[go: up one dir, main page]

CA3101114C - Triphenylphosphonium salt compounds, preparation method and use thereof - Google Patents

Triphenylphosphonium salt compounds, preparation method and use thereof Download PDF

Info

Publication number
CA3101114C
CA3101114C CA3101114A CA3101114A CA3101114C CA 3101114 C CA3101114 C CA 3101114C CA 3101114 A CA3101114 A CA 3101114A CA 3101114 A CA3101114 A CA 3101114A CA 3101114 C CA3101114 C CA 3101114C
Authority
CA
Canada
Prior art keywords
formula
compound
group
site
range
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CA3101114A
Other languages
French (fr)
Other versions
CA3101114A1 (en
Inventor
Zhaohai Qin
Jiayao WANG
Xuelian LIU
Dachao TANG
Yumei Xiao
Jiaqi Li
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
China Agricultural University
Original Assignee
China Agricultural University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by China Agricultural University filed Critical China Agricultural University
Publication of CA3101114A1 publication Critical patent/CA3101114A1/en
Application granted granted Critical
Publication of CA3101114C publication Critical patent/CA3101114C/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds
    • A01N57/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds
    • A01N57/20—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds containing acyclic or cycloaliphatic radicals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds
    • A01N57/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds
    • A01N57/22—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds containing aromatic radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/54—Quaternary phosphonium compounds

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Agronomy & Crop Science (AREA)
  • Dentistry (AREA)
  • Plant Pathology (AREA)
  • Pest Control & Pesticides (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Disclosed are a quaternary triphenylphosphonium salt compound, a preparation method therefor, and the uses thereof. The structure of the quaternary compound is as shown in formula I. The preparation method comprises carrying out a nucleophilic reaction of the compound shown of formula VII and triphenylphosphine in an organic solvent with or without a catalyst to obtain the compound as shown in formula I. The compound as shown in formula I can be used for preventing and treating diseases caused by a plurality of germs such as oomycetes, basidiomycetes, ascomycetes and semi-known fungi on a variety of plants. Excellent results have been obtained in powdery mildew, corn rust, watermelon anthracnose and the like, and a good control effect can be ensured at low concentrations.

Description

TRIPHENYLPHOSPHONIUM SALT COMPOUNDS, PREPARATION METHOD AND
USE THEREOF
Field of the Invention The present invention relates to the technical field of pesticides, and in particular to a class of triphenylphosphonium salt compounds, and preparation methods and use thereof.
Background of the Invention Quaternary phosphonium salts and derivatives thereof have been developed rapidly since the synthesis of tetrahydroxymethyl phosphonium salts by Messinger et al. in 1888.
Alkyl quaternary phosphonium salt compounds, which have been produced and used since 1990, are a new generation of efficient and broad-spectrum fungicides. With the advantages of high efficiency, broad spectrum, strong surface activity, strong slime stripping and cleaning effects, low foaming, low dose, low toxicity, no environmental pollution, good compatibility, wide use ranges of pH values (pH 2-12), good chemical stability, etc., this kind of fungicides is the representative of a new generation cationic surfactant fungicides, and widely used in various fields such as medical and health, oil field exploitation, water treatment, food industry, agriculture, and daily life.
At the same time, due to high affinity to mitochondria, the phosphonium salts are widely used in the field of mitochondrial targeted delivery of drugs. The phosphonium salts have a 1000 times higher targeted aggregation ability in mitochondria than non-targeted drugs, and help to reduce the amount of drugs used and decrease side effects.
Summary of the Invention One objective of the present invention is to provide a triphenylphosphonium salt compound and a preparation method thereof.
The triphenylphosphonium salt compound provided by the present invention has a general structural formula as shown in formula I:
Ph Ph ,1, X Q
y- n Formula I

4 ' wherein in formula I, X is selected from the group consisting of CH2, N, S.
and 0; Y is any one selected from the group consisting of halogen (Cl, Br, or I), CH3S03, CF3CO2, CH3CO2, CF3S03, PhCO2, HOC6H4CO2, (CH2CO2)2, (CHCO2)2, and formula W; n is an integer in the range from 0 to 16; and Q is selected from the group consisting of formula Ia and formula Ib;

,11, Ar 'µ W
R1 41 SO3 I :SS5' u - Q2 Qi w 1a lb wherein in formula W, RI represents H or Ci-C12 alkyl;
wherein in formula Ia, Ar is any one selected from the group consisting of Ai-A8 below, and Qi is any one selected from the group consisting of H and BI-Bil;
(ROm (R.Op ri .s''= ,./
/

At = = A3= A A4=
(R3)0 (1Z5)q 0 0(R-6)r A5¨ A,5=
¨
Af= I) _______________________________________________ <

0 0 0 0õ0 0 ¨
B 1 = I ''''*)')1.1' B2¨ ** I '' ' B ¨ CsKIL/
C 1 3¨ B4= I
N -.---''CF3 0 0 (R7), B5= rl)t../ B6= 1`?X A B7= ' B8 =
N CI 'INT
/ Rg 7--- S

A
B9 -'=== is B 10= NYA' B11=
= 0 and wherein in formula lb, U is any one selected from the group consisting of 0, NH, S, 0C-0, SC=0, NHC=0, and NHC=S, and Q2 is any one selected from the group consisting of Cl-C4;
0 0 0 so yt, c 1.= C2= c3. C4=

_1z MCH3 N OCH3 Iz MCH3 H3C0 H3C0' wherein, in formulas Ai, Az, and As among AI-A8, R2, R3, R4, R5, and R6 are each at least one selected from the group consisting of hydrogen, Ci-Cs alkyl, CI-Cs alkoxy, C t-Cs alkylthio,
2 Ci-Cs fluoroalkyl, Ci-Cs fluoroalkoxy, halogen, nitro, cyano, phenoxyl, pyridyloxyl, methanesulfonyl, and trifluoromethylsulfonyl, the halogen being any one selected from the group consisting of fluorine, chlorine, bromine, and iodine; m is an integer in the range from 0 to 4; o, q, and r are each integers in the range from 0 to 5; p is an integer in the range from 0 to 3;
and the binding sites of R2, R3, its and R6 are at least one of remaining five binding sites, wherein, when m, o, q, and r> 1, R2, R3, Rs, and R6 may be the same or different; and the binding sites of R4 are at least one of remaining three binding sites, wherein, when p> 1, R4 may be the same or different; in formula Az, N may be at any site of sites 3, 4, 5, and 6;
wherein in formula Bi among BI-B10, R7 is at least one selected from the group consisting of hydrogen, CI-Cs alkyl, CI-Cs alkoxy, CI-05 fluoroalkyl, CI-05 fluoroalkoxy, halogen, nitro, cyano, phenoxy, pyridyloxy, carboxyl, methylsulfonyl, and trifluoromethylsulfonyl, the halogen being any one selected from the group consisting of fluorine, chlorine, bromine, and iodine; s is an integer in the range from 0 to 5; the binding sites of R7 are at least one of remaining 5 binding sites, wherein R7 may be the same or different when s> 1; in formula 86, R8 and R9 are each any one selected from the group consisting of hydrogen, CI-Cs alkyl, CI-Cs alkoxy, Ci-05 fluoroalkyl, CI-05 fluoroalkoxy, and halogen; and wherein in formulas Ci and C3 among C1-C4, Z is selected from the group consisting of N
and CH, and M is selected from the group consisting of NH and 0.
The general structural formula of the phosphonium salt compounds provided by the present invention is shown in formula I. Preferably, in formula I, X is CH2 or 0; Y is any one selected from the group consisting of halogen, AcO(CH3CO2), p-toluenesulfonyl (Ts0), PhCO2, and HOC6H4CO2; n is an integer in the range from 4 to 11; and Q is Ia or II).
More preferably, in formula Ia, Ar is Ai, A3, A4, or A6, and Q1 is H; and in formula Ib, U is any one selected from the group consisting of 0, OC=0, and SC=0, and Qz is any one selected from the group consisting of CI-C4.
The terms as used in the definitions of the compound of formula I of the present invention represent the following substituents.
The term "halogen" refers to fluorine, chlorine, bromine, and iodine.
The term "alkyl" represents straight or branched alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, and tert-amyl.
The aryl and the aryl moiety in the aryloxy include phenyl, pyridyl, furyl, etc.
In addition, in the compounds of formula I of the present invention, geometric isomers are formed due to the connection to different substituents by a carbon-carbon double bond or a carbon-nitrogen double bond (different configurations are represented by Z and E,
3 respectively). The compound of formula I of the present invention can be a Z-isomer, an E-isomer, or a mixture at any proportions of the two.
The compound of formula I of the present invention can be in particular selected from the compound numbered as follows.
Fip Ph Ar Ph)LNAr y n n Iana Ianb Number Y Qt Ar Ia.4-1 ta-1-4a4-11b-1 Br H At/[(R2)m=H (R3)0=H]
Ia4-1 Ai/[(R2)m=H (R3)0=2-C1]
Ia4-11a-3¨Ia4-111)-3 H At/[(R2)m=H (R3)0=3-C1]
Ia4-11 tb-4 H Aid(R2)m=H (R3)0=4-C1]
1u-11a-5-1u-1lb-5 H At/[(R2)m=H (R3)0=3,4-2C1]
Ia4-tia-6-4a4-11b-6 H At/[(R2)m=H (R3)0=2-CH31 Ia4-1 ta-7¨Ia44113-7 H Ai/[(R2)m=H (R3)0=3-CH3]
la4-na-8¨Ia4-11b-8 H A t/[(R2)m=H (R3)0=4-CH3]
Ia4-11a-9¨Ia4_11b-9 H At/[(R2)m=H (R3)0=3,5-2CH3]
At/[(R2)m=H (R3)0=4-C(CH3)3]
la4-11a-11¨la4-tib-1 1 H At/[(R2)m=H (R3)0=4-SCH31 Ia4-ita-12¨la4-11b-12 H At/[(R2)m=H (R3)0=4-Br]
Ia4-11a-13---la4.11b-13 H At/[(R2)m=H (R3)0=4-F]
1u-11a-14-1m-1lb-14 H At/[(R2)m=H (R3)0=3-F1 Ia4-11a-15¨Ia4-ttb-15 H At/[(R2)m=H (R3)0=2,4-2F]
Iaa_ita-16¨Ia4-tib-16 H At/[(R2)m=H (R3)0=3,4-2F1 Ia4-na-17¨Ia4-11b-17 H A1/[(R2)m=H (R3)03 ,4,53F]
Ia4-Ita-18¨Ia4-11b-18 H At/[(R2)m=H (R3)0=4-0CH3]
Ia4-tia-19¨Ia4-1113-19 H At/[(R2)m=H (R3)0=3-0CH3]
Ia4-t 1a-20¨M4-1lb-20 H At/[(R2)m=H (R3)0=4-CF3]
Ia4-11a-21¨Ia4-11b-21 H At/[(R2)m=H (R3)0=4-CN]
a411 a-22-Jas- tb22 H A t/[(R2)m=4-F (R3)0=11]
1u-11a-23-1m-1lb-23 H Ai/[(R2)m=4-F (R3)0=2-C1]
Ia4-11a-24-1a4-11b-24 H Al/KR2)m=4-F (R3)0=3-C1]
ib-25 H Ai/[(R2)m=4-F (R3)0=4-C1]
Ia4-ita-26¨Ia4-1 lb-26 H At/[(R2)m=4-F (R3)0=3,4-2C1]
Ia4-I ta-27¨Ia4-11b-27 H At/[(R2)m=4-F (R3)0=2-CH3]
Ia4-11a-28¨Ia4-11b-28 H At/[(R2)m=4-F (R3)0=3-CH3]
ib-29 H At/[(R2)m=4-F (R3)0=4-CH3]
Ia4-11a-30¨Ia4-nb-30 H At/[(R2)m=4-F (R3)0=3,5-2CH3]
Ia4-I i a-31¨Ia4-11b-31 H At/[(R2)m=4-F(R3)0=4-C(CH3)3]
4 V
1 i 1a4.11a-32-1a4-lib-32 H At/[(R2)m=4-F (R3)0=4-SCH3]
1u-11a-33¨W-1lb-33 H A1/[(R2)m=4-F (R3)0=4-Brj 1a4-11a-34-1a4-11b-34 H Ai/[(R2)m=4-F (R3)0=-4-F]
1m-11a-35-1u-1lb-35 H A1/[(R2)m=4-F (R3)0=-3-F]
1a411a-36-1a4-lib-36 H At/[(R2)m=4-F (R3)0=2,4-2F]
1a4-11a-37-1a4-11b-37 H A1/[(R2)m=4-F (R3)0=3,4-2F1 1a,µIta-38-1a4-11b-38 H A1/[(R2)m=4-F(R3)0=3,4,5-3F]
1a4-na-39-1a4-11b-39 H AL/[(R2)m---4-F (R3)0=4-0CH3]
la4- 1 1 a-40-1a4-1113-40 H AJ/[(R2)m=4-F (R3)0=3-0CH3]
1a4-Iia-41¨Ia4-1ib-41 H A1/[(R2)m=4-F (R3)0=4-CF3]
13.4- 1 1 a-42¨Ia4-iib-42 H Ai/[(1Z2)ra--4-F (R3)0=4-CN]
_ Ia4-lia-43-1a4-iib-43 H A2/N=site 3 [(R4)p=H
(R5)q=H]
1u-11a-44-1u-1 ib-44 H A2/[N=site 3 (11.4)p=H
(R5)q=2-01 1a4-t1a-45-1a4-ilb-45 H A2/[N=site 3 (R4)p=H (R5)q=3-C1]
la4-lia-46-1a4-iib-46 H A2/[N=site 3 (R4)p=H (Rs)q4-CI}
1u-11a-47-1m-1lb-47 H A2/[N=site (R4)p=H (Rs)q=3,4-2C1]
Ia4-tia-48-1a4-itb-48 H A2/[N=site 3 (R4)p=H (R5)q=2-Ia4-11a-49-1a4-1113-49 H A2/[N=site 3 (R)pH (R5)q=3-CH3]
Ia4-t1a-504a4-11b-50 H A2/[N=site 3 (R4)p=H (Rs)q=4-CH3) , H A2/[N=site 3 (R)p=H
18.4-na-51-4a4-11b-51 (R5)q=3,5-2CH3]
H A2/[N=site 3 (R4)p=H
Ia4-ila-52-1a4-1113-52 (Rs)q=4-C(CH3)3]
H A2/[N=site 3 (R4)p=H
1a4-11a-53-1a4-.11b-53 (%)q=4-SCH31 La4-i ta.-54¨Ia4-t ib-54 H A2/[N=site 3 (R4)p=H (R5)q=4-Br]
1a4_iia-55-1a4-1ib-55 H A2/[N=site 3 (R4)p=H (Rs)q=4-1a4-11a-56¨Ia4-11b-56 H A2/[N=site 3 (R4)pH (Rs)q=3-1a4-iia-57-1a4-1ib-57 H A2/[N=site 3 (R4)p=--H
(R5)q=2,4-2F1 H A2/[N=site 3 (R4)p=H
Ia4.11a-58-1a4-11b-58 (Rs)q=3,4,5-3F]
H A2/[N=site 3 (R4)p=H
1a4-Ita.-59¨Ia4-utb-59 (R5)q=4-0CH3]
H A2/[N=site 1a4-11a-60-1a4-I ib-60 (R.4)p=H(Rs)q----3-0CH3]
Ia4-iia-61-1a4-ilb-61 H A2/[N=site 3 (R4)p=H (R5)q=4-CF3]
1a4-1 1 a-62¨Ia4-i ib-62 , H
, A2/[N=site 3 (R4)pH (R5)q=4-CN]
la4-lia-63-1a4-11b-63 H A3 1a:4_11a-64-1u-1lb-64 H A4 la4-11a-65-1a4-11b-65 H 4 As/[0)1=H
_}
1u-11a-66¨M4-1lb-66 H A5/[(R6)r=2-CH3]
la4-iia-67-1a4-1 1 b-67 H A5/[(R6)1=3-CH3]
1a4-Iza-68-1a4-11b-68 H A5/[(R6),=2-CN]
Ia4-1la-69-1a4-ttb-69 H A5/[(Ro)r=2-CF3]

1u-11a-70¨M4-1lb-70 H A5/[(R6),=2,6-2CH3]
Ia.4-t a-7 1 ¨Ia4-11 b-7 1 H A5/[(R6)r=2-C1-4-NO2]
1u-11a-72¨M4-i 113-72 H As/[(R6)r=2-NO2-4-CF3]
Ia4-11a-73¨Ia4-11b-73 H A5/[(R6)t=2,3-2C1-4-0H]
Ia4-11a-74-4a4.11b-74 H A5/[(R6)r=2,6-2C1-4-0CF3]
A5/[(R6)r=3-CI-4-CH3]
Ia4-11a-76¨Ia4-nb-76 H A5/[(R6)r=3-0CH(CH3)2]
A5/[(R6),=4-CHCH3CH2CH
Ia4-11a-77--Ia4-nb-77 (CH3)21 Ia4-t a-78¨Ia4- lib-7 8 H A6 Ia4-i a-79¨Ia4-nb-79 H A7 Ia4-t a-80¨Ia4-1113-80 H As B [(R7)s=2 A3 Ia4- I a-8 1¨Ia4-11b-8 I
-I]
s Ia4-1 a-82¨Ia4-11b-82 B [(R7)=2 A4 -I]
B [(1(7)s=2 A5/[(R6)r=H]
Ia4-11a-83¨Ia4-nb-83 -I]
B [(R7)s=2 A6 1u-11a-84-1u-1lb-84 -I]
Ia4-11a-8 5--Ia4-11b-8 5 B [(R7)s=2 A3 -CH3]
B

Ia4-11a-86¨Ia4- ib-86 [(R7)s=2 A4 -CH3]
Ia4-11a-87¨Ia4-1113-87 B [(R7)s=2 A5/[(R6)r=3 -OCH(CH3)2]
-CH3]
Ia4-11 a-8 8¨Ia4-i ib-88 B [(R7)s=2 A6 -CH3]
Ia4- a-89¨Ia4-nb-89 B[(R7)s=2 A3 -CF3]
1u-11a-90-1u-I ib-90 B [(R7)s=2 A4 -CF3]
a4_11 a-9 1 ¨Ia4-1113-9 1 B [(R7)s=2 A5/[(R6)r=3-0CH(CH3)21 I
-CF3]
Ia4-11a-92¨Ia4-i 113-92 B [(R7)s=2 A6 -CF3]
Ia4-11a-93¨Ia4-1113-93 B [(R7)s=2 As -CF3]
B
1a4-11a-94-1a4-nb-94 1[(R7)s=2 A3 ,6-2CI]
1m-11a-95-1a/4-1lb-95 B [(R7)s=2 A4 ,6-2CI]
Ia4-11a-96-1a4-11b-96 B [(R7)s=2 A6 ,6-20]

BIRR7)s=2 A8 1a4-11a-97'4a4-111)-97 ,6-2C1]
Bi [(R7)s=3 A3 1a4-iia-98-1a4-1 ib-98 ,4,5,6-4C1 -2-COOH]
BI[(R7)s=3 A4 1a4-11a-99-1a4-1113-99 ,4,5,6-4C1 -2-COOH]
BIRR7)s=3 A5/[(R6)r=2,3-2C1 ,4,5,6-4C1 -2-COOH]
BI[(R7)5=3 Ia4-na-101-Ia4-nb-101 ,4,5,6-4C1 A6 -2-COOH]
Ia4.11a-102-4a4-11b-102 B2 Ai/[(R2)m=H (R3)03 ,42F]
13441a-103-1u-1 lb-103 B2 A3 1a4-1 a-104-Ia4-nb-104 B2 A4 las-t a-105-1a4-11b-105 B2 A6 la4-11a-106-4a4-11b-106 B3 Al /[(R2)m=H (R3)0=H]
1a441a-107-4a4-1ib-107 B3 A3 1u-11a-108-U4-1lb-108 B3 A4 Ia4-tia-109-4a4-nb-109 B3 A5/[(R6)r=H]
Ia4-I a-110--Ia4-11b-110 B3 A6 Ia4-11a-111-Ia4-11b-111 B4 A3 1a4-iia-112---1a4-11b-112 B4 A4 1a4-11a-113-1a4-11b-113 B4 As/[(R6)r=H]
1a4-11a-114-4a4-11b-114 B4 A6 1a4-11a-115-4a4-t ib-115 B5 Ai/[(R2)m=H (R3)0=4-C1]
1a4-lia-116-1a4-nb-116 B5 A3 Ia4-t a-117-1a4-1 ib-117 B5 A4 1a4-11a-118-1a4-111)-118 B5 A5/[(R6)r=H]
1a4-11a-119-1a4-11b-119 B5 A5/[(R6)r=2-CH2CH3]
1a4-11a-120-1a4-111)-120 B5 A5/[(R6)r=2-0CH2CH3]
1a4-11a-121-1a4-11b-121 B5 A5/[(R6)r=2-0CH(CH3)2]
Ia4-I a-122-1a4-1 ib-122 B5 A5/[(R6),=3-CH2CH3]
1114-11a-123-1a4-11b-123 B5 A5/ [(R6)/=3 -OCH2CH3]
Ia4_11a-124-1a4-1113-124 B5 A5/[(R6)r=3-0CH(C113)2]
la4-1Ia-125-1a4-ub-125 B5 A6 B6/[R8=H; A3 Ia4-1 a-126-1a4-1 ib-126 R9=CF3]
B6/[Rs=H; A4 Ia4-na-127-1a4-nb-127 R9=CF3]
1a4-11a-128-1a4-1113-128 Bel[R8=H;A5/[(R6),=H]
R9=CF31 136/[R8=H;
1a4-11a-129-1a4-1113-129 , A5/[(R6)r=2-CH2CH3]
R9=CF3]
B6/[14=H;
1u-11a-130¨U4-1lb-130 , A5/[(R6),=2-0CH2CH3]
R9=CF3]
B6/[R8=H;
1a4-11a-131-1a4-111)-131 , A5/[(R6),--2-0CH(CH3)2]
R9=CF3]
B6/[118=H;
1a4-11a-132-1a4-nb-132 A5/[(R6),3-CH2CH3]
R9=CF3]
B6/[1t8=H;
la4-iia-133-1a4-nb-133 A.5/[(R6),---3-0CH2CH3]
R9=CF3]
B6/[R8=H;
1a4-11a-134-1a4-111)-134 A5/[(R6),=3 -OCH(CH3)2]
R9=CF3]
B6/[12.8=H; A5/[(R6)r=4-CHCH3CH2CH
Ia41 a-135¨Ia4- nb-135 R9=CF3] (CH3)2]
B6/[lts=H; A
la4- a-136--1a4-1113-136 H6 R9=CF3]
B6/[1t8=H;
1u-11a-137-1m-1lb-137 H7 R9=CF3]
1a4-1 a-138¨Ia4-Hb-138 B6/[R8=C1 A3 ; R9=CH3]
B6/[1t8=C1 A4 la4-na-139-1a4-11b-139 ; R9=CH3]
B6/[R8=C1 Ia4- iia-140--la4-11b-140 A5/[(R6)r=H]
; R9=CH3]
1a4-11a-141-1a4 B6/[11.8=C1-11b-141 A5/[(R6)r=2-C112C113]
; R9=CH3]
B6/[R8=C1 Ia4-1 a-142-1a4- ib-142 A5/[(R6),=2-0CH2CH3]
; R9=CH3]
B6/[1t8=C1 1a4-iia-143-1a4-1113-143 , , A5/[(R6)r=2-0CH(CH3)2]
; R9=CH3]
B6/[1t8=C1 A5/[(R6)r=4-CHCH3CH2CH
1a:1_11a-144-4a44 1b-144 ; R9=CH3] (CH3)2]
1a4-iia-145-1a4-1 ib-145 B6/[1t8=C1A6 ; R9=CH3]
B6/[14=C1 Ia4-1 a-146-1a4-11b-146 , , A7 ; R9=Cr13 ]
B6/[14=H; A3 Ia4- a-147¨Ia4-ub-147 R9=CF3]
B6/[1t8=H; A4 1a4-11a-148-1a4- lib-148 R9=CF3]
Ia4- a-149-1a4-1113-149 B6/[R8=H;A5/[(R6),=H]
R9=CF3]
B6/[1t8=H;
1a4-iia-150-1a4-11b-150 õ A5/[(R6)r=2-CH2CH3]
R9=CF3]

=
1a4-ua-151-1a4-u B6/[R8=H; b-151 A5/[(R6)r=2-0CH2CH3]
R9=CF3j 1a4-ua-152-1a4-tib-152 =CF3J , A5/[(R6)r=2-0CH(CH3)2]

136/[12.8=H; A5/[(R6)r=4-CHCH3CH2CH
1a4-11a-153-1a4-1 ib-153 R9=CF3] (CH3)2]
1a4- lla-154-4a4-n B6/[R8=H;b-154 A6 R9=CF3]
B6/[R8=H;
1a4-na-155-1a4-ub-155 , H7 R9=CF3]
1a4.11a-156^-1a4-11b-156 B7 A3 Ia4_ua-157^1a4-11b-157 B7 A4 1a4-iia-158-1a441b-158 B7 As/[(R6),==11]
13.4-na-159-1a4-ub-159 B7 As/[(R6)r=2,6-2Br-4-0CF3]
1a4-11a-160-1m-1lb-160 B7 A6 1a4-1 1a-161-4u-1lb-161 B7 A7 1u-11a-162-M44 ib-162 Bs A3 Ia4-1 1a-163-M4-1lb-163 Bs A4 1a4-11a-164--1a4-1 ib-164 Bs A5/[(R6)r=11]
1a4-1 a-165-1a4-1 lb-165 B8 As/[(R6)r=2,6-2Br-4-0CF3]
1u-11a-166-1a:1-I ib-166 Bs A6 la4-113.-167-1a4-11b-167 Bs A7 Ia4-1 ia-168-Ia4-nb-168 B9 A3 1a4-11a-169-1a4-ub-169 B9 A4 lac' 1a-170-1m-1lb-170 B9 As/[(R6)r=11]
1u-11a-171-1m-1lb-171 B9 A6 1a44 la-172-1a4-iib-172 D9 A7 1a4-11a-173-1a4-ub-173 _ BIO A3 1a4-11a-174-1a4-11b-174 B10 A4 Ia4-1 a-175-1a4-nb-175 Blo A5/[(R6)r=11]
la4-1 a-176-1a4-ub-176 Bio As/[(R6).=-3-C1-4 CH3]
1a4-1 a-177-Ia4-Hb-177 Blo A6 1a4_11a-178-1a4-ub-178 Blo A7 Ia4-1 a-179-1a4-i ib-179 B11 A3 la4-11a-180-1a4-1ib-180 B11 A4 1a4-lla-181--Ia4-11b-181 Bu As/[(R6),=H]
1a4-11a-182-1a4-11b-182 B11 A5/[(R6)r=2,6-2CH3]
1a4-ua-1834a4-nb-183 B11 A6 1a4-ua-184-1a4-11b-184 B11 A7 ib-185 Ac0 H At/[(R2)m=H (R3)0=11]
1a4-1 ia-186---1a4-11b-186 H Al/[(R2)m=H (R3)0=2-C1]
1a4-113.-187--1a4-11b-187 Al/[(R2)m=H (R3)0=3-C1]
1a4-1 a-188-Ia4-ub-188 H A1/[(R2)m=H (R3)0=4-C1]

I I .
=
la4-tta-189-4a4-11b-189 H At/[(R2)m=H (R3)0=3,4-2C1]
1u-11a-190-1m-1lb-190 H At/[(R2)nn=H (R3)0=2-CH3]
1u-11a-191-1u-1lb-191 H At/[(R2)m=H (R3)0=3-CH3]
1u-11a-192-1u-1lb-192 H A1/[(R2)m-H (R3)0=4-CH3]
1a4-Ita-193-Ia4-Itb-193 H Al/KR2)m=H (R3)0=3,5-2CH3]
1a4-11a-194-1a4-11b-194 H At/[(R2)m=H (R3)0=4-C(CH3)3]
1a4-ita-195-1a4-11b-195 H At/[(R2)m=H (R3)0-4-SCH3]
1a11a-196-N4-1lb-196 H At/[(R2)m=H (R3)0=4-Br]
1u-11a-197-1u-1lb-197 H At/[(R2)m=H (R3)0=4-F]
1a4-11a-198-1a4-11b-198 H At/[(R2)m=H (R3)0=3-F]
1u-11a-199-1u-1lb-199 H At/[(R2)m=H (R3)0=2,4-2F]
1u-11a-200-1u-1 lb-200 H At/[(R2)m=H (R3)0=3,4-2F]
1a4_tia-201-Ia4-11b-201 H At/KR2)m=H (R3)03 ,4,53F]
1a4-tta-202-Ia4-1tb-202 H At/[(R2)m=H (R3)0=4-0CH3]
1a4-113.-203-1a4-11b-203 H At/KR2)m=H (R3)0=3-0CH3]
lai-tia-204-Ia4-11b-204 H At/[(R2)m=H (R3)0=4-CF3]
Ia4-tia-205-4a4-11b-205 H At/[(R2)m=H (R3)0=4-CN]
Ia4_ 11a-206-1u-1lb-206 H A1/[(R2)m=44 (R3)0=H]
1a4_tta-207-Ia4-ttb-207 H At/[(R2)m=-4-F (R3)0=2-C1]
Ia4-11 a-208-4a4-11b-208 H At/[(R2)m=4-F (R3)0=3-C1]
1a4-ita-209-1a4-11b-209 H Al/KR2)m=4-F (R3)0=4-C1]
la4-tia-210-1a4-11b-210 H At/KR2)m=4-F (R3)03 ,42C1]
la4_tta-2114a4-ttb-211 H At/[(R2)m=4-F (R3)0=2-CH3]
1a4-11a-212-1a4-tib-212 H A1/[(R2)m-4-F (R3)0=3-CH3]
1u-11a-213-1u-1lb-213 H At/[(R2)m=4-F (R3)0=4-CH3]
1u-11a-214-1a:1-1lb-214 H At/[(R2)m=4-F (R3)0=3,5-2CH3]
1a4-ita-215-1a4-tib-215 H At/[(R2)m=4-F (R3)0=4-C(CH3)3]
1a4_11a-216-1a4-11b-216 H At/[(R2)m=4-F (R3)0=4-SCH3]
1a4_11a-217-1a4-11b-217 H At/[(R2)m=4-F (R3),=4-Br]
1a4.11a-218-1a4-11b-218 H At/[(R2)m=4-F (R3)0=4-F]
1u-11a-219-4a4-1lb-219 H At/[(R2)m=4-F (R3)0=3-F]
la4-tia-220-4a4-tib-220 H At/[(R2)m=4-F (R3)0=2,4-2F]
1u-11a-221-1u-1lb-221 H At/[(R2)m=4-F (R3)03 ,42F]
Iaa_tia-222-1a4-1 lb-222 H Al/KR2).=4-F (R3)03 ,4,53F]
1a4-11a-223--Ia4-1113-223 H At/[(R2)m=4-F (R3),=4-0CH3]
_ 1a.4-11 a-224-1a4-11b-224 H At/[(R2)m=4-F (R3)0=3-0CH3]
1a4-tta-225--Ia4-1tb-225 H Al/KR2)m=4-F (R3)0=4-CF3]
1u-11a-226-1u-1lb-226 H At/[(R2)m=4-F (R3)0=4-CN]
'&1_11a-227-1u-1lb-227 H A2/N=site 3 [(R4)p=H
(Rs)q=11]
1u-11a-228-1u-1lb-228 H A2/[N=site 3 (R4)p=H (R5)q=2-C1]
Ia4-ita-229-1a4-11b-229 H A2/[N=site 3 (R4)p=H (R.5)q=3-C1]
Ia4-tia-230-1a4-11b-230 H A2/[N=site 3 (R4)p=H (Rs)q=4-C1]
H A2/[N=site 3 (R4)p=H
1a4-11a-231-1a4-11b-231 (R5)q=3,4-2CI]
io r r i Ia.4-1 1 a-232¨Ia4-i ib-232 H A2/[N=site 3 (R4)p=H (R.5)q=2-Ia4-i ia-233¨Ia4-ilb-233 H A2/[N=site 3 (R.4)p=H (R5)q=3-CH3] , 1a4-11a-234--Ia4-11b-234 - H A2/[N=site 3 (12.4)p¨H
(R5)q=4-CH3]
H A2/[N=site 3 (R4)p=H
Ia.4-11a-235--1a4-11b-235 - (R5)q=3,5-2CH3]
_ H A2/[N=site 3 (11.4)p=H
1a4-11a-236¨Ia4-1)b-236 (R5)q=4-C(CH3)3]
II A2/[N=site 3 (R4)p=H
Ia4.iia-237¨Ia4-] ib-237 , (R.5)q=4-SCH3]
Ia4-iia-238¨Ia4-11b-238 _ H , A2/[N=site 3 (R4)p=H
(R5)q=4-Br]
Ia4.1 i a-239¨Ia4-11b-239 H A2/[N=site 3 (R4)pH (R5)q=4-F]
_ 1u-11a-240-1a4-i lb-240 H A2/[N=site 3 (R4)p=H (R5)q=3-F]
Ia4-) i a-241¨Ia4-1 ib-241 H A2/[N=site 3 (R4)p---H
(R5)q=2,4-2F]
H A2/[N=site 3 (11.4)p=t1 Ia4-11a-242¨Ia4-11b-242 (R5)q=3,4,5-3F1 1-1 A2/[N=site 3 (R4)p=H
1u-11a-243-1a4-I lb-243 (R.5)q=4-0CH3]
H A2/[N=site 3 (R4)p=H
Ia4-iia-244¨Ia4-11b-244 (R5)q=3-0CH3]
_ Ia4-lia-245-1a4-11b-245 H A2/[N=site 3 (R4)p=H (R5)q=4-CF3]
L
Ia4-iia-246¨Ia4-1113-246 H A2/[N=site 3 (R4)p=H (R5)q=4-CN]
1a4-1 1 a-247-1a4-1113-247 H A3 _ Ia4.11a-248-4a4-lib-248 . H A4 Jag- iia-249---Ia4-11 b-249 H As/[(R6),=H]
Ia4 ti a-250-4a4-I tb-250 H A5/[(R.6)1=2-CH3]
Ia4-11a-251-1a4-1113-251 _ H As/[(R6),--3-CH3]
Ia4-11a-252-1a4-1113-252 H A5/[(R6):=2-CN]
Ia4-11a-253¨!a4-i lb-253 , H A5/[(R6)r=2-CF3]
Ia4-1 1 a-254¨IaAA lb-254 _ H A5/[(R6)r=2,6-2CH3]
Ia4-ua-255¨Ia4-1113-255 H A5/[(R6)r=2-C1-4-NO2]
Ia.4.11a-256¨Ia4,1113-256 H As/[(R6)r=2-NO2-4-CF31 1a:1-11a-257-1u-1lb-257 , H A5/[(R6)r=2,3-2C1-4-0H]
Ia4-11a-258-1a4-1113-258 11 A5/[(R6)r=2,6-2C1-4-0CF3]
Ia4-ii a-259¨Ia4-I i b-259 H A5/[(R6)r=3-C1-4-CH3]
134-11a-260,-4a4-] ib-260 H A5/[(R6)1=3-0CH(CH3)2]
H As/RR6)r=4-CHCH3CH2CH
Ia4-1 1 a-261--Ia4-11b-261 (CH3)2]
Ia4-1ia-262--Ia4-11b-262 H A6 Ia4-lia-263-1a4-l1b-263 H A7 Im_zia-264-1a4-1113-264 H A8 B I [(R7)s=2 A3 Ia4- 1 1 a-265¨Ia4-t lb-265 -I]
BIRR7)s=2 A4 Ia4- 1 l a-266¨Ia4-nb-266 -I]

BIRR2)s--=2 A5/[(12.6)r=H]
1a4-11a-267¨Ia4-1113-267 -I]

1a4-It a-268-1a4-ii 13-268 Bi[(1t7)s=2 -I]
1a441a-269-1a4-1lb-269 Bi [(1Z7)s=2 A3 -CH3]
Ia4- a-270-1a4-11 b-270 BI[(R7)s=2 A4 -CH3]
Ia4-1 a-271¨Ia4-tib-271 B1[(R2)s=-2 As/[(R6)1---3-0CH(CH3)21 -CH3]
BIRR2)s=2 A6 1u-11a-272-1u-1lb-272 -CH3]
Ia4-11a-273¨Ia4- ib-273 Bi[(R7)s=2 A3 -CF3]

1a4_11a-274-1a4-1 ib-274 1 [(R)s2 A4 -CF3]
1u-11a-275-1m-1lb-275 131[(1t7)s=2 A5/[(1tOr=3-0CH(CH3)2]
-CF3]
=
1u-11a-276-1a4-i ib-276 B [(1t7)s2 A6 -CF3]
B=
1u-11a-277-1u-1lb-277 1RR7)s2 As 13.4_11a-278-1a/4-1lb-278 Bi[(lti)s=2 A3 ,6-2C1]
=
1114_11 a-279¨Ia4_ lb-279 Bi[(R7)s2 A4 ,6-2CI]
B [(It7)s=2 A6 1a4-iia-280-1a4-1 ib-280 ,6-2C1]
1a4_11a-281-4 wt. lb-28 I BIRR7)s=2 A8 _ B [(R7)s=3 A3 1a4-11a-282-1a4-1ib-282 ,4,5,6-4C1 -2-COOH]
Bi[(1t7)s=3 A4 1114- 1a-283-1m-1 lb-283 -2-COOH]
Bi[(1t7)s=3 A5/[(R6)r--2,3-2C1 1a/441a-284-1u-1lb-284 -2-COOH]
BI[(It7)s=3 1m-11a-285-1m-1lb-285 ,4,5,6-4C1 A6 -2-COOH]
1m-11a-286-1m-1lb-286 B2 Al /[(R2)tn=H (R3)0=3,4-2F]
1u-11a-287¨M4_1lb-287 B2 A3 1u-1'a-288-184-1lb-288 B2 A4 Ia4-1 a-289-4a4- lb-289 B2 A6 1a4-11a-290-4a4-11b-290 B3 Al/[(R2)m=H (R3)0=14]
1a4-ita-291-1a4-11b-291 B3 A3 1a4-11a-292-1a4-11b-292 B3 A4 1m-11a-293-M4-1lb-293 133 As/[(R6)r=1-1]
Ia4-11a-294-1a4-iib-294 B3 A6 laA- a-295-1a4-lib-295 B4 A3 1m-11a-296-1a4A ib-296 B4 A4 1a4-tia-297-1a4-1111-297 B4 As/[(R6)r=H]
la4-11a-298-1a4-11b-298 B4 A6 Ia4-11a-299-1a4-11b-299 Bs Ai/[(R2)m=H (R3)0=4-C1]
1a4-l1a-300-1a44 lb-300 B5 A3 1a4-113.-301-1a4-ub-301 Bs A4 Ia4-t a-302--1a4-11b-302 B5 As/[(R6),=H]
1a4-I a-303-1a4-1113-303 135 As/[(R6)r=2-CH2CH3]
Ia4-i 1a-304-M4-a-304 Bs As/[(R6),=2-0CH2CH3]
Bs As/[(R6)1=2-0CH(CH3)2]
Ia4-I1a-307-Ia4- lb-307 Bs As/[(R6)r=3-CH2CH3]
la4-11a-308-1a4-1111-308 Bs As/[(R6),--3-0CH2CH3]
Ia4-t a.-309-1a441b-309 Bs As/[(R6)r=3-0CH(CH3)2]
la.4- 1a-310-1m-I ib-310 Bs A6 B6/[R8=H; A3 Ia4-1 R9=CF3]
Ia4- i ia-312-1a4-11b-312 B6/[R8=H; A4 R9=CF3]
B6/[R8=H;
Ia4-1 a-313-1a4-11b-313 As/[(R6)r=H]
R9=CF3]
B6/[R8=H;
Ia4-11a-314---1a4-11b-314 As/[(R6)r=2-CH2CH3]
R9=CF3]
1a4-11a-315-1a.4.11b-315 B6/[R8=H;As/[(R6)1=2-0CH2CH3]
R9=CF3]
B6/[R8=H;
1a4-iia-316-1a4-11b-316 , A5/[(R6)r=2-0CH(CH3)2]
R9=CF3]
B6/[R8=H;
Ia4-11a-317-1a4-1113-317 , As/[(R6)r=3-CH2CH3]
R9=CF3]
B6/[R8=H;
1m-11a-318-M4-i ib-318 As/[(R6)r=3-0CH2CH3]
R9=CF3]
B6/[R8=H;
Ia4-1 a-319-1a4-11b-319 As/[(R6)r=3-0CH(CH3)2]
R9=CF3]
136/[R8=H; As/[(R6)r=4-CHCH3CH2CH
1a4-I la-320-1a4-I ib-320 R9=CF3] (CH3)21 B6/[R8=H;
Ia4- a-321-Ia4-11b-321 A6 R9=CF3]

=
B6/[R8=H;
Ia4-1 a-322-Ia4-11b-322 , A7 R9=CF3]
Ia4- 1a-323-U4-1lb-323 B6/[R8=C1 A3 ; R9=CH3]
B6/[1t8=C1 A4 1u-11a-324-1u-1lb-324 ; R9=CH3]

Ia4- a-325-4a4-u B6/[1t=C1 b-325 A5/[(R6)r=1-1]
; R9=CH3]
B6/[118=C1 Ia4- tia-326-1a4- 1 ib-326 A5/[(R6)2=2-CH2CH3]
; R9=Cri, 3j Ia4-11a-327-1 B6/[12.8=C1a4-1ib-327 A5/[(R6)r=2-0CH2CH3]
; R9=CH3]
B6/[1t8=C1 1a4_11a-328-1a4-11b-328 , A5/[(R6)r=2-0CH(CH3)2]
; R9=CH3]
B6/[14=C1 A5/[(R6)r=4-CHCH3CH2CH
Ia4-11a-329-1a4-1111-329 ; R9=CH3] (CH3)2]
Ia4- B6/[1t8=C1 a-330--la4-11b-330 , A6 ; R9=CH3]
1u-11a-331-1u Bd[R8=C1-1lb-331 H7 ; R9=CH3]
1a4-ila-332-1a4-1113-332 B6/[14=H; A3 R9=CF3]
Ia4- l a-333---Ia4- lib-333 Bd[R8=H; A4 R9=CF3]
Ia4- a-334-Ia4- 1 lb-334 B6/[12_8=H;, A5/[(R6)r=1-1]
R9=CF3]
1u-11a-335-1u B6/[R8=H;-1lb-335 A5/[(R6)r=2-CH2CH3]
R9=CF3]
1u-11a-336-1u B6/[12.8=H;-I b-336 A5/[(R6)r=2-0CH2CH3]
R9=CF3]
B6/[R8=H;
1u-11a-337-1a41i b-337 A5/[(R6)r=2-0CH(CH3)2]
R9=CF3]
B6/[R8=H; A5/[(R6)r=4-CHCH3CH2CH
1u-11a-338-1u-1lb-338 R9=CF3] (CH3)21 la4-11a-339---1a4-11b-339 B6/[R2=H;, A6 R9=CF3]
Ia4-1 a-340- B6/[R8=H;Ia4- ib-340 A7 R9=CF3]
1u-11a-341-1u-1lb-341 B7 A3 1u-11a-342-1u-I ib-342 B7 A4 1a4_11a-343-1a4-1113-343 B7 A5/[(R6),=1-1]
1u-11a-344-1u-1lb-344 B7 As/[(R6)r=2,6-2Br-4-0CF3]
Ia4-1 1a-345-1u-I ib-345 B7 A6 1u-11a-346-1u-1lb-346 B7 A7 , , 1 w la4-lia-347-1a4-iib-347 Bs A3 1a4-11a-348---Ia4-111)-348 Bs A4 1a:141a-349-1m- i lb-349 , Bs A5/[(R6)r=H]
1a4-11a-350--1a4-nb-350 Bs A5/[(R6),--2,6-2Br-4-0CF3]
la4ma-351-1a4-11b-351 - B8 A6 1a4ma-352-1a4-i1b-352 Bs , A7 1a4-iia-353--la4-lib-353 B9 , A3 1a4-1ia-354--Ia4-11b-354 B9 A4 1u-11a-355-W4 lb-355 B9 A5/[(R6),=H]
1a4-11a-356--1a4-lib-356 B9 A6 1a4-iia-357--1a4-1113-357 B9 A7 Ia4_l1a-358-1a4-nb-358 B10 , A3 1m-11a-359-1m-11b-359 r Bo A4 1m-11a-360-1u-1i b-360 r BIO A5/[(R6)r=H]
la4-11a-361--laa-lib-361 BD) _ A5/[(R6)r=3-C1-4 CH3]
1a4-1 1 a-362-1a4-ilb-362 _ BIO A6 1m-11a-363-1u-11b-363 BIO _ A7 1u-11a-364-1m-11b-364 B11 A3 1a4-lia-365-Ia4-11b-365 Bil , A4 1m-11a-366-1m-1lb-366 Bn A5/[(R6)1=}1]
.
1a4-lia-367-1a4-11b-367 B11 A5/[(R6)1---2,6-2CH3]
la4-na-3684a4-lib-368 B11 A6 1a4-11a-369-1a4-11b-369 B11 A7 laA-] 1a-370-1m-1lb-370 Ts0 H At/[(R2)m=H (R3)0=H]
1a4-Iia-371-1a4-11b-371 H A1/[(R2)m=H (R3)0=2-C1]
1u-11a-372-1m-1lb-372 H Ai/[(R2)m=H (R3)0=3-C1]
1a4-11a-373--1a4-iib-373 H A1/[(R2)m=H (R3)0=4-C1]
1u-11a-3744a:1-i ib-374 H , Al/KR2)m=H (R3)0=3,4-2C1]
1a4-iia-375-1a4-111)-375 H Ai/[(R2)m-H (R3)0=2-CH3]
la4-11a-376-1a4-Iib-376 H Al/[(R2)m=H (R3)0=3-C113]
1a4-iia-377--Ia4-ilb-377 H Al/[(R2)m=H (R3)0=4-CH3]
1a4-11a-378-1a4-nb-378 H Al/RR2)m=H (R3)0=3,5-2CH3]
1a4-11a-379-4a4-11b-379 H A1/r(R2)m=H (R3)0=4-C(CH3)3J
1a4-11a-380--1a4-nb-380 H Ai/[(R2)m=H (R3)0=4-SCH3]
1a4-ila-381--laa-lib-381 H Ai/RR2)m=H (R3)0=4-Br]
1a4-na-382-1a4-11b-382 H Al/RR2)nr=H (R3)0=4-F1 1a4-na-383-Ia4-11b-383 H A1/[(R2)m=H (R3)0---3-F]
1a4-11a-384-1a4-11b-384 H Al/[(R2)m=H (R3)0=2,4-2F1 1u-11a-385-U44lb-385 H Al/[(R2)m----H (R3)0=3,4-2F1 1a4-Iia-386-4a4-1 b-386 H , Al/[(R2)m-H (R3)0=3,4,5-3F1 Ia4-iia-387-Ia4-nb-387 H A1/[(R2)m=H (R3)0=4-0CH3]
1a4-11a-388-1a4-11b-388 H A1/[(R2)m=H (R3)0=3-0CH3]
la4-lia-389-4a4-lib-389 H Ai/[(R2)m=H (R3)0=4-CF3]
1m-11a-390-M4-1lb-390 H Ai/RR2)m=H (R3)0=4-CN]

;
t 1u-1'a-391-4u-1th-391 H Al/[(R2)rn=4-F (R3)0=H]
Ia4-Iia-392---Ia4- i'1)-392 H Al/[(R2)m=4-F (R3)0=2-C1]
1u-11a-393-4a4-I lb-393 H Al/[(R2)nf=4-F (R3)0=3-C1]
1a4-11a-394-1a4-11b-394 H Ai/[(R2)m-=4-F (R3)0=4-C1]
1a4-11a-395-1a4-nb-395 H A1/[(R2)m---4-F (R3)0=3 ,4-2C1]
Ia4-iia-396-1a4-nb-396 H A1/[(R2)m=4-F (R3)0=2-CH3]
Ia4- 1 ta-397-1a4-tib-397 , H ' At/[(R2)m=4-F (R3)0=3-CH3]
Ia4-11a-398-1a4-111)-398 H Ai/[(R2)m=4-F (R3)0=4-CH3]
. 1a4-11a-399-1a4-11b-399 H Ai/[(R2)In=4-F (R3)0=3,5-2CH3]
Ia4-tia-400--Ia4-iib-400 H A1/[(R2)m.----4-F (R3).=--4-C(CH3)3]
Ia4-11a-401-1a4-11b-401 H A1/[(R2)m---4-F (R3)9=4-SC113]
1u-11a-402-1a4-1i 13-402 H Ai/[(R2)m=4-F (R3)0=--4-Br]
1u-11a-403-1a44lb-403 H At/[(R2)m=4-F (R3)0=4-F]
1a4-11a-404-1a4-11b-404 H Ai/[(R2)m=4-F (R3)0=3-F]
la441a-405-1a4-11b-405 H Ai/[(R2)m=4-F (R3)0=-2,4-2F]
la4- t ta-406-1a4-iib-406 H Ai/RIZ.2)m=4-F (R3)0=3,4-2F]
1a4_11a-407-4a4-itb-407 H Al/[(R2)m=4-F (R3)0=3 ,4,5-3F]
1u-11a-408-4a-1lb-408 H Al/[(R2),e--4-F (R3)0=4-0CH3]
1u-1,1a-409-M4-11b-409 , H At/[(R2)m=4-F (R3)0=3-0CH3]
Im_lia-410-4a4-nb-410 H A1/[(R2)m-=4-F (R3)0=4-CF3]
1a4-11a-411-1a4-11b-411 H Ai/[(R2)m=4-F (R3)0=4-CN]
1a4-iia-412-1a4-lib-412 H A2/N=site 3 [(R4)p=H (R.5)q=11]
1a4-l1a-413-Ia4-nb-413 H A2/[N=site 3 (R4)p=H (R5)q=2-C1]
1a4-11a-414-1a4-nb-414 H A2/[N=site 3 (R4)p=H (Rs)q=3-C1]
1a4-i1a-415--Ia4-11b-415 . H A2/[N=site 3 (R4)p=H (Rs)q4-CI]
H A2/[N=site 3 (R4)PH
1a4-Ila-416-1a4-111)-416 (Rs)q-=3,4-2C1]
1a4-lia-417-1a4-tib-417 H A2/[N-=site 3 (R)p=H (Rs)q=2-CH3]
1a4-11a-418-1a4-11b-418 H A2/[N=site 3 (R4)p=H (R.5)q=3-CH3]
1a4.11a-419-1a4-nb-419 H A2/[N=site 3 (R)pH (R5)q=4-CH3]
H A2/[N=site 3 (1Z4)p=H
la4-11a-420-1a4-nb-420 (Rs)q=3,5-20113]
H A2/[N=site 3 (R4)p=H
1a4-ila-421-1a4-11b-421 (Rs)cr-4-C(CH3)3]
_ H A2/[N=site 3 (R4)p=H
1m-11a-422-h4- t tb-422 (R5)q=4-SCH3]
1a4-11a-423-4a4-1ib-423 H A2/[N=site 3 (R4)p=H (R5)q4-Br) 1a4-11a-424-1a.4- 1 t b-424 H A2/[N=site 3 (R4)p=H (Rs)g=4-F]
1m-11a-425-1u-1lb-425 H A2/EN=site 3 (R4)p----H (Rs)q=3-F]
Ia4-tia-426-1a4-1 lb-426 H A2/[N=site 3 (R)pH (R.5)q=2,4-2F]
H A2/[1\1=-site 3 (R4)p=H
Ia4-11a-427-1a4-11b-427 (R.5)q=3,4,5-3F]
H A2/[N=--site 3 (R4)p=H
la4-Iia-428--1a4-nb-428 (R5)q=4-0CH3]

Ail[N=site 3 (R4)p=H
Ia4-11a-429-1a4-1 b-429 (R5)q=3-0CH3]
Ia4-11 a-430¨Ia4-i 1)-430 H A2/[N=site 3 (1k4)p=H (R.5)q=4-CF3J
1u-11a-431-1u-1lb-431 H A2/[N=site 3 (R4)PH (R5)q=4-CN]
Ia4_ a-432¨Ia4-11b-432 H A3 Ia4-1 a-433-1a4-1 b-433 H A4 Ia4-1 1 a-43 4¨Ia4-1 b-434 H A5/[(R6)r=H]
1a4-112-435---1a4-iib-435 H As/[(R6)r=2-CH3]
Ia4-1 I a-43 6-1a4-11b-436 H A5/[(R6)r=3 -CH3]
1a4-11a-437-1a4-nb-437 H A5/[(R6)r=2-CN]
1a4-11a-438-1a4-1113-438 H A5/[(R6),=2-CF3]
1a4.11a-439-1a4. ib-439 A5/[(R6)r=2,6-2CH3]
Ia4-ii a-440-1a4- lb-440 H A5/[(R6),=2-C 1-4-NO2]
1a4-11a-441-1a4-11b-441 H A5/[(R6)r=2-NO2-4-CF3]
1a4-11a-442-1a4-11b-442 H A5/[(R6)1=2,3-2C1-4-0H]
1a:4-11a-443-1u-1lb-443 H A5/[(R6)r=2,6-2C1-4-0CF3]
Ia4-11a-444-1a4-jib-444 H A5/[(R6)1=3-C1-4-CH3]
Iaa_lia-445-1a4-1113-445 H A5/[(R6)r=3 -OCH (CH3)2]
A5/[(R6)r=4-CHCH3CH2CH
1u-11a-446-1u-1lb-446 (CH3)2]
1.u-11a-447-1u-1lb-447 H A6 Lail- a-448-1a4-11 b-448 H A7 Ia4-iia-449-1a4-nb-449 H A8 1a4-11a-450-1a4-11b-450 Bi[(R7)s=2 A3 -I]
Bi[(R7)s=2 A4 '&4-11a-451-1u-1lb-451 -I]
B [(R7)s=2 A5/[(R6)r=H]
1a4-11a-452-1a4-11b-452 -I]
BIRR7)s=2 A6 la4-11a-453-1a4-1 ib-453 Bi [(R7)s=2 A3 Ia4-1 ib-454 -CH3]
s=
Ia4- a-455---Ia4-11b-455 BI[(R7)2 A4 -CH3]
Bi[(R7)2=2 A5/[(R6)/=3-0CH(CH3)2]
1u-11a-456-1u-1 lb-456 -CH3]
Bi [(12.7)s=2 A6 Ia4- a-457¨Ia4-11b-457 -CH3]
B [(R7)s=2 A3 1a4-11a-458-4a4-11b-458 -CF3]
BI[(R7)s=2 A4 1a4-1ta-459¨Ia4-11b-459 -CF3]
1a4-I ta-460--Ia4-11b-460 Bi[(R7)s=2 A5/[(R6)r=3-0CH(CH3)21 -CF3]
Bi[(R7)s=2 A6 1a4-1 1a-461-1u-I b-461 -CF3]
'&4-11a-462-1u-I lb-462 B1[(R7)s=2 A8 -CF3]
BIRR7)s=2 Ia4_ ia-463--la4-11b-463 A3 ,6-2C1]
Ia4-11a-464-4a4-11b-464 Bi[(117)s=2 A4 ,6-2C1]
Ia4-11a-465-1a4-11b-465 13i[(R7)s=2 As ,6-2C1]
=s Ia4-11a-466-1a4-1ib-466 Bi[(R7)s2 A
,6-2C1]
Bi[(R7)s=3 A3 1a4-11a-467-1a4-11b-467 ,4,5,6-4C1 -2-COOH]
B1[(R7)s=3 A4 1a4-11a-468--1a4-11b-468 ,4,5,6-4C1 -2-COOH]
BIL(R7)s=3 A5/[(R6)r=2,3-2C1 Ia4-11a-469-1a4-11b-469 ,4,5,6-4C1 -2-COOH]
Bi[(R7)s=3 1a4_11a-470-1a4-iib-470 ,4,5,6-4C1 A6 =2-00011]
1a4-11a-471-1a4-11b-471 B2 A 1 /[(R2)m=H (R3)0=3 ,4-2F]
1a4-tia-472--1a4-11b-472 B2 A3 Ia441a-473-1u-1lb-473 B2 A4 1a4-tia-474-1a4-11b-474 B2 A6 Ia4-11a-475-1a4-1 b-475 B3 A 1 /[(R2)m=H (R3)0=111 1a4-tia-476-1a4-iib-476 B3 A3 1a4-iia-477-1a4-1113-477 B3 A4 Ia4_11 a-478¨Ia4-ii b-478 B3 As/[(Rs)r¨H]
la.4-11a-479-1a4-1 lb-479 B3 A6 1a4-11a-480-1a4-1 03-480 B4 A3 1a4-1 a-481--1a4-1 ib-481 B4 A4 1a4-lia-482-1a4-11b-482 134 A5/[(11.6)r=H]
1a:141a-483-1u- nb-483 B4 A6 Ia4-11a-484-1a4-iib-484 B5 A1/[(R2)m=H (R3)0=4-C1]
1a4-11a-485-4a4-11b-485 B5 A3 Ia4-11a-486-1a4-11b-486 B5 A4 Ia4-1 a-487-4a4-1 ib-487 B5 A5/[(R6)r=H]
1a4-I a-488¨Ia4-Ib-488 B5 A5/[(R6)r=2-CH2CH3]

1u-11a-489-1u-I 113-489 Bs A5/[(R6),---=-2-0CH2CH3]
Ia4-11 a-490-Ia4- b-490 Bs A5/[(R6)r=2-0CH(CH3)2]
Ia4-11a-491-1a4-1113-491 B5 A5/[(R03-CH2CH3]
1a4-11a-492-1a4-I ib-492 B5 A5/[(R6),-=3-0CH2CH3]
1a4-11a-493-1a4-1 ib-493 B5 A5/[(R6),-..---3-0CH(CH3)2]
1a4-11a-494-4a4-1113-494 Bs A6 B6/[R8=H; A3 1u-11a-495-1a:1-1lb-495 R9=CF3]
B6/[R8=H; A4 1u-11a-496-1m-1lb-496 R9=CF3]
B6/[R8=H;
Ta4-11a-497-1a4-1113-497 , A s/[(R6),---H]
R9=CF3j B6/[R8=H;
Ia4-11a-498-1a4-11 b-498 A5/[(R6),--2-CH2C H3]
R9=CF31 B6/[R8=H;
1u-11a-499-U4-i lb-499 , A5/[(R6)r=2-0CH2CH3]
R9=CF3j B6/[R8=H;
1a4_11a-500-1a4-11b-500 , A5/KR6),--2-0CH(CH3)2]
R9=CF3j B6/[R8=H;
Ia4_ a-501-1a4-11b-501 A5/[(R6),=3-CH2CH3]
R9=CF31 B6/[R8=H;
Ia4-11a-5 02-1a4- b-502 As/[(R6)r=3-0CH2CH3]
R9=CF3j B6/[R8=H;
a-503--1a4-11b-503 As/[(R6),=-3-0CH(CH3)2]
R9=CF3j B6/[R8=H; As/[(R6),=4-CHCH3CH2CH
1a4-11a-504-4a44 lb-504 R9=CF3] (CH3)2]
B6/[12s=H;
Ia4-I a-505-Ia4-t lb-505 , H6 R9=CF3J
B6/[R8=H; , 1a4-11a-506---1a4-11b-506 õ H7 R9=CF3]
Bd[R8=C1 A3 Ia4-11a-507-1a4-11b-507 ; R9=CH3]
B6/[R8=C1 A4 Ia4-11a-508-1a4-1113-508 ; R9=CH3]
B6/[R8=C1 1a.4-11a-509-1a4-1 lb-509 A5/[(R6)1=H]
; R9=CH3}
B6/[R8=C1 Ia4-11a-510-4a4- lb-510 A s/[(R6)r=2-CH2CH3]
; R.9=CH3]
136/[R8=C1 , , õõ l....õ , Ia4-iia-511-Ia4-1113-511 115/ t(c.6)1 l.11=z-u2r13 J
; R9=CH31 B6/[R8=C1 Ia4-11a-512-1a4-1113-512 A5/[(R6)r=2-0CH(CH3)2]
; R9=CH3]
B6/[R8=C1 A5/[(R6)1=4-CHCH3CH2CH
1a4-113.-5134a4-11b-513 ; R9=CH3] (CH3)2]

=
B6/[R8--=C1 Ia4- a-514--la4-11b-514 _ , A6 ; R9=Cr13]
B6/[R8=C1 1a4-11a-515-1a4-11b-515 H7 ; R9=CH3]
B6/[1:18=H; A3 1a4-I 1a-516-4u-1lb-516 R9=CF3]
B6/[11.8=H; A4 1a4-11a-517-1a4-11b-517 R9=CF3]
B6/[128=H;
1a4.11a-518-4a4-iib-518 , A5/ [(R6)r=1-1]
R9=CF3}
B6/[1t8=H;
1a4-11a-519-1a4-11b-519 A5/[(R6)r=2-CH2CH3]
R9=CF3]
B6/[1t8=H;
Ia4-11a-520-4a4-11b-520 A5/[(R6),--2-0CH2CH3]
R9=CF3]
la4-11a-521--la4-11b-521 B6/[1t8=H;A5/[(R6),=2-0CH(CH3)2]
R9=CF3]
B6/[12.8=H; A5/[(R6),--4-CHCH3CH2CH
1a4-11a-522-1a4-lib-522 R9=CF3] (CH3)2]
la4- I 1a-523¨M B6/[lts=H;4-1lb-523 A6 R9=CF3]
=
Ia4- B6/[12.8H;
la-524-1a4-ilb-524 , H7 R9=CF3]
1a4-1 a-525-1a4-nb-525 B7 A3 1a4-11a-526-4a4-ilb-526 B7 A4 Ia4-11a-527-1a4-11b-527 B7 A5/[(R6)r=1-1]
1a4_11a-528-1a4-1113-528 B7 A5/[(R6)r=2,6-2Br-4-0CF3]
1a4_11a-529-1a4-11b-529 1257 A6 1a4_11a-530-1a4- lb-530 B7 A7 1a4-11a-531-1a4- lb-531 Bs A3 1u-11a-532-1u-1lb-532 B8 A4 1a4-11a-533-1a4-1113-533 Bs A5/[(R6)r=1-1]
1a4-11a-534-1a4-11b-534 Bs A5/[(R6),----2,6-2Br-4-0CF3]
1a4-11a-535-1a4-11b-535 Bs AG
1a4-na-536-1a4-111)-536 Bs A7 la4- a-537-1a4-11b-537 B9 A3 1a4-11a-538-1a4- lb-538 B9 A4 1a4_11a-539-1a4-11b-539 B9 A5/[(R6),=1-1]
1a4-lia-540-1a4-11b-540 B9 A6 Ia4- a-541--1a4-11b-541 B9 A7 1a4-11a-542¨Ia4-ub-542 Bio A3 Ia4-1 a-543-1a4-11b-543 Blo A4 1u-11a-544-1u-1lb-544 By) A5/[(R6)r=1-1]
Ia4- a-545---Ia4- lb-545 Bit, A5/[(R6)r=3-C1-4 CH3]
1u-11a-546-1u-1 ib-546 B10 A6 1a:1-11a-547-1u- 1 03-547 BIO A7 Ia.4-1ia-548-1a4-11b-548 Bil A3 Ia4- 1 1a-549-1u-I ib-549 B11 A4 1a4_11a-550-1a4-1113-550 B11 A5/[(R6)r=11]
laa-na-551-1a4-11b-551 Bil A5/[(R6)r=2,6-2CH3]
1m-11a-552¨M4-1lb-552 B11 A6 Ia4-11a-553^1a4-11b-553 B11 A7 Ia4- 1 1a-554-1u-1lb-554 PhCO2 H Al/[(R2)m=H (R3)0=11]
1a4-11a-555-1a4-11b-555 H A1/[(R2)10=H (R3)0=2-C1]
1a4-11a-556--lai-lib-556 H Adi(R2)r0=1-1 (R3)0=3-C1]
Ia.4-11a-557-1a4-11b-557 H A1/[(R2)01=H (R3)0=4-C1]
1a4-11a-558-1a4.11b-558 H Al/[(R40,=H (R3)0=3,4-2C1]
Ia4-iia-559¨Ia4-ub-559 H Ati[(R2)0,--11 (R3)0=2-CH3J
Iai_iia-560-1a4-nb-560 H At/[(R2)00=H (R3)0=3-CH3]
Ia4-11a-561-1a4-11b-561 H At/[(R2)m=H (R3)0=4-CH3]
la4-iia-562-1a4-11b-562 H Al/[(R2)0,=H (R3)0=3,5-2CH3]
Ia.4-1 i a-563-1a4-1113-563 H Ai/[(R2)m=H (R3)0=4-C(CH3)31 Ia4-11a-564-1a4-11b-564 H Ai/[(R2)01=H (R3)0=4-SCH3]
Ia411a-565-1a4-1113-565 H A1/[(R2)01=H (R3)0=4-Br]
Ia4-11a-566-4a4-iib-566 H Ai/[(R2)10=-H (R3)0=4-F]
Ia4-1 ia-567-1a4-1113-567 H Ai/[(R2)(0=H (R3)0=3-F]
Ia4-11a-568-1a4-11b-568 H Ai/[(R2),0=H (R3)0=2,4-2F]
1a4-11a-569-1a4-11b-569 H Ai/[(R2)0,=H (R3)0=3,4-211 1a4-11a-570-1a4-ub-570 H A1/[(R.2)m---H (R3)0=3,4,5-3F]
1a4-ila-571-1a4-1113-571 H A.1/[(R2)0,=H (R3)0=4-0CH3]
1a4-lla-572--1a411b-572 H Al/[(R2),0=H (R3)0=3-0CH3]
1a4-11a-573-1a4-lib-573 H A1/[(R2.),0=H (R3)0=4-CF3]
1a4-11a-574-1a4-lib-574 H Ai/[(R2).0=H (R3)0=4-CI=1]
la.4-lia-575,--1a4-11b-575 H Ai/KR2),0=4-F (R3)0=11]
Ia4-na-576¨Ia4-lib-576 H At/[(R2),0=4-F (R3)0=2-C11 Ia4-1 1 a-577-1a4-tib-577 H A1/[(R.2)m=4-F (R3)0=3-C1]
1a4_11a-578-1a4-11b-578 H Al/[(R2),0=4-F (R3)0=4-C1]
Ia.4-lia-579--1a4-Iib-579 H Ai/[(R2)m=4-F (R3)0=3,4-2C1]
1a4_11a-580-1a4-tib-580 H Ai/[(R2)01=4-F (R3)0=2-CH3]
1a4-Iia-581-4a4-11b-581 H Ail[(R2)0,----4-F (R3)0=3-CH3] .
Ia4-lia-582--la4-11b-582 H Ai/[(R2)01=4-F (R3)0=4-CH3]
1a4-11a-583¨Ia4-nb-583 H Ai/[(R2),0-4-F (R3)0=3,5-2CH3]
1a4-na-584-1a4-1113-584 , H Ai/[(R2)m=4-F (R3)0=4-C(CH3)3]
1a4-11a-585-1a4-11b-585 H A1/[(R2)01=4-F (R3)0=4-SCH3]
1a4-na-586-1a4-11b-586 H A1/[(R2)m=4-F (R3)0=4-Br]
la.441a-587-1a4-nb-587 H A1/f(R2)01=4-F (R3)0=4-F]
1a4-ita-588-1a4-11b-588 H A1/[(R2)01=4-F (R3)0=3-11 1a4-iia-589-1a4-11b-589 . H AI/[(R2),0-4-F (R3)0=2,4-211 1u-11a-590¨M44i b-590 H Al/[(R2),0=4-F (R3)0=3,4-211 = . 4 , 1u-11a-591-4u-1lb-591 H A1/[(R2)m=4-F (R3)0=3,4,5-3F]
Ia4-11 a-592-Ia4-11 1)-592 H Al/KR.2)m=4-F (R3)0=4-0CH3]
Ia4-11a-593-4a4-1ib-593 H Al/[(R2)m=4-F (R3)0=3-0CH3]
1a4.11a-594-1a4-11b-594 H Ai/[(R2)m=4-F (R3)0=4-CF3]
Ia4-11a-595-1a4-11b-595 H A i/[(R2)m=4-F (R3)0=4-CN]
1u-11a-596-1u-1 ib-596 H A2/N=site 3 [(R4)p=H
(Rs)q=11]
_ Ia4-1 1 a-597-1a4-1113.-597 H A2/[N=site 3 (R4)r=H (Rs)q=2-C1]
1u-11a-598-1u-1lb-598 H A2/[N=site 3 (R4)PH (Rs)q=3-C1]
1u-11a-599-1u-1lb-599 _ H A2/[N=site 3 (R4)p=H (R5)q=4-C1]
H A2/[N=site 3 (Iti)p=H
Ia4-11a-600-1a4-nb-600 (Rs)q=3,4-2C1]
1ai.tia-601-Ia4-tib-601 H A2/[N=site 3 (R4)p=H (its)q=2-CH3] , , 1a4-iia-602-1a4-1113-602 H A2/[N=site 3 (R)pH (R5)q=3-CH3]
_ ta4-11a-603-1a4-1113-603 H A2/[N=site 3 (R4)PH (R5)q=4-CH3]
H A2/[N=site 3 (R4)p=H
1u-11a-604-ha-I ib-604 (R5)q=3,5-2CH3]
H A2/[N=site 3 (R4)p-H
la4-lia-605-1a4-11b-605 (R5)q=4-C(CH3)3]
H A2/[N=site 3 (R4)p=H
1a4-11a-606--1a4-1113-606 (R5)q=4-SCH3]
13.4-11a-607-1a4-1113-607 H A2/[N=site 3 (1t4)p=H (R5)q=4-Br]
1u-11a-608-1u-1lb-608 H A2/[N=site 3 (R4)p=H (R5)q=4-1a4-iia-609-1a4-11b-609 H A2/[N=site 3 (R4)p=H (Rs)q=3-F]
1a4-lia-610-1a4-nb-610 H A2/[N=site 3 (R4)p=H
(Rs)q=2,4-2F]
H A2/[N=site 3 (R4)p=H
Ia4-11a-611-Ia4-tib-611 (R5)q=3,4,5-3F]
H A2/11N=site 3 (R4)P=H
Ia4-11a-612-1a4-ilb-612 (Rs)q=4-0CH3]
H A4N=site 3 (R4)p=H
1a4-11a-613-1a4-11b-613 (R5)q=3-0CH3]
1a4-tia-6144a4-11b-614 H A2/[N=site 3 (R4)p-(R5)q=4-CF3]
Ia4-11a-615-4a4-11b-615 H A2/[N=site 3 (R4)p=H (Rs)q=4-CN]
1a4-11a-616-1a4-1113-616 1-1 A3 1a4-11a-617-1a4-lib-617 H A4 1a4-lia-618-Ia4-Iib-618 H A5/[(R6)r=11]
1a4-Iia-619-4a4-11b-619 H A5/[(R6)r=2-CH31 Ia4-11a-620-4a4-Iib-620 H A5/[(R6)r=3-CH3]
1a4-11a-621-1a4-iib-621 H A5/[(R6)1=2-CN]
1a4-11a-6224a4-1 lb-622 H A5/[(R6)1=2-CF3]
1u-11a-623-1u-I ib-623 H A5/[(R6)r=2,6-2CH3]
Ia4-11a-624-4a4-11b-624 H A5/[(R6)r=2-C1-4-N021 194-11a-625-1a4-1lb-625 H A5/[(R6)r=2-NO2-4-CF3]
13.4-11a-626-1a4-1113-626 H A5/[(R6)r=2,3-2C1-4-0H]
1a4-11a-627-1a4-1 ib-627 H A5/[(R6),=2,6-2C1-4-0CF3]

. , la4-11a-628¨Ia4-11b-628 H A5/[(R6)g---3-CI4-CH3]
Ia4-iia-629¨Ia4-1113-629 H As/KR6),-=3-0CH(CH3)2]
H A5/[(R6)r=4-CHCH3CH2CH
Ia4-11a-630¨Ia4- 1 lb-630 (CH3)2]
1u-11a-631-1u-11b-631 H A6 Ia4-11a-632--Ia4-1113-632 H A7 Ia4-t 1a-633-1a:4-1lb-633 H A8 Ia4-iia-634--Ia4-11b-634 BI[(R7)s=2 A3 -I]
s ha- 1 l a-635¨Ia4-1113-635 Bi[(R7)--2 A4 -I]
BIRR7)s.--2 A5/ [(R6)r=H]
1u-11a-636-1u-I lb-636 -I]
Ia4-Iia-637¨Ia4-1 ib-637 B1[(R7)s=2 A6 -I]
1u-11a-638¨U4-1lb-638 Bi[(R7)s=2 A3 -CH3]
1a:1-11a-639-1u-1lb-639 BIRR7)s=2 A4 -CH3]
Ia4 1 1 a-640Ia4- 1 ib-640 Bi[(R7)s=2 As/[(R6)r=3-0CH(CH3)2]
- ¨
-CH3]
B
1u-11a-641¨W-1lb-641 1[(R7)s=2 A6 -CH3]
Ia4-11a-642¨Ia4-1113-642 Bi[(R7)s=2 A3 -CF3]
Ia4-11a-643¨Ia4-11 13-643 Bi[(R7)s=2 A4 -CF3]
1u-11a-644-4u-I ib-644 BIKR7)s=2 A5/[(R6)r=3-0CH(CH3)21 -CF3]
1u-11a-645¨W-1 ib-645 Bi[(R7)s=2 A6 -CF3]
Ia4- ii a-646-4a4-1113-646 BI[(R7)s=2 As -CF3]
=
Ia4- I 1 a-647-4a4-11b-647 BI[(R7)s2 A3 ,6-2C1]
BIRR7)s=2 A4 1u-11a-648¨W-1lb-648 ,6-2CI]
1U-11a-649-1u-I ib-649 BI[(R7)s=2 A6 ,6-2CI]
1a4-11a-650--4a4- II b-650 BI[(R7)s=2 As ,6-2C1]
BI[(R7)s=3 A3 la4-11a-651-1a4-11b-651 ,4,5,6-4C1 -2-COOH]

BI[(R7)s=3 A4 Ia4- a-652¨Ia4-nb-652 ,4,5,6-4C1 -2-COOH]
Bi[(R7)s=3 A5/RIt6)r=2,3-2C1 1m-11a-653-1a:1-1lb-653 ,4,5,6-4C1 -2-COOH]
Bi[(117)s=3 As Ia4-11a-654-1a4-1113-654 ,4,5,6-4C1 -2-COOH]
1a4-11a-655-1a4-111)-655 B2 A i/[(R2)m=H (R3)0=3,4-2F]
1a4-lia-656-1a4-ub-656 B2 A3 1a:1_11a-657-1a:1-11b-657 B2 A4 Ia4-11 a-658¨Ia4-11b-658 B2 A6 1m-11a-659-1a4-1lb-659 B3 Al/KR2)m=H (R3)0=H]
1a4-11a-660-1a4-iib-660 B3 A3 Ia4-1 a-661¨Ia4-nb-661 B3 A4 Ia4-11 a-662-1a4-111a-662 B3 Asi[(Rs)r=H]
Ia4_ a-663¨Ia4- ib-663 B3 A6 1a4-11a-664-1a4-11b-664 B4 A3 Ia4-11a-665-1a4-11b-665 B4 A4 Ia4-11a-666-1a4-1 ib-666 B4 A5/[(R6),---H]
Ia4-1 a-667-1a4-1113-667 B4 A6 1a4-11a-668-1a4-11b-668 Bs At/[(R2)m=H (R3)0=4-C1]
1a4-11a-669-1a4-11b-669 Bs A3 1a4-11a-670-1a4-11b-670 B5 A4 1a4-11a-671-1a4-111)-671 Bs As/[(Rs)r=H]
Ia4- iia-672¨M4-1lb-672 Bs A5/[(12.6)r=2-CH2CH3]
Ia4-1I a-673¨Ia4-11 b-673 B5 A5/[(R6)r=2-0CH2CH3]
1a4-11a-6744a4-111)-674 Bs A5/[(11.6)r=2-0CH(CH3)2]
Ia4-11a-675¨Ia4-1113-675 Bs A5/[(R6)r=3-CH2CH3]
1m-11a-676¨M44lb-676 B5 A5/[(R6)1=3-0CH2CH3]
1a4-11a-677-1a4-1111-677 B5 A5/[(12.6)r=3-0CH(CH3)2]
1a4_11a-678-1a4-111)-678 Bs A6 1a4-11a-679-1a4-11b-679 Bd[Rs=H; A3 R9=CF3]
a6/[R8=H; A4 Ia4-11a-680-1a4-11b-680 R9=CF3]
B6/[R8=H; As/[(Rs)r=H]
1a4_11a-681-1a4-1 ib-681 R9=CF3]
Bd[Rs=H; A5/[(11.6)1=2-CH2CH3]
1a4-1 la-682-4a4-IIb-682 R9=CF3]
136/[14=H; As/[(it6)r=2-0CH2CH3]
1a4-11a-683-1a4-11b-683 R9=CF3]
Ia4- ii a-684-1a4-11b-684 136/[14=H; As/[(R6)1=2-0CH(CH3)2]

R9=CF3]
Ia4- t ta-685-1a4-ttb-685 B6/[R8=H; A5/[(R6)r=3-CH2CH3) R9=CF3]
Bd[Rs=H; As/KR6)r=3-0CH2CH3]
Ia4-1t a-686-1a4-11b-686 R9=CF3]
Ia4-11a-687-1a4-11b-687 B6/[R8=H; A5/[(R6)r=3-0CH(CH3)21 R9=CF3]
Ia4-1 i a-688--1a4-11b-688 B6/[R8=H; A5/[(R6)r=4-CHCH3CH2CH
R9=CF3] (CH3)2]
=
Ia4-11a-689-1a4-11 1)-689 B6/[12.8H; A6 R9=CF3}
s=
1a4-ila-690--Ia4-11 b-690 B6/[RH; A7 R9=CF3) B6/[1t8=C1 A3 Ia4- a-691. t b-691 ; R9=CH3]
1a4-11a-692--Ia4-11 b-692 B6/[14=C1 A4 ;
-1a4-11a-693-1a4-t tb-693 B6/[R8C1 A5/[(R6)r=H}
; R9=CH3]
Bd[Rs----C1 A5/[(R6)r=2-CH2CH3]
Ia4-tia-694-1a4-1 lb-694 ; R9=CH3]
1a411a-695--1a4.11b-695 B6/[R8=C1 As/[(126)r=2-0CH2CH3]
.
; R9=CH3]
1a4-11a-696-4a4.11b-696 B6/[Re---C1 As/[(R6)r=2-0CH(CH3)2]
; R9=CH3]
1a4-11a-6974a4-11b-697 B6/[R8=C1 As/[(R6) -r-4-CHCH3CH2CH
; R9=CH3] (CH3)21 la4-11a-698-1a4-11b-698 B6/[Rs=C1 A6 ; R9=CH3]
Ia4-t a-699-1a4-ttb-699 B6/[1:4=C1 A7 ; R9=CH3]
Ia4-11a-700-1a4-1113-700 B6/[R8=H; A3 R9=CF3]
1m-11a-701-M44 lb-701 B6/[Rs=H; A4 R9=CF3) B6/[14.--H; A5/[(R6)a-H]
la4-Ita-702--Ia4-11b-702 R9=CF3]
1a4_11a-703-4a4-11b-703 B6/[R8=11; A5/[(R6)1=2-CH2CH31 R9=CF3]
Ia4-11 a-704-1a4_11 b-704 B6/[R8=H; A5/[(R6),=2-0CH2CH3]
R9=CF3]
1a4-Ita-705-4a4-11 b-705 B6/[R8=H; As/[(R6),=2-0CH(CH3)2]
R9=CF3]
Ia4-tia-706-1a4-11b-706 B6/[R8=H; A5/[(R6)r=4-CHCH3CH2CH

R9=CF3] (CH3)2]
B6/[1t8=H; AG
1a4-11a-707-1a4-11b-707 R9=CF3]
B6/[12.8=H; A7 Ia4-11a-708-4a4-11b-708 R9=CF3]
1a4-11a-709-1a4-11b-709 B7 A3 1a4-11a-710-1a4-11b-710 B7 A4 Ia4-11 a-711-1a4- ib-711 B7 A5/[(R6)r-1-1]
1a4-11a-712¨La4-I ib-712 B7 A5/[(R6)r---2,6-2Br-4-0CF3]
la4-1 a-713¨Ia4-nb-713 B7 A6 1u-11a-714¨to4-I 113-714 B7 A7 1a4- a-715¨Ia4-11b-715 Bs A3 Ia4-11a-716-1a4-1 lb-716 Bs A4 1a4-11a-717-1a4-11b-717 B8 A5/[(R6)r=1-1]
Iao-lia-718-1a4-11b-718 B8 A5/[(R6)r=2,6-2Br-4-0CF3]
1u-11a-719¨to4-I lb-719 Bs A6 1m-11a-720-1a4- nb-720 Bs A7 la4-1 a-721-1a4-nb-721 B9 A3 Ia4-11a-722-1a4-1 113-722 B9 A4 Ia4-11a-723-1a4-ilb-723 B9 A5/[(R6)1=1-1]
too- a-724¨Ia4-11b-724 B9 A6 1a4-11a-725-1a4-1113-725 B9 A7 1a4-11a-726-1a4-1ib-726 B10 A3 Ia4-11a-727-1a4-1 ib-727 B10 A4 too- a-728-1a4- lb-728 Bio A5/[(R6)r=11]
1a4-11a-729-1a4-11b-729 B10 A5/[(R6)r=3-0-4 CH3]
1a4-11 a-730-1a4-11b-730 B10 A6 la4-1 a-731¨Iao-nb-731 B10 A7 la-732-1a4-iib-732 B11 A3 Ia4-11a-733-1a4- lb-733 B11 A4 lao-ila-734-1a4-11b-734 B11 A5/[(R6)r=f1]
1a4-11a-735-1a4-1 ib-735 B11 As/[(R6)r=2,6-2CH3]
too- 1a-736¨too-I lb-736 Bli A6 1a4-11a-737-1a4-ilb-737 B11 A7 1a4-iia-738-1a4-11 13-738 HOC6H H Ai/[(R2)m=H(R3)0=1-1]
Iao-lia-739-1a4-11b-739 4CO2 H Al/[(R2)m=H (R3)0=-2-C1]
too-I a-740-1a4-11b-740 H Ai/RR2)m=H (3)0=3-C1]
1u-11a-741¨U4-1lb-741 H A1/[(R2)m=H (R3)0=4-C1]
Iao-tia-742-1a4-1ib-742 H Ai/[(R2)m=H (R3)0=3 ,4-2C1]
la4-lia-743-1a4-1 1)-743 H At/[(R2)m=H (R3)0=2-CH3]
1m-11a-744¨to4-II b-744 H Ai/[(R2)m---11 (R3)0=3-CH3]
1a4-Ila-745-1a4-iib-745 H Al/t(R2)m=H (R3)0=4-CH31 1a4-11a-746-1a4- ib-746 FT Al/[(R2)m-=-H (R3)0=3 ,5-2C113]
1a4-Iia-747-1a4-1 lb-747 H Ai/[(R2)m=H (R3)0=4-X(CH3)3]

. . .
1u-11a-748-1u-1lb-748 H Ai/[(R2)01=H (R3)0=4-SCH3]
1u-11a-749-1u-1lb-749 _ H Ai/[(R2)m=H (R3)0=4-Br]
1a441a-750-1a4-1113-750 H Al/[(R2)m=H (R3)0=4-F]
_ la4-11a-751-1a4-11b-751 H A.1/[(R2)0,=H (R3)0=3-F]
1a4-11a-752-1a4-11b-752 H Ai/[(R2)01=H (R3)0=2,4-2F]
1a441a-753-1a44113-753 H , A1/[(R2)01=-H (R3)0=3,4-2F]
Ia4-11a-754-1a4-11b-754 H Al/[(R2)0,=H (R3)0=3,4,5-3F]
1a441a-755-1a4-11b-755 H Ai/[(R2)01=H (R3)0=4-0CH3]
1u-11a-756-1u-1 lb-756 H A1/[(R2)01=H (R3)0=3-0CH3]
Ia44ia-757-1a44ib-757 H Ai/[(R2)m=H (R3)0=4-CF3]
1u-11a-758-14-1lb-758 H Ai/[(R2)01=H (R3)0=4-CN]
1a4-11a-759-1a4-11b-759 H Al/[(R2)01=4-F (R3)0=-H]
1a441a-760-1a441b-760 _ H At/[(R2)01=4-F (R3)0=--2-0]
Ia441a-761-1a4-11b-761 H Ai/[(R2)01=4-F (R3)0=-3-C1]
1m-11a-762-1u-1i b-762 H Ai/[(R2)01=4-F (R3)0=-4-C1]
1a4-11a-763-1a4-11b-763 H Al/KR2)m=4-F (R3)03 ,42C1]
1u-11a-764-1u-1i 1)-764 H Ai/[(R2)m=4-F (R3)0=-2-CH3]
, _ '&441a-765¨M44lb-765 H Al/[(R2)01=4-F (R3)0=3-CH3]
1a4-11a-766-1a4-1113-766 H Al/[(R2)m=4-F (13)0=4-CH3]
.
1a4-lia-767-1a4-11b-767 _H Ai/[(R2),0=4-F (R3)0=3 ,5 -2 CH3]
1u-11a-768-1u-1lb-768 H Al/[(R2)10=4-F (R3)0=4-C(CH3)3]
1u-11a-769¨M44lb-769 , H A1/[(R2)01=4-F(R3)0=4-SCH3]
Ia441a-770-1a4-1ib-770 H A1/[(R2)0,=4-F (R3)0=4-Br]
1u-11a-771¨M44)13-771 H Ai/[(R2)m=4-F (R3)0=4-F]
1u-11a-772¨M4-1i b-772 . H At/RR2)m=4-F (R3)0=3-F]
1u-11a-773¨M44 113-773 H At/[(R2)01=4-F (R3)0=2,4-2F]
la4-11a-774-1a441b-774 H A1/KR2)10=4-F (R3)0=3 ,4-2F]
Ia44 I a-775-1a44 lb-775 H Ai/[(R2)m=4-F (R3)0=3,4,5-3F]
1u-11a-776¨M44lb-776 H Ai/[(R2)01=4-F (R3)0=-4-OCH3]
1a4-11a-777-1a4-11b-777 H Al/[(R2)m=4-F (R3)0=3-0CH31 1a4-11a-778-1a4-1113-778 H Ai/KR2)01=4-F (R3)0=4-CF3]
1a4-iia-779-1a4-11b-779 H Ai /[(R2)17)=4-F R3)0=4-CN]
1u-11a-780¨M44lb-780 , 11 A2/N=site 3 [(R4)p=H (R5)q=1-1]
1a4-11a-781-1a4-1113-781 H A2/[1µ1=site 3 (R4)p=H
(R.5)q=2-C1]
la4-11a-782-1a4-11b-782 H A2/[N=site 3 (R4)p=H (R5)q=3-C1]
1a4-iia-783-1a4-l1b-783 H A24N=site 3 (R4)p=H (R5)q=4-C1]
H A2/[N=site 3 (R4)p=H
1u-11a-784-1u-1l b- 784 (R5)q=3,4-2C1]
Ia44 1 a-785-1a4-11b-785 H A2/[N=site 3 (R4)p=H (R5)q=2-CH3]
1a4-11a-786-1a44ib-786 H A2/[N=site 3 (R4)pH (R5)q=3-CH3]
1u-11a-787-1u-1lb-787 H A2/[N=site 3 (R4)1,=H (R5)q=4-CH3]
H A2/[N=site 3 (R4)p=H
la4-ita-788-1a44ib-788 (R5)q=3,5-2CH3]
1a4-ita-789-1a4-11b-789 1-1 A2/[N=site 3 (R4)p=H

=
=
(R5)q----4-C(CH3)3]
A2/[N=site 3 (R4)p=H
Ia.4.1 a-790¨Ia4-ilb-790 (R5)q=4-SCH3]
1u-11a-791-1u-11b-791 H A2/[N=site 3 (R4)p=H (R5)q=4-Br]
Ia4-11a-792¨Ia4-11b-792 H A2/[N=site 3 (R4)p=H (R5)q=4-F]
Ia4.41a-793¨Ia4-iib-793 H A2/[N=site 3 (R4)p=H (Rs)ri=3-F]
A2/[N=site 3 (Its)p=H (R5)q=2,4-2F]
Ail[N=site 3 (R4)p=H
Ia4-ila-795¨Ia4-1 ib-795 (R5)q=3,4,5-3F]
A2/[N=site 3 (Iti)p=H
Ia4-lia-796¨Ia4-1113-796 (R5)q=4-0CH3]
A2/[N=site 3 (R4)PH
Ia4-iia-797¨Ia4-I lb-797 (R5)(1=3 -OCH3]
Ia4- a-798-1a4-11 b-798 H A2/[N=site 3 (R4)p=H (R5)q=4-CF3]
Ia4-11a-799¨Ia4-11b-799 H A2/[N=site 3 (R4)p=H (R5)q=4-CN]
Ia4-lia-800-1a44 lb-800 H A3 Ia4- a-801.--Ia4-11b-801 H A4 113-802 H A5/[(R6)r=11]
1a4-11a-803¨Ia4-1113-803 H A5/[(R6)r=2-CH3]
Ia4-11 a-804--1a4-11b-804 H A5/[(R6)r=3 -CH3]
Ia.4-11a-805-1a4-11b-805 H A5/[(R6),=2-CN]
1u-11a-806-1u-11b-806 H A5/[(R6)r=2-CF3]
1a4,11a-807,---Ia4-11 b-807 H A5/[(R6)r=2,6-2CH3]
Ia4-i1a-808-1a4-11b-808 H A5/[(R6)r=2-C1-4-NO2]
Ia4-11a-809-4a4_11b-809 H A5/[(R6)r=2-NO2-4-CF3]
Ia4-11a-810¨Ia4- b-810 H A5/[(R6)r=2,3-2C1-4-0H]
1a4- ii a-811¨Ia4-i lb-811 H A5/[(R6)r=2,6-2C1-4-0CF3]
Ia4-I a-812¨Ia4-111)-812 H A5/[(R6)r=3-C1-4-CH3]
Ia4-11a-813¨Ia4- lb-813 A5/[(R6)r=3 -OCH(CH3)2]
A5/[(R6),=4-CHCH3CH2CH
Ia4-1 a-814¨Ia.4-11b-814 (CH3)2]
1u-11a-815¨L4-i 13-815 H AG
1u-11a-816-1u-11b-816 H A7 Ia4-11a-817-1a4-nb-817 HA8 Bi[(It.7)s=2 A3 Ia4-11a-818¨Ia4-11b-818 -I]
B1[(12.7)s=2 A4 Ia4-11a-819¨Ia4-tib-819 -I]
BIRR7)s--2 As/[(R6)r=11]
Ia4-11a-820--Ia4-1 ib-820 -I]
B [(R7)s=2 A6 ta-821¨Ia4-111:0-82 I
-I]
B1[(R7)s=2 A3 -CH3]

, = .
la4-11a-823-1a4-11b-823 B 1 [(10)s=2 A4 -CH3]
1u-11a-824-1m-I 113-824 BIRR7)s=2 A5/[(R6)r=3-0CH(CH3)2]
-CH3]
1a4-11a-825-1a4-1 lb-825 Bi[(R7)s=2 A6 -CH3]
1a4-11a-826-1a4-11b-826 Bi[(R7)s=2 A3 -CF3]
Bi[(11.7)s-,--2 A4 1u-11a-827-1m-1i 1)-827 -CF3]
Ia4-11a-828-1a4-11b-828 Bi[(R7)s=2 A5/[(R6)r=3-0CH(CH3)2]
-CF3]
1a4-11a-829-1a4-11b-829 Bi[(127)s=2 A6 -CF3]
1u-11a-830-1m-1lb-830 BI[(R7)s=2 As -CF3]
Ia4-1 la-831-1a4-11b-831 B1[(R7)s=2 A3 ,6-2C1]
1u-11a-832-1m-1lb-832 BI[(R7)0=2 A4 ,6-2C1]
1u-11a-833-1u-1lb-833 Bi[(R7)s=2 A6 ,6-2C1]
1m-11a-834-1u-I ib-834 BI[(R7)s=2 As ,6-2C1]
Bi[(R7)s=3 A3 1a4- 1 1 a-835-4a4-lib-835 ,4,5,6-4C1 -2-COON]
Bi[(R7)s=3 A4 1a4-11a-836-1a4-1 ib-836 ,4,5,6-4C1 -2-COOH]
BIRIZ7),=--3 A5/[(R6)r=2,3-2C1 1u-11a-837-1u-1i b-837 ,4,5,6-4C1 -2-COOH]
BI[(R7)s==3 A6 Ia4-1 ia-838-Ia4-nb-838 ,4,5,6-4C1 -2-COOH]
1u-11a-839-1m-1lb-839 B2 A 1 /[(R2)m=H (R3)0=3 ,4-2F3 1u-11a-840-4a4-i ib-840 B2 A3 Ia4-11a-841-1a4- 1 ib-841 B2 A4 1a4-11a-842-1a4-11b-842 B2 A6 13.4-11a-843-4a4-11b-843 B3 A 1 /[(R2)m=H (1t3)0=1-11 1a4-lia-844--1a4-l1b-844 B3 A3 1u-11a-845-1a4- i ib-845 B3 A4 Ia4-11a-846-1a4-1113-846 B3 A5/[(R6)r=H]

Ia4- I 1 a-847-4a4-1 lb-847 B3 A6 la4-tia-848-1a4-11b-848 B4 A3 1a4.1 a-849--1a4-11b-849 B4 A4 1u-11a-850-U4-I ib-850 B4 A5/[(R6)1=H]
la4-11 a-851--la4-11b-851 B4 A6 1a4-11a-852--4a4-1113-852 B5 A1/[(It2)m-H (R3)0=4-C11 Ia4-1 a-853-Ia4-nb-853 B5 A3 1a4-113.-854-1a4-11b-854 B5 , A4 Ia4_11a-855-1a4- ib-855 B5 A5/[(R6),---1-1]
1a4-iia-856-1a4-1113-856 B5 A5/[(R6)r=2-CH2CH3]
Ia4-11 a-857-Ia4-ub-857 B5 As/[(R6)r=2-0CH2CH3]
1a4_11a-858-1a4-1111-858 B5 A5/[(R6)r=2-0CH(CH3)2]
1a4.11a-859-1a4-nb-859 B5 A5/[(R6)1=-3-CH2CH3]
1a4-iia-860-1a4-11b-860 B5 A5/[(R6)r=3-0CH2CH3]
Ia4-1 1a-861-1a4-1lb-861 B5 A5/[(R6)r=3-0CH(CH3)2]
Ia4-11a-862-1a4- ib-862 B5 A6 1a4-11a.-863---1a4-11b-863 B6/[118=H; A3 R9=CF3]
1a4..11 a-864-1a4.11b-864 B6/[R8=H; A4 R9=CF3]
B6/[R8=H; A5/[(R6)1=H]
1a4-11a-865--1a4-11b-865 R9=CF3]
B6/[11.8=H; A5/[(R6),=2-CH2CH3]
1a4-11a-866-1a4-11b-866 R9=CF3]
B6/[1Z8=H; A5/[(R6)r=2-0CH2CH3]
1a4-11a-867--1a4-111)-867 R9=CF3]
B6/[11.8=H; A5/[(R6)r=2-0CH(CH3)2]
1a4_Il a-868-1a4-I b-868 R9=CF3]
B6/[R8=H; A5/RR6)r=3-CH2CH3]
Ia4_11 a.-869---Ia4- lb-869 R9=CF3]
B6/[R8=H; A5/[(R6)r=3-0CH2CH3]
la4-11a-870-1a4-1113-870 R9=CF3]
B6/[it8=H; A5/RR6)r=3-0CH(CH3)2]
la4-1 ia-871-1a4-11b-871 R9=CF3]
B6/[R8=H; A5/[(R6),=4-CHCH3CH2CH
1a4-lia.-872-1a4-11b-872 R9=CF3] (CH3)2]
la4-11a-873-1a4-1113-873 B6/[R8=H; A6 R9=CF3]
1a4-11a-874-1a4-11b-874 B6/[R8=H; A7 R9=CF3]
B6/[R8=C1 A3 1a4-11a-875-1a4-1 ib-875 ; R9=CH3]
1a4-11a-876-1a4- tb-876 B6/[R8=C1 A4 ; R9=CH3]

B6/[Rs--C1 As/KR6)r=H]
Ia4-11a-877-4a4-1ib-877 ; R9=CH3]
B6/[lts--C1 A5/[(R6)r=2-CH2CH3]
Ia4-1I a-878-1a4-11b-878 ; R9=CH3]
1a4.11a-879-1a4.11b-879 B6/[R8=C1 A5/[(R6)r=2-0CH2CH3]
; R9=CH3]
1u-11a-880-1a4-1lb-880 B6/[12.8=C1 A5/KR6),=2-0CH(CH3)2]
; R9=CH3]
Ia4-11a-88 I --h4-1113-881 B6/[lt8=C1 A5/[(R6)r=4-CHCH3CH2CH
; R9=-CH3] (CH3)2]
Ta4.11a-882-104-1113-882 B6/[R8=0. A6 ; R9=CH3]
1a4-11a-883-1a4-1113-883 B6/[12.8=C1 A7 ; R9=CH3]
1a4-11a-884-4a4-11b-884 B6/[R8=H; A3 R9=CF3]
Ia4-11a-885-4a4-nb-885 B6/[R8=H; A4 R9=CF3]
B6/[its=H; As/[(R6)r=H]
1a4-11a-886--b4-11b-886 R9=CF3]
Ia4-11a-887-1a4- b-887 B6/[Rs=H; A5/KR6)r=2-CH2CH31 R9=CF3]
1a4-1ib-888 B6/[R8=H; A5/[(R6)r=2-0CH2CH3]
R9=CF3]
Ia4_11a-889-1a4-nb-889 B6/[R8=H; A5/[(R6)r=2-0CH(CH3)2]
R9=CF3]
la4-11a-890-4a4-11b-890 B6/[R8=H; As/[(R6)r=4-CHCH3CH2CH
R9=CF3] (CH3)2]
=
1a4-11a-891-1a4-11b-891 B6/[128H; A6 R9=CF3]
1a4-11a-892-1a4-11b-892 B6/[R8=H; A7 R9=CF3]
1a4-iia-893-1a4-iib-893 B7 A3 1a4-iia-894-1a4.11b-894 B7 A4 ib-895 B7 A5/[(R6)1-=H]
1a4-na-896-4a4-11b-86 B7 A5/[(R6)e=2,6-2Br-4-0CF3]
1a4_11a-897-1a4-nb-897 B7 A6 1a4-t1a-898-Ia4-iib-898 B7 A7 1a4-11a-899--Ia4- ib-899 Bs A3 1a4-iia-9004a4-1 ib-900 B8 A4 1a4-11a-901--Ia4-1 ib-901 Bs A5/[(R6)r=H]
1u-11a-902-1u-I b-902 B8 A5/[(R6)r=2,6-2Br-4-0CF3]
1a4-iia-903-1a4iib-903 B8 A6 = . , 1u-11a-905-M4-1lb-905 B9 A3 Ia4-11a-906-Ia4-11b-906 B9 A4 1u-11a-907-4u-1lb-907 B9 A5/[(R6)r=I-I]
1a4-iia-908-4a4-i ib-908 B9 A6 Ia4-11a-909-Ia4-1113-909 B9 A7 Ia4-l1a-910-1a4-11b-910 B10 A3 Ia4-iia-911-Ia4-lib-911 Blo A4 la4-11a-912--Ia4-1ib-912 Bito A5/[(R6),-I-1]
1u-11a-913-4u-1lb-913 Blo A5/[(R6)r=3-CI-4 CH3]
1u-11a-914-4m-1lb-914 B10 A6 Ia4-na-915-Ia4-itb-915 Bo A7 Ia4-11a-916-Ia4-1ib-916 B11 A3 Ia4-iia-917--Ia4-11b-917 B11 A4 1u-11a-918-1m-1lb-918 B11 As/[(R6)r=1-1]
la4-11a-919-4a4-11b-919 B11 A5/[(R6)1=2,6-2CH3]
1u-11a-920-1a/4-1lb-920 B11 A6 Ia4-11a-921-Ia4-11b-921 B11 A7 The compound of formula I of the present invention can be in particular selected from the compounds numbered as follows.
Ph Ph 0 Ph 0 Ph; I Ph I Ph, I
Pt, Ph ,-----,-0, h P;Kt,r\A ,Q2 1-7 ---- Q2 0 Ph' S
Y- n y- n y- n Ibna Ibnb Ibnc . -4..... . ....:-.
....:-o o o o cia= C ib= Cc= Cid=

i H3C0õCH
H3C0õCH

'N
-\ is . so 40 \ lik 41, 0 \

C3a C3b C3 C3d 0 _IL

-CH
,CH
H3CO" H3C0 N

-Number Y Q2 Ib4-lia-1-Ib4-tic-1 Br C la Ib4-1 ia-2-Ib4-11c-2 C 1 b Ib4-l1a-3-Ib4-lic-3 Cio lb4-l1a-4-1b4-nc-4 C id Ib4.ija-5--Ib4J c-5 C2 C3a C3b C3c 1134-11a-9¨Ib4-11c-9 C3d Ib4-na-10-1b4-1 ic-10 C4 Ib4-11a-11^4b4-11C-11 Ac0 CI a 1134-lia-12-1b4-nc-12 Clb Ib4-11a-13^4b4-11C-13 Clc 1134-1 ia-14-1b4-1 c-14 CI d 11)4-11a45-4b4-1 ic-15 C2 Ib4-11a-16"-M4-11C-16 C3a 1b4-11a47-1b4-1 tc-17 C3b 1b4-11a48¨Ib4-11C-18 C30 Ib4-1 ia-19¨Ib4-nc-19 C3d Ib4-1 ia-21-1b4n Ts0- c-21 CI a 1134-na-22--1411c-22 CI b 1b4-11a-23=Ab4-11C-23 C 1 c I134-11a-24-1b4-11c-24 Cld 1134-1ia-25---1134-tic-25 C2 1134-Iia-26-1134-11c-26 C3a Ib4_11a-27-1134-11c-27 C3b 1134-11a-28-1134-11c-28 C30 1b4-11a-29-1134-iic-29 C3d 1134-11a-30-14nc-30 C4 1b4_11a-31-4b4-iic-31 PhCO2 Cla 141 ia-32-1b4-1 ic-32 Clb 1134-11a-33-1134-1 ic-33 C

=
1134-l1a-34-1114-11 c-34 Cid INA ia-35-1NAic-35 C2 INAia-36¨INA1c-36 C3a INAia-37-113441c-37 C3b 11:441a-38-1N4ic-38 C3c INAia-39¨INA IC-39 C3d INA ia-40¨INA c-40 C4 INAia-41¨INAic-41 HOC61-14CO2 CI a IN-11a-42-1NA c-42 CI b INA ia-43¨INA ic-43 Cic INA1a-44¨INAic-44 Cid INA a-45-1NA ic-45 C2 111441a-46¨INAic-46 C3a IN-11a-47-1134..itc-47 C3b INA ia-48¨INA ic-48 C3c INA1a-49¨INAic-49 C3d INA ia-50-11:0441c-50 C4 Another objective of the present invention is to provide a preparation method of the above phosphonium salt compounds (the compound as shown in formula I).
The preparation method of the phosphonium salt compounds (the compound as shown in formula I) provided by the present invention includes the step of carrying out a nucleophilic reaction between a compound shown in formula VII and triphenylphosphine, in an organic solvent in the presence or absence of a catalyst, to obtain the compound as shown in formula I.
YX-C/
formula VII

In formula VII, the definitions of Y, Q, X, and n are the same as those in formula I. In the above preparation method, the catalyst is sodium iodide or potassium iodide.
The molar ratio of the catalyst to the compound as shown in formula VII may be (0.01-0.1): 1.
The reaction temperature of the nucleophilic reaction may be in the range from 25 to 180 C, preferably in the range from 80 to 115 C, and in particular may be 82 C. The reaction time is in the range from 4 to 24 h, and in particular may be in the range from 8 to 12 h.
The molar ratio of the compound as shown in formula VII to triphenylphosphine may be 1: (1-2), and in particular may be 1: (1-1.3).
The organic solvent may be at least one selected from the group consisting of acetonitrile, glycol dimethyl ether, benzene, toluene, and 1,2-dichloroethane.
The nucleophilic reaction can be carried out in the following steps:
performing vacuumization and nitrogen filling of the bottle containing catalyst, triphenylphosphine and the compound as shown in formula VII, and magneton; adding the organic solvent under the protection of nitrogen, followed by stirring at room temperature for 5-10 min, and then reacting at temperatures in the range from 80 to 115 C for 8-12 h to obtain the compound as shown in formula I.
In the above preparation method, the compound as shown in formula VII is prepared as follows: reacting a compound shown in formula IV (or a compound shown in formula V) with a compound shown in formula VI in an organic solvent in the presence of a catalyst (or an acid binding agent) to obtain the compound as shown in formula VII.
N ,Ar Q2 ¨BriSH " XHn formula IV formula V formula VI
In formula IV, the definitions of Q1 and Ar are the same as those in formula Ia; in formula V, the definition of Q2 is the same as that in formula Ib; in formula VI, the definitions of X, Y, and n are the same as those in formula I; and the definition of U is the same as that in formula Ib. When formula IV reacts with formula VI, U is OC-0 group. In the above preparation method, the acid binding agent may be selected from the group consisting of pyridine, triethylamine, ethylenediamine, potassium carbonate, cesium carbonate, NMM (N-methylmorpholine), and NaH; and the catalyst may be selected from the group consisting of EDCl/HOBT, CDI, DMAP/DCC, HATU/DIPEA, DIC, etc.

The molar ratio of the acid binding agent to the compound as shown in formula IV may be (2-5): 1, and particularly can be (2-3): 1. The molar ratio of the catalyst to the compound as shown in formula IV may be (1-2.5): 1, and particularly can be (1.2-2): 1.
The molar ratio of the compound as shown in IV to the compound as shown in formula VI may be 1: (1-2), and particularly can be 1:1.05.
The molar ratio of the acid binding agent to the compound as shown in formula V may be (2-5): 1, and particularly can be (2-3): 1. The molar ratio of the catalyst to the compound as shown in formula V may be (1-2.5): 1, and particularly can be (1.2-2): 1.
The molar ratio of the compound as shown in V to the compound as shown in formula VI may be 1:
(1-2), and particularly can be 1:1.05.
The reaction temperature may be in the range from -20 to 35 C, and the reaction time may be in the range from 1 to 6 h.
The organic solvent may be selected from the group consisting of dichloromethane, tetrahydrofuran, acetonitrile, N,N-dimethylformamide (DMF), 1,4-dioxane, and toluene.
The reaction may be carried out according to the following steps (taking the reaction between the compound as shown in formula IV and the compound as shown in formula VI
as an example): performing vacuumization and nitrogen filling of the bottle containing the compound as shown in formula IV, catalyst DMAP/DCC, and magneton; adding the organic solvent under the protection of nitrogen; reducing the temperature to -10 C
in an ice salt bath, followed by stirring for 5-10 min; then diluting the compound of formula V into the solvent, which is dropwise added into the reaction bottle slowly, followed by reactions for 0.5-4 h, to obtain the compound as shown in formula VII.
Ar¨NH2 Q1¨C1 formula II formula III
In the above preparation method, the compound as shown in formula IV may be prepared as follows: reacting the compound as shown in formula II and the acid binding agent with the compound as shown in formula III in an organic solvent to obtain the compound as shown in formula IV.
In formula II, Ar is defined as in formula I; in formula III, RI is defined as in formula I.
In the above preparation method, the acid binding agent may be selected from the group consisting of pyridine, triethylamine, ethylenediamine, potassium carbonate, cesium carbonate, and NaH.

The molar ratio of the catalyst to the compound as shown in formula II may be (2-5): 1, and particularly can be (2-3): 1. The molar ratio of the compound as shown in II to the compound as shown in formula III may be 1: (1-1.2), and particularly can be 1:1.05.
The reaction temperature may be in the range from -20 to 35 C, and the reaction time may be in the range from 1 to 6 h.
The organic solvent may be selected from the group consisting of dichloromethane, tetrahydrofuran, acetonitrile, N,N-dimethylformamide (DMF), 1,4-dioxane, and toluene.
The reaction can be particularly carried out in the following steps:
performing vacuumization and nitrogen filling of the bottle containingthe acid binding agent and the compound as shown in formula II, and magneton; adding an organic solvent under the protection of nitrogen; reducing the temperature to -10 C under an ice salt bath, followed by stirring for 5-10 min; then diluting the compound of formula III into the solvent, which is then dropwise added into the reaction bottle slowly, followed by reaction for 0.5-4 h, to obtain the compound as shown in formula IV.
The compounds of formula II, formula III, formula V, and formula VI in the present invention can be purchased commercially or obtained through one-step reactions from raw materials. For example, the compound of formula II can be in particular 2-aminobiphenyl comprising various substituents, arylpyridylamines comprising various substituents, anilines comprising various substituents, benzylamines comprising various substituents, and various heterocyclic amines comprising various substituents. the compound as shown in formula III
can be obtained through one-step reactions of various substituted benzoic acids, phenylacetic acids, heterocyclic acids, and the like.
The present invention further seeks protection of a fungicide composition and a preparation method thereof.
The composition comprises the phosphonium salt compound (the compound as shown in formula I) and an agriculturally acceptable carrier, wherein the phosphonium salt compound (active ingredient) in the single agent has a mass percentage content of 0.1-99%, which can be specifically 30-60%.
The phosphonium salt compound can be either a single compound of the present invention or a mixture of several compounds of the present invention.
The preparation method of the fungicide composition provided by the present invention comprises the following steps: mixing the phosphonium salt compound (the compound as shown in formula I) and an agriculturally acceptable carrier uniformly to obtain the fungicide composition.

, CA 03101114 2020-11-20 1 , The agriculturally acceptable carrier has the following characteristics: 1) after being formulated with an active ingredient, it can be readily administered to a site to be treated such as a plant, a seed or soil; 2) it is convenient for storage, transportation, or operation;
and 3) it can be a solid or liquid, including a substance which is usually a gas but has been compressed into a liquid. In a word, all the carriers commonly used in the preparation of agricultural fungicides can be used in the present invention.
The agriculturally acceptable carrier can be in particular selected from a solid carrier and/or a liquid carrier.
The solid carrier may be at least one selected from the group consisting of a natural or synthetic silicate, ammonium sulfate, calcium sulfate, aluminum silicate oxide, a natural or synthetic resin, polychlorophenol, starch, bentonite, and wax, wherein the natural or synthetic silicate particularly can be at least one selected from the group consisting of magnesia, talc, aluminum silicate, diatomite, mica, montmorillonite, and calcium silicate;
the natural or synthetic resin can be at least one selected from the group consisting of benzofuran resin, a styrene polymer (with a molecular weight in the range from 50,000-200,000), and a styrene copolymer (such as a styrene-butadiene copolymer); and the wax can be selected from the group consisting of beeswax and/or paraffin.
The liquid carrier may be at least one selected from the group consisting of water, CI-C4 alcohols, C3-C8 ketones, aromatic hydrocarbons, petroleum fractions, and chloroalkanes, wherein the alcohol can in particular be ethanol and/or glycol;
the ketone can in particular be at least one selected from the group consisting of acetophenone, acetone, methyl ethyl ketone, and cyclohexanone; the aromatic hydrocarbon can in particular be at least one selected from the group consisting of benzene, toluene, and xylene;
the petroleum fraction can in particular be kerosene and/or mineral oil; and the chloroalkane can in particular be at least one selected from the group consisting of carbon tetrachloride, dichloromethane, and trichloroethane.
The general fungicide composition is usually processed into the form of a concentrate for transport, and diluted by the user prior to administration.
In order to facilitate dilution, the fungicide composition provided by the present invention can also comprise a surfactant.
The added amount of the surfactant may be an acceptable amount in agricultural fungicides.
The surfactant can be at least one selected from the group consisting of an emulsifier, a dispersant, a wetting agent, and a penetrant.

. CA 03101114 2020-11-20 , =
, The emulsifier can be at least one selected from the group consisting of agricultural pesticide emulsifier #500 (calcium alkylbenzenesulfonate), agricultural pesticide emulsifier #600 phosphate (phenylphenol polyoxyethylene ether), agricultural pesticide emulsifier #700 (alkylphenol formaldehyde polyoxyethylene ether), agricultural pesticide emulsifier #1600 (phenylethyl phenol polyoxyethylene polypropylene ether), polyoxyalkenylenealkylaryl ethers, and ethylene oxide-propylene oxide block copolymers.
The dispersant can be at least one selected from the group consisting of polycarboxylate, lignosulfonate, alkylphenol polyoxyethylene formaldehyde condensate sulfate, an alkylbenzene sulfonate calcium salt, a benzenesulfonate formaldehyde condensate sodium salt, sodium lauryl sulfate, sodium castor oil sulfate, sodium alkylaryl sulfonate, alkylphenol polyoxyethyleneether, polyoxyethylene fatty acid, and ester polyoxyethylene ether.
The wetting agent can in particular be at least one selected from the group consisting of sodium dodecyl sulfate, sodium dodecyl benzenesulfonate, nekal BX, saponin powder, silkworm sand, and sapindus powder.
The penetrant can in particular be at least one selected from the group consisting of siloxane polyoxyethylene ether, sulfonic alkylaryl ester, alcohol ether succinate, and phenol ether succinate.
Of course, in the fungicide composition of the present invention, other auxiliary agents can be added appropriately.
The added amount of the other auxiliary agents can be an acceptable amount in agricultural fungicides.
The other auxiliaries can be at least one selected from the group consisting of a disintegrating agent, a defoamer, an antifreeze, and a thickener.
The disintegrating agent is at least one selected from the group consisting of bentonite, urea, ammonium sulfate, aluminum chloride, and glucose.
The defoamer is at least one selected from the group consisting of silicone oil, a silicone compound, a Cio-C2o saturated fatty acid compound, and a C8-C10 fatty alcohol compound.
The antifreeze is at least one selected from the group consisting of glycol, propylene glycol, glycerol, and polyethylene glycol.
The thickener is at least one selected from the group consisting of xanthan gum, polyvinyl alcohol, and polyethylene glycol.
The fungicide composition prepared by the present invention can be added with corresponding components according to a method known to a person skilled in the art, thus to prepare various formulations such as a wettable powder, a powder, a granule, a concentrated emulsion, emulsifiable oil, a suspending agent, aerosol, or aerosol. At the same time, based on different crops and diseases, effective amounts of the fungicide composition of the present invention can be administered by foliar spray, seed treatment, or soil treatment.
The present invention further seeks protection of a composition comprising at least two active components.
The active components of the composition comprise the phosphonium salt compound (the compound as shown in formula I) and at least another active compound.
Said another active compound can be at least one selected from the group consisting of known fungicides, acaricides, nematicides, insecticides, herbicides, fertilizers, growth regulators, safety agents, and chemical pheromones, further preferably fungicides and insecticides.
The composition is a fungicidal composition, which refers to a composition prepared by the compound as shown in formula I and one or several other fungicides, and a formulation thereof, for expanding the prevention and cure scope of the product. Said other fungicides include: 2-(thiocyanatomethylthio)-benzothibzole, 2-phenylphenol, 8-hydroxyquinoline sulfate, ametoctradin, amisulbrom, antimycin, ampelomyces quisqualis, azaconazole, azoxystrobin, Bacillus subtilis, benalaxyl, benomyl, benthiavalicarb-isopropyl, benzovindiflupyr, diphenyl, bismerthiazol, bitertanol, bixafen, blasticidin-S, borax, bordeaux mixture, boscalid, bromuconazole, bupirimate, captafol, captan, carbendazim, carboxin, cycloimide, carvone, chloroneb, chlorothalonil, chlozolinate, coniothyrium minitans, copper hydroxide, copper isooctanate, copper oxychloride, cupric sulfate, cuprous oxide, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dazomet, debacarb, diethyl metformin, dichlofluanid, dichlorophen, diclocymet, diclomezin, dicloran, diethofencarb, difenoconazole, diflumetorim, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinobuton, dinocap, diphenylamine, dithianone, dodemorph, dodine, edifenphos, enestroburin, epoxiconazole, ethaboxam, ethoxyquin, chloroquine, famoxadone, fenamidone, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil, fenpropidine, fenpropimorph, fenpyrazamine, triphenyltin, ferbam, ferimzone, fluazinam, fludioxonil, flumorph, fluopicolide, fluopyram, fluoroimide, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil, flutolanil, flutriafol, fluxapyroxad, folpet, fosetyl-alumin, furathiocarb, furalaxyl, furametpyr, hexachlorobenzene, hexaconazole, hymexazol, imazalil, imibenconazole, iminoctadine, iminoctadine acetate, ipconazole, iprobenfos, iprodione, iprovalicarb, isoprothiolane, isopyrazam, isotianil, kasugamycin, lcresoxim-methyl, laminarin, mancopper, mancozeb, mandipropamid, maneb, metalaxyl, metalaxyl-M, mepanioyrim, meproil, metham-sodium, metconazole, methasulfocarb, methyl isothiocyanate, metiram, metominostrobin, metrafenone, mildiomycin, myclobutanil, nabam, nitrothal-isopropyl, nuarimol, octhilinone, fenfuram, oleic acid, orysastrobin, oxadixyl, oxine-copper, oxpoconazole-fumarate, oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen, pentachlorophenol, pentachlorophenol laurate, penthiopyrad, phthalide, picoxystrobin, polyoxins, polyoxorim, thiabendazole, prochloraz, procymidone, propamocarb, propiconazole, propineb, proquinazid, prothioconazole, pyraclostrobin, pyraclostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyrimorph, pyriofenone, chloroqualone, quinoclamine, quinoxyfen, quintozene, sedaxane, silthiofam, simeconazole, sodium pentachlorophenol, spiroxamine, sulfur, tebuconazole, isobutyl ethoxyquinoline, tecnazene, tetraconazole, thiabendazole, thifluzamide, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazoxide, tricyclazole, tridemorph, trifloxystrobin, triflumizole, triforine, triticonazole, validamycin, valeriamine, valifenalate, vinclozolin, zineb, ziram, zoxamide, Fusarium oxysporum, benodanil, benquinox, phenamacril, benzamorf, binapacryl, buthiobate, carbamorph, chlobenthiazone, chloraniformethan, phenyl imidazole bacteria, chlorquinox, cyflufenamid, cyanazin, cyprofuram, decafentin, dichlone, dichlozoline, diclobutrazol, dimethirimol, dinocton, dinosulfon, dinoterbon, dipyrithione, plondrel, dodicin, drazoxolon, etaconazole, dexon, propanenitrile, fenitropane, fluotrimazole, furoxime, furconazole, furmecyclox, furophanate, griseofulvin, quinoline acrylate, cyclohexanol sulfur phosphorus, isopamphos, chlorphenicone, mepronil, mecarbinzid, mechlorobactone, methfuroxam, metsulfovax, milneb, mucochloric anhydride, myclozolin, natamycin, phosdiphen, prothiocarb, pyracarbolid, pyridinitril, pyroxychlor, pyroxyfur, quinacetol, quinazolamide, fluquinconazole, rabenzazole, salicylanilide, sultropen, thiadifluor, thicyofen, thiochlorfenphim, thioquinox, thiocyanin benzamide, triamiphos, triarimol, triazbutil, trichlamide, urbacid, fenoxanil, etc.
The composition is a fungicidal and insecticidal composition, which refers to a composition prepared by the compound as shown in formula I and one or several other insecticides, and a formulation thereof, for expanding the prevention and control scope of the product. Said other insecticides include avermectin, acephate, acetamiprid, acethion, acetoprole, fenvalerate, alanycarb, aldicarb, aldicarb sulfone, allethrin, allosamidin, allyxycarb, a-cypermethrin, a-ecdysone, endosulfan, amidithion, aminocarb, amiton, phoxim, amitraz, anabasine, athidathion, azadirachtin, azamethiphos, azinos, azinphos-methyl, azothoate, barthrin, bendiocarb, benfuracarb, bensultap, 0-cyfluthrin, P-cypermethrin, bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bistrifluron, bromfenvinfos, bromocyclen, bromophos, bufencarb, buprofenzin, butacarb, butathiofos, butocarboxim, butonate, butoxycarboxim, cadusafos, toxaphene, carbanolate, carbaryl, mitarway, carbophenothion, benfuracarb, padan, chlorantraniliprole, borneol, chlordane, chlordecone, chlordimeform, chlorethoxyfos, chlorfenapyr, chlorfenvinphos, butazone, chlormephos, nitrochloroform, chlorphoxim, clopidophos, chlorpyrifos, chlorpyrifos-methyl, phosphite, chromafenozide, cinerin, cismethrin, cloethocarb, closantel, clothianidin, coumaphos, toxicphos, crotamiton, ciodrin, crufomate, surecide, cyanophos, cyanthoate, cyantraniliprole, cypermethrin, cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, cyphenothrin, cyromazine, cythioate, DDT, carbofuran, deltamethrin, demephion, demephion, thiotephos, systox, demeton-S-methyl, diafenthiuron, dialifos, diazinon, dicapthon, dichlofention, dichlorvos, phosphor, dicyclanil, dieldrin, diflubenzuron, dimefluthrin, dimefox, dimetan, dimethoate, pyrethrin, dimethylvinphos, dimetilan, phenol, propanol, dinosam, dinotefuran, diofenolan, salithion, dioxacarb, delnav, disulfoton, thiofuran, doramectin, ecdysterone, emamectin, empenthrin, endosulfan, endothion, endrin, epofenonane, eprinomectin, allethrin, fenvalerate, ethiofencarb, diethion, ethiprole, ethoprophos, ethofenprox, etrimfos, famphur, phenamiphos, phenylester, fenchlorphos, fenethacarb, fenfluthrin, fenitrothion, fenobucarb, fenoxacrim, fenoxycarb, fenpirithrin, fenpropathrin, fensulfothion, fenthion, fenthion-ethyl, fenvalerate, fipronil, flonicamid, flubendiamide, flucofuron, flucycloxuron, flucythrinate, flufenerim, flufenoxuron, flufenprox, tau-fluvalinate, fonofos, formetanate, formothion, formparanate, fosmethilan, fosthietan, furathiocarb, furethrin, y-cyhalothrin, halfenprox, halofenozide, heptachlor, heptenophos, heterophos, hexaflumuron, hydramethylnon, hydroprene, quinoline, imidacloprid, imiprothrin, indoxacarb, isazofos, isobenzan, isocarbophos, isodrin, isofenphos, isoprocorb, isoprothiolane, isofenphos, isoxathio, ivermectin, jasmonate, iodofenphos, juvenile hormone I, juvenile hormone II, juvenile hormone III, kelevan, pronoprotein, reomycin, leptophos, acetamiprid, lufenuron, quinazoline, malathion, mitaconitrile, mazidox, mecarbam, mecarphon, azidithion, mephosfolan, fenthionsulfoxide, metaflumizone, methacrifos, methamidopho, methidathion, mesurol, methocrotophos, methomyl, methoprene, methoxychlor, methoxyfenozide, metofluthrin, tsumacide, metoxadiazone, mevinphos, mexacarbate, milbemectin, milbemycin oxime, propylene phosphorus fluoride, mirex, monosultap, monocrotophos, phosphorodithioicacid, moxidectin, naftalofos, dibrom, nifluridide, nitenpyram, nithiazine, nitrilacarb, novaluron, noviflumuron, oxamyl, oxydemeton-methyl, oxydeprofos, oxydisulfoton, parathion, parathion-methyl, penfluron, permethrin, henkapton, permethrin, phenthoate, thimet, phosalone, phosfolan, phosemet, phosnichlor, phosphamidon, phoxim, phoxim-methyl, pirimetaphos, aphid resistant phosphorus, pirimiphos-ethyl, pirimiphos-methyl, prallethrin, precocene I, precocene II, precocene III, amidopyrimiphos, profenofos, trifluralin, promacyl, phenol, propaphos, propetamphos, propoxur, ethyl thiazolium, prothiofos, prothoate, protrifenbute, pyraclofos, pyrafluprole, pyrazophos, pyresmethrin, pyrethrins, pyridaben, pyridalyl, pyridaphenthione, pyrifluquinazon, pyrimidifen, pirimiphos-ethyl, pyriprole, pymetrozine, pyripropoxyfen, mersosin, quinalphos, methyl quinalphos, quinothion, rafoxanidum, rotenone, ryanodine, sabadilla, schradan, selamectin, silafluofen, formocarbam, spinosad, spinetoram, spirodiclofen, spirotetramat, sulcofuron, sulcofuron-sodium, sulfluramid, sulfotep, sulfoxaflor, sulphurtap, tau-fluvalinate, tazimcarb, tebufenozide, tebufenpyrad, tebupirimfos, eflubenzuro, tefluthrin, temephos, methenthrin, tertap, insecticide, tetramethrin, meperfluthrin, beta-cypermethrin, thiacloprid, thiamethoxam, quinoline phosphorus, thiocarboxime, thiocyclam, thiocyclam hydrogen oxalate, thiodicarb, thiofanox, thiometon, bisultap, thuringiensin, tolfenpyrad, tralomethrin, transfluthrin, triarathene, triaguron, triazophos, dipterex, trichlormetaphos-3, trichloronate, phosphorus oxychloride, triflumuron, trimethacarb, triprene, vamidothion, flurozole, xylylcarb, triazophos, etc.
Further, use of the compound as shown in formula I and the composition comprising the compound as shown in formula I in the preparation of a fungicide also fall within the protection scope of the present invention.
The compound as shown in formula I of the present invention has broad-spectrum and excellent fungicidal activity, and can be used for prevention and cure of diseases caused by four major pathogenic fungi, i.e., ascomycetes, basidiomycetes, deuteromycotina, and oomycetes, on a variety of crops. Good prevention and cure effects can be obtained at very low doses. At the same time, such compounds as shown in formula I have certain absorbability and can be used as leaf and soil fungicides to prevent and cure diseases on a variety of crops. The following diseases can be particularly prevented and cured:
phytophthora blight of pepper, tomato early blight, tomato late blight, tomato gray mold, rice blastwheat leaf spot, ring spot, rice sheath blight, rice false smut, rice bakanae disease, wheat powdery mildew, wheat fusarium head blight, rape sclerotinia rot, cucumber downy mildew, cucumber blight, cucumber gray mold, cucumber powdery mildew, apple powdery mildew, watermelon anthracnose, cercospora brown spot of peanut, rot of melon and fruit, damping-off and cottony leak of melon, cotton blight, cotton verticillium wilt, cotton damping-off.
Brief Description of Drawings Fig. 1 is a flow chart for the preparation of the compound as shown in formula I.

=
Detailed Description of Embodiments In the following, the present invention will be described through specific examples.
However, the present invention is not limited to this. Any amendment, equivalent replacement, improvement, and the like made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.
The experimental methods used in the following examples are conventional methods unless otherwise specified.
The materials, reagents, and the like used in the following examples can be obtained commercially unless otherwise specified.
I. The preparation examples of the compounds as shown in formula I are provided as follows, and the corresponding preparation flow chart is shown in Fig. 1.
Example 1 Preparation of compound Ia8a-1 (i.e., compound as shown in formula Tana, wherein n=8, Y=Br, QI=H, Ar=A1/[(R2)m=H, (R3)0H]) 1. Preparation of N-[(1,1'-bipheny1)-2-y1]-11-bromoundecylamide A 250 mL three-necked bottle was taken, into which 2 g (9.13 mmol) of 2-iodoaniline, 1.3 g (10.96 mmol) of phenylboronic acid, and 2.5 g (18.26 mmol) of potassium carbonate were added. 120 mL of a mixed solution with toluene: ethanol: water =10:1:1 was added, followed by stirring. 300 mg (0.26 mmol) of tetra(triphenylphosphine) palladium was then added. After full reaction under heat and reflux for 8 hours, 1.4 g of o-aminobiphenyl was obtained at a yield of 91%.
1 g (3.77 mmol) of 11-bromoundecanoic acid, EDCI (0.72 g, 3.77 mmol), and HOBT

(0.5 g, 3.77 mmol) were added into a 100 mL round-bottom flask, and 40 mL of dichloromethane was added to react for 15 min. Then o-aminobiphenyl (0.61 g, 3.6 mmol) and NMM (0.77 g, 7.55 mmol) were added. After reactions for 4 hours, 1.35 g of N-[(1,1'-biphenyl)-2-y1]-11-bromoundecanoamide was obtained at a yield of 86%
NMR (300 MHz, CDC13) 8 8.21 (d, J=8.2 Hz, 1H), 7.45-7.24 (m, 611), 7.17-7.13 (m, 1H), 7.12-7.04 (m, 2H), 3.32 (t, J=6.8 Hz, 2H), 2.10 (t, J=7.5 Hz, 2H), 1.84-1.68 (m, 2H), 1.54-1.42 (m, 2H), 1.38-1.28 (m, 2H), 1.18 (s, 10H).
13C NMR (75 MHz, CDC13) ö 170.86, 137.88, 134.45, 131.82, 129.65, 128.95, 128.72, 128.08, 127.63, 123.86, 121.24, 37.48, 33.66, 32.48, 29.01, 28.95, 28.91, 28.74, 28.39, 27.81, 25.10.
2. Preparation of compound Ia8a-1 0.6 g (1.45 mmol) of N-[(1,1'-biphenyl)-2-y1]-11-bromoundecanoamide, 0.5 g (1.9 mmol) of triphenylphosphine, 12 mg (0.72 ummol) of potassium iodide and magneton were added into a 100 mL three-necked bottle, followed by vacuumization and nitrogen filling.
30 mL of acetonitrile was added under the protection of nitrogen, followed by stirring at room temperature for 5-10 min, and refluxing under heating at 90 C for 12 h.
Column chromatography was performed for separation to obtain 0.87 g of white solid powder at a yield of 90%.
Confirmation data of structural formula were as follows.
1H NMR (300 MHz, CDC13) 6 8.11 (d, J=8.2 Hz, 1H), 7.78-7.59 (m, 15H), 7.43-7.30 (m, 3H), 7.27-7.18 (m, 411), 7.14 (dd, J=7.6, 1.6 Hz, 111), 7.06 (t, J=7.4 Hz, 111), 3.47 (s, 211), 2.08 (t, J=7.5 Hz, 2H), 1.61-1.37 (m, 611), 1.21-1.04 (m, 10H).
13C NMR (75 MHz, CDC13) 8 170.94, 137.32, 134.74, 134.69, 134.48, 133.28, 133.14, 132.19, 130.25, 130.08, 129.63, 129.33, 128.62, 127.62, 123.81, 121.38, 118.42, 117.28, 37.25, 30.09, 29.89, 28.77, 28.74, 28.65, 28.57, 24.98, 22.74, 22.23, 22.18, 22.08.
The compounds numbered Ia4.11a-1-4a4.11b-1 to Ia4-iia-80-1a4-11b-80 were each prepared with reference to the method in Example 1. The NMR data of some of the compounds were as follows.
The 11-1 NMR and 13C NMR of compound 1asa-3 were as follows.
1H NMR (300 MHz, CDC13) 8 7.93 (d, J=8.0 Hz, 111), 7.76-7.56 (m, 15H), 7.40-7.27 (m, 211), 7.25-7.13 (m, 4H), 7.13-7.02 (m, 2H), 3.54-3.35 (m, 2H), 2.10 (t, J=7.5 Hz, 2H), 1.63-1.33 (m, 6H), 1.21-0.99 (m, 10H).
13C NMR (75 MHz, CDC13) 6 171.22, 139.94, 134.85, 134.82, 134.23, 134.15, 133.27, 133.14, 130.33, 130.16, 129.89, 129.51, 128.77, 128.27, 127.49, 127.01, 124.47, 122.94, 118.19, 117.06, 37.12, 30.11, 29.90, 28.71, 28.61, 28.58, 25.04, 23.02, 22.35, 22.17, 22.11.
The NMR and 13C NMR of compound 1a8a-5 were as follows.
1H NMR (300 MHz, CDC13) 6 7.79-7.57 (m, 15H), 7.37 (dd, J=8.3, 5.1 Hz, 211), 7.24-7.15 (m, 211), 7.13-7.06 (m, 2H), 3.51-3.30 (m, 2H), 2.15 (t, J=7.5 Hz, 2H), 1.62-1.33 (m, 611), 1.24-0.97 (m, 1011).
13C NMR (75 MHz, CDC13) 6 171.55, 138.69, 134.89, 134.85, 134.20, 133.26, 133.13, 132.35, 132.10, 131.17, 130.50, 130.34, 130.27, 130.18, 129.48, 128.46, 128.33, 125.03, 124.40, 118.18, 117.04, 36.87, 30.09, 29.88, 28.67, 28.59, 28.48, 25.08, 23.03, 22.36, 22.16, 22.10.
The 'H NMR and 13C NMR of compound Iasa-21 were as follows.
1H NMR (300 MHz, CDC13) 8 8.12 (s, 1H), 7.79-7.59 (m, 16H), 7.51 (dd, J=30.9, 8.3 Hz, 4H), 7.22 (dd, J=7 .7 , 4.0 Hz, 1H), 7.14 (d, J=4.2 Hz, 2H), 3.47-3.31 (m, 2H), 2.16 (t, J=7.4 Hz, 2H), 1.67-1.45 (m, 4H), 1.45-1.31 (m, 211), 1.28-1.01 (m, 10H).

= CA 03101114 2020-11-20 13C NMR (75 MHz, CDC13) 6 171.75, 144.03, 134.92, 134.88, 134.16, 133.26, 133.13, 131.84, 130.35, 130.18, 129.62, 129.44, 128.66, 125.41, 118.56, 118.18, 117.04, 110.37, 36.60, 30.09, 29.89, 28.67, 28.64, 28.54, 28.41, 25.01, 22.98, 22.32, 22.15, 22.09.
The 111 NMR and 13C NMR of compound Ia8a-26 were as follows.
NMR (300 MHz, DMSO) 8 8.80 (s, 1H), 7.78-7.57 (m, 15H), 7.47 (dd, J=8.7, 5.4 Hz, 1H), 7.37 (d, J=2.0 Hz, 1H), 7.35-7.28 (m, 1H), 7.25 (dd, J=8.3, 2.0 Hz, 1H), 6.84 (ddd, J=11.8, 8.4, 2.9 Hz, 2H), 3.54-3.25 (m, 2H), 2.18 (t, J=7.5 Hz, 2H), 1.65-1.45 (m, 4H), 1.45-1.29 (m, 2H), 1.26-1.00 (m, 10H).
13C NMR (75 MHz, CDC13) 8 172.22, 161.45, 158.20, 138.26, 136.25, 134.85, 134.82, 133.18, 133.05, 131.81, 131.18, 130.61, 130.28, 130.11, 130.02, 128.15, 118.26, 117.12, 116.05, 115.75, 114.88, 114.59, 36.25, 30.00, 29.80, 28.57, 28.51, 28.33, 25.04, 22.78, 22.12.
Example 2 Preparation of compound Ia8a-115 (i.e., compound as shown in formula Iana, wherein n=8, Y=Br, Q1=B5, Ar=A1/[(R2)m=H, (R3)0=4-C1]) 1. Preparation of 2-chloro-N-(4-chlorobipheny1-2-y1)-N-(11-bromoundecanoyl) nicotinamide 1 g (3.77 mmol) of 11-bromoundecanoic acid, EDCI (0.72 g, 3.77 mmol), and HoBt (0.5 g, 3.77 mmol) were added into a 100 mL round-bottom flask, and 40 mL of dichloromethane was then added to react for 15 min. 1.24 g (3.6 mmol) of Boscalid (2-chloro-N-(4'-chloro-[1,1'-biphenyl]-2-y1) nicotinamide} was then added.
After reactions of 4 hours, 1.5 g of 2-Chloro-N-(4-chlorobipheny1-2-y1)-N-(11-bromoundecanoyl) nicotinamide was obtained at a yield of 93%.
Confirmation data of structural formula were as follows.
1H NMR (300 MHz, CDC13) 8 8.40 (dd, J=4.8, 1.9 Hz, 1H), 7.59-7.39 (m, 7H), 7.33-7.24 (m, 3H), 3.42 (t, J=6.8 Hz, 2H), 2.39-2.23 (m, 1H), 2.05 (d t, J=17.3, 7.2 Hz, 1H), 1.94-1.80 (m, 2H), 1.50-1.04 (m, 15H).
DC NMR (75 MHz, CDC13) 8 174.45, 168.36, 149.49, 145.31, 139.63, 136.13, 136.05, 135.08, 134.20, 133.52, 130.97, 129.69, 129.64, 129.21, 129.13, 128.60, 121.91, 36.58, 33.71, 32.46, 28.94, 28.84, 28.82, 28.46, 28.34, 27.78, 23.64.
2 Preparation of compound Ia8a-115 0.78 g (1.32 mmol) of 2-chloro-N-(4'-chloro-[1,1'-bipheny1]-2-y1)-N-(11-bromondecanoy1)-nicotinamide, 0.53 g (2 mmol) of triphenylphosphine, 12 mg (72 ummol) of potassium iodide and magneton were added into a 100 mL three-necked bottle, followed by vacuumization and nitrogen filling. Under the protection of nitrogen, 30 mL of acetonitrile was added, followed by stirring at room = CA 03101114 2020-11-20 temperature for 5-10 min, and reflux under heating at 90 C for 10 h. Column chromatography was performed for separation to obtain 1 g of white solid powder at a yield of 88%.
Structure confirmation data were as follows.
11-1 NMR (300 MHz, CDC13) 8 8.23 (dd, J=4.8, 1.9 Hz, 1H), 7.74-7.57 (m, 15H), 7.47-7.14 (m, 10H), 3.60-3.42 (m, 2H), 2.28-1.79 (m, 2H), 1.48 (4, 6H), 1.25-0.87 (m, 12H).
'3C NMR (75 MHz, CDC13) 8 174.42, 168.27, 149.35, 145.29, 139.46, 136.01, 135.96, 134.90, 134.73, 134.69, 134.02, 133.47, 133.27, 133.13, 130.94, 130.24, 130.07, 129.66, 129.23, 129.05, 128.49, 121.96, 118.42, 117.29, 36.48, 30.06, 29.86, 28.65, 28.59, 28.29, 23.52, 22.75, 22.25, 22.19, 22.08.
The compounds numbered Iaa_i1a-81¨Ia4_i1b-81 to Ia4-iia-184¨Ia4-iib-184 were each prepared according to the method in Example 1; the compounds numbered Ia4-11a-185-1a4-iib-185 to Ia4-1 la-553¨Iaa-tib-553 were each prepared with reference to the methods in Example 1 and Example 2.
Example 3 Preparation of compound Ib6a-2 (i.e., compound as shown in formula Ibna, wherein n=6, Y=Br, Q2=Cib) 2.35 g (8.2 mmol) of methyl (E)-2-(2-bromomethyl)pheny1-2-methoxyiminoacetate, 8-bromo-octanol (1.8 g, 8.61 mmol), 30 mL of a THF solution were added into a 100 mL
three-necked bottle, and cooled to below 5 C. 3.91 g (12 mmol) of Cs2CO3 was added, followed by stirring for lh. The temperature was raised to room temperature (25 C ) and reactions continued for 8 h. Vacuum spin drying and column chromatography were performed to obtain 2.7 g of the product, methyl (E)-242-(8-bromooctoxy)methylene)pheny1-2-methoxyiminoacetate at a yield of 80%.
111 NMR (300 MHz, CDC13) 8 7.49-7.32 (m, 3H), 7.21-7.14 (m, 1H), 4.38 (s, 2H), 4.04 (s, 3H), 3.87 (s, 3H), 3.39 (dt, ./=13.6, 6.8 Hz, 4H), 1.93-1.79 (m, 2H), 1.49-1.38 (m, 2H), 1.32 (s, 6H).
1.07 g (2.59 mmol) of methyl (E)-2-[2-(8-bromooctoxy) methylene)pheny1-2-methoxyiminoacetate, 0.82 g (3.1 mmol) of triphenylphosphine, 18 mg (108 ummol) of potassium iodide and magneton were added to a 100 mL three-necked bottle, followed by vacuumization and nitrogen filling. 30 mL of acetonitrile was added under the protection of nitrogen, followed by stirring at room temperature for 5-10 min, and refluxing under heating at 90 C for 10 h. Column chromatography was then performed for separation to obtain 0.74 g of a white solid powder at a yield of 42%.

111 NMR (300 MHz, CDC13) 6 7.81-7.59 (m, 15H), 7.36-7.20 (m, 3H), 7.09-7.02 (m, 1H), 4.26 (s, 211), 3.92 (s, 3H), 3.73 (s, 3H), 3.57 (s, 211), 3.24 (t, J=6.6 Hz, 2H), 1.58-1.47 (m, 2H), 1.45-1.34 (m, 2H), 1.24-1.10 (m, 6H).
The series of compounds numbered Ib4_i la were each prepared according to the method in Example 3.
Example 4 Preparation of compound 1b8b-2 (i.e. compound as shown in formula Ibrib, wherein n=8, Y=Br, Q2=Cib) 30 mL of a TI-IF solution comprising 2.4 g (9 mmol) of 11-bromoundecanoic acid was added into a 100 mL three-necked bottle, and cooled to below 5 C. 3.91 g (12 mmol) of C52CO3 as added. After stirring for 1 h, 2.35 g (8.2 mmol) of methyl (E)-2-(2-bromomethyl)pheny1-2-methoxyiminoacetate was added. The temperature was heated to room temperature (25 C), and reactions continued for 8 h. After vacuum spin drying, a yellow viscous liquid was obtained. Column chromatography was performed to obtain 3.2 g of a pink viscous liquid at a yield of 83%.
111 NMR (300 MHz, CDC13) 8 7.47-7.34 (m, 3H), 7.20-7.13 (m, 1H), 4.97 (s, 2H), 4.03 (s, 3H), 3.86 (s, 3H), 3.62 (t, J=6.5 Hz, 211), 2.28 (td, J=7.6, 2.1 Hz, 2H), 1.69-1.50 (m, 6H), 1.27 (s, 10H).
1.2 g (2.59 mmol) of methyl (E)-2-[2-(11-bromoundecanoyloxy) methylene)pheny1-2-methoxyiminoaceate, 0.82 g (3.1 mmol) of triphenylphosphine, 18 mg (108 ummol) of potassium iodide and magneton were added into a 100 mL three-necked bottle, followed by vacuumization and nitrogen filling. 30 mL of acetonitrile was added under the protection of nitrogen, followed by stirring at room temperature for
5-10 min, and refluxing under heating at 90 C for 10 h. Column chromatography was then performed for separation to obtain 0.99 g of a white solid powder at a yield of 52%.
'H NMR (300 MHz, DMSO-d6) 6 7.96-7.85 (m, 3H), 7.86-7.71 (m, 12H), 7.48-7.35 (m, 3H), 7.25-7.18 (m, 1H), 4.87 (s, 2H), 3.92 (s, 311), 3.74 (s, 3H), 3.56 (s, 2H), 2.22 (t, J=7.4 Hz, 211), 1.46 (s, 6H), 1.33-1.12 (m, 10H).
13C NMR (75 MHz, DMSO-d6) 6 172.52, 162.77, 148.93, 134.98 (d, J=3.1 Hz), 133.69 (d, J=9.8 Hz), 130.34 (d, J=12.4 Hz), 129.33, 128.90, 128.65, 128.15, 119.28, 118.15, 63.92, 63.45, 52.69, 33.34, 30.00, 28.98-28.58 (m), 28.50, 28.16, 24.33.
The compounds numbered Ib4-1113 and Iba-tic were each prepared according to the method in Example 4.
Among the compounds, compound Ib2b-2 was a viscous liquid, with a yield of 53%
and 'H NMR as follows.

= = CA 03101114 2020-11-20 NMR (300 MHz, Chloroform-d) 8 7.69-7.55 (m, 9H), 7.51 (td, J=7.6, 3.7 Hz, 6H), 7.23-7.13 (m, 314), 6.97 (dq, J=5.3, 2.5 Hz, 1H), 4.71 (s, 2H), 3.79 (s, 314), 3.61 (s, 3H), 3.59-3.41 (m, 2H), 2.19 (t, J=6.7 Hz, 2H), 1.80 (p, J=7.1 Hz, 2H), 1.54 (p, J=7.8, 7.3 Hz, 2H).
II. The examples of the composition comprising the compound as shown in formula I
are provided as follows (the following components are all calculated by mass percentages, and the active components are added after being calculated in percentages).
Example 5 Preparation of a wettable powder comprising 50% the compound as shown in formula I
The composition of the wettable powder: the compound as shown in formula I
(50%), dispersant polycarboxylate (5%), wetting agent sodium dodecyl sulfate (3%), and solid carrier or disintegrator bentonite (42%). The components were mixed according to the proportions to obtain a mixture, which was crushed by air flow to obtain the wettable powder comprising 50% the compound of formula I.
Example 6 Preparation of amissible oil comprising 30% the compound as shown in formula I
The composition of the missible oil: the compound as shown in formula I (30%), emulsifier polyoxyalkenylenealkylaryl ether (12%), penetrant alkylaryl sulfonate (10%), and liquid carrier cyclohexanone (48%). The components were mixed according to the proportions to obtain a transparent solution comprising 30% the compound of formula I.
Example 7 Preparation of a water dispersing granule comprising 60% the compound of formula I
The composition of the water dispersing granule: the compound as shown in formula I
(70%), dispersant calcium alkylbenzene sulfonate (3%), dispersant lignosulfonate (3%), wetting agent sodium dodecyl sulfate (4%), and solid carrier or filler starch (20%). The components were mixed according to the proportions to prepare the water dispersing granule comprising 70% the compound of formula I.
III. Bioassay Example 8 Assay of bactericidal activity The compound of formula I of the present invention was used to test various fungus diseases of plants. The test method was as follows.
Mycelial growth rate assay method: according to the Agricultural Industry Standard of the People's Republic of China (NY/T 1156.2-2006), the mycelial growth rate method was used for the assay. On a super clean experimental platform, activated pathogens were drilled with a hole punch having a diameter of 5 mm under sterile conditions. A fungus cake was , =
= = CA 03101114 2020-11-20 cut, inoculated in the center of a cooled medium containing medicine with a No.11 scalpel, covered with a dish cover, and then cultured at inversion in a 25 C
incubator. Three such fungus cakes were placed in parallel, and an average value was taken as a result.
When the CK diameters each reached 6-8 cm, the diameters of treated colonies were each measured by the cross method. Growth diameters of the colonies were calculated by formula (1), and an average value was taken.
Growth diameter of colony = Diameter of colony ¨ Diameter of fungus cake (1) Assay results: the growth inhibition rate of each compound to the mycelium of a pathogen was calculated by the growth diameter of a blank control colony and the growth diameter of the treated colony, as shown in the formula (2) below.
Growth inhibition rate for mycelium (%) = (Growth diameter of control colony ¨
Growth diameter of drug treated colony)/ Growth diameter of control colony x 100 (2) RI
W
I-, Table 1 Com tarison test results of ftmjcidal activit ' of 121 series cum t minds I-, IA Sthrotinia 80* PtirAthory 1105**811 arra717 1,61Z11 PAROAVVW Filsiffarn 107 ii/e1 Collanktimm Igmarimm Iv iliniont gruTunnwor 0 RAVOOTim Cinfrtn p3p41 nom*
richiArafa gari OM tplavildermatim at.

Pysiderates o 9952 1 9.42 76.74 36.31 9541 -N
I 5124 8723 0.78 92.51 7243 724 cia io In iv mrprommmiusim_ 69 man mem iii=
co 6 .34 71.49 unimENT1517.,__ 1933 11111111MI"
NW=NO 43 63.42 81.29 61.S2 17111 71.05 21.3 1A.08 99.93 6.1.22 M5 7162 MM. 71.36 MI x.23 CA
44-1 0 S4.42 61.62 3041 me.67.37 ii1101 66:7.3.834 6162 IIIIMMI 7149 2514 _ .. , .. .. .. ___ .., lata-1 1 9111 6194 3325 %91 70 22,92 _ In 9/ .39 . tatdo 12.07 on 111111:n1111 UM 7 a II NA 27.01 amminumppm -BEIM 71.39 9113 1 KM 9.46 Mil UM
__ 111121111111 11511.22 10.21 95.3S 3199 . 72 r. 61/4 11:6 30.46 MA ICE
nill90.44 61.73 91.41 61.19 WO 7249 712 11.75 /Sir 111=
IE_BIM

According to the results of sterilization experiments, 11 compounds of formula I series each showed excellent broad-spectrum fungicidal activity at a concentration of 0.07 M. Compared with the control agent Boscalid, each drug had similar or even better fungicidal activity. Especially, Ia8a-3, Ia8a-13, Ia8a-14, Iasa-15, and Ia8a-21 showed good fungicidal effect on Bohytis cinerea, Phytophthora capsici, Colletotrichum lagenarium, and Phytophthora infestans.

Table 2 Comparison test results of fun !4'cida1 activity of lb srics compounds .
Pydriunt Rhizoctonia Phytophthora Botryospuaeria &alba Phytophthora 0 .07 11M Boyd: einerea 910idennatuni Sakai eaptici bereugerktna graminearn *stalls _ _ _ _ 10-2 3,60 (1.65 47,50 64,72 8,89 15.03
6,14 61).2 24.72 0.68 69.17 86.88 46.00 20,26 52,41 91.22 56,80 78,75 88,01 70,44 24,62 79,82 Kresoxim=metbyl 69.89 50,44 _45.31 22,21 47.11 30,07 68,42 u, =

Table 2 Comparison test results of fungicidal activity of lb series compounds Pythium Rhizoctonia Phytophthora Botryospuaeria FusaHum Phytophthora 0.07 M Botrytis cinerea aphanidermatum solani capsici berengeriana graminearum infestans Ib2b-2 3.60 (1.65) 47.50 64.72 8.89 15.03 6.14 -Ib51)-2 24.72 0.68 69.17 86.88 46.00 20.26 52.41 Ib8b-2 91.22 56.80 78.75 88.01 70.44 24.62 79.82 Kresoxim-methyl 69.89 50.44 45.31 22.21 47.11 30.07 68.42 .
OH
E a HH
A
I V

E a I VI

Table 2 Comparison test results of fun !4'cida1 activity of lb srics compounds .
Pydriunt Rhizoctonia Phytophthora Botryospuaeria &alba Phytophthora 0 .07 11M Boyd: einerea 910idennatuni Sakai eaptici bereugerktna graminearn *stalls _ _ _ _ 10-2 3,60 (1.65 47,50 64,72 8,89 15.03 6,14 61).2 24.72 0.68 69.17 86.88 46.00 20,26 52,41 91.22 56,80 78,75 88,01 70,44 24,62 79,82 Kresoxim=metbyl 69.89 50,44 _45.31 22,21 47.11 30,07 68,42 u, =

' . . CA 03101114 2020-11-20 The fungicidal experiment results showed that at a concentration of 0.07 uM, three lb series compounds Ib8b-2 and Ib5b-2 showed excellent broad-spectrum fungicidal activity. Compared with the control agent kresoxim-methyl, Ib813-2 and Ib513-2 had similar or even better fungicidal activity. Especially, 1[1,813-2 had a good fungicidal effect on Pythium aphanidermatum, Botrytis cinerea, Phytophthora capsici, Botryospuaeria berengeriana, and Phytophthora infestans.
Industrial Application The triphenylphosphonium salt compound shown in formula I of the present invention has broad-spectrum and excellent fungicidal activity, and can be used to prevent and cure diseases caused by four major pathogenic fungi: i.e., ascomycetes, basidiomycetes, deuteromycotina, and oomycetes, on a variety of crops. Good prevention and cure effects can be obtained at a low dose. The compound is widely used in plant pro tec tants .

Claims

. =
We claim:
1 A compound having a general structural formula as shown in formula I:
Ph =
Ph, :
PliPX-Q
y- n Formula I
wherein in formula I, X is selected from the group consisting of CH2, N, S, and 0; Y is any one selected from the group consisting of:halogen, CH3S03, CF3CO2, CH3CO2, CF3S03, PhCO2, FIOC6H4CO2, (CH2CO2)2, (CHCO2), and formula W; the halogen is any one selected from the group consisting of chlorine, bromine, and iodine; n is an integer in the range from 0 to 16; and Q is selected from formula Ia or formula Ib below;

,Ar , N ' ,ss ' n =i , RI Ai S03 W la Ib wherein in forrnula W, RI represents H or Ci-Cp alkyl;
wherein in formula Ia, Ar is any one selected from the group consisting of Alto A4 and A6 tO Ag below, and Qi is any one selected from the group consisting of H and Bi-Bii; and , A IL: Az= A 3 = \ / A A 4-=
....- ...."
_i_az1 4-GRI 0 .. r,. ,y24....
...../
A4-1CoaK A ¨ 1)--t ¨ .."
0 0 0 0\ 0 0 ,,,t B1= 1 ._,,i= I B3= I B4= I
(R7)5 -'N"--CF3 0 R9 0 .1' C2H3 0 B5= i B
B6= LN i F3C 0 yi B =-7= N ''' ' 8 NY"
. C2H5HN
\ ii0 B9= 0 ---- A Blo= N.--rsi' 5)1' B11= 0 A
CA 3101114 2023-05-24 =

. -wherein in formula Ib, U is any one selected from the group consisting of 0, =
NH, S, 0C-0, SC=0, NHC-0, and NHC¨S, and Q2 iS any one selected from the group consisting of Ci-C4;
o C1= c2= MCH3 N C3= C4= )0CH3 MCH3 --N)'LOCH3 iz OCH3 OCH3 H3CO' H3CO' wherein, in formulas Ai, Az, and As among Ai -A8, R2, R3, Ra, R5, and R6 are each at least one selected from the group consisting of hydrogen, C1-C8 alkyl, Ci-C8 alkoxy, Ci-C8 alkylthio, Ci-C8 fluoroalkyl, Ci-C8 fluoroalkoxy, halogen, nitro, cyano, phenoxy, pyridyloxy, methanesulfonyl, and trifluoromethylsulfonyl, the halogen being any one selected from the group consisting of fluorine, chlorine, bromine, and iodine; o, q, and r are each integers in the range from 0 to 5; m is an integer in the range from 0 to 4; p is an integer in the range from 0 to 3; and the,binding sites of R2, R3, and R6 are at least one of remaining five binding sites, wherein, when m, 0, q, and r > 1, R2, R3, R5, and R6 are the same or different; and the binding sites of R4 are at least one of remaining three binding sites, wherein, when p > 1, R4 are the same or different; in formula A2, N is at any site of sites 3, 4, 5, and 6;
wherein in forrnula Bi among Bi-B10, R7 is at least one selected from the group consisting of hydrogen, Ci-05 alkyl, CI-Cs alkoxy, C1-05 fluoroalkyl, Ci-Cs fluoroalkoxy, halogen, nitro, cyano, phenoxy, pyridyloxy, carboxyl, = methylsulfonyl, and trifluoromethylsulfonyl, the halogen being any one selected from the group consisting of fluorine, chlorine, bromine, and iodine;

s is an integer in the range from 0 to 5; the binding sites of R7 are at least one of rernaining 5 binding sites, wherein R7 are the same or different when s >
1; in formula B 6, R8 and R9 are each any one selected from the group consisting of hydrogen, CI-Cs alkyl, C i-05 alkoxy, CI-Cs fluoroalkyl, Ci-05 = fluoroalkoxy, and halogen; and wherein in formulas Cl and C3 among formulas C1-C4, Z is N or CH, and M is NH or O.
2. The compound according to claim 1, wherein in fOrmulaiI,' X
is CH2 or 0; Y is any one selected from the group consisting of halogen, CH3CO2, p-toluenesulfonyl, PhCO2, and HOC6H4CO2; n is an integer in the range from 4 to 11.

3. The compound according to claim 1 or claim 2, whereimin formula Ia, Ar is any one selected from the group consisting of Ai, A3, A4, and A6, Q1 is selected from H; in forrnula Ib, U is any one selected frorn the group consisting of 0, OCO, and SC=0, and Q2 is any one selected from the group consisting of C i-C4.
4. A preparation method of the compound of formula I according to any one of clairns 1 to 3, comprising the step of: carrying out a nucle9philic reaction between a compound of formula VII and triphenylphosphine, in the presence or absence of a catalyst, to obtain the cornpound of formula I;
"n formula VII
wherein in formula VII, Y, Q, X, and n are each defined in the same way as in formula I.
= 5. The preparation method according to claim 4, wherein the catalyst is sodium iodide or potassium iodide;
wherein the molar ratio of the catalyst to the compound as shown in formula VII
is (0.01-0.1): 1;
wherein the reaction temperature of the nucleophilic reaction is in the range from 25 to 180 C, and the reaction time is in the range from 4 to 24 h;
= wherein the molar ratio of the cornpound as shown in formula VII to triphenylphosphine is 1: (1-2); and wherein the nucleophilic reaction is carried out in an organic solvent which is at least one selected from the group consisting of acetonitrile, glycol dimethyl ether, benzene, toluene, and 1,2-dichloroethane.
= 6. The preparation method according to claim 5, wherein the reaction temperature of the nucleophilic reaction is in the range from 80 to 115 C, and the reaction tirne is in the range from 8 to 12 h, 7. The preparation,method according to any one of claims 4 to 6, wherein the nucleophilic reaction is carried out in the following steps: performing vacuumization = and then nitrogen filling on the catalyst, triphenylphosphine, and the compound as shown in formula VII, and magneton; adding the organic solvent under the protection - of nitrogen, followed by stirring at room temperature for 5-10 min, and then reacting at ternperatures in the range from 80 to 115 C for 8 to 12 h, to qbtain the compound as shown in formula I.

, =
8. A compound with a general structural formula as shown in formula VII:
Yl¨r.XQ
formula VII !' wherein in formula VII, Y, Q, X, and n are each defined in the same way as in formula I.
9. A preparation method of the compound of formula VII according to claim 8, comprising the steps of:
reacting a compound of forrnula IV with a compound of foimula VI in the presence of a catalyst, or reacting a compound of formula V with the compound of forrnula VI, in the presence of an acid binding agent, to obtain the compound of formula VII;
' Q2--Br/SH X-UH
forrnula IV formula V forrnula VI
wherein in formula IV, Qi and Ar are each defined in the same way as in formula = la in claim 1; in formula V, Q2 is defined in the same way as in formula Ib in claim 1;
in forrnula VI, X, Y, and n are each defined in the same way as in formula I, and U is defined in the same way as in formula Ib in clairn 1; when the compound of formula IV reacts with the compound of formula VI, U is 0C-0 group.
10. The preparation method according to claim 9, wherein:
the acid binding agent is at least one selected from the group consisting of pyridine, triethylamine, ethylenediamine, potassium carbonate, cesium carbonate, N-methylmorpholine, and NaH; and the catalyst is at least one selected from the group consisting of EDCl/HOBT, CDI, DMAP/DCC, HATU/DIPEA and DIC;
the molar ratio of the acid binding agent to the cornpound as shown in formula IV is (2-5): 1;
the molar ratio of the catalyst to the compound as shown in formula IV is (1-2.5):
1, wherein the molar ratio of the compound as shown in formula IV to the compound as shown in formula VI is 1: (1-2);
the molar ratio of the acid binding agent to the compound as shown in forrnula V
is (2-5): 1; the molar ratio of the catalyst to the compound as shown in formula V is (1-2.5): 1; wherein the molar ratio of the compound as shown in V to the compound as shown in formula VI is 1: (1-2);

the reaction ternperature is in a range from -20 C to 35 C, and the reaction time is 1-6 h;
the reaction is carried out in an organic solvent, which is at least one selected from the group consisting of dichloromethane, tetrahydrofuran, acetonitrile, N,N-dimethylformamide, 1,4-dioxane, and toluene.
11. A compositiOn, Comprising the compound as shown in formula I according to any one of claims 1 to 3 and an agriculturally acceptable carrier.
12. The composition according to claim 11, wherein the mass percentage content of the compound as shown in formula I in the composition is in the range from 0.1%
to 99%.
13. The composition according to claim 12, wherein the mass percentage content of the compound as shown in formula I in the composition is in the range from 30%
to 60%.
14. The composition according to any one of claims 11 to 13, wherein the composition further comprises at least another active compound, which is at least one selected from the group consisting of a known fungicide, acaricide, nematicide, insecticide, herbicide, fertilizer, growth regulator, safety agent, and chemical pheromone.
15. The composition according to claim 14, wherein the at least another active compound is selected from the group consisting of a bactericidal agent and a pesticide.
16. The composition according to any one of claims 11 to 13, wherein the agriculturally acceptable carrier is at least one selected from the:group consisting of a solid carrier and liquid carrier;
wherein the solid carrier is at least one selected from the group consisting of a natural or synthetic silicate, ammonium sulfate, calcium sulfate, aluminum silicate oxide, natural or synthetic resin, polychlorophenol, starch, bentonite, and wax, wherein the natural or synthetic silicate is 'at least one .elected from the group consisting of attapulgite, talcum, aluminum silicate, diatomite, mica, rnontmorillonite, and calcium silicate; the natural or synthefic resin is at least one selected from the group consisting of phenylpropyl furan resin, styrene polymer, and styrene copolyrner; and the wax is at least one selected from the group consisting of beeswax and paraffin; and wherein the liquid carrier is at least one selected from the group consisting of water, a CI-C.4 alcohol, a C3-C8 ketone, an aromatic hydrocarbon, a petroleum fraction, and a C6-C 12 chloroalkane, wherein the alcOhol is ethanol and/or glycol;
the ketone is at least one selected from the group consisting of acetophenone, acetone, methyl ethyl ketone, and cyclohexanone; the aromatic hydrocarbon is at least one selected from the group consisting of benzene, toluene, and xylene;
the petroleum fraction is kerosene and/or mineral oil; and the chloroalkane is at least one selected from the group consisting of carbon tetrathloride, dichloromethane, and trichloroethane;
= wherein the composition further comprises a surfactant, which is at least one selected from the group consisting of an emulsifier, a dispersant, a wetting agent, and a penetrant;
wherein the emulsifier is at least one selected from the group consisting of calcium alkylbenzenesulfonate, phenylphenol polyoxyethylene ether, alkylphenol formaldehyde resin polyoxyethylene ether, phenylethyl phenol polyoxyethylene polypropylene ether, polyoxyalkenylenealkylaryl ether, and ethylene oxide propylene oxide block copolymer;
wherein the dispersant is at least one selected from the group consisting of polycarboxy late, lignosulfonate, alkylphenol polyoxyethylene formaldehyde condensate sulfate, an alkylbenzene sulfonate calcium salt, a benzenesulfonate formaldehyde condensate sodium salt, sodium lauryl sulfate, sodium castor oil sulfate, sodium alkylaryl sulfonate, alkylphenol polyoxyethyleneether, polyoxyethylene fatty acid, and ester polyoxyethylene ether; and wherein the wetting agent is at least one,selected from the group consisting of sodium dodecyl sulfate, sodium dodecyl benzene sulfonate, nekai BX, saponin powder, silkworm sand, and sapindus powder; and wherein the composition further comprises other auxiliaries, which are at least one selected from the group consisting of a disintegrating agent, a defoamer, an antifreeze, and a thickener;
I!
=
CA 31013.14 2023-05-24 . =
wherein the disintegrating agent is at least one selected from the group =
consisting of bentonite, urea, amrnonium sulfate, aluminum chloride, and glucose;
wherein the defoamer is at least one selected frorn the group consisting of silicone oil, a silicone compound, a Clo-C20 saturated fatty acid compound, and a C8-C10 fatty alcohol compound;
wherein the antifreeze is at least one selected from the group consisting of glycol, propylene glycol, glycerol, and polyethylene glycol; and wherein the thickener is at least one selected frorn the group consisting of xanthan gum, polyvinyl alcohol, and polyethylehe glSfcol.
17. Use of the compound of formula I according to any one of claims 1 to 3 in the preparation of a plant fungicide and/or soil fungicide.
18. The use according to claim 17, wherein the plant fungicide and/or soil fungicide are used for prevention and cure of diseases, caused by,4 least one fungi of Eumycetes selected froth the group consisting of ascomycetes, basidiomycetes, deuteromycotina, and oomycetes.
19. Use of the composition according to any one of claims 11 to 16 in the preparation of a plant fungicide and/or soil fungicide.
20. The use according to claim 19, wherein the plantfUngickle and/or soil fungicide are used for prevention and cure of diseases caused by at least one fungi of Eumycetes selected from the group consisting of ascomycetes, basidiomycetes, deuteromycotina, and oomycetes.
CA3101114A 2018-08-17 2018-08-17 Triphenylphosphonium salt compounds, preparation method and use thereof Active CA3101114C (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2018/100964 WO2020034181A1 (en) 2018-08-17 2018-08-17 Quaternary triphenylphosphonium salt compound, preparation method therefor, and uses thereof

Publications (2)

Publication Number Publication Date
CA3101114A1 CA3101114A1 (en) 2020-02-20
CA3101114C true CA3101114C (en) 2024-04-09

Family

ID=69524547

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3101114A Active CA3101114C (en) 2018-08-17 2018-08-17 Triphenylphosphonium salt compounds, preparation method and use thereof

Country Status (3)

Country Link
AU (1) AU2018436544B2 (en)
CA (1) CA3101114C (en)
WO (1) WO2020034181A1 (en)

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009047240A1 (en) * 2007-10-09 2009-04-16 Smithkline Beecham Corporation Indole derivatives useful as ppar activators
CN102757459B (en) * 2011-04-29 2016-01-27 上海源力生物技术有限公司 For the synthesis of the intermediate and preparation method thereof of prostanoid medicine
WO2013172979A1 (en) * 2012-05-14 2013-11-21 University Of Southern California Methods and compositions for positron emission tomography myocardial perfusion imaging
CN107226791B (en) * 2017-06-13 2020-07-10 贵州医科大学 Anti-tumor application of nitric oxide as novel histone deacetylase inhibitor

Also Published As

Publication number Publication date
AU2018436544A1 (en) 2020-12-10
WO2020034181A1 (en) 2020-02-20
AU2018436544B2 (en) 2022-09-08
CA3101114A1 (en) 2020-02-20
WO2020034181A9 (en) 2020-08-13

Similar Documents

Publication Publication Date Title
US11751568B2 (en) Picolinamide compounds with fungicidal activity
AU2016265932B2 (en) Antifungal compounds
CN107205399A (en) It is used as the picolinamide of fungicide
CN106456601A (en) Macrocyclic picolinamides as fungicides
TW201609685A (en) Use of macrocyclic picolinamides as fungicides
US9957252B2 (en) Metalloenzyme inhibitor compounds as fungicides
TWI379635B (en) Isomeric mixtures of dinitro-octylphenyl esters and synergistic fungicidal mixtures therefrom
US20220220068A1 (en) Fungicidal aryl amidines
CN109053801A (en) A kind of triphenyl phosphonium salt compound and the preparation method and application thereof
CA3101114C (en) Triphenylphosphonium salt compounds, preparation method and use thereof
TW201811177A (en) Thiopicolinamide compounds with fungicidal activity
CN103547153A (en) Synergistic fungicidal and algicidal compositions including 7-hydroxy-indanone benzoylhydrazones and copper
US8557866B2 (en) Isomeric mixtures of dinitro-octylphenyl esters and synergistic fungicidal mixtures therefrom
WO2024188052A1 (en) Substituted pyrrolidone compound, preparation method therefor, composition, and use thereof
AU2005295774B2 (en) Isomeric mixtures of dinitro-octylphenyl esters and synergistic fungicidal mixtures therefrom
CN120829389A (en) Pyridinamide compounds and application thereof

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20210929

EEER Examination request

Effective date: 20210929

EEER Examination request

Effective date: 20210929

EEER Examination request

Effective date: 20210929

EEER Examination request

Effective date: 20210929

EEER Examination request

Effective date: 20210929

EEER Examination request

Effective date: 20210929

EEER Examination request

Effective date: 20210929

EEER Examination request

Effective date: 20210929