To the suspension was added 2.04 g (7.79 mmol) of 7-oxabicyclo[2.2.1]heptan-2-ol, 1,4-dimethyl-6-[(phenylmethoxy)methyl]-(exo, racemic), mixed with regioisomer in 20 ml dimethylacetamide at ambient temperature over 20 minutes. The mixture was stirred at 65 0 C for 2 hours, then 1.66 g (9.73 mmol) of benzyl bromide in 10 ml dimethylacetamide was added I 25 at o0C. The mixture was warmed to ambient temperature. After 20 hours, the mixture was poured into 100 ml methylene chloride and 100 ml water. The phases were separated and the aqueous layer was extracted three times with methylene chloride. The combined organic layers were washed with brine, a dried, and concentrated in vacuo to yield 4.00 g of a light yellow oil. Flash chromatography in 2:1 hexanes:ether on 150 g of silica gel yielded 1.97 g of a light oil containing a 2:1 mixture of isomers.

WO 91/03464 PCT/US90/04953 37 NMR (CDC13): 7.32 10H), 4.58-4.36 4H), 3.54 2H), 3.20 1H), 2.02 1H), 1.88 1H), 1.8-1.6 1H), 1.47, 1.45 and 1.43 6H total), 1.2-1.05 2H).

IR (CH 2 C12): 1605, 1587, 1495, 1452, 1385, 1372, 1360, 1333, 1203, 1185, 1085, 1013, 860 cm- 1 MS 353 335, 261, 246, 245, 244, 215, 181, 155, 137, 119, 91.

EXAMPLE 2 Step A: 7-oxabicyclo[2.2.1]hept-5-ene-2-carboxylic acid, methyl ester (exo and endo, racemic) To a mixture of 93.0 g (1.37 mmol) of furan and 0.50 g (8.6 mmol) of propylene oxide was added 47.0 g (0.52 mmol) acryloyl chloride at ambient temperature. The mixture was stirred under a nitrogen atmosphere for three days in the dark. The mixture was then added to a solution of 45.0 ml (0.556 mol) pyridine and 45.0 ml of methanol in 100 ml methylene chloride at 0 C. The mixture was warmed to ambient temperature after the addition was complete. After 1 hour, water was added to the mixture and the layers were separated. The aqueous layer was extracted two times with methylene chloride. The combined organic layers were washed with water, brine and dried over magnesium sulfate and concentrated in vacuo to yield 66.3 g of dark oil containing a 2:1 ratio of exo:endo isomers. Flash chromatography of 4.0 g in 20:1 hexanes:ethyl acetate on 320 g of silica gel separated the endo and exo isomers.

WO 91/03464 PCT/US90/04953 38 NMR (CDC1 3 endo: 6.44 (dd, 1H), 6.21 (dd, 1H), 5.17 (dd, 1H), 5.03 (dd, 1H), 3.64 3H), 3.10 (ddd, 1H), 2.10 (ddd, 1H), 1.58 (dd, 1H).

NMR (CDC1 3 exo: 6.37 (dd, 2H), 5.10 (dd, 2H), 3.73 3H), 2.44 (dd, 1H), 2.18 (dt, 1H), 1.56 (dd, 1H).

Step B: 7-oxabicyclo[2.2.1]hept-5-ene, 2-(l-ethyl-lmethoxypropyl), exo-, (racemic-) To 20 ml (40 mmol) of 2M ethylmagnesium bromide in tetrahydrofuran at 0°C was added 3.0 g (19.5 mmol) of 7-oxabicyclo[2.2.1]hept-5-ene-2-carboxylic acid, methyl ester (exo, racemic) in 20 ml tetrahydrofuran. The mixture was warmed to reflux. After eight hours, the mixture was cooled to 00 and 20 ml water was added. The mixture was acidified to pH3 with 10% hydrochloric acid, then extracted two times with ether. The combined organic layers were combined, washed with brine, dried over magnesium sulfate and concentrated in vacuo to yield 2.3 g of light yellow oil. This intermediate was dissolved in ml tetrahydrofuran and added to 0.65 g (45.1 mmol) of 60% sodium hydride in oil at 0°C. The solution was warmed to ambient temperature and stirred minutes. Iodomethane (1.3 g, 40.0 mmol) was added and the mixture was refluxed. After 20 hours, the mixture was cooled and poured into 100 ml water. The layers were separated, and the aqueous layer was extracted twice with ether. The organic layers were combined and washed with brine, dried over magnesium sulfate and concentrated in vacuo to yield 1.69 g of yellow oil. Flash chromatography in 6:1 hexanes: ethylacetate yielded 1.27 g of a pale yellow oil.

WO 91/03464 PCr/US90/04953 39 NRM (CDC1 3 6.40 (dd, 1H), 6.28 (dd, 4.95 (dd, 2H), 3.19 3H), 1.77 (dd, 1H), 1.60 4H), 1.47 (dd, 1H), 1.33 (dd, 1H), 0.9 (dt, 6H).

Step C: 7-oxabicyclo[2.2.l]heptane, 2-(l-ethyl-lmethoxypropyl)-6-(phenylmethoxy)-, [exo-(2alpha, 6-alpha)] Following procedures similar to those described in Steps D, E and F in Example 1, reaction of 1.27 g (6.48 mmol) of 7-oxabicyclo[2.2.l]heptane, 2-(l-ethyl- 1-methoxy-propyl)(exo, racemic) with 1.9 g (6.6 mmol) of m-chloroperbenzoic acid gave 0.75 g of a yellow oil. Consequent reaction with 10 ml (10 mmol) of lithium triethylborohydride yielded 0.9 g of a pale yellow oil. Treatment with benzyl bromide, followed by flash chromatography yielded 0.20 g of a colorless oil.

NMR (CDC1 3 7.33 5H),'4.55 4H), 3.64 (dd, 1H), 3.16 3H),.1.85-1.31 9H), 0.89 and 0.88 t, 6H).

EXAMPLE 3 Step A: cis-7-oxabicyclo[2.2.1]hept-5-ene-2,3-dimethanol, (exo)- Furan (85.0 ml, 1.17 mol) was added to maleic anhydride (81.0 g, 0.827 mol) in 100 ml ether at ambient temperature. After 20 hours, the precipitated solid was filtered off and washed with ether to give 104 g of white crystalline solid.

Reduction of 34.0 g of the Diels-Alder adduct with lithium aluminum hydride, as described previously, yielded 28.0 g oil. The NMR spectrum was i WO 9 1/03464 PCI! US9O/04953 the same as that reported in the literature [Das et al., J. Med. Chem., U1, 930 (1988)].

NMR (CDCl 3 6.40 2H), 4.70 2H), 4.00 (br, 2H), 3.80 (in, 4H), 1.95 (mn, 2H).

Step B: 7-ozabicycloi2.2.1]heptale, 2,3-bis(ethoxy- [2 exo.-(2 alpha, 3 alpha, 5 alpha)] Alkylation of 14.0 g (0.0897 mol) cis-7-oxabicyclo[2.2.l]-hept-5-ene-2,3-dimethalol using ethyl iodide and sodium hydride was accomplished as described previously to give 15.0 g of the bisether. Epoxidation using m-chloroperbenzoic acid, followed by reductive opening with lithium triethylborohydride, as described previously, yielded 4.00 g of oil.

NMR (CDCl 3 4.49 1H), 4.23 1H), 3.96 (brt, 1H), 3.5-3.2 (in, 8H), 2.12 (brid, 1H), 1.95 (mn, 3H), 1.55 (ddt, 1H), 1.17 6H).

MS 231 259, 185.

Step C: 7-oxabicycloll2.2.1]heptane, 2,3-bis(ethoxy- [2 exo-(2 alpha, 3 alpha, 5 alpha))- Coupling of 7-oxabicyclo[2.2.1]heptane, 2,3-bis(ethoxyrnethoxy)-5-(phenylmethoxy)-, [2 exo-(2 alpha, 3 alpha, 5 alpha)) (0.5 g, 2.17 nunol) with benzylbromide in the presence of sodium hydride, as described earlier, yielded 0.40 g of colorless oil.

NMR (CDCl 3 7.33 (mn, 5H), 4.52 (mn, 4H), 3.75 (did, 3.5-3.2 (mn, 8H), 2.0-1.7 (mn, 4H), 1.21 and 1.20 t, 6H).

WO 91/03464 PCT/US90/04953 41 EXAMPLE 4 Step A: (+)-4-methyl-4-cyclohexene-1,2-dicarboxylic anhydride To 50 ml (0.50 mol) of isoprene cooled to 0 C was added 25 g (0.26 mol) of maleic anhydride portionwise. The reaction mixture was warmed to ambient temperature and stirred for 4 hours. The excess isoprene was removed under vacuum to give 40.5 g of a white solid, m.p. 63-65 0

C.

NMR (CDC1 3 5.70 (brs, 1H), 3.45 2H), 2.50 (m, 4H), 1.81 3H).

IR (KBr): 2900, 1840, 1770, 1445, 1235, 965, 920, 800.

Step B: (±)-cis-4-methyl-4-cyclohexene-l,2-dimethanol To 300 ml of tetrahydrofuran at 0°C was added 16.0 g (0.42 mol) lithium aluminum hydride portionwise keeping the reaction temperature between 0°C and 5 0 C. A solution of 33.0 g (0.20 mol) of 4-methyl-4-cyclohexene-l,2-dicarboxylic anhydride in 100 ml of tetrahydrofuran was added dropwise over 2 hours keeping the temperature between 0°C and 10 0

C.

The reaction mixture was warmed to ambient temperature and stirred for 2 hours. The reaction was cooled to 0°C and 35 ml of ethyl acetate was added dropwise, followed by dropwise addition of ml isopropanol and 35 ml water. The reaction mixture was filtered through celite using acetone, dried with MgSO 4 and concentrated to 33.0 g of oil. Flash chromatography in 3:1 hexanes:ethyl acetate, followed by 1:1 hexanes:ethyl acetate and finally ethyl acetate alone yielded 18.2 g of oil.

WO 91/03464 PCI',US9O/04953 42 NMR (CDCl 3 5.35 (brs, 1H, 3.68 (mn, 2H), 3.60 (mn, 2H), 3.10 (brs, 2H), 2.05 (brs, 6H), 1.64 3H).

IR (neat): 3500-3100, 1730W, 1440, 1010.

MS 157 139, 121.

Step 2-endo,4-exo-(±)-4-hydroxy-5-methyl-6oxabicyclot3 octane-2-methanol To a suspensionn of 39.0 g (0.124 mol) of m-chloro-perbenzoic acid in 400 ml methylene chloride at 0 0 C was added 19.4 g (0.124 mol) of (±)-cis-4-methyl-l,4-cycJlohexene-1,2-dimethanol in 100 ml methylene chloride over 15 minutes keeping the temperature less than 80C. The reaction mixture was warmed to ambient temperature and stirred for 24 hours. The reaction was cooled to 0 0 C and 30 ml of a saturated aqueous solution of Na 2

S

2

O

3 was added dropwise keeping the temperature less than 80C. The reaction mixture was dried with MgSQ 4 filtered and concentrated. Flash chromatography in 3:1 hexanes:ethyl acetate, 1:1 hexanes:ethyl acetate, then ethyl acetate alone yielded 6.1 g oily solid.

NMR (CDCl 3 3.80 (brd, 2H), 3.60 (brd, 1H), 3.45 2H), 2.70 (brs, 2H), 2.42 (brs, 1H), 2.0 1.33 3H).

IR (neat): 3400-3200, 2900, 1450, 1400, 1380, 1060, 1000, 820.

MS 173 213, 155.

StpD (±)-2-endo,4-exo-4-hydroxy-2-(methoxymethyl)- 5-methyl-6-oxabicyclo[3 ijoctane To 1.45 g (0.036 mol) of hexane-washed sodium hydride was added 100 ml tetrahydrofuran. THe IL- l~~i PC/US90/04953 WO 91/03464 43 reaction was cooled to 0°C and 6.1 g (0.035 mol) of (±)-2-endo,4-exo-4-hydroxy-5-methyl-6-oxabicyclo- [3.2.l]octan-2-methanol in 70 ml tetrahydrofuran was added dropwise over 45 minutes keeping the temperature between o0C and 5 0 C. The reaction mixture was warmed to ambient temperature and 2.5 ml (0.04 mol) of methyliodide was added. An additional 1.0 g (0.025 mol) of 60% sodium hydride and 2.0 ml (0.03 mol) of methyliodide was added to the reaction. After 48 hours, the reaction was cooled to 0°C and 25 ml of water was added dropwise. The reaction mixture was extracted with ether, and then with methylene chloride. The combined organic layers were dried with MgSO 4 filtered and concentrated to 7.26 g oil. Flash chromatography in 3:1 hexanes:ethyl acetate yielded 2.0 g of oil.

NMR (CDC1 3 3.80 2H), 3.60 (brs, 1H), 3.32 (s, 3H), 3.20 2H), 2.40 (brs, 1H), 2.18 1I 2.10 1H), 1.50 3H), 1.33 3H).

MS 187 204, 169, 155.

Step E: (±)-2-endo-2-(methoxymethyl)-5-methyl-6oxabicyclo[3.2.1]octan-4-one To 21.0 ml (0.042 mol) of 2M oxalylchloride in methylene chloride at -78 0 C was added 4.2 ml (0.06 mol) dimethyl sulfoxide. The reaction mixture was stirred for 15 minutes, then 3.9 g (0.021 mol) of (±)-2-endo,4-exo-4-hydroxy-2-(methoxymethyl)-5methyl-6-oxabicyclo[3.2.1]octane in 10 ml methylene chloride was added dropwise and the reaction mixture was stirred for 45 minutes. Triethylamine (16.5 ml, 0.12 mol) was added dropwise and the reaction mixture was warmed to ambient temperature. Water was added ml) and the reaction mixture was extracted with PCr/US90/04953 WO 91/03464 PTU9/45 44 mnethylene chloride, dried over.,MgSO 4 1 filtered and concentrated. Flash chromatography in 3:1 hexanes:ethyl acetate yielded 0.96 g of oil.

NMR (CDCl 3 4.10 (in, 2H), 3.34 (mn, 5H), 2.69 (brs, 1H), 2.5-2.0 (mn, 4H), 1.80 1H), 1.34 3H).

IR (neat): 2920, 2870, 1720s, 1445, 1105, 975.

MS 185 202, 199, 216.

Step FJ: (+)-2-endo,4-endo-4-hydroxy-2-(methoxyiethyl)-5-methyl-6-oxabicyclo[3.2 octane To 2.2 g (0.012 mol) of (±)-2-endo,4-endo-4hydroxy-2- (methoxymethyl) -5-methyl-6-oxabicyclot3.2.ljoctan-4-one in tetrahydrofuran at -78 0 C was added a slight excess of 1 M lithium triethylborohydride in tetrahydrofuran. After minutes 10 ml of water was added and the reaction mixture was warmed to ambient temperature. The reaction mixture was extracted with methylene chloride, dried over MgSO 4 filtered and concentrated. Flash chromatography in 1:1 hexanes:ethyl acetate yielded 1.2 g of oil.

NMR (CDCl 3 3.83 (brd, 2H), 3.40 (in, 1H), 3.32 (s, 3H), 3.20 2H), 2.40 (brs, 1H), 2.05-1.9 1.52 1H)f 1.34 3H).

Step G: 2-endo,4-endo-2-(niethoxyrnethyl)-5-methyl- 4-(phenylinethoxy)-6-oxabicyclo[3 1]octane TVo 0.12 g (3 mmcl) of hexane-washed sodium hydride in tetrahydrofuran was added 0.35 g (1.8 mmcl) of (±+)-2-endo,4-endo-2-(niethoxymethyl)-5methyl-6-oxabicyclo[3.2.l]octan-4-ol in WO 9 1/03464 PCT/ US90/04953 tetrahydrofuran. The reaction mixture was stirred at 0 C for 24 hours. Water was added and the reaction mixture was extracted with ether, dried over MgSO 4 filtered and concentrated. Flash chromatography in 20:1 hexanes:ethyl acetate yielded an oil.

NMR (CDCl 3 7.32 (in, 5H), 4.62 1H), 4.42 (d, 1H), 3.82 (d+dd, 2H), 3.32 3H), 3.2-2.2 (in, 3H), 2.39 (brs, 1H), 2.03 (dt, 1H), 1.8 (mn, 2H), 1.49 (d, 1H), 1.37 3H), 1.25 (mn, 1H).

IR (neat): 2900, 1450, 1360, 1080, 1000, 960, 850, 730, 690.

MS 277 294.

EXMPL

Step.A (±)-diethyl 3,6-dihydro-4-inethyl-2Hpyran-2 ,2-dicarboxylate To 50 g (0.70 mol) isoprene was added5 25 g (0.14 inol) diethylketoinalonate and 0.78 g (2.4 inmol) zinc iodide. The reaction mixture was stirred at room temperature for 48 hours. The excess isoprene was removed under vacuum. Flash chromatography in 20:1 hexanes:ethyl acetate yielded 1.2 g of oil.

NMR (CDCl 3 5.40 (brs, 1HI), 4.34 (mn, 2H), 4.28 (q, 4H), 2.58 (brs, 2H), 1.75 (brs, 3H), 1.29 6H).

MS 243 283, 225, 169.

StpB (±).-3,6-dihydro-4-methyl-2H-pyrani-2,2diniethano 1 To 200 ml tetrahydrofuran at 0 0 C was added g (0.105 mol) lithium aluminum hydride portionwise.

A solution of 12.5 g (0.052 mol) of (±)-diethyl 3,6dihydro-4-methyl-2H-pyran-2,2-dicarboxylate in 60 ml WO 91/03464 PCT/US90/04953 46 tetrahydrofuran was added dropwise over '30 minutes.

The reaction mixture was warmed to ambient temperature. After 2 hours, the reaction was cooled to 0°C and successively treated with 30 ml ethyl acetate, 30 ml isopropanol, 30 ml water dropwise keeping the temperature under 10 0 C. The reaction mixture was filtered through celite with acetone, dried over MgSO 4 filtered, and concentrated to an oil. Flash chromatography in 1:1 hexanes:ethyl acetate followed by ethyl acetate alone yielded 5.5 g oil.

NMR (CDC1 3 5.42 (brs, 1H), 4.18 (brs, 2H), 3.71 2H), 3.65 2H), 1.84 (brs, 2H), 1.7 3H).

IR (neat): 3300 broad, 2900, 1435, 1380, 1110, 1020.

MS 159 173, 141, 127.

Step C: (±)-exo-4-hydroxy-5-methyl-2,6-dioxabicyclo- [3.2.1]octan-l-methanol To a suspension of 11.0 g (0.035 mol) m-chloroperbenzoic acid in 100 ml methylene chloride at o0C, was added 5.5 g (0.035 mol) of (±)-3,6-dihydro-4-methyl-2H-pyran-2,2-dimethanol in 100 ml methylene chloride. The reaction mixture was warmed to ambient temperature. After 20 hours, the reaction mixture was cooled to 0°C and 30 ml of a saturated aqueous solution of Na 2

S

2 03 was added dropwise. The reaction mixture was dried over MgSO 4 filtered, and concentrated. Flash chromatography in 1:1 hexanes:ethyl acetate followed by ethyl acetate yielded 1.7 g of oil.

NMR (CDC1 3 4.13 (dd, 1H), 4.08 1H), 3.86 (m, 2H), 3.78 1H), 3.62 1H), 3.45 1H), 2.22 1H), 1.40 1H), 1.40 3H).

MS 175 192, 157.

PCr/US90/04953 WO 91/03464PT/L9045 47 Stp D: (+)-4-exo-1-(ethoxymethyl)-4-hydroxy-5methyl-2,6-dioxabicylco[3.2.1]octane To 0.3 g (0.007 mol) of 60% sodium hydride in tetrahydrofuran was added 1.2 g (0.007 rnol) of -exo-4-hydroxy-5-methyl-2, 6-dioxabicyclo [3 .2 octan-1-methanol in tetrahydrofuran followee by 0.6 ml (0.013 mol) ethyliodide. After 24 hours at ambient temperature, water was added and the reaction mixture was extracted with methylene chloride, dried over MgSO 4 filtered, and concentrated. Flash chromatography yielded an oil.

NMR (CDCl 3 4.18 (dd, 1H), 4.09 (dd, 1H), 3.95 (d, 1H), 3.81 (in, 2H), 3.65-3.4 (mn, 4H), 2.20 1H), 1.50 1H), 1.40 3H), 1.19 3H).

MS 203 220, 185.

dioxabicyclo octan.-4-one To 4 ml (0.008 inol) of 2 M oxalylchloride in methylene chloride at -78 0 C was added successively 0.7 ml (0.01 mol) diiethylsulfoxide, 1.2 g (0.0058 inol) of (±)-4-exo-.l-(ethoxymrethyl)-4-hydroxy-5iethyl-2,6-dioxabicyclo[3.2.l]octane and 2.79 ml (0.02 mol) triethylamine. The reaction mixture was warmed to ambient temperature, and water was added.

The reaction mixture was ex~tracted with methyl chloride, dried over MgSO 4 1 filtered and concentrated. Flash chromatogarphy yielded 1.0 g oil.

NMR (CDCl 3 4.50 1H), 4.21 (in, 3H), 3.57 (mn, 4H), 2.20 1H), 2.10 1H), 1.40 3H), 1.21 3H) WO 91/03464PC/U9/43 PCT/US90/04953 48 step E: (±L)-4-endo-l-(ethoxymethyl)-5-methyl-5methyl-4-(phenylmethoxy)-2, 6-dioxabicyclo[3.2.iloctane To a slight excess of lithium triethylborohydride in tetrahydrofuran at -78 0 C was added 1.0 g (0.0049 mol) of (±)-1-(ethoxyrnethyl)-5-methyl-2,6dioxabicyclo[3.2.ljoctani-4-one. After 5 minutes water was added and the reaction mixture was warmed to ambient temperature. The reaction mixture was extracted with methylene chloride, dried over MgSO 4 filtered, and concentrated to give 0.5 g of oil. To 0.2 g (0.97 mn'ol) of this oil was added 0.1 g mmol) of 60% sodium hydride and 0.25 g (1.5 mmol) of benzylbromide in tetrahydrofuran. After 24 hours at 0 C, water was added and the reaction mixture was extracted with ether, dried over MgSO 4 filtered, and concentrated. Flash chromatography in 20:1 hexanes:ethyl acetate yielded 0.38 g oil.

NMR (CDCl 3 7.32 (brs, 5H), 4.55 2H), 4.00 (d+d dd, 3M), 3.68 1H), 3.40 (in, 4H), 3.38 (dd, 1H), 1.79 (dd, 2H), 1.40 3M), 1.18 3M).

EXAMLE

Step: (±)-exo,exo,exo-(z-diethyl-5,6-bishydroxy- 7-oxabicyclo[2.2.ljheptane-2-methanoI To 26.5 g (0.146 mol) of 2-(1-ethyl-l-hydroxypropyl)-7-oxabicyclo[2.2.1]hept-5-ene in 100 ml acetone at 0 0 C was added 17.6 g (0.15 mol) N-methyl morpholine N-oxide and 10 ml of 4% osmium tetroxide in water. The reaction mixture was warmed to ambient temperature and stirred for 4 days. A saturated W091/3464PCF/US9O/04953 49 aqueous solution of Na 2

S

2

O

3 was added. The reaction mixture was extracted with ethyl acetate twice and the combined extracts were washed with water and brine, and dried over MgSO 4 filtered, and concentrated. Flash chromatography yielded 12.0 g thick oil.

NMR (CDCl 3 4.44 1H), 4.38 1H), 3.85 (mn), 1.8-1.7 0.84 6H).

MS 217 234.

Step B: (±)-exo,exo,exo-a,cx-diethyl-6-[ (2-f luorophenyl)methoxy] -5-hydroxy-7-oxabicyc lo- [2.2.ljheptane-2-methanol To 1.2 g (0.03 mol) of 60% sodium hydride in tetrahydrofuran at 0OC was added 6.0 g (0.028 mol) of 6-bishydroxy-7-oxabicyclot2.2.llheptan-2-methanol in tetrahydrofuran. The reaction mixture was warmed to ambient temperature and 3.4 ml (0.03 mol) of 2-fluorobenzylbronide was added. After 24 hours, water was added and the reaction mixture was extracted with ether, dried over MgSO 4 filtered and concentrated. Flash chromatography yielded 1.3 g oil.

NMR (CDCl 3 7.5-7.0 (in, 4H), 4.69 2H), 4.50 1H), 4.40 1H), 3.92 (dd, 1H), 3.61 1H), 3.20 1H), 1.2-2.0 0.80 (mn).

MS 324 342.

propyl luorophenyl )methoxy) 2-methoxy-7-oxabicyclo[2 llheptane To 1.3 g (4.0 minol) of (±)-exo,exo,eo-a,cLdiethyl-6- luoropheniyl)rnethoxy] -5-hydroxy-7- WO 91/03464 PCT/US90/04953 oxabicyclo[2.2.1]hexane-2-methanol in dimethylformamide was added excess sodium hydride and methyliodide. The reaction mixture was stirred at 0 C for 12 hours. Following aqueous workup, flash chromatography yielded 0.25 g oil.

NMR (CDC1 3 7.6-7.0 4H), 4.71 (brs, 2H), 4.45 2H), 3.66 1H), 3.52 1H), 3.52 1H), 3.42 3H), 3.15 3H), 1.8-1.2 0.80 6H).

MS 353 370, 338.

Tables 1-5 present examples of species of the present invention. It is understood that these enumerated examples are merely representative of the range of species contemplated by the present invention. The notation "Ph" connotes a phenyl group. Compounds in Tables 10-15 have the group syn with respect to the oxygen-containing bridge. The endo/exo notation refers to the configuration of the C(R 3

)(R

4

)OR

5 group. The indicated ratios (Table10) refer to cases where the compounds of invention are formed in an inseparable mixture with compounds of Formula (18).

The ratio is given in the form 0 I I OX0 R')OR5 Ondo (R)(R4)oR'

L

WO 91/03464 PTU9/45 PCT/US90/04953 R 3 R4) ORe 1 (18) The species of Tables 1-8 correspond to the Formulas I-VIII of the compounds of the present invention. Thus, the first compound identified in Table 1 (with RlmH; R 2

R

3

-CH

3

CH

2

R

4

-CH

3

C{

2

R

5

-CH-

3 and W-2-FPh) is a species of the compound identified as Formula 1.

WO 91/03464 PUCf US9O/04953 52

R'

X

p 2 X and Y are C(R 3

)(TR

4 )0R 5 (unless specified)

R

1

-R

2 -H (unless specified)

E

3 C E4CH R5 3 QH(-Fh

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (3-FPh) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (4-FPh) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (4,-FPh) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2,4-F 2 ph) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2,4-.F 2 Ph) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2,6-F 2 Ph) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2,-lPh) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (3-ClPh) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (4-ClPh) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (24-CIPh) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2,6-Cl 2 Ph) H

CH

3

CH

2 CH1 3

CH

2

CH

3

CH

2 (2,-CPh) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (3-.DrPh) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (4-BrPh) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (Z4-rPh) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2,6-Br 2 Ph) H

CH

3 CH2 CH 3

CH

2

CH

3

CH

2 (2,-0CH 3 Ph) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (3-(0CH 3 )Ph) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (4-(OCH 3 )Ph) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (4-(CH 3 )Ph) H WO 91/03464 PCT/US9O/04953 53

CH-

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2,3-(CH 3 2 Ph) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2,4-(CH 3 2 Ph) H

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2 (2,5-(CH 3 2 Ph) H,

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2 (2,6-(CH 3 2 Ph) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2-(CH 3

CH

2 )Ph) H

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2 (4-(CH 3

CH

2 )Ph) H

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2 (2-(OH)Ph) H

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2 (2-(CN)Ph) H

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2 (4-(CN)Ph) H

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2 (2-(CF 3 )Ph) H

CR

3

CH

2

CH

3

CH

2

CR

3

CH

2 (4-(CF 3 )Ph) H

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2 (2-(OCF 3 )Ph) H

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2 (4-(Q)CF 3 )Ph) H

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2 (2-(SCH 3 )Ph) H

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2 (4-(SCH 3 )Ph) H

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2 (2-(CH 2 CH=CH)Ph) H

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2 (4-(CH 2 CH=CH)Ph) H

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2

H

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2 (4-(HC=EC)Ph) H

CH

3

CH

2

C

3

CH

2

C

3

C

2 (2-pyridyl)H

CH

3

CH

2 CH CH CR 3

CH

2 (3-pyridyl) H

CH

3

CH

2 CH CH CR 3 CH(-f ~ranyl)2( H

CH

3

CR

2

CH

3

CH

2

CR

3

CH

2 (2-(3-CI)pyridyl) H CHCH C 3

C

2

R

3

C

2 (3-(2-C1)pyridyl)

H

CH

3

H

2 CHCH C 3

C

2 (2-(3-Br)thiophenyl)

H

CH

3

CH

2

CH

3

CH

2

CR

3 CH(3(-rtihey) H CH CH 2 CH CH 2

CR

3

CH

2 (-5C 3 frnl CHCH C 3

C

2

R

3

C

2 (3-2-iophnyl) y H

CH

3

CH

2 CH CH, CH 3

CH

2 (-hohnl

CH

3

CH

2

CH

3 CH2. CR 3

CH

2 (2-thiaoheyl) H

CH

3

CH

2

CH

3 Ci:. CR 3

CH

2 (2-imidazolyl) H

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2 (2-pyrazoyl) H

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2 (2-ozazolyl) H WO 91/03464PC/U9/95 PCY/US90/04953 54 R3 E4 R5 Q

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2-isozazolyl) H

CH

3

CH

2

CH

3

CH

2

CM

3

CH

2 (2-pyrrolyl) H

CM

3

CH

2

CH

3

CH

2

CM

3

CH

2 (2-pyrirnidinyl) H

CH

3

CH

2

CH

3

CH

2 CH 3

CH

2 (2-pyrazinyl) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2-tetrahydropyranyl) H

CH

3

CH

2

CH

3

CH

2

CM

3

CH

2 (2-tetrahydrofuranyl) H

CH

3

CH

2 CH 3

CH

2

CM

3 Q-1 H

CH

3

CH

2

CH

3

CH

2

CM

3 Q-2 H

CM

3

CM

2

CH

3

CH

2

CM

3 Q-3 H

CH

3

CH

2

CH

3

CH

2

CM

3 Q-4 H

CH

3

CH

2

CH

3

CH

2

CM

3 Q-5 H

CH

3

CH

2

CH

3

CH

2

CM

3 Q-6 H

CH

3

CH

2

CH

3

CH

2

CH

3 Q-7 H

CH

3

CH

2

CH

3

CH

2

CM

3 Q-B H

CH

3

CH

2

CH

3

CH

2

CM

3 Q-9 H

CH

3

CH

2 CH 3

CH

2

CM

3 Q-10 H

CH

3

CH

2

CH

3

CH

2

CHM

3 Q-11 H CH CH 2

CM

3

CH

2

CM

3 Q-12 H

CH

3

CH

2

CH

3

CH

2

CM

3 0-13 H

CH

3

CH

2 CH 3

CH

2

CM

3 Q-14 H

CM

3

CH

2

CH

3

CH

2

CM

3 0-15 H

CH

3 CH 2

CH

3

CH

2

CM

3

CH

2 (Ph) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

2 (2-FPh) H

CM

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

2 (2-CIPh) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

2 (2-BrPh) H

CH

3

CH

2

CH

3

CH

2 CH 3

CH

2

CH

2 (2-(CH 3 )Ph) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

2 (2-(OCH 3 )Ph) H

CH

3

CH

2

CH

3

CM

2

CM

3

CH

2

CH

2 (2-(CN)Ph) H

CH

3

CH

2 CH 3

CH

2

CH

3

CH

2

CH

2 (2-(CF 3 )Ph) H

CH

3

CH

2 CH 3

CM

2

CH

3

CH

2

CH

2 (2-(OCF 3 )Ph) H CH 3

CH

2 CH 3

CH

2 CH 3

CH

2 CH 2 (2-(SCH 3 )Ph) H

CH

3

CM

2

CH

3

CH

2 CH 3

CH

2 CH 2

(SCH

3 )Ph) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

2 2 Ph) H PCT/US90/04953 WO 91/03464

CH

3

CM

2

C

3

CH

2

CH

3

CM

2

CH

3

CH

2

CHM

3

CH

2

CH

3

CM

2

CH

3

CM

2

CH

3

CM

2

CM

3

CM

2

C

3

CH

2

CH

3

CH

2

CH

3

CH

2

CM

3

CM

2

CH

3

CH

2

CM

3 C 2

CH

3

CH

2

CM

3

CH

2

CH

3

CM

2

CM

3

CM

2

CM

3

CM

2

CH

3

CM

2

CM

3

CM

2

CH

3

CH

2 CH3 CHM 2 CH 3

CH

2

CHM

3

CM

2 CH 3

CM

2

CHM

3

CM

2 CH 3

CM

2

CHM

3 CH 2 CH3CM 2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CH

3 CM2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3 C C 2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2 C 3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CH

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2 CM CM 2

CM

3

CM

2

CM

3

CM

2

CM

3

CH

2

CM

3 CH 2

CH

3

CM

2

CM

3

CM

2

CM

3

CM

2

CHM

3

CM

2

CM

3

CM

2 CM 3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CH

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3 CM2 CM 2

CM

3 CM2 CM 2

CM

3 CM2 CM 2 CM 3

CM

2

CM

2 CM 3

CM

2

CM

2

CM

3

CM

2

CM

2

CM

3 CM2 CM 2

CM

3 CM2 CM 2 CM 3

CH

2

CM

2

CHM

3

CM

2

CM

2

CM

3

CM

2 CM 2 CM 3

CM

2

CM

2

CM

3

CM

2

CM

2 CM 3

CM

2

CM

2

CH

3

CM

2

CH

2 CM 3CM 2

CM

2

CM

3

CM

2

CM

2

CM

3

CM

2

CM

2

CM

3

CM

2

CM

2

CM

2 (2,6-(C1) 2 Ph)

CM

2 (2-pyridyl)

CM

2 (2-furaiyl)

CM

2 (2-tetraiiydrofuran)

CM

2 (2-tetrahydropyran)

CM

2 (2-thiophenyl)

CM

2 (2-isoxazolyl)

CM

2 (2-pyrazinyl)

CM

2 (Ph) 0.-i 0-3 Q-6 Q-7

CM

2 2-FPh)

CM

2 (2-ClPh)

CM

2 2-BrPh)

CH

2 (2-(CM 3 )Ph)

CM

2 (2-(OCM 3 )Ph)

CH

2 (2-(CN)Ph)

CH

2 (2-(CF 3 )Ph)

CH

2 (2-(OCF 3 )Ph)

CM

2 (2-(SCH 3 )Ph)

CM

2 2 Ph)

CH

2 (2,6-(C1) 2 Ph)

CM

2 (2-pyridyl)

CM

2 (2-furanyl)

CM

2 (2-tetrahydrofuran)

CH

2 2-tetrahydropyran)

CM

2 (2-thiophenyl)

CM

2 (2-isozazolyl)

CM

2 (2-pyrazinyl)

CH

2 (Ph) p WO 91/03464 PiIU9/45 PCr/US90/04953

CH

3

CH

2

CH

3

CH

2

CR

3

CR

2

CR

3

CH

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

C

3

CH

2

CH

3

CH

2

CR

3

CR

2

CH

3

CH

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2 C1 3

CR

2

CR

3

CR

2

CR

3

CR

2

CH

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CH

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CH

3

CH

2

CR

3

CR

2

CR

2

CR

3

CR

2

CR

2

CR

3

CR

2

CR

2

CR

3

CR

2

CR

2

CR

3

CR

2

CR

2

CR

2

CH=CH

2

CR

2

CR=CH

2

CR

2

CH=CH

2

CR

2

CR=CH

2

CH

2

CH=CH

2

CR

2

CH=CH

2

CR

2

CH=CH

2

CH

2

CH=CH

2

CR

2

CH=CH

2

CH

2

CH=CH

2

CR

2

CR=CR

2

CR

2

CH=CH

2

CR

2

CH=CH

2

CR

2

CH=CH

2

CH

2 CR CH 2

CH

2

CH=CH

2

CR

2

CH=CH

2

CR

2

CH=CH

2

CR

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CR

2

CH=CR

2

CR

2

CH=CH

2

CH

2

C=SCH

CH

2

C=-CH

CR

2

C=EC

CH

2

C=-CH

Q- 1 Q- 3 Q-6 0-7 Q-

CR

2 2-FPh)

CR

2 (2-CIPh)

CR

2 (2-BrPh)

CR

2 (2-(CR 3 )Ph)

CR

2 (2-(OCR 3 )Ph)

CR

2 (2-(CN)Ph)

CR

2 (2-(CF 3 )Ph)

CH

2 (2-(OCF 3 )Ph)

CH

2 (2-(SCH 3 )Ph)

CR

2 2 Ph)

CH

2 (2,6-(C1) 2 Ph)

CR

2 (2-pyridyl)

CR

2 (2-furanyl)

CR

2 (2-tetrahydrofuran)

CR

2 (2-tetrahydropyran)

CH

2 2-thiophenyl)

CR

2 (2-isoxazolyl)

CR

2 (2-pyrazinyl)

CR

2 (Ph) Q-1 Q-3 0-6 Q-7 0-15

CH

2 (2-FPh)

CR

2 (2-C1F~h)

CR

2 (2-BrPh)

CH

2 (2-(CH 3 )Ph) WO 91/03464 PCT/IUS9O/04953 57 R3 R4

CH

3

CH

2

CH

3

CH

2

CH

2 C=-CH CH 2 (2-(0CH 3 )Ph) H

CH

3

CH

2

CH

3

CH

2

CH

2 c=-CH CH 2 (2-(CN)Ph) H

CH

3

CH

2

CH

3

CH

2

CH

2 C=-CH CH 2 (2-(CF 3 )Ph) H

CH

3

CH

2

CH

3

CH

2

CH

2 C=-CH CH 2 (2-(OCF 3 )Ph) H

CH

3

CH

2

CH

3

CH

2

CH

2 CE-cH CH 2 (2-(SCH 3 )Ph) H

CH

3

CH

2

CH

3

CH

2

CH

2 CE-CH CH 2 2 Ph) H

CH

3

CH

2

CH

3

CH

2

CH

2 c-=CH CH 2 (2,6-(C1) 2 Ph) H

CH

3

CH

2

CH

3

CH

2

CH

2 C=-CH CH 2 (2-pyridyl) H

CH

3

CH

2

CH

3

CH

2

CH

2 CRCH CH 2 (2.-pyridyl) H

CH

3

CH

2

CH

3

CH

2

CH

2 CE=CH CH 2 (2-furanyl) H

CH

3

CH

2

CH

3

CH

2

CH

2 CE=CH CH 2 (2-tetrabydrofuran) H

CH

3

CH

2

CH

3

CH

2

CH

2 C=-CH CH 2 C2-tetrahydropyran) H

CH

3

CH

2

CH

3

CH

2

CH

2 C-=CH CH 2 (2-thiophenyl) H

CH

3

CH

2

CH

3

CH

2

CH

2 CE=CH CH 2 (2-isoxazoly.) H

CH

3

CH

2

CH

3

CH

2

CH

2 CE-CH CH 2 (2-pyrazinyl) H

CH

3

CH

2

CH

3

CH

2

CH

2 CE=CH CH 2 (Ph) H

HCH

2 CH CH 2 CH CRCH Q-1 H

CH

3

CH

2

CH

3

CH

2 cH 2 C=-CH Q-3 H

CH

3

CH

2

CH

3

CH

2

CH

2 C-=cH Q-6 H

CH

3

CH

2

CH

3

CH

2

CH

2 C-=CH Q-7 H

CH

3

CH

2

CH

3

CH

2

CH

2 CE=CH Q-15 H

CH

3

CH

2

CH

3

CH

2

CH

2 Ph CH 2 (2-FPh) H

CH

3

CH

2

CH

3

CH

2

CH

2 Ph CH (2-C1Ph) H

CH

3

CH

2

CH

3

H

2

CH

2 Ph C 2 (-rhH

CH

3

CH

2

CH

3

CH

2

CH

2 ph CH 2 (2-(CH 3 Ph) H

CH

3

CH

2

CH

3

CH

2

CH

2 ph CH 2 (2-(CH 3 )Ph) H

CH

3

CH

2 CH CH 2 CH Ph CH 2 (-C)h

CH

3 CH CH 3

H

2 CHPh C 2 (2-(C 3 )Ph)H CH CH 2 CH CH 2 CH Ph CH 2 (2-(0CF)Ph) H

CH

3

CH

2

CH

3

CH

2

CH

2 Ph CH 2 (2-(CF 3 )Ph) H

CH

3

CH

2

CH

3

CH

2

CH

2 Ph CH 2

H

CH

3

CH

2

CH

3

CH

2

CH

2 Ph CH 2 2 Ph) H

CH

3

CH

2

CH

3

CH

2

CH

2 Ph CH 2 (2-pyridyl) H WO 91/03464 PCT/US9O/04953 58

C

3 CH RHCH 4HP RH(-urnl

H

CH 3

CH

2 CH 3

CH

2

CH

2 Ph CH 2 (2-tryofuran H

CH

3

CH

2

CH

3

CH

2

CH

2 Ph CH 2 (2-tetrahydropyran) H CH 3

CH

2

CH

3

CH

2

CH

2 Ph CH 2 (2-thiopheyrp) an H CH 3

CH

2

CH

3 CH 2 CH 2 Ph CH 2 (2-tiopzoyl) H CH 3

CH

2 CH 3

CH

2

CH

2 Ph CH 2 (2-isyrazoyl) H CH 3

CH

2

CH

3 CH 2 CH 2 Ph CH 2 (2pyrz) yl H CH 3

CH

2 CH 3

CH

2

CH

2 Ph CH-1 h H CH 3

CH

2 CH 3

CH

2

CH

2 Ph Q-1 H CH 3

CH

2

CH

3

CH

2

CH

2 Ph Q-3 H CH 3

CH

2

CH

3

CH

2

CH

2 Ph Q-6 H CH 3

CH

2

CH

3

CH

2

CH

2 Ph Q-17 H CH 3CH 2

CH

3

CH

2

CH

2

CH

3 QH- h H CH 2

CH

2

CH

3

CH

2

CH

2

OCH

3

CH

2 (2-ClPh) H CH 2

CH

2

CH

3 CH 2

CH

2

OCH

3

CH

2 (2-BrPh) H CH 2

CH

2

CH

3 CH 2

CH

2

OCH

3

CH

2 (2-(CH 3 Ph) H CH 2

CH

2

CII

3 CH 2

CH

2 0CH 3

CH

2 (2-(oaH 3 )Ph) H CH 2

CH

2

CH

3

CH

2

CH

2 0CH 3

CH

2 (2-(OON)Ph) H CH 2

CH

2

CH

3

CH

2

CH

2 0CH 3

CH

2 (2-(CF 3 )Ph) H CH 2

CH

2

CH

3

CH

2

CH

2 0CH 3

CH

2 (2-(0CF 3 )Ph) H CH 2

CH

2

CH

3

CH

2

CH

2 OCH 3

CH

2 (2-(SCF 3 )Ph) H CH 2

CH

2

CH

3

CH

2

CH

2

OCH

3

CH

2

H

CH 2

CH

2

CH

3

CH

2

CH

2 0CH 3

CH

2

(C)

2 Ph) H CH 2 CH 2

CH

3 CH 2

CH

2

OCH

3

CH

2 (2,-(Cridyl) H CH 2

CH

2

CH

3

CH

2

CH

2 0CH 3

CH

2 (2-furidyl) H1 CH 2

CH

2

CH

3

CH

2

CH

2 0CH 3

CH

2 (2-trarfuran H CH 2

CH

2

CH

3 CH 2

CH

2

OCH

3

CH

2 (2-tetrahydropyran) H CH 2

CH

2

CH

3

CH

2

CH

2

OCH

3

CH

2 (2-tetrpheyrp) an H

CH

2

CH

2

CH

3 CH 2

CH

2 0CH 3

CH

2 (2-tioazoyl) H CH 2

CH

2

CH

3

CH

2

CH

2 0CH 3

CH

2 (2-isorazony) H

CH

2

CH

2

CH

3

CH

2

CH

2 0CH 3

CH

2 (2pyrz) y H

CH

2

CH

2

CH

3

CH

2

CH

2

OCH

3 0-1Ph H

CH

2

CH

2

CH

3

CH

2

CH

2

OCH

3 Q-3 H

I

WO 91/03464PC!SO/45 PCT/US90/04953

CM

2

CM

2

CH

2

CH

2

CH

2

CM

2

CM

3

CH

2

CH

2

CM

3

CM

2

CM

2

CM

3

CH

2

CM

2

CM

3

CM

2

CH

2

C

3

CM

2

CM

2

CH

3

CM

2

CM

2

CM

3

CM

2

CM

2

CM

3

CM

2

CM

2

CM

3

CH

2

CH

2

CH

3

CH

2

CM

2

CH

3

CM

2

CM

2

CM

3

CH

2

CH

2

CM

3

CM

2

CM

2

CH

3

CM

2

CM

2

CH

3

CM

2

CM

2

CH

3

CH

2

CH

2

CH

3

CH

2

CH

2

CH

3

CH

2

CH

2

CM

3

CH

2

CH

2

CM

3 CH 2

CH

2

CH

3

CM

2

CH

2

CM

3

CM

2

CM

2

C

3

CM

2

CM

2

CM

3

CH

2

CM

2

CM

3

CM

2

CH

2

CM

3

CH

2

CH

2

CH

3

CH

2

CM

2

CM

3

CM

2

CM

2

CM

2 CH 3

CH

2

CM

2

CM

2

CH

3

CM

2

CH

2

CH

2

CM

3

CM

2

CHM

3 CH 2

CM

3

CM

2

C

3

CM

2

CM

2 CH 3

CH

2

CH

2

CM

3

CM

2

CM

2

CH

3

CH

2

CH

2

CHM

3

CM

2

CM

2

CH

3

CM

2

CM

2

CH

3

CH

2 CH2 CH 3 CH 2

CM

2

CH

3

CH

2

CM

2

CM

3

CH

2

CM

2

CH

3

CM

2

CM

2

CHM

3

CH

2

CH

2

CHM

3

CH

2

CH

2

CHM

3

CM

2 C C 2

CM

3

CM

2

CM

2

CM

3

CM

2

CM

2 CM 3CM 2

CM

2

CM

3

CM

2

CM

2 CM 3 C 2 CM 2

CM

3

CM

2

CM

2 CHM CM 2

CM

CM 3

CM

2

CM

2

C

3

CM

2

CM

2

CHM

3

CM

2

CM

2

CM

3

CM

2

C

2 CH 3

CH

2

CH

2

CM

3

CH

2

CM

2

CM

3

CM

2

CM

2

CM

2 CH 3

CH

2

CFI

2

CH

2 CH 3

CH

2

CH

2

CH

2

CM

2 0CM 3

CH

2 0CM 3

CM

2 0CM 3

CM

3

CHM

3

CM

3

CM

3

CM

3 CM 3

CM

3 CM 3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CHM

3

CM

3

CM

3

CM

3

CM

3

CM

2

CM

3 CM 3

CHM

3 Q-6 Q-7 0-15

CM

2 (2-FPh)

CM

2 (2-CIPh)

CM

2 (2-BrPh)

CM

2 (2-(CM 3 )Ph)

CM

2 0CM 3 Ph)

CM

2 (2-(CN)Ph)

CM-

2 (2-(CF 3 )Ph)

CM

2 (2-(OCF 3 )Ph)

CM

2 (2-(SCM 3 )Ph)

CM

2 2 Ph)

CM

2 C 2 Ph)

CM

2 (2-pyridyl)

CM

2 (2-furanyl)

CM

2 (2-tetrahydrofuran)

CM

2 (2-tetrahydropyran)

CM

2 (2-thiophenyl)

CM

2 2-isoxazolyl)

CM

2 (2-pyrazinyl)

CH

2 (Ph) 0-1 0-3 Q-6 0-7 0-15

CH

2 (Ph)

CM

2 (Ph)

CH

2 (Ph)

CM

2 (2-FPh)

CM

2 (2-CIPh) C1 2 (2-BrPh) WO 91/03464PCILS0/45 PCY/US90/04953

CR

3

CR

2

C

2

CH

2

CR

3 CH 2

CM

2

CM

2

CM

3

CR

2

C

2 c C 2

CR

3

CR

2

CM

2

CR

2

CR

3

CH

2

CR

2

CR

2

CH

3

CR

2

C

2

CR

2 CH 3

CR

2

CR

2

C

2

CH

3

CH

2

CR

2

CM

2

CH

3

CH

2

CM

2 c C 2

CH

3

CH

2

CR

2

CH

2

CH

3 H C 2

CH

2 CH 2

CH

3

CM

2

CH

2 C C 2

CH

3

CR

2

CM

2

CH

2

CH

3

C

2

CM

2

CM

2

CH

3

CR

2

CR

2

CM

2

CHM

3

CM

2 C C 2

CH

2 CH 3CR 2

CR

2

CH

2

CH

3

CM

2 C C 2

C

2 CH 3

CH

2

CH

2

CH

2

CR

3 CM2C C 2

CM

2

CH

3

CR

2 C C 2

CM

2 CH3CM 2 CM2 CM2

CR

3

CR

3

CM

3

CR

3

CH

3 CH 3

CH

3

CH

3

CR

3

CH

3

CR

2

CH

2

CR

2

CR

3

CR

2

C

2

CM

2

CH

3

CR

2

CM

2

CR

2

CM

3

CM

2

CR

2

CM

2

CR

3

CR

2

CR

2

CR

2

CM

3

CR

2

CR

2 f

CM

3

CR

2

CM

2

CM

2

CM

3

CR

2 cM 2

CH

2

CM

3

CR

2

CH

2

C

2

CM

3 CM2 CM 2

C

2

CH

3

CM

2

C

2

CH

2 CM 3CR 2 CM2 CM 2

CM

3

CR

2

CM

2

CH

2

CH

3

CR

2

CR

2

CM

2

CM

3

CR

2

CH

2

CH

2

CM

3

CM

2

CM

2

CH

2

CH

3 C 2 0CM 2

CM

2

CM

3

CH

2

CM

2

CM

2 CM 3 CM2 CR2CM 2

CM

3

CR

2

CH

2

CR

2

CM

3

C

2

CM

2

CM

2 CM3 CM2 CM2 CM 2 CM1 3

CH

2

CM

3

CM

2

CM

3

CH

2

CM

3

CM

2

CM

3

CR

2

CH

3

CH

2 CH3CH 2

CR

3

CH

2

CM

3

CH

2

CR

3

CR

3

CM

3

CM

3

CR

3

C

3

CM

3

CM

3

CR

3

CR

3

CM

3

CM

3

CR

3

CM

3

CM

3

CR

3

CM

3

CM

3

CH

3

CM

3

CR

3

CM

3

CM

3

CM

3

CR

3

CM

3

CH

3

CM

3

Q

CM

2 (2-(CM 3 )Ph)

CR

2 (2-(OCM 3 )Ph)

CR

2 (2-(CN)Pb)

CR

2 (2-(CF 3 )Ph)

CM

2 (2-(0CF 3 )Ph)

CM

2 (2-(SCH 3 )Ph)

CM

2 2 Ph)

CM

2 2 Ph) Cl- 2 (2-pyridy.)

CM

2 (2-furanyl)

CM

2 2-tetrahydrof uran)

CM

2 2-tetrahydropyran)

CM

2 (2 -thiophenyl)

CR

2 (2-isoxazolyl)

CM

2 2-pyrazinyl)

CH

2 (Ph) 0-1 0-3 Q-6 Q-7 0-15

CM

2 (Ph)

CM

2 (2-FPh)

CM

2 2-CIPh)

CH

2 (2-(CH 3 )Ph)

CH

2 (2,6-Cl 2 Ph)

CH

2 2-CF 3 Ph)

CM

2 2-tetrahydropyran)

CM

2 (2 -pyridyl)

CM

2 (Ph) 0-1 WO 91/03464 PcT/US9O/04953 61 R3 R~4 R

CH

3

CH

3

CH

2

CH

3 Q-3 H

CH

3

CH

3

CH

2

CM

3 Q-6 H

CH

3

CH

3

CH

2

CH

3 Q-7 H

CH

3

CH

3

CH

2

CH

3 Q-15 H

CH

2

CH=CH

2

CM

2

CH=CH

2

CM

3

CH

2 (2-FPh) H

CH

2 cH=CH 2

CH

2

CM=CH

2

CH

3

CH

2 (2-CIPh) H

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

3

CH

2 (2-(CH 3 )Ph) H

CH

2

CH=CH

2

CH

2 cH=CH 2

CM

3

CH

2 (2,6-Ca 2 Ph) H

CH

2 cH=CH 2

CH

2 cH=CH 2

CH

3

CH

2 (2-CF 3 ph) H

CH

2 cH=CH 2

CH

2

CH=CM

2

CH

3

CH

2 (2-tetraiiydropyran) H

CH

2

CH=CH

2

CH

2

CH=CH

2

CM

3

CH

2 (2-pyridyl) H

CH

2 cH=CH 2

CH

2

CH=CH

2

CM

3

CH

2 (Ph) H

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

3 Q-1 H

CH

2

CH=CH

2

CH

2

CH=CH

2

CM

3 Q-3 H

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

3 0-6 H

CH

2

CH=CH

2

CH

2

CH=CH

2

CM

3 Q-7 H

CH

2

CH=CH

2

CM

2

CH=CH

2

CM

3 Q-15 H

CH=CH

2

CH=CH

2

CM

3

CH

2 (2-FPh) H

CMC

2

CH=CH

2

C

3

C

2 (2-ClPh)H

CH=CH

2

CH=CH

2

CH=CH

2 CH=CH2

CH=CH

2

CH=CH

2

CH=CH

2

CH=CH

2

CH=CH

2

CH=CCH

CH

2

C=CH

CH

2

C=CH

CMr=CHn 2

CH=CH

2

CH=CH

2 CM =CH 2

CB=CH

2 CM =C 2

CHCH

2

CH=CH

2

CH=CH

2

CHCH

2

CH

2

C=ECH

CH

2

C=SCH

CH

2 (2,6-Ca 2 Ph)

CM

2 (2-CF 3 ph)

CM

2 (2-tetrahydropyran)

CH

2 (2-pyridyl)

CH

2 (ph) 0-1 0-6 0-7

CH

2 (2-FPh)

CH

2 2-CiPh)

CH

2 (2-(CH 3 )Ph) WO 91/03464 PCT/US9O/04953 62 R3 R

CH

2 CE=CH CH 2 CRCH CH 3 cH 2 (2,6-Cl 2 Ph) H

CH

2 C=-CH CH 2 CE-CH CH 3

CH

2 (2-CF 3 Ph) H

CH

2 C=CH CH 2 CH C 3

C

2 (2-tetrahydropyran) F.

CH

2 C=CH CH 2 CECH CH 3 CH (2-pyridyl) H

CH

2 CEH CHCECH CH 3

CH

2 (h

CH

2 C=CH CH 2 CH C 3 0-1h H

CH

2 CE=CH CH 2 C-=CH CH 3 Q-1 H

CH

2 CE=CH CH 2 cE-CH CH 3 Q-3 H

CH

2 CECH CH 2 CECH CH 3 Q-7 H

CH

2 C=CH CH 2 CECH CH Q-17 H

CH

2 OC=H CH 2 OC-H CH 3 QH- h H

CH

2

OCH

3

CH

2 0CH 3

CH

3

CH

2 (2-ClPh) H

CH

2

OCH

3

CH

2

OCH

3

CH

3

CH

2 (2-CH 3 Ph) H

CH

2

OCH

3

CH

2 0CH 3

CH

3

CH

2 (2-CH3Ph) H

CH

2 0CH 3

CH

2

OCH

3

CH

3

CH

2 (2,-C 3 Ph) H

CH

2 0CH 3

CH

2

OCH

3

CH

3

CH

2 (2-tetrahydoyr H

CH

2 0CH 3

CH

2

OCH

3

CH

3

CH

2 (2-teyradropr H

CH

2

OCH

3

CH

2 0CH 3

CH

3

CH

2 (2ph) iyl H

CH

2

OCH

3

CH

2 0CH 3

CH

3 CH2P1 H

CH

2

OCH

3

CH

2

OCH

3

CH

3 Q-1 H

CH

2 0CH 3

CH

2

OC!!

3

CH

3 0-6 H

CH

2

OCH

3

CH

2 0CH- 3

CH

3 0-7 H

CH

2

OCH

3

CH

2 0CH 3

CH

3 Q-75 H

HCH

3

CH

2 0 CH 3 CH- h H

CH

3

CH

2 H CH 3

CH

2 (2.-CPh) H

CH

3

CH

2 H CH 3

CH

2 (2-CHPh) H

CH

3

CH

2 H CH 3

CH

2 (2-CH3)h) H CH CH 2 H CH 3

CH(-C

3

)H

CH

3

CH

2 H CH 3

CH

2 (2-CFPyrd) H

CH

3

CH

2 H CH 3

CH

2 (Ph) H

CH

3

CH

2 H CH 3 Q-1 H

CH

3

CH

2 H CH 3 Q-3 H PCT/US90/04953 WO 91/03464 PTU9/45

CR

3

CH

2

CR

3

CH

2

CR

3

CH

2

CH

2

CH

2

CH

3

C

2

CH

2

CH

3

CH

2

CH

2

CH

3

CH

2

CH

2

CM

3

CH

2

CR

2

CH

3

CH

2

CH

2

CH

3

CH

2

CH

2

CM

3

CH

2

CH

2

CH

3

CH

2

CH

2

CH

3

CH

2

CH

2

CH

3

CR

2

CH

2

CH

3

CH

2

CH

2

CH

3

CR

2

CH

2

CH

3

CH

3

CH

2

CH

2

CH

2

CH

3

CH

2 CR 2 C 2

CH

3

CR

2

CR

2

C

2

CH

3

CH

2

CH

2

CH

2

CH

3

CR

2 CH 2CR 2

CH

3

CH

2

CH

2

CH

2 CH 3CR 2

CH

2

CR

2

CH

3

CH

2

CH

2

CH

2

CR

3

CH

2

CH

2

CR,

CR

3

CH

2

CM

2

CH

2

CR

3

C

2

CR

2

CH

2

CH

3

CH

2

CH

2

CH

2

CH

3

CH

2

CH

2

CH

2

CR

3

CR

3

CH

3

CR

3

CH

3

CH

3

CR

3

CH

3

CH

3

CH

3

CM

3

CH

3

CH

3

CH

3

CR

3

CH

3

CH

3

CH

3

CR

3

CH

3 CH 3 CH 3

CH

3

CH

3

CH

3

CR

3

CR

3

CH

3

CH

3

CH

3

CR

3

CH

3

CH

3

CR

3

CH

3 Q-6 0-7

CH

2 (2-FPh)

CM

2 2-CIPh)

CR

2 (2-(CH 3 )Ph)

CR

2 6-C1 2 Ph

CR

2 (2-CF 3 Ph)

CH

2 2-t :ahydropyran)

CR

2 (2-pyridyl)

CR

2 (Ph) Q-1 0-3 0-6 Q-7 0-15

CH

2 2-FPh)

CR

2 (2-CIPh)

CH

2 (2-(CH 3 )Ph)

CM

2 6-C1 2 Ph)

CR

2 (2-CF 3 Ph)

CR

2 2-tetrahydropyrian)

CM

2 (2-pyridyl)

CH

2 (Ph) Q-1 0-3 0-6 Q-7 0-15

CM

2 2-FPh)

CR

2 2-CiPh)

CH

2 (2-(CH 3 )Ph)

L

PC-I-IUS9O/04953 WO 91/03464 64 3 4 5 Ql CH CH QH CH(,XC2h

CH

3

CM

3

CH

3

CH

2 (2-CaPh) H

CH

3

CH

3

CH

3

CH

2 (2-tetrahydropyran) H

CH

3

CM

3

CM

3

CH

2 (2-pyridyl) H

CM

3

CH

3

CM

3

CH

2 (Ph) H

CH

3

CM

3

CH

3 Q-1 H

CM

3

CM

3

CM

3 Q-3 H

CM

3

CH

3

CH

3 Q-6 H

CM

3

CM

3

CM

3 Q-7 H

CM

3

CM

3

CM

3 Q-15 H 1 2 3 B-4

CM

3

CH

3 H H CM 3 CH(2FhH

CM

3

CM

3 H CM 3

C

2 (2-C1Ph)H-

CM

3

CM

3 H H CM 3

CH

2 (2-BrPh) H

CM

3

CM

3 H H CM 3

CH

2 (2-(CH 3 Ph) H

CM

3

CM

3 H H CM 3

CH

2 (2-(CH 3 )Ph) H

CH

3

CM

3 H H CM 3

CH

2 )Ph)

CM

3

CM

3 H CM 3

C

2 (2-(C)H)J

CM

3

CM

3 H H CM 3

CH

2 (2-(OCF)Ph) H

CM

3

CM

3 H H CM 3

CH

2 (2-(CH 3 )Ph)H CM C 3 H H C 3

C

2 (2,-F 2 h H

C

3

CM

3 H H CM 3 CH 2 Ph)H

CM

3

C

3 H H C 3

C

2 (2-prdl H

CH

3

CM

3 H H CM 3 CH 3-uanl H

C

3

C

3 H H C 3

C

2 (2-tetra)h)ourn

CH

3

CM

3 H H CM 3 CH (2-etrahdoyrn H

CM

3

CM

3 H H CM 3

CH

2 (2,-hio2Phey) H

CM

3

CM

3 H H CM 3

CH

2 (2-isoxezyl) H

CH

3

CM

3 H H CM 3

CH

2 (2-pyrazinyl) H

CM

3

CM

3 H H CM 3

CH

2 (Ph) H WO 91/03464 PTU9/45 PCr/US90/04953 1 2 ~3 4

CR

3

CR

3

CH

3 CH 3

CH

3

CH

3

CH

3

CR

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3 Cu 3 CH 3

CH

3

CH

3

CR

3

CR

3 Cu 3

CR

3

CH

3

CH

3

CH

3

CH

3

CR

3

CR

3

CH'

CH

3

CH

3

CH

3

CH

3 Cu 3

CH

3 Cu 3

CH

3 Cu 3 CH 3 Cu 3 Cu 3 Cu 3 CHu 3 Cu 3 Cu 3 Cu 3 Cu 3 Cu 3 Cu 3 Cu 3

CH

3

CR

3 Cu 3 Cu 3

CR

3 Cu 3

CR

3 Cu 3 cu 3

CH

3 cu 3

CHR

3 Cu 3

CR

3 Cu 3 Cu 3 Cu 3 Cu 3

CH

3 Cu 3

CR

3

CR

2 Cu 3

CR

2

CH

3

CR

2

CH

3

CR

2 Cu 3

CR

2

CH

3

CH

2

CR

3

CR

2 Cu 3

CR

2 Cu 3 Cu 2

CR

3 Cu 2

CH

3

CR

2 Cu 3 Cu 2

CR

3

CR

2 Cu 2

HCRHC

2 Cu 2

CR=CH

2

CR

2

CHC

2

CM

2

CR=CH

2

CR

2 HCuC1 2 Cu 2 CR=Cu 2 Cu 2

CR=CH

2

CR

2

HCRHC

2 CuzCu=Cu 2 Cu 2

CR=CR

2

CR

2

CR=CR

2

CR

2

HCRHC

2 Cu 2 cu=cu 2

CH

2 Ph

CH

2 Ph Q-1 Q-3 Q-6 Q-7 0-15

CR

2 (2-FPh)

CH

2 (2-ClPh) Cu 2

CR

3 )Ph)

CR

2 6-F 2 Ph)

CR

2 (2-BrPh)

CH

2 6-Cl 2 Ph)

CR

2 (2-pyridyl)

CH

2 (Ph) Q-1 Q-3 Q-6 Q-7

CR

2 2-FPh) Cu 2 (2-CIPh)

CR

2 (2-(CH 3 )Ph)

CR

2 (2 f 6-C1 2 Ph)

CR

2 (2-CF 3 Ph)

CR

2 (2-tetrahydropyr an)

CR

2 (2-pyridyl)

CH

2 Ph) Q-1 0-3 Q-6 Q-7 0-15

CH

2 (Ph)

CH

2 (2-FPh) WO 91/03464 PCT/US9O/04953 66 R4

R

CM

3

CM

3 CH 3

CH

3

CH

3

CH

3

CM

3

CH

3

CM

3

CH

3

CM

3

CM

3

CH

3

CM

3

CM

3

CM

3

CM

3

CM

3

CHM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

2

CH

3

CM

2

CH

3

CM

2

CM

3

CM

2 CM 3

CM

3

CHM

3

CM

3

CM

3

CM

3

CM

3

CHM

3

CM

3

CM

3 CM 3

CM

3

CM

3

CM

3 CM 3 CM 3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

2

CM

3

CHM

2 CM 3

CH

2

CM

3

CM

2

CM

3

CM

2 Ph

CM

2 Ph

CM

2 Ph

CM

2 CM=C (C C 3

CM

2 CM=C

CM

3

CM

2 CM=C (C C 3

CM

2 CM=CM CH 3

CM

2 CM=CM(C

C

3

CM

2 0CM 3

CM

2 0CM 3

CM

2

OCH

3

CM

2 0CHM 3

CM

2 0CM 3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3 CM2H

CM

2 C C 3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CH

3

CM

2 2-(CM 3 )Ph)

CH

2 (2,6-C2 2 Ph) 0-3

CH

2 (Ph)

CM

2 (2-FPh)

CM

2 (2-(CM 3 )Ph)

CM

2 (2,6-C1 2 Ph) 0-3

CM

2 (Ph)

CM

2 (2-FPh)

CM

2

CM

3 )Ph)

CM

2 (2,6 -C1 2 Ph) 0-3

CM

2 Ph)

CM

2 (2-FPh)

CH

2 (2-(CH 3 )Ph)

CM

2 6-Ca 2 Ph) Q-3

CM

2 (Ph)

CHM

2 (2-FPh)

CM

2

CM

3 )Ph)

CM

2 (2 ,6-Ca 2 Ph) Q-3

CH

2 (Ph)

CM

2 (2-FPh)

CH

2 (2-(CH 3 )Ph)

CM

2 (2,6 -C1 2 Ph) Q-3

CM

2 (Ph)

CH

2 2-FPh)

CH

2 2-(CH 3 )Ph)

CH

2 (2,6 -C2 2 Ph)

CM

2

CH

2

CM

3

CH

2

CM

2

CM

3 CM 2 CM2 CM

CM

2

CM

2

CM

CM

2 CM2 CM

H

H

H

H

PCT/US90/04953 WO 91/03464 PTU9/45 R1 2 R3

CH

2

CM

3

CH

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CH

3

CM

2

CM

3

CM

2

CM

3

CM

2

CH

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CH

2 CH 3

CH

2

CH

3

CM

2

CM

3

CM

2

CH

3

CH

2

CH

3

CM

2

CM

3

CH

2

CH

3

CM

2

CH

3 CM 2

C

3

H

H

H

H

H

H

H

H

H

H

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2 CM 3

CM

2

CM

3 CM =CM 2

CH=CM

2 CM CM 2

CH=CH

2

CH=CH

2

CECH

CRCH

CE CM CE CM

CECH

H

H

H

H

H

H

H

M

H

H

H

CM

3

CM

3

CM

3

CM

3

CM

3

CM

2

CM

2 CM 3

CM

2

CM

2

CM

3

CM

2

CM

2

CM

3

CM

2 CM 2CM3

CM

2

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CH

2

CH

3

CM

2

CM

3

CH

2

CM

3

H

H

H

H

H

H

H

H

H

H

H

CM

3

CM

3

CM

3

CM

3

CM

3

CM

2

CM

2 CM3

CM

2 CM2 CM3

CM

2 CM2 CM3

CM

2

CM

2

CM

3

CM

2 CM2 CM3

CM

2

CM

3

CM

2

CM

3

CM

2 CM 3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2 H CM

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

3

CM

2

CM

3

CH

2

CH=CB

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CM

2

CH=CH

2

CM

3

CM

3

CM

3

CM

3

CM

3

CM

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3 Q-3

CM

2 (Ph)

CM

2 2-FPh)

CM

2 (2-(CM 3 )Ph)

CM

2 6-C1 2 Ph) Q-3

CM

2 (Ph)

CM

2 (2-FPh)

CH

2 (2-(CH 3 )Ph)

CH

2 (2,6-CI 2 Ph) Q-3

CM

2 (Ph)

CM

2 (2-FPh)

CH

2 (2-(CH 3 )Ph)

CH

2 6-Cl 2 Ph) 0-3

CM

2 (Ph)

CM

2 (2-FPh)

CH

2 (2-(CH 3 )Ph)

CH

2 (2,6-C1 2 Ph) 0-3

CM

2 (Ph)

CM

2 (2-FPh)

CH

2 (2-(CH 3 )Ph)

CH

2 2, 6-C1 2 Ph) 0-3

CH

2 (Ph)

CH

2 (2-FPh)

CH

2 (2-(CH 3 )Ph)

CM

2 6-C1 2 Ph) Q-3 H Ph CH 2

CH

3

CMC

2 (h CH3 CH2(Ph) i WO 91/03464 R 1 R£2 PCT/ LIS90/04953 H Ph H Ph H Ph H Ph H CH 2

OCH

3 H CH 2

OCR

3 H CH 2

OCH

3 H CH 2 0CH 3 H CH 2

OCH

3 H H H H

CR

3

CH

3

CH

3

CH

3

CR

3

CR

3

OH

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

OH

3

CR

3

CR

3

CR

3

CH

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

OH

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CH

3

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CH

2

CR

3

CR

2 CR 3

CR

2

CR

3

CR

2

CR

3

CH

2 CH 3

CR

2

CR

2

C

3

OH

2 H C 2

CR

3

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

CR

2

CR

3

OH

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2 CR3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2 CR 3

CR

2

CR

2

CR

3

CR

2 CR2 CR 3

H

R

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

CR

3

CR

3

CR

3

CR

3

CR

3

CH

3

CR

3

CR

3

CR

3 (2-FPh

CR

3

CR

3

CR

3

CR

3

CH

3

CR

3

CR

3

CR

3 CR3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3 )Ph

CR

2 2-FPh)

CR

2 (2-(CH 3 )Ph)

CR

2 6-Cl 2 Ph) Q-3

CR

2 (Ph)

CH

2 2-FPh)

CR

2

CH

3 )Ph)

CR

2 6-Ca 2 Ph) 0-3

CH

2 (2-(CR 3 )Ph)

CR

2 (2-FPh)

CR

2 2-FPh)

CR

2 (2-CIPh)

CR

2 (2-BrPh)

CR

2

CR

3 )Ph)

CH

2 (2-(OCH 3 )Ph)-

CR

2 (2-(CN)Ph)

CH

2 (2-(CF 3 )Ph)

CH

2 2-(OCF 3 )Ph)

CH

2 (2-(SCH 3 )Ph)

CH

2 2 Ph)

CH

2 (2,6-(C1) 2 Ph)

CR

2 (2-pyridyl)

CR

2 (2-furanyl)

CR

2 (2-tetrahydrofuran)

CH

2 (2--tetrahydropyran)

CR

2 (2-thiophenyl)

CR

2 (2-icoxazoly.)

CR

2 (2-pyrazinyl)

CH

2 (Ph) WO 91/03464 PrU9/45 PCr/US90/04953 1 2 R3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CH

3

CH

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3 3

CM

3

C

3

CM

3

C

3

CM

3

C

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3 CM 3

CH

3

CM

3 CM 3

CM

3

CM

3 CM 3 CM 3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3 CM 3

CH

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

2

CH=CH

2

CM

2

CH=CH

2

CM

2

CH=CH

2

CM

2

CH=CH

2

CM

2

CH=CH

2

CH

2 CM CM 2

CM

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=C.,

CM

2 cM=CH 2 cM 2 cM=CM 2

CH

2 cM=CM 2 Q-1 Q- 3 0-6 0-7

CM

2 (2 -FPh)

CM

2 (2-CIPh)

CM

2 (2-(CH 3 )Ph)

CM

2 6-F 2 Ph)

CH

2 (2-BrPh)

CM

2 6-C2 2 Ph)

CM

2 (2-pyridyl)

CH

2 (Ph) 0-1 0-3 0-6 0-7 0-15

CH

2 (2-FPh)

CM

2 (2-Ciph)

CH

2 (2-(CH 3 )Ph)

CH

2 (2,6-Cl 2 Ph)

CM

2 (2-CF 3 Ph)

CM

2 (2-tetrahydropyran) C1 2 2-pyridyl)

CH

2 (Ph) 0-1 3 0-6 0-7 0-15 WO 91/03464 WO 9103464PCT/US90/04953 RI R2 R3

CH

3 C3

CH

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CH

3

C

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CH

3

CR

3 H3 H3 C3

CH

2 Ph CH2Ph CR;!Ph

CR

2 Ph

CR

2 Ph

CR

2

CR=CR(CH

3 CM 2 CR=CH (CR 3

CR

2 HCR R( CR 3

CR

2 HCR R( CR 3

CR

2

OCR

3

CR

2

OCR

3

CR

2

OCR

3

CH

2 0CR 3

CR

2 (Ph)

CR

2 2 -FPh)

CR

2

CR

3 )Ph)

CR

2 6-CI 2 Ph) Q-3

CR

2 (Ph)

CR

2 (C2-FPh)

CR

2 (2-(CH 3 )Ph)

CR

2 6-Cl 2 Ph) 0-3

CR

2 (Ph)

CR

2 2-FPh)

CR

2

CR

3 Ph

CR

2 (2,6-Cl 2 Ph) WO 91/03464 PTU9/45 PCr/US90/04953 R 2 R3 R4

CH

3

CH

3

CH

3

CR

3

CR

3

CR

3

CH

3

CH

3

CH

3

CR

3

CH

3

CR

3

CH

3

CR

3

CR

3

CH

3

CR

2

CR

3

CH

2

CH

3

CR

2

CH

3

CR

2

CR

3

CH

2

CR

3

CR

2

CR

3

CH

2

CR

3

CR

2

CR

3

CH

2

CR

3

CR

2

CR

3

CR

2

CR

3

CH

2

CR

3

CR

2

CR

3

CH

2

CR

3

CH

2

CH

3

CH

2

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CH

2

CH

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CH

2

CR

3

CR

2

CH

3

CR

2

CR

3

CR

2

CR

3

CH

2

CH

3

CH

2

CH

3

H

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

2

CR

2

CR

3

CR

2

CR

2

CR

3

CR

2

CR

2

CR

3

CR

2

CR

2 CR 3

CR

2

CR

2 CR3

R

R

H

R

R

H

H

R

H

H

H

H

R

H

H

CH

3

CR

2

OCR

3

CH

3

CR

3

CR

3

CH

3

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CH

3

CIH

2

CH

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CH

3

CR

3

CR

3

CR

3

CR

2

CR

3

CH

2

CR

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CH=CH

2

CH

2

CH=CH

2

CR

2

CR=CR

2

CR

2

CR=CH

2

CH

2

CH=CH

2

CR

3 Q-3

CR

2 Ph)

CR

2 (2-FPh)

CR

2 (2-(CR 3 )Ph)

CR

2 6-Cl 2 Ph) Q-3

CR

2 (Ph)

CR

2 2-FPh)

CR

2 (2-(CR 3 )Ph)

CR

2 6-C1 2 Ph) 0-3

CH

2 (Ph)

CR

2 (2-FPh)

CH

2 (2-(CH 3 )Ph)

CR

2 6-Cl 2 Ph) 0-3

CH

2 (ph) CR1 2 (2-FPh)

CR

2 (2-(CH 3 )Ph)

CH

2 (2,6-Ca 2 Ph) 0-3

CR

2 (Ph)

CR

2 (2-FPh)

CR

2

CR

3 )Ph)

CH

2 (2,6-Cl 2 Ph) 0-3

CR

2 (Ph)

CH

2 (2-FPh)

CH

2 (2-(CH 3 )Ph)

CR

2 6-C1 2 Ph) Q-3

CH

2 (Ph) WO 91/03464 [/U9045 PCY/US90/04953 R1 R2 E3

CH

2

CH

3

CH

2

CR

3

CH

2

CR

3

CH

2

CH

3

CH

2

CR

3

CH

2

CH

CH

2

CR

3

CH

2

CH

3

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

$i

H

H

H

H

CR

2

CH

3

CR

2

CR

3

CH

2

CH

3

CH

2 C R 3

CH

2

CR

3

CH

2

CR

3

CH

2

CH

3 CH 2

CR

3

CH

2 CH 3

CH=CH

2

CH=CH

2

CH=CR

2

CH=CH

2

CH=CH

2 C= CH CE CH CE CH CE CH Ph Ph Ph Ph Ph

CH

2 0OCR 3

CR

2 0CH 3

CH

2 0OHR 3

CH

2

OCR

3

CHR

2

OCR

3

H

H

CH

3

CH

3

CH

3

CH

3

CH

2

CH

2

CR

3

CH

2

CH

2

CR

3

CH

2

CH

2

CH

3

CR

2

CR

2

CR

3

CH

2

CR

2

CH

3

CH

2

CR

3

CH

2

CH

3

CR

2

CH

3

CR

2

CH

3 CR 2

CR

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CR

2

CH

3 CH 2 CH 3

CH

2

CR

3

CH

2

CH

3

CH

2

CH

3

CR

2

CR

CR

2

CH

3

CR

2

CR

3 CR 2

CR

3

CH

2

CH

3

CR

2

CR

3

CH

2

CR

3

CH

2

CR

2

CR

3

CH

2

CH

2

CR

3

CR

3

CR

3

CH

3

CR

3

CH

2

CH

2

CR

3

CH

2

CH

2

CH

3

CH

2

CH

2

CH

3

CH

2

CH

2

CH

3

CH

2

CH

2

CH

3

CH

2

CR

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3 CR 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CR

3 CR 2

CH

3

CR

2

CH

3

CH

2

CH

3

CR

2

CR

3

CH

2

CR

3

CR

2

CR

3

CR

2

CR

CH

2

CH

2

CR

3

CH

2

CR

2

CH

3

CR

3

CR

3

CR

3

CR

3

CR

3

CH

3

CR

3

CR

3

CR

3

CH

3

CR

3

CH

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CH

3

CR

3 C11 2 (2(CR 3 )Ph (2-FPh)

CR

2 (2-FPh)

CR

2

CR

3 Ph)

CR

2 6-Cl 2 Ph) Q-3

CH

2 (Ph)

CR

2 (2-FPh)

CH

2 (2-(CH 3 )Ph)

CR

2 (2,6-C2 2 Ph) 0-3

CR

2 (Ph)

CR

2 (2-FPh)

CR

2

(CR

3 )Ph)

CH

2 (2,6-Cl 2 Ph) Q-3

CH

2 (Ph)

CR

2 (2-FPh-

CH

2 (2-(CR 3 )Ph)

CH

2 (2,6-C1 2 Ph) 0-3

CH

2 (Ph)

CR

2 (2-FPh)

CH

2 (2-(CH 3 )Ph)

CH

2 (2,6-Cl 2 Ph) Q-3

CR

2 (Ph)

CR

2 (2-FPh)

CR

2

CR

3 Ph

CR

2 6-Cl 2 Ph) 0-3

CH

2 3 )Ph)

CH

2 (2-FPh) WO 91/03464 PTU9/45 PCr/US90/04953 73 1 2 34 H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-FPb-) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-CIPh) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-BrPh) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(0CH 3 )Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(CN)Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(CF 3 )Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(OCF 3 )Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(SCH 3 )Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 2 Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2,6-(C1) 2 Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-pyridyl) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-turanyl) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-tetrahydrofuran) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-tetrahydropyran) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-thiophenyl) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-isozazolyl) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-pyrazinyl) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

3 Q-1 H H H CH 2

CH

3

CH

2

CH

3

CH

3 0-3 H H H CH 2

CH

3

CH

2

CH

3

CH

3 0-6 H H H CH CH 3 CH CH 3

CH

3 0-7 H H H CH 2

CH

3

CH

2

CH

3

CH

3 Q-15 H H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2-FPh) H H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2-ClPh) H H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2-(CH 3 )Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2j6-Cl 2 pfi) H H 14 CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2-CF 3 Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2-tetrahydropyran) H H H C11 2

CH

3

CH

2

CH

3

CH

2

CH

3

CU

2 (2-pyridyl) H H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (Ph) H PCT/US90/04953 WO 91/03464 PIU9/45 R I R 2

H

H

H

H

H

H

H

H

H

H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2

CM

3

CH

2

CH

3

CH

2

CM

3

CH

2

CH

3

CH

2 CH 3

CM

2

CH

3 H23

H

H

H

H

H

H

H

H

H

H

H

CH

2

CH

3

CM

2

CM

CM

2

CR

3

CM

2

CM

3

CH

2

CM

3

CH

2

CM

3

CM

2

CM

3

CM

2

CM

3 CII ,CM 3

CM

2

CH

3

CM

2

CH

3

CMHCH

3

CM

2

CM

3

CM

2

CM

3

CH

2

CH

3

CM

2

CM

3

CM

2

CM

3

CM

2

CR

3

H

H

H

H

H

H

H

H

it

H

H

H

H

CH

2

CR

3

CM

2

CM

3

CM

2

CI

3

CM

2

CR

CH

2

CR

3

CH

2

CH=CH

2

CM

2 CR CH 2

CM

2 CH= CH 2

CH

2

CM=CH

2

CM

2

CH=CH

2

CH

2

CH=CH

2

CM

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CM

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CM=CH

2

CM

3

CH

3

CH

3

CM

3

CH

3

CH

3

CM

3

CH

3

CM

3

CM

3

CH

3

CM

3

CH

3 Q-1 Q-3 0-6 0-7

CR

2 2 -FPh)

CH

2 (2-C1Ph)

CH

2 (2-(CH 3 )Ph)

CM

2 6-Cl 2 Ph)

CH

2 (2-CF 3 Ph)

CM

2 (2-tetrahydropyran)

CM

2 (2-pyridyl)

CH

2 (Ph) 0-1 0-3 0-6 0-7 0-15

CM

2 (2-FPh)

CH

2 2-CIPh)

CH

2 (2-(CH 3 )Ph)

CH

2 (2,6-Ca 2 Ph)

CH

2 (2-CF 3 Ph)

CR

2 (2 -tetrahydropyran)

CH

2 (2-pyridyl)

CH

2 (Ph) 0-1 0-3 0-6 Q-7 0-15 WO 9 1/03464 PCT! 1S90/04953 El1R2 23B4FQx H H H H CH 2

CH

3

CH

2 (2-FPh) H H H H H CH 2

CH

3

CH

2 (2-C1Ph) H H H H H CH 2

CH

3

CH

2 (2-(CH 3 )Ph) H H H H H CH 2

CH

3

CM

2 (2,6-C1 2 Ph) H H H H H CH 2

CH

3

CH

2 (2-CF 3 Ph) H H Hi H H CH 2

CH

3

CH

2 (2-tetrahydropyran) H H H H H CH 2

CH

3

CH

2 (2-pyridyl) H H H H H CH 2

CH

3

CM

2 (Ph) H H H H H CH 2

CH

3 Q-1 H H H H H CH 2

CH

3 Q-3 H H H H H CH 2

CH

3 Q-6 H H H H H CH 2

CH

3 Q-7 H H H H H CH 2

CH

3 Q-15 H H H CM 3

CH

3

CH

3

CH

2 (2-FPh) H H H CH 3

CH

3

CM

3

CH

2 (2-ClPh) H H H CM 3

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) H H H CH 3

CH

3

CH

3

CH

2 (2,6-CI 2 Ph) H H H CH 3

CH

3

CM

3

CH

2 (2-CF 3 Ph) H H H CM 3

CM

3

CH

3

CH

2 (2-tetrahydropyran) H H H CM 3

CH

3

CM

3

CH

2 (2-pyridyl) H H H CM 3

CH

3

CH

3

CH

2 (Ph) H H H CM 3

CH

3

CH

3 Q-1 11 H H CH 3

CH

3

CM

3 Q-3 H H H CM 3

CH

3

CH

3 Q-6 H H H CM 3

CH

3

CM

3 0-7 H H H CM 3

CM

3

CH

3 Q-15 H

CH

3

CH

3 CH CH 3 CH CH 3

CM

3 CH (-FPh) H C 3 C 3 C 2 C 3 C 2 3 C 3 C 2 2 1 h

CM

3

CM

3

CH

2

CH

3

CH

2

CH

3

CM

3

CH

2 (2-(CH 3 Ph) H

CM

3

CH

3

CH

2

CH

3

CH

2

CM

3

CH

3

CH

2 (2-CH3Ph) H

CM

3

CM

3

CH

2

CH

3

CH

2

CH

3

CM

3

CH

2 (2,-C 3 Ph) H

CH

3

CM

3

CH

2

CH

3

CH

2

CH

3

CM

3

CH

2 (2-tetrahydropyran) H WO 9 1/03464 PCTIUS90/04953 76 1 2 R3 R45 Q

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-.pyridyl) H

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (Ph) H

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-1 H

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-3 H

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-6 H

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-7 H

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-15 H

CH

3

CH

3

CH

3

CH

3

CH

3

CH

2 (2-FPh) H

CH

3

CH

3

CH

3

CH

3

CH

3

CH

2 (2-ClPh) H

CH

3

CH

3

CH

3

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) H

CH

3

CH

3

CH

3

CH

3

CH

3

CH

2 (2,6-Cl 2 Ph) H

CH

3

CH

3

CH

3

CH

3

CH

3

CH

2 (2-CF 3 Ph) H

CH

3

CH

3

CH

3

CH

3

CH

3

CH

2 (2-tetrahydropyran) H

CH

3

CH

3

CH

3

CH

3

CH

3

CH

2 (2-pyridyl) H

CH

3

CH

3

CH

3 CH.4 CH 3 CH (Ph) H 3

C

3

C

3

C

3

H

3 2-

CH

3

CH

3

CH

3

CH

3

CH

3 0-3 H

CH

3

CH

3

CH

3

CH

3

CH

3 Q-6 H

CH

3

CH

3

CH

3

CH

3

CH

3 Q-6 H

CH

3

CH

3

CH

3

CH

3

CH

3 Q-15 H

CCH

3

CH

2 3

CH

2 3

CH

2 3

CH

3 QH- h H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CB

2 (2-C1Ph) H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-CI 3 Ph) H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2,-CH)Ph) H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2,-C 3 Ph) H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-tetrahydoyr H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-ter~d) ra H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2pyri) l H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 0-1ph H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-1 H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 0-6 H

CH

2 C1 3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3 Cl 3 0-6 H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 0-15 H WO 91/03464 PCT/ US9O/04953 77 El1 2 P3 R 5 x

CH

3

CH

3 H H CH 3

CH

2 (Ph)

H

CH

3

CH

3 H H CH 3

CH

2 (2-FPh)

H

CH

3

CM

3 H H L'H 3

CH

2 (2-(CH 3 )Ph) H

CH

3

CH

3 H H CH 3

CH

2 (2,6-Cl 2 Ph) H

CH

3

CH

3 H H CM 3 Q-3

H

CH

3

CH

3

CH

3

CH

3

CM

3

CH

2 (Ph)

H

CH

3

CH

3

CH

3

CH

3

CH

3

CH

2 (2-FPh)

H

CH

3

CH

3

CH

3

CH

3

CH

3

CH

2 (2-(CM 3 )Ph) H

CH

3

CM

3

CM

3

CH

3

CH

3

CH

2 (2,6-Cl 2 Ph) H

CH

3

CH

3

CH

3

CM

3

CH

3 Q-3

H

CH

2

CH

3

CH

2

CH

3 H H CH 3

CH

2 (Ph)

H

CH

2

CH

3

CH

2

CH

3 H H CH 3

CH

2 (2-FPh)

H

CH

2

CH

3

CH

2

CH

3 H H CM 3

CM

2 C2-(CH 3 )Ph) H

CH

2

CH

3

CH

2

CH

3 H H CM 3

CH

2 (2,6-Ca 2 Ph)

H

CH

2

CH

3

CH

2

CM

3 H H CM 3 Q-3

H

CH

2

CH

3

CH

2

CH

3

CH

3

CH

3

CM

3

CM

2 (Ph)

H

CH

2

CH

3

CM

2

CH

3

CM

3

CM

3

CH

3

CH

2 (2-FPh)

H

CH

2

CH

3

CH

2

CH

3

CM

3

CH

3

CH

3

CH

2 (2-(CH 3 )Ph)

H

CH

2

CH

3

CH

2

CH

3

CH

3

CH

3

CM

3

CH

2 (2,6-Ca 2 Ph) H

CH

2

CH

3

CH

2

CH

3

CM

3

CM

3

CM

3 Q-3 H CH 3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (Ph)

H

H CM 3

CH

2

CH

3

CH

2

CH

3

CM

3

CH

2 (2-FPh)

H

H CM 3

CH

2

CM

3

CH

2

CH

3

CM

3

CH

2 (2-(CH 3 )Ph)

H

H CH 3

CM

2

CH

3

CH

2

CH

3

CM

3

CH

2 (2,6-Cl 2 Ph)

H

H CM 3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-3

H

WO 91/03464PllS9/45 PCT/US90t'04953 R I R 2

R

CH

2

CM

2

CH

3

CM

2

CH

2

CM

3

CH

2

CH

2

CH

3

CH

2

CH

2

CH,

CH

2 CH(C 3 )~2

CH

2

CH(CH

3 )2

CH

2

CH(CH

3 2

CH

2

CM(CH

3 )2

CH

2

CH(CM

3 2

CM

2

CM

3

CM

2

CM

3

CH

2

CH

3

CM

2

CH

3

CM

2

CM

3 CM

CM

2

CH=CH

2

CH=CH

2

CH=CH

2

CM=CH

2

CH

3

CM

3

CM

3

CM

3

CM

3

CM

3

CH

3

CM

3 CH3

CH

3 CM 2

CM

2 CH 3

CM

2

CH

2

CH

3

CM

2

CM

2

CM

3

CM

2

CH

2

CM

3

CH

2

CM

2

CH

3

CH

2

CH(CH

3 )2

CH

2

CH(CM

3 )2

CM

2

CH(CM

3 )2

CH

2

CH(CH

3 )2

CH

2

CH(CH

3 )2

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CH

2

CM

3

CM

2

CM

3 CM =CM 2

CH=CH

2 C CM 2

CH=CH

2

CH=CH

2

CM

2

CM

2

CM

3

CM

2

CM

2

CM

3

CM

2 CM2 CM 3

CM

2

CM

2 C C 3

CM

2

CM

2

CM

3

CM

2

CM

2

CM

2

C

3

CM

2

C

2

CM

2

CM

3

CM

2

CM

2

CM

2 CM 3

CM

2

CM

2 C C 2

CM

3

CM

2

CM

2

CM

2

CM

3

CH

2 2 Ph)

CH

2 2 Ph)

CM

2 (4-FPh)

CH

2 (3-FPh)

CH

2 (3-C1 Ph)

CH

2 5-(F) 2 Ph)

CH

2 C2,4-(F) 2 Ph)

CH

2 (4-FPh)

CM

2 (3-FPh)

CM

2 3-CIPh)

CH

2 2 Ph)

CM

2 C2,4-(F) 2 Ph)

CM

2 (4-FPh)

CH

2 (3-FPh)

CM

2 (C3-.CJPh)

CH

2 5-(F) 2 Ph)

CH

2 2 Ph)

CM

2 (4-FPh)

CM

2 3-FPh)

CM

2 (C3-CIPh)

CM

2 5-(F 2 Ph)

CH

2 2 Ph)

CH

2 (4-FPh)

CH

2 3-FPh)

CM

2 (C3-CIPh)

CM

2 5-(F 2 Ph)

CH

2 2 Ph)

CH

2 (4-FPh)

CH

2 (3-FPh)

CM

2 (3-CIPh) PC'F/US90/04953 WO 91/03464 p-iU9/45 R1 2 E3 H H CH 3 H H CH 3 H H CH 3 H H CH 3 H H CH 3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CM

3

CH

2 2 Ph) H

CM

3

CH

2 2 Ph) H

CH

3

CH

2 (4-FPh) H

CH

3

CH

2 (3-FPh) H

CM

3

CH

2 (3-ClPh) H WO 9 1/03464 PCT/ 1S90/04953 TABLE 2 RI 0

Y

p 2

II

X and Y are C(R 3

)(R

4 )0R 5 (unless specified) Hl H2 CH 2 CH 4 HCH CH 3 Rl R H(-h

H

H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-clPh)

H

H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-CrPh)

H

H H CH 2

CH

3

CH

2

CH

3 CH3 CH 2 (2-(CH 3 Ph) H H H CH 2

CH

3

CH

2 CH3 CH 3

CH

2 (2-(0CH 3 )Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(CF 3 )Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(OCF 3 )Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(SCF 3 )Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2,6-(cl) 2 Ph) H H H4 CH 2

CH

3

CH

2

CH

3 CH3 CH 2 (2,-yridyl)

H

H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-puriy.)

H

H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-traofuran

H

H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-tetrahydropyran)

H

H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-teiopheyrp) an H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-tioazoyl)

H

H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-pyraznyl)

H

H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2pyrz) yl H WO 91/03464 PTU9/45 PCT/US90/04953 81 1 2 R3=R R9=10

H

H

H

H

H

H

B

H

H

H

H

H

H

H

H

H

H

H

H

H

CH

2

CM

3

CH

2

CM

3

CM

2

CH

3

CM

2 H C 3

CM

2

CM

3

CM

2

CH

3

CH

2

CH

3 CH 2

CH

3 CH 2

CH

3

CM

2

CM

3

CH

2

CH

3

CM

2

CM

3

CH

2

CH

3

CH

2 CH 3

CM

2 C C 3

CH

2

CH

3

CH

2 CH 3

CH

2

CH

3 CH 2

CM

3

CH

2

CH

3

CH

2

CM

3

CM

2 C C 3

CM

2

CH

3

CH

2

CH

3

CH

2

CM

3

CH

2

CM

3

CM

2

CH

3

CM

2

CM

3

CH

2

CH

3

CH

2

CM

3

CH

2

CH

3

CH

2

CH

3

CM

2

CM

3

CM

2

CM

3

CM

2 C C 3

CM

2

CM

3

CM

2

CH

3

CM

2 C C 3

CM

2

CM

3

CM

2 C C 3

CH

2

CM

3

CH

2

CM

3

CM

2 C C 3

CM

2

CM

3

CM

2

CM

3

CM

2 C C 3 CM 2

CM

3

CM

2

CM

3

CM

2 C C 3

CM

2

CM

3

CM

2

CM

3

CM

2 C C 3

CM

2

CM

3

CM

2 C C 3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CH

2

CM

CM

3

CM

3

CM

3 CM 3

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2 H C 3

CM

2

CM

3

CM

2

CM

3

CM

2 H C 3

CM

2

CM

3 CM 2 C C 3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2 CM 3

CHM

2 CM =CH 2

CM

2

CH=CH

2

CM

2

CH=CH

2

CH

2

CM=CH

2

CM

2

CH=CH

2

CM

2

CH=CH

2

CM

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2 CF 7H 2

CH

2 CM M 2

CM

2

CH=CH

2

CH

2

CH=CH

2 Q- 1 Q-3 Q-6 Q-7 0-15

CM

2 (2-FPh)

CM

2 (2-CiPh)

CM

2 (2-(CM 3 )Ph)

CM

2 6-C1 2 Ph)

CM

2 (2-CF 3 Ph)

CM

2 (2-tetrahydropy-an)

CM

2 (2-pyridyl)

CM

2 (Ph) Q-1 0-3 Q-6 Q-7

CM

2 2-FPh)

CM

2 (2-CIPh)

CM

2 (2-(CM 3 )Ph)

CM

2 6-C1 2 Ph)

CM

2 (2-CF 3 Ph)

CM

2 (2-tetrahydropyran)

CM

2 (2-pyridyl)

CH

2 (Ph) 0-1 0-3 6 Q-7 0-15 pC/US9O/04953 WO 91/03464 82 I1 R9E1 H H H H CH 3

CH

2 (2-FPh) H H H H H CH 3

CH

2 (2-ClPh) H H H H H CH 3

CH

2 (2-(CH 3 )Ph) H H H H H CH 3

CH

2 (2,6-Cl 2 Ph) H H H H H CH 3

CH

2 (2-CF 3 Ph) H H H H H CH 3

CH

2 (2-tetrahydropyran) H H H H H CH 3

CH

2 (2-pyridyl) H H H H H CH 3

CH

2 (Ph) H H H H H CH 3 Q-1 H H H H H CH 3 Q-3 H H H H H CH 3 Q-6 H H H H H CH 3 Q-7 H H H H H CH 3 Q-15 H H H CH 3

CH

3

CH

3

CH

2 (2-FPh) H H H CH 3

CH

3

CH

3

CH

2 (2-C1Ph) H H H CH 3

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) H H H CH 3

CH

3

CH

3

CH

2 (2,6-C1 2 ph) H H H CH 3

CH

3

CH

3

CH

2 (2-CF 3 Ph) H H H CH 3

CH

3

CH

3

CH

2 (2-tetrahydropyran) H H H CH 3

CH

3

CH

3

CH

2 (2-pyridyl) H H H CH 3

CH

3

CH

3

CH

2 (Ph) H H H CH 3

CH

3

CH

3 Q-1 H H H CH 3

CH

3

CH

3 Q-3 H H H CH 3

CH

3

CH

3 Q-6 H H H CH 3

CH

3

CH

3 Q-7 H H H CH 3

CH

3

CH

3 Q-15 H

CH

3 H CH 2

CH

3

CH

2

CH

3

CR

3

CH

2 (2-FPh) H

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-ClPh) H

CH

3 H CH 2

CH

3

CH

2

CH

3

CR

3

CH

2 (2-(CH 3 )Ph) H

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2,6-CI 2 Ph) H

CR

3 H CH 2

CH

3

CH

2

CH

3

CR

3

CH

2 (2-CF 3 Ph) H WO 91/03464 PTU9/45 PCr/US90/04953 83 I1 2 R3R E9=10R5 Q

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-tetrahydropyran) H

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-pyridyl) H

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (Ph) H

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3 Q-1 H

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3 Q-3 H

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3 Q-6 H

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3 Q-7 H

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3 Q-15 H

CH

2

CH

3 H CH 3

CH

3

CH

3

CH

2 (2-FPh) H

CH

2

CH

3 H CH 3

CH

3

CH

3

CH

2 (2-ClPh) H

CH

2

CH

3 H CH 3

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) H

CH

2

CH

3 H CH 3

CH

3

CH

3

CH

2 (2,6-Cl 2 Ph) H

CH

2

CH

3 H CH 3

CH

3

CH

3

CH

2 (2-CF 3 Ph) H

CH

2

CH

3 H CH 3

CH

3

CH

3

CH

2 (2-tetrabydropyran) H

CH

2

CH

3 H CH 3

CH

3

CH

3

CH

2 (2-pyridyl) H

CH

2

CH

3 H CH 3

CH

3

CH

3

CH

2 (Ph) H

CH

2

CH

3 H CH 3

CH

3

CH

3 Q-1 H

CH

2

CH

3 H CH 3

CH

3

CH

3 Q-3 H

CH

2

CH

3 H CH 3

CH

3

CH

3 0-6 H

CH

2

CH

3 H CH 3

CH

3

CH

3 0-7 H

CH

2

CH

3 H CH 3

CH

3

CH

3 0-15 H

I

WO 91/03464 PCI! US9O/04953 R1 E2 R3 =E 4 R 9

=R

10 CH 3 H H

CH

3 H H CH 3 H H

CH

3 H H

CH

3 H H

CH

3 H H CH 3 H H

CH

3 H H CH 3 H H

CH

3 H H CH 3 H H

CH

3 H H

CH

3 H H

CH

3 H CH 3

CH

3 H CH 3

CH

3 H CH 3

CH

3 H CH 3

CH

3 H CH 3

CH

3 H CH 3

CH

3 H CH 3

CH

3 H CH 3

CH

3 H CH 3

CH

3 H CH 3

CH

3 H CH 3

CH

3 H CH 3 CH 3 H CH 3 CH 3

CH

3

CH

3 CH 3

CH

3

CH

3 CH 3

CH

3

CH

3

CH

3 CH 3

CH

3

CH

3

CH

3

CH

3 Q-1 H Q-3 H Q-6 H Q-7 H Q-15 H

CH

2 (2-FPh) H

CH

2 C2-CIPh) H

CH

2 (2-(CH 3 )Ph) H

CH

2 (2,6-Cl 2 Ph) H

CH

2 (2-CF 3 Ph) H

CH

2 (2-tetrahydropyran) H

CH

2 (2-pyridvl) H

CH

2 (Ph) H Q-1 H 0-3 H 0-6 H Q-7

H

Q-15 H

CH

2 (2-FPh) H

CH

2 (2-C1Ph) H

CH

2 (2-(CH 3 )Ph) H

CH

2 (2,6-C1 2 Ph) H

CH

2 (2-CF 3 Ph) H

CH

2 (2-tetrahydropyran) H

CH

2 (2-pyridyl) H

CH

2 (Ph) H Q-1

H

Q-3

H

Q-6

H

Q-7

H

Q-15

H

PCT/US90/04953 WO 91/03464 PTU9/45 R~ 1 2 R3=R4 R9=E

CH

3

CM

3

CM

3

CH

3

CM

3

CH

3

CM

3

CH

3

CM

3

CH

3

CH

3

CM

3

CH

3

CH

3

CH

3

CH

3

CH

3

CM

3 CH 3

CH

3

CM

3

CH

3

CH

3

CHM

3

CH

3 H M

CM

3 H H

CH

3 H H

CH

3 H H

CM

3 H H

CH

3 H H

CM

3 H H

CM

3 H H

CM

3 H H

CM

3 H H

CM

3 H H

CM

3 H H

CM

3 H H

CM

3 H H

CHM

3 H H

CM

3 H H

CM

3 H H

CM

3 H H

CM

3 H H

CM

3 H H

CM

3 H H

CM

3 H H

CH

2 (2-FPh) H

CH

2 C2-C1Ph) H

CM

2

(CH

3 )Ph) H

CH

2 (2,6-Cl 2 Ph) H

CH

2 (2-CF 3 Ph) H

CH

2 (2-tetrahydropyran) H

CH

2 (2-pyridyl) H

CH

2 (Ph) H Q-1 H 3H Q-6 11 Q-7 H Q-15 H

CH

2 (2-FPh) H

CM

2 (2-CIPh) H

CH

2 3 )Ph) H

CH

2 (2,6-Cl 2 Ph) H

CH

2 (2-CF 3 Ph) H

CH

2 (2-tetrahydropyran) H

CH

2 (2-pyridyl) H

CH

2 (Ph) H

CM

2

CM

3

CM

2 C C 3

CM

2

CM

3

CH

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CH

2 2-FPh)

CH

2 (2-CIPh)

CH

2 (2-(CH 3 )Ph)

CH

2 (2,6-CI 2 Ph)

CM

2 (2-CF 3 Ph) WO 91/03464 PCFIUS9O/04953 86 £1R 2 E3. 4 gE1 R 5 Qx

CH

3 H H CH 2

CH

3

CH

3

CH

2 (2-tetrahiydropyran) H

CH

3 H H CH 2

CH

3

CH

3

CH

2 (2-pyridyl) H

CH

3 H H CH 2

CH

3

CH

3

CH

2 (Ph) H

CH

3 H CH 3 H CH 3 Q-1 H

CH

3 H CH 3 H CH 3 Q-3 H

CH

3 H CH 3 H CH 3 Q-6 H

CH

3 H CH 3 H CH 3 Q-7 H

CH

3 H CH 3 H CH 3 Q-15 H

CH

3 H CH 3 H CH 3

CH

2 (2-FPh) H

CH

3 H CH 3 H CH 3

CH

2 (2-CIPh) H

CH

3 H CH 3 H CH 3

CH

2 (2-(CH 3 )Ph) H

CH

3 H CH 3 H CH 3

CH

2 (2,6-Cl 2 Ph) H

CH

3 H CH 3 H CH 3

CH

2 (2-CF 3 Ph) H

CH

3 H CH 3 H CH 3

CH

2 (2-tetrahydropyran) H

CH

3 H CH 3 H CH 3

CH

2 (2-pyridyl) H

CH

3 H C 3

HC

3

C

2 (Ph) H El E2 R 3 =0 4 R9=-1O R5 Q

CH

3 H CH 2

CH

3 H CH 2

CH

3

CH

2 (2Fh

CH

3 H CH 2

CH

3 H CH 2

CH

3

CH

2 (2-ClPh) H

CH

3 H CH 2

CH

3

HCH

2

CH

3

CH

2 (2-(CH 3 )Ph)H

CH

3 H CH 2

CH

3 H CH CH 3 CH 2 Ph

CH

3 H CH 2

CH

3 H CH 2

CH

3

CH

2 (2-CF 3 Ph) H

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-tetrahydropyran) H

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-pyridyl) H

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (Ph) 1

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3 Q-1 H

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3 Q-3 H

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3 0-6 H

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3 Q-7 H

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3 Q-15 H WO091/03464 PcT/US90/ 04953 87 El BH H CH 3 4 H Rg=E 10(-Fh

CH

2

CH

3 H CH 3

CH

3

CH

3 Cl1 2 (2-F1Ph) H

CH

2

CH

3 H CH 3 CH3 CH 3

CH

2 (2-(CH 3 Ph) H

CH

2

CH

3 H CH 3

CH

3

CH

3

CH

2 (2-CH3Ph) H

CH

2

CH

3 H CH 3

CH

3

CH

3

CH

2 (2,-C 3 Ph) H

CH

2

CH

3 H CH 3

CH

3

CH

3

CH

2 (2-tetrhydoyr H

CH

2

CH

3 H CH 3

CH

3

CH

3

CH

2 (2-terady) ra H

CH

2

CH

3 H CH 3

CH

3

CH

3

CH

2 (2ph) iyl H

CH

2

CH

3 H CH 3

CH

3 CH3 CH-1 h H

CH

2

CH

3 H CH 3

CH

3

CH

3 Q-1 H

CH

2

CH

3 H CH 3

CH

3

CH

3 Q-3 H

CH

2

CH

3 H1 CH 3

CH

3

CH

3 Q-7 H

£H

2

CH

3 H CH 3

CH

3 CH Q-15 H C 3 H HC 3

H

CCH

3 H H H CH 3 Q-35 H

CH

3 H H H1 CH 3 Q-6 H

CH

3 H H H CH 3 Q-3 H

CH

3 H H H CH 3 Q-16 H

CH

3 H3 H H CH 3 QH-7~ h H

CH

3 H H H CH 3 QH- Ph H

CH

3 H H H CH 3

CH

2 (2-(CFPh) H

CH

3 H H H CH 3

CH

2 (2,-C1Ph) H

CH

3 H H H CH 3 CHZ(2-(C 3 Ph) H

CH

3 H H H,1 CH 3

CH

2 (2,-etrahdoyr H

CH

3 H H H CH 3

CH

2 (2-CFPyrd) H H3 H H H H C22ttabdoy n) H

CH

3 H HHCH 3

CH

2 (2ph) dy)

CH

3 H H H CH 3 0-1Ph H

CH

3 H CH 3

CH

3

CH

3 0-1 H

CH

3 H CH 3

CH

3

CH

3 0-3 H

CH

3 H CH 3

CH

3

CH

3 Q-7 H

CH

3 H CH 3

CH

3

CH

3 0-75 H WO 91/03464 PT '9/45 PCT/US90/04953 88 F1 2 R3=E4 F9R1

CR

3 H CR 3

CH

3

CR

3

CH

2 (2-FPh) H

CH

3 H CH 3

CH

3

CH

3

CH

2 (2-CIPh) H

CR

3 H CH 3

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) H

CR

3 H CH 3

CH

3

CH

3

CH

2 (2,6-Cl 2 Ph) H

CH

3 H CH 3

CH

3

CH

3

CH

2 (2-CF 3 Ph) H

CH

3 H CR 3

CR

3

CR

3

CH

2 (2-tetrahydropyran) H

CR

3 H CR 3

CR

3

CR

3

CH

2 (2-pyridy.) H

CR

3 H CR 3

CR

3

CR

3

CH

2 (Ph) H

CR

3

CR

3

CR

3

CR

3

CR

3 Q-1 H

CR

3

CH

3

CR

3

CR

3

CR

3 Q-3 H

CH

3

CR

3

CR

3

CH

3

CH

3 Q-6 H

CR

3

CR

3

CH

3

CR

3

CR

3 Q-7 H

CR

3

CR

3

CR

3

CR

3

CR

3 Q-15 H

CR

3

CR

3

CR

3

CR

3

CR

3

CH

2 (2-FPh) H

CR

3

CR

3

CR

3

CR

3

CR

3

CH

2 (2-C.Ph) H

CR

3

CR

3

CR

3

CR

3

CR

3

CH

2 (2-(CH 3 )Ph) H

CR

3

CR

3

CR

3

CR

3

CR

3

CH

2 (2,6-C1 2 Ph) H

CR

3

CR

3

CR

3

CR

3

CR

3

CH

2 (2-CF 3 Ph) H

CR

3

CR

3

CR

3

CR

3

CR

3

CH

2 (2-tetrahydropyran) R

CR

3

CR

3

CR

3

CR

3

CR

3

CH

2 (2-pyridyl) H

CR

3

CR

3

C

3

C

3

C

3

C

2 (Ph) R

CR

3 H R CH 3

CR

3 Q-1 H

CR

3 H R CR 3

CR

3 Q-3 H

CR

3

CR

3

CR

3 Q-6 H

CR

3 H HCH 3

CH

3 Q-7 H

CR

3 H H CR 3

CR

3 Q-15 H

CR

3 H H CH 3

CR

3

CH

2 (2-FPh) H

CR

3 H H CR 3

CR

3

CH

2 (2-CIPh) H

CR

3 H H CR 3

CR

3

CH

2 (2-(CH 3 )Ph) H

CR

3 H H CR 3

CR

3

CH

2 (2,6-Cl 2 Ph) H

CR

3 H H CR 3

CR

3

CH

2 (2-CF 3 Ph) H WO 91/03464 pun US9O/04953 1 2 R3=4 R=l

CH

3 H H CH 3

CH

3

CH

2 (2-tetrahydropyral)

H

CH

3 H H CH 3

CH

3

CH

2 (2-pyridyl)

H

CH

3 H H CH 3

CH

3

CH

2 (Ph)

H

CH

3 H H CH 2

CH

3

CH

3 Q-1

H

CH

3 H H CH 2

CH

3

CH

3 Q-3

H

CH

3 H H CH 2

CH

3

CH

3 Q-6

H

CH

3 H H CH 2

CH

3

CH

3 Q-7

H

CH

3 H H CH 2

CH

3

CH

3 Q-15

H

CH

3 H H CH 2

CH

3

CH

3

CH

2 (2-FPh) H

CH

3 H H CH 2

CH

3

CH

3

CH

2 (2-ClPh) H

CH

3 H H CH 2

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) H

CH

3 H H CH 2

CH

3

CH

3

CH

2 (2,6-Cl 2 Ph) H

CH

3 H H CH 2

CH

3

CH

3

CH

2 (2-CF 3 Ph) H

CH

3 H H CH 2

CH

3

CH

3

CH

2 (2-tetrahydropyran) H

CH

3 H H CH 2

CH

3

CH

3

CH

2 (2-pyridyl) H

CH

3 H H CH 2

CH

3

CH

3

CH

2 (Ph) H

CH

3 H CH 3 H CH 3 Q-1

H

CH

3 H CH 3 H CH 3 Q-3 H

CH

3 H CH 3 H CH 3 Q-6

H

CH

3 H CH 3 H CH 3 Q-7

H

CH

3 H CH 3 H CH 3 Q-15 H

CH

3 H CH 3 H CH 3

CH

2 (2-FPh) H

CH

3 H CH 3 H CH 3

CH

2 (2-C1Ph) H

CH

3 H CH 3 H CH 3

CH

2 (2-(CH 3 )Ph) H

CH

3 H CH 3 H CH 3

CH

2 (2,6-Cl 2 Ph) H

CH

3 H CH 3 H CH 3

CH

2 (2-CF 3 Ph) H

CH

3 H CH 3 H CH 3

CH

2 (2-tetrahydropyran) H CH H3 HC3CH(-yrdl

CH

3 H CH 3 H CH 3

CH

2 (-Pyriyl H WO 91/03464 PCI! US9O/04953 x y 0 r \p 10

RI

X and Y are C(R 3

)(R

4 )0R 5 (unless specified) E1 2 R3=4 E9.RlO R5 Q H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-FPh) H H H CH 2

CH

3

CH

2

CH

3

CM

3

CH

2 (2-CIPh) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-BrPh) H H HCH 3 CH CH 3

CH

3 CH (2-(CH 3 )Ph) H H H CH 2

C

3 CCH C 3 CH(-0H))H H H CH 2

CH

3

CH

2

CM

3

CH

3

CH

2 (2-(C)CH)Ph) H H H CH 2

CH

3

CH

2

CH

3

CM

3

CH

2 (2-(CF)Ph) H H H C 2

CH

3

H

2

CH

3

CH

3 C(2-(CF )Ph)H H H CH 2

CH

3

CH

2

CH

3

C

3

CH

2 3

))H

H H CH 2

CH

3

CH

2

CH

3

CM

3

CH

2 (2-(F3)Ph) H H H CH 2

CH

3

CH

2

CH

3

CM

3

CH

2 (2-(CH) 2 Ph) H H H CH 2

CH

3

CH

2

CH

3

CM

3

CH

2 (2,-yridyl) H H H H 2 CH CHCH 3

CH

3 CH Phfray )H H H CH 2

CH

3

CH

2

CH

3

C

3

C

2 (2,-eraydopra) H H CH 2

CH

3

CH

2

CH

3

CM

3

CH

2 (2-thipdyl) H H HCH 3 CH CH 3

CH

3 CH (2-isoayl) H H H CH CH 3 CH CH 3

CH

3 CH(-yrzy)H H H CH 2

CH

3

CH

2

CH

3

CM

3

CH

2 (P-h ohnl H H H CH 2

CH

3

CH

2

CH

3

CM

3 Q-1 H H H CH 2

CH

3

CH

2

CH

3

CM

3 Q-3 H WO 91/03464 WO 9103464PCT/US90/04953 91 E1 2 R3=4 R9=B1

CHM

2

CH

3

CH

2

CM

3

CH

2

CM

3

CH

2

CH

3

CM

2

CM

3

CM

2

CM

3

CM

2

CH

3

CM

2

CH

3

CM

2

CM

3

CM

2

CH

3

CH

2

CH

3

CM

2

CH

3

CM

2

CM

3

CH

2

CH

3

CM

2

CM

3

CH

2

CM

3

CH

2

CH

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CH

2 C C 3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CH

2

CH

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2 CM 3

CM

2

CM

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2 C C 3

CM

2

CM

3

CM

2

CM

3

CM

2 C C 3 CM 2 CM 3

CM

2

CM

3

CM

2 C C 3

CM

2 C C 3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2 C C 3

CM

2 C C 3

CM

2

CM

3

CM

3

CM

3

CM

3

CM

2

CM

3

CM

2

CM

3 CM,

CM

3

CM

2

CM

3

CM

2

CHM

3

CM

2

CM

3

CM

2 C C 3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2 C C 3

CM

2

CM

3

CM

2 CH=CH 2

CM

2 CM=CM 2

CM

2 CH=CH 2

CH

2

CH=CH

2

CH

2 CH=CH 2

CM

2

CH=CH

2

CM

2 CH=CH 2

CH

2

CH=CH

2

CM

2

CH=CH

2

CM

2 CH=CH 2

CH

2 CH=CH 2

CH

2 CH=CH 2

CM

2

CH=CH

2 0-6 0-7

CM

2 2 -FPh)

CH

2 (2-CIPh)

CM

2 (2-(CH 3 )Ph)

CM

2 6-C1 2 Ph)

CM

2 (2-CF 3 Ph)

CM

2 (2-tetrabhydropyran)

CM

2 (2-pyridyl)

CM

2 (Ph) Q-1 Q-3 Q-6 Q-7

CM

2 (2-FPh)

CH

2 (2-CIPh)

CM

2 (2-(CM 3 )Ph)

CH

2 2, 6-Cl 2 Ph)

CH

2 (2-CF 3 Ph)

CM

2 (2-tetrahydropyran)

CM

2 (2-pyridyl)

CH

2 (Ph) Q-1 0-3 Q-6 Q-7 WO 91/03464 PCT/US9O/04953 92 Ri R 2 R R4 E= n 9 1 0 R5 Q YX H H H H CH 3

CH

2 (2-FPh) H H H H H CH 3

CH

2 (2-C1Ph) H H H H H CH 3

CH

2 (2-(CH 3 )Ph) H H H H H CH 3

CH

2 (2,6-Cl 2 Ph) H H H H H CH 3

CH

2 (2-CF 3 Ph) H H H H H CH 3

CH

2 (2-tetrahydropyran) H H H H H CH 3

CH

2 (2-pyridyl) H H H H H CH 3

CH

2 (Ph) H H H H H CH 3 Q-1 H H H H H CH 3 -Q-3 H H H H H CH 3 Q-6 H H H H H CH 3 Q-7 H H H H H CH 3 Q-15 H H H CH 3

CH

3

CH

3

CH

2 (2-FPh) H H H CH 3

CH

3

CH

3 CH (2-ClPh) H H H C 3

H

3

C

3

C

2 (2(H)h H H CH 3

CH

3

CH

3

CH

2 (2-CH3Ph) H H H CH 3

CH

3

CH

3 CH (2,-C 3 Ph) H H H C 3

C

3

C

3 C2-ttayrprn H H H CH 3

CH

3

CH

3 CH (2-CFPhrd) H H C 3

C

3

C

3

C

2 (h H H H CH 3

CH

3

CH

3 0CH H H C 3

C

3

C

3 2(-e-3hdoprn

H

H H CH 3

CH

3

CH

3 0-62pyidl H H H CH 3

CH

3

CH

3 0-7Ph H H H CH 3

CH

3

CH

3 0-15 H H H CHCH CHCH CH 3 QH-3~ H H H CH 2 3

CH

2 3

CH

3 QH-6 1h H H H CHCH CH 2 H CH 3 QH-7 C 3

H

CH

3 H CH CH~ CH CH 3

CH

3

CH(,-CP)H

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-CF 3 Ph) H WO 91/03464 PCT/ US9O/04953 93 R E3=R4 Rg=E1O R5 Q x

CH

3 H CH 2

CH

3

CH

2

CM

3

CM

3

CH

2 (2-tetrahydropyran) H

CM

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-pyridyl) H

CM

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (Ph) H

CM

3 H CH 2

CH

3

CH

2

CH

3

CH

3 Q-1 H

CH

3 H CH 2

CH

3

CM

2

CH

3

CH

3 Q-3 H

CM

3 H CH 2

CH

3

CH

2

CH

3

CM

3 Q-6 H

CM

3 H CH 2

CH

3

CH

2

CH

3

CM

3 Q-7 H

CM

3 H CH 2 CH3 CH 2

CH

3

CM

3 Q-15 H

CH

2

CH

3 H CH 2

CH

3

CH

2

CM

3

CM

3

CM

2 (2-FPh) H

CH

2

CH

3 H CM 2

CM

3

CH

2

CH

3

CM

3

CH

2 (2-ClPh) H

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3

CM

3

CH

2 (2-(CH 3 )Ph) H

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3

CM

3

CH

2 (2,6-C1 2 Ph) H

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3

CM

3

CM

2 (2-CF 3 Ph) H

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3

CM

3

CH

2 (2-tetrahydropyran) H

CH

2

CH

3 H CH 2

CH

3

CM

2

CH

3

CM

3

CM

2 (2-pyridyl) H

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3

CM

3

CH

2 (Ph) H

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3

CM

3 Q-1 H CH CH 3 H CH CH 3 CH CH 3

CM

3 Q-3 H

C

2

CH

3

C

2

C

3

C

2

CH

3

C

3 0-H

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3

CM

3 Q-6 H

I.CH

2

CH

3 H CH 2

CH

3

CM

2

CH

3

CM

3 Q-75 H CH2H CH CH 2

CH

3

CH

2

CH

3

CM

3 QM-1 h H H CM 3

CHCH

3 CH CH 3

CM

3

CH

2 (-1h

HCM

3

CH

2

M

3

C

2

CH

3

C

3

C

2 (2-(CFPh) H H CM 3

CM

2

CH

3 CH CH 3

CM

3 CH(26CP)H H M 3

CHC

3

C

2

CH

3

C

3

C

2 (2-CF 3 Ph) H H CM 3

CH

2

CH

3

CH

2

CH

3

CM

3

CH

2 (2-(Cetrahdoyr H H CH 3

CH

2

CH

3 CH CH 3

CM

3 CH Phyrdy) H H CM 3

CH

2

CH

3 CH CH CH 3

CH

2 Ph) H H CM 3

CH

2

CM

3

CH

2

CH

3

CM

3 0-1Ph H H CM 3

CH

2

CH

3

CH

2

CH

3

CM

3 0-3 H WO 91/03464PC/U9/95 PCr/US90/04953 94 1 R2 R 3

=F

4 RqF1 H CH 3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-6 H H CH 3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-7 H H CH 3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-15 H H H CH 3 H CH 3

CH

2 (2-FPh) H H H CH 3 H CH 3

CH

2 (2-ClPh) H H H CH 3 H CH 3

CH

2 (2-(CH 3 )Ph) H H H CH 3 H CH 3

CH

2 (2,6-C1 2 Ph) H H H CH 3 H CH 3

CH

2 (2-CF 3 Ph) H H H CH 3 H CH 3

CH

2 (2-tetrahydropyran) H H H CH 3 H CH 3

CH

2 (2-pyridyl) H H H CH 3 H CH 3

CH

2 (Ph) H H H CH 3 H CH 3 Q-1 H H H CH 3 H CH 3 0-3 H H H CH 3 H CH 3 0-6 H H H CH 3 H CH 3 Q-7 H H H CH 3 H CH 3 0-15 H

CH

3 H H CH 3

CH

3

CH

2 (2-FPh) H

CH

3 H H CH 3

CH

3

CH

2 (2-ClPh) H

CH

3 H H CH 3

CH

3

CH

2 (2-(CH 3 )Ph) H

CH

3 H H CH 3

CH

3

CH

2 (2,6-C1 2 ph) H

CH

3 H H CH 3

CH

3

CH

2 (2-CF 3 Ph) H

CH

3 H H CH 3

CH

3

CH

2 (2-tetrahydropyran) H

CH

3 H H CH 3

CH

3

CH

2 (2-pyridyl) H

CH

3 H H CH 3

CH

3

CH

2 (Ph) H

CH

3 H H CH 3

CH

3 0-1 H Cl 3 H H CH 3

CH

3 0-3 H Cl 3 H H Cl 3

CH

3 0-6 H

CH

3 H H Cl 3

CH

3 Q-7 H

CH

3 H H CH 3

CH

3 Q-15 H WO 91/03464 PCT/ US90/04953 El R2 R 3 =E 4 E£9E1O

CH

3 H H H CH 3

CH

2 (2-FPh) H

CH

3 H H H CH 3

CH

2 (2-CIPh) H CH3 H H H CH 3

CH

2 (2-(CH 3 )Ph) H

CH

3 H H H CH 3

CH

2 (2,6-C1 2 Ph) H

CH

3 H H H CH 3

CH

2 (2-CF 3 Ph) H

CH

3 H H H CH 3

CH

2 (2-tetrahydropyran) H

CH

3 H H H CH 3

CH

2 (2-pyridyl) H

CH

3 H H H CH 3

CH

2 (Ph) H

CH

3 H H H CH 3 Q-i H

CH

3 H H H CH 3 Q-3 H

CH

3 H H H CH 3 Q-6 H

CH

3 H H H CH 3 Q-7 H

CH

3 H H H CH 3 Q-15 H

CH

3 H CH 3

CH

3

CH

3

CH

2 (2-FPh) H

CH

3 H CH 3

CH

3

CH

3

CH

2 (2-CIPh) H

CH

3 H CH 3

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) H

CH

3 H CH 3

CH

3

CH

3

CH

2 (2,6-Cl 2 Ph) H

CH

3 H CH 3

CH

3

CH

3 C.i 2 (2-CF 3 Ph) H

CH

3 H CH 3

CH

3

CH

3

CH

2 (2-tetrabhydropyran) H

CH

3 H CH 3

CH

3

CH

3

CH

2 (2-pyridyl) H

CH

3 H CH 3

CH

3

CH

3

CH

2 (Ph) H

CH

3 H CH 3

CH

3

CH

3 Q-1 H

CH

3 H CH 3

CH

3

CH

3 Q-3 H

CH

3 H CH 3

CH

3

CH

3 Q-6 H

CH

3 H CH 3

CH

3

CH

3 Q-7 H

CH

3 H CH 3

CH

3

CH

3 Q-15 H E1 R£2 E 3=E 4 R=Rl 10 H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-FPh) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-ClPh) H

A

WO 91/03464 P7U9/45 PCT/US90/04953 96 I1 2 R3=R4 E9R1 H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-BrPh) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(OCH 3 )Ph) H H C 2

C

3 CH CH 3

CH

3 CH (2-(CN)Ph) H H H CH 2

CH

3

CHC

3

C

3 C(-(F)hH H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(CF 3 )Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(SCF 3 )Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2

H

H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2,6-(C1) 2 Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2,-yridyl) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-furinyl) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-traofuran H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-tetrahydropyran) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-thiopheyrp) a H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-tioazoyl) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-isyrazoyl) H H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2pyrz)yl H H HCH 3 CH CH

C

H CH (Ph) H H H CH 2

C

3 CCH CH 3H H H CH 2

CH

3

CH

2

CH

3

CH

3 Q-6 H H H CH CH 3 CH CH 3 CH Q-3 H H H CH 2

CH

3

CH

2

CH

3

CH

3 Q-65 H H HCH 3 CH CH 3 CHCH QH-~ h H H H CH 2 CH HC 3

C

2 H H(-1h H H CH 2

CH

3

CH

2

CH

3

CH

2 3 QH- 3 )h H H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2-Ph) H H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2-CF 3 Ph) H H H CHCH CHCH C 2

C

3

C

2 )Prh)doyrn H H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2-pyrdy) H H CH 2 3 2 3 232(CH 3 CH CH 3 CH CH 3 CH 2 P Ph H H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3 0-12CFPh H H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3 Q-3 H b6.- PCr/US90/04953 WO 91/03464 PTU9/45 E I R2 F 3 =4 R 9

=R

1 0

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

CH

2 CH 3

CH

2

CH

3 CH 2

CH

3

CH

2

CH

3

CH

2

CM

3

CH

2 CH 3

CM

2

CH

3

CH

2

CM

3

CH

2

CH

3

CH

2

CH

3

CH

2

CM

3

CH

2

CM

3

CH

2

CM

3

CH

2

CH

3

CM

2

CH

3

CH

2

CH

3

H

H

H

H

H

H

H

H

H

H

H

H

H

CHM

2

CH

3

CM

2

CM

3 CH 2

CM

3

CH

2

CH

3

CM

2

CH

3

CH

2

CH

3 CMi 2

CH

3

CH

2

CM

3

CH

2

CH

3

CH

2 CH3

CH

2

CM

3

CH

2

CH

3

CH

2

CM

3

CH

2

CH

3

CH

2 H3

CH

2

CM

3

H

H

H

H

H

H

H

H

H

H

H

H

H

CH

2 H3

CH

2

CH

3

CH

2

CM

3

CH

2 cH=CM 2

CM

2

CH=CH

2

CH

2

CH=CH

2

CH

2 cH=CH 2

CH

2

CH=CH

2

CM

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2 cB 2

CH=CH

2

CM

2 CM CH 2

CH

2

CM=CH

2

CM

2 CM CH 2

CH

2

CH=CH

2 C3

CH

3

CH

3 C3

CH

3

CH

3

CM

3

CM

3

CH

3 C3

CH

3

CH

3

CH

3 Q-6 Q-7 0-15

CM

2 2 -FPh)

CH

2 2-CIPh)

CM

2 (2-(CH 3 )Ph)

CH

2 6-Cl 2 Ph)

CM

2 (2-CF 3 Pb)

CH

2 2-tetrahydropyran)

CM

2 (2-pyridyl)

CH

2 (Ph) Q-1 0-3 Q-6 Q-7

CM

2 (2-FPh)

CM

2 (2-CIPh)

CH

2 (2-(CH 3 )Ph)

CH

2 (2,6-C1 2 Ph)

CH

2 (2-CF 3 Ph)

CH

2 (2-tetrahydropyran)

CM

2 (2-pyridyl)

CM

2 (Ph) Q-1 Q-3 Q-6 Q-7 PCT/US90/04953 WO 91/03464 ciU9/43 98 I1 F-2 R 3 =4 R 9=R10 H H CH 3

CH

3

CH

3

(H

2 (2-FPh) H H H CH 3

CH

3

CH

3

CH

2 (2-ClPh) H H H CH 3

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) H H H CH 3

CH

3

CH

3

CH

2 (2,6-C1 2 Ph) H H H CH 3

CH

3

CH

3

CH

2 (2-CF 3 Ph) H H H CH 3

CH

3

CH

3

CH

2 (2-tetrahydropyran) H H H CH 3

CH

3

CH

3

CH

2 (2-pyridyl) H H H CH 3

CH

3

CH

3

CH

2 (Ph) H H H CH 3

CH

3

CH

3 Q-1 H H H CH 3

CH

3 CH., Q-3 H H H CH 3

CH

3

CH

3 Q-6 H H H CH 3

CH

3

CH

3 Q-7 H H H CH 3

CH

3

CH

3 Q-15 H H H CH 3

CH

3

CH

3

CH

2 (2,4-FPh) H H H CH 3

CH

3

CH

3 CH 2 Ph) H H H C 3

CH

3

CH

3 CH 2 Ph) H H H CH 3

CH

3

CH

3

CH

2 (2-BrPh) H

CH

3 H HHCH 3 CH (2-FPh) H

CH

3 H H H CH 3

C

2 PhH

CH

3 H H H CH 3 CH (2-BrPh) H H H H2

C

3

CH

3 CH (2-(CH )Ph)

CH

3 H HHC 3

C

2 (2(C 3

)P)

HH H H HC

CH

3 H HHCH 3

C

2 (2(C )Ph)H

CH

3 H HCH 3 CH (2-(CF 3 )Ph)H

CH

3 H H H CH 3

C

2

)H

CH

3 H H H CH 3

CH

2 (2-(CF 3 )Ph) H

CH

3 H H H CH 3 CH 2 h

CH

3 H H H CH 3

CH

2 2 Ph) H

CH

3 H H H CH 3

CH

2 (2-pyridyl) H

CH

3 H H H CH 3

CH

2 (2-furanyl) H

CH

3 H H H CH 3

CH

2 (2-tetrahydrofuran) H WO 91/03464 PTU9/45 PCT/US90/04953 E 1 £R2 R R 9E 1

F

CM

3

H

CH

3

H

CH 3

H

CH

3

H

CH

3

H

CM

3

H

CH 3

H

CH

3

H

CH 3

H

CH

3

H

CH

3

H

CM

3

H

CM 3

H

CH

3

H

CH

3

H

CH

3

H

CM

3

H

CM

3

H

CM

3

H

CM

3

H

CM

3

H

CM 3

H

CM

3

H

CM

3

H

CM

3

H

CM

3

H

CM

3

H

CM

3

H

CM

3

H

CM

3

H

CH

3

H

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CPA

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3 CM 2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CM

2

CM

3

CH

2

CH=CH

2 CVr' 2

C=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2 CM 2 2-tetraLhydropyran)

CM

2 (2-thiophenyl)

CM

2 2-iSOazolyl)

CM

2 (2-pyrazinyl)

CM

2 (Ph) Q-1 Q-3 Q-6 Q-7

CH

2 (2f4-(F) 2 Ph)

CH

2 2 Ph)

CM

2 2-F, 6-CIPh)

CM

2 (2-FPh)

CM

2 (2-CIPh)

CH

2 2-(CM 3 )Ph)

CM

2 6-Cl 2 Ph) CM 2 2-CF 3 Ph)

CM

2 (2-tetrahydropyran) CM 2 (2-pyridyl)

CM

2 (Ph) Q-1 0-3 0-6 0-7 0-15

CH

2 2 Ph) C1 2 (2-FPh) CM 2 2-CIPh) CH 2 (2-(CH 3 )Ph

CH

2 (2,6-C1 2 Ph, '1 ~WO 91/03464PCIU9/45 pCr/US90/04953 R 2 3R R 9

=E

10 R

CM

3

CM

3

CM

3 CH 3

CM

3

CM

3

CM

3

CH

3 CH 3

CH

3

CH

2

CM

3

CM

2 CH 3

CHM

2 CH 3

CM

2 CH 3

CM

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CHM

3

CM

2

CM

3

CH

2

CM

3

CM

2 CH 3 CH 3 CM 3

CH

3 CH 3

CHM

3 CH 3

CH

3

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

CH

3

CH

3

CM

2

CH=CH

2

CM

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CM

2

CM

2

CH=CH

2

CM

2

CH=CH

2

CM

2

CH=CH

2

CM

2

CH=CH

2

CH

2

CH=CH

2

CM

3 C3

CM

3

CH

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3 CM 3

CH

3

CHM

3

CH

2 (2-CF 3 Ph)

CM

2 (2-tetrahydropyran)

CM

2 (2-pyridyl)

CM

2 (Ph) Q-1 Q-3 Q-6 Q-7

CM

2 2-FPh)

CM

2 (2-CIPh)

CM

2

CM

3 Ph)

CM

2 6-C1 2 Ph)

CM

2 (2-CF 3 Ph)

CM

2 (C2-tetrahydropyran)

CM

2 (C2-pyridyl)

CM

2 Ph) Q-1 Q-3 Q-6 Q-7 0-15

CH

2 2 Ph)

CH

2 (2-FPh)

CM

2 (2-ClPh)

CH

2 2-(C C 3 Ph)

CH

2 (2,6-C1 2 Ph)

CH

2 2-CF 3 Ph)

CM

2 (C2-tetrahydropyran)

CM

2 (C2-pyridyl)

CH

2 (CPh) WO 91 /03464 pr/US90/04953 101 R1 R2 R3R4 F9E1

CH

3 H CH 3

CH

3

CH

3 Q-1 H

CM

3 H CH 3

CHM

3

CM

3 Q-3 H

CM

3 H CH 3

CH

3

CM

3 0-6 H

CHM

3 H CH 3

CH

3

CM

3 Q-7 H

CH

3 H CM 3 CH 3

CM

3 Q-15 H

CM

3 H CH 2

CH

3

CH

2

CM

3

CM

3

CM

2 (2-FPh) H

CM

3 H CH 2

CH

3

CH

2

CH

3

CM

3

CM

2 (2-C1Ph) H

CM

3 H CH 2

CH

3

CH

2

CH

3

CM

3

CH

2 (2-(CH 3 )Ph) H

CM

3 H CH 2

CH

3

CH

2

CH

3

CM

3

CM

2 (2,6-C1 2 Ph) H

CM

3 H CM 3 CM 3

CM

3

CH

2 2 Ph) H

CH

3 H CM 3 CH 3

CM

3

CH

2 2 Ph) H

CM

3 H CH 2 CM 3

CHM

2

CM

3

CM

3

CM

2 (2-tetrahydropyran) H

CM

3 H CH 2

CH

3 CH 2

CM

3

CM

3

CH

2 (2-pyridyl) H

CM

3 H CH 2

CH

3

CH

2

CM

3

CM

3

CH

2 (Ph) H

CH

3 H CH 2 CH 3

CHM

2

CH

3

CM

3 Q-1 H

CM

3 H CH 2 CH 3 CH 2

CM

3

CM

3 Q-3 H

CM

3 H CM 2 CH 3

CH

2

CH

3

CM

3 Q-6 H

CM

3 H CH 2

CH

3

CHM

2

CM

3

CM

3 Q-7 H

CM

3 H CH 2 CH 3 CH 2

CH

3

CH

3 Q-15 H

CM

3 H CC 3

C

2

CM

3

C

3

C

2 2 Ph

CH

2

CM

3 H CM 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-FPh) 14 CH 2

CH

3 H CM 2

CM

3 CH 2

CH

3

CM

3

CH

2 (2-C1Ph) H

CM

2

CM

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) H

CM

2

CH

3 11 CH 2

CH

3

CH

2

CH

3

CM

3

CH

2 (2,6-C1 2 Ph) H

CH

2

CM

3 H CH 2

CH

3 CH 2

CM

3

CH

3

CH

2 (2-CF 3 Ph) H CH 2 CH 3 H CM 2

CH

3 CH 2

CH

3

CM

3

CH

2 (2-tetrahydropyran) H CH CH 3 H CH CH 3 CH CH CH 3 CH(2prd)M

CH

2

CM

3 H CH 2

CH

3 CH 2

CH

3

CM

3

CH

2 (Ph) H

CH

2

CH

3 H CH 2 CH 3 CH 2 CH 3

C!H

3 Q-3 H CH 2

CH

3 H CH 2 CH 3 CH 2 CH 3 Cil 3 0-3 H

CH

2

CH

3 H CH 2 CH 3

CHM

2 CM 3

CM

3 Q-6 H PCI-IUS90/04953 WO 91/03464 102 J.2 E 3 E9=Rl R x

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3 Q-7

H

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3 Q-15 H

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-FPh) H

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-ClPh) H

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) H CH3 CH 3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2,6-C1 2 Ph) H

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-CF 3 Ph) H

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-tetrahydropyran) H

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-pyridy.) H

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (Ph) H

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-1. H H CH 3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-3 H H CH 3

CH

2

CIJ

3

CH

2

CH

3

CH

3 Q-6 H H CH 3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-7 H CH 3

CH

2

CH

3

CA

2

CH

3

CH

3 Q-15 H

CH

3 H CH 3 H CH 3

CH'

2 (2-FPh) H

CH

3 H CH 3 H CH,~ CH 2 (2-C1Ph) H CH 3 H CH 3 H CH 3

CH

2 (2-(CH 3 )Ph) H

CH

3 H CH 3 H CH 3

CH

2 (2,6-C1 2 Ph) H

CH

3 H CH 3 H CH 3

CH

2 (2-CF 3 Ph) H

CH

3 H CH 3 H CH 3

CH

2 (2-tetrahydropyran) H

CH

3 H CH 3 H CH 3

CH

2 (2-pyridyl) H

CH

3 H CH 3 H CH 3

CH

2 (Ph) H

CH

3 H CH 3 H CH 3 Q-1. H

CH

3 H CH 3 H CH 3 Q-3 H

CH

3 H CH 3 H CH 3 Q-6 H

CH

3 H CH 3 H CH 3 Q-7 H CH.- H CH 3 H CH 3 Q-15 H

CH

3 H CH 3 H CH 3

CH

2 2 Ph) H

CH

3 H H CH 3

CH

3 Q-1 H

CH

3 H H CH 3

CH

3 Q-3 H WO 91/03464 PCI! US90104953 103 F-2 R3 =F4 Rg9R10 R5 Q x

CH

3 H H CH 3

CH

3 Q-6

H

CH

3 H H CH 3

CH

3 Q-7

H

CM

3 H H CM 3

CH

3 Q-15

H

CH

3 H H CH 3

CM

3

CH

2 (2-FPh)

H

CM

3 H H CH 3

CM

3

CH

2 (2-ClPh)

H

CH

3 H H CM 3

CM

3

CH

2 (2-(CB 3 )Ph) H

CH

3 H H CH 3

CM

3

CH

2 (2,6-Ca 2 Ph) H

CH

3 H H CH 3

CH

3

CH

2 (2-CF 3 Ph) H

CM

3 H Hi CH 3

CM

3

CH

2 (2-tetrabhydropyran) H

CH

3 H H CM 3

CH

3

CH

2 (2-pyridyl)

H

CH

3 H H CM 3

CM

3

CH

2 (Ph) H

CH

3 H H CH 3

CH

3 Q-1

H

CH

3 H H CM 3

CH

3 Q-3

H

CH

3 H H CH 3

CH

3 Q-6 H

CM

3 H H CM 3

CH

3 Q-7

H

CH

3 H H CH 3

CM

3 Q-15

H

CM

3 H H CH 2

CH

3

CM

3

CM

2 2 Ph) H

CH

3 H H CH 2

CH

3

CM

3

CH

2 (2-FPh) H

CH

3 H H CH 2

CH

3

CM

3

CH

2 (2-CIPh) H

CM

3 H H CH CH 3

CM

3 CH (2-(CH)Ph) H

CH

3 H H CM 2

CM

3

CM

3

CM

2 (2,6-C1 2 Ph) H

CH

3 H H CH 2

CH

3

CH

3

CH

2 (2-CF 3 Ph) H

CM

3 H H CH 2

CH

3

CM

3

CM

2 (2-tetrahydropyran) H

CM

3 H H CH 2

CH

3

CM

3

CH

2 (2-pyridyl) H

CH

3 H H CH 2

CH

3

CM

3

CH

2 (Ph) H

CM

3 H H CH 2

CH

3

CM

3 Q-1 H

MCM

3 H H CH 2

CH

3

CM

3 Q-3 H

CM

3 H H CM 2

CM

3

CM

3 0-6 H

CM

3 H H CH 2

CM

3 C1 3 Q-7 H

CM

3 H H CM 2

CH

3

CM

3 Q-15 H WO 91 /03464 PTU9/45 PCT/US90/04953 104 FHCH H RM R M 4M F 9=E-10hR

H

CH

2

CH

3 H CM 3 CH 3

CHM

3

CH

2 (2-C1Ph) H

CH

2 CH 3 H CM 3

CHM

3

CHM

3

CH

2 (2-(Cl 3 Ph) H

CH

2

CH

3 H CH 3 CH 3 CH 3

CH

2 (2-CH3Ph) H

CH

2 CH 3 H CM 3 CH 3 CM 3 CH 2 (2-CF 3 Ph) H

CH

2

CH

3 H CM 3 CM 3 CM 3

CHM

2 (2-tLetrahydropyran) H

CH

2

CH

3 H CM 3 CM 3 CH 3 CH 2 (2-pyridyl) H

CH

2

CH

3 H CM 3 CH 3 CH 3

CH

2 (Ph) H

CH

2 CH 3 H CM 3

CHM

3

CM

3 Q-1 H

CH

2 CH 3 H CM 3

CM

3 CM 3 Q-3 H

CH

2 CH 3 H CM 3 CM 3

CM

3 Q-6 H

CH

2 CH 3 H CM 3

CM

3 CM 3 Q-7 H

CH

2 CH 3 H CM 3

CM

3 CH 3 Q-15 H Pcr/US90/04953 WO 91/03464 PiIU9/45 X C(R 3

)(R

4 )0R 1i 2 R3 E4 CH 3

CH

2 C 3

CR

2

CH

3

CM

2

CM

3

CH

2 Cl- 3

CH

2

CM

3

CM

2

CH

3

CM

2

CH

3

CH

2

CM

3

CM

2

CH

3

CM

2

CM

3

CM

2 C 3 CM 2

CH

3

CM

2

CH

3

CH

2

CH

3

CM

2

CM

3

CM

2

CH

3

CM

2

CH

3

CH

2

CM

3

CM

2 CH 3 CH 2 CH 3

CH

3

CH

2 CHi 3 CH 3

C

2 CH 3

CHM

3

CM

2

CM

3 CH 3

C

2 CH 3 CH 3

CH

2

CHM

3

CH

3

CM

2 CM 3

CHM

3

CH

2

CHM

3

CH

3

CM

2

CM

3

CH

3

CH

2 CH 3

CH

3

CH

2

CHM

3

CH

3

CH

2

CM

3

CH

3

CH

2 CH 3

CH

3

CH

2

CM

3 CH 3

C

2

CM

3

CH

3

CM

2

CM

3

CH

3

CH

2

CM

3

CH

3

CM

2

CM

3 CH 3

C

2

CM

3

CM

2 (2-FPh)

CH

2 (2-CIPh)

CM

2 (2-BrPh)

CM

2

(CM

3 )Ph)

CM

2 (22- (0CH 3 )Ph)

CM

2 (2-(CN)Ph)

CM

2 (2-(CF 3 )Ph)

CH

2 (2-(OCF 3 )Ph)

CM

2 (2-(SCH 3 )Ph)

CH

2 6-(F) 2 ph)

CH

2 6-(C1) 2 Ph)

CM

2 (2-pyridyl)

CM

2 (2-furanyl)

CM

2 (2-tetrahydrofuran)

CM

2 (2 -tetrahydropyran)

CM

2 ('.-thiophenyl)

CM

2 2-isoxazolyl)

CH

2 2-pyraziriyl)

CM

2 (Ph)

A

WO 91/03464 WO 9103464PCT/US90/04953 106 1 R 2 3 4 CH 3

CR

2 CH 3

CR

2 CH 3

CH

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

C

3

CH

2

CHR

3 CR 2

CR

3

CR

2 CR 3

CR

2 CH 3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2 CH 2

CR

3

CR

2

CH

3

CH

2

CR

3

CR

2

CR

3

CH

2 CR 3

CH

2

CR

3

CR

2 CR 3

CR

2

CR

3

CR

2

CR

3

CR

2 CR 3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2 CH 3

CR

2

CR

3

CR

2

CR

3

CR

2 CR 3

CR

2

CR

3

CR

2

CH

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

2

CH

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

CR

2

CR

3

CH

2

CH

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

CR

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2 CH 3

CR

2 CR 3 CH 2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2 CR 3

CR

2 CR 3

CR

2

CR

3

CR

2

CR

3

CR

2 CR 3

CR

2 CR 2

CR=CH

2

CR

2

CR=CR

2

CH

2

CH=CH

2

CR

2

CR=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CR

2

CR=CH

2

CR

2

CH=CR

2

CR

2

CR=CH

2 Q-1 Q-3 Q-6 Q-7

CR

2 2-FPh)

CR

2 (2-CIPh)

CR

2 (2-(CH 3 )Ph)

CR

2 (2,6-Cl 2 Ph)

CR

2 (2-CF 3 Ph)

CR

2 (2-tetrahydropyran)

CR

2 (2-pyridyl)

CR

2 (Ph) Q-1 0-3 Q-6 Q-7

CR

2 (2-FPh)

CR

2 2-CIPh)

CR

2 (2-(CH 3 )Ph)

CR

2 2,6-C1 2 Ph)

CH

2 (2-CF 3 Ph)

CR

2 (2-tetrahydropyran)

CR

2 (2-pyridyl)

CH

2 (Ph) Q-1 Q-3 Q-6 Q-7

A

pCy/uS9O/0495 3 WO 91/03464 107 1 2 R3 R4 H H H H CH 3

CF!

2 (2-FPh) H H H H CF! 3

CH

2 (2-C1Ph) H H H H CF! 3

CH

2 (2-(CF! 3 )Ph) H H H H CF! 3

CF

2 (2,6-Cl 2 Ph) H H H H CF! 3

CH

2 (2-CF 3 Ph) H H H H CF! 3

CH

2 (2-tetrahydropyral) H H H H CF! 3

CH

2 (2-pyridyl) H H H H CF! 3

CH

2 (Ph) H H H H CF! 3 Q-1 H H H H CF! 3 Q-3 H H H H CF! 3 Q-6 F! H H H CF! 3 Q-7 H H H H CF! 3 H H CH 3

CF!

3

CF!

3

CF!

2 (2-FPh) H H CF! 3

CF!

3

CF!

3

CF!

2 (2-C1Ph) H F! CF! CF! CF! CH (-H)Ph) F! F! CF! 3

CF!

3

CF!

3

CF

2 (2,6-C1 2 Ph) F! F! CF! 3

CF!

3

CF!

3

CF!

2 (2-CF 3 Ph) H F! CF! 3

CF!

3

CF!

3

CF

2 (2-tetrahydropyran) F! H CF! 3

CF!

3

CF!

3

CF

2 (2-pyridyl) F! F! CF! 3

CF!

3

CF!

3

CF!

2 (Ph) F! F! CF! 3

CF!

3

CF!

3 Q-1 F! F! CF! 3

CF!

3

CF!

3 Q.-3 H H CF! 3

CF!

3

CF!

3 Q-6 F! H CF! 3

CF!

3

CF!

3 Q-7 F! H CF! 3

CF!

3

CF!

3 CF! CF! CH! 2 CF! CH! 2 CH CF! CH 2 (2-FPh)

CF!

3

CF!

3

CF!

2

CF!

3

CF!

2

CF!

3

CF!

3

CF!

2 (2-CIPh)

CF!

3

CF!

3

CF!

2

CH

3

CH

2

CH

3

CF!

3

CH

2 (2-(CH 3 )Ph)

CF!

3

CF!

3

CH

2

CH

3

CH

2

CF!

3

CF!

3

CH

2 (2,6-C1 2 Ph)

CF!

3

CF!

3

CH

2

CF!

3

CF!

2

CF!

3

CF!

3

CH

2 (2-CF 3 Ph) WO 91/03464 PCT/ US90/04953 108

CM

3

CM

3

CH

2

CH

3

CH

2

CM

3

CH

3

CM

2 (2-tetrahydropyran)

CH

3

CM

3

CH

2

CH

3

CH

2 CH 3

CH

3 C11 2 (2-pyridyl)

CH

3

CH

3

CM

2

CH

3

CM

2

CH

3

CH

3

CH

2 (Ph)

CHM

3

CH

3

CH

2

CH

3

CH

2

CM

3

CH

3 Q-1

CM

3

CH

3 CH 2 CH 3

CH

2

CM

3

CM

3 Q-3

CM

3

CM

3

CH

2

CH

3

CH

2

CH

3

CM

3 Q-6

CM

3 CM 3

CH

2 CM 3

CM

2

CH

3

CM

3 Q-7 CM 3

CM

3

CH

2 CM 3

CH

2

CH

3

CM

3

CH

2

CH

3

CH

2 CH 3

CH

2

CH

3

CH

2

CH

3

CM

3

CH

2 (2-FPh)

CH

2 CH 3

CM

2

CM

3

CH

2 CH 3

CH

2

CH

3

CM

3

CH

2 (2-C1Ph)

CH

2

CH

3

CH

2 CH 3

CM

2

CH

3

CM

2

CH

3

CM

3

CH

2 (2-(CH 3 )Ph)

CH

2 CH 3 CH 2

CH

3

CH

2

CM

3

CH

2 CM 3

CM

3

CH

2 (2,6-C1 2 Ph)

CH

2 CH 3

CH

2

CH

3

CH

2 CH 3

CH

2

CM

3

CM

3

CM

2 (2-CF 3 Ph)

CM

2 CH 3 CH 2

CH

3

CM

2

CM

3

CH

2

CM

3

CM

3

CM

2 (2-tetrabydropyran)

CH

2

CM

3

CHM

2

CH

3 CH 2

CH

3

CM

2 CH 3

CM

3

CM

2 (2-pyridyl)

CH

2

CH

3

CH

2

CH

3

CM

2

CM

3

CM

2 CM CM 3

CM(H

CM

2

M

3 CM CH C 2 C 3

C

2

C

3

C

3 2(P1

CM

2

CH

3

CH

2

CH

3

CM

2 CH CH CH 3

CM

3 0- CCM CMC 3

C

2

CM

3

M

2

M

3

C

3 0-6 CHM CM 2

CH

3 CH CH 3 CH CH CM 3 Q-3

CH

2

CM

3

CH

2

CH

3

CM

2

CM

3 CH CH CM 3 0-15 CM2 3 CH2 CH 2

CH

3

CH

2 CM1 3

CM

3 QH-~h CM2 3 H2 CM 2

CH

3

CM

2

CM

3

CM

3 QM- Ph CMH H CH CH 3

CM

2

CH

3

CM

3 CH (2-(CPh)

C

3 2 CMC 3

C

2 C 3 C 2 (26C 2

CM

3 H CH 2

CM

3

CM

2

CH

3

CM

3

CM

2 (2-CF 3 Ph)

CM

3 H CH CH 3 CH CH 3 CH1 CH 2 2ttayrpr

CM

3 M CM 2

CH

3

CM

2

CM

3

CM

3

CM

2 (2-pyriPh)

CM

3 M CH 2 CM 3

CM

2

CH

3

CM

3

CM

2 (Ph)

CM

3 H CM 2

CM

3

CH

2

CM

3

CM

3 0-1 PCT/US90/04953 WO 91/03464 PIIU9/45 109 1 2 F3 R4 E5 Q

CH

3 H CH 2

CH

3

CH

2 CH 3

CH

3 Q-3 CH 3 H CH 2

CH

3

CH

2 CH 3 CH 3 Q-6 CH 3 H CH 2

CH

3

CH

2

CH

3

CH

3 Q-7 CH 3 H CH 2

CH

3

CH

2

CH

3

CH

3 0-15

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-FPh)

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-ClPh)

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(CH 3 )Ph)

CH

2 CH 3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2,6 -C' 2 Ph)

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-CF 3 Ph)

CH

2

CH

3 H CH 2

CH

3

CH

2 CH 3

CH

3

CH

2 (2-tetrahydropyran)

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(pyridyl)

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3 CH 3

CH

2 (Ph)

CH

2

CH

3 H CH 2

CH

3 CH 2

CH

3 CH3 Q-1

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3 CH 3 0-3

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3 Q-6

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3 Q-7

CH

2

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

Q,,

mmmd WO 91/03464 PCT/ US9O/04953 110

R

1 j p 2

V

X C(R 3

)(R

4 )0R ~1 E2 B3=4 E9=E1 H H CH 2

CH

3

CH

2

CH

3 CH 3

CH

2 (2-FPh) H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-C1Ph) H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-BrPh) Hi H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2

(CH

3 )Ph) H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(OCH 3 )Ph) H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(CN)Ph) H H CH 2

CH

3

CH

2

CH

3

CH

3

CR

2 (2-(CF 3 )Ph) H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (Z-(0CF 3 )Ph) H H CH 2

CH

3

CH

2

CH

3

CH

3 C1 2 (2-(SCH 3 )Ph) 1H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2

(F)

2 Ph) H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2,6-(C1) 2 Ph) H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-pyridyl) H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-furanyl) H H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-tetrahydrofuran) H H CH 2

CH

3

CH

2

CH

3 CH 3

CH

2 (2-tetrahydropyran) H H CH 2

CH

3

CH

2

CH

3 CH 3

CH

2 (2-thiophenyl) H H CH 2

CH

3

CH

2

CH

3 Cl 3 C1 2 (2-isozazolyi) H H CH 2

CH

3

CH

2

CH

3 CH 3

CH

2 (2-pyrazinyl) H H CH 2

CH

3 CH 2

CH

3

CH

3

CH

2 (Ph) WO 91/03464 PCT/US90/04953 R1 F2 R3=E4 R9= 1

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CV

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3 CH 2

CH

3

C.H

2

CH

3

CH

2

CH

3 CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CM

3

CH

2

CM

CH

2

CH

3

CH

2

CH

3

CH

2

CM

3

CM

2

CH

3

CH

2

CH

3

CH

2

CM

3

CM

2

CH

3

CM

2

CH

3

CM

2

CH

3

CH

2

CH

3

CM

2

CH

3

CM

2

CM

3

CM

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CM

2

CH

3

CH

2

CH,

CH

2

CH

3

CH

2

CH

3

CH

2

CM

3

CM

3

CM

3

CH

3

CM

3

CH

3

CM

2

CM

3

CH

2

CH

3

CH

2

CH

3

CM

2

CH

3

CM

2

CM

3

CM

2

CM

3

CH

2

CH

3

CH

2

CM

3

CH

2

CM

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH=CH

2

CH

2 CM CH 2

CH

2

CH=CH

2

CM

2

CH=CH

2

CH

2 cH=CH 2

CH

2

CH=CH

2

CH

2

CH--.CH

2

CM

2

CM=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2 CH=C11 2

CH

2

CH=CH

2

CH

2

CH=CH

2 Q-1 0-3 Q-6 Q-7

CH

2 2 -FPh)

CM

2 (2-CIPh)

CH

2 (2-(CH 3 )Ph)

CH

2 (2,6-C1 2 Ph)

CH

2 (2-CF 3 Ph)

CH

2 (2-tetrahydropyran)

CH

2 (2-pyridyl)

CM

2 (Ph) Q-1 0-3 Q.-6 Q-7

CM

2 (2-FPh)

CH

2 2-CIPh)

CH

2 (2-(CH 3 )Ph)

CH

2 6-C1 2 Ph)

CH

2 (2-CF 3 Ph)

CH

2 (2-tetrahydropyran)

CH

2 (2-pyridyl)

CH

2 (Ph) Q- 1 0-3 0-6 Q-7 WO 91/03464 pun US90/04953 112 El E2 R3E4 R9E11 H H H H CH 3

CH

2 (2-FPh) H H H H CH 3

CH

2 (2-C1Ph) H H H H CH 3

CH

2 (2-(CH 3 )Ph) H H H H CH 3

CH

2 (2,6-C' 2 Ph) H H H H CH 3

CH

2 (2-CF 3 Ph) H H H H CH 3

CH

2 2-tetra~hydropyran) H H H H CH 3

CH

2 (2-pyridyl) H H H H CH 3

CH

2 (Ph) H H H H CH 3 Q-1 H 11 H H CH 3 -Q-3 H H H H CH 3 Q-6 H H H H CH 3 Q-7 H H H H CH 3 H H CH 3

CH

3

CH

3

CH

2 (2-FPh) H H CH 3

CH

3 CH 3

CH

2 (2-C1Ph) H H CH 3

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) H H CH 3

CH

3

CH

3

CH

2 (2,6-Cl 2 Ph) H H CH 3

CH

3

CH

3

CH

2 (2-CF 3 Ph) H H CH 3

CH

3

CH

3

CH

2 (2-tetrahydropyran) H H CH 3

CH

3

CH

3

CH

2 (2-pyridyl) H H CH 3

CH

3

CH

3

CH

2 (Ph) H H CH 3

CH

3

CH

3 Q-1 H H CH 3

CH

3

CH

3 Q-3 H H CH 3

CH

3 CH 3 Q-6 H H CH 3

CH

3

CH

3 Q-7 H H CH 3

CH

3

CH

3 0-15

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-FPh)

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-C1Ph)

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(CH 3 )Ph)

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2,6-C1 2 Ph)

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-CF 3 Ph) WO 91/03464 PCT/US9O/04953 113 Ri R 2 R 3 =R4 9R t Q

CM

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-tetrahydropyran)

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-pyridyl)

CM

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (Ph)

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3 Q-1

CM

3 H CH 2

CH

3

CH

2

CH

3

CH

3 Q-3

CM

3 H CH 2

CH

3

CH

2

CH

3

CH

3 Q-6

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3 0-7

CH

3 H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2

CH

3 H CM 3

CH

3

CM

3

CH

2 (2-FPh)

CH

2

CH

3 H CH 3

CM

3

CM

3

CH

2 (2-C1Ph)

CH

2

CH

3 H CH 3

CH

3

CM

3

CH

2 (2-(CH 3 )Ph)

CH

2

CH

3 H CM 3

CM

3

CM

3

CH

2 (2,6-Ca 2 Ph)

CH

2

CH

3 H CM 3

CM

3

CM

3

CH

2 (2-CF 3 Ph)

CH

2

CH

3 H CM 3

CH

3

CM

3

CH

2 (2-tetrahydropyran)

CH

2

CH

3 H CH 3

CH

3

CH

3

CH

2 (2-pyridyl)

CH

2

CH

3 H CM 3

CM

3

CM

3

CM

2 (Ph)

CH

2

CH

3 H CM 3

CM

3

CM

3 0-1

CH

2

CH

3 H CM 3

CM

3

CM

3 Q-3

CH

2

CM

3 H CM 3

CM

3

CM

3 Q-6

CH

2

CH

3 H CM 3

CM

3

CM

3 0-7

CH

2

CH

3 H CM 3

CM

3

CM

3 0-15 WO 91/03464 E 2 R 3 =R 4 =E1 PCT/ US90/04953

CH

3 H H

CH

3 H H CH 3 H H

CH

3 H H

CH

3 H H

CR

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CR

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CR

3 H CR 3

CH

3 H CH 3

CH

3 H CH 3

CR

3 H CH 3

CR

3 H CH 3

CH

3 H CH 3 CH 3 H CH 3

CR

3 H CR 3

CR

3 H CH 3

CH

3 H CH 3

CH

3 H CH 3

CH

3 H CR 3

CR

3 H CH 3 CH 3

CH

3

CH

3 CH 3

CH

3

CHR

3

CH

3

CR

3

CR

3

CH

3 CH 3

CHR

3

CR

3

CH

3

CR

3 Q-1 0-3 Q-6 Q-7

CH

2 (2-FPh)

CH

2 (2-C!Ph)

CH

2 (2-(CH 3 )Ph)

CH

2 2, 6-C1 2 Ph)

CR

2 (2-CF 3 Ph)

CH

2 2-tetrahydropyran)

CR

2 (2-pyridyl)

CH

2 (Ph) Q-1 Q-3 Q-6 Q-7 0-15

CH

2 (2-FPh)

CH

2 2-CIPh)

CR

2 (2-(CH 3 )Ph)

CR

2 6-Cl 2 Ph)

CH

2 2-CF 3 Ph)

CH

2 (2-tetrahydropyran) C11 2 (2-pyridyl)

CH

2 (Ph) Q-1 0-3 0-6 0-7 WO 91/03464 PTU9/45 PCr/US90/04953 R I E2 R E9= £~10

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H H

CH

3 H3

CH

3

CH

3 H3 H3 H3

CH

3 H3

CH

3 H3 C3 H3

CH

3 H3

CH

3

CH

3 H3 H3

CH

3 H3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-FPh)

CH

3

CH

2 (2-CIPh)

CH

3

CH

2 (2-(CH 3 )Ph)

CH

3

CH

2 (2,6-C1 2 Ph)

CH

3

CH

2 (2-CF 3 Ph)

CH

3

CH

2 (2-tetrahydropyran)

CH

3

CH

2 (2-pyridyl)

CH

3

CH

2 (Ph)

CH

3 Q-1

CH

3 0-3

CH

3 Q-6

CH

3 Q-7

CH

3

CH

3

CH

2 (2-FPh)

CH

3

CH

2 (2-C1Ph)

CH

3

CH

2 (2-(CH 3 )Ph)

CH

3

CH

2 (2,6-Cl 2 ph)

CH

3

CH

2 (2-CF 3 Ph)

CH

3

CH

2 (2-tetrahydropyran)

CH

3

CH

2 (2-pyridyl)

CH

3

CH

2 (Ph)

CH

3 Q-1

CH

3 Q-3

CH

3 Q-6 Cl 3 0-7

CH

3

CH

3

CH

2 (2-FPh) Cl 3

CH

2 (2-ClPh)

CH

3

CH

2 (2-(CH 3 )Ph)

CH

3

CH

2 (2,6-Cl 2 Ph)

CH

3

CH

2 (2-CF 3 Ph) WO 91/03464 PCT/US90/04953 116

CH

3 H H CH 2

CH

3

CH

3 CH,(2-tetrahydropyran)

CH

3 H H CH 2

CH

3

CH

3

CH

2 (2-pyridyl)

CH

3 H H CH 2

CH

3

CH

3

CH

2 (Ph)

CH

3 H CH 3 H CH 3 Q-1

CH

3 H CH 3 H CH 3 Q-3

CH

3 H CH 3 H CH 3 Q-6

CH

3 H CH 3 H CH 3 Q-7

CH

3 H CH 3 H CH 3

CH

3 H CH 3 H CH 3

CH

2 (2-FPh)

CH

3 H CH 3 H CH 3

CH

2 (2-C1Ph)

CH

3 H CH 3 H CH 3

CH

2 (2-(CH 3 )Ph)

CH

3 H CH 3 H CH 3

CH

2 (2,6-C1 2 Ph)

CH

3 H CH 3 H CH 3

CH

2 (2-CF 3 Ph)

CH

3 H CH 3 H CH 3

CH

2 (2-tetrahydropyran)

CH

3 H CH 3 H CH 3

CH

2 (2-pyridyl)

CH

3 H CH 3 H CH 3

CH

2 (Ph) PCT/US90/04953 WO 91/03464 117 i* Z C(R 3

)(R

4 )0R El F3=R4 Rg=E10 E 5 Q H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-FPh) H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-ClPh) H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-BrPh) H CH 2

CH

3

CH

2

CH

3

CH

3 C11 2 (2-(CH 3 )Ph) H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(0CH 3 )Ph) H CH 2

CH

3

CH

2

CH

3 01 3

CH

2 (2-(CN)Ph) H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(CF 3 )Ph) H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(OCF 3 )Ph) H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(SCH 3 )Ph) H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 2 Ph) H CH 2

CH

3

CH

2

CH

3 CH3 CH 2 (2,6-(C1) 2 Ph) H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-pyridyl) H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-furanyl) H CH 2 CH3 CH 2

CH

3

CH

3

CH

2 (2-tetrahydrofuran) H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-.tetrahydropyran) H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2.-tkiiophenyl) H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-iSoxazolyl) H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-pyrazinyl) H CH 2

CH

3

CH

2

CH

3

CH

3

CH

2 (Ph) WO 91/03464 PIIU9/45 PCT/US90/04953 R1 R3= 94

R

9 =R 1 0 R

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

H

CR

2

CH

3

CH

2

CH

3

CR

2

CR

3

CR

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CR

2

CR

3

CR

2

CH

3

CR

2

CH

3

CR

2

CH

3

CH

2

CH

3

CR

2 CH 3

CH

2

CH

3

CR

2

CR

3 CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CR

3

CR

2

CR

3

CR

2

CR

3

CH

2

CH

3

CR

2

CR

3

CR

2

CH

3

CR

2

CM

3

CH

2

CR

3

CH

2

CR

3

CH

2

CH

3

CR

2

CH

3

CH

2

CR

3

CH

2

CH

3

CH

2

CM

3

CH

2

CM

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CR

2

CH

3

CH

2

CR

3 C 2 CR 3

CR

2

CR

3

CH

2

CR

3

CH

2

CH

3

CH

2

CH

3

CH

2

CR

3

CR

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CR

3

CR

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3 CH1 2

CH

3

CR

2

CH

3

CH

2

CR

3

CH

2

CH

3

CH

2

CR

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2

CR

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CH

2

CH=CH

2

CH

2

CH=CR

2

CH

2

CH=CH

2

CR

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CR

2

CR=CR

2

CR

2

CH=CH

2

CH

2 CR CH 2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2 0-1 Q-3 Q- 6 Q-7 0-15

CR

2 (2-FPh)

CR

2 (2-CIPh)

CH

2 (2-(CH 3 )Ph)

CB

2 (2,6-Cl 2 Ph)

CR

2 (2-CF 3 Ph)

CH

2 (2-tetra-hydropyran)

CR

2 (2-pyridyl)

CR

2 (Ph) Q-1.

Q-3 Q-6 Q-7 0-15

CH

2 2-FPh)

CR

2 (2-CIPh)

CH

2 (2-(CR 3 )Ph)

CH

2 (2,6-Ci 2 Ph)

CH

2 (2-CF 3 Ph)

CR

2 (2-tetrahydropyran)

CR

2 (2-pyridyl)

CH

2 (Ph) Q-1 Q-3 Q-6 0-7 PCr/US9O/04953 WO 91/03464 H H H CH 3

CH

2 (2-FPh) H H H CH 3

CH

2 (2-C1Ph) H H H CH 3

CH

2 (2-(CH 3 )Ph) H H H CH 3

CH

2 (2,6-Cl 2 Ph) H H H CH 3

CH

2 (2-CF 3 Ph) H H H CH 3

CH

2 (2-tetrahydropyran) H H H CH 3

CH

2 (2-pyridyl) H H H CH 3

CH

2 (Ph) H H H CH 3 0- H H H CH 3 Q-3 H H H CH 3 Q-6 H H H CH 3 Q-7 H H H CH 3 H CH 3

CH

3

CH

3

CH

2 (2-FPh) H CH 3

CH

3

CH

3

CH

2 (2-C1Ph) H C3 CH 3

CH

3

CH

2 (2-(CH 3 )Ph) H CH 3

CH

3

CH

3

CH

2 (2,6-Cl 2 Ph) H CH 3

CH

3

CH

3

CH

2 (2-CF 3 Ph) H CH 3

CH

3

CH

3

CH

2 (2-tetrahydropyran) H CH 3

CH

3

CH

3

CH

2 (2-pyridyl) H CH 3

CH

3

CH

3

CH

2 (Ph) H CH 3

CH

3

CH

3 Q-1 H CH 3

CH

3

CH

3 Q-3 H CH 3

CH

3

CH

3 Q-6 H CH 3

CH

3

CH

3 Q-7 IAH

CH

3

CH

3

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-FPh)

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-C1Ph)

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(CH 3 )Ph)

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2,6-C1 2 Ph)

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-CF 3 Ph) WO 9 1/03464 pCy/US90/04953 120 El

E

3 -R4 R- 9

=R

10 R

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-tetrahydropyral)

CH

3

CM

2

CH

3

CH

2

CH

3

CM

3

CH

2 (2-pyridyl)

CH

3

CH

2

CM

3

CH

2

CM

3

CH

3

CH

2 (Ph)

CM

3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-1

CH

3

CM

2

CH

3

CH

2

CH

3

CH

3 Q-3

CH

3

CH

2

CH

3

CM

2

CM

3

CH

3 Q-6

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-7

CH

3

CH

2

CH

3

CM

2

CH

3

CM

3

CH

2

CM

3

CH

3

CH

3

CM

3

CH

2 (2-FPh)

CH

2

CH

3

CH

3

CH

3

CH

3

CH

2 (2-ClPh)

CH

2

CH

3

CM

3

CM

3

CH

3

CH

2 (2-(CH 3 )Ph)

CH

2

CH

3

C

3

C

3

C

3

C

2 (2,6-C1 2 h

C

2

CH

3

C

3

C

3

C

3

C

2 (2-CF 3 Ph

CH

2

CH

3

CM

3

CH

3

CH

3

CH

2 (2-tetrahydropyran)

CH

2

CH

3

CM

3

CH

3

CH

3

CH

2 (2-pyridyl)

CH

2

CH

3

CH

3

CM

3

CH

3

CH

2 (Ph)

CH

2

CH

3

CM

3

CM

3

CM

3 Q-1 CH2CH3 CH3 CH3 CH3 Q-3 CM2C 3 CH MH CM 3 Q-6 CM2C 3 MH CH CM 3 Q-7 CM2C 3 CH CH CM 3

CM

3 H H CM 3 QM-1~h

CH

3 H H CM 3 0M-3 1h

CM

3 H H CM 3 Q-62(C 3

CM

3 H H CM 3

CH

2 (2-Ph)

CM

3 H H CH 3

CH

2 (2-CFPh)

CM

3 H H CM 3

CH

2 (2-tetrahydropyran) WO 91/03464 PCT/US90/04953 121.

CH

3 H H CM 3

CH

2 (2-pyridy.)

CH

3 H H CH 3

CH

2 (Ph)

CH

3

CH

3

CM

3

CH

3 Q-1

CH

3

CM

3

CH

3

CH

3 Q-3

CH

3

CH

3

CH

3

CM

3 Q-6

CM

3

CH

3

CM

3

CH

3 Q-7

CM

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CM

3

CH

2 (2-FPh)

CH

3

CH

3

CH

3

CM

3 CH2(2-CIPh)

CM

3

CH

3

CH

3

CH

3

CH

2 (2-(CH 3 )Ph)

CM

3

CH

3

CM

3

CH

3

CH

2 (2,6-Cl 2 Ph)

CM

3

CM

3

CH

3

CM

3

CH

2 (2-CF 3 Ph)

CM

3

CH

3

CH

3

CH

3

CH

2 (2-tetrahydropyran)

CM

3

CH

3

CH

3

CH

3

CM

2 (2-pyridyl)

CM

3

CM

3

CM

3

CM

3

CM

2 (Ph)

CM

3 H CH 3

CH

3 Q-1

CM

3 H CM 3

CH

3 Q-3

CH

3 H CM 3

CM

3 0-6

CM

3 H CM 3

CM

3 Q-7

CM

3 H CM 3

CM

3

CH

3 H CM 3

CM

3

CH

2 (2-FPh)

CM

3 H CM 3

CM

3 CH (2-C1Ph)

CM

3 H CM 3

CM

3

CH

2 (2-(CH 3 )Ph)

CM

3 H CM 3

CM

3 CH (2,6-C1Ph)

C

3

HC

3

C

3

C

2 (2-C 3 2 CMH H CM 3

CM

3 CH (-CFtrPh)doyr

C

3

HC

3

C

3

C

2 (2-pr3yl

CM

3 H CM 3

CM

3

CH

2 (2-etaydo)rn

CM

3 H CHCH CH C

CH

3 H CH 2

CH

3

CM

3 Q-3

CM

3 H CH 2

CH

3

CM

3 0-6

CM

3 H CH 2

CM

3

CM

3 Q-7 WO 91/03464 PCT'/US90/04953 122 R 3= 4 Rg=E 10

R

CH

2

CH

3

CH

2

CH

3

CH

2 H3

CH

2

CH

3

CH

2

CH

3

CH

2

CM

3

CH

2 CH3

CH

2

CH

3

CH

2

CH

3

H

H

H

H

H

H

H

H

H

H

H

H

H

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CM

3

CH

3

CH

3

CM

3

CH

3

CH

3

CH

3

CH

3

CM

2 (2-FPh)

CH

2 (2-CiPh)

CH

2 (2-(CH 3 )Ph)

CM

2 6-Cl 2 Ph)

CM

2 (2-CF 3 Ph)

CM

2 (2-tetrahydropyran)

CM

2 (2-pyridyl)

CH

2 (Ph) Q-1 Q-3 0-6 Q-7

CH

2 (2-FPh)

CM

2 (2-ClPh)

CH

2 (2-(CH 3 )Ph)

CH

2 6-C1 2 Ph)

CM

2 2-CF 3 Ph)

CM

2 (2-tetrahydropyran)

CH

2 (2-pyridyl)

CH

2 (Ph) 1.* PCT/ US90/04953 WO 91/03464 123 7ABLE 7 X and Y are C(R 3

)(R

4 )0R 5 (unless specified) 1 3=E4 Eg=E 10 R 5

CH

2

CH

3 CH 2 CR 3

CH

2

CH

3

CH

2

CH

3

CH

2

CR

3

CH

2

CH

3

CH

2

CH

3 CH2CH3

CHCH

CH

2

CH

3

CH

2

CR

3

CH

2

CH

3

CH

2 CH3

CH

2 CR3

CH

2

CH

3

CR

2

CR

3

CH

2

CH

3

CH

2

CR

3

CR

2

CR

CH

2

CH

3

CH

2

CH

3

CR

2

CR

3

CH

2

CR

3

CR

2

CR

3 CR 2 CH 3

CR

2

CH

3

CH

2

CH

3

CR

2

CR

3

CH

2

CH

3

CH

2

CH

3

CH

2

CR

3 CR2C

C

3

CH

2

CH

3

CR

2

CH

3

CH

2

CH

3

CH

2

CR

CH

2 C C 3

CR

2

CR

3

CR

2

CH

3

CH

2 CR 3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

3

CH

3

CR

3

CH

3

CH

3

CR

3

CH

3

CH

3

CH

3

CR

3

CR

3

CR

3

CR

3

CH

3

CR

3

CR

3

CR

3

CH

3

CH

3

Q

CR

2 2 -FPh)

CR

2 C 2-CIPh)

CR

2 (C2-BrPh)

CR

2 2-(CH 3 )Ph)

CH

2 (2-(OCH 3 )Ph)

CR

2 (2-(CN)Ph)

CH

2 (2-(CF 3 )Ph) CH 2 (2-(OCF 3 )Ph)

CH

2 (2-(SCH 3 )Ph)

CH

2 2 Ph)

CH

2 (2,6-(C1) 2 Ph)

CR

2 (2-pyridyl)

CR

2 (2-furanyl)

CR

2 (2-tetrahydrofuran)

CR

2 (2-tetrahydropyran)

CH

2 2-thiophenyl)

CR

2 (C2-isozazolyl)

CH

2 2-pyrazinyl)

CH

2 Ph) Q-1 Q- 3 WO 91/03464ruiU9/45 PCT/US90/04953 124 EI R3=E4 R =E10 ~5

X

H CH 2

CH

3

CH

2

CH

3

CH

3 0-6 H H CH 2

CH

3

CH

2

CH

3

CH

3 Q-7 H H CH 2

CH

3

CH

2

CH

3

CH

3 0-15 H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2-FPh) H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2-ClPh) H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2-(CH 3 )Ph) H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2,6-Cl 2 Ph) H H CH 2 CH 3

CH

2

CH

3

CH

2

CH

3

CH

2 (2-CF 3 Ph) H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (2-tetrahydropyran) H H CH 2

CH

3

CH

2

CH

3

CH

2 CH 3

CH

2 C2-pyridyl) H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2 (Ph) H H CH 2 CH 3

CH

2

CH

3

CH

2

CH

3 Q-1 H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3 Q-3 H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3 Q-6 H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3 0-7 H H CH 2

CH

3

CH

2

CH

3

CH

2

CH

3 Q-15 H H CH 2

CH

3

CH

2

CH

3

CH

2

CH=CH

2

CH

2 (2-FPh) H H CH 2

CH

3

CH

2

CH

3

CH

2

CH=CH

2

CH

2 (2-C1Ph) H H CH 2 CH 3

CH

2

CH

3

CH

2

CH=CH

2 CH 2 (2-(CH 3 )Ph) H H CH 2

CH

3

CH

2

CH

3

CH

2

CH=CH

2

CH

2 (2,6-Cl 2 Ph) H H CH 2 CH 3

CH

2

CH

3

CH

2

CH=CH

2

CH

2 (2-CF 3 Ph) H H CH 2

CH

3

CH

2

CH

3

CH

2

CH=CH

2

CH

2 (2-tetrahydropyran) H H CH 2

CH

3

CH

2

CH

3

CH

2

CH=CH

2

CH

2 (2-pyridyl) H H CH 2

CH

3

CH

2

CH

3

CH

2

CH=CH

2

CH

2 (Ph) H H CH 2

CH

3

CH

2

CH

3

CH

2

CH=CH

2 0-1 H H CH 2

CH

3

CH

2

CH

3

CH

2

CH=CH

2 0-3 H H CH 2

CH

3

CH

2

CH

3

CH

2

CH=CH

2 0-6 H H CH 2

CH

3

CH

2

CH

3

CH

2

CH=CH

2 0-7 H H CH 2

CH

3

CH

2

CH

3

CH

2 CH=C1 2 Q-15 H P07 LJS9O/04953 WO 91/03464 125 1 R4 R9E1 H H H CH 3

CH

2 (2-FPh) H H H H CH 3

CH

2 (2-ClPh) H H H H CH 3

CH

2 (2-(CH 3 )Ph) H H H H CH 3

CH

2 (2,6 -C' 2 Ph) H H H H CH 3

CH

2 (2-CF 3 Ph) H H H H CH 3

CH

2 (2-tetrahydropyran) H H H H CH 3

CH

2 (2-pyridyl) H H H H CH 3

CH

2 (Ph) H H H H CH 3 Q-1 H H H H CH 3 Q-3 H H H H CH 3 Q-6 H H H H CH 3 Q-7 H H H H CH 3 Q-15 H H CH 3

CH

3

CH

3

CH

2 (2-FPh) H H CH 3

CH

3

CH

3

CH

2 (2-CIPh) H H CH 3

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) H H CH 3

CH

3

CH

3

CH

2 (2,6-C1 2 Ph) H H CH 3

CH

3

CH

3

CH

2 (2-CF 3 Ph) H H CH 3

CH

3 CH 3

CH

2 (2-tetrahydropyran) H H CH 3

CH

3

CH

3

CH

2 (2-pyridyl) H H CH 3

CH

3

CH

3 C11 2 (Ph) H H CH 3

CH

3

CH

3 Q-1 H H CH 3

CH

3

CH

3 Q-3 H H CH 3

CH

3

CH

3 0-6 H H CH 3

CH

3

CH

3 Q-7 H H CH 3

CH

3

CH

3 0-15 H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 d11 2 (2-FPh) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 CH 2 (2-C1Ph) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) H

CH

3 t2H 2

CH

3

CH

2

CH

3

CH

3

CH

2 (2,6-C1 2 Ph) H

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-CF 3 Ph) H WO 91/03464 PCT/LtS9O/04953 126

CH

3

C

2

CH

3

C

2

CH

3

C

3

C

2 (2-tetraliydropyran) H

CH

3

CH

2 CH 3

CH

2

CH

3

CH

3 CH 2 (2-pyridyl) H CH 3

CH

2 CH 3

CH

2

CH

3

CH

3 CH 2 (Ph) H

CH

3

CH

2 CH 3

CH

2 CH 3

CH

3 Q-1 H CH 3

CH

2

CH

3

CH

2

CH

3

CH

3 0-3 H

CH

3

CH

2 CH 3

CH

2

CH

3

CH

3 Q-6 H CH 3

CH

2 CH 3

CH

2

CH

3

CH

3 0-7 H

CH

3 CH 2 CH 3

CH

2

CH

3

CH

3 Q-15 H

CH

2 CH 3

CH

2 CH 3

CH

2

CH

3 CH 3

CH

2 (2-FPh) H

CH

2 CH 3

CH

2 CH 3

CH

2

CH

3 CHY CH 2 (2-CIPh) H

CH

2

CH

3

CH

2 CH 3

CH

2 CH 3 CH 3 CH 2 (2-(CH )Ph) H

CH

2

C

3

CHCH

3

CH

2

C

3

C

3 CH(2,-C1 2 h)3

CH

2

CH

3

CH

2 CH 3

CH

2

CH

3

CH

3

CH

2 (2,-C 3 Ph) H

CH

2

CH

3

CH

2 CH 3

CH

2

CH

3 CH 3 CH 2 (2-CFPhrd) H CH CH 3 CH CH 3 CH CH 3

CH

3

CH

2 (h CH 2

CH

3

CH

2 CH 3

CH

2

CH

3

CH

3 0-12pyidl H CH 2

CH

3

CH

2 CH 3

CH

2

CH

3

CH

3 0-3(Ph H

CH

2

CH

3

CH

2 CH 3

CH

2

CH

3 CH 3 Q-1 H

HCH

3 CH CH 3 CH CH 3

CH

3 0-7 H

CH

2

CH

3

CH

2 CH 3

CH

2

CH

3 C12 3 0-15 H WO 9 1/03464 PCT/ US90/04953 127 El R=0E= 10 FO5£ 0 H CH 3 H CH 3 cH 2 (2-FPh) H H CH 3 H CH 3

CH

2 (2-CIPh) H Hi CH 3 H CH 3

CH

2 (2-(CH 3 )Ph) H H CH 3 H CH 3 CH.,(2,6-Cl 2 Ph) H H CH 3 H CH 3

CH

2 (2-CF 3 Ph) H H CH 3 H CH 3

CH

2 (2-tetrahydropyran) H H CH 3 H CH 3

CH

2 (2-pyridyl) H H CH 3 H CH 3

CH

2 (Ph) H H CH 3 H CH 3 0-1 H H CH 3 H CH 3 Q-3 H H CH 3 H CH 3 0-6 H H CH 3 H CH 3 0-7 H H CH 3 H CH 3 Q-15 H

CH

3 H CH 3

CH

3

CH

2 (2-FPh) H

CH

3 H CH 3

CH

3

CH

2 (2-C1Ph) H

CH

3 H CH 3

CH

3

CH

2 (2-(CH 3 )Ph) H

CH

3 H CH 3

CH

3

CH

2 (2,6-C1 2 Ph) H

CH

3 H CH 3

CH

3

CH

2 (2-CF 3 Ph) H

CH

3 H CH 3

CH

3

CH

2 (2-tetrahydropyran) H

CH

3 H CH 3

CH

3

CH

2 (2-pyridyl) H

CH

3 H CH 3

CH

3

CH

2 (Ph) H

CH

3 H CH 3

CH

3 0-1 H

CH

3 H CH 3

CH

3 0-3 H

CH

3 H CH 3

CH

3 0-6 H

CH

3 H CH 3

CH

3 Q-7 H

CH

3 H CH 3

CH

3 0-15 H PCY/US90/04953 WO 91/03464 PTU9/45 128 RH H H2 CH 3 El Z5(-Fh H

CH

3 H H CH 3

CH

2 (2-ClPh) H

CH

3 H H CH 3

CH

2 (2-(CH 3 P) H

CH

3 H H CH 3

CH

2 (2,-CH 3Ph) H

CH

3 H H CH 3

CH

2 (2,-C 3 Ph) H

CH

3 H H CH 3

CH

2 (2-tetrabydropyran) H

CH

3 H H CH 3

CH

2 (2-pyridyl) H

CH

3 H H CH 3

CH

2 (Ph) H

CH

3 H H CH 3 Q-1 H

CH

3 H H CH 3 Q-3 H

CH

3 H H CH 3 Q-6 H

CH

3 H H CH 3 Q-7 H

CH

3 H H CH 3 Q-15 H

CH

3

CH

3 CH 3

CH

3 CH 2 (2-FPh) H CH 3

CH

3 CH 3

CH

3

CH

2 (2-ClPh) H

CH

3

CH

3 CH 3

CH

3 CH 2 2-(CH 3 )Ph) H C11 3

CH

3 CH 3

CH

3

CB

2 (2..6-IC1 2 Ph) H

CH

3

CH

3 CH 3

CH

3

CH

2 (2-CF 3 Ph) H

CH

3

CH

3 CH 3

CH

3

CH

2 (2-tetrahydropyran) H

CH

3

CH

3 CH 3

CH

3

CH

2 C2-pyridyl) H

CH

3

CH

3

CH

3 CH 3

CH

2 (Ph) H

CH

3

CH

3 CH 3

CH

3 0-1 H

CH

3

CH

3 CH 3

CH

3 0-3 H

CH

3

CH

3

CH

3

CH

3 0-6 H CH 3

CH

3

CH

3

CH

3 0-7 H

CH

3

CH

3

CH

3

CH

3 0-15 H R1 I Rg 9 ja 0 E5 Q x

CH

3 H H CH 3

CH

2 (2-FPh) H

CH

3 H H CH 3

CH

2 2-CIPh) H womommommoft- ft

A

WO 91/03464 PUT, US9O/04953 129

CH

3 H H CH 3

CH

2 (2-BrPh) H

CH

3 H H CH 3

CH

2 (2-(CH 3 )Ph) H

CH

3 H H CH 3

CH

2 (2-(OCH 3 )Ph) H

CH

3 H H CH 3

CH

2 (2-(CN)Ph) H

CH

3 H H CH 3

CH

2 (2-(CF 3 )Ph) H

CH

3 H H CH 3

CH

2 (2-(OCF 3 )Ph) H

CH

3 H H CH 3 CH2(2-(SCH 3 )Ph) H

CH

3 H H CH 3

CH

2 2 Ph) H

CH

3 H H CH 3

CH

2 2 Ph) H

CH

3 H H CH 3

CH

2 (2-pyridyl) H

CH

3 H H CH 3

CH

2 (2-furanyl) H

CH

3 H H CH 3

CH

2 (2-tetrahydrofuran) H

CH

3 H H CH 3

CH

2 (2-tetraihydropyran) H

CH

3 H H CH 3

CH

2 (2-thiophenyl) H

CH

3 H H CH 3

CH

2 (2-isoxazo1y1) H

CH

3 H H CH 3

CH

2 (2-pyrazinyl) H

CH

3 H H CH 3

CH

2 (Ph) H

CH

3 H H CH 3 Q-1 H

CH

3 H H CH 3 Q-3 H

CH

3 H H CH 3 Q-6 H

CH

3 H H CH 3 0-7 H

CH

3 H H CH 3 Q-15 H

CH

3 H H CH 2

CH

3

CH

2 (2-FPh) H

CH

3 H H CH 2

CH

3

CH

2 (2-C1Ph) H

CH

3 H H CH 2

CH

3

CH

2 (2-(CH 3 )Ph) H

CH

3 H H CH 2

CH

3

CH

2 (2,6-C1 2 Ph) H

CH

3 H H CH 2

CH

3

CH

2 (2-CF 3 Ph) H

CH

3 H H CH 2

CH

3

CH

2 (2-tetrahydropyran) H

CH

3 H H CH 2

CH

3 C11 2 (2-pyridyl) H

CH

3 H H CH 2

CH

3

CH

2 (Ph) H

CH

3 H H CH 2

CH

3 0-1 H

CH

3 H H CH 2

CH

3 Q-3 H WO 91/03464PC/U9/45 PCr/US90/04953 130 R 3 =E 4 R 9=R10 R CH

I

3

CH

3

CH-

3 Cl-I 3 Cl-I 3

CR

3 Cl- 3 CH 3

CR

3

CHR

3 Cu 3 CH 3

CH

3 Cl-I 3 CH 3 Cl- 3

CH

3

CH

2

CHI

3

CH

2

CH

3 Cl- 2 CH 3 Cl- 2

CH

3

CH

2 CH 3

CH

2 CH 3

CH

2

CR

3

CH

2 CH 3

CH

2 CH 3 Cu 2 CH 3

CH

2

CH

3

CR

2 CH 3 Cl- 2

CH

2

CH

3

CR

2 Cu 3

CH

2

CH

3

CH

2

CH=CH

2

CH

2

CH=CH-

2 CH 2

CH=CH

2 CH 2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2

C=CH-

2 Cu 2

CH=C-

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2 CR C 2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

3

CH

3 CH 3 CH 3

CH

3

CH

3

CH

3 Cu 3

CH

3

CR

3

CR

3 Cu 3 Cu 3 Q-6 0-7

CR

2 (2-FPh)

CB

2 (2-C1Ph)

CB

2 (2-(CH 3 )Ph)

CR

2 (2,6 -C' 2 Ph) Cl- 2 2-CF 3 Ph)

CH

2 (2-tetrahydropyran) Cl- 2 2-pyridyl) Cu 2 (Ph) Q-1 Q-3 Q-6 Q-7 0-15

CH

2 2-FPh) Cl- 2 (2-CIPh)

CH

2 (2-(CH 3 )Ph)

CH-

2 2, 6-C 2 Ph)

CH

2 (2-CF 3 Ph)

CR

2 (C2-tetrahydropyran)

CH-

2 (2-.pyridyl)

CH

2 (Ph) Q-1 Q-3 0-6 Q-7 WO 91/03464 pCU/ US9O/04953 131 £1 3~ Rg1O R5 Qx

CM

3

CM

3

CH

3

CH

3

CH

2 (2-FPh)

H

CH

3

CH

3

CH

3

CH

3

CH

2 (2-ClPh) H

CH

3

CM

3

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) H

CM

3

CM

3

CM

3

CH

3

CH

2 (2,6-Cl 2 Ph) H

CM

3

CM

3

CH

3

CM

3

CH

2 (2-CF 3 Ph) H

CM

3

CM

3

CM

3

CM

3

CM

2 (2-tetrahydropyran) H

C

3

CH

3 CMH CH 3 CH(2-pyridyl) H

CM

3

CM

3

CM

3

CM

3

CM

2 (Ph) H

CM

3

CM

3

CM

3

CM

3 Q-1 H

CM

3

CM

3

CM

3

CM

3 Q-3 H

CM

3

CM

3

CM

3

CM

3 Q-6 H

CM

3

CM

3

CM

3

CM

3 Q-7 H

CM

3

CM

3

CM

3

CM

3 Q-15 H

CM

3

CH

2

CH

3

CM

2

CM

3

CM

3

CM

2 (2-FPh) H

CM

3

CM

2

CH

3

CH

2

CM

3

CM

3

CH

2 (2-C1Ph) H

CM

3

CM

2

CH

3

CM

2

CM

3

CM

3

CM

2 (2-(CM 3 )Ph) H

CM

3

CH

2

CM

3

CH

2

CH

3

CM

3

CM

2 (2,6-Cl 2 Ph) H

CM

3

CM

3

CM

3

CH

3

CH

2 2 Ph) H

CM

3

CM

3

CM

3

CM

3

CM

2 2 Ph) H

CM

3

CM

2

CM

3

CM

2

CH

3

CM

3

CM

2 (2-tetrahydropyran) H

CM

3

CH

2

CP

3

CM

2

CM

3

CM

3

CM

2 (2-pyridyl) H

CM

3

CM

2

CH

3

CH

2

CM

3

CH

3

CM

2 (Ph) H

CM

3

CM

2

CH

3

CM

2

CM

3

CM

3 Q-1 M

CM

3

CM

2

CH

3

CH

2

CM

3

CH

3 Q-3 H

CM

3

CM

2

CH

3

CH

2

CM

3

CM

3 Q-6 H

CM

3

CH

2

CH

3

CH

2

CH

3

CM

3 Q-7 H

CM

3

CM

2

CM

3

CH

2

CM

3

CH

3 Q-15 H

CM

3

CH

2

CM

3

CM

2

CM

3

CM

3

CM

2 2 Ph) H

CH

2

CH

3

CH

2

CH

3

CM

2

CH

3

CM

3

CH

2 (2-FPh)

CH

2

CM

3

CM

2

CM

3

CH

2

CM

3

CM

3

CH

2 (2-C1Ph) H

CH

2

CM

3

CM

2

CH

3

CM

2

CM

3

CM

3

CH

2 (2-(CH 3 )Ph) H

CH

2

CH

3

CM

2

CM

3

CM

2

CM

3

CM

3

CM

2 (2,6-Cl 2 Ph) H WO 9 1/03464 PCT/US9O/04953 132 E 4 0 I

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-CF 3 Ph) H

CHC

3 CH CH 3 CH CH 3

CH

3 CH (2-tetrahydropyran) H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-pyridyl) H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (Ph) H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-1 H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-3 H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-6 H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-7 H

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-15 H CH3

C

H CH 3

CH

2 (2-FPh) H

CH

3

CH

3 H CH 3

CH

2 (2-C1Ph) H

CH

3

CH

3 H CH 3

CH

2 (2-(CH 3 )Ph) H

CH

3

CH

3 H CH 3

CH

2 (2,6-Cl 2 Ph) H

CH

3

CH

3 H CH 3

CH

2 (2-CF 3 Ph) H

CH

3

CH

3 H CH 3

CH

2 (2-tetrahydropyran) H

CH

3

CH

3 I CH 3

CH

2 (2-pyridyl)H

CH

3

CH

3 H CH 3 CH (Ph) H

C

3

CH

3 H CH 3 Q-1 H

C

3

CH

3 H CH 3 Q-3 H

CH

3

CH

3 H CH 3 Q-6 H

C

3

C

3

HC

3 0-H

CH

3

CH

3 H CH 3 Q-15 H CH CH H CH 3 QH- h H

C

3 H3 H C 3 1 (2 2)H

CH

3 H CH 3

CH

3 CH(-CH) )H

CH

3

HC

3

C

3 C1 2 (2,-CPh) H aCH 3 B CH 3

CH

3

CH

2 (2-CF 3 Ph) H

CH

3

HC

3

C

3

H

2 (2-tetrahdoyr H

CH

3 H CH 3

CH

3

CH

2 (2-pyriPh) H

CH

3 H CH 3

CR

3

CH

2 (Ph) H

CH

3 H CH 3

CR

3 Q-1 H WO 91/03464 PCT/US9O/04953 133 El 3=0 Eg=E1O

CM

3 H CH 3

CM

3 Q-3 H

CH

3 H CH 3

CM

3 Q-6 H

CH

3 H CH 3

CH

3 Q-7 H

CH

3 H CH 3

CH

3 Q-15 H

CH

3 H CM 2

CH

3

CH

3

CH

2 (2-FPh) H

CH

3 H CH 2

CH

3

CH

3

CH

2 (2-C1Ph) H

CM

3 H CH 2

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) H

CH

3 H CH 2

CH

3

CM

3

CH

2 (2,6-C1 2 Ph) H

CM

3 H CH 2

CH

3

CM

3 Cr1 2 (2-CF 3 Ph) H

CM

3 H CH 2

CH

3

CM

3

CH

2 (2-tetrahydropyran) H

CM

3 H CH 2

CH

3

CM

3

CH

2 (2-pyridyl) H

CM

3 H CH 2

CH

3

CM

3

CH

2 (Ph) H

C

3 CH CH 3

CH

3 Q-1 H

CM

3 H CH CH 3

CM

3 Q-3 H

C

3 HCH CH 3

CM

3 Q-6 H

CM

3 H CH CH 3

CH

3 Q-7 H

CM

3 H CH 2

CH

3

CM

3 Q-15 H

CH

2

CH

3

CM

3

CM

3

CM

3

CH

2 (2-FPh) H

CH

2

CH

3

CM

3

CM

3

CM

3

CH

2 (2-C1Ph) H

CH

2

CH

3

CM

3

CM

3

CM

3

CH

2 (2-(CH 3 )Ph) H CH CH 3

CH

3

CM

3

CH

3

CH

2 26C h H

C

2

CH

3

C

3

C

3

C

3

C

2 (2-C 3 Ph)H

CH

2 C CM 3 CMH CM 3

CH

2 Ptrh)doyr H

CHC

3

C

3

C

3

C

3

C

2 (2-pyrdy)

CM

2

CH

3

CM

3

CM

3

CM

3

CH

2 (2-erahdo)rn H

CH

2

CH

3

CM

3

CM

3

CM

3

CH

CM

2 CH C H 3

CM

3

CM

3 CH-3 H

CH

2

CH

3

CM

3

CH

3

CM

3 Q-3 H

CH

2

CH

3

CM

3

CM

3

CM

3 Q-7 H

CH

2

CH

3

CM

3 CH.' CM 3 Q-15 H 1 WO 91/03464 PCT/ US90104953 134 R 3=R4 R9R1 H H H CH 3

CH

2 (2-FPh) H H H H CH 3

CH

2 (2-CIPh) H H H H CH 3

CH

2 (2-(CH 3 )Ph) H H H H CH 3

CH

2 (2..6-C1 2 Ph) H H H H CF! 3

CH

2 (2-CF 3 Ph) H H H H CF! 3

CH

2 (2-tetrahydropyran) H H H H CF! 3

CH

2 (2-pyridyl) H H H H CH 3 CH 2 (Ph) H H H H CH 3 Q-1 H H H H Cl! 3 Q-3 H H H H CH 3 Q-6 H H H H CH 3 Q-7 H H H H CF! 3 Q-15 H PCT/US9O/04953 WO 91/03464 viii

C(R

3

)(R

4 )0R 1 2 E3

H

H

H

H

H

H

H

H

H

H

H

CH

2

CH

3

CE

2

CH

3

CE

2

CH

3

CE

2

CH

3

CE

2

CH

3

CE

2

CH

3

CH

2

CH

3

CH

2

CE

CH

2

CH

3

CH

2

CE

3

CE

2 CE 3

CH

2

CH

3

CH

2 CE 3 CE 2

CE

3

CH

2

CH

3

CH

2 CH 3

CE

2

CH

3

CH

2

CE

3

CE

2 CH 3

CE

2

CH

3

CE

2

CH

3

CH

2

CH

3

CE

2 CH 3

CE

2

CE

3

CE

2

CE

3

CH

2

CH

3

CE

2

CH

3

CH

2

CE

3

CE

2

CH

3

CE

2

CE

3

CHE

2

CH

3

CE

2

C

2

CE

2 CH3

CE

3

CH

3

CH

3

CE

3

CH

3

CE

3

CH

3

CH

3

CE

3

CE

3

CE

3

CE

3

CE

3

CH

3

CE

3

CH

3

,.H

3

CE

3

CE

3

CH

2 (2-FPh)

CE

2 (2-CIPh)

CE

2 (2-BrP~a)

CH

2 (2-(CH 3 )Ph)

CE

2 (2-(OCH 3 )Ph)

CE

2 (2-(CN)Ph)

CH

2 (2-(CF 3 )Ph)

CH

2 (2-(OCF 3 )Ph)

CH

2 (2-(SCH 3 )Ph)

CH

2 2 Ph)

CE

2 Cl) 2 Ph)

CH

2 2-pyridyl)

CH

2 2-furanyl)

CE

2 (2-tetrahydrofuran)

CE

2 (2-tetrahydropyran)

CH

2 (2--hiophenyl)

CE

2 (2-isoxazolyl)

CE

2 (2-pyrazinyl)

CE

2 (Ph)

CE

3

CE

3

CE

3

CE

3

CH..

CE

3

CE

3

CE

3

CE

3

CE

3

CE

3

CE

3

CE

3

CE

3

CE

3

CE

3

CE

3

CE

3

CE

3 PCT/US90/04953 WO 91/03464PTIU9/45 1 2 R3 R4

CR

2

CH

3

CH

2

CH

3

CH

2

CR

3

CR

2 CH3

CR

2

CR

3 H2CH3

CH

2

CR

3

CR

2

CH

3

CR

2

CH

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CH

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

CR

2 C C 3

CR

2

CR

3

CR

2

CR

3 CH 2 CR 3

CR

2

CR

3

CR

2

CR

3

CH

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2 C C 3

CR

2

CH

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CH

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2 CR 3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CH

2

CR

CR

2

CR

3

CH

2

CH

3

CR

3

CR

3

CR

3

CR

3

CR

3

CR

2

CR

3

CR

2

CR

3 C 2

CR

3

CR

2

CR

3

CR

2

CR

3 CR 2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CH

2

CH=CH

2

CH

2

CH=CH

2

CR

2

CH=CH

2

CR

2

CR=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2 C!1 2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2 CH 2

CH=CH

2 CH 2

CH=CH

2

CH

2

CH=CH

2 Q-1 0-3 Q-6 Q-7 Q-15

CR

2 (2-FPh)

CR

2 (2-CIPh)

CR

2 (2-(CR 3 )Ph)

CR

2 6-C1 2 Ph)

CH

2 (2-CF' 3 Ph)

CR

2 (C2-tetrahydropyran)

CR

2 (C2-pyridyl)

CH

2 (Ph) Q-1 0-3 0-6 Q-7 0-15

CR

2 2-FPh)

CR

2 (2-CIPh)

CR

2 (2-(CR 3 )Ph)

CR

2 2, 6-C1 2 Ph)

CR

2 (C2-CF 3 Ph)

CR

2 (2-tetrahydropyran)

CH

2 (C2-pyridyl)

CH

2 (CPh Q-1 0-3 0-6 0-7 0-15

CR

3

CR

3

CR

3

CR

3

CR

3

CR

2

CR

3

CH

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CH

2 CR 3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CR

3

CR

2

CH=CH

2

CH

2

CH=CH

2

CR

2

CR=CH

2

CR

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CRZ=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2

CH

2

CH=CH

2 WO 91/03464 PCI'!US9O/04953 137 I R 4 B5 QR H H H H CH 3

CH

2 (2-FPh) CH 3 B H H H CH 3

CH

2 (2-CIPh) CH 3 H H H H CH 3 0H 2 (2-(CH 3 )Ph) CH 3 H H H H CH 3

CH

2 (2,6-C1 2 Ph) CH 3 H H H H OH 3

CH

2 (2-CF 3 Ph) OH 3 H H H H CH 3

CH

2 (2-tetrahydropyran) CH 3 H H H H CH 3

CH

2 (2-pyridyl) CH 3 H H H H CH 3

CH

2 (Ph) OH 3 H H H H CH 3 Q-1 CH 3 H H H H OH 3 0-3 CH 3 H H H H OH 3 Q-6 CH 3 H H H H CH 3 Q-7 CH 3 H H H H CH 3 Q-15 CH 3 H H H H CH 2 CH 3

CH

2

CH

2

CH

3 H H H H CH 2

CH

3 CH 2 (2-C1Ph) CH 2

OH

3 H H H H CH 2 CH 3

CH

2 (2-(CH 3 )Ph) CH 2

CH

3 H H H H CH 2

CH

3

CH

2 (2,6-Cl 2 p CH 2 CH 3 H H H H CH 2

CH

3

CH

2 (2-CF 3 Ph) CH 2

CH

3 H H H H CH 2

CH

3

OH

2 (2-tetrahydropyran) CH 2 CH 3 H H H H CH 2

CH

3 CH 2 (2-pyridyl) CH 2

CH

3 H H H H CH 2 CH 3

CH

2 (Ph) CH 2

CH

3 H H H H CH 2 CH 3 0-1 CH 2

CH

3 H H H H CH 2 CH 3 0-3

CH

2

CH

3 H H H H CH 2

CH

3 0-6

CH

2

CH

3 H H H H CH 2 CH 3 Q-7

CH

2

CH

3 H H H H CH 2 CH 3 0-15

CH

2

CH

3 H H CH 3 CH 3 CH 3

CH

2 (2-FPh)

OH

3 H H CH 3 CH 3 CH 3

CH

2 (2-CIPh) OH 3 H H OH 3

OH

3 CH 3 C1 2 (2-(CH 3 )Ph) OH 3 H H 0113 CH13 C113 CH 2 (2,6-C1 2 Ph) 0113 H H CH 3 CH 3 CH 3 C11 2 (2-CF 3 Ph) CH 3 k6. WO 91/03464 PCT/ US9O/04953 138 El1 2 R3 R4 R5 QR H H CH 3

CH

3

CH

3

CH

2 (2-tetrahydropyran) CH 3 H H CH 3

CH

3

CH

3

CH

2 (2-pyridyl) CH 3 H H CH 3

CH

3

CH

3

CH

2 (Ph) CH 3 H H CH 3

CH

3

CH

3 Q-1 CH 3 H H CH 3

CH

3

CH

3 Q-3 CH 3 H H CH 3

CH

3

CH

3 0-6 CH 3 H H CH 3

CH

3

CH

3 Q-7 CH 3 H H CH 3

CH

3

CH

3 Q-15 CH 3

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-FPh) CH 3

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-CiPh) CH 3

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-(CH 3

CH

3

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2,6-Cl 2 Ph) CH 3

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-CF 3 Ph) CH 3

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-tetrahydropyran) CH 3

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (2-pyridyl) CH 3

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (Ph) CH 3

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 0-1 CH 3

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 0-3 CH 3

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-6 CH 3

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 Q-7 CH 3

CH

3

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3 0-15 CH 3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

2 (2-FPh) CH 3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

2 (2-C1Ph) CH 3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) CH 3

CH

3

CH

3

CH

3

CH

3

CH

3 C1H 2 (2,6-Ci 2 Ph) CH 3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

2 (2-CF 3 Ph) CH 3

CH

3

CH

3

CH

3

CH

3 Cl 3

CH

2 (2-tetrahydropyran) Cl 3 Cl 3 Cl 3

CH

3 Cl 3 Cl 3

CH

2 (2-pyridyl) CH 3 Cl 3

CH

3

CH

3 Cl 3 Cl 3 C1 2 (Phl) Cl 3

CH

3

CH

3

CH

3 Cl 3

CH

3 0-1 CH 3 WO 91/03464 PIIU9/45 PCr/US90/04953 139 123

CH

3

CH

3

CH

3

CM

3

CM

3 Q-3 CM 3

CM

3

CM

3

CH

3

CM

3

CM

3 0-6 CM 3

CH

3

CM

3

CM

3

CH

3

CM

3 0-7 CM 3

CH

3

CH

3

CH

3

CH

3

CM

3 0-15 CM 3

CH

2

CM

3

CH

2

CM

3

CH

2

CH

3

CM

2

CH

3

CH

3

CH

2 (2-FPh) CH 3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CM

3 C11 2 (2-C1Ph) CH 3

CH

2

CH

3

CH

2

CH

3

CM

2

CH

3

CH

2

CH

3

CH

3 C11 2 (2-(CH 3 )Ph) CM 3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CM

3

CH

2 (2,6-C1 2 Ph) CH 3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CM

3

CH

2 (2-CF 3 Ph) CM 3

CH

2

CH

3

CM

2

CH

3

CH

2

CM

3

CH

2

CH

3

CM

3

CH

2 (2-tetrahydropyran) CH- 3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CM

3

CH

2 (2-pyridyl) CM 3

CH

2

CH

3

CM

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

2 (Ph) CM 3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CM

3 Q-1 CH 3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CM

3 0-3 CM 3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CH

2

CH

3

CM

3 Q-6 CM 3

CH

2

CM

3

CM

2

CH

3

CH

2

CM

3

CM

2

CH

3

CM

3 0-7

CM

3

CM

2

CH

3

CH

2

CM

3

CM

2

CH

3

CM

2

CH

3

CM

3 0-15 CM 3

CM

3

CM

3 H H CM 3

CM

2 (Ph) CM 3

CM

3

CM

3 M M CM 3

CM

2 (2-FPh) CM 3

CH

3

CM

3 M M CM 3

CM

2 (2-(CH 3 )Ph) CM 3

CM

3

CM

3 M M CM 3

CM

2 (2,6-Cl 2 Ph) CM 3

CM

3

CH

3 M M CM 3 0-3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

3

CH

2 (Ph) CM 3

CM

3

CM

3

CM

3

CM

3

CM

3

CM

2 (2-FPh) CM 3

CM

3

CM

3

CM

3

CM

3

CM

3

CH

2 (2-(CM 3 )Ph) CM 3

CM

3

CM

3

CM

3

CM

3

CM

3

CH

2 (2,6-Cl 2 Ph) CM 3

CM

3

CM

3

CM

3

CM

3

CM

3 0-3

CM

3

CH

2

CM

3

CM

2

CM

3 H M CM 3

CH

2 (Ph) CM 3

CM

2

CM

3

CH

2

CM

3 H H CM 3

CH

2 (2-FPh) CM 3

CH

2

CH

3

CH

2

CH

3 H H CM 3

CH

2 (2-(CH 3 )Ph) CM 3

CM

2

CM

3

CH

2

CH

3 H H CM 3

CH

2 (2,6-Cl 2 phk) CM 3

CH

2

CH

3

CH

2

CH

3 H H CM 3 0-3

CM

3 b WO 91/03464 PCT/ US9O/04953 140 F R2 R3 R4 R5 QR

CH

2

CH

3

CH

2

CR

3

CR

3

CH

3

CH

3

CH

2 (Ph) CR 3

CH

2

CH

3

CH

2

CR

3

CR

3

CH

3

CH

3

CH

2 (2-FPh) CR 3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) CH 3

CH

2

CH

3

CH

2

CH

3

CH

3

CH

3

CH

3

CH

2 (2,6-C1 2 Ph) CR 3

CR

2

CH

3

CH

2

CH

3

CR

3

CH

3

CR

3 Q-3 CR 3 H CR 3

CH

2

CH

3

CH

2

CH

3

CR

3

CH

2 (Ph) CH 3 H CH 3

CH

2

CH

3

CH

2

CH

3

CR

3

CH

2 (2-FPh) CR 3 H CR 3

CH

2

CH

3

CH

2

CH

3

CR

3

CH

2 (2-(CH 3 )Ph) CR 3 H CH 3

CR-

2

CH

3

CH

2

CH

3

CR

3

CH

2 (2,6-Cl 2 Ph) CH 3 H CR 3

CH

2

CH

3

CH

2

CH

3

CR

3 Q-3 CR 3 WO 91/03464 PCY/US90/04953 141 Formulations Useful formulations of the compounds of Formula I can be prepared in conventional ways. They include dusts, granules, pellets, solutions, suspensions, emulsions, wettable powders, emulsifiable concentrates and the like. Many of these may be applied directly. Sprayable formulations can be extended in suitable media and used at spray volumes of from a few liters to several hundred liters per hectare. High strength compositions are primarily used as intermediates for further formulation. The formulations, broadly, contain about 0.1% to 99% by weight of active ingredient(s) and at least one of about 0.1% to 20% surfactant(s) and about 1% to 99.9% solid or liquid diluent(s). More specifically, they will contain these ingredients in the following approximate proportions: Table 9 Weight Percent* Active Inaredient Diluent(s) Surfactant(s) Wettable Powders 5-60 39-94 1-10 Emulsifiable 3-80 20-95 0-20 Concentrates Dusts 1-25 70-99 SGranules and Pellets 0.1-50 50-99.9 0-15 Active ingredient plus at least one of a Surfactant or a Diluent equals 100 weight percent.

Lower or higher levels of active ingredient can, of course, be present depending on the intended use WO 91/03464 PC/US90/04953 142 and the physical properties of the compound. Higher ratios of surfactant to active ingredient are sometimes desirable, and are achieved by incorporation into the formulation or by tank mixing.

Typical solid diluents are described in Watkins, et al., "Handbook of Insecticide Dust Diluents and Carriers", 2nd Ed., Dorland Books, Caldwell, New Jersey, other solids, either mined or manufactured, may be used. The more absorptive diluents are preferred for wettable powders and the denser ones for dusts. Typical liquid diluents and solvents are described in Marsden, "Solvents Guide," 2nd Ed., Interscience, New York, 1950. Solubility under 0.1% is preferred for suspension concentrates; solution concentrates are preferably stable against phase separation at 0°C. "McCutcheon's Detergents and Emulsifiers Annual", MC Publishing Corp., Ridgewood, New Jersey, as well as Sisely and Wood, "Encyclopedia of Surface Active Agents", Chemical Publishing Co., Inc., New York, 1964, list surfactants and recommended uses. All formulations can contain minor amounts of additives to reduce foaming, caking, corrosion, microbiological growth, etc.

The methods of making such compositions are well known. Solutions are prepared by simply mixing the ingredients. Fine solid compositions are made by blending and, usually, grinding as in a hammer or fluid energy mill. Suspensions are prepared by wet a milling (see, for example, Littler, U.S. Patent 3,060,084). Granules and pellets may be made by spraying the active material upon preformed granular carriers or by agglomeration techniques. See J. E.

Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp. 147ff. and "Perry's Chemical 1^_11_ 11 WO 91/03464 PCT1/US90/04953 143 Engineer's Handbook", 5th Ed., McGraw-Hill, New York, 1973, pp. 8-57ff.

For further information regarding the art of formulation, see for example: H. M. Loux, U.S. Patent 3,235,361, February 1966, Col. 6, line 16 through Col. 7, line 19 and Examples 10 through 41; R. W. Luckenbaugh, U.S. Patent 3,309,192, March 14, 1967, Col. 5, linx 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; H. Gysin and E. Knusli, U.S. Patent 2,891,855, June 23, 1959, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; G. C. Klingman, "Weed Control as a Science", John Wiley and Sons, Inc., New York, 1961, pp. 81-96; and J. D. Fryer and S. A. Evans, "Weed Control Handbook", 5th Ed., Blackwell Scientific Publications, Oxford, 1968, pp. 101-103.

In the following examples, all parts are by weight unless otherwise indicated.

Example A Wettable Powder 2-(l-ethyl-l-methoxypropyl)-6-(phenylmethoxy)-7oxabicyclo[2.2.l]heptane sodium alkylnaphthalenesulfonate 2% sodium ligninsulfonate 2% synthetic amorphous silica 36% The active ingredient is first sprayed onto the amorphous silica, then the ingredients are blender', hammer-milled until all the solids are essentially under 50 microns, reblended, and packaged.

WO 91/03464 PC~/US90/04953 144 Example B Wettable Powder 2-(l-ethyl-l-methoxypropyl)-6-(phenylmethoxy)-7oxabicyclo[2.2.l]heptane sodium alkylnaphthalenesulfonate 2% low viscosity methyl cellulose 2% diatomaceous earth 46% The active ingredient is first sprayed onto the diatomaceous earth then,the ingredients are blended, coarsely hammer-milled and then air-milled to produce particles essentially all below 10 microns in diameter. The product is reblended before packaging.

Example C Granule Wettable Powder of Example B attapulgite granules 20-40 mesh; 0.84-0.42 mm) A slurry of wettable powder containing solids is sprayed on the surface of attapulgite granules in a double-cone blender. The granules are dried and packaged.

Example D Emulsifiable Concentrate 2-(1-ethyl-l-methoxypropyl)-6-(phenylmethoxy)-7oxabicyclo[2.2.llheptane Atlox 3403F 3% Atlox 3404F 3% xylene 54% The active ingredient and Atlox emulsifiers are dissolved in the solvent, filtered and packaged.

Atlox 3403F and 3404F are blends of anionic and ionic emulsifiers from ICI Americas, Inc.

C -iaL I WO 91/03464 P~r/US90/04953 145 Example E Low Strenath Granule 2-(l-ethyl-l-methoxypropyl)-6-(phenylmethoxy)-7oxabicyclo[2.2.1]heptane attapulgite granules 20-40 mesh) The active ingredient is dissolved in a solvent and the solution is sprayed upon dedusted granules in a double-cone blender. After spraying of the solution has been completed, the material is warmed to evaporate the solvent. Ti material is allowed to cool and then packaged.

Example F Granule 2-(l-ethyl-l-methoxypropyl)-6-(phenylmethoxy)-7oxabicyclo[2.2.1]heptane wetting agent 1% crude ligninsulfonate salt (containing 5-20% of the natural sugars) attapulgite clay 39% The ingredients are blended and milled to pass through a 100 mesh screen. This material is then added to a fluid bed granulator, the air flow is adjusted to gently fluidize the material, and a fine spray of water is sprayed onto the fluidized material. The fluidization and spraying are continued until granules of the desired size range are made. The spraying is stopped, but fluidization is continued, optionally with heat, until the water content is reduced to the desired level, generally less than The material is then discharged, screened to the desired size range, generally 14-100 mesh (1410-149 microns), and packaged for use.

WO 91/03464 PCT/US90/04953 146 Exam le G Concentrated Emulsion 2-(l-ethyl-l-methoxypropyl)-6-(phenylmethoxy)-7oxabicyclo[2.2.l]heptane xylene Atlox 3404F G1284 ethylene glycol 8% water 32% The active ingredient, solvent and emulsifiers are blended together. This solution is added to a mixture of the ethylene glycol and water with stirring.

Example H Solution 2-(l-ethyl-l-methoxypropyl)-6-(phenylmethoxy)-7oxabicyclo[2.2.1]heptane water The compound is added directly to the water with stirring to produce the solution, which may then be packaged for use.

Example I Dust 2-(l-ethyl-l-methoxypropyl)-6-(phenylmethoxy)-7oxabicyclo[2.2.1]heptane attapulgite Pyrophyllite The active ingredient is sprayed onto the attapulgite and then passed through a hammer-mill to a produce particles substantially all below 200 microns. The ground concentrate is then blended with powdered pyrophyllite until homogeneous.

c PCT/US90/04953 WO 91/03464 147

UTILITY

Test results indicate compounds of this invention are active postemergence and, in particular, preemergence herbicides. Many compounds in this invention are useful for the control of selected grass and broadleaf weeds with tolerance to important agronomic crops such as alfalfa (Medicaao sativa), barley (Hordeum vulaare), corn (Zea mays), cotton (Gossvpium hirsutum), rape (Brassica napui), rice (Orvza sativa), soybean (Glvcine max), sugar beet (Beta vulaaris), and wheat (Triticum aestivum).

Grass and broadleaf weed species controlled include, but are not limited to, barnyardgrass (Echinochloa crus-aalli), blackgrass (Alopecurus myosuroides), crabgrass (Diaitaria spp.), foxtail (Setaria spp.), lambsquarters (Chenopodium spp.), teaweed (Sida spinosa), umbrella sedge (Cvyerus difformis), and waterchestnut (Eleocharis spp.). Several compounds in this invention are particularly useful for the control of barnyardgrass and selected broadleaf weeds such as umbrella sedge and waterchestnut in upland and paddy rice.

These compounds also have utility for weed control of selected vegetation in specified areas such as around storage tanks, parking lots, highways, and railways; in fallow crop areas; and in citrus and plantation crops such as banana, coffee, oil palm, and rubber. Alternatively, these compounds are useful to modify plant growth.

Rates of application for compounds of this invention are determined by a number of factors.

These factors include: formulation selected, method of application, amount and type of vegetation present, growing conditions, etc. In general terms, c WO 91/03464 PCT/US90/04953 148 the subject compounds should be applied at rates from 0.01 to 20 kg/ha with a preferred rate range of 0.03 to 1 kg/ha. Although a small number of compounds show no herbicidal activity at the rates tested, it is anticipated these compounds have herbicidal activity at higher application rates. One skilled in the art can easily determine application rates necessary for the desired level of weed control.

Compounds of this invention may be used alone or in combination with other commercial herbicides, insecticides, or fungicides. The following list exemplifies some of the herbicides suitable for use in mixtures. A combination of a compound from this invention with one or more of the following herbicides may be particularly useful for weed control.

PCT/US9O/04953 WO 91/03464 149 Common Name acetochia r acifluorfen acrolein alachior ani lofos amet ryn ami trole

AMS

asulam atrazine ba rban benefin bensulfuron methyl bensulide bent azon Chemical Name 2-chloro-N- (ethoxymethyl (2-ethyl-6-methylphenyl) acetamide 5-12-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoic acid 2-propenal 2-chloro-N- 6-diethylphenyl (methoxymethyl) acetamide S-4-chloro-N-isopropylcarbani loylmethyl-O,O-dimethyl phosphorodithioate N-ethyl-N' 1-methylethyl) -6- (methylthio)-l,3, 5-triazine-2,4diamine 1H-1, 2, 4-triazol-3-amine ammonium sulfamate methyl ((4-aminophenyl)sulfonylJcarbamate 6-chloro-N-ethyl-N' 1-methylethyl) 1,3, 5-triazine-2, 4-diamine 4-chloro-2-butynyl 3-chlorocarbamate N-butyl-N-ethyl-2, 6-dinitro-4-(trif luoromethyl )benzenamine 2-E 6-dimethoxy-2-pyrimidinyl)aminojmethylcarbonyl) amino) sulfonyllmethyll benzoic acid, methyl ester O,O-bis(l-methylethyl) S-t2- [(phenylsulfonyl) amino) ethyl) phosphorodithio ate 3-(1-methylethyl)-(1H)-2, 1,3benzothiadiazin- 4(3H)-one, 2,2-dioxide 1 WO 91 /e,3464 pci',US9O/04953 150 Common Name Chemical Name benzofluor benzoylprop bifenox bromaci 1 bromoxyni 1 butachlor buthidazole butralin butylate cacodylic acid

CDAA

CDEC

CGA 142,464 chlorarnben c hlo r bromu ron chiorimuron ethyl N-[4-(ethylthio)-2-(trifluoromethyl) phenyl 3methanesulfonamide N-benzoyl-N- 4-dichiorophenyl) -DLa lanine methyl 5-(2,4-.dichlorophenoxy)-2nitrobenzoate 5-brorno-6-methyl-3- -methylpropyl) 2,4 (lH, 3H)pyrimidinedione 3, 5-dibromo-4-hydroxybenzonitrile N-(butoxymethyl)-2-chloro-N-(2, 6diethyiphenyl) acetamide 3- 1, 1-dimethylethyl)-1, 3, 4-thiadiazol-2-ylI -4-hydroxy-l-methyl-2imidazolidinone 1-dimethylethyl)-N-(l-methylpropyl)-2, 6-dinitrobenzenamine S-ethyl bis(2-methylpropyl)carbamothioate dimethyl arsinic oxide 2-chloro-N ,N-di-2-propenylacetamide 2-chloroallyl diethyldithiocarbamate 3-(4 ,6-dimethoxy-1, 3, 5-triazin-2-yl)- 1- [2-(2-methoxyethoxy) -pehnylsulfonyl] -urea 3-amino-2,5-dichlorobenzoic acid 3-(4-bromo-3-chlorophenyl )-l-methoxy-lmethylurea 2-f ft (4-chloro-6-methoxy-2-pyrimidinyl)ethylaminoJ carbonyl) amino) sulfonyl) benzoic acid, ethyl ester PCT/US90/04953 WO 91/03464 PTU9/45 151.

Common Name Chemical Name chiormethoxynil chiornitrofen chioroxuron chiorpropham chlorsulfuron chlortoluron cinmethylin clethodim c loma zone cloproxydim clopyrailid

CMA

cyanazine cyrtoate cy Iuron cyperquat 2,4-dichlorophenyl 4-nitro-3methozyphenyl ether 2,4, 6-trichlorophenyl-4-nitrophenyl ether N'-[4-(4-chlorophenoxy)phenyl]-N,Ndimethylurea 1-methylethyl 3-chlorophenylcarbamate 2-chloro-N-t I(4-methoxy-6-methyl-1,3,5triazin-2-yl) amino] carbonyl] benzenesulfonamide N' -(3-chloro-4-methylphenyl) -N,Ndimethylurea exo-l-methyl-4-(l-methylethyl)-2-t (2methylphenyl )methoxy] -7-oxabicyc lollheptane t(3-chloro-2-propenyl)oxy] iminolpropyl]-5-[2-(ethylthio)propyl] -3 4 hydroxy-2-cyclohexen-1-one 2-['(2-ch~orophenyl)methyl] 4-di'methyl- 3-isozazo lidinone (E,E)-2-[l-[[(3-chloro-2-propenyl)oxy)irinolbutyl]-5-t2-(ethylthio)propyl] 3-hydroxy-2-cyc lohexen-1-one 3,6-dichloro-2-pyridinecarboxylic acid calcium salt of MA.A [4-chloro-6-(ethylamino)-1,3 azin-2-yl] amino] -2-methylpropanenitri le S-ethyl cyclohexylethylcarbamothioate 3-cyclooctyl-1, 1-dimethylurea l-methyl-4-phenylpyridinium

MMA

WO 91/03464 PTU9/4~ pcy/uS90/04953 152 Common Name cyprazine cyprazole cypromid dalapon dazomet Chemical Name

DCPA

desmediphan desmet ryn diallate 2-chloro-4-(cyclopropylamino) isopropylamino) -B-triazine N-t5-(2-chloro-1, l-dimethylethyl)-l, 3,4thiadiazol-2-yl] cyclopropanecarboxamide 3' ,4 '-dichiorocyclopropanecarboxani lide 2,2-dichioropropanoic acid tetrahydro-3 ,5-dimethyl-2H-l, 3, di azine-2--thione dimethyl 2,3,5,6-tetrachloro-1,4-benzenedicarboxylate ethyl r3-r[(phenylamino)carbonyl~oxy)phenyl] carbamate 2-(isopropylamino)-4-(methylamino)-6- S-23-dichloro-2-propenyl)bis(lmethylethyl )carbamothioate 3, 6-dichloro-2-methoxybenzoic acid 2, 6-dichlorobenzonitrile ,4-dichiorophenoxy) propanoic acid (±)-2-[4-(2,4-dichlorophenoxy)phenoxy] propanoic acid, methyl ester N--(chloroacetyl)-N-(2,6-diethylphenyl)glycine 1, 2-dimethyl-3, 5-diphenyl-1H-pyrazolium S-1-methyl-l-phenylethylpiperidinel-carbothioate

N

3

,N

3 -diethyl-2,4-dinitro-6-(irifluoromethyl) 3-benzenediamine di camb a dichlobeni 1 dichlorprop dichiofop diethatyl difenzoquat dimepiper ate dinitramine WO 91/03464 PCT/US9O/04953 Commron Name Chemical Name dinoseb diphenamid dipropetryn diguat diuron

DNOC

D SMA dym ron endothal 1

EPTC

esproca rb (SC29 57) ethaifluralin 2-(1-methylpropyl)-4 ,6-dinitrophenol N, N-dimethyl-a-phelylbeflzefeacetamide 1,3, 5-triazine-2, 4-diamine 6, 7-dihydrodipyrido [1,2-a pyrazinedium ion N' ,4-dichlorophenyl)-N,N-dimethyllrea 2-methyl-4, 6-dinitrophenol disodium salt of MAA N- (4-methyiphenyl) -N'-(l-methyl- 1-phenylethyl)urea 7-oxabicyclo[2 1)heptane-2 ,3-dicarboxylic acid S-ethyl dipropylcarbamothioate S-benzyl-N-ethyl-N- 2-dimethyl) propyl) thiolcarbamate N-ethyl-N-(2-methyl-2-propenyl)-2, 6dinitro-4-(trifluoromethyl)benzenamine -2-ethoxy-2, 3-dihydro-3 ,3-dimethylrethanesulfonate 2,3,6-trichloroberizeneacetic acid (6-chloro-2-benzoxazolyl)oxylphenoxy~propanoic acid N,N-dimethyl-N' -phenylurea Salt of fenuron and TCA N-benzoyl-N-(3-chloro-4-fluorophenyl) DL-alanine ethofurnes ate fenac fenoxaprop fenuron fenuron TCA flamprop PC'r/US9/04953 WO 91/03464 Common-Name Chemical Name f luazif op f luazifop-P fluchioralin f luometuron f luorochioridone fluorodifen f luoroglycofen fluridone fomes afen fosamine glyphosate haloxyfop hexaflurate hexazinone imazamethabenz [5-(trifluoromethyl)-2-pyridinylloxylpherioxylpropanoic acid (R)-2-[4-[([5-(trifluoromethyl)-2-pyridinylloxylphenoxylpropaloic acid N-(2-chloroethyl)-2,6-diflitro07N-propyl- 4- (trifluoromethyl) benzenamine N,N-dimethyl-N' 3-(trifluoromethyl)phenyl] urea 3-chloro-4-(chloromethyl)-l- [3-(trif luoromethyl )phenyl] -2-pyrrolidinone p-tolyl ether carboxymethyl 5-(2-chloro-4-(trifluoromethyl)phenoxy] -2-nit robenzoate 1-methyl-3-phenyl-5- t3-(trifluoromethyl)phenyl] -4 (lH)-pyridirione 5-f 2-chloro-4-(trifluoromethyl)pheloxy) N-(methylsulfonyl) -2-nitrobenzamide ethyl hydrogen (aminocarbonyl)phosphate N- (phosphonomethyl) glycine [3-chloro-5-(trifluoromethyl)-2pyridinylloxylphenoxyjpropanoic acid potassium hexafluoroarsenate 3-cyclohexyl-6- (dimethylamino) -1-methyl- 1,3,5-triazine-2,4(lH,3H)-dione 6- (4-isopropyl-4-methyl-5-oxo-2imidazolin-2-yl)-rn-toluic acid, methyl ester and 6-(4-isopropyl- 4-methyl-5-oxo-2-imidazolin-2-yl) R-toluic acid, methyl ester PCr/US90/04953 WO 91/03464 PTU9/45 155 Common Name imazapyr imazaquin 0 imazethapyr ioxyni 1 isopropalin i soproturon i sou ron 0 isoxaben karbuti late lactofen Chemical Name (+)--[45-dihydro-4-methyl-4-( 1-methylethyl) -5-oxo-lH-imidazol-2-yl)-3pyridinecarboxylic acid 5-dihytlro-4-methyl-4-(l-methylethyl) -5-oxo-lH-imidazol-2-yl] -3quinolinecarboxylic acid 5-dihydro-4-methyl-4- (1-methylethyl)-5-oxo-lH-imidazol-2-yl] ethyl.-3-pyridinecarboxylic acid 4-hydroxy-3, 5-diiodobenzonitri le 4- -methylethyl) 6-dinitro-N ,Ndipropylbenzenamine N-(4-isopropylphenyl)-N' ,N'-dimethylurea N'-[5.-(1,-dimethylethyl)-3-isoxazolyl)- N, N-dimethylurea N- -ethyl-l-methylpropyl) isoxazolyl)-2, 6-dimethoxybenzamide t(dimethylamino)carbonyl) amino)phenyl-(l, l-dimethylethyl)cacbamate (±)-2-ethoxy-l-methyl-2-oxoethyl 5-[2chloro-4-(trifluoromethyl)phenoxy]- 2-nitrobenzoate 3-cyclohexyl-6 ,7-dihydro-lH-cyclopentapyrimidine-2 ,4(3H, N' ,4-dichlorophenyl)-N-methoxy-Nmethylurea methylarsonic acid monoammonium salt of MAA (4-chloro-2-methylphenoxy)acetic acid 4- (4-chloro-2-methylphenoxy) butanoic acid lenaci 1 linuron

MAA

MAM4A

MCPA

MCPB

WO 91/03464 C/S /043 PC-r/US90/04953 156 Common Name Chemical Name MON 7200 mecoprop mefenacet mef luidide metha1propalin methabenzthi azuron metham methazole methoxuron metolachior metribuzin metsulfuron methyl S, S-dimethyl-2-(difluoromethyl)-4- (2-methylpropyl) -6-(trifluoromethyl) 3, (4-chloro-2-methylphenoxy) propanoic acid 2- (2-benzothiazolyloxy-N-methyl-Nphenylacetamide N-t2,4-dimethyl-5-[ [(trifluorornethyl)sulfonyl) aminolphenyl] acetamide N-(2-methyl-2-propenyl)-2, 6-dinitro-Npropyl-4-(trifluoromethyl) benzenamide 1, 3-dimethyl-3-(2-benzothiazolyl)urea methylcarbamodithioic acid 2-(3 -dichlorophenyl)-4-methyl-1, 2,4oxadiazolidine-3, N (3 -chloro,4-rnethoxyphenyl Ndimethylurea 2-chloro-N- (2-ethyl-6-methylphenyl) -N- (2-methoxy-l-methylethyl) acetamide 4-amino-6-(Il -dimethylethyl)-3-(methylthio)-l,2, 4-triazin-5(4H)-one 2([[(4-methoxy-6-methyl-1, 3, azin-2-yl) arrino) carbonyl) aminolstufonyllbenzoic acid, methyl ester l12-dihydro-3, 6-pyridazinedione S-ethyl hexahydro-lH-azepine-l-carbothioate 3- (p-chlorophenyl )-l-methoxy-l-methylurea

MH

rnolinate ronolinuron I WO 91/03464 PCr/US90/04953 157 Common-Name Chemical Name monuron monuron TCA

MSMA

napropamide napta lam nebu ron nitralin nitrofen nitrofluorfen N (4-chiorophenyl N-dimethylurea Salt of monuron and TCA monosodium salt of MAA N, N-diethyl-2- -naphitha lenyloxy) propanamide (-naphthalenylamino)carbonyl)benzoic acid 1-butyl-3- 4-dichlorophenyl )-1-methylurea 4-(meth 'lsulfonyl)-2, 6-dinitro-N,Ndipropylani line 2,4-dichloro-l-(4-nitrophenoxy)benzene 2-chloro-l-(4-nitrophenoxy) -4-(trifluoromethyl) benzene N,N-dimethyl-N'-(octahydro-4 ,7-methano- 3aa,- 4a, 5a, 7c,7aa-isomer 4-chloro-5-(methylamino)-2- [3-(trif luoromethyl )phenyl] -3 (2H) pyridazinone 4-(dipropylamino)-3, benzenesul fonamide 3- 4-dichloro-5-( 1-methylethoxy) phenyl3-5-(1, 1-dimethylethyl)- 1, 3.4-oxadiazol-2(3H)-one 2-chloro-l-(3-ethoxy-4-nitrophenoxy) -4- (trifluoromethyl) benzene 1,1'-dimethyl-4,4'-dipyridinium ion S-propy. butylethylcarbamothioate N-(1-ethylpropyl)-3 ,4-dirnethyl-2 ,6dinitrobenzenamine norea norf lurazon ovty zal1in oxadiazon oxyf luorfen paraquat pebulate pendimethalin

I

PCI] US9O/0495.3 WO 91/03464 158 Common-14ame Chemical Name perfluidone phenmedipham picloram PPG- 1013 preti lachior procyazine profluralin prometon promet ryn pronamide propachior propanil propazine propham prosulfalin prynachior 1,1, 1-trifluoro-N-[2-methyl-4-(phelylsulfonyl) phenyl ]methanesulfonamide 3-[(methoxycarbonyl)amino)phenyl (3methyiphenyl )carbamate 4-amino-3 6-trichloro-2-pyridinecarboxylic acid 5- [2-chloro-4-(trifluoromethyl)phenoxy] -2-nit roacetophenone oxime-O-acetic acid, methyl ester a-chloro-2, 6-diethyl-N- (2-propoxyethyl) acetanilide 2- [[4-chloro-6- (cyclopropylamino) -1,3,5triazine-2-yl) amino]-2-methylpropanenitrile N-(cyclopropylmethyl)-2, 6-diriitro-Npropyl-4- (trifluoromethyl )benzenamine 6-methoxy-N,N' -bis(l-methylethyl)-1, triazine-2 ,4-di amine N,N'-bis(l-methylethyl)-6-(methylthio)- 1,3, 5-triazine-2,4-diamine 3, 5-dichloro-N- 1-dimethyl-2-propynyl )benzamide 2-chloro-N- -methylethyl phenylacetamide N-(3 ,4-dichlorophenyl)propanamide 6-chloro-N,N' -bis (l-rnethylethyl) 1,3, 5-triazine-2 ,4-diamine 1-methylethyl phenylcarbamate N-I 14-(dipropylarnino)-3, phenyl] sulfonyl]-S,S-dimethylsulfilimine 2-chloro-N- (l-methyl-2-propynyl) acetanilide WO 91/03464rcU9/45 PCr/US90/04953 159 Common Name pyrazolate pyrazon pyrazosulfuron ethyl quinclorac quizalofop ethyl secbumeton sethoxydim siduron simazine SK-233 sul1fometuron methyl.

TCA

tebuthiuron terbuchior Chemical Name 4-(2 ,4-dichlorobenzoyl) 3-dimethyl- 5-amino-4-chloro--2-phenyl-3 (2H) pyridazinone ethyl S- t3-(4 ,6-dimethoxypyrimidin-2yl)ureadosulfonyl] -1-methylpyrazole- 4-carboxylate 3,7-dichloro-8-quinoline carboxylic acid (±)-2-[4-[(6-chloro-2-quinoxalinyl)oxylpherzoxylpropanoic acid, ethyl ester N-ethyl-6-methoxy-N' 1-methylpropyl) 1,3, 5-triazine-2 ,4-diamine 2-[l-(ethoxyimino)butyl] [2-(ethylthio)propyl] -3-hydroxy-2-cyclohexen- 1-one N-(2-methylcyclohexyl)-N t-phenylurea 6-chloro-N,N'-diethyl-l,3, 2, 4-diamine phenyl )urea 2-t 6-dimethyl-2-pyrimidinyl)aminolcarbonyljaminolsulfonyllbenzoic acid, methyl. ester trichloroacetic acid l-dimethylethyl)-1,3,4-thiadiazol-2-yl]-N,NI -dimethylurea 5-chloro-3- 1-dimethylethyl) -6methyl-2 ,4 (1H, 3H) -pyrimidinedione dimethylethyl)-6-methylphenyl] acetamide -7- WO 91/03464 WO 91/03464PCI-IUS9O/04953 160 Common Name terbuthylazine terbutol terbutryn thifensulfuron methyl thiobencarb triallate tribenuron In methyl Chemical Name 2- (tert-butylamino) -4-chloro-6- (ethylamino) -§-triazine bamate N-Cl, 1-dimethylethyl -ethyl-6- (methylthio)-1,3, 2, 4-diamine 3-Eli [(4-methoxy-6-methyl-1, 3, 2-yl)aminolcarbonyl] aminolsulfonyl] 2-thiophenecarboxylic acid, methyl ester S-[(4-chlorophenyl)methyl] diethylcarbamothio ate S-(2,3,3-trichloro-2-propenyl) bis(lmethylethyl) carbamothioate 2-ti I[N-(4-methoxy-6-methyl-1,3,5triazine-2-yl)-N-methylamino] carbonyl] amino] sulfonyl] benzboic acid, methyl ester 6-trichloro-2-pyridinyl) oxylacetic acid 3, 5-dichlorophenyl trichioroethyl) oxirane 2, 6-dinitro-N,N-dipropyl--4-(trif luorornethyl )benzenamine 1- (p-chlorophenyl 3-trimethylpseudourea (2,4-dichlorophenoxy)acetic acid 4-(2,4-dichlorophenoxy)butanoic acid S-propyl dipropylcarbamothioate 2-chloro-N- 3-dimethyiphenyl) -N- (1-methylethyl) acetamide triclopyr tridiphane trifluralin trimeturon 2, 4-D 2, 4 -DB vernolate xylachlor WO 91/03464 PCr/S90/0953 161 Herbicidal properties of the subject compounds were discovered in a number of greenhouse tests.

Test procedures and results follow.

p 1 -"Iv- WO 91/03464 PCi, US9O/04953 TABLE (18) Physical Properties Configuration Q Ratio Crnpd R 1

R

2

R

3

R

4

R

5 Partial NMR 6) 1 CH 3

CH

3 H B CH 2 Ph 2 CH 3

CH

3 H H CH 2

CH=CH

2

CH

2 (Ph)

CH

2 2-FPh) oil, exo, 1: 2 oil, exo, 1: 2 4.58-4.36 (rn,2H), 3.54 (m,2H), 3.20 (m,lH), 5.90 (nm,lH), 5.32-5.06 (m,2H), 4.54 (dq,2H), 3.94 (m,211), 3.6-3.43 (m,2H), 3.16 (m,1H) 5.90 (m,1H), 5.28-5.15 (m,2H), 4.44 (dg,2H), 3.84 (m,2H), 3.55-3.43 (m,211), 3.15 (nM,lH) 3 CFI 3

CH

3 H H CH 2

CH=CH

2

CH

2 (2-(CH 3 )Ph) oil, exo, 1:2 PCri US9O/04953 WO 91/03464 Physical Properties Configuration Q Ratio Partial NMR (6) Cmpd R 1

R

2

R

3

R

4

R

5 4 CH 3

CH

3 H H CH 2

CH=CH

2

CH

3

CH

3 H H CH3 6 CH 3

CH

3 H H CH 2

CH

3 7 CH 3

CH

3 H H CH 2

CH

3 8 CH 3

CH

3 H H CH 2

CH

3 9 CH 3

CH

3 H H CH 2

CH

3

CH

3

CH

3 H H CH 3

CH

2 (Ph)

CH

2 (2-FPh) Oil, exo, 1: 2 oil, exo,

CH

2 (2,6-F 2 Ph) oil, endo

CH

2 (2,6 -C' 2 Ph) oil, endo 5.90 (rn,l), 5.3-5.16 (m,2H) 4.49 (dq,2H), 3.94 (m,2H), 3.58-3.42 (m,MH, 3.16 (rn,lH) 4.52 (dd,2H), 3.56 (dd,lH), 3.43 (dd,lH), 3.3 (s,3H), 3.12 (dd,lH) 3.3 (m,4H), 4.60 (d,lH), (d,lH), 3.76 (dd,lH) 4.76 (d,lH), 4.66 (d,1H), 3.74 (dd,lH), 3.3 (rn,4H), 4.58 (d,lH), 4.45 (dflH), 3.56 (dd,1H), 3.4-3.1 (m,4B) 4.73 (dd,lH), 4.64 (dd,lH), 3.4-3.1 (m,4H) 4.73 (dd,1H)f 4.64 (dd,lH), (m,2H), 3.08 (dd+dd, 1H-1:1 ratio)

CH

2 2-FPh)

CH

2 6-Cl 2 Ph)

CH

2 6-Cl 2 Ph) oil, exo, 3: 1 oil, emo, 2: 1 oil, exo, 1:1 WO 91/03464PC/U9043 PCr/US90/04953 Physical Properties Configuration Ratio Cmpd Fl. R 2

R

3

R

4

R

5 Partial NMR (6) 11 CH 3

CH

3 H H Et 12 CH 3

CH

3 H H CH 3 13 CH 3

CH

3 H H Et 14 CH 3

CH

3 H H Et

CH

2 (2-BrPh) oil, exo, 2:1

CH

2 (2-BrPh) oil, exo, 1:1

CH

2 (2-ClPh) oil, endo

CH

2 (2-BrPh) oil, endo 4.56 (d,lH), 4.43 (dd,lH), 3.60 (ddlH), (m,3H), 3.12 (dd+dd,lH), 4.58 (d~lH), 4.42 (dd,lH), 3.61 (dd,lH), 3.45 (m,lH) 3.3 (s+s,3H), 3.1 (dd+dd..lH) 4.61 (d,lH), 4.56 (d,lH), 13.82 (dd,lH), 3.35 (m,4H) 4.59 (d,lH), 4.43 (d,lH), 3.84 (dd,1H), 3.25 (m,4H), 5.61 (mi,2H), 4.56 (d,1H), 4.50 (d,lH), 3.9 (d+d,2H) (dd+dd,2H), 3.14 (dd~lH) 4.56 (dd+s,4H), 3.81 (dd,lH), 3.45 (dd,2H), 3.29 (s,3H) CH 3

CH

3 H H CH 2

CH=CH(CH

3

CH

2 (2-FPh) oil, exo 16 CH 3

CE

3 H H CH 2

OCH

3

CH

2 (2-FPh) oil, endo PCT/US90/04953 WO 91/03464PCIU9/95 Physical Properties Configuration g Ratio Cnipd R 1

R

2

R

3

R

4

R

5 Partial NMR(6) 17 CH 3

CH

3 18 H H 21 H H H CH 2

CH

3

CH

2 (2-(CH 3 )Ph) oil, exo

CH

3

CH

3

CH

3

CH

3

CH

3

CH

3

CH

2 (2-(CH 3 )Ph) oil, exo

CM

2 Ph) 22 CM 3

CH

3

CH

3

CH

3

CH

2

CH

3

CH

2 (2-FPh) 23

CM

3

CH

3

CM

3

CM

3

CH

2

CM

3

CH

2 (Ph) oil, exo oil, exo oil, exo oil, exo oil, exo 4.53 (d,lM), 4.35 (d,lH), 3.45 (m,4H), 3.13 (dd,lH) 4.6 (br,lH), 4.50 (m,3M), 3.65 3.18 (s,3H) 4.55 (t,lH), 4.49 (rn,3H), 3.64 (dd,1H), 3.16 (s,3H) 4.59 (d,lM), 4.45 (d,lH), 3.55 (dd,lH), 3.38 (dq,2H) 4.52 (dd,lH), 4.40 (dd,lH), 3.52 (dd,lM), 3.37 (dg,2H) 4.65 (m,4H), 3.72 (dd,lH), 3.22 (s,3H) 4.75 (dd,2H), 4.59 (m,2H), 3.75 (dd,lH), 3.18 (s,3H) 4.7 (ni,4H), 3.7 (dd,lH), 3.2 (s,3H) H H Et Et CM 3 26 H H Et Et CM 3

CM

2 (Ph)

CH

2 6-Cl 2 Ph) 27 H H Et Et CH 3

CH

2 (2-(CH 3 oil, exo PcT/US90/04953 WO 91/03464PC!U9/45 Physical Properties Configuration Q Ratio Cmpd R 1

R

2

R

3

R

4 R5 Partial NMR(6) 28 H H Et Et CH 3 29 H H Et Et CH 3 H H Et Et CH 3 31 H H Et Et CH 3 32 H H n-Pr n-Pr CH 3 33 H H n-Pr n-Pr CH 3 34 H H n-Pr n-Pr CH 3 H H n-Pr n-Pr CH 3 36 H H n-Pr n-Pr CH 3

CH

2 2-FPh)

CH

2 (2-ClPh)

CH

2 (2-BrPh)

CH

2 2, 6-F 2 Ph)

CH

2 (Ph)

CH

2 (2-(CH 3 )Ph)

CH

2 2-FPh)

CH

2 2-CiPh)

CH

2 (2-BrPh) oil, exo oil, exo oil, exo oil, exo oil, exo oil, exo oil, exo oil, exo oil, exo 3.73 3.72 (dd,lH), 3.2 (s,3H) 4.59 (b,4H), 3.71 (dd,lH), 3.18 (s,3H) 4.56 (br,4H), 3.68 (dd,lH), 3.17 (s,3H) 4.52 (m,4H), 3.62 (dd,lH), 3.15 (s,3H), 4.50 (t,lH), 4.48 (dd,lH), 4.45 3.62 (d,lH), 3.19 (s,3H), 4.45 (ri,4H), 3.65 (dd,lH), 3.19 (s,3H) 4.50 (mr,4H), 3.68 (dd,lH), 3.176 (s,3H) 4.50 (nm,4H), 3.69 (dd,lH), 3.17 (s,3H) Physica].

Properties Configuration Ratio Partial NMR Cmpd R 1 R 2

R

3 37 H H n-Pr H H Pr 41 H H n-Pr n-Pr Pr n-Pr

CH

3

CH

2 Ph

CH

2 6-F 2 Ph) CH 2 (Ph) oil, exo oil, exo 4.50 (m,4H), 3.67 (dd,1H), 3.16 (s,3H) 4.9-4.6 (m,6H), 3.8 (dd,lH)

CH

2 (2-CH 3

CH

2 (2-(CH 3 )Ph) oil, exo 4.6-4.4 (m,6H), 42 H H n-Pr 48 H H CH=CH 2 n-Pr CH 2 (2-F(Ph)) CH 2 (2-FPh)

CH

2 (Ph) oil, exo oil, exo

CH=CH

2

CH

2 CH 3 3. 6 (dd,1IH) 4.6 (m,6H), 3.72 (dd,lH) 5.95-5.7 (m,2H), 5.4-5.1 (m,4H), 4.6-4.45 (m,4H), 3.68 (dd,lH), 3.35 (q,2H) Physical Properties Configuration Ratio Cmpd RI R 2

R

3 Partial NMR 8) 49 H H CH=CH 2 H H CH-CH 2

CH=CH

2

CH

2

CH

3

CH=CH

2

CH

2

CH

3

CH

2 (2-CH 3 )Ph) oil, exo

CH

2 2-FPh)

CH

2 Ph) oil, exo oil, exo 5.95-5.7 (m,2H), 5.4-5.15 (m,411), 4.65-4.4 (m,4H), 3.68 (dd,lH), 3.33 (q,lH) 5.95-5.6 (m,2H), 5.36-5.16 (m,4H), 4.57 (m,4H), 3.72 (dd,lH), 3.33 (q,2H) 6.0-5.8 (m,2H), 5.15-5.0 (ni,4H), 4.61=4.4 (m,4H), 3.62 (dd,lH), 3.45 (q,2h) 51 H H CH 2

CH=CH

2 CH 2 CH=CH 2

CH

2 CH 3 Physical Properties Configuration Ratio Cmpd RI R 2 R 3 Partial NMR( 6) 52 H H CH 2 CH=CH 2 CH 2

CH=CH

2 CH2CH 3 53 H H CH 2

CH=CH

2 CH 2

CH=CH

2 CH 2

CH

3 54 H H CH 2

CH=CH

2 CH 2

CH=CH

2

CH

3

CH

2 (2-(CH 3 )Ph) oil, exo

CH

2 (2-FPh)

CH

2 (Ph) oil, exo oil, exo 5.8-6.0 (rn,2H), 5.15-5.0 (m,4H), 4.6-4.4 (m,4H), 3.62 (dd,lH), 3.46 (q,2H) 6.0-5.72 (m,2H), 5.2-4.95 (m,4H), 4.58 (m,4H), 3.65 (dd,lH), 3.45 (q,2H) 6.0-5.75 (m,2H), 5.15-5.0 (m,4H), 4.62-4.4 3.62 (dd,lH), 3.25 (s,3H) Physical Properties Configuration Ratio Cmpd RI R 2

R

3 Partial NMR S) H H CH 2

CH=CH

2 CH 2

CH=CH

2

CH

3 56 H H CH 2

CH=CH

2 CH 2

CH=CH

2 CH 3 57 H H CH 2

CH=CH

2

CH

2

CH=CH

2 CH 3

CH

2 (2-(CH 3 )Ph) oil, exo CH 2 (2-FPh) oil, exo 5.9 (m,2H), 5.15-5.0 (m,411), 4.6-4.4 (m,4H), 3.62 (dd,lH), 3.26 (s,3H) 6.0-5.75 (m,2H), 5.1-5.0 (m,4H), (m,4H), 3.65 (dd,lH), 3.26 (s,3H) 6.95-6.8 (dd,2H), 6.04-5.75 (m,2H), 5.15-5.00 (m,2H), 4.55 (m,4H), 3.66 (dd,lH), 3.26 (s,3H)

CH

2 2 Ph) oil, exo Physical Properties Configuration Partial Ratio NMR(S) Cmpd R R 2

R

3 0 R 58 H HI CH 2

CH=CH

2

CH

2

CHC

2 C3 CH 2 (2,6-(Cl) 2 Ph) oil, exo oil, exo 59 H H CH 2

CH

2

CH

3 CH 2

CH

2

CH

3

CH

2 CH=CH 2 C11 2 (Ph) 6.02-5.75 (m,2H), 5.15-5.04 (m,4H), 4.8-4.55 (m,4H), 3.70 (dd,lH), 3.27 (q,3H) 6.0-5.8 (dd 1H), 5.28 (dd,1H), 5.10 (dd,lH), 4.58 (brs,2H), 4.51 3.82 3.62 (dd,lH) Us

W'

Physical Properties Configuration Partial Ratio NMR(S) Cmpd RI R 2

R

3 H H CH 2

CH

2

CH

3 61 H H CH 2 CH 2 CH 3

CH

2

CH

2

CH

3 CH 2 CH 2

CH

3

CH

2 CH=C1 2

CH

2 2-FPh) CH 2 CH=CH 2

CH

2 2 Ph) oil, exo oil, exo oil, exo 6.0-5.8 (ni,1H), 5.26 (dd,1H), 5.10 (dd,lH), 4.58 (br,4H), 3.85 3.65 (dd, 1H) 6.88 (t,211), 6.0-5.79 (ni,1HL, 5.28 (did,1H), 5.10 (dd,lH), 4.56 (m,4H), 3.87 3.65 (dd,lH) 6.0-5.78 (m,1H), 5.27 (dd,1H), 5.09 (dd.1ll), 4.59 (br,2H), 4.50 (dd,2H) 62 H H CH 2

CH

2

CH

3

CH

2

CH

2 CH 3

CH

2

CH

2

=CH

2 CH 2 (2-(CH 3 )Ph) Physical Properties Configuration Partial R4R5 0 Ratio NMR(S) Cmpd RI R 2

R

3 63 H H CH 2

CH(CH)

3 64 H H CH 2

CH(CH)

3 H H CH 2

CH(CH)

3

CH

2

CH(CH)

3

CH

2

CH(CH)

3

CH

2

CH(CH)

3 CH 3

CH

2 (Ph)

CH

3 C11 2 (2-FPh)

CH

3

CH

2 (2-ClPh) oil, exo oil, exo oil, exo 4.66 (m,2H), 4.58 (rn,2H), 3.73 (dd,lH), 3.27 (s,3H) 4.62(rn,lH), 3.72 (dd,lH). 3.28 (s,3H) 4.66 (ni,4H), 3.75 (dd,lH), 3.26 (s..3H) 4.65 (m,2H), (dd,lH), 3.26 (s,3H) 4.59 (m,4H), 3.72 3.24 (s..3H) 66 H H CH 2

CH(CH)

3 67 H H CH 2

CH(CH)

3

CH

2 CH(CH) 3 CH 2

CH(CH)

3 Cl! 3

CH

2 (2-(CH 3 )Ph)

CH

3

CH

2 (2-BrPh) oil, exo oil, exo

I

Physical Properties Configuration Partial 0 Ratio tIMR(S) Cmpd R 1 R 2 R 3 68 H H CH 2

CH(CH)

3 69 H H CH 2

CH(CH)

3 H H CH 2

CH

3

CH

2 CI(CH 3

CH

2

CH(CH)

3

CH

2

CH

3 C1 2 2 Ph)

CH

2 (2,6-(Cl) 2 Ph) oil, exo oil, exo oil. exo oil, exo

CH

2

CH=CH

2 C1 2 (Ph)

CH

3

CH

2 (Ph) 4.58 (m,4H), 3.7 (dd,lH), 3.26 (s..3H) 4.78 (m,3H), 3.83 (dd,lH), 3.22 (s,3H) 6.0-5.8 (m,IH), 5.4-5.05 4.55 3.9 (dd,2H), 3.65 (dd,2H) 4.55 (ni,4H), 3.63 (dd,lH), 3.15 31) 71 H H CH 2

CH

2

CH

2

CH

3

CH

2

CH

2

CH

2

CH

3 Physical Properties Configuration Partial Ratio NMR(S) Cinpd R' R 2

R

3 72 H H CH 2

CH

2

CH

2

CH

3

CH

2

CH

2

CH

2

CH

3 CH 3 73 H H CH 2

CH

2

CH

2 CH 3

CH

2

CH

2

CH

2 CH 3 CH 3 74 H H CH 2

CH

2

CH

2

CH

3

CH

2

CH

2

CH

2

CH

3 CH 3 H H CH 2

CH

2

CH

2 CH 3

CH

2

CH

2

CH

2 CH 3 CH 3 76 H H CH 2

CH

2 CH 2

CH

3

CH

2

CH

2

CH

2 CH 3 CH 3

CR

2 2-FPh)

CH

2 (2-ClPh)

CH

2

CH

3 Ph)

CH

2 (2-BrPh) CH 2 2 Ph) oil, exo oil, exo oil, exo oil, exo oil, exo 4.58 (m,4H, 3.63 (dd,lH), 3.17 3H) 4.6 (m,4H), 3.69 (dd,lH), 3.17 3H) 4.6-4.42 (m,4H), 3.62 (dd,1H), 3.17 (s,3H) 4.58 (m,4H), 3.7 (dd,LH), 3.17 (s,3H) 4.57 (m,4H), 3.63 (dd,1H), 3.16 3H) Physical Properties Configuration Partial Ratio NMR(S) Cmpd RI R 2

R

3 77 H H CH 2

CH

2 CH 2

CH

3

CH

2

CH

2

CH

2

CH

3 CH 3 78 H H CH 2

CH

2

CH

3 79 H H CH 2

CH

2

CH

3 H H CH 2

CH

2

CH

3

CH

2

CH

2

CH

3

CM

3

CH

2

CH

2

CH

3

CM

3

CH

2

CH

2

CH

3

CH

3

CH

2 (2,6-(Cl) 2 Ph)

CH

2 (2,4-IF' 2 Ph

CH

2 (4-FPh)

CH

2 (3-FPh) oil, exo oil, exo oil, exo oil, exo 4.74(brm,2H), 4.58 (br,2H), 3.70 (dd,lM) 3.17 (s,3H) 6.8 (m,2H), 4.59 4.51 3.64 (dd,lH), 3.17 (s,3H) 4.61 (t,lH), 4.54 4.48 3.16 (s,3H) 4.55 (t+d+ds,41), 4.64 3.18 3H) Physical Properties Configuration Partial Ratio NMR(S) Cmpd R 1

R

2

R

3 81 H H CH 2

CH

2

CH

3 82 H H CH 2

CH

2

CH

3 83 H H CH 2

CH(CH

3 )2 84 H H CH 2

CH(CH

3 )2

CH

2

CH

2

CH

3

CH

2 C1 2 CH 3 Cl! 3 C1 2 2 Ph)

C!

2 3-CiPh)

CH

2 2 Ph) oil, exo oil, exo oil, exo oil, exo 4.5 (m,4H), 3.64 (dd,lH), 3.17 (s,311) 4.6 (t,1H, 4.55 4.48 3.62 (dd,lH), 3.16 (s,311) 6.8 (m,211), 4.53 (m,411), 3.68 (dd,lH), 3.28 (S,311) 4.6-4.5 (in,41), 3.62 (dd,1H), 3.22 31)

CH

2

CH(CH

3 2

CH

2

CH(CH

3 )2 CH 2 (4-FPh) Physical Properties Configuration Partial Ratio NMR(F) Cnipd R' R 2 R 3 H H CH 2

CH(CH

3 )2 86 H H CH 2

CH(CH

3 )2 87 H H CH 2

CH(CH

3 )2 88 H H CH 2

CH

3 89 H H CH 2

CH

3

CH

2 CH(C11 3 2

CH

2

CH(CH

3 )2

CH

2

CH(CH

3 )2

CH

2 CH 3 CH 2 CH 3 CH 2 (3-FPh) CH 2 2 Ph) CH 2 (3-ClPh)

CH

2 2 Ph)

CH

2 (4-FPh) oil, exo oil, exo oil, exo oil, exo oil, exo 4.6-4.5 (m,4H), 3.63 (dd,lH), 3.23 (s,3H) 4.6 (m,4H), 3.66 (dd,1H), 3.23 (s,3H) 4.62 (m,2H), 3.62 (dd,1H), 3.28 (s,3H) 4.6-4.5 (m,4H), 3.64 (dd,1H), 3.17 (s,3H) 4.6-4.5 (m,4H), 3.61 (dd,1H), 3.16 3H) U1n 0 Physical Properties Configuration Partial Ratio NMR(S) Cnipd RI R 2

R

3 H H CH 2

CH

3 91 H H CH 2

CH

3 92 H H CH 2 C11 3 93 H H CH 3 94 H H CH 3

CH

2

CH

3

CH

2

CH

3 CH 2

CH

3

CH

2 (3-FPh)

CH

2 2 Ph) CH 2 3-CiPh) CH 2 (Ph)

CH

2 (2-FPh) oil, exo oil, exo oil, exo oil, exo oil, exo 4.7-4.4 (m,4H), 3.64 (dd,lH), 3.16 (s,3H) 4.8-4.5 (ni,4H), 3.70 (dd,lH), 3.18 (s,3H) 4.7-4.4 (m,4H), 3.63 (dd,lH), 3.17 3H) 4.6-4.5 (m,4H), 3.65 (dd,lH), 3.15 (s,3H) 4.58 (m,4H), 3.7 (dd,lH), 3.16 (s,3H)

CH

2

CH

2

CH

3

CH

3

CH

2

CH

2

CH

3

CH

3 L- Physical Properties Configuration Partial Ratio N4R( 8) Cmpd R' R 2

R

3 RI H CH=CH 2 96 H H CH=CH 2 97 H H CH=CH 2

CH=CH

2

CH=CH

2

CH=CH

2

CH

2 (Ph)

CH

2 2-FPh)

CH

2 2 Ph) oil, exo oil, exo oil, exo 5. 8 2H) 5.3 4.54 3.69 (dd,1H), 3.15 (s,311) 5.8 (ni,2H), 5.27 (wn,4H), 4.57 3.70 (dd,lH), 3.16 3H) 5.8 (m,2H), 5.3 (ni,4H), 4.53 3.70 (dd,lH), 3.16 (s,3H) Physical

D

Properties Configuration Partial Ratio NMR(S) Cmpd RI T;2 R*3 98 H H CH=CH 2 99 H H CH=CH 2 100 H H CH=CH 2

CH=CH

2

CH=CH

2

CH=CH

2 CH 2 (4-FPh) CH 2 2 Ph)

CH

2 2 Ph) oil, exo oil, exo oil, exo 5.8 (m,2H), 5.3 (ni,4H), 3.65 (dd,lH), 3.16 (s,3H) 5.8 5.3 4.51 3.70 (dd,lH), 3.16 (s,3H) 5.8 (ni,2H), 5.3 4.55 (ni,4H), 3.70 (dd,lH), 3.17 (s,3H) r- I I Physical Properties Configuration Partial Q Ratio HMR(S) Cmpd R 1 R 2 R 3 R 4 R 5 101 H H H 102 H H CH 3 103 'H H CH 3 104 H H CH 3

CH

2

CH

2

CH

3

CH

2

CH

2

CH

3

CH

3

CH

2

CH

2

CH

3

CH

3

CH

2

CH

2

CH

3

CH

3

CH

2 2-CiPh)

CH

2 2 Ph)

CH

2 (2-(CH 3 )Ph) CH 2 2 Ph) oil, exo oil, exo oil, exo oil, exo 4.61 (br,4H), 3.71 (dd,lH), 3.17 (s,3H) 4.57 (m,4H), 3.7 (dd,lH), 3.17 (s..3H) 4.6 (ni,2H), (d+d,21) 3.64 (dd,lH), 3.16 (s,3H) 4.58 (br,2H), 4.52 (br,2H) 3.7 (dd,lH), 3.16 3H) 0 '0 Physical Properties Configuration Partial Ratio NMR(S) Cinpd R I R 2

R

3 105 H H CH 2

CH

3 106 H H CH 2

CH

2

CH

3 107 H H CH 3 108 H H CH 3

CH

2

CH

3

CH

2

CH

2 CH 3

CH

2 CH 3

CH

2

CH

3 CH 2 (2-tetrahydropyran)

CH

2 (2-tetrahydropyran)

CH

2 Ph)

CH

2 (2-FPh) oil, exo oil, exo oil, exo oil, exo 4.59 (t,lH), 4.5 (s,lH) (dd,lH), 3.4 (m,211), 3.31 3.18 (s,311) 4.5 (t+s,1H), 3.5 -3.3 (ni,6H) 3.17 (s,3H) 4.5 (m,4H), 3.7 (dd,1H) 3.15 (s,3H) 4.59 (brs,4H), 3.7 (dd,1H) 3.16 (s,3H) Physical Properties Configuration Partial 0 Ratio NMR(S) Cmpd R 1

R

2

R

3 109 H H CH 3 110 H H CH 3 ill H H CH 3 112 N, H CH 3

CH

2

CH

3

CH

2

CH

3

CH

2 2 Ph)

CH

2 (2-(CH 3 )Ph)

CH

2 (Ph)

CH

2 (2-FPh) oil, exo oil, exo oil, exo oil, exo

CH

2

CH

2

CH

2

CH

3 CH 3

CH

2

CH

2

CH

2

CH

3

CH

3 4.58 (brs,4H), 3.71 (dd,1H) 3.17 (s,3H) 4.5 (m,4H), 3.69 (dd,lH) 3.16 (s,3H) 4.5 (m,4H), 3.69 (dd,lH) 3.15 (s,3H) 4.58 (m,4H), 3.7 (dd,lH) 3.16 (s..3H) 4.6 (m,4H), 3.71 (dd,1H) 3.17 (s,3H) 113 H H CH 3

CH

2

CH

2

CH

2

CH

3

CH

3

CH

2 (2-ClPh) oil, exo Physical

D

Properties Configuration Partial Q Ratio Cmpd RI R 2 R 3 114 H H CH 3 115 H H CH 3 116 H H CH 3 117 H H CH 3

CH

2

CH

2

CH

2 CH 3

CH

3

CH

2

CH

2

CH

2 CH 3 CH 3

CH

2

CH

2

CH

2 CH 3

CH

3

CH

2 CH 2

CH

2 CH 3

CH

3

CH

2 (2-(CH 3 )Ph)

CH

2 2 Ph)

CH

2 (2,f C L1) 2 Ph)

CH

2 2 Ph) oil, exo oil, exo oil, exo oil, exo 4.5 (m,4H), 3.69 (dd,1H) 3.16 3H) 4.57 (m,4H), 3.7 (dd,lIH) 3.17 (s,3H) 4.61 (s,lH), 4.59 (E,lH), 3.71 (dd,lH) 3.17 (s,3H) 4.5 (m,1H), 3.7 (dd,1IH) 3.16 js.3H) WO 91/03464 PCr/ US90/04953 TABLE 11

:(R

3 )CR')0R Physical Properties w Configuration Crnpd R 2

R

2

R

3

R

4

R

5 Partial

NMR(S)

43 H H H H CH 2

CH

3 44 H H H H CH 3 H H H H CH 3 2 -FPh Ph 2-FPh ezo, oil, exo exo, oil, exo exo, oil, exo exo, oil, exo exo, oil, exo 4.5 (d,d,4H), 3.78 (dd,1H), 3.45-3.28 (m,8H) 4.52 (d,d,4H), 3.63 3.5-3.3 (s+s,6H), 4.62 (d,lH), 4.51 (d,1H), 3.6-3.3 (m,13H) 4.48 (d,d,4H), 3.75 (dd,1H), 3.4 (ni,8H) 4.5 (m,4H), 3.75 (dd,lH), 3.4 (rn,8H) 46 H H H H CH 2

CH

3 2-(CH 3 )Ph 47 H H H H CH 2

CH

3 pCTI US9O/04953 WO 91/03464 R 3

(R

4 0R (111) Physical Properties Configuration Cmrpd R 1

R

3 R4 R 5

R

9 Rio Q Partial NMR(& 118 CH 3 H H CH 3 H H CH 2 (Ph) 119 CH 3 H H CH 3 H H CH 2 (2-FPh) oil, endo oil, endo 4.64 (d,l1H) 4.44 (d,lH), 3.82 (m,2H), 3.32 (s,3H), 3.21 3H) 4. 6 (m~,1H) 3. 8 2H) 3.31 (s,3H), 4.65 4.48 (d,1H), 3.78 (m,ZH), 3.32 (s,3H), 3. 2 3H) 120 CH 3 H H CH 3 H H CH 2 2 Ph) oil, endo WO 91/03464 WO 91/3464 Cri US9O/04953 Physical Properties Configuration Partial NfMR 6) Cnmpd R 1

R

3 R4 R 5

R

9 Rio Q 121 H H H CH 2

CH

3 H H CH 2 (Ph) 122 H H H CH 3 123 H H H CH 3 124 H H H CH 3 H H CH 2 (Ph) H H CH 2 (2-FPh) H H CH 2 (2-(CB 3 )Ph) oil, endo oil, endo oil, endo oil, endo 4.36 (d~d,1H), 4.40 (d,1H), 3.91 (d,MH, 3.759 (dd,lH), 3.45 (rn,3H), 3.25 0d,2H) 4.40 (d,1H), 3,90 (d,lH), 3.7 (dd,2H), 3.31 (s,3H), 3.3 (m,1H) 3.1 (rn,2H) 4.62 (s,MH) 4.40 (d,1H), 3.90 (d,lH), 3.71 (dd,lH), 3.32 (s,3H), 3.21 (m,2H) 4.53 (dd,2H), 4.39 (d,1H), 3.90 (d,1H), 3.7 (dd,1H), 3.31 (s,3H), 3.31 (M,1H), 3.10 (m,2H) pCi-IUS9O/04953 WO 91/03464 Physical Properties Configuration Partial NMdR(6 Crnpd R' R 3 R4 R 5

R

9 Rio Q 125 H H H CH 3 126 H H H CH 3 127 H H H CH 3 128 H H H CH 3 H H CH 2 (2-ClPh) oil, endo H H CH 2 2,6-(F) 2 Ph) oil, endo 4.64 (s,2H), 4.40 (d,1H), 3. 9 1H) 3.72 (dd,1H), 3.4 (dd,1H), 3.32 (s,3H), 3.2 (rn,2H) 4.61 (s,2H), 4.4 (d,1H), 3.9 (d,lH), 3.7 (dd,1H), 3.38 (dt,lH), 3.32 (s,3H), 3.2 (d+d,2H) 4.56 (s,2H), 4.38 (d,1H), 3.89 (d,lH), 3.72 (dd,1H), 3.38 (m~lH), 3.31 (s,3H), 3.20 (d+d,2H) 4.59 (s,2H), 4.40 (d,1H), 3.90 (d,1H), 3.75 (dd,1H), 3.38 (m,1H), 3.33 (s,3H), 3.2 (m,2H) H H CH 2 2 Ph) oil, endo H H CH 2 2 Ph) oil, endo WO 91/03464 prU9/45 PCT/US90/04953 Physical Properties Configuration Cnipd RI R 3 R4 R

R

9 Ri Partial NMR 6 129 H H H CH 3 130 CH 3 H H CH 3 H H CH 2 (2,6-(Cl) 2 Ph) oil, endo H H CH 2 (2-(CH 3 )Ph) oil, endo 131 CH 3 H H CH 2

CH

3 H H CH 2 (Ph) oil, endo oil, endo 4.78 (dd,2H), 4.43 (d,lH), 3.9 (d,lH), 3.7 (dd,1H), 3.4 (m,MH, 3.32 (s,3H), 3.2 (dd,2H) 4.63 (d,1H), 4.41 (d,lH), 3.84 (rn,lH), 3.4-3.2, 6H) 4.65 (d,lH), 4.45 (d,lH), 3.85 (d+dd~lH), 3.44 (dg,6H), 3.26 (m,3H) 4.7 (d,lH), (d,lH), 3.87 (d+dd,2H), 3.43 (dq,2H), 3.28 (d+m,3H) 4.63 (d,1H), 4.40 (d,1H), 3.83 (d+dd,2H), 3.42 (dq,2H), 3.27 (dein,3H) 132 CH 3 H H CH 2

CH

3 H H CH 2 (2-FPh) 133 CH 3 H H CH 2

CH

3 H H CH 2 (2-(CH 3 )Ph) oil, endo WO 91/03464 WO 9103464PCY/US9O/04953 Physical Properties Configuration Crnpd RH'R R4 R 5

R

9 Rio Q Partial NMR 6 134 CH 3 H H CH 2

CH

3 H H CH 2 2 Ph) oil, endo 135 CH 3 H H CH 2

CH

3 H H CH 2 (2-ClPh) oil, endo oil, endo 136 CH 3 H H CH 3 137 CH 3 H H CH 3 138 H CH 3 CH 3 CH 3 139 H CH 3 CH 3

CH

3 H H CH 2 (2-ClPh) 4.71 (d,lH), 4.50 (d,lH), 3.8 (d+dd,2H), 3.42 (dq,2H), 3.27 (d+m,3H) 4.72 (d,1H), (d~lH), 3.82 (d+dd,2H), 3.45 (dq,2H), 3.3 (m,3H) 4.71 (d,1H), 4.54 (d,lH), 3.88 (m,2H), 3.3 (m,6H) 4.83 (d,lH), 4.72 (d,lH), 3.9 (rn,2H), 3.33 (s,3H), 3.33 (m,1H), 3.23 (rn,2H) 4.65 (d+d,2H), 4.40 (d,lH), 3.3 (t,1H), 3.15 (s,3H) 4.65 (d+d,2H), 4.39 (d,1H), 3.31 (t,1H), 3.15 (s,3H) H H CH 2 (2,6-(Cl) 2 Ph) oil, endo

CH

3

CH

3

CH

2 (Ph)

CH

3 CH 3

CH

2 (2-FPh) endo nm.p. 78-801C e ndo m.p. 84-86 0

C

WO 91/03464PC!S9/45 PCT/US90/04953 Cmpd R 1

R

3 R4 R 5 R9 R 1 o Q Physical Properties Configuration endo M.P. 50-52*C Partial NMR S8) 140 H CH 3

CH

3

CH

3

CH

3

CH

3 CH 2 (2-ClPh) 141 H CH 3 CH 3

CH

3

CH

3

CH

3

CH

2 2 Ph) 142 H CH 3

CR

3

CH

3 CH 3

CH

3

CH

2 (2.-(CH 3 )Ph) e ndo M. P. 102-104 0

C

endo rn.p. 49-501C 143 H CR 3

CR

3

CR

3

CH

3

CR

3

CH

2 (2,6-(Cl) 2 Ph) endo MT.P. 100-101 0

C

4.65 4.42 (d,1H), 3.38 (t,lH), 3.16 (s..3H) 4.66 (d+d,2R), 4.39 (d,lH), 3.31 (t,4H), 3.14 (s,3H) 4.6 (d+d,2H), 4.4 (d,1H), 3.29 (t,lR), 3.15 (s..3H) 4.82 (s,2H), 4.4 (d,1H), 3.3 (t,1H), 3.14 (s.3H) 4.6 (d+d,2H), 4.39 (d,lH), 3.11 (t,1H), 3.15 (s,3H) 4.64 (d.1H), 4.46 (d,1R), 3.50 (dd,1H), 3.34 (s,3H), 3.21 (dd,1R) 144 H CHR 3

CH

3

CHR

3 CH 3

CH

3

CH

2 2 Ph) 145 CR 3 Hi H CH 3

CR

3

CH

3

CH

2 (Ph) e ndo M~.P. 102 -103 0

C

oil, endo pC-riUS90/04953 WO 91/03464 Physical Properties Configuration Partial NMR( 6 Crnpd R 1

R

3 R4 R 5

R

9 Ri 0 146 CH 3 H H CH 3

CH

3 147 CH 3 H H CH 3

CH

3 148 CH 3 H H CH 3

CH

3

CH

3

CH

2 (2-F(Ph) oil, endo

CH

3

CH

2 2 Ph) oil, endo

CH

3

CH

2 (2-ClPh) 149 CH 3 H H CH 3

CH

2

CH

3

CH

2

CH

3

CH

2 (Ph) 150 CH 3 H H CH 3

CH

2

CH

3

CH

2

CH

3

CH

2 (2-FPh) oil, endo oil, endo oil, endo 4.69 (d,lH), 4,50 (d,1H), (dd,1H), 3.4 (dd,lH), 3.35 3H) 3.25 (dd,lH) 4.70 (d,lH), 4.50 (d,lH), 3.50 (dd,1H), 3.40 (dd,lH), 3.35 (s,3H) 3.21 (d+d,1H) 4.72 (d,lH), 4.52 (d,1H), 3.52 (dd,1H), 3.39 (dd,1H), 3.35 (s,3H) 3.30 (dd,1H) 4.64 (d,lH), 4.48 (d,lH), 3.45 (dd,lH), 3.34 (s,3H) 3.34 (dd,1H) 3.20 (dd,lH) 4.68 (d,1H), 4.52 (d,1H), 3.45 (dd,lH), 3.34 (s+dd,4H) 3.24 (dd,1H) WO 91/03464 ciS9/45 PCT/US90/04953 Physical Properties Configuration Partial NMR( S6) Cmrpd

R

1 RR4 R 5

R

9 151 CH 3 H H CH 3

CH

2

CH

3

CH

2

CH

3

CH

2 2 Ph) oil, endo 152 CH 2

CH

3 H H CH 3

H

153 CH 2 CH 3 H H CH 3

H

154 CH 2

CH

3 H H CH 3

H

155 CH 2

CH

3 H H CH 3

H

H CH 2 (Ph) H CH 2 (2-FPh) oil, endo oil, endo 4. 7 (d,1IH) 4. 5 1H) 3.45 (s+dd,lH), 3.24 (dd,1H) 4.65 (d,1H), 4.40 (d,1H), 3.9 (d,1H), 3.78 (dd,lH), 3.36 (dd,2H), 3.33 (s,3H), 3.24 (dd+dd,2H) 4.7 (d,lH), 4.45 (d,1H), 3.9 (d,lH), 3.79 (dd,1H), 3.4 (dd,2H), 3.33 (s,3H), 3.24 (dd+dd,2H) 4.7 (d,1H), 4.47 (d,1H), 3.89 (d.1H), 3.78 (dd,1H), 3.39 (dd,2H), 3.36 (s,3H), 3.26 (dd+dd,2H) 4.75 (d,lH), 4.46 (d,lH), 3.91 (d,lH), 3.8 (dd,1H), 3.44 (dd,2H), 3.34 (S,3H), 3.25 (dd+dd,2H) H CH 2 2 Ph) oil, endo H CH 2 (2-ClPh) oil, endo WO 91/03464 ciU9/45 PCY/US90/04953 Physical Properties Configuration Cmpd R 1 R R4 R 5

R

9 RIO Q Partial NMR(S 156 CH 2

CH

3 H H CH 3 H H CH 2 (2,6-(Cl) 2 Ph) endo m.p. 77-77.5*C 157 CH 2 CH 3 H H CH 3 H H CH 2

(CH

3 )Ph) 158 CH 2 CH 3 H H CH 3 H H CH 2 (2-BrPh) oil, endo oil, endo 4.82 (d,1H), 4.69 (d,1H), 3.89 (d,lH), 3.79 (dd,lH), 3.4 (dd,2H), 3.34 (s,3H), 3.24 (s+s,2H) 4.85 (d,1H), 4.38 (d,lH), 3.9 (d,1H), 3.8 (dd,1H), 3.39 (dd,2H), 3.34 (s,3H), 3.22 (m,2H) 4.71 (d,1H), 4.41 (d,lH), 3.92 (d,lH), 3.80 (dd,lH), 3.46 (dd,2H), 3.33 (s,3H), 3.24 (m.,2H) WO 91/03464 PUU9/45 PCr/US90/04953 196 TABLE 13 R3 )R4 R

(III)

Cnmpd R 1

R

3 R 4

R

5

R

9 Rio Q~ Physical Properties Configuration Ratio Partial NMR 6) 159 CH 3 H H CH 3 H H CH 2 (Ph) 160 CH 3 H H CH 3 H H CH 2 P(2-FPh) oil, endo oil, endo 4.64 (d,1H), 4.44 (d,lH), 3.88 (d,1H), 3.32 (s,3H), 3.2 (mT,3H) 4.7 (d,1H), 4.52 (d.1H), 4.88 (d,1H), 4.81 (dd,1H), 3.33 (s,MH, 3.3-3.2 (nm,3H) 4.7 (d,1H), (d,1H), 3.85 (d,1H), 3.8 (dd,1H), 3.33 (s.,WH, 3.22 (m,3H) 161 CH 3 H H CH 3 H H CH 2 P(2,6-(F) 2 Ph) oil, endo PCT/ULS90104953 WO 91/03464 jC(R)C XR) (111) Physical Properties Configuration Cmpd RI R 3 R 4~ R5 9

RIO

0

Q

Partial NMR S6) 162 H H H CH 3

CH

3 H CH 2 (Ph) 163 H H H CH 3

CH

3 H CH 2 (2-FPh) 164 H H H CH 3

CH

3 H CH 2 (Ph) oil, endo oil, endo oil, endo 4.62 (d,1H), 4.52 (d,1H), 4.35 (s,lH), 4.09 (q,1H), 3. 5 IH) 3.4 (dd,1H), 3.32 (dd,lH), 3.36 (s..3H) 4.62 (d~d,2H), 4.36 (s,1H), 4.06 (q,1H), (t,1H), 3.4 (dd,lH), 3.36 (s.3H), 4.62 (d,2H), 4.54 (d,1H), 4.23 (s~nm,2H), 3.4 (d,2H), 3.34 (m..1H)

I

WO 91/03464 PCT/US90/04953 Crnpd R 1

R

3 R 4

R

5

R

9 Rio Q Physical Properties Configuration 165 H H H CH 3 Cl 3 H CH 2 (2-FPh) oil, endo Partial NMR(6 4.63 (d+d,2H), 4.24 (m+s,2H), 3.41 (d,2H), 3.35 (s,3H), WO 91/03464 PTU9/45 PCT/US90/04953 Cnmpd R' R 3

R

4

R

5 1 R 9 Physical Properties Configuration Partial NMR (6) 166 CH 3 H H CH 2

CH

3 H CH 2 (Ph)

CH

2 2 -FPh) oil, endo oil, endo 167 CH 3 H H CH 2

CH

3 H H 168 CH3H H CH 2

CH

3 H H 4.55 (s,2H), (d+d+dd, 3H), 3.68 1H) 3. 4 (nm,4H), 3.38 (dd, 1H) 4.6 (d~d,2H), 4.07 (t~d,2H), 3.9 (d,1H), 3.69 (dd,l1-I), 3.4 (m,4H), 3.4 (dd,lH) 4.55 (d+d,2H), 4.05 (d,1H), 4.04 (dd,1H), 3.9 (d,lH), 3.69 (t,1H), 3.49 (rr,4H), 3.35 (dd,JIH)

CH

2 (2-(CH 3 )Ph) oil, endo WO 9 1/03464 PCTI US9O/04953

I

(VIII)

R 3

R

4 Physical Properties Configuration Partial NMR 6) Cmpd RI R 2 169 H H CH 2

CH

3

CH

2

CH

3

CH

2 (Ph) CH 2 (ph) oil, endo 170 H H CH 2

CH

3

CH

2

CH

3 CH 2 (2-FPh) CH 2 (2-FP'h) oil, endo 4.67 (m,4H), 4.51 (s+d,2H), 3.65 (d+d,2H), 3.13 (s,3H) 4.70 (d,4H), -4.52 (6+d,2H), 3.7 (d+d,2H), 3.15 (s,3H) 4.71 (brs,2H), 4.45 (s~d,2H), 3.66 (d,1H), 3.52 (d,lH), 3.42 (s,3H), 3.15 (s,3H) 171 H H CH 2

CH

3

CH

2

CH

3

CH

3 CH 2 (2-FPh) oil, endo i 0 WO 91/03464 PCT/US90/04953 201 TEST A Seeds of barley (Hordeum vulaare), barnyardgrass (Echinochloa crus-galli), cheatgrass (Bromus secalinus), cocklebur (Xanthium pensylvanicum), corn (Zea mays), cotton (Gossypium hirsutum), crabgrass (Digitaria spp.), giant foxtail (Setaria faberi), morningglory (Ipomoea spp.), rice (OrYza sativa), sorghum (Sorghum bicolor), soybean (G1vcine Max), sugar beet (et vulgarisjj), velvetleaf (Abutilon theophrasti), wheat (Triticum aestivum), and wild oat (Avena fatua) and purple nutsedge (Cyp.erus Xtanius) tubers were planted and treated preemergence with test chemicals dissolved in a non-phytotoxic solvent. At the same time, these crop and weed species were also treated with postemergence applications of test chemicals. Plants ranged in height from two to eighteen cm (two to three leaf stage) for postemergence treatments. Treated plants and untreated controls were maintained in a greenhouse for approximately sixteen days, after which all species were compared to untreated controls and visually evaluated. Plant response ratings, summarized in Table A, are based on a scale of 0 to where 0 is no effect and 10 is complete control.

A dash response means no test result.

PCT/US90/04953 WO 91/03464 piIU9/45 COMPOUND COMPOUND Rate (2000 g/ha) 43 44 45 46 47

POSTEMERGENCE

Barley 0 0 0 0 0 Barnyardgrass 0 0 0 0 0 Cheatgrass 0 0 0 0 0 Cocklebur 3 0 0 0 0 Corn 0 0 0 0 0 Cotton 0 0 0 0 0 Crabgr ass 3 0 0 3 Giant foxtail 0 0 0 0 0 Morningglory 0 0 0 0 0 Nutsedge 0 0 0 0 Rice 0 0 0 0 0 Sorghum 0 0 0 0 0 Soybean 0 0 0 0 0 Sugar beet 0 0 0 0 0 Velvetleaf 0 0 0 0 0 Wheat 0 0 0 0 0 Wild Oat 0 0 0 0 0 Rate (2000 g/ha) 43 44 45 46 47

PREEMERGENCE

Barley 0 0 0 0 0 Barnyardgrass 0 2 2 0 0 Cheatgrass 0 0 0 0 0 Cocklebur 0 0 0 0 0 Corn 0 0 0 0 0 Cotton 0 0 0 0 0 Crabgrass 4 0 0 0 2 Giant foxtail 5 2 3 5 3 Morningglory 0 0 0 0 0 Nutsedge 0 0 0 Rice 0 0 0 0 0 Sorghum 0 0 0 0 0 Soybean 0 0 0 0 0 Sugar beet 0 0 0 0 0 Velvetleaf 0 0 0 0 0 Wheat 0 0 0 0 0 Wild Oat 0 0 0 0 0 L- mwsmumwm WO 91/03464 PCr/US90/04953 203

COMPOUND

Rate (400 g/ha) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 16

POSTEMERGENCE

Barley 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 Barnyardgrass 6 0 0 0 9 9 0 9 3 2 3 2 6 0 0 Cheatgrass 0 0 0 0 0 0 0 0 0 0 0 0 0 3 0 Cocklebur 2 1 2 1 4 1 0 3 2 3 2 1 2 0 0 Corn 0 0 0 0 5 1 0 5 0 0 0 0 2 0 0 Cotton 8 0 0 0 0 0 0 2 0 0 0 0 0 0 0 Crabgrass 0 0 0 0 8 2 0 9 3 0 3 0 2 0 Giant foxtail 0 0 0 0 8 4, 0 9 2 0 0 0 0 2 4 Morningglory 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Nutsedge 0 00 90 00 0 000 0 0 Rice 1 1 0 0 0 0 0 6 0 0 0 0 0 0 0 Sorghum 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Soybean 3 0 1 0 3 0 0 2 0 0 0 0 0 0 0 Sugar beet 0 0 0 0 0 2 0 0 0 0 0 0 1 2 0 Velvetleaf 1 0 0 0 0 0 0 0 0 6 0 2 0 0 0 Wheat 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Wild Oat Wild Oa 0000 000 0 000 00 0 WO 91/03464PC!U9/43 PCIF/US90/04953 204

COMPOUND

Rate (400 g/ha) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 16 P RE EMERGEN CE Barley 0 3 0 2 5 0 0 2 0 0 0 0 0 0 0 Barnyardgrass 10 10 910 109 01 7 8 9 880 7 Cheatgrass 0 0 0 0 6 3 0 4 0 0 2 3 0 0 2 Cocklebur 0 0 0 0 3 4 0 5 0 0 0 5 0 0 Corn 0 3 0 3 6 4 0 4 0 0 0 0 0 0 2 Cotton 0 0 0 0 2 0 0 3 0 0 0 0 0 0 0 Crabgrass 9 9 7 9 9 6 0 9 7 8 7 7 0 3 0 Giant foxtail 9 9 8 9 9 6 0 9 7 7 8 7 2 0 Morningglory 0 0 0 0 0 0 0 0 0 5 0 0 0 0 0 Nutsedge 0 0 0 0 0 4 0 2 0 0 0 0 0 0 0 Rice 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Sorghum 0 9 0 8 7 0 0 5 0 0 0 0 0 0 6 Soybean 0 0 0 1 6 0 0 3 2 0 0 0 0 0 0 Sugar beet 0 1 0 0 2 4 0 3 0 0 0 0 0 0 0 Velvetleaf 1 1 1 1 7 0 0 6 2 5 2 6 0 0 1 Wheat 0 0 0 0 2 0 0 3 0 0 0 0 0 0 0 Wild Oat 0 0 0 0 3 2 0 0 0 0 2 0 0 0 0 m 0

COMPOUND

Rate (200 g/ha) 18 21 22 23 25 26 27 28 29 30 31 32 33 35 36 37 40 41 42 43 44 45 46 47 48 49 50 51 52

POSTEMERGENCE

Barley 0 0 0 0 6 0 0 0 0 3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Barnyardgrass 0 0 0 2 9 0 0 3 0 0 6 9 0 0 0 5 0 0 0 0 0 0 0 0 0 0 2 0 0 Cheatgrass 0 0 0 0 0 0 0 0 0 0 2 3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 4 0 0 Cocklebur 1 1 1 1 2 3 4 1 1 1 1 6 4 2 1 1 1 0 0 0 0 0 0 0 1 1 2 1 1 Corn 0 0 0 0 7 0 0 4 0 0 2 5 0 0 0 0 0 0 0 0 0 0 0 0 0 3 0 0 0 Cotton 0 0 0 0 0 0 0 0 0 0 0 2 0 0 4 0 0 0 0 0 0 0 0 0 0 0 1 0 0 Crabgrass 0 0 0 3 6 4 0 3 0 0 8 0 0 0 3 0 0 0 0 0 0 0 0 0 0 7 Giant foxtail 2 0 0 0 2 0 0 0 0 0 9 9 0 0 0 8 0 0 0 0 0 0 0 0 0 2 0 1 0 Morningglory 0 0 0 0 0 0 1 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Nutsedge 0 0 0 0 7 0 8 0 9 0 0 0- 0 0 0 0 0 0 0 Rice 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 Sorghum 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Soybean 0 0 0 0 1 0 0 2 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 Sugarbeet 0 0 0 0 0 0 0 2 0 0 2 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 4 0 0 Velvetleaf 0 0 0 0 0 1 8 0 8 0 3 7 0 2 3 0 0 0 0 0 0 0 0 0 1 1 5 1 Wheat 0 0 0 0 7 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Wild Oat 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

U'

COMPOUND

0 Rate (200 g/ha) 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81

POSTEMERGENCE

Barley 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Barnyardgrass 3 0 0 6 0 2 0 0 2 3 1 0 0 0 0 0 0 2 2 0 0 0 0 0 0 3 0 3 3 Cheatgrass 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 6 Cocklebur 0 1 1 1 2 1 1 3 2 1 1 3 0 1 1 1 0 1 1 1 2 1 1 1 1 0 1 1 1 Corn 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Cotton 0 0 0 1 3 0 0 0 0 0 3 3 2 0 0 6 5 0 0 0 0 0 0 0 0 0 0 0 0 Crabgrass 0 0 0 0 0 3 8 4 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Giant foxtail 0 0 2 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5 0 0 0 Morningglory 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Nutsedge 6- 0 0 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Rice 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 4

S

Sorghum 0 0 0 0 0 0 5 3 0 3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Soybean 0 0 0 0 1 0 0 1 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Sugar beet 3 0 0 5 3 3 4 2 2 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 Velvetleaf 0 1 0 5 1 1 6 1 2 3 3 2 2 2 1 1 0 0 0 0 0 0 0 0 0 Wheat 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Wild Oat 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3

LI

wa

COMPOUND

0 Rate (200 g/ha) 82 83 84 85 86 87 88 89 90 92 93 94 95 96 97 98 99 100 101 102 103 104 107 111 112 113

POSTEMERGENCE

Barley 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Barnyardgrass 0 0 0 0 2 0 0 0 0 0 8 8 0 0 7 0 0 0 3 4 4 0 5 0 7 0 Cheatgrass 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Cocklebur 0 0 5 0 0 0 1 1 2 1 2 2 4 2 3 1 1 1 1 1 1 1 1 1 1 Corn 0 0 0 0 0 0 0 0 0 2 2 2 0 0 0 0 0 0 0 0 0 0 6 0 1 0 Cotton 0 0 0 0 0 0 0 0 0 0 0 7 0 0 0 0 0 0 0 0 0 0 0 0 0 Crabgrass 0 0 0 0 0 0 2 2 0 0 2 2 0 2 0 1 0 0 2 3 0 0 0 0 0 0 Giant foxtail 0 0 0 0 0 0 0 0 2 0 4 2 0 0 7 0 0 0 0 5 3 0 4 0 0 0 Morningglory 0 0 0 0 0 0 0 0 0 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Nutsedge 0 0 0 0 0 0 0 0 4 0 0 0 0 0 0 0 0 0 0 0 0 0 Rice 0 0 0 0 0 0 0 0 0 0 2 2 0 0 0 0 0 0 0 5 0 0 0 .0 0 0

C

Sorghum 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 0 0 0 0 0 0 Soybean 0 0 0 0 0 0 0 0 0 0 2 0 1 3 1 0 0 0 1 1 3 0 0 0 0 0 Sugar beet 0 0 0 0 0 0 0 0 0 0 1 0 0 2 4 0 0 0 0 0 0 0 0 0 0 0 Velvetleaf 0 0 2 0 0 0 0 3 0 1 2 0 0 2 0 1 0 0 0 0 0 Wheat 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Wild Oat 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

U.

COMPOUND

Rate (200 g/ha) 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135

POSTEMERGENCE

Barley Barnyardgrass Cheatgrass Cocklebur Corn Cotton Crabgrass Giant foxtail Morningglory Nutsedge Rice Sorghum Soybean Sugar beet Velvetleaf Wheat Wild Oat 6 9 0 0 0 0 9 9 0 0 0 0 9 9 0 0 0 0 1 1 0 1 1 8 9 0 0 0 0 0 3 2 0 0 0 9 9 0 0 0 0 9 9 0 0 0 0 1 0 0 0 0 0 8 0 0 0 9 9 0 3 1 1 7 4 1 2 2 7 9 9 0 0 0 0 0 2 0 1 0 1 1 0 0 0 0 0 0 0 0 3 0 0 0 0 0 6 0 9 8 6 -8 0 0 0 4 0 0 1 4 4 2 0 0 2 0 0 0 7 5 4 3 0 9 0 0 0 0 0 0 0 0

COMPOUND

136 137 138 139 140 141 142 145 146 147 148 149 150 151 152 153 154 155 156 157 158 166 Rate (200 g/ha)

POSTEMERGENCE

Barley Barnyardgrass Cheatgrass Cocklebur 7 0 8 1 6 0 0 3 0 0 9 9 3 9 8 0 Corn Cotton Crabgrass Giant foxtail Morningglory Nutsedge Rice Sorghum Soybean Sugar beet Velvetleaf Wheat Wild Oat 0 0 0 0 0 0 0 0 0 0 0 3 0 0 8 6 9 0 0 0 0 0 2 2 0 0 0 0 0 1 1 1 1 2 2 7 0 2 2 1 1 1 1 1 7 2 0 0 0 0 0 3 6 5 0 1 0 2 8 8 9 2 0 8 0 0 1 0 0 0 0 0 0 0 0 1 0 0 0 0 8 2 6 5 4 3 3 0 2 2 3 0 0 0 0 0 0 6 1 0 0 0 9 9 9 8 4 9 2 0 0 9 0 0 0 0 0 0 2 9 2 0 0 3 9 9 9 9 3 8 7 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 6 9 7 0 0 0 0 0 1 0 0 0 0 0 4 0 9 0 0 0 0 9 9 9 3 0 2 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 6 5 0 3 3 0 0 0 5 3 0 0 0 0 0 0 1 0 0 0 0 0 8 5 2 3 2 2 2 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 3 0 0 1 0 0 0 0 5 5 0 0 0 0 0 3 2 1 1 3 0 2 7 3 8 6 6 8 4 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 2 7 6 0 0 7 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 0 0 0 0 0 if PCrIUS90/04953 WO 91/03464 210

COMPOUND

Rate (200 g/ha) 167 168

POSTEMERGENCE

Barley 0 0 Barnyardgrass 1 2 Cheatgrass 0 0 Cocklebur 1 1 Corn 0 0 Cotton 0 0 Crabgrass 0 0 Giant foxtail 2 -0 Morningglory 0 0 Nutsedge 0 0 Rice 0 0 Sorghum 0 0 Soybean 0 0 Sugar beet 0 0 Velvetleaf 2 0 Wheat 0 0 Wild Oat 0 0

COMPOUND

Rate (200 g/ha) 18 21 22 23 25 26 27 28 29 30 31 32 33 35 36 37 40 41 42 43 44 45 46 47 48 49 50 51 52

PREEMERGENCE

Barley 0 0 2 0 3 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Barnyardgrass 2 9 9 9 9 0 9 10 9 6 9 9 9 9 8 9 0 0 0 0 0 0 0 0 10 8 10 3 0 Cheatgrass 0 3 2 2 7 0 0 3 0 0 6 0 0 0 0 2 0 0 0 0 0 0 0 0 0 3 2 0 0 Cocklebur 0 0 0 0 0 3 7 8 0 0 0 0 0 0 0 0 0 4 0 0 0 0 0 7 0 0 Corn 0 0 0 0 3 0 0 1 2 0 2 3 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 Cotton 0 0 0 0 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Crabgrass 2 5 5 6 8 7 0 8 8 2 0 4 2 1 5 8 2 0 0 0 2 0 0 0 3 4 7 0 3 Giant foxtail 2 9 8 6 9 6 8 9 5 6 9 9 8 9 7 9 0 0 0 0 0 0 0 0 9 6 9 2 3 Morningglory 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Nutsedge 0 0 0 0 0 0 3 0 0 0 0 0 0 0 0 0 0 0 0 0 4 0 0 0 0 0 0 0 0 Rice 0 0 0 0 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Sorghum 0 0 0 0 8 0 0 8 0 0 2 9 0 0 0 2 0 0 0 0 0 0 0 0 0 3 7 0 0 Soybean 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Sugar beet 0 0 0 0 3 0 0 3 0 2 0 0 0 0 0 0 5 0 0 0 0 0 0 0 0 0 0 0 0 Velvetleaf 2 2 1 1 5 0 2 4 8 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 Wheat 0 0 0 0 3 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 Wild Oat 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 "0j

COMPOUND

0 Rate (200 g/ha) 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81

PREEMERGENCE

Barley 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Barnyardgrass 3 9 0 9 10 2 10 10 2 0 9 5 0 0 0 0 0 7 7 8 0 0 0 4 0 9 9 9 9 Cheatgrass 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 0 Cocklebur 0 0 0 3 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 Corn 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Cotton 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Crabgrass 0 4 0 6 0 4 0 0 0 6 0 2 0 0 0 0 0 0 0 0 0 0 0 2 0 4 2 0 0 Giant foxtail 4 7 4 4 6 2 9 9 8 0 8 8 1 4 1 4 0 7 6 5 2 0 1 7 3 9 8 8 8 Morningglory 0 0 0 1 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Nutsedge 0 0 10 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Rice 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Sorghum 0 4 0 5 3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 Soybean 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Sugar beet 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 Velvetleaf 0 0 1 3 2 0 0 0 2 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Wheat 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Wild Oat 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 U't 0~ 0

COMPOUND

Rate (200 g/ha)

PREEMERGENCE

Barley Barnyardgrass Cheatgrass Cocklebur Corn Cotton Crabgrass Giant foxtail Morningglory Nutsedge Rice Sorghum Soybean Sugar beet Velvetleaf Wheat Wild Oat 82 83 84 85 86 87 88 89 90 92 93 94 95 96 97 98 99 100 101 102 103 104 107 Il1. 112 113 0 20 0 10 10 1 02 4 00 8 0 63 00 2 09 9 4 10 10 00 1 0 0 10 00 0 02 2 00 0 00 0 00 0 00 0 00 0 00 0 ~010 10 1010 7 2 24 20 0 03 0 -0 0 00 2 30 0 00 0 00 0 3 3q 9 52 0 99 9 78 00 0 00 0 36 0 00 0 0 0 020 0 02 7 00 0 00 0 00 0 00 3 10 0 77 5 02 0 00 2 00 0 00 0000 0 0 000 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

COMPOUND

Rate (200 g/ha) 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135

PREEMERGENCE

Barley Barnyardgrass Cheatgrass Cocklebur Corn Cotton Crabgrass Giant foxtail ?orningglory Nutsedge Rice Sorghum Soybean Sugar beet Velve ticaf Wheat Wild Oat 9 9 9 0 10 10 10 10 9 7 10 2 0 6 3 2 5 9 8 0 0 4 7 0 10 10 10 8 10 10 10 9 0 2 3 0 0 4 9 0 9 9 10 0 10 10 10 0 9 8 9 0 4 3 5 0 7 8 8 0 7 8 9 0 4 6 8 0 0 5 0 10 0 3 0 0 0 7 0 0 2 10 8 10 0 1 0 10 0 7 0 9 0 8 0 2 4 7 0 5 0 0 0 9 0 10 10 8 10 0 0 1 0 3 9 3 3 3 0 10 10 10 10 1 1 0 0 5 0 7 9 0 9 10 9 5 9 1 2 5 2 7 2 0 8 0 0 7 0

COMPOUND

Rate (200 g/ha) 136 137 138 139 140 141 142 145 146 147 148 149 150 151 152 153 154 155 156 157 158 166

PREEMERGENCE

Barley Barnyardgrass Cheatgrass Cocklebur Corn Cotton C rabgr ass Giant foxtail Mo rningglory Nutsedge Rice Sorghum Soybean Sugar beet Velvetleaf Wheat Wild Oat 1 0 10 10 5 2 0 9 0 2 0 10 9 10 9 0 0 0 0 1 0 10 2 6 0 7 7 7 7 1 0 3 0 0 1 10 10 5 0 0 0 5 6 0 0 9 10 9 9 0 0 0 10 0 0 9 8 0 0 0 0 0 5 2 3 0 0 0 7 8 10 10 10 0 7 7 2 9 3 0 10 10 0 1 2 3 10 10 5 10 10 0 2 3 0 10 10 0 10 9 0 10 10 0 9 9 0 4 5 0 9 9 0 8 6 0 6 2 8 0 0 10 10 9 5 2 3 1 0 9 3 0 6 1 0 10 10 9 10 10 9 2 0 0 0 0 0 8 2 0 9 4 0 8 2 0 7 6 3 9 6 7 8 0 0 3 2 0 L- WO 91/03464PC!U9/45 PC'F/US90/04953 216

COMPOUND

Rate (200 g/ha) 167 168

PREEMERGENCE

Barley 0 0 Barnyardgrass 10 7 Cheatgrass 2 0 Cocklebur 0 0 Corn 1 0 Cotton 0 0 Crabgrass 9 Giant foxtail 10 7 Morningglory 0 0 Nutsedge 0 0 Rice 5 0 Sorghum 2 0 Soybean 1 0 Sugar beet 4 0 Velvetleaf 1 2 Wheat 0 0 Wild Oat 0 0 6- mnmmffiwm

COMPOUND

Rate (100 g/ha)

POSTEMERGENCE

Barley Barnyardgrass Cheatgrass Cocklebur Corn Cotton Crabgrass Giant foxtail Morningglory Nutsedge Rice Sorghum Soybean Sugar beet Velvetleaf Wheat Wild Oat 1 2 3 4 5 6 7 8 9 10 11 12 13 1415 16 1734 40 4142105106 0 0 0 0 0 1 3 0 0 0 0 0 3 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0

I

COMPOUND

Rate (100 g/ha)

PREEMERGENCE

Barley Barnya rdgras s Cheatgrass Cocklebur Corn Cotton Crabgrass Giant foxtail.

Morningglory Nutsedge Rice Sorghum Soybean Sugar beet Velvetleaf Wheat 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 34 40 41 42 105 106 Wild Oat 0il Oa 0 00 00 0000 00 00 000000 0 0 0 0 I -i

COMPOUND

O

Rate (50 g/ha) 18 21 22 23 25 26 27 28 29 30 31 32 33 35 36 37 40 41 42 43 44 45 46 47 48 49 50 51 52

POSTEMERGENCE

Barley 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Barnyardgrass 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Cheatgrass 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Cocklebur 1 1 0 1 0 2 0 2 0 0 1 1 1 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 Corn 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Cotton 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Crabgrass 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 Giant foxtail 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Morningglory 0 0 u 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Nutsedge 0 0 0 0 0 0 8 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Rice 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Sorghum 0 0 0 0 0 0 0 0 0 0 0 0 0- 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Soybean 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Sugar beet 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Velvetleaf 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 Wheat 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Wild Oat 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

C

JI

L c r

COMPOUND

Rate (50 g/ha)

POSTEMERGENCE

Barley Barnyardgrass Cheatgrass Cocklebur Corn Cotton Crabgrass Giant foxtail Morningglory Nutsedge Rice Sorghum Soybean Sugar beet Velvetleaf Wheat Wild Oat 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 1 0 0 0 0 2 0 0 0 0 0 0 6 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 -0 -0 000 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 U u 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 000 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

COMPOUND

Rate (50 g/ha)

POSTEMERGENCE

Barley Ba rnyardgrass Cheatgrass Cocklebur Corn Cotton Cr abgras s Giant foxtai-l Morningglory Nutsedge Rice Sorghum Soybean Sugar beet Velvetleaf Wheat Wild Oat 82 83 84 85 86 87 88 89 90 92 93 94 95 96 97 98 99 100 101 102 103 104 107 108 109 110 00 0 00 0 00 0 0-1I 00 0 00 0 00 0 00 0 00 0 00 00 0 00 0 00 0 00 0 0 0 2 0 0 0 3 0 0 0 0 2 0 0 0 0 0 4 0 0 0 G- 0 0 0 0 0 0 0 0 0 0 0 -1I 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 02 0 00 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

COMPOUND

0 Rate (50 g/ha) 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132

POSTEMERGENCE

Barley 0 0 0 0 0 0 0 0 0 5 0 0 0 0 0 0 0 0 0 0 0 0 Barnyardgrass 0 0 0 0 0 0 0 9 3 8 0 0 0 0 0 0 0 0 0 6 0 0 Cheatgrass 0 0 0 0 0 0 0 2 3 8 0 0 0 0 0 0 0 0 0 0 0 0 Cocklebur 0 0 0 1 1 0 1 1 2 1 0 0 0 0 0 0 0 0 0 1 0 1 Corn 0 0 0 0 0 0 0 7 0 9 0 0 0 0 0 0 0 0 0 0 0 0 Cotton 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 Crabgrass 0 0 0 0 0 0 0 7 9 9 0 0 0 0 0 0 0 0 0 2 0 0 Giant foxtail 0 0 0 0 0 0 0 9 9 9 0 0 0 0 0 0 0 0 0 4 3 6 Morningglory 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Nutsedge 0 0 0 0 0 0 0 5 0 0 0 0 Rice 0 0 0 0 0 0 0 2 0 8 0 0 0 0 0 0 0 0 0 0 0 0 Sorghum 0 0 0 0 0 0 0 3 0 7 0 0 0 0 0 0 0 0 0 0 0 0 M Sorghum 0 0 0 0 0 0 0 3 0 7 0 0 0 0 0 0 0 0 0 0 0 0

N

Soybean 0 0 0 0 0 0 0 0 0 2 0 0 0 .0 0 0 0 0 0 1 2 1 Sugar beet 0 0 0 0 0 0 0 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Velvetleaf 0 0 0 0 0 0 0 3 1 6 0 0 0 0 0 0 0 0 0 0 0 1 Wheat 0 0 0 0 0 0 0 2 0 7 0 0 0 0 0 0 0 0 0 0 0 0 Wild Oat 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 '0 0 '0 Il

COMPOUND

0 Rate (50 g/ha) 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154

POSTEMERGENCE

Barley 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Barnyardgrass 1 1 0 0 3 0 0 0 0 0 0 0 0 1 0 0 0 2 0 9 8 9 Cheatgrass 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 4 Cocklebur 1 1 1 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 1 1 Corn 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 6 4 Cotton 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Crabgrass 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 3 3 7 Giant foxtail 3 5 2 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 9 9 9 Morningglory 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Nutsedge 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 3 Rice 0 2 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 8 8 Sorghum 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 0 0 Soybean 0 1 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 2 0 Sugar beet 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Velvetleaf 1 0 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 2 2 Wheat 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Wild Oat 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0g

Q

Cl) s 0 LIl WO 91/03464 PCT/US9O/04953 224

COMPOUND

Rate (50 g/ha) 155 156 157 155 166 167 168

POSTEMERGENCE

Barley 0 0 0 0 0 0 0 Barnyardgrass 4 0 6 2 0 0 0 Cheatgrass 0 0 0 0 0 0 0 Cocklebur 1 1 2 1 0 1 1 Corn 0 0 0 0 0 0 0 Cotton 0 0 3 0 0 0 0 Crabgrass 0 2 0 0 0 0 0 Giant foxtail 2 0 8 0 0 0 0 Morningglory 0 0 0 0 0 0 0 Nutsedge 0 0 0 0 0 0 Rice 0 0 0 0 0 0 0 Sorghum 2 0 0 0 0 0 0 Soybean 1 0 0 0 0 0 0 Sugar beet 0 0 0 0 0 0 0 Velvetleaf 3 2 2 2 0 0 0 Wheat 0 0 0 0 0 0 0 Wild Oat 0 0 0 0 0 0 0

CMPOUND

0 Rate (50 g/ha) 18 21 22 23 25 26 27 28 29 30 31 32 33 35 36 37 40 41 42 43 44 45 46 47 48 49 50 51 52

PREEMERGENCE

Barley 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Barnyardgrass 0 0 0 0 9 0 0 9 2 0 8 9 0 0 0 1 0 0 0 0 0 0 0 0 2 0 3 0 0 Cheatgrass 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Cocklebur 0 0 0 0 0 3 1 7 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Corn 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Cotton 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Crabgrass 0 3 0 0 7 7 4 7 0 3 0 2 0 0 2 2 0 0 0 0 0 0 0 0 0 0 0 0 2 Giant foxtail 0 2 0 0 6 2 0 8 4 2 6 8 5 5 0 7 0 0 0 0 0 0 0 0 2 0 2 0 1 Morningglory 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 ia 0 0 0 0 0 0 0 Nutsedge 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Rice 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Sorghum 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Soybean 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Sugarbeet 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Velvetleaf 0 0 0 0 0 0 0 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Wheat 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 WildOat 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

U)

X0 '0 UIt

COMPOUND

Rate (50 gfha) PREEM4ERGENCE Barley Barnyardgrass Cheatgrass Cocklebur Corn Cotton Crabgrass Giant foxtail Horningglory rHutsedge Rice Sorghum Soybean Sugar beet Velvetleaf Wheat Wild Oat 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 0 0 0 0 0 0 00 00 0 00 0 0 0 0 0 00 0 0 00 00 00 0 0 100 62 0 0 0000 00 00 00 20 00 00 05 00 0 00 00 00 0 000 00 00 00 00 00 00 00 00 00 0 00 0 200 -0 00 00 00 00 00 00 00 00 0 000 0 0 0 00 00 0000 00 00 00 00 00 00 00 00 00 0 00 00 00 00 00 0 000 00 00 0 000 00 00 00 0 0 4 0 40 2 30 0 0 0 0 0 0 00 0 0 00 00 0 00 0 0 0 0 0 00 2 2 0 00 2 5 2 0 00 0 00 0 0 0 00 0 03 40 0 0 00 00 00 00 00 00 00 0 00 000 00 00 0 000 00 0G0 00 0000 00 00 00 0 -00 0 00 0 00 00 0 0 00 00 00 00 00 0 00 00 00 00 00 0 000 00 0 0 00 00 00 00 0006-00 00 00 00 00 00 00 00 0 0 0 00 00 00 00 00 00 00 00 00 00 00 00 000 00 0 000 00 00 00 00 00 00 0 000 00 00 00 0 0 0 0 10 0 0 0 0 0 0 00 0 0 0 0 0 0 00 0 00 00 00 0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 0 0 00 00 00 00 00 00 00 0 00 GO0 00 00 00 00 0 L

P

COMPOUND

v0 ^0 Rate (50 g/ha) 82 83 84 85 86 87 88 89 90 92 93 94 95 96 97 98 99 100 101 102 103 104 107 108 109 110

PREEMERGENCE

Barley 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Barnyardgrass 0 0 0 0 0 0 3 2 2 0 9 9 9 6 7 1 0 0 0 9 5 2 7 10 3 Cheatgrass 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Cocklebur 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Corn 0 0 0 0 0 0 0 2 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Cotton 0 0 0 O 0 0 0 0 O O 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Crabgrass 0 0 0 0 0 0 0 0 0 0 0 3 2 3 2 0 0 0 0 4 0 0 5 3 1 2 Giant foxtail 0 0 0 3 2 0 4 5 6 0 9 9 8 7 5 2 0 0 3 9 6 9 9 9 8 7 Morningglory 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Hutsedge 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 Rice 0 0 0 0 O 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 4 0 0 Sorghum 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Soybean 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Sugar beet 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Velvetleaf 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 0 0 1 0 0 0 0 0 1 Wheat O 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 WIld Oat 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 cr \0 0

&J

L,

COMPOUND

Rate (50 g/ha) 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132

PREEMERGENCE

Barley 0 0 0 0 0 0 0 2 3 7 0 0 0 0 0 0 0 0 0 0 0 0 Barnyardgrass 8 6 0 0 3 0 0 10 10 10 5 0 0 0 0 0 0 0 0 9 10 Cheatgrass 0 0 0 0 0 0 0 8 3 2 0 0 0 0 0 0 0 0 0 3 0 4 Cocklebur 0 0 0 0 0 0 0 0 0 0 0 0 0 0 8 0 0 0 0 0 9 Corn 0 0 0 0 0 0 0 2 3 7 0 0 0 0 0 0 0 0 0 3 3 3 Cotton 0 0 0 0 0 0 0 0 4 5 0 0 0 0 0 0 0 0 0 0 0 1 Crabgrass 0 0 0 0 1 0 0 10 9 9 0 0 5 2 0 0 0 0 0 9 10 9 Giant foxtail 6 5 3 2 7 0 2 10 9 10 3 5 5 4 0 6 2 0 0 9 9 Morningglory 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 Nutsedge 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5 8 0 Rice 0 0 0 0 0 0 0 2 3 7 0 0 0 0 0 0 0 0 1 0 0 tJ Sorghum 0 0 0 0 0 0 0 9 0 9 0 0 0 0 0 0 0 0 0 2 7 7 Soybean 0 0 0 0 0 0 0 2 3 7 0 0 0 0 0 0 0 0 0 0 5 1 Sugar beet 0 0 0 0 0 0 0 2 0 7 0 0 0 0 0 0 0 0 0 0 3 2 Velvetleaf 0 0 0 0 0 0 0 3 3 6 0 1 0 0 0 0 0 0 0 3 2 3 Wheat 0 0 0 0 0 0 0 0 2 3 0 0 0 0 0 0 0 0 0 0 0 0 Wild Oat 0 0 0 0 0 0 0 0 2 3 0 0 0 0 0 0 0 0 0 0 0 0 4J, 0 0 '0 w

COMPOUND

Rate (50 g/ha)

PREEHERGENCE

Barley Barnyardgrass Cheatgrass Cocklebur Corn Cotton Crabgrass Giant foxtail Morningglory Nutsedge Rice Sorghum Soybean Sugar beet Velvetleaf Wheat Wild Oat 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 0 0 3 2 2 10 10 0 2 6 2 0 2 3 0 8 3 3 0 0 2 2 0 10 10 9 2 10 10 0 0 0 0 0 2 0 0 0 4 6 6 0 5 3 0 0 9 5 0 3 2 2 0 6 6 7 0 2 3 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 2 2 WO091/03464PC!S0/45 PCT/US90/04953 230

COMPOUND

Rate (50 g/ha)

PREEMERGENCE

Barley Barnyardgrass Cheatgrass Cocklebur Corn Cotton Crabgrass Giant foxtail Morningg lory Nutsedge, Rice Sorghum Soybean Sugar beet Velvetleaf Wheat Wild Oat 155 156 157 158 166 167 168 0 0 9 0 2 0 0 0 0 0 0 0 9 9 0 0 0 0 0 0 0 0 0 0 2 0 1 3 0 0 0 0 WO 91/03464 PCT/US90/04953 231 TEST B Seeds of barley (Hordeum vulgare), barnyardgrass (Echinochloa crus-galli), blackgrass (Alopecurus mrVosuroides), cheatgrass (Bromus secalinus), chickweed (Stellaria media), cocklebur (Xanthium pensylvanicum), corn (Z-e mays), cotton (Gossvypium hirsutum), crabgrass (Digitaria spp.), Galium (Galium aparine), giant foxtail (Setaria faberii), lambsquarters (Chenopodium album), morningglory (Ipomoea hederacea), rape (Brassica napus), rice (QrYza sativa), sorghum (Sorghum bicolor), soybean (Glycine max), sugar beet (Beta.

vulgaris), velvetleaf (Abutilon theophrasti), wheat (Triticum aestivum), wild buckwheat (Polvygonum convolvulus), and wild oat (Atven fatua) and purple nutsedge (Cvoerus rotundus) tubers were planted and treated preemergence with test chemicals dissolved in a non-phytotoxic solvent. At the same time, these crop and weed species were also treated with postemergence applications of test chemicals. Plants ranged in height from two to eighteen cm (one to four leaf stage) for postemergence treatments. Treated plants and untreated controls were maintained in a greenhouse for approximately fifteen to twenty days, after which all treated plants were compared to untreated controls and visually evaluated. Plant response ratings, summarized in Table B, are based on a scale of 0 to 10 where 0 is no effect and 10 is complete control. A dash response means no test result.

PCT/US90/0495 3 WO 91/03464 232

COMPOUND

169 170

COMPOUND

169 170 Rate (400 g/ha)

POSTEMERGENCE

Barley Barnyardgrass Blackgrass Cheatgrass Chickweed Cocklebur Corn Cotton Crabgrass Galium Giant foxtail Lambsqua rters Morningg lory Nut sedge Rape Rice Sorghum Soybean Sugar beet Velvetleaf Wheat Wild buckwheat Wild oat Rate (400 g/ha)

PREEMERGENCE

Barley Barnyardgrass Blackgrass Cheatgrass Chickweed Cocklebur Corn Cotton Crabgrass Galium Giant foxtail Lambsquarters Morningglory Nut sedge Rape Rice Sorghum Soybean Sugar beet Velvetleaf Wheat Wild buckwheat Wild oat PC-VUS90/049-53 WO 91/03464PCYUO/45 233

COMPOUND

Rate (200 g/ha)

POSTEMERGENCE

Barley Barnyardgrass Blackgrass Cheatgrass Chickweed Cocklebur Corn Cotton Crabgrass Galium Giant foxtail Lambsquarters Morningglory Nut sedge Rape Rice Sorghum Soybean Sugar beet Velvetleaf Whea t Wild buckwheat Wild oat 162 163 164 165 171 PCT/CTS90/04953 WO 91/03464 C!U9/45 234

COMPOUND

Rate (200 g/ha) PRE EME RG E NCE Barley Barnyardgrass Blackg rass Cheatgrass Chickweed Cocklebur Corn Cotton Crabgrass Galium Giant foxtail Lambsquarters Morningg lo'y Nut sedge Rape Rice Sorghum Soybean Sugar beet Velvetleaf Whe at Wild buckwheat Wild oat 162 163 164 165 171 WO 91/03464 rrU9/45 PCr/US90/04"-3 235

COMPOUND

169 170

COMPOUND

169 170 Rate (100 g/ha)

POSTEMERGENCE

Barley Barnyardgrass Blackgrass Cheatgrass C hi ckwee d Cocklebur Corn Cotton Crabgrass Galium Giant foxtail Lambsquarters Morningglory Nut sedge Rape Rice Sorghum Soybean Sugar beet Velvetleaf Whe at Wild buckwheat Wild oat Rate (100 g/ha)

PREEMERGENCE

Barley Barnyardgrass Blackg rass Cheatg rass Chickweed Cocklebur Corn Cotton Crabgrass Galium Giant foxtail Lambsquarters Morningglory Nut sedge Rape Rice Sorghum Soybean Sugar beet Velvetleaf Wheat Wild buckwheat Wild oat WO 91/03464 WO 9103464PCT/US90/04953 2.36

COMPOUND

Rate (50 g/ha)

POSTEMERGENCE

Barley Barnyardgrass Blackgrass Cheatg rass Chickweed Cocklebur Corn Cotton Crabgrass Galium Giant foxtail Lambsquarters Morningglory Nut sedge Rape Rice Sorghum Soybean Sugar beet Velvetleaf Wheat Wild buckwheat Wild oat 162 163 164 165 171 WO 91/03464 PrU9/45 PCT/US90/04953 237

COMPOUND

Rate (50 g/ha) 162 163 164 165 171

PREEMERGENCE

Barley 0 0 0 0 0 Barnyardgrass 0 0 0 0 9 Blackgrass 2 2 2 2 Cheatgrass 2 0 0 0 2 Chickweed 0 5 0 0 Cocklebur 0 0 Corn 0 0 0 0 3 Cotton 0 0 0 0 2 Crabgrass 0 0 0 0 Galium 0 0 0 0 2 Giant foxtail 0 0 0 0 9 Lambsquarters 0 0 0 1 Morningglory 0 0 0 0 2 Nutsedge 0 0 0 0 Rape 0 0 0 0 1 Rice 0 0 0 0 2 Sorghum 0 0 0 0 0 Soybean 0 0 0 0 2 Sugar beet 0 2 2 2 0 Velvetleaf 0 0 0 0 4 Wheat 0 0 0 0 0 Wild buckwheat 0 0 0 0 0 Wild oat 0 0 0 0 0 WO 91/03464 PCT/US90/04953 238 TEST C Seeds of barley (Hordeum vulare), barnyardgrass (Echinochloa crus-galli), blackgrass (Alopecurus myosuroides), chickweed (Stellaria media), cocklebur (Xanthium pensylvanicum), corn (Za- Mays), cotton (Gossvyium hirsutum), crabgrass (Diaitaria spp.), downy brome (Bromus tectorum), giant foxtail (Setaria faberi), green foxtail (Setaria viridis), jimsonweed (Datura stramonium), johnsongrass (Sorghum halepense), lambsquarters (Chenopodium album), morningglory (Iomoea spp,), rape (Brassica navus); rice (Q..ryz sativa), sicklepod (Cassia tusifolia), soybean (Glvcine max), sugar beet (Deta vuloaris), teaweed (Sida spinosa), velvetleaf (Abutilon theophrasti), wheat (Triticum aetivum), wild buckwheat (PolvYQonum convolvulus), and wild oat (Avena fatua) and purple nutsedge (Cyperus tundus) tubers were planted and treated preemergence with test chemicals dissolved in a non-phytotoxic solvent, At the same time, these crop and weed species were also treated with postemergence applications of test chemicals. Plants ranged in height from two to eighteen cm (two to three leaf stage) for postemergence treatments. Treated plants and untreated controls were maintained in a greenhouse for approximately 24 days, after which all treated plants were compared to untreated controls and visually evaluated, Plant response ratings, summarized in Table C, are reported on a 0 to scale where 0 is no effect and 10 is complete control. A dash response means no test result, c PC'/US90/04953 WO 91/03464 239

COMPOUND

Rate (500 g/ha) 32 34 93

POSTEMERGENCE

Barley 0 0 0 Barnyardgrass 10 7 7 Blackgrass 0 0 4 Chickweed 0 0 0 Cocklebur 0 0 3 Corn 0 0 3 Cotton 0 0 0 Crabgrass Downy brome Giant foxtail Green foxtail Jimsonweed Johnsongrass Lambsquarters Morningglory Nutsedge Rape Rice Sicklepod Soybean Sugar beet Teaweed Velvetleaf Wheat Wild buckwheat Wild oat Rate (500 g/ha)

PREEMERGENCE

Barley Barnyardgrass Blackgrass Chickweed Cocklebur Corn Cotton Crabgrass Downy brome Giant foxtail Green foxtail Jimsonweed Johnsongrass Lambsquarters Morningglory Nutsedge Rape Rice Sicklepod Soybean Sugar beet Teaweed Velvetleaf Wheat Wild buckwheat Wild oat

COMPOUND

32 34 93 0 0 8 10 10 9 5 4 0 6 0 9 10 8 0 0 0 9 9 9 4 0 0 10 10 10 10 0 0 0 10 10 9 0 0 3 3 7 0 0 3 0 0 0 5 3 0 7 6 4 0 5 6 0 3 0 0 0 0 0 3 0 0 0 0 0 0 0 0 3 6 3 0 0 0 0 4 0

I

PCTi US9O/04953 WO 91/03464

COMPOUND

Rate (250 g/ha)

POSTEMERGENCE

Barley Barnyardgras s B).ackgras s Chickweed Cocklebur Corn Cotton Crabgrass Downy brome Giant foxtail Green foxtail Jimnsonweed Johnsongrass Lambsquarters Morningglory Nutsedge Rape Rice Sicklepod Soybe an Sugar beet Teaweed Velvetleaf Wheat Wild buckwheat Wild oat 2 25 32 34 93 94 102 118 120 130 131 132 133 134 135 0 00 00 0 6 8 10 7 5 2 0 30 03 3 0 00 00 0 0 60 0 05 0 00 00 0 0 00 00 0 5 00 0 00 0 00 03 0 0 33 34 5 0 0 000 2 0 0 0 300 0 00 00 0 7 53 0 0 00 0 00 0 00 00 0 4 00 30 0 0 02 0 00 0 20 00 0 0 2 00 00 0 -0 33 4 0 00 0 50 -5 52 0 00 0 30 3 350 0 0 0 000 0 0 0 5 0 8 10 10 10 10 7 8 10 0 7 6 0 0 2 0 0 1 0 0 0 4 2 9 0 1 4 5 10 10 0 10 10 0 5 0 3 4 6 0 10 3 4 0 0 0 0 0 0 0 3 9 6 0 0 3 0 3 3 6 2 6 0 6 4 0 3 3 0 6 3 1.0 10 0 3 6 4 3 8 6 4 0 2 7 4 6 4 0 4 0 0 4 0 0 3 3 3 6 7 0 6 0 4 0 6 8 6 3 4 0 7 2 0 5 7 0 0 0 2 3 6 3 0 6 4 3 4 7 7 0 0 PCT/L'S90/04953 WO 91/03464

COMPOUJND

Rate (250 g/ha) PRE EM ER GENC E Barley Barnyardgrass Blackgrass Chickweed Cocklebur Corn Cotton Crabgrass Downy brome Giant foxtail Green foxtail Jimsonweed Johnsongrass Laznbsquarters Morningglory N utsedge Rape Rice Sicklepod Soybean Sugar beet Teaweed Velvetleaf Wheat Wild buckwheat Wild oat 2 25 32 34 93 94 102 118 120 130 131 132 133 134 135 0 00 0 73 4 10 10 10 10 10 10 10 7 10 8 5 9 7 6 0 62 0 64 9 0 7 0 0 7 10 3 2 33 0 80 2 0 00 0 03 0 8 9 2 8 9 10 0 22 0 04 3 10 10 10 10 10 10 10 9 10 1010 9 7 0 60 0 03 3 8 10 8 7 8 6 4 3 10 6 0 10 0 0 0 4 3 0 00 0 05 0 2 32 0 00 0 0 00 0 -6 3 0 30 3 73 3 0 00 0 00 0 0 40 0 00 6 0 9 25 27 3 3 05 3 28 0 00 0 05 3 4 0 50 06 0 7 0 32 0 24 3 7 10 5 10 10 10 7 10 7 7 7 8 4 3 6 10 10 4 3 9 5 6 3 10 10 7 6 7 8 10 7 5 3 2 3 7 0 10 10 6 9 9 3 0 8 0 4 0 PCT/US90/04953 WO 91/03464 C/S9/45

COMPOUND

Rate (125 g/ha) POSTE4ERGENqCE Barley Barnyardgras s Blackgrass Chickweed Cocklebur Corn Cotton Crabgrass Downy brome Giant foxtail Green foxtail Jim so nwe ed Johnsongras 6 Landbsguarters Morningglory Nutsedge Rape Rice Sicklepod Soybean Sugar beet Teaweed Velvetleaf Wheat Wild buckwheat Wild oat 2 25 32 34 94 102 118 119 120 130 131 132 133 134 135 00 00 0 24 4 70 0 0 000 0 00 00 0 50 00 00 00 0 0 -00 0 00 00 0 00 00 0 0 000 2 00 00 0 0 000 0 0 000 0 5 400 0 0 000 00 00 0 00 00 0 00 0 00 0 2 000 00 00 0 05 00 3 00 00 54 0 0 00 00 0 0 00 0 00 00 0 0 0 5 9 6 10 9 10 3 0 9 9 0 5 6 6 0 0 1 0 0 0 0 0 0 1 0 3 2 5 9 0 0 7 4 3 7 9 10 0 9 4 10 0 0 0 0 0 4 0 0 5 9 8 2 0 1 0 0 0 0 0 0 0 0 0 0 3 6 0 0 3 0 0 0 0 3 4 0 6 4 0 0 2 2 0 0 6 6 2 0 7 6 0 9 9 10 0 0 7 5 0 0 0 9 5 7 9 4 3 7 4 3 0 0 0 0 0 0 2 0 0 3 3 0 0 9 6 0 0 2 0 0 2 0 0 0 3 5 4 3 0 0 0 0 0 0 0 0 0 3 0 0 0 0 0 0 0 6 3 0 0 3 0 0 2 3 3 0 7 6 6 3 0 0 WO 91/03464 P-!U9/45 PCT/US90/04953 COM4POUJND Rate (125 g/ha)

PREEHERGENCE

Barley Barnyardgrass Blackgrass Chickweed Cocklebur Corn Cotton Crabgrass Downy brorne Giant foxtail Green foxtail Jimsonweed Johnsongras s Lambsguarter s Morningglory Nutsedge Rape Rice Sicklepod Soybe an Sugar beet Teaweed Velvetleaf Wheat Wild buckwheat 2 25 32 34 93 94 102 118 119 120 130 131 132 133 134 135 0 00 03 0 10 10 10 10 10 10 3 10 6 3 7 3 0 30 0 43 0 00 00 5 0 23 02 0 0 00 00 2 2 72 38 9 0 00 00 3 9 10 8 10 10 10 7 6 7 10 10 6 0 30 00 0 5 78 75 5 2 3- 0 60 0 04 0 00 0 03 0 0 000 0 0 00 03 0 0 0 00 -0 0 00 00 0 0 30 00 0 05 0 20 6 2 01 00 3 0 00 03 2 0 00 03 0 0 00 0 03 0 2 10 10 3 6 3 7 0 4 0 5 0 3 7 10 2 5 8 10 5 10 0 0 2 10 5 3 0 0 3 0 0 0 2 0 5 0 5 3 7 0 0 8 3 0 5 9 0 4 .0 10 4 7 7 8 5 0 3 2 5 0 .0 10 3 3 .0 10 .0 10 2 5 8 10 0 8 3 0 4 0 0 0 6 5 6 0 4 4 6 6 5 5 6 4 0 9 7 7 0 0 7 3 9 7 0 3 0 3 0 0 5 0 0 0 6 0 7 7 7 7 4 0 0 0 0 2 0 0 7 3 5 0 7 6 3 3 6 6 4 0 7 7 Wild oat Wiot0 0 6 2 0 3 3 0 4 0 WO 91/03464 PiIU9/45 PCT/US90/04953

COMPOUND

Rate (62 g/ha)

POSTEMERGENCE

Barley Barnyardgras 6 Blackgrass Chickweed Cocklebur Corn Cotton Crabgrass Downy brome Giant foxtail Green foxtail Jimsonweed Johnsongras s Lambsguarters Morningglory Nutsedge Rape Rice Sicklepod Soybean Sugar beet Teaweed Velvetleaf Wheat Wild buckwheat Wild oat 32 34 94 102 118 120 130 131 132 133 134 135 00 0 03 0 0 00 00 0 00 0 0 00 0 00 0 00 00 0 0 00 0 00 0 00 0 00 0 0- 0 00 0 00 00 0 0 00 00 00 0 00 0 00 0 30 0 0 00 0 00 00 0 0 0 1 0 9 0 0 4 0 0 3 0 0 0 0 0 0 0 0 0 7 0 0 0 0 5 0 8 0 0 0 0 0 0 0 8 0 0 0 0 0 0 0 0 0 0 0 6 0 0 0 0 0 2 3 0 0 0 0 2 0 0 0 0 0 0 9 2 0 0 0 ly, I 'I WO 91/03464 rrU9/45 PCr/US90/04953 COMdPOUND Rate (62 g/ha)

PREEMERGENCE

Barley Barnyardgrass Blackgrass Chickweed Cocklebur Corn Cotton Crabgrass Downy brome Giant foxtail Green foxtail Jimisonweed Johnsongrass Lambsguarters ?4orningglory Nutsedge Rape Rice Sicklepod Soybe an Sugar beet Teaweed Velvetleaf Wheat Wild buckwheat Wild oat 2 25 32 34 93 94 102 118 119 120 130 131 132 133 134 135 0 00 00 0 8 10 10 10 10 7 0 7 2 3 0 0 0 00 00 0 0 00 0- 3 0 00 00 0 0 00 0 00 0 6 0 0 0 6' 0 00 0 00 7 10 7 7 2 4 5 67 72 4 0 30 0 00 2 52 40 0 0 08 0 00 00 4 00 00 0 0 00 00 0 0 00 00 0 0 00 06 0 0 0 000 0 0 00 00 0 0 50 2- 6 -0 0 00 0 0 00 00 0 0 0 000 0 0 00 00 0 0 0 6 2 0 3 3 9 10 10 10 10 10 10 3 6 0 7 10 3 5 5 7 3 5 7 0 5 0 0 2 7 6 7 0 4 0 0 0 0 0 2 0 0 3 0 5 0 4 10 10 10 10 0 0 5 3 2 7 10 9 10 10 5 10 10 10 10 0 0 0 2 2 0 7 7 6 3 3 0 9 8 0 0 4 0 3 3 0 0 0 0 0 0 0 0 0 5 8 0 0 2 6 3 2 0 0 3 3 0 0 4 5 5 4 0 3 8 3 0 8 6 7 4 0 0 4 3 0 3 5 7 8 4 0 0 4 0 0 B 7 0~ 0 2 0 0 9 0 2 8 10 4 7 7 7 7 3 3 4 0 0 0 0 3 5 6 3 0 5 6 4 6 0 3 0 2 7 7 0 2 WO 91/03464 PCT/US90/04953 246

COMPOUJND

Rate (31 g/ha) 94 102 118 120 130 131 132 133 134 135 P OS TEME RG ENC E Barley 0 0 0 0 0 0 0 0 0 0 Barnyardgrass 0 0 4 10 0 3 3 0 6 4 Blackgrass 0 0 0 0 0 0 0 0 0 0 Chickweed 0 0 0 0 0 0 0 0 0 0 Cocklebur 0 0 0 0 0 0 0 0 Corn 0 0 0 0 0 0 0 0 0 0 Cotton 0 0 0 0 0 0 0 0 0 0 Crabgrass 0 0 0 0 0 0 0 0 0 0 Downy brome 0 0 0 0 0 0 0 0 0 0 Giant foxtail 0 0 2 8 0 0 0 0 4 3 Green foxtail 0 0 0 3 0 0 0 0 0 0 Jimnsonweed 0 0 0 0 0 0 0 0 2 0 Johnsongrass 0 0 0 0 0 0 0 0 0 0 Lambsquarters 0 2 3 0 0 0 0 Mornincjglory 0 0 0 0 0 0 0 0 3 0 Nutsedcje 0 0 0 0 0 0 0 0 0 0 Rape 0 0 0 0 0 0 0 0 0 0 Rice 0 0 0 0 0 0 0 0 3 0 Sicklepod 0 0 0 0 0 0 0 0 0 0 Soybean 0 0 0 0 0 0 0 0 0 0 Sugar beet 0 0 0 0 0 0 0 0 3 0 Teaweed 0 0 0 2 0 0 0 0 0 0 Velvetjleaf 0 0 0 0 0 0 0 0 3 3 Wheat 0 0 0 0 0 0 0 0 0 0 Wild buckwheat 0 0 6 0 3 0 4 0 4 0 Wild oat 0 0 0 0 0 0 0 0 0 0 PCI, US9O/049-5-3 WO 91/03464

COMPOUND

Rate (31 g/ha)

PREEMERGENCE

Barley Barnyardgras s Blackgrass Chickweed Cocklebur Corn Cotton Crabgrass Downy brome Giant foxtail Green foxtail Jimsonweed Johnsongrass Lambuarters Morningglory Nutsedge Rape Rice Sicklepod Soybe an Sugar beet Teaweed Velvetleaf Wheat Wild buckwheat Wild oat 2 25 94 102 118 119 120 130 131 132 133 134 135 00 0 3 10 5 00 0 00 0 0 -0 0 00 00 0 0 65 0 00 2 93 36 3 03 0 0 50 0 0- 00 4 00 0 00 0 00 0 0 00 0 00 0 00 05 6 00 0 00 0 00 0 00 0 0 0 2 0 4 10 10 10 0 4 3 4 0 0 7 6 0 0 0 0 0 0 0 0 0 0 0 4 0 8 9 9 0 0 3 0 5 6 8 4 9 9 6 0 0 0 0 0 5 4 4 3 0 9 0 0 3 0 0 0 0 0 0 0 0 0 0 2 0 0 2 4 3 0 0 0 0 0 2 3 4 0 5 3 6 0 2 5 3 0 0 3 0 2 6 6 0 0 3 0 0 0 0 4 10 10 2 3 5 WO 91/03464 PCT/US90/04953 248 TEST D Compounds evaluated in this test were formulated in a non-phytoxic solvent and applied to the soil surface before plant seedlings emerged (preemergence application), to water that covered the soil surface (paddy application), and to plants that were in the one-to-four leaf stage (postemergence application). A sandy loam soil was used for the preemergence and postemergence tests, while a silt loam soil was used in the paddy test. Water depth was approximately 2.5 cm for the paddy test and was maintained at this level for the duration of the test.

Plant species in the preemergence and postemergence tests consisted of barley (Hordeum vulgare), blackgrass (Alopecurus mosuroides), chickweed (Stellaria media), corn mays), cotton (Gossvoium hirsutum), crabgrass (Diaitaria sanouinalis), downy brome (Bromus tectorum), galium (Galium aparine), giant foxtail (Setaria faberii), lambsquarters (Chenopodium Album), morningglory (Ipomoea hederacea), pigweed (Amaranthus retroflexus), rape (Brassica napus), ryegrass (Lolium multiflorum), sorghum (Sorghum bicolor), soybean (G1vcine mx), speedwell (Veronica persica), sugar beet (Beta vulaaris), velvetleaf (Abutilon theophrasti), wheat (Triticum aestivum), wild buckwheat (Polygonum rconvolvulus), and wild oat (Avena fatua). All plant species were planted one day before application of compounds for the preemergence portion of this test. Plantings of these species were adjusted to produce plants of appropriate size for the postemergence portion of the test. Plant species in the paddy test consisted of barnyardgrass (Echinochloa crus-galli), rice (Oryza sativa), and umbrella sedge (Cyperus difformis).

j_ WO 91/03464 PCT/US90/04953 249 All plant species were grown using normal greenhouse practices. Visual evaluations of injury expressed on treated plants, when compared to untreated controls, were recorded approximately fourteen to twenty-one days after application of test compounds. Plant response ratings, summarized in Table D, were recorded on a 0 to 10 scale where 0 is no injury and 10 is plant death. A dash response means no test result.

PCY/,US90/04953 WO 91/03464 250 Table D

COMPOUIND

Rate (250 g/ba) 136 145 146 147 152 153 154 155 157 158

POSTEMERGENCE

Barley Blackgrass Chickweed Corn Cotton Cr abg ras s Downy brome Gal i w Giant foxtail Laxbsquarters Morningglory P i gwee d Rape Ryegrass So rghumn Soybean Speedwel11 Sugar beet Velvetleaf Wheat Wild buckwheat Wild oat 5 6 9 4 4 0 2 3 0 0 7 8 0 2 2 0 8 8 0 0 0 3 0 0 o 0 7 6 3 4 0 0 0 0 8 9 9 9 9 8 8 7 3 3 8 7 7 8 8 6 7 8 8 9 2 0 7 7 0 0 8 9 6 8 6 6 9 10 4 0 8 9 6 6 0 3 3 6 6 5 0 4 4 8 7 8 6 0 0 0 0 2 7 0 6 0 2 7 9 6 9 4 4 0 9 7 5 0 0 0 10 10 2 4 6 7 4 6 8 6 0 10 10 0 3 8 6 WO 91/03464 PTU9/45 PC'F/US90/04953 251

COMPOUND

Rate (250 g/ha) 136 145 146 147 152 153 154 155 157 158

PA.DDY

Barnyardgrass Rice Umbrella sedge 9 9 8 8 10 10 10 10 10 8 7 7 7 9 9 9 8 9 7 9 4 8 8 10 9 10 9 9 9

COMPOUND

Rate (250 g/ha) 136 145 146 147 152 153 154 155 157 158 PREEMERGEN CE Barley Blackgrass Chickweed Corn Cotton Crabgr ass6 Downy brorne Gal i ur Giant foxtail Larnbsguarters Morningglory P igwee d Rape Ryegrass So rghumi Soybe an Speedwell Sugar beet Velvetleaf Wheat Wild buckwheat Wild oat 3 3 2 4 5 7 5 3 3 0 8 10 10 10 10 10 10 7 9 7 7 7 7 8 9 9 8 8 9 8 4 3 2 3 5 6 7 0 0 0 0 3 2 3 5 5 4 2 3 2 10 9 10 10 10 10 10 10 10 3 3 0 0 5 6 7 0 4 3 3 0 0 6 10 10 10 10 10 10 10 10 10 9 10 10 9 9 8 9 9 8 0 2 0 2 0 0 0 0 0 0 7 3 0 2 8 8 7 7 7 7 5 0 0 0 0 6 0 4 3 3 7 10 10 10 10 10 10 3 7 5 3 4 8 10 10 6 4 6 3 3 1 0 2 7 8 0 0 0 0 9 8 10 7 8 7 9 6 0 0 9 8 9 8 8 7 8 7 5 7 8 8 8 8 7 8 4 3 3 4 5 5 5 0 4 0 9 5 5 4 9 9 8 7 8 6 4 4 0 3 10 10 6 0 0 WO 91/03464 252

COMPOUND

Rate (125 g/ha) 136 145 146 147 152 153 154 155 157 158 PCT/US90/04953

POSTEMERGENCE

Barley Blackgrass 0hickweed Corn Cotton Crabgrass Downy brone Gal iurn Giant foxtail Lambsquarters Morningglory P igwee d Rape Ryegrass Sorghum Soybe an Speedwel1l Sugar beet Velvetleaf Whe at Wild buckw~heat Wild oat 5 5 4 8 6 o 7 7 2 6 6 o 2 2 7 4 5 o 5 5 o0 3 7 7 7 o 7 6 2 0 0 o 3 5 o o 0 6 4 7 3 3 3 o 4 3 o 6 9 0 8 4 3 3 5 5 3 6 o 8 9 o 3 5 6 0 4 6 3 7 8 5 7 6 0 6 o 0 0 7 0 3 5 0 4 6 2 3 7 4 7 6 7 o 0 0 3 0 0 o 0 0 7 0 4 2 0 0 o 0 0 8 7 9 6 6 5 5 0 6 0 4 6 3 3 0 3

COMPOUND

Rate (125 g/ha) 136 145 146 147 152 153 154 155 157 158

PADDY

Barnyardgras s Rice Umbrella sedge 9 6 6 6 10 10 10 10 10 7 3 4 7 8 8 9 5 8 2 9 3 4 4 9 9 9 8 9 8 PCY/US90/04953 WO 91/03464

COMPOUND

Rate (125 g/ha) 136 145 146 147 152 153 154 155 157 158 P RE EME RGEN CE Barley Blackgrass Chickweed Corn Cotton Crabgrass Downy brome Gal i ur Giant foxtail Lambsquarters Morningglory P igwee d Rape Ryegrass Sorghum Soybe an Speedwell Sugar beet Velvetleaf Wheat Wild buckwheat Wild oat 2 0 0 3 5 4 3 0 2 0 8 7 7 8 10 10 7 6 8 4 7 7 6 7 9 8 8 8 8 8 1 1 0 2 3 2 3 0 0 0 0 2 1 2 0 3 3 0 2 0 10 9 10 10 10 10 10 10 10 2 0 0 0 3 4 5 0 3 0 0 0 0 7 0 0 10 9 10 9 10 10 10 10 10 8 10 10 9 9 8 9 8 8 0 0 0 2 0 0 0 0 0 0 7 2 0 0 7 7 6 6 3 6 5 0 0 0 0 3 0 3 0 2 7 7 5 10 5 6 8 0 5 0 4 1 2 1 10 10 3 3 3 0 0 0 0 0 4 6 0 0 0 0 7 8 8 8 6 7 6 9 5 0 0 8 7 8 8 6 6 7 3 5 5 7 8 8 7 6 6 3 0 0 3 4 4 4 0 3 0 9 3 4 3 8 8 7 6 7 4 3 0 0 2 3 10 3 0 0 WO 91/03464 PCT/US90/04953 254

COMPOUND

Rate (62 g/ha) 136 145 146 147 152 153 154 155 157 158

POSTEMERGENCE

Barley 0 0 0 4 4 2 3 0 2 0 Blackgrass 4 0 0 0 5 4 4 0 2 0 Chickweed 2 0 0 0 7 6 6 0 5 0 Corn 0 0 0 0 3 2 4 0 0 0 Cotton 0 0 0 0 0 2 0 0 0 2 Crabgrass 2 0 2 0 3 3 6 0 3 2 Downy brome 0 0 0 0 4 0 3 0 3 0 Galiun 0 0 0 0 0 2 5 0 0 Giant foxtail 2 0 3 2 4 6 7 0 4 3 Lambsguarters 3 0 0 0 5 4 5 4 4 Morningglory 0 0 0 0 0 0 0 0 0 0 Pigweed 0 0 0 0 0 4 0 0 0 3 Rape 0 0 0 0 0 0 0 0 0 0 Ryegrass 0 0 0 4 3 0 4 0 4 0 Sorghum 0 0 0 2 0 0 1 0 0 0 Soybean 0 0 0 0 2 2 0 0 0 2 Speedwell 0 0 0 0 6 6 8 4 8 0 Sugar beet 0 0 0 0 0 5 2 3 0 Velvetleaf 2 0 0 0 3 4 3 3 0 0 Wheat 0 0 0 3 3 4 5 0 1 0 Wild buckwheat 4 0 0 0 9 6 0 4 0 Wild oat 0 0 0 0 0 2 2 0 0 0 PCT/US90/04953 WO 91/03464 255

COMPOUND

Rate (62 g/ha) 136 145 146 147 152 153 154 155 157 158

PADDY

Barnyardgrass 9 4 5 4 10 10 10 10 9 Rice 4 1 1 3 7 8 8 3 6 0 Umbrella sedge 9 2 2 2 9 9 9 7 9 8

COMPOUND

Rate (62 g/ha) 136 145 146 147 152 153 154 155 157 158

PREEMERGENCE

Barley 0 0 0 0 3 3 2 0 0 0 Blackgrass 7 3 3 6 7 7 6 4 6 0 Chickweed 5 6 6 7 9 8 7 7 7 7 Corn 0 0 0 0 0 0 0 0 0 0 Cotton 0 0 0 0 0 0 2 0 0 0 Crabgrass 10 9 9 10 10 10 10 10 9 9 Downy brome 0 0 0 0 0 3 3 0 3 0 Galium 8 0 0 0 0 3 0 0 0 Giant foxtail 10 8 8 8 10 10 10 10 10 Lambsquarters 5 10 10 7 9 8 7 8 Morningglory 0 0 0 0 0 0 0 0 0 0 Pigweed 6 0 0 0 6 6 5 3 0 4 Rape 2 0 0 0 0 0 0 0 0 0 Ryegrass 4 3 0 7 4 6 5 0 3 0 Sorghum 2 0 0 0 6 3 2 0 0 0 Soybean 0 0 0 0 2 3 0 0 0 0 r Speedwell 2 8 8 7 6 6 Sugar beet 8 3 0 0 7 6 6 6 6 Velvetleaf 5 2 2 5 5 6 7 3 4 3 Wheat 0 0 0 0 3 3 3 0 0 Wild buckwheat 8 3 3 0 7 7 6 4 4 3 Wild oat 2 0 0 0 0 0 0 0 0 0 WO 91/03464 PTU9/45 PCr/US90/04953 256

COMPOUND

Rate (31 g/ha) 136 145 146 147 152 153 154 155 157 158 POSTEMERG ENCE Barley 0 0 0 0 0 0 3 0 0 0 Blackgrass 3 0 0 0 0 0 0 0 0 Chickweed 0 0 0 0 0 2 3 0 0 0 Corn 0 0 0 0 0 0 2 0 0 0 Cotton 0 0 0 0 0 0 0 0 0 2 Crabgrass 0 0 0 0 2 2 3 0 3 0 Downy brome 0 0 0 0 0 0 2 0 0 0 Galium 0 0 0 0 0 0 0 0 0 0 Giant foxtail 0 0 0 0 0 4 4 0 3 0 Lambsguarters 0 0 0 0 0 3 0 4 0 0 Morningglory 0 0 0 0 0 0 0 0 0 0 Pigweed 0 0 0 0 0 3 0 0 0 0 Rape 0 0 0 0 0 0 0 0 0 0 Ryegrass 0 0 0 0 0 0 0 0 0 0 Sorghum 0 0 0 0 0 0 0 0 0 0 Soybean 0 0 0 0 0 0 0 0 0 0 Speedwell 0 0 0 0 0 3 4 0 0 0 Sugar beet 0 0 0 0 0 0 2 0 0 Velvetleaf 2 0 0 0 2 0 0 0 0 0 Wheat 0 0 0 2 0 2 0 0 0 0 Wild buckwheat 0 0 0 0 6 0 0 0 0 Wild oat 0 0 0 0 0 0 0 0 0 0 pCT/USgo/04953 WO 91/03464 rru9/45

COMPOUND

Rate (31 g/ha)

PADDY

Barnyardgrass Rice Umbrella sedge 136 145 146 147 152 153 154 155 157 158 6 3 4 3 9 9 10 10 9 9 2 0 1 1 4 2 4 2 2 0 7 0 0 0 9 9 2

COMPOUND

Rate (31 g/ha) P RE EM ERGENC E Barley Blackgrass Chickweed Corn Cotton Crabgrass Downy brorne Gal i ur Giant foxtail Lambsquarter s Morningglory P i gwee d Rape Ryegras s So rghum~ Soybe an Speedwell Sugar beet Velvetleaf Wheat Wild buckwheat Wild oat 136 145 146 147 152 153 154 155 157 158 0 0 0 5 0 0 4 3 5 0 0 0 0 0 0 a3 7 9 0 0 0 8 0 0 8 4 6 0 10 10 0 0 0 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 7 0 0 3 2 2 0 0 0 5 0 0 0 0 0 0 0 0 0 3 5 6 3 7 7 8 7 0 0 0 0 0 0 0 0 9 10 10 10 0 0 0 0 0 0 0 7 10 10 10 3 5 0 0 0 0 0 5 3 0 0 0 0 0 3 3 3 3 0 3 2 0 0 2 0 0 6 6 6 0 6 5 4 0 3 0 4 0 0 0 0 0 6 6 4 0 0 0 0 0 0 3 3 5 7 0 0 0 0 7 8 0 0 0 0 9 5 8 0 0 0 0 0 0 0 0 0 0 0 0 4 6 4 2 0 3 0 0 3 2 0 0 WO 91/03464 ciUO/43 PCr/US90/04953

COMPOUND

Rate (16 g/ha)

POSTEMERGENCE

Barl1ey Blackgrass Chickweed Corn Cotton Crabgrass Downy brome Gal ium Giant foxtail Lam~bsquarters Morningglory P igweed Rape Ryegrass Sorghum Soybean Speedwell Sugar beet Velvetleaf Wheat Wild buckwheat Wild oat 145 146 147 152 153 154 155 157 158 o 0 o 0 o 0 o 0 o 2 o 0 o 0 o 0 o 0 o 0 o 0 o 0 o 0 o 0 o 0 o 0 o 0 0 o 0 o 0 0 o 0

COMPOUND

Rate (16 g/ha)

PADDY

Barnyardgras s Rice Umbrella sedge 145 146 147 152 153 154 155 157 158 0 2 3 9 8 8 9 8 9 0 0 1 2 1 2 0 0 0 0 0 0 WO 91/03464 PfU9/45 Pcr/US90/04953

COMPOUND

Rate (16 g/ha)

PREEMERGENCE

Barley Blackgrass Chickweed Corn Cot ton Crabgrass Downy brome Gal i un Giant foxtail Lainbsguarters Morningglory P igwee d Rape Ryegrass Sorghum~ Soybe an Speedwell Sugar beet Velvetleaf Wheat Wild buckwheat Wild oat 145 146 147 152 153 154 155 157 158 o 0 0 0 o 3 3 3 4 6 7 o 0 o 0 o 0 0 0 5 10 8 8 0 0 0 0 0 0 0 2 8 10 10 0 0 3 0 0 0 0 0 4 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5 5 4 0 3 3 3 0 0 0 0 0 0 0 0 0 4 3 3 0 0 0 0 0 0 3 0 3 0 0 0 0 0 6 3 0 0 0 0 6 3 3 0 0 0 0 0 0 0 0 0 0 0 0 3 3 3 0 0 0 0 0 0 0 0 0 WO 91/03464 PCT/US90/04953 260 TEST E Plastic pots were partially filled with silt loam soil. The soil was then saturated with water.

Indica and/or Japonica rice (Oryza sativa) seedlings at the 2.0 to 2.5 leaf stage; seeds of barnyardgrass (Echinochloa crus-aalli), bulrush (Scirpus mucronatus), duck salad (Heteranthera limosa), and umbrella sedge (Cvyerus difformis); and tubers of arrowhead (Saaittaria spp.) and waterchestnut (Eleocharis spp.) were planted into this soil.

Several days after planting, water levels were raised to 3 cm above the soil surface and maintained at this level throughout the test. Chemical treatments were formulated in a non-phytotoxic solvent and applied directly to the paddy water. Treated plants and untreated controls were maintained in a greenhouse for 21 days, after which all treated plants were compared to untreated controls and visually evaluated. Plant response ratings, summarized in Table E, are reported on a 0 to 10 scale where 0 is no effect and 10 is complete control. A dash response means no test result.

COMPOUND

Rate (500 g/ha)

PADDY

Arrowhead Barnyardgrass Bulrush Duck salad Indica rice Japonica rice Umbrella sedge Waterchestnut Rate (250 g/ha)

PADDY

Arrowhead Barnyardgrass Bulrush Duck salad Indica rice Japonica rice Umbrella sedge Waterchestnut 5 8 25 26 27 28 29 30 31 32 50 51 53 54 56 58 59 107 110 118 119 130 149 150 151 7 8 0 10 10 10 8 9 10 10 9 10 10 10 10 10 10 10 6 7 9 0 7 8 7 0 0 7 8 8 4 0 6 6 0 0 10 9 10 10 10 10 10 10 10 10 10 10 10 0 0 4 3 7 0 0 4 0 0 3 0 0 5 0 0 2 7 7 5 0 4 7 0 0 5 5 3 0 0 4 0 0 3 10 10 10 10 10 10 10 10 10 10 10 8 0 7 10 0 0 10 9 6 0 0 0 0 0 0 5 5 0 0 0 0 0 9

COMPOUND

5 8 25 26 27 28 29 30 31 32 50 51 53 54 56 58 59 93 107 110 118 119 130 149 150 151 10 0 0 8 9 10 6 9 10 7 8 10 10 10 9 7 9 0 0 4 0 0 0 6 6 5 0 10 7 10 10 10 10 10 8 10 10 0 0 6 0 0 0 0 0 3 0 2 0 0 0 2 4 0 0 4 4 0 0 10 10 10 10 10 9 10 8 10 10 10 7 8 9 0 0 0 0 0 0 0 0 0 0 9 10 AO 0 4 9 5 10 10 0 3 0 0 3 0 0 7 10 0 0 0 3 0 8 8 9 0 0 0 8 10 9 7 10 9 10 3 0 4 0 5 0 10 10 10 10 10 1 0 0 0 5 2 5 3 10 9 6 4 0 6 6 5 1 1 1 8 10 10 10 1 1 0 0 5 7 8 0 1 3

I

COMPOUND

Rate (125 g/ha)

PADDY

Arrowhead Barnyardgrass Bulrush Duck salad Indica rice Japonica rice Umbrella sedge Waterchestnut 5 8 25 26 27 28 29 30 31 32 50 51 53 54 56 58 59 93 107 110 118 119 130 149 150 151 0 0 7 5 4 0 0 0 6 810 06 9 74 810 98 810 84 710 5 4 10 10 8 0 0 0 6 00 00 00 0 04 000 40 0 02 -10 0 71010 010 6106 010 60 0-101010 1010 1 0 0 0 0 0 20 000 00--00 -0 0 3 0 0 0 0 0 00 00 40 00 00 00 00 0 00 2 0 4 4 4 1 0 1 10 10 10 0 9 810 010 106 50 50 00 8 8 1010 10 0 0 0 0 90 00 0 0000 0 00 00 00 2 2 0 2 5 5 0 0 0

COMPOUND

Pate (64 g/ha)

PADDY

Arrowhead Barnyardgras s Bulrush Duck salad Indica rice Japonica rice Umbrella sedge Waterchestnut 5 8 25 26 27 28 29 30 31 32 50 51 53 54 56 58 59 93 107 110 118 119 130 149 150 151 0 0 4 5 10 00 0 -8 00 0 00 0 9 10 10 00 0 5 96 0 00 8 10 10 00 0 00 0 9 0 10 00 0 4 7 10 00 0 0 10 6 00 00 0 0 10 4 00 0 7 9 0 0 0 10 0 0 0 0 0 4 0 0 0 0 6 2 2 0 0 0 7 10 4 2 7 7 7 0 0 0 0 2 0 0 10 9 10 10 10 0 0 0 0 0 0 00 0 0 3 3 1 0 0 0 0 4 6 10 10 10 0 0 00 2 2 0 0 5 2 0 0

COMPOUND

Rate (32 g/ha)

PADDY

Arrowhead Barnyardgrass Bulrush Duck salad Indica rice Japonlica rice Umbrella sedge Waterchestnut 5 8 25 26 27 28 29 30 31 32 50 53 54 56 58 59 93 107 110 118 119 130 149 150 151 0 0 0 10 0 0 5 0 0 0 0 5 8 0 0 8 3 0 0 8 10 0 0 0 0 0 10 0 0 6 10 0 0 9 0 0 0 0 8 0 0 0 0 0 2 0 0 0 0 0 6 05 7 0 0 6 4 5 0 0 0 0 0 0 2 0 0 0 10 9 10 9 10 0 0 0 0 0 0 0 0 0 00 0 0 2 2 0 0 0 0 0 0 0 0 2 10 9 10 0 0 0 0 00 2 2 0 0 4 2 0 0 0

COMPOUND

Rate (16 g/ha)

PADDY

Ba rnyardgras s Bulrush Indica rice Japonica rice Waterchestnut ~c PCT/US90/04953 WO 91/03464 264 TEST F Seeds of spring and winter barley (Hordeum vulaare), blackgrass (Alopecurus myosuroides), black nightshade (Solanum nigrum), bluegrass (pQA annua), cheatgrass (Bromus secalinus), downy brome (Bromus tectorum), field pennycress (Thlaspi arvense), field violet (Yiola arvensis), galium (Galium aparine), green foxtail (Setaria viridis), ivyleaf speedwell (Veronica hederaefolia), jointed goatgrass (Aeailops cylindrica), kochia (Kochia scoparia), lambsquarters (Chenopodium album), Persian speedwell (Veronica persica), rape (Brassica napus), Russian thistle (Salsol hali), ryegrass (Lolium multiflorum), scentless chamomile (Matricaria inodora), sugar beet (Beta vulaaris), spring and winter wheat (Triticum aestivum), wild buckwheat (Polvygonum convolvulus), and wild oat (Aena faItua) were planted and treated preemergence with the test chemical dissolved in a non-phytotoxic solvent. At the same time, these crop and weed species were also treated with postemergence applications of the test chemical. Plants ranged in height from two to twenty-four cm for postemergence treatments. Blackgrass and wild oat were treated postemergence at two growth stages. The first growth stage was at the 1-2 leaf stage while the second stage was at the four leaf stage. Treated plants and untreated controls were maintained in a greenhouse for approximately 21 days. All treated plants were then compared to untreated controls and visually evaluated for injury. Plant response ratings, summarized in Table F, are based on a zero to ten scale where 0 is no effect and 10 is complete control.

ILM

I

WO 91/03464 PCT/US90/04953 265 COMPOUND COMPOUND Rate (500 g/ha)

POSTEMERGENCE

Barley (Spring) Barley (Winter) Blackgrass (1) Blackgrass (2) Blk. nightshade Bluegrass Cheatgrass Downy brome Fld. pennycress Fld. violet Galium Green foxtail Ivylf speedwell Jntd. goatgrass Kochia Lambsquarters Prsn. speedwell Rape Russian thistle Ryegrass Snls. chamomile Sugar beet Wheat (Spring) Wheat (Winter) Wild buckwheat Wild oat (1) Wild oat (2) Rate (500 g/ha)

PREEMERGENCE

Barley (Spring) Barley (Winter) Blackgrass Blk. nightshade Bluegrass Cheatgrass Downy brome Fld. pennycress Fld. violet Galium Green foxtail Ivylf speedwell Jntd. goatgrass Kochia Lambsquarters Prsn. speedwell Rape Russian thistle Ryegrass Snls. chamomile Sugar beet Wheat (Spring) Wheat (Winter) Wild buckwheat Wild oat Ili WO 91/03464 PC/US90/04953 266 COMPOUND COMPOUND Rate (250 g/ha)

POSTEMERGENCE

Barley (Spring) Barley (Winter) Blackgrass (1) Blackgrass Blk. nightshade Bluegrass Cheatgrass Downy brome Fld. pennycress Fld. violet Gallum Green foxtail Ivylf speedwell Jntd. goatgrass Kochia Lambsquarters Prsn. speedwell Rape Russian thistle Ryegrass Snls. chamomile Sugar beet Wheat (Spring) Wheat (Winter) Wild buckwheat Wild oat (1) Wild oat (2) Rate (250 g/ha)

PREEMERGENCE

Barley (Spring) Barley (Winter) Blackgrass Blk. nightshade Bluegrass Cheatgrass Downy brome Fld. pennycress Fld. violet Galium Green foxtail Ivylf speedwell Jntd. goatgrass Kochia Lambsquarters Prsn. speedwell Rape Russian thistle Ryegrass Snls. chamomile Sugar beet Wheat (Spring) Wheat (Winter) Wild buckwheat Wild oat WO 91/03464 P(T/US90/0953 267

COMPOUND

Rate (125 g/ha)

POSTEMERGENCE

Barley (Spring) Barley (Winter) Blackgrass (1) Blackgrass (2) Blk. nightshade Bluegrass Cheatgrass Downy brome Fld. pennycress Fld. violet Galium Green foxtail Ivylf speedwell Jntd. goatgrass Kochia Lambsquarters Prsn. speedwell Rape Russian thistle Ryegrass Snls, chamomile Sugr beet Wheat (Spring) Wheat (Winter) Wild buckwheat Wild oat (1) Wild oat (2)

COMPOUND

Rate (125 g/ha)

PREEMERGENCE

Barley (Spring) 2 Barley (Winter) 1 Blackgrass 2 Blk. nightshade 0 Bluegrass 7 Cheatgrass Downy brome 0 Fld. pennycress 4 Fld. violet 0 Galium 0 Green foxtail Ivylf speedwell 0 Jntd. goatgrass 0 Kochia 0 Lambsquarters 1 Prsn. speedwell 2 Rape 2 Russian thistle 0 Ryegrass 9 Snls. chamomile 0 Sugar beet 3 Wheat (Spring) 1 Wheat (Winter) 0 Wild buckwheat 0 Wild oat 0 -1 WO 91/03464 PCY1/US90/04953 268 COMPOUND COMPOUND Rate (64 g/ha)

POSTEMERGENCE

Barley (Spring) Barley (Winter) Blackgrass (1) Blackgrass (2) Blk. nightshade Bluegrass Cheatgrass Downy brome Fld. pennycress Fld. violet Galium Green foxtail Ivylf speedwell Jntd. goatgrass Kochia Lambsquarters Prsn. speedwell Rape Russian thistle Ryegrass Snls. chamomile Sugar beet Wheat (Spring) Wheat (Winter) Wild buckwheat Wild oat (1) Wild oat (2) Rate (64 g/ha)

PREEMERGENCE

Barley (Spring) Barley (Winter) Blackgrass Blk. nightshade Bluegrass Cheatgrass Downy brome Fld. pennycress Fld. violet Galium Green foxtail Ivylf speedwell Jntd. goatgrass Kochia Lambsquarters Prsn. speedwell Rape Russian thistle Ryegrass Snls. chamomile Sugar beet Wheat (Spring) Wheat (Winter) Wild buckwheat Wild oat i WO 91/03464 PCY/ULS90/4953 269 COMPOUND COMPOUND Rate (32 g/ha)

POSTEMERGENCE

Barley (Spring) Barley (Winter) Blackgrass (1) Blackgrass (2) Blk. nightshade Bluegrass Cheatgrass Downy brome Fld. pennycress Fld. violet Galium Green foxtail Ivylf speedwell Jntd. goatgrass Kochia Lambsquarters Prsn. speedwell Rape Russian thistle Ryegrass Snls. chamomile Sugar beet Wheat (Spring) Wheat (Winter) Wild buckwheat Wild oat (1) Wild oat (2) Rate (32 g/ha)

PREEMERGENCE

Barley (Spring) Barley (Winter) Blackgrass Blk. nightshade Bluegrass Cheatgrass Downy brome Fld. pennycress Fld. violet Galium Green foxtail Ivylf speedwell Jntd. goatgrass Kochia Lambsquarters Prsn. speedwell Rape Russian thistle Ryegrass Snls. chamomile Sugar beet Wheat (Spring) Wheat (Winter) Wild buckwheat Wild oat i.

I re WO 91/03464 PCT/US90/04953 270 TEST G Seeds, rhizomes, or tubers of alfalfa (Medicago sativa), barnyardgrass (Echinochloa crus-alli), bermudagrass (Cynodon dactylon), broadleaf signalgrass (Brachiaria plantaginea), field bindweed (Convolvulus arvensis), guineagrass (Panicum maximum), johnsongrass (Sorghum halepense), large crabgrass (Digitaria sanouinalis), pitted morningglory (Ipomoea lacunosa), purple nutsedge (Cyperus rotundus), purslane (Portulaca oleracea), ragweed (Ambrosia artemisiifolia), sandbur (Cenchrus echinatus), smooth crabgrass (Digitaria ischaemum), Texas panicum (Panicum texanum), tropical kudzu (Pueraria javanica), and yellow nutsedge (Cyperus esculentus) were planted into greenhouse pots containing greenhouse planting medium. Each pot contained only one plant species. Test compounds were dissolved in a non-phytotoxic solvent and applied to the soil surface (preemergence). These applications were made within one day of planting.

Control pots receiving no test treatments and treated pots were maintained under greenhouse conditions for 13 to 21 days after herbicide application. Growth of treated plants was compared to that of untreated controls and visually evaluated. Plant response ratings, summarized in Table G, are based on a zero to 10 scale where zero is no injury, and 10 is plant death. A dash response means no test result.

WO 91/03464 PCT/US90/04953 271 Table G

COMPOUND

Rate (250 g/ha) 118 132 136 147 153 154 157

PREEMERGENCE

Alfalfa 2 5 3 0 2 4 3 Barnyardgrass 10 10 10 10 10 10 Bermudagrass 10 10 10 10 10 10 Brdlf sgnlgrass 10 10 10 10 10 10 Field bindweed 0 5 1 0 1 1 0 Guineagrass 10 10 9 10 10 10 Johnsongrass 8 10 2 2 10 10 Large crabgrass 9 10 10 10 10 10 Pitted mrnglory 0 3 2 1 0 3 2 Purple nutsedge 10 10 10 7 10 3 8 Purslane 7 10 8 1 9 9 7 Ragweed 1 6 2 0 5 10 9 Sandbur 10 Smooth crbgrass 10 10 10 10 10 10 Texas panicum 6 10 5 9 10 10 9 Trop. kudzu 6 10 9 7 9 9 9 Yellow nutsedge 6 10 2 0 8 2 1 WO 91/03464 WO 91/3464 CrF US90/ 04953 272

COMPOUND

Rate (125 g/ha) 118 132 136 147 153 154 157

PREEMERGENCE

Alfalfa 0 3 1 0 1 4 Barnyardgrass 10 10 10 10 10 10 Bermudagrass 10 10 10 10 10 10 Brdlf sgnlgrass 10 10 10 7 10 10 9 Field bindweed 0 0 1 0 1 1 0 Guineagrass 10 8 9 8 10 10 Johnsongrass 4 10 2 0 9 9 Large crabgrass 9 10 10 10 10 10 9 Pitted mrnglory 1 0 1 0 1 3 2 Purple nutsedge 10 8 10 0 7 1 3 Purslane 5 7 3 0 10 6 2 Ragweed 0 3 0 0 1 9 9 Sandbur 10 Smooth crbgrass 10 10 10 10 10 10 Texas panicum 1 9 2 8 10 9 8 Trop. kudzu 5 6 10 0 9 9 9 Yellow nutsedge 1 4 0 0 1 1 0 WO091/03464PllS9/45 PCT/US90/04953 273

COMPOUND

Rate (64 g/ha)

PREEMERGENCE

Alfalfa Barnyardgrass Be rmud a gras s Brdlf sgnlgrass Field bindweed Guineagrass Johnsongrass Large crabgrass Pitted rnrnglory Purple nutsedge Purs lane Ragweed Sandbur Smooth crbgrass Texas panicum Trop. kudzu Yellow nutsedge 118 132 136 147 153 154 157 Q 3 1 10 10 8 9 10 1 2 10 4 0 2 0 9 9 10 1 3 0 3 10 4 0 0 0 10 10 10 3 2 2 0 0 0 10 10 10 10 0 3 1 0 4 0 0 3 0 0 0 2 1 0 10 10 10 10 10 2 9 10 9 0 2 1 0 1 9 9 0 10 6 8 3 10 10 9 0 1 1 2 0 1 0 1 0 2 6 1 0 8 6 9 10 10 9 1 8 8 6 0 9 9 9 0 1 0 0 WO 91/03464 PCT/US90/04953 274

COMPOUND

Rate (32 g/ha) 118 132 136 147 153 154 157

PREEMERGENCE

Alfalfa 0 2 0 0 1 0 1 Barnyardgrass 0 10 7 0 10 10 Bermudagrass 2 9 9 10 10 10 9 Brdlf sgnlgrass 0 10 0 0 9 9 7 Field bindweed 0 0 0 0 1 0 0 Guineagrass 0 9 1 0 9 9 4 Johnsongrass 0 2 0 0 3 2 1 Large crabgrass 1 6 0 0 9 8 7 Pitted mrnglory 0 0 0 0 0 1 2 Purple nutsedge 1 0 0 1 0 0 Pu:rslane 0 0 0 0 1 2 0 Ragweed 0 0 0 7 2 6 53andbur 10 Smooth crbgrass 3 10 7 2 9 8 7 Texas panicun 0 3 1 0 6 7 7 Trop. kudzu 0 0 0 0 6 8 9 Yellow nutsedge 0 2 0 0 1 0 0

Claims (37)

1. The compounds of the formulas selected from the group consisting of: uLB JB~t- ET t WO 91/03464 PTU9/45 PCT/US90/04953 276 VIIa Vill and stereoisomers thereof, wherein X and Y are independently H or C(R 3 )(R 4 OR 5 Z is C(R 3 )(R 4 OR 5 R 1 is H or a straight-chain Cl-C 3 alkyl; A WO 91/03464 PCI! US9O/04953 277 R 2 is H, Cl-C 6 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, phenyl or Cl-C 4 alkyl substituted by Ph, OH, CN, ORB, SO 2 R 8 PhSO 2 N 3 C0 2 R 8 or CO 2 H; R 3 R 4 R9 and RIO are independently H, Cl-C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl or lC alkyl substi ated with OCH 3 or OCH 2 CH 3 R5 is Cl-C 3 alkyl, C 2 -C 4 alkenyl, C 3 -C 4 alkynyl, benzyl or C 1 -C 4 alkyl substituted with OR 8 OCF 3 R 8 is C 1 -C 3 alkyl; Q is WCH 2 or R q R q W is phenyl optionally substituted with 1-3 substituents selected from F, Cl, Br, CI-C 3 alkyl, Cl-C 3 alkoxy, OH, CN, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, Cl-C 3 alkylthio, C 2 -C 4 alkenyl and C 2 -C 4 alkynyl, or W is a 5 or 6-niemrbered heterocyclic ring containing 0-2 nitrogens, 0-2 oxygens or 0-2 sulfurs, each ring optionally substituted with 1-2 substituents selected from F, Cl, Br, CH 3 and OCH 3 pCT/US90/04953 WO 91/03464 278 Z 1 is CH 2 NRa, O, S or may be taken to form a double bond with an adjacent carbon; Ra is H or C 1 -C 3 alkyl; R 6 is H, halogen, R 8 OR 8 SR 8 or CN; R 7 is H, F, Cl, CH 3 OCH 3 OH or OR 8 q 1 is 0, 1 or 2; and q is 0, 1 or 2. provided that 1) at least one of X and Y is C(R 3 )(R 4 )OR 5 2) R 3 R 4 R 9 and R 10 each contains no more than four carbon atoms; 3) in Formula II, if R 1 is H then X is C(R 3 )(R 4 )OR 5 and Y is H; 4) the sum of q and ql is 0, 1 or 2; and if the sum of q and q 1 is 0 then Z 1 is CH 2

2. The compounds of Formulas I, II, III, IV, V, VI, VII, or VIII according to Claim 1 wherein: W is phenyl optionally substituted by 1-2 substituents selected from F, Cl, Br, CH 3 and OCH 3 or W is tetrahydropyran, tetrahydrofuran, thiophene, isoxazole, pyridine or pyrazine, each ring optionally substituted with 1-2 substituents selected from F, Cl, Br, CH 3 or OCH 3 WO 91/03464PC!S9/45 PCT/US90/04953 279 Q is Ro -a P6 -C I Ro f 1 R WO 91/03464 PI!U9/45 PCT/US90/04953 280 Ra R R6 b?, Q-1 0 Q-1 11 9-1 2 Q-1 Q-1 3 0-14 R a is H or C 1 -C 3 alkyl; and R 5 is other than benzyl.

3. The compounds of Claim 2 wherein R 2 is H, C 1 -C 3 alkyl, C 2 -C 3 alkenyl or C 2 -C 3 alkynyl.

4. The compounds of Claim 3 wherein R 3 is H, C 1 -C 3 alkyl, C 3 C 4 alkenyl or C 3 -C 4 alkynyl; R4 is H, C 1 -C 3 alkyl, C 3 -C 4 alkenyl or C 3 -C 4 alkynyl; R 5 is H, Cl-C 3 alkyl, C 3 -C 4 alkenyl or C 3 -C 4 alkynyl; PCrUS9004953 WO 91/03464 281 R 9 is H, C 1 -C 3 alkyl, C 3 -C 4 alkenyl or C 3 -C 4 alkynyl; R 10 is H, C1-C 3 alkyl, C 3 -C 4 alkenyl or C 3 -C 4 alkynyl; The compounds of Claim 4 wherein Q is Q-l, Q-3, Q-6, Q-7 or

6. The compounds of Claim compound is of Formula I.

7. The compounds of Claim compound is of Formula II.

8. The compounds of Claim compound is of Formula III.

9. The compounds of Claim compound is of Formula IV. The compounds of Claim compound is of Formula V.

11. The compounds of Claim compound is of Formula VI.

12. The compounds of Claim compound is of Formula VII.

13. The compounds of Claim compound is of Formula VIII. 5 wherein the 5 wherein the 5 wherein the 5 wherein the 5 wherein the 5 wherein the 5 wherein the 5 wherein the

14. The compound of Claim 6 which is: 2-(l-ethyl-l-methoxypropyl)-6-(phenyl- WO 91/03464 PCT/US90/04953 282 methoxy)-7-oxabicyclo[2.2.1]heptane, (2-exo, 6-exo). The compound of Claim 8 which is: 2-(ethoxymethyl)-5-methyl-4-(phenyl- methoxy)-6-oxabicyclo[3.2.1]octane, (2-endo, 4-endo).

16. An agriculturally suitable composition for controlling the growth of undesired vegetation comprising an effective amount of the compound of Claim 1 and at least one of the following: surfactant, solid or liquid diluent.

17. An agriculturally suitable composition for controlling the growth of undesired vegetation comprising an effective amount of the compound of Claim 2 and at least one of the following: surfactant, solid or liquid diluent.

18. An agriculturally suitable composition for controlling the growth of undesired vegetation comprising an effective amount of the compound of Claim 3 and at least one of the following: surfactant, solid or liquid diluent.

19. An agriculturally suitable composition for controlling the growth of undesired vegetation comprising an effective amount of the compound of Claim 4 and at least one of the following: surfactant, solid or liquid diluent.

20. An agriculturally suitable composition for controlling the growth of undesired vegetation i WO 91/03464 PCT/US90/04953 283 comprising an effective amount of the compound of Claim 5 and at least one of the following: surfactant, solid or liquid diluent.

21. An agriculturally suitable composition for controlling the growth of undesired vegetation comprising an effective amount of the compound of Claim 6 and at least one of the following: surfactant, solid or liquid diluent.

22. An agriculturally suitable composition for controlling the growth of undesired vegetation comprising an effective amount of the compound of Claim 7 and at least one of the following: surfactant, solid or liquid diluent.

23. An agriculturally suitable composition for controlling the growth of undesired vegetation comprising an effective amount of the compound of Claim 8 and at least one of the following: surfactant, solid or liquid diluent.

24. An agriculturally suitable composition for controlling the growth of undesired vegetation comprising an effective amount of the compound of Claim 9 and at least one of the following: surfactant, solid or liquid diluent. An agriculturally suitable composition for controlling the growth of undesired vegetation comprising an effective amount of the compound of Claim 10 and at least one of the following: surfactant, solid or liquid diluent. WO 91/03464 PCT/US90/04953 284

26. An agriculturally suitable composition for controlling the growth of undesired vegetation comprising an effective amount of the compound of Claim 11 and at least one of the following: surfactant, solid or liquid diluent.

27. An agriculturally suitable composition for controlling the growth of undesired vegetation comprising an effective amount of the compound of Claim 12 and at least one of the following: surfactant, solid or liquid diluent.

28. An agriculturally suitable composition for controlling the growth of undesired vegetation comprising an effective amount of the compound of Claim 13 and at least one of the following: surfactant, solid or liquid diluent.

29. An agriculturally suitable composition for controlling the growth of undesired vegetation comprising an effective amount of the compound of Claim 14 and at least one of the following: surfactant, solid or liquid diluent. An agriculturally suitable composition for controlling the growth of undesired vegetation comprising an effective amount of the compound of Claim 15 and at least one of the following: surfactant, solid or liquid diluent.

31. A method for controlling the growth of undesired vegetation which comprises applying to the locus to be protected an effective amount of a compound of Claim i. WO 91/03464 PCT/US90/04953 285

32. A method for controlling the growth of undesired vegetation which comprises applying to the locus to be protected an effective amount of a compound of Claim 2.

33. A method for controlling the growth of undesired vegetation which comprises applying to the locus to be protected an effective amount of a compound of Claim 3.

34. A method for controlling the g-owth of undesired vegetation which comprises applying to the locus to be protected an effective amount of a compound of Claim 4. A method for controlling the growth of undesired vegetation which comprises applying to the locus to be protected an effective amount of a compound of Claim

36. A method for controlling the growth of undesired vegetation which comprises applying to the locus to be protected an effective amount of a compound of Claim 6. 1 s

37. A method for controlling the growth of undesired vegetation which comprises applying to the locus to be protected an effective amount of a t *compound of Claim 7.

38. A method for controlling the growth of undesired vegetation which comprises applying to the locus to be protected an effective amount of a compound of Claim 8. WO 91/03464 PCT/IUS90/04953 286

39. A method for controlling the growth of undesired vegetation which comprises applying to the locus to be protected an effective amount of a compound of Claim 9. A method for controlling the growth of undesired vegetation which comprises applying to the locus to be protected an effective amount of a compound of Claim

41. A method for controlling the growth of undesired vegetation which comprises applying to the locus to be protected an effective amount of a compound of Claim 11.

42. A method for controlling the growth of undesired vegetation which comprises applying to the locus to be protected an effective amount of a- compound of Claim 12.

43. A method for controlling the growth of undesired vegetation which comprises applying to the locus to be protected an effective amount of a compound of Claim 13.

44. A method for controlling the growth of undesired vegetation which comprises applying to the locus to be protected an effective amount of a compound of Claim 14. A method for controlling the growth of undesired vegetation which comprises applying to the locus to be protected an effective amount of a compound of Claim INTERNATIONAL SEARCH REPORT International Application No PCT/US 90/04953 I. CLASSIFICATION OF SUBJECT MATTER (if several classification symbols apply, indic:te all) 6 According to International Patent Classification (IPC) or to both National Classification and IPC 5 CU/D4YJ/Ub AU1N 43/90//(C07D493/08,319:00,311:00),(CO7D493/08,311:00,311:00),(CO7D493/08, 311:00,307:00),(C07D493/08,307:00,307:00) II. FIELDS SEARCHED Minimum Documentation Searched 7 Classification System Classification Symbols C 07 D; A 01 N Documentation Searched other than Minimum Documentation to the Extent that such Documents are Included in Fields Searched 8 III. DOCUMENTS CONSIDERED TO BE RELEVANT 9 Category Citation of Document,' 1 with indication, where appropriate, of the relevant passages 12 Relevant to Claim No. 1 3 X EP, A2, 0081893 (SHELL INTERNATIONALE RESEARCH 1-45 MAATSCHAPPIJ 22 June 1983, see the whole document X GB, A, 2188931 (SHELL INTERNATIONALE RESEARCH 1-45 MAATSCHAPPIJ 14 October 1987, see the whole document X US, A, 4486219 (JAMES E. POWELL) 1-45 4 December 1984, see the whole document SSpecial categories of cited documents: 10 'T later document published after the International filing date document defining the qeneral state of the art which is not or priority dale and not in conllict with the application but cons red to e o prtclar reevance art whh s ot ed ounderstand the principle or theory underlying the consered to e I particular relevance nvention 'E earlier document but published on or after the international document of particular relevance, the claimed nvention filing date document of particular relevance, the claimed Invention cannot be considered novel or cannot be considered to document which may throw doubts on priority clalm(s) or involve an inventive step which is cited to establish the publication date of another citation or other special reason (as specified) Y' document of partlcular relevance, the claimed invention ii r rcannot be considered to nvolve an inventive step when the document referring to an oral disclosure, use, exhibition or document is combined with one or more other such doced other means e ,Such combination being obvious to a person skilled document published prior to the international filing date but the same p t later than the priority date claimed document member of the same patent family IV. CERTIFICATION Date of the Actual Completion of the International Search Date of Mailing of this International Search Report 21st January 1991 19 2. 91 International Searching Authority Signature of Authorized Officer EUROPEAN PATENT OFFICEi ;=ES Form PCTlSA/210 (second sheet) (January 1985) _F 1 International Application No. PCT/US 90/04953 III. DOCUMENTS CONSIDERED TO BE RELEVANT (CONTINUED FROM THE SECOND SHEET) Category Citation of Document, with indication, where appropriate, of the relevant passages Relevant to Claim No US, A, 4798621 (ROBERT C. ACKERSON ET AL.) 17 January 1989, see the whole document WO, Al, 8902219 DU PONT DE COMPANY) 23 March 1989, see the whole document WO, Al, 8911481 DU PONT DE COMPANY) 30 November 1989, see the whole document WO, Al, 9009383 DU PONT DE COMPANY) 23 August 1990, see the whole document NEMOURS AND NEMOURS AND NEMOURS AND 1-45 1-45 1-45 1-45 'or PCT/ISA/210 (extra sheet) (January 1985) 'A ANNEX TO THE INTERNATIONAL SEARCH REPORT ON INTERNATIONAL PATENT APPLICATION NO.PCT/US 90/04953 SA 41144 This annex lists the patent family members relating to the patent documents cited in the above-mentioned international search report. The members are as contained in the European Patent Office EDP file on 28/12/90 The European Patent office is in no way liable for theseparticulars which are merely given for the purpose of information. Patent document Publication Patent family Publication cited in search report date member(s) date EP-A2- 0081893 22/06/83 AU-B- 557933 15/01/87 AU-D- 9138082 23/06/83 CA-A- 1221685 12/05/87 JP-A- 58110591 01/07/83 OA-A- 7277 30/12/84 SU-A- 1322967 07/07/87 US-A- 4670041 02/06/87 US-A- 4542244 17/09/85 US-A- 4554366 19/11/85 US-A- 4567283 28/01/86 GB-A- 2188931 14/10/87 AU-B- 596406 03/05/90 AU-D- 7144587 15/10/87 BE-A- 1002100 03/07/90 CH-A- 674364 31/05/90 DE-A- 3712464 15/10/87 FR-A- 2597101 16/10/87 JP-A- 62249980 30/10/87 NL-A- 8700865 02/11/87 US-A- 4486219 04/12/84 US-A- 4536586 20/08/85 US-A- 4798621 17/01/89 JP-A- 63139101 10/06/88 WO-Al- 8902219 23/03/89 EP-A- 0308170 22/03/89 EP-A- 0383785 29/08/90 WO-A1- 8911481 30/11/89 EP-A- 0343859 29/11/89 WO-A1- 9009383 23/08/90 EP-A- 0383469 22/08/90 For more details about this annex see Olticlal Journal of the European patent Ofllce, No. 12182 EPO FORM P0479 _.A